University of Groningen. Physical activity and fitness in patients with COPD Altenburg, Wytske Agatha

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1 University of Groningen Physical activity and fitness in patients with COPD Altenburg, Wytske Agatha DOI: /j.rmed /j.rmed /j.rmed IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2015 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Altenburg, W. A. (2015). Physical activity and fitness in patients with COPD: Making a change [Groningen]: University of Groningen DOI: /j.rmed , /j.rmed , /j.rmed Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 Physical activity and fitness in patients with COPD Making a change Wytske Altenburg

3 The studies described in this thesis were financially supported by: University Medical Centre Groningen and Boehringer Ingelheim BV, the Netherlands. Printing of this thesis was financially supported by: University of Groningen, University Medical Centre Groningen, Stichting Beatrixoord Noord Nederland, Stichting Astmabestrijding, Boehringer Ingelheim BV, Teva Nederland BV. ISBN: Cover design: Lydia van Dijk-Altenburg en Paul van Dijk Layout: Wytske Altenburg Printed by: CPI Koninklijke Wöhrmann B.V., Zutphen W.A. Altenburg 2015 All rights reserved. No part of this publication may be reproduced or transmitted, in any form or by any means, without permission of the author, or when appropriate, of the pulishers of the publications.

4 Physical activity and fitness in patients with COPD Making a change Proefschrift ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen op gezag van de rector magnificus prof. dr. E. Sterken en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op maandag 15 juni 2015 om uur door Wytske Agatha Altenburg geboren op 24 september 1980 te Sneek

5 Promotor Prof. dr. H.A.M. Kerstjens Copromotores Dr. J.B. Wempe Dr. N.H.T. ten Hacken Dr. M.H.G. de Greef Beoordelingscommissie Prof. dr. T. Troosters Prof. dr. E.J. Scherder Prof. dr. R. Sanderman

6 Paranimfen Maaike Oostergetel Lydia van Dijk-Altenburg

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8 Contents Chapter 1 CHapter 2 CHAPTER 3 CHAPTER 4 CHAPTER 5 CHAPTER 6 CHAPTER 7 CHAPTER 8 General introduction Functional and psychological variables both affect daily physical activity in COPD: a structural equations model Short- and long-term effects of a physical activity counseling program in COPD: a randomized controlled trial Dropout from a physical activity counseling program in COPD: results from a randomized controlled trial in three healthcare settings A better response in exercise capacity after pulmonary rehabilitation in more severe COPD patients Changes in the endurance shuttle walk test in COPD patients with chronic respiratory failure after pulmonary rehabilitation: the minimal important difference obtained with anchor- and distribution-based method Summary and general discussion Nederlandse samenvatting Dankwoord

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10 CHAPTER 1 General introduction

11 Chapter 1 Introduction Definition and impact of COPD Chronic obstructive pulmonary disease (COPD) is a major health problem with a prevalence of 1.83% for men and 1.55% for women in the Dutch population. In the Dutch population COPD was reported to be the fifth leading cause of death in Worldwide COPD is currently the fourth leading cause of death and is expected to be the third in COPD is defined as a common preventable and treatable disease, which is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and lung to noxious particles or gases. 3 Exacerbations and comorbidities contribute importantly to the perceived burden of disease in individual patients. The most important risk factor for COPD is tobacco smoking, including secondhand or passive smoke exposure. Other risk factors include indoor and outdoor air pollution, occupational dusts and chemicals, and frequent lower respiratory infections during childhood. 4 Pathophysiology Several processes underlie the physiologic abnormalities and symptoms which are present in patients with COPD. Inflammation and narrowing of the central and peripheral airways leads to a decrease in forced expiration volume in one second (FEV 1 ). Parenchymal destruction also contributes to airflow limitation and decreased oxygen uptake. In addition, carbon dioxide retention may occur resulting from higher work of breathing and a reduced ventilatory capacity or drive. Besides that, peripheral airway obstruction and reduced lung recoil may lead to trapped air, hyperinflation and reduced inspiratory capacity. Subsequently, dyspnea, especially during exercise, increases, thereby limiting exercise capacity. Recently, there has been more attention for systemic inflammation as a key factor in COPD. Inflammatory mediators in the circulation may contribute to skeletal muscle wasting and cachexia and initiate or worsen comorbidities such as ischemic heart disease, heart failure, osteoporosis, diabetes, metabolic syndrome and depression. 3 Symptoms Prominent symptoms of COPD are chronic cough, mucus production, dyspnea and decreased exercise capacity. Patients often enter a downward spiral of dyspnea, avoidance of physical activity and deconditioning. Exercise capacity may be affected by lung-related factors such as ventilatory limitation, dynamic hyperinflation and diminished oxygen uptake in the lung, but also by factors outside the lung such as early lactate production, muscle dysfunction and cardiovascular deconditioning. The latter features may at least partially be induced by the sedentary lifestyle present in these patients, caused by experienced dyspnea during physical activities or exercise training. In the early stages of COPD patients may not experience limitations in their exercise capacity yet, because ventilatory reserves are still large and hyperinflation or gas exchange problems are modest. Nevertheless, physical activity is known to be decreased already in the early stages of COPD (from GOLD stage II) compared to healthy subjects. 5 Physical activity and physical fitness Physical activity and physical fitness are closely related but not exchangeable concepts. Physical activity is defined as any bodily movement produced by skeletal muscles that requires energy 10

12 General Introduction expenditure. 6 Physical fitness can be defined as the ability to carry out daily tasks with vigor and alertness, without undue fatigue, and with ample energy to enjoy leisure time. Physical fitness can be divided into performance and health related fitness, whereas the latter includes cardiorespiratory fitness, muscular strength and endurance, body composition and flexibility. 7 Unfortunately, physical activity and physical fitness are frequently used in the same way, although there are important differences. As explained above physical activity reflects what a person actually does in daily life, whereas physical fitness indicates what a person is capable of. This implies that physical activity also has a behavioral component, as a person has the choice to use his abilities or not. Important aspects and consequences of both concepts will now be described in more detail. Also the tools to measure these concepts will be addressed. Physical activity Physical activity is recognized by the WHO as an important feature to improve cardiorespiratory and muscular fitness, bone health and reduce the risk of noncommunicable diseases and depression. Therefore the WHO recommends adults to be physically active at a moderate intensity for at least 150 minutes throughout the week, or at vigorous intensity for at least 75 minutes throughout the week, or an equivalent combination of these. Physical activity on an aerobic level should be performed in bouts of at least 10 minutes duration. For additional health benefits the amount of physical activity should even be further increased. 8 Moreover, a recent study showed that in a general population exercising at moderate intensity for 15 min a day or 90 minutes per week already reduced all cause mortality with 14% and increased life expectancy with 3 years. 9 Every additional increase of 15 minutes of physical activity beyond this minimum of 15 minutes per day further reduced all cause mortality by 4 %. Low physical activity has negative consequences and has been associated with higher age, higher BMI and being a woman in healthy elderly subjects. 10 Besides that, physical inactivity increases the risk of many adverse health conditions such as coronary heart disease, type 2 diabetes, breast and colon cancer and shortens life expectancy. 6 Recently it has been shown that physical inactivity is the fourth leading cause of mortality globally and thereby responsible for 6% of all deaths. 1 Physical activity level in COPD patients generally is low, mean step counts ranging from have been shown in different studies In studies that compared COPD patients and healthy subjects mean steps for healthy subjects were higher and ranged from ,18 In addition, physical activity level is also more reduced in COPD patients than in populations with other chronic diseases. 19,20 The associations with and risks of physical inactivity found in healthy (elderly) subjects might as well yield for COPD patients. Furthermore, in COPD low physical activity level has been associated with lower FEV 1 5,13,18,21,22, VO 2 peak 21,23,24, 6 minute walking distance 5,12,21-24, quality of life 13, self efficacy 22,25, and higher risk for all-cause and respiratory mortality Interestingly, associations between physical activity and physical variables have been investigated more extensively than associations with psychological variables. How physical activity, physical variables and psychological variables interact and whether these interactions differ between COPD stages is therefore an interesting research topic. Physical activity has been measured in several ways using direct observation, doubly labeled water, motion sensors or questionnaires. Direct observation and doubly labeled water are often too expensive and time consuming. Questionnaires are inexpensive and easy to use 11

13 Chapter 1 but rely on the memory and interpretation of patients and are therefore subjective and less accurate. Motion sensors are an objective way to measure physical activity. Pedometers are uni-axial motion sensors, which can only measure walking or running related activities, whereas tri-axial accelerometers measure movements in more than one plane and should thus be able to monitor all movements. Both devices have been used in COPD patients and have their advantages and disadvantages. Tri-axial accelerometers are able to measure the intensity of physical activity and accelerometry counts show a linear relationship with energy expenditure. 30,31 Pedometers only measure step counts, but are easier to interpret for the user and are less expensive. All the same, measurement of some movements (e.g. upper body, graded terrain and cycling) remains problematic for both kind of devices. Importantly, walking and running are the most common forms of physical activity, which makes the application of pedometers very valuable. Physical fitness Physical fitness is decreased in COPD, which is demonstrated by loss of exercise capacity and muscle strength. It remains unclear to what extent this deterioration of physical fitness is caused directly by consequences of COPD, such as systemic inflammation and oxidative stress, although studies in COPD patients have shown elevated levels of biomarkers such as TNF-α and CRP. 32 It is known that the normal aging process is also characterized by a progressive decline of skeletal muscle function called sarcopenia. 33 Finally, physical inactivity is an important factor in this process. The fact that in general the deterioration of physical fitness is accelerated in COPD patients compared to healthy older adults underlines the importance of enhancing physical fitness and physical activity. In COPD, physical fitness (health related) is a concept that is frequently objectified by measuring exercise capacity, and muscle strength. The latter can be measured using different measurement tools such as a hand-held dynamometer or a computerized dynamometer for arm as well as leg strength. Different methods of strength testing and their advantages and disadvantages have been described in detail elsewhere. 34 Exercise capacity in COPD can be distinguished in peak exercise capacity and endurance exercise capacity. Peak exercise capacity is determined by peak oxygen uptake, which is the highest oxygen uptake obtainable for a given form of ergometry despite further work rate increases and effort by the subject. 35 Endurance exercise capacity has been defined as the ability to sustain a high proportion of individual maximal oxygen uptake. 36 Exercise capacity, both peak and endurance, have been measured using several measurement tools. Exercise testing can be performed in a highly standardized way in the lab, e.g. the incremental cycle ergometer or treadmill test or in a less standardized way by using field tests such as the 6 minute walking distance (6MWD), incremental shuttle walking test (ISWT) and endurance shuttle walking test (ESWT). Incremental exercise testing is often used in COPD patients to assess exercise limitation, which may be influenced by factors such as reduced ventilatory capacity, dynamic hyperinflation, diminished oxygen uptake, early lactate production, muscle dysfunctioning and cardiovascular deconditioning. 37,38 An incremental exercise test is a symptom-limited test using for example 1 minute increments of 5 or 10 W on a cycle ergometer, to the limit of tolerance of the patient. During such tests peak work rate, pulmonary oxygen uptake, carbon dioxide output and minute ventilation can be measured 12

14 General Introduction with a mixing chamber. Electrocardiography is used to measure heart rate, and arterial blood gasses may monitor gas exchange performance during exercise. Measuring all these variables gives a detailed and large amount of information on how exercise capacity is limited. Although, incremental cycle ergometry or treadmill testing is regarded as the gold standard to measure exercise capacity, field tests, such as the 6MWD, the ISWT and ESWT might be a good alternative. These field tests are less expensive and do not require sophisticated equipment and resources that are not available in all facilities or to all clinicians. It has been shown that in COPD patients these field tests often elicit a peak cardiorespiratory response similar to incremental cycle ergometry and treadmill testing. 39,40 Both incremental and endurance exercise capacity have been investigated extensively, however, the latter might be a more relevant measure in COPD, because endurance exercise intensity levels reflect activities of daily life better than maximal exercise intensity levels. The ability to carry out activities of daily life might be more important to the patient than his peak exercise capacity. Therefore submaximal and endurance exercise capacity are considered to be important outcome measures. 1 Two important field tests to measure submaximal and endurance exercise capacity in COPD are the 6MWD and the ESWT. The 6MWD, a self paced field test, is a frequently used measure of (sub)maximal exercise capacity in COPD. During this test patients have to walk as far as possible in 6 minutes. 41 The test has shown to be responsive to treatment in several studies However, there is no consensus on what is considered to be a clinically relevant change in 6MWD. Studies investigating this topic reported values of change in 6MWD ranging from 25-54m as minimally important difference (MID) in different COPD populations and with different treatments The ESWT, another field test, measures endurance exercise capacity. The ESWT is externally paced and therefore less affected by motivation and pacing ability than the 6MWD. The ESWT is performed on a 10 m long course at a speed corresponding with 85% of VO 2 peak, which can be estimated from the incremental shuttle walking test that is performed before the ESWT. Patients are instructed to walk for as long as possible at a speed dictated by an auditory signal. 50 The ESWT has shown high responsiveness to treatment with bronchodilators 51 and pulmonary rehabilitation 52 in patients with COPD. In addition, the ESWT might be more responsive to treatment than the 6 MWD. 52 The MID of the ESWT has been investigated less extensively than the MID of the 6MWD. One study attempted to estimate the MID of the ESWT after bronchodilation and PR, but only succeeded in determining a MID after bronchodilation. This MID was considered to be seconds (13%) or m (15%) change in ESWT. Until now a clear MID of the ESWT after PR remains unknown. Improving and maintaining physical fitness and physical activity Improving physical fitness PR is an important treatment option for patients with COPD. 3 PR programs are multidisciplinary and in general contain different training forms (cycling, walking, strength exercises and cardiofitness), education and psychological or dietetic interventions if necessary. Improving physical fitness is one of the most prominent aims of PR. PR programs should have a minimum of 20 sessions given at least 3 times a week to achieve desirable physiologic benefits. Ideally, endurance training should be performed for at least 30 minutes at high intensity levels (>60% peak work rate). Although high intensity exercise produces greater physiologic benefits, low 13

15 Chapter 1 intensity exercise is also effective for those patients who cannot achieve a high intensity exercise level. However, when patients are highly symptomatic and not able to achieve this low intensity level, then interval training is also a good alternative. Exercise training should be aimed at both upper and lower extremities and a combination of endurance and strength exercise generally has multiple beneficial effects. 53 The amount of research investigating the beneficial effects of PR programs is large. A review of Lacasse et al, including 31 trials, shows that PR programs improve health related quality of life and exercise capacity. 54 With regards to quality of life the meta-analysis in this review showed a statistically significant and clinically relevant treatment effect in the Chronic Respiratory Questionnaire (CRQ). In other words, the common effect size on each domain of the questionnaire (dyspnea, fatigue, emotional function and mastery) exceeded the MID (0.5 on a 7-point scale). For the St. George Respiratory Questionnaire (SGRQ), the common effect size on each domain as well as the total score also exceeded the MID (4 points on a 100-point scale). With regards to exercise capacity, the common effect of PR on change in 6 MWD was an increase of 48 meters, suggesting a positive effect of PR. The common effect of PR on incremental cycle ergometry was 8.4 Watts. Despite the large amount of evidence for the positive effects of PR it is unclear which patients respond best to exercise training. Some studies have investigated this topic but there is no consensus yet on which patient should be enrolled in PR and what kind of program is most effective. Better insight in this topic might help to better tailor programs to the patients needs. Maintaining physical fitness after pulmonary rehabilitation PR programs show positive short term results, which are often only partly maintained in the long term. 55 An interesting question in this perspective is: what can be done to maintain the effects of PR? Several programs aiming at maintenance of PR results have been investigated. 56 All these programs used supervised exercise training (ranging from once a month to 3 times per week) as part of the program, which was combined with phone calls in the studies with supervised exercise training only once a month. The duration of these programs ranged from 9-15 months and consisted of aerobic exercise (walking and cycling) and in most studies also lower and/or upper extremity strength training. Meta-analysis of these studies shows that supervised exercise programs after PR are superior to usual care in the medium term, as benefits in exercise capacity were sustained after 6 months. 56 However, these effects were not sustained after 12 months. In addition, there were no differences in health related quality of life (measured by CRQ or SGRQ) between the supervised exercise groups and usual care at any time. 56 Another important contributor to maintenance of effects is the extent to which patients show adherence to a program. Nonadherence to and dropout from PR programs and maintenance exercise programs is considerable with compliance rates ranging from 39-76% after 1 year, with a mean compliance rate of 60%. 56 With regards to health related quality of life, maintenance programs might be more effective when not only exercise training is included. For example, weekly phone calls could contribute to increased health status. In addition, a 24-month disease management program in less advanced COPD patients, including exercise, 14

16 General Introduction nutritional intervention, smoking cessation support and post exacerbation rehabilitation, still showed significant differences between the intervention and usual care group in both exercise tolerance and health related quality of life after 2 years in favor of the intervention group. 57 Possibly, such a disease management program might also be effective to maintain results after completion of a PR program. Counseling physical activity during exercise programs An important problem in COPD patients is sustaining the complex behavioral change that is initiated by PR. With regards to exercise and physical activity level there is limited relevant research about maintenance of the effects after PR. Because the long term maintenance of exercise capacity and physical activity level involves behavior change, programs including behavioral treatment components, such as physical activity counseling, might be effective in the long term. Two pilot studies using a physical activity counseling protocol in COPD patients have been conducted till now: one combined PR with physical activity counseling in a multidisciplinary PR setting 58, the other compared physical activity counseling to usual care in a hospital outpatient clinic setting 59. Both studies showed promising results in the short term, as in the first study, patients receiving PR and physical activity counseling improved more in steps per day than the PR only group. Although this difference was not statistically significant it was clinically relevant, with an effect size >.80. The other study comparing physical activity counseling to usual care showed an increase in steps of 11% in the physical activity counseling group, whereas the usual care group decreased 18%. Moreover, a significant beneficial effect in the physical activity counseling group was found in arm and leg strength, quality of life and intrinsic motivation scores. Therefore physical activity counseling might be a feasible treatment option to maintain or even further improve and extend the effects of PR on exercise capacity and physical activity level in COPD. 1 Counseling physical activity instead of exercise programs An important reason to explore the possibilities of improving physical activity in daily life instead of following a structured exercise program is that it is less expensive and accessible to a larger part of the COPD population. Enhancement of physical activity in daily life using behavioral counseling, could thus be given autonomous of PR or structured exercise programs, however the question is whether this is equally effective. We know that physical activity levels in COPD patients are already reduced in the mild stages of COPD 5 and that reduced physical activity is associated with reduced physical fitness 5,12, Therefore patients with reduced physical activity level could be an attractive target population for physical activity counseling as it might improve physical fitness or prevent further deterioration and the need for PR in these patients. What also advocates for behavioral counseling in earlier disease stages is the fact that self-efficacy, which is a modifiable factor, is a predictor of physical activity in milder COPD. 60 PA counseling may help patients to make better use of their capabilities by discussing barriers for being physically active and setting achievable goals to enhance physical activity level. Therefore, it is very interesting to investigate the effects of a physical activity counseling program over a longer period in a larger population of COPD patients including those with mild COPD. It would also be interesting to investigate the reasons for and predictors of dropping out from such a study, as it has been shown that compliance to PR maintenance programs consisting only of exercise training generally is low. 15

17 Chapter 1 In summary, physical activity counseling could be an attractive treatment option, in different settings of healthcare. The counseling could be performed adjunct to PR or exercise programs or as a stand-alone treatment. Prolonged effects of counseling on physical activity and physical fitness need to be investigated. Behavioral principles of physical activity counseling As described above, physical activity is what someone actually does. This implicates that behavior is involved in choosing to be active or not. The physical activity counseling program used in the randomized controlled trial we conducted (the COACH study) is based on principles from different behavioral theories, which will be explained in more detail below. Firstly, parts of the Transtheoretical Model were applied. This model suggests that behavior change is a process consisting of five different stages (Stages of Change) The precontemplation stage, in which subjects have no intention to or need for behavior change. 2. The contemplation stage, in which subjects are more or less convinced that they should change their behavior, but are actually not planning to do so. 3. The preparation stage, in which subjects have the intention to change behavior and are actually planning to execute it. 4. The action stage, in which subjects are actually changing behavior e.g. becoming more active according to physical activity guidelines. 5. The maintenance stage in which the new behavior needs to be consolidated and become part of the daily life routine. The model is cyclic, as patients might relapse and have to repeat the stages of change again. An important feature in this theory is the decisional balance, which means weighing the benefits and barriers for behavior change. When the benefits outweigh the barriers the change process is mostly effective and can be started. This decisional balance is most important in the first three stages of change. Self-efficacy, the confidence in own abilities to change, has an important catalyzing effect on this behavior change cycle. In the counseling protocol there is specific attention for discussing the benefits and barriers to change physical activity behavior. When needed alternatives are discussed that can help overcome the barriers a patient experiences. On the other hand, discussing the benefits can help a person to get convinced that action to change physical activity behavior is needed. Secondly, principles of the Self Determination theory, which distinguishes intrinsic an extrinsic motivation to change behavior, were used. 62 Intrinsically motivated subjects have a perceived locus of causality that lies within the subject, making behavior change more productive, creative, spontaneous and flexible. Intrinsic motivation in this theory has been linked to universal human needs like competence, autonomy and social relatedness, which together determine the extent of self determination. A sub-theory of the Self Determination Theory, the Cognitive Evaluation Theory states that positive feedback improves confidence, social support enables the need for autonomy, and experienced empathy increases social relatedness. The counseling program uses positive feedback, social support and empathy to strengthen the competence, social relatedness and autonomy patients experiences thus making them more prone for intrinsic motivation in order to actually change behavior. 16

18 General Introduction Thirdly, principles of the Goal Setting theory were embedded in the applied physical activity counseling program The central idea of this theory is that subjects are more motivated to achieve goals when five important criteria are met: 1. Goals need to be specific and clearly formulated, 2. Goals need to be challenging but achievable 3. The subject is committed to his/her goal to 4. The extent to which goals are public (others knowing of the goals) stimulates the subject to realize them 5. The extent to which reaching goals leads to a reward stimulates subjects to attain their goals. Challenging and achievable goals need to be explicitly formulated and have to be: specific, measurable, important to the subject, realistic and achievable, and have to be set in time, to be effective. During the counseling program, insight is given in current physical activity behavior by visually presenting steps per day of a complete week. Patients are asked how much they think they can increase their physical activity level, in what way they are planning to do so and when. This makes it possible to formulate explicit goals, which are discussed at the next appointment. Patients get feedback of their performance of the pedometer they wear and during the counseling appointments. At every appointment the results are presented visually and boundaries can be changed or goals can be adjusted. 1 Fourthly, principles of the Implementation Intention and Goal Attainment theory were applied in the physical activity counseling program. Implementation intentions are clear instructions ( if then plans ) that subjects use to decide whether it is effective to realize their goal. Specific cues, for example time of the day, can be used to fit the behavioral change into the daily routine. Implementation intentions support goal intentions which specify what goal is aspired, whereas implementation intentions specify when, where and how a goal is aspired. In reality only 53% of the intentions for healthy behavior are actually converted to healthy behavior. 66 The goals set in the counseling program are explicitly formulated in amount of physical activity, frequency and time of the day patients and can be seen as implementation intentions to achieve the long term goal of increasing physical activity level. Finally, principles of the Achievement Goal theory were used in the physical activity counseling program. 67,68 The Achievement Goal theory discriminates mastery goals and performance goals. Mastery goals aim at improving competences and are characterized by a strong intrinsic motivation, the use of adequate self regulating strategies ( if then plans ), persistent behavior, and a strong feeling of self-efficacy. Performance goals aim at appreciation and recognition of achieved performance, which is characterized by attention for extrinsic rewards such as recognition for success, performing and realizing plans for others and wanting to perform better than others. When performance goals are aspired failure is often attributed to external factors, such as lack of time, no cooperation from others or the goal being too complex, to protect self esteem. This phenomenon is called self-sabotaging or self-handicapping as subjects are looking for excuses to explain why they failed to reach their goal. Often these subjects set unrealistic goals. When patients use these self-sabotaging principles it is discussed what they can do themselves to overcome the barriers or what alternative ways there are to change physical activity behavior. 17

19 Chapter 1 Most of the above described behavioral theories are still analytical and theoretical but several behavior change techniques, such as self-monitoring, goal setting, problem solving and feedback techniques have been based on these theories and have been performed in practice. The Goal Setting theory might be effective, as a dose relation was shown in increased physical activity level with changes in goal setting, satisfaction, self-efficacy, commitment and intention, all consistent with the goal setting theory, in a successful workplace intervention. 69 Furthermore, it has been shown that education programs to enhance physical activity using any behavioral strategy elicit larger effect sizes in chronically ill patients than programs that do not incorporate such strategies. 70 A meta-analysis of interventions to increase physical activity in healthy adults showed similar results, although the effect size for physical activity was higher in chronically ill patients. 71 This meta-analysis also showed that face-to-face, individual and standardized interventions show higher effect sizes. 71 This evidence supports the importance and relevance of investigating the effectiveness of a physical activity counseling program in COPD patients. Design of the COACH study The current study, the COACH study, was designed to investigate the effect of a physical activity counseling program in COPD patients on physical activity level, quality of life and exercise capacity. Patients from all GOLD stages were included in a randomized controlled trial. Patients were recruited in three different settings: general practices, hospital outpatient clinics and a specialized PR centre. The intensive intervention period was 3 months in which 5 counseling sessions took place. After that there was a follow up period of 12 months in which three additional counseling sessions were scheduled, one of which was a phone call. A brief overview of the time schedule and counseling themes is shown in Figure 1 and Table 1. In the actual counseling sessions motivational interviewing techniques were used. Motivational interviewing is a non-directive interviewing technique using listening reflectively, asking open questions, summarizing, confirming and supporting. 72 Table 1 shows how the different themes of the counseling sessions were planned. Counseling T1 + C1 C2 C3 C4 T2 + C5 C6 T3 + C7 T4 + C8 Physician asks patient to participate Wk 1 Wk 3 Wk 6 Wk 9 3 months 6 months 9 months 15 months T1 T2 T3 T4 Usual Care T= test session C= counseling session Figure 1. overview of the COACH-study 18

20 General Introduction Table 1. Themes of counseling sessions Activation: three months Counseling 1 : motivation for physical activity Counseling 2 : personal activity goal: stage 1 Counseling 3 : shifting boundaries Counseling 4 : personal activity goal: stage 2 Counseling 5 : consolidation Consolidation: 12 months Counseling 6 (tel) : consolidation Counseling 7 : fight back when activity level is decreased Counseling 8 : evaluation of new activity level, adjust personal activity goals 1 Aims and outline of thesis This thesis will address a number of topics all related to physical activity and physical fitness in COPD patients as is shown in Figure 2. Environmental and biological variables might also influence physical activity but are not addressed in this thesis. Possible relationships between physical activity, physical fitness, psychological variables, PR and physical activity counseling are shown in the middle of the figure. The topics of investigation are represented by corresponding letters in the figure (a-e). Factors not discussed in this thesis Physical activity counseling Rehabilitation Interventions Environmental factors - physical - social Biological factors - heredity - age - gender b c Physical activity Psychological factors a d Physical fitness Factors interacting with physical activity and physical fitness in COPD Daily steps Daily physical activity HADS SRQ-E LIVAS ESWT 6MWD e Measurement Tools Topics adressed in thesis Other possible interactions not adressed in this thesis Figure 2. Analytical model of variables interacting with physical activity and fitness in COPD HADS: Hospital Anxiety and Depression Scale; SRQ-E: Self Regulation Questionnaire for exercise; LIVAS: Lichamelijke Vaardigheden schaal, Dutch version of the perceived Physical Ability Subscale; ESWT: Endurance shuttle walk test; 6MWD: six minute walking distance 19

21 Chapter 1 Below the aims of the thesis are described: Physical activity Chapters 2, 3 and 4 will focus on the results of the COACH study. In this study we aimed to investigate: a. The relationship between physical variables, psychological variables and daily physical activity. Direct as well as indirect relationships between those variables were studied cross-sectionally. (Chapter 2) b. The effects of the COACH intervention on physical activity, exercise capacity and quality of life in patients from general practices, outpatient clinics and a rehabilitation centre. (Chapter 3) c. The reasons for and predictors of drop-outs from our COACH study. (Chapter 4) Physical fitness Chapter 5 en 6 will focus on a specific outcome measure of physical fitness namely the ESWT. In these studies we aimed to investigate: d. Variables explaining the change in endurance exercise capacity in COPD patients, measured by the ESWT. Thereby gaining insight in whether there is a patient profile associated with improved exercise capacity after PR (Chapter 5) e. The clinically relevant change of the ESWT in a population of COPD patients with chronic respiratory failure. (Chapter 6) 20

22 General Introduction References WHO: Chronic Obstructive Pulmonary Disease. 3. Global Strategy for the Diagnosis, Management and prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2010;. 4. WHO: Chronic Obstructive Pulmonary Disease. 5. Watz H, Waschki B, Meyer T, Magnussen H. Physical activity in patients with COPD. Eur Respir J 2009; 33: WHO: Physical Activity. 7. Bouchard C SR. Physical activity, fitness, and health: International proceedings and consensus statement. 1994;. 8. WHO: Physical Activity. 9. Wen CP, Wai JP, Tsai MK, Yang YC, Cheng TY, Lee MC, et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 2011; 378: Tudor-Locke C, Hart TL, Washington TL. Expected values for pedometer-determined physical activity in older populations. Int J Behav Nutr Phys Act 2009; 6:59, Pitta F, Takaki MY, Oliveira NH, Sant anna TJ, Fontana AD, Kovelis D, et al. Relationship between pulmonary function and physical activity in daily life in patients with COPD. Respir Med 2008; 102: Moy ML, Matthess K, Stolzmann K, Reilly J, Garshick E. Free-living physical activity in COPD: assessment with accelerometer and activity checklist. J Rehabil Res Dev 2009; 46: McGlone S, Venn A, Walters EH, Wood-Baker R. Physical activity, spirometry and quality-of-life in chronic obstructive pulmonary disease. COPD 2006; 3: Camillo CA, Pitta F, Possani HV, Barbosa MV, Marques DS, Cavalheri V, et al. Heart rate variability and disease characteristics in patients with COPD. Lung 2008; 186: Waschki B, Spruit MA, Watz H, Albert PS, Shrikrishna D, Groenen M, et al. Physical activity monitoring in COPD: Compliance and associations with clinical characteristics in a multicenter study. Respir Med 2012; 106: Watz H, Waschki B, Boehme C, Claussen M, Meyer T, Magnussen H. Extrapulmonary effects of chronic obstructive pulmonary disease on physical activity: a cross-sectional study. Am J Respir Crit Care Med 2008; 177: Troosters T, Sciurba F, Battaglia S, Langer D, Valluri SR, Martino L, et al. Physical inactivity in patients with COPD, a controlled multi-center pilot-study. Respir Med 2010; 104: Schonhofer B, Ardes P, Geibel M, Kohler D, Jones PW. Evaluation of a movement detector to measure daily activity in patients with chronic lung disease. Eur Respir J 1997; 10: Tudor-Locke C, Washington TL, Hart TL. Expected values for steps/day in special populations. Prev Med 2009; 49: Arne M, Janson C, Janson S, Boman G, Lindqvist U, Berne C, et al. Physical activity and quality of life in subjects with chronic disease: chronic obstructive pulmonary disease compared with rheumatoid arthritis and diabetes mellitus. Scand J Prim Health Care 2009; 27: Pitta F, Troosters T, Spruit MA, Probst VS, Decramer M, Gosselink R. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 171:

23 Chapter Belza B, Steele BG, Hunziker J, Lakshminaryan S, Holt L, Buchner DM. Correlates of physical activity in chronic obstructive pulmonary disease. Nurs Res 2001; 50: Garcia-Rio F, Lores V, Mediano O, Rojo B, Hernanz A, Lopez-Collazo E, et al. Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation. Am J Respir Crit Care Med 2009; 180: Hernandes NA, Teixeira Dde C, Probst VS, Brunetto AF, Ramos EM, Pitta F. Profile of the level of physical activity in the daily lives of patients with COPD in Brazil. J Bras Pneumol 2009; 35: Lemmens KM, Nieboer AP, Huijsman R. Designing patient-related interventions in COPD care: empirical test of a theoretical model. Patient Educ Couns 2008; 72: Garcia-Aymerich J, Lange P, Benet M, Schnohr P, Anto JM. Regular physical activity reduces hospital admission and mortality in chronic obstructive pulmonary disease: a population based cohort study. Thorax 2006; 61: Esteban C, Quintana JM, Aburto M, Moraza J, Arostegui I, Espana PP, et al. The health, activity, dyspnea, obstruction, age, and hospitalization: prognostic score for stable COPD patients. Respir Med 2011; 105: Garcia-Rio F, Rojo B, Casitas R, Lores V, Madero R, Romero D, et al. Prognostic value of the objective measurement of daily physical activity in COPD patients. Chest 2012;. 29. Waschki B, Kirsten A, Holz O, Muller KC, Meyer T, Watz H, et al. Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. Chest 2011; 140: Bouten CV, Westerterp KR, Verduin M, Janssen JD. Assessment of energy expenditure for physical activity using a triaxial accelerometer. Med Sci Sports Exerc 1994; 26: Freedson PS, Melanson E, Sirard J. Calibration of the Computer Science and Applications, Inc. accelerometer. Med Sci Sports Exerc 1998; 30: MacNee W. Systemic inflammatory biomarkers and co-morbidities of chronic obstructive pulmonary disease. Ann Med 2013; 45: Montero-Fernandez N, Serra-Rexach JA. Role of exercise on sarcopenia in the elderly. Eur J Phys Rehabil Med 2013; 49: Robles PG, Mathur S, Janaudis-Fereira T, Dolmage TE, Goldstein RS, Brooks D. Measurement of peripheral muscle strength in individuals with chronic obstructive pulmonary disease: a systematic review. J Cardiopulm Rehabil Prev 2011; 31: Wasserman K, Hansen J, Sue D, Stringer W, Sietsema K, Sun X, et al. Principles of exercise testing and interpretation. 5th ed. : Wolters Kluwer Lippincott & Wilkins; Morgan M, Singh S. Practical Pulmonary Rehabilitation. 1997;. 37. O Donnell DE. Ventilatory limitations in chronic obstructive pulmonary disease. Med Sci Sports Exerc 2001; 33:S O Donnell DE, Laveneziana P. Dyspnea and activity limitation in COPD: mechanical factors. COPD 2007; 4: Singh SJ, Morgan MD, Hardman AE, Rowe C, Bardsley PA. Comparison of oxygen uptake during a conventional treadmill test and the shuttle walking test in chronic airflow limitation. Eur Respir J 1994; 7: Hill K, Dolmage TE, Woon L, Coutts D, Goldstein R, Brooks D. Comparing peak and submaximal cardiorespiratory responses during field walking tests with incremental cycle ergometry in COPD. Respirology 2012; 17:

24 General Introduction 41. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166: Oga T, Nishimura K, Tsukino M, Hajiro T, Ikeda A, Izumi T. The effects of oxitropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease. A comparison of three different exercise tests. Am J Respir Crit Care Med 2000; 161: Young P, Dewse M, Fergusson W, Kolbe J. Respiratory rehabilitation in chronic obstructive pulmonary disease: predictors of nonadherence. Eur Respir J 1999; 13: Goldstein RS, Gort EH, Stubbing D, Avendano MA, Guyatt GH. Randomised controlled trial of respiratory rehabilitation. Lancet 1994; 344: Ries AL, Kaplan RM, Myers R, Prewitt LM. Maintenance after pulmonary rehabilitation in chronic lung disease: a randomized trial. Am J Respir Crit Care Med 2003; 167: Puhan MA, Frey M, Buchi S, Schunemann HJ. The minimal important difference of the hospital anxiety and depression scale in patients with chronic obstructive pulmonary disease. Health Qual Life Outcomes 2008; 6: Holland AE, Hill CJ, Rasekaba T, Lee A, Naughton MT, McDonald CF. Updating the minimal important difference for six-minute walk distance in patients with chronic obstructive pulmonary disease. Arch Phys Med Rehabil 2010; 91: Puhan MA, Chandra D, Mosenifar Z, Ries A, Make B, Hansel NN, et al. The minimal important difference of exercise tests in severe COPD. Eur Respir J 2011; 37: Redelmeier DA, Guyatt GH, Goldstein RS. Assessing the minimal important difference in symptoms: a comparison of two techniques. J Clin Epidemiol 1996; 49: Revill SM, Morgan MD, Singh SJ, Williams J, Hardman AE. The endurance shuttle walk: a new field test for the assessment of endurance capacity in chronic obstructive pulmonary disease. Thorax 1999; 54: Brouillard C, Pepin V, Milot J, Lacasse Y, Maltais F. Endurance shuttle walking test: responsiveness to salmeterol in COPD. Eur Respir J 2008; 31: Eaton T, Young P, Nicol K, Kolbe J. The endurance shuttle walking test: a responsive measure in pulmonary rehabilitation for COPD patients. Chron Respir Dis 2006; 3: Spruit MA, Singh SJ, Garvey C, ZuWallack R, Nici L, Rochester C, et al. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med 2013; 188:e Lacasse Y, Martin S, Lasserson TJ, Goldstein RS. Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. A Cochrane systematic review. Eura Medicophys 2007; 43: Ochmann U, Jorres RA, Nowak D. Long-term efficacy of pulmonary rehabilitation: a state-of-the-art review. J Cardiopulm Rehabil Prev 2012; 32: Beauchamp MK, Evans R, Janaudis-Ferreira T, Goldstein RS, Brooks D. Systematic Review of Supervised Exercise Programs After Pulmonary Rehabilitation in Individuals With COPD. Chest 2013; 144: van Wetering CR, Hoogendoorn M, Mol SJ, Rutten-van Molken MP, Schols AM. Short- and long-term efficacy of a community-based COPD management programme in less advanced COPD: a randomised controlled trial. Thorax 2010; 65: de Blok BM, de Greef MH, ten Hacken NH, Sprenger SR, Postema K, Wempe JB. The effects of a lifestyle physical activity counseling program with feedback of a pedometer during pulmonary rehabilitation in patients with COPD: a pilot study. Patient Educ Couns 2006; 61:

25 Chapter ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166: Oga T, Nishimura K, Tsukino M, Hajiro T, Ikeda A, Izumi T. The effects of oxitropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease. A comparison of three different exercise tests. Am J Respir Crit Care Med 2000; 161: Young P, Dewse M, Fergusson W, Kolbe J. Respiratory rehabilitation in chronic obstructive pulmonary disease: predictors of nonadherence. Eur Respir J 1999; 13: Goldstein RS, Gort EH, Stubbing D, Avendano MA, Guyatt GH. Randomised controlled trial of respiratory rehabilitation. Lancet 1994; 344: Ries AL, Kaplan RM, Myers R, Prewitt LM. Maintenance after pulmonary rehabilitation in chronic lung disease: a randomized trial. Am J Respir Crit Care Med 2003; 167: Puhan MA, Frey M, Buchi S, Schunemann HJ. The minimal important difference of the hospital anxiety and depression scale in patients with chronic obstructive pulmonary disease. Health Qual Life Outcomes 2008; 6: Holland AE, Hill CJ, Rasekaba T, Lee A, Naughton MT, McDonald CF. Updating the minimal important difference for six-minute walk distance in patients with chronic obstructive pulmonary disease. Arch Phys Med Rehabil 2010; 91: Puhan MA, Chandra D, Mosenifar Z, Ries A, Make B, Hansel NN, et al. The minimal important difference of exercise tests in severe COPD. Eur Respir J 2011; 37: Redelmeier DA, Guyatt GH, Goldstein RS. Assessing the minimal important difference in symptoms: a comparison of two techniques. J Clin Epidemiol 1996; 49: Revill SM, Morgan MD, Singh SJ, Williams J, Hardman AE. The endurance shuttle walk: a new field test for the assessment of endurance capacity in chronic obstructive pulmonary disease. Thorax 1999; 54: Brouillard C, Pepin V, Milot J, Lacasse Y, Maltais F. Endurance shuttle walking test: responsiveness to salmeterol in COPD. Eur Respir J 2008; 31: Eaton T, Young P, Nicol K, Kolbe J. The endurance shuttle walking test: a responsive measure in pulmonary rehabilitation for COPD patients. Chron Respir Dis 2006; 3: Spruit MA, Singh SJ, Garvey C, ZuWallack R, Nici L, Rochester C, et al. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med 2013; 188:e Lacasse Y, Martin S, Lasserson TJ, Goldstein RS. Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. A Cochrane systematic review. Eura Medicophys 2007; 43: Ochmann U, Jorres RA, Nowak D. Long-term efficacy of pulmonary rehabilitation: a state-of-the-art review. J Cardiopulm Rehabil Prev 2012; 32: Beauchamp MK, Evans R, Janaudis-Ferreira T, Goldstein RS, Brooks D. Systematic Review of Supervised Exercise Programs After Pulmonary Rehabilitation in Individuals With COPD. Chest 2013; 144: van Wetering CR, Hoogendoorn M, Mol SJ, Rutten-van Molken MP, Schols AM. Short- and long-term efficacy of a community-based COPD management programme in less advanced COPD: a randomised controlled trial. Thorax 2010; 65: de Blok BM, de Greef MH, ten Hacken NH, Sprenger SR, Postema K, Wempe JB. The effects of a lifestyle physical activity counseling program with feedback of a pedometer during pulmonary rehabilitation in patients with COPD: a pilot study. Patient Educ Couns 2006; 61:

26 General Introduction 59. Hospes G, Bossenbroek L, Ten Hacken NH, van Hengel P, de Greef MH. Enhancement of daily physical activity increases physical fitness of outclinic COPD patients: results of an exercise counseling program. Patient Educ Couns 2009; 75: Hartman JE, ten Hacken NH, Boezen HM, de Greef MH. Self-efficacy for physical activity and insight into its benefits are modifiable factors associated with physical activity in people with COPD: a mixed-methods study. J Physiother 2013; 59: Prochaska O, Redding CA, Evers KE. The transtheoretical model and stages of change. In: Glanz K, Rimer BK, Lewis FM, editors. Health behaviour and health education: theory, research and practice. : Jossey-Bass, San Fransisco; p. 99, Deci EL RM. Intrinsic motivation and self-determination in human behavior. New York: Plenum Publishing Co.; Shalley CE. Effects of coaction, expected evaluation, and goal setting on creativity and productivity. Academy of Management Journal 1995; 38: Locke EA, Latham GP. Building a practically useful theory of goal setting and task motivation. A 35-year odyssey. Am Psychol 2002; 57: Locke EA, Latham GP, Smith KJ. A theory of goal setting & task performance. Englewood Cliffs, N.J.: Prentice Hall; Sheeran P. Intention-behavior relations: A conceptual and empirical review. In: Stroebe W, editor. European review of social psychology. : wiley, Chichester UK; p. 1, Gollwitzer P. The volitional benefit of planning. In: Gollwitzer P, Bargh J, editors. The psychology of action: Linking cognition and motivation to behavior. New York: Guilford; p. 287, Gollwitzer P. Goal achievement: The role of intentions. In: Stroebe W, Hewstone M, editors. European review of social psychology. New York, USA: Wiley; p. 141, Dishman RK, Vandenberg RJ, Motl RW, Wilson MG, DeJoy DM. Dose relations between goal setting, theory-based correlates of goal setting and increases in physical activity during a workplace trial. Health Educ Res 2010; 25: Conn VS, Hafdahl AR, Brown SA, Brown LM. Meta-analysis of patient education interventions to increase physical activity among chronically ill adults. Patient Educ Couns 2008; 70: Conn VS, Hafdahl AR, Mehr DR. Interventions to increase physical activity among healthy adults: metaanalysis of outcomes. Am J Public Health 2011; 101: Miller WR, Rollnick S. Motivational interviewing : preparing people to change addictive behavior. New York, NY etc.: The Guilford Press;

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28 CHAPTER 2 Functional and psychological variables both affect daily Physical physical activity in in COPD: A a structural equations model. Wytske A. A. Altenburg, Linda Linda Bossenbroek, Mathieu Mathieu H.G. de H.G. Greef, de Huib Greef, A.M. Huib Kerstjens, A.M. Kerstjens, Nick H.T. ten Nick Hacken, H.T. ten Johan Hacken, B. Wempe Johan B. Wempe Respiratory Medicine, 2013 Nov;107(11):1740-7

29 Chapter 2 Abstract Background: Daily physical activity (DPA) level is reduced in patients with COPD. The aim of this study was to investigate the association of DPA with functional and psychological variables in these patients. Methods: 155 COPD patients (102 males, median (IQR) age 62 years (54-69 years), predicted FEV 1 60% (40%-75%) were included. We assessed DPA (DigiWalker SW-200), functional capacity and psychological factors. Results: DPA level was significantly associated with all functional capacity variables and two psychological variables (Perceived Physical Ability Subscale, depression subscale of the Hospital Anxiety and Depression Scale). The six-minute walking distance and Saint George Respiratory Questionnaire activity score explained 37% of the variance of DPA in a regression analysis. A structural equations model revealed that psychological variables indirectly explained DPA through functional capacity variables. DPA was stronger associated with functional capacity variables and weaker with psychological variables in patients with lower functional status than in patients with higher functional status. Conclusions: Higher levels of DPA are associated with better functional capacity, but interestingly, DPA is also affected by psychological factors, though only indirectly, via functional capacity. The effect of specific treatment addressing psychological factors on DPA level and exercise tolerance needs further investigation. Clinical Trial Registration: ClinicalTrials.gov, NCT

30 Variables affecting physical activity in COPD Introduction Patients with COPD may enter a vicious circle of reduced lung function, activity-induced dyspnea, immobilization, muscle deconditioning and muscle fatigue. In addition, psychosocial consequences like depression and social isolation may appear ( This vicious circle may affect daily physical activity level (DPA) in COPD patients, assessed using accelerometers 1-6 and pedometers 7,8. Lower DPA level is related to lower FEV 1 1-3,7,8, VO 2 peak 1,4,5 and 6MWD 1-6. In addition, a very low DPA level was associated with a higher risk for all-cause and respiratory mortality The association of DPA with psychological variables such as anxiety, depression, self-efficacy and motivation has not been investigated extensively; depression was not associated with DPA level in two studies 6,13, whereas self-efficacy has been shown to correlate positively with DPA 3,14. In addition, DPA counseling has been shown to improve intrinsic motivation for physical activity. 15 We hypothesized that variables reflecting functional capacity as well as psychological variables influence DPA. In addition, we hypothesize that variables reflecting functional capacity affect DPA more in patients with a low functional status and psychological affect DPA more in patients with high functional status. To investigate this a broad group of COPD patients is included from the primary (general practitioner), secondary (hospital outpatient clinic) and tertiary (pulmonary rehabilitation centre) healthcare setting. 2 As we were interested in both direct and indirect relationships between DPA, functional and psychological variables, we performed, in contrast to previous studies 1-8, a path analysis using the structural equations modeling (SEM) technique, which allows estimation of direct and indirect associations of groups of variables. Methods Subjects Patients with stable COPD (n=155) from seven general practices, four hospital outpatient clinics and one pulmonary rehabilitation centre were included. These patients participated in a controlled study of a physical activity counseling program. Inclusion criteria were diagnosis of COPD according to the GOLD criteria 16 and age between 40 and 80 years. Exclusion criteria were significant comorbidities interfering with physical activity and exacerbation or respiratory tract infection in the past two months. All patients signed a written informed consent. The study was approved by the local medical ethics committee of the University Medical Center Groningen (METc2006/143) and registered in ClinicalTrials.gov: NCT Measurements Performance-based daily physical activity Performance-based DPA (steps/day) was measured with the Digiwalker SW-200 pedometer (Yamax; Tokyo, Japan), which is an accurate measurement tool to detect steps taken Patients were instructed to wear the pedometer during two weeks (from waking up until going to bed) and to record the number of steps per day in a diary. The mean of the last week of steps was used for further analyses. Data from this week were only used when more than 5 days of 7 were filled out. 29

31 Chapter 2 Physiological characteristics Weight, height and fat-free mass were measured, the latter by a bioelectrical impedance analysis (Bodystat 1500). 21 Functional Capacity Performance-based functional capacity was assessed by lung function using a spirometer (Jaeger MS-IOS) and bodyplethysmograph (Masterlab version 4.52i) according to standardized guidelines. 22 Reference values used were those of the European Community for Coal and Steel. 22 The six minute walking distance (6MWD) was used to assess functional exercise capacity and was performed in accordance with international standards. 23 Self-reported functional capacity was assessed by multiple questionnaires. Independent functioning in daily living was assessed by the Groningen Activity Restriction Scale (GARS). 24 Disease specific health-related quality of life was assessed by the St. George Respiratory Questionnaire (SGRQ). 25 The domains of this questionnaire containing items about functional capacity (activity and impacts scales) were selected for further analysis. Health status was assessed by the Short Form 36 (SF-36) (general) and Clinical COPD Questionnaire (CCQ) (disease specific). 26,27 The physical functioning scale (SF-36) and functional status scale (CCQ) were used for further analysis. Fatigue due to daily activities in household, body care and social activities were measured with the Dutch Exertion and Fatigue Scale (DEFS). 28 Psychological capacity Anxiety and depression were measured with the Hospital Anxiety and Depression Scale (HADS). 29 Self-efficacy was measured by the Perceived Physical Ability Subscale (PPAS) of the physical self-efficacy scale. 30 The level of intrinsic motivation for physical activity was measured using the Self-Regulation Questionnaire for Exercise (SRQ-E). This questionnaire deals with the reason why a person engages in physical activities and is based on the format of Ryan and Connell. 31 Statistical analysis Univariate and multivariate analysis Because of non-normal distribution of the primary outcome measure steps/day, Spearman s correlations of DPA with psychological and functional variables were calculated in the total group and in 2 subgroups based on functional status measured by the 6MWD (split by the median of 6MWD). Multiple linear regression models (method stepwise) were constructed including 1) all variables (functional and psychological) that correlated significantly with steps/day, and 2) only psychological variables (anxiety, depression, self-efficacy and motivation). These statistical analyses were performed using Scientific Package of Social Sciences (SPSS) version To test the null hypothesis alpha was set at Structural equations model A path analysis (LISREL 8.7) was used to test the hypothesized model, in which the direct effects of functional variables on DPA and simultaneously the indirect effects of psychological variables on DPA mediated through functional variables were estimated. In this model latent 30

32 Variables affecting physical activity in COPD constructs were conceptualized by DPA, functional capacity and psychological capacity. DPA was a latent construct estimated by taking the natural logarithm of steps/day. Indicators of the latent construct functional capacity were performance-based (FEV 1, 6MWD) and selfreported (GARS, SGRQ activity and impacts, SF36 physical functioning, CCQ functional and DEFS) functional capacity. The latent construct psychological capacity was indicated by HADS anxiety, HADS depression, SRQ-E and PPAS. Variables were chosen based on their significant correlation with DPA in the univariate analysis or because they were thought to be interesting from a theoretical point of view. Of the lung function variables only FEV 1 was used, and not RV%TLC because both variables were highly associated with each other, but FEV 1 had a higher correlation with DPA. To allow for mutual comparisons between path coefficients, the completely standardized solution was used. For model fit we used multiple criteria as suggested by Bentler and Bonett. 32 The first criterion used for model fit is a non-significant χ 2 indicating that a non-significant amount of variance in the data remains unexplained. However, a statistically significant χ 2 can often be produced as an artifact of sample size and of small variations in the data. 33 The second criterion is the ratio of χ 2 to the degree of freedom, a ratio ranging from 2 to 5 has been recommended as acceptable for good model fit. 34,35 The last criterion used is the root mean square error of approximation (RMSEA), which assesses how well the model approximates the data by determining the lack of fit of the model to the population covariance matrix, expressed as the discrepancy per degree of freedom. 36 An RMSEA with values of less than 0.05 indicates a good fit to the data although values up to 0.08 are acceptable as well. 36 However, values greater than 0.10 strongly suggest an unsatisfactory model fit

33 Chapter 2 Results Data from 155 patients with COPD from GOLD stage I (n=32), II (n=65), III (n=38) and IV (n=20) were used for all analyses. The median (IQR) DPA level for the total group was 4206 ( ) steps/day (Table 1). Baseline scores of the questionnaires are shown in Table 2. Table 1. Baseline characteristics (n=155) Clinical characteristics Age, y 62 (54-69) Gender, m/f 102/53 Healthcare setting, GP/outpatient cl./pr (n) 48/46/61 Medication (n) Short acting beta agonist 43 Short acting muscarinic antagonist 35 Long acting beta agonist 21 Long acting muscarinic antagonist 83 ICS 32 Combination (ICS + long acting beta agonist) 99 Pack years 33 (17-50) BMI, kg/m ( ) FFMI, kg/m ( ) FEV 1,% pred 60 (40-75) FEV 1 %FVC, % 45 (34-59) RV%TLC, % 47 (41-54) 6MWD, m 452 ( ) DPA, steps/day 4206 ( ) Values are presented as median (IQR) unless otherwise indicated. GP: general practice; PR: pulmonary rehabilitation; ICS: inhaled corticosteroids; FEV 1 : Forced Expiration Volume in 1 s; BMI: body mass index; 6MWD: six minute walking distance; DPA: daily physical activity Correlations Spearman s correlations for all variables with DPA are shown in Table 3. Correlations of functional variables with psychological variables are shown in the supplementary material (e-table 1). In general, patients with low functional status show weaker associations of DPA with psychological factors (anxiety, depression, self-efficacy; all rho s 0.20 and non-significant) and stronger associations of DPA with variables reflecting functional capacity (except SGRQ impacts all rho s >0.20, all p<0.05) (Table 4). 32

34 Variables affecting physical activity in COPD Table 2. Baseline questionnaire scores GARS total score 23 (18-33) SF 36 physical functioning 21 (16-26) SF 36 social functioning 8 (7-10) SF 36 physical role 6 (4-8) SF 36 emotional role 6 (5-6) SF 36 mental health 25 (21-27) SF 36 vitality 16 (13-18) SF36 pain 50 (44-60) SF 36 general health perception 13 (10-16) SF 36 health change 4 (3-4) CCQ symptoms 2.0 ( ) CCQ functional 1.3 ( ) CCQ mental 0.0 ( ) CCQ total 1.4 ( ) SGRQ symptoms 56 (36-70) SGRQ activity 59 (30-79) SGRQ impacts 26 (11-40) SGRQ total 40 (22-54) DEFS total score 3 (1-7) PPAS total score 30 (24-35) HADS anxiety 5 (3-8) HADS depression 4 (2-6) SRQ-E 10.1 ( ) Values are presented as median (IQR) GARS: Groningen Activity Restriction Scale; SF-36: Short Form 36; CCQ: Clinical COPD Questionnaire; SGRQ: St George Respiratory Questionnaire; DEFS: Dutch Exertion and Fatigue Scale; PPAS: Perceived Physical Ability Subscale of the Physical Self Efficacy Scale (Dutch version); HADS: Hospital Anxiety and Depression Scale; SRQ-E: Self Regulation Questionnaire for Exercise. 2 For patients with higher functional status associations of DPA with psychological variables are significant for self-efficacy and depression. In addition, in patients with higher functional status, less of the variables reflecting functional capacity are significantly associated with DPA than in patients with low functional status (only 6MWD, SGRQ activity, CCQ function and DEFS). 33

35 Chapter 2 Table 3. Spearman s correlations of DPA with functional and psychological variables DPA (steps/day) FEV 1, l ** RV%TLC, % ** 6MWD, m ** GARS total ** SF-36 physical functioning ** SGRQ activity ** SGRQ impacts ** CCQ functional ** DEFS ** PPAS ** HADS anxiety HADS depression * SRQ-E *. Correlation is significant at the 0.05 level (2-tailed). **. Correlation is significant at the 0.01 level (2-tailed). FEV 1 : Forced Expiration Volume in 1 s; DPA: daily physical activity; 6MWD: six minute walking distance; GARS: Groningen Activity Restriction Scale; SF-36: Short Form 36; SGRQ: St George Respiratory Questionnaire; CCQ: Clinical COPD Questionnaire; DEFS: Dutch Exertion and Fatigue Scale; PPAS: Perceived Physical Ability Subscale of the Physical Self Efficacy Scale (Dutch version); HADS: Hospital Anxiety and Depression Scale; SRQ-E: Self Regulation Questionnaire for Exercise. Regression analyses In the stepwise multiple linear regression model 6MWD and SGRQ activity were predictors of DPA (Table 5). The model explains 37% of the variance, in which psychological variables did not contribute significantly. To further assess the contribution of psychological factors on DPA we performed a stepwise multiple linear regression containing only the psychological variables (Table 6). This model explains 16% of the variance with only PPAS (self-efficacy) as a significant independent predicting variable. 34

36 Variables affecting physical activity in COPD Table 4. Correlations of DPA for low and high functional status separately Low functional status High functional status (6MWD< 452) (6MWD 452) DPA (steps/day) p DPA (steps/day) p FEV1 (l) MWD (m) < GARS total SF 36 physical function SGRQ activity SGRQ impacts CCQ function DEFS PPAS HADS anxiety HADS depression SRQ-E p-values<0.05 printed bold FEV1: Forced Expiration Volume in 1 s; DPA: daily physical activity; 6MWD: six minute walking distance; GARS: Groningen Activity Restriction Scale; SF-36: Short Form 36; SGRQ: St George Respiratory Questionnaire; CCQ: Clinical COPD Questionnaire; DEFS: Dutch Exertion and Fatigue Scale; PPAS: Perceived Physical Ability Subscale of the Physical Self Efficacy Scale (Dutch version); HADS: Hospital Anxiety and Depression Scale; SRQ-E: Self Regulation Questionnaire for Exercise Structural equations model Based on the results of the regression analyses we hypothesized that psychological variables might indirectly affect DPA by affecting variables reflecting functional capacity. Path coefficients (standardized regression coefficients) are shown in Figure 1 indicating a possible causal linkage between the latent variables psychological capacity and functional capacity (0.45) and between the latent variable functional capacity and steps/day (0.62). Analysis of the model fit shows a χ 2 = 161.8, (df=63); p<0.001 and RMSEA= The model shows a clear, but indirect, association between psychological variables and DPA. A model with a direct association of psychological capacity with DPA was tested as well, but this association was very low and not significant. The fit of the model meets the criteria of the relative normed χ 2 (χ 2 /df) of Wheaton et al. and the criteria of the RSMEA. 34,35 35

37 Chapter 2 Table 5. Resulting multiple regression model for explaining DPA from functional and psychological variables (method stepwise) Unstandardized Coefficients Standardized Coefficients B Std. Error Beta t Sig. (Constant) MWD (m) SGRQ activity R 2 =0.37, adjusted R 2 =0.36 6MWD: six minute walking distance; SGRQ: St George Respiratory Questionnaire Table 6. Resulting multiple regression model for explaining DPA from psychological variables (method stepwise) Unstandardized Coefficients Standardized Coefficients B Std. Error Beta t Sig. (Constant) PPAS <0.001 R 2 =0.16, adjusted R 2 =0.15 PPAS: Perceived Physical Ability Subscale of the Physical Self Efficacy Scale (Dutch version) 36

38 Variables affecting physical activity in COPD Self-reported Performance-based Fatigue (DEFS) Function (CCQ) Impacts (SGRQ) Activity (SGRQ ) Physical functioning (SF-36) Activity restriction (GARS) Exercise capacity (6MWD) Lung function (FEV1) Daily physical activity Functional capacity Psychological capacity Ln (steps/day) χ 2 : df:63 P< RMSEA:0.10 Motivation (SRQ-E ) Depression (HADS) Anxiety (HADS) Self-efficacy (PPAS) Figure 1. The path diagram shows the causal relationships (bold arrows) between the latent variables psychological capacity, functional capacity and DPA. The strength of this relationship is shown by the path coefficient (standardized regression coefficient). The relationship of the observed variables with the latent variables is specified by the correlation coefficient. FEV 1 : Forced Expiration Volume in 1 s; 6MWD: six minute walking distance; GARS: Groningen Activity Restriction Scale; SF-36: Short Form 36; SGRQ: St George Respiratory Questionnaire; CCQ: Clinical COPD Questionnaire; DEFS: Dutch Exertion and Fatigue Scale; PPAS: Perceived Physical Ability Subscale of the Physical Self Efficacy Scale (Dutch version); HADS: Hospital Anxiety and Depression Scale; SRQ-E: Self Regulation Questionnaire for Exercise. 2 37

39 Chapter 2 Discussion DPA level in our COPD population was low, with a median (IQR) of 4206 ( ) steps per day, which is considered to be sedentary. 38 In the univariate analysis, DPA was significantly associated with variables reflecting functional capacity (performance-based and self-reported), and with psychological variables (depression and self-efficacy). When subjects were divided in having lower or higher functional status, DPA in patients with a lower functional status showed significant associations with seven of the variables reflecting functional capacity (i.e. FEV 1, 6MWD, GARS total, SF-36 physical function, SGRQ activity, CCQ function and DEFS), whereas DPA in patients with a higher functional status showed significant associations with only four of these variables (i.e. 6MWD, SGRQ activity, CCQ function and DEFS). In addition, DPA in patients with a higher functional status was significantly associated with two psychological variables (i.e. self-efficacy and depression), which was not found in patients with low functional status.. Multivariate analysis showed only two significant variables, both reflecting functional capacity (6MWD and SGRQ activity) explaining 37% of the variance of DPA. However, the structural equations model (SEM) suggests that psychological variables indeed do contribute to DPA, but indirectly, through an effect on variables reflecting functional capacity. Functional capacity and daily physical activity The observed associations of DPA with variables reflecting functional capacity in the regression analyses and structural equations model are in line with other studies in COPD showing a relationship of higher DPA with higher FEV 1 1-3,7,8,14 higher general quality of life (SF-36) 3,6, and higher disease specific quality of life (SGRQ and CCQ) 4,8,14 The 6MWD, which explained the largest part of the variance in our multiple regression model, was also found to be a determining factor in three other studies. 1,3,4 We hypothesize that the relationship between functional capacity and DPA is reciprocal: better functional capacity indeed enables a higher DPA level, but on the other hand a higher DPA level will lead to better functional capacity. The relationship of DPA with variables reflecting functional capacity has also been demonstrated in other populations. For example, a moderate positive association of DPA with peak exercise VO 2 has been shown in healthy subjects 18, and in patients with diabetes mellitus 39. In patients with heart failure a higher 6MWD was associated with higher DPA level. 40 In our study, DPA was negatively associated with disability (GARS), which has to our knowledge not been reported before. In addition, fatigue (DEFS) was negatively associated with DPA, which has been found as well in one other study in COPD. 41 Fatigue is particularly interesting as it is increasingly recognized as an important outcome in COPD 42 and other populations, such as frail elderly 43. Fatigue may negatively affect DPA level, which leads to deconditioning and consequently contributes to the vicious circle of dyspnea and fatigue. Psychological capacity and daily physical activity The relationship of DPA with psychological factors in COPD is less clear than the relationship with variables reflecting functional capacity. In our study, having higher self-efficacy and less depressive symptoms were associated with higher DPA. However, self-efficacy and depressive symptoms were not independent determinants of DPA in a multiple regression model which also included variables reflecting functional capacity. Nevertheless, in a model that included only psychological variables, self-efficacy explained a considerable part of the total variance 38

40 Variables affecting physical activity in COPD (16%). This relationship of higher DPA with higher self-efficacy has been shown as well in two other studies in COPD. 3,14 Depressive symptoms, however, were not related to DPA in two earlier studies. 2,6 This difference in findings might be caused by the use of a different questionnaire (Beck Depression Index) 2 or lack of power in the second, small study 6. In other populations than COPD there is some evidence for a relationship of DPA with psychological variables. For instance, in healthy elderly 44,45 and in subjects at risk for diabetes 46 higher scores on self-efficacy were related to higher DPA levels. In addition, in subjects at risk for diabetes having less symptoms of anxiety and depression was also related to higher DPA levels. 46 Interaction of functional and psychological capacity Psychological variables affected DPA indirectly by influencing functional variables in our study, which is supported by several other studies in COPD. Cross-sectionally it has been shown in one study that a higher score on depressive symptoms is predictive for a lower walking distance (6MWD). 47 In addition, two longitudinal studies aiming at treatment of symptoms of depression and anxiety gave insight into the relationship between psychological factors and 6MWD. The first study demonstrated that cognitive behavioral therapy and education both improved levels of depression and anxiety and performance in 6MWD. 48 The second study compared pulmonary rehabilitation combined with psychotherapy to pulmonary rehabilitation alone. Both treatment arms improved walking distance, but it appeared that only pulmonary rehabilitation + psychotherapy improved scores of anxiety and depression. 49 In summary, the results suggest at least a close, but not clearly understood, relationship between psychological variables and variables reflecting functional capacity, which might be reciprocal. 2 A strong point in our study is the use of structural equations modeling (SEM), which provides a more extensive insight in the complex relationship of DPA with functional and psychological variables. In addition, the broad group of studied COPD patients warrants better validity than studies with more specific groups of patients did 3,8. Although the number of participants per subgroup (healthcare setting) seems limited we belief we selected sufficient patients from three different healthcare settings. We think that our results are therefore valid for patients as they are present in usual care. Moreover, our extensive set of instruments covered more aspects of related factors than earlier studies. There are some limitations. The patient group in this study was rather small to perform a path analysis, which might have caused the moderate fit of the model. 33 However, the values in the model are well interpretable and no negative error variance or associations >1 were shown, which indicates a fair causal model. Another limitation is that DPA was measured with a pedometer, which is less accurate than an accelerometer. The Yamax Digiwalker 200, however, has shown to be the most accurate pedometer at moderate to slow gate speed and only tended to underestimate the number of steps at very low gate speed. 50 Furthermore, pedometers are more accurate than questionnaires and diaries, less expensive and time consuming than double labeled water or direct observation, and easy to use, and therefore allow inclusion of a large cohort

41 Chapter 2 In conclusion, DPA levels in COPD are low. A better functional capacity is strongly and independently associated with higher levels of DPA. Psychological factors such as anxiety, depression and self-efficacy also affect DPA, but indirectly by an effect on functional capacity. Finally, the influence of psychological factors seems larger in patients with better functional capacity. There is a need for investigating whether treatment of psychological factors should be addressed when patients enroll in an exercise training or physical activity counseling program and whether the effects depend on functional capacity. 40

42 Variables affecting physical activity in COPD References 1. Pitta F, Troosters T, Spruit MA, Probst VS, Decramer M, Gosselink R. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 171: Watz H, Waschki B, Meyer T, Magnussen H. Physical activity in patients with COPD. Eur Respir J 2009; 33: Belza B, Steele BG, Hunziker J, Lakshminaryan S, Holt L, Buchner DM. Correlates of physical activity in chronic obstructive pulmonary disease. Nurs Res 2001; 50: Garcia-Rio F, Lores V, Mediano O, Rojo B, Hernanz A, Lopez-Collazo E, et al. Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation. Am J Respir Crit Care Med 2009; 180: Hernandes NA, Teixeira Dde C, Probst VS, Brunetto AF, Ramos EM, Pitta F. Profile of the level of physical activity in the daily lives of patients with COPD in Brazil. J Bras Pneumol 2009; 35: Moy ML, Matthess K, Stolzmann K, Reilly J, Garshick E. Free-living physical activity in COPD: assessment with accelerometer and activity checklist. J Rehabil Res Dev 2009; 46: Schonhofer B, Ardes P, Geibel M, Kohler D, Jones PW. Evaluation of a movement detector to measure daily activity in patients with chronic lung disease. Eur Respir J 1997; 10: McGlone S, Venn A, Walters EH, Wood-Baker R. Physical activity, spirometry and quality-of-life in chronic obstructive pulmonary disease. COPD 2006; 3: Garcia-Aymerich J, Lange P, Benet M, Schnohr P, Anto JM. Regular physical activity reduces hospital admission and mortality in chronic obstructive pulmonary disease: a population based cohort study. Thorax 2006; 61: Esteban C, Quintana JM, Aburto M, Moraza J, Arostegui I, Espana PP, et al. The health, activity, dyspnea, obstruction, age, and hospitalization: prognostic score for stable COPD patients. Respir Med 2011; 105: Garcia-Rio F, Rojo B, Casitas R, Lores V, Madero R, Romero D, et al. Prognostic value of the objective measurement of daily physical activity in COPD patients. Chest 2012;. 12. Waschki B, Kirsten A, Holz O, Muller KC, Meyer T, Watz H, et al. Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. Chest 2011; 140: Watz H, Waschki B, Boehme C, Claussen M, Meyer T, Magnussen H. Extrapulmonary effects of chronic obstructive pulmonary disease on physical activity: a cross-sectional study. Am J Respir Crit Care Med 2008; 177: Lemmens KM, Nieboer AP, Huijsman R. Designing patient-related interventions in COPD care: empirical test of a theoretical model. Patient Educ Couns 2008; 72: Hospes G, Bossenbroek L, Ten Hacken NH, van Hengel P, de Greef MH. Enhancement of daily physical activity increases physical fitness of outclinic COPD patients: results of an exercise counseling program. Patient Educ Couns 2009; 75:

43 Chapter Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007; 176: Crouter SE, Schneider PL, Karabulut M, Bassett DR,Jr. Validity of 10 electronic pedometers for measuring steps, distance, and energy cost. Med Sci Sports Exerc 2003; 35: Tudor-Locke C, Williams JE, Reis JP, Pluto D. Utility of pedometers for assessing physical activity: construct validity. Sports Med 2004; 34: Schneider PL, Crouter SE, Bassett DR. Pedometer measures of free-living physical activity: comparison of 13 models. Med Sci Sports Exerc 2004; 36: Schneider PL, Crouter SE, Lukajic O, Bassett DR,Jr. Accuracy and reliability of 10 pedometers for measuring steps over a 400-m walk. Med Sci Sports Exerc 2003; 35: Kyle UG, Genton L, Mentha G, Nicod L, Slosman DO, Pichard C. Reliable bioelectrical impedance analysis estimate of fat-free mass in liver, lung, and heart transplant patients. JPEN J Parenter Enteral Nutr 2001; 25: Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl 1993; 16: ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166: Kempen GI, Miedema I, Ormel J, Molenaar W. The assessment of disability with the Groningen Activity Restriction Scale. Conceptual framework and psychometric properties. Soc Sci Med 1996; 43: Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George s Respiratory Questionnaire. Am Rev Respir Dis 1992; 145: Ware JE,Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: van der Molen T, Willemse BW, Schokker S, ten Hacken NH, Postma DS, Juniper EF. Development, validity and responsiveness of the Clinical COPD Questionnaire. Health Qual Life Outcomes 2003; 1: Tiesinga LJ, Dassen TW, Halfens RJ. DUFS and DEFS: development, reliability and validity of the Dutch Fatigue Scale and the Dutch Exertion Fatigue Scale. Int J Nurs Stud 1998; 35: Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983; 67: Bosscher RJ, Laurijssen L, de Boer E. Measuring physical self-efficacy in old age. Percept Mot Skills 1993; 77: Ryan RM, Connell JP. Perceived locus of causality and internalization: examining reasons for acting in two domains. J Pers Soc Psychol 1989; 57: Bentler PM BD. Significance Tests and Goodness of Fit in the Analysis of Covariance-Structures. Psychological Bulletin 1980; 88:

44 Variables affecting physical activity in COPD 33. Hu LT BP. Structural Equation Modelling: Concepts, Issues and applications. In: Hoyle RH, editor. Evaluating Model Fit. Thousand Oaks, CA: Sage; p. 77, Tabachnick BG, Fidell LS. Using Multivariate Statistics. 5th ed. : Allyn and Bacon, New York; Wheaton B, Muthen B, Alwin DF, Summers G. Assessing Reliability and Stability in Panel Models. Sociological Methodology 1977; 8:84, Browne M. Alternative ways of assessing model fit. In: Bollen K, editor. Testing structural equation models. Newbury Park, CA: Sage; p. 136, Hu LT BP. Cutoff criteria for fit indexes in covariance structure analysis: conventional criteria versus new alternatives. Structural Equation Modeling 1999; 6:1, Tudor-Locke C, Hatano Y, Pangrazi RP, Kang M. Revisiting how many steps are enough?. Med Sci Sports Exerc 2008; 40:S Bjorgaas M, Vik JT, Saeterhaug A, Langlo L, Sakshaug T, Mohus RM, et al. Relationship between pedometer-registered activity, aerobic capacity and self-reported activity and fitness in patients with type 2 diabetes. Diabetes Obes Metab 2005; 7: Witham MD, Argo IS, Johnston DW, Struthers AD, McMurdo ME. Predictors of exercise capacity and everyday activity in older heart failure patients. Eur J Heart Fail 2006; 8: Waschki B, Spruit MA, Watz H, Albert PS, Shrikrishna D, Groenen M, et al. Physical activity monitoring in COPD: Compliance and associations with clinical characteristics in a multicenter study. Respir Med 2012; 106: Baltzan MA, Scott AS, Wolkove N, Bailes S, Bernard S, Bourbeau J, et al. Fatigue in COPD: prevalence and effect on outcomes in pulmonary rehabilitation. Chron Respir Dis 2011; 8: Theou O, Jones GR, Overend TJ, Kloseck M, Vandervoort AA. An exploration of the association between frailty and muscle fatigue. Appl Physiol Nutr Metab 2008; 33: Van Dyck D, Cardon G, Deforche B, Giles-Corti B, Sallis JF, Owen N, et al. Environmental and psychosocial correlates of accelerometer-assessed and self-reported physical activity in Belgian adults. Int J Behav Med 2011; 18: Pan SY, Cameron C, Desmeules M, Morrison H, Craig CL, Jiang X. Individual, social, environmental, and physical environmental correlates with physical activity among Canadians: a cross-sectional study. BMC Public Health 2009; 9: Delahanty LM, Conroy MB, Nathan DM, Diabetes Prevention Program Research Group. Psychological predictors of physical activity in the diabetes prevention program. J Am Diet Assoc 2006; 106: Spruit MA, Watkins ML, Edwards LD, Vestbo J, Calverley PM, Pinto-Plata V, et al. Determinants of poor 6-min walking distance in patients with COPD: the ECLIPSE cohort. Respir Med 2010; 104: Kunik ME, Veazey C, Cully JA, Souchek J, Graham DP, Hopko D, et al. COPD education and cognitive behavioral therapy group treatment for clinically significant symptoms of depression and anxiety in COPD patients: a randomized controlled trial. Psychol Med 2008; 38: de Godoy DV, de Godoy RF. A randomized controlled trial of the effect of psychotherapy on anxiety and depression in chronic obstructive pulmonary disease. Arch Phys Med Rehabil 2003; 84:

45 Chapter Bassett DR,Jr, Ainsworth BE, Leggett SR, Mathien CA, Main JA, Hunter DC, et al. Accuracy of five electronic pedometers for measuring distance walked. Med Sci Sports Exerc 1996; 28: Hartman JE, Boezen HM, de Greef MH, Bossenbroek L, ten Hacken NH. Consequences of physical inactivity in chronic obstructive pulmonary disease. Expert Rev Respir Med 2010; 4:

46 Variables affecting physical activity in COPD Supplementary Data e-table 1. Spearman s correlations of variables reflecting functional capacity and psychological capacity HADS depression DEFS PPAS HADS anxiety CCQ functional SGRQ impacts SF-36 SGRQ activity GARS total 6MWD (m) FEV 1 (l) 6MWD (m) ** GARS total ** ** SF-36 physical funct ** ** ** SGRQ activity ** ** ** ** SGRQ impacts ** ** ** ** ** CCQ functional ** ** ** ** ** ** DEFS ** ** ** ** ** ** ** PPAS ** ** ** ** ** ** ** ** HADS anxiety * * ** ** ** ** ** HADS depression * ** ** ** ** ** ** ** ** SRQ-E * * *p<0.05, ** p <0.01 FEV1: Forced Expiration Volume in 1 s; 6MWD: six minute walking distance; GARS: Groningen Activity Restriction Scale; SF-36: Short Form 36; SGRQ: St George Respiratory Questionnaire; CCQ: Clinical COPD Questionnaire; DEFS: Dutch Exertion and Fatigue Scale; PPAS: Perceived Physical Ability Subscale of the Physical Self Efficacy Scale (Dutch version); SRQ-E: Self Regulation Questionnaire for Exercise. 2 45

47

48 CHAPTER 3 Short- and long-term effects of a physical activity counseling program in COPD: a randomized controlled trial Wytske A. Altenburg, Nick H.T. ten Hacken, Linda Bossenbroek, Huib A.M. Kerstjens, Mathieu H.G. de Greef, Johan B. Wempe Respiratory Medicine, 2015 Jan;109(1):112-21

49 Chapter 3 Abstract Background: We were interested in the effects of a physical activity (PA) counseling program in three groups of COPD patients from general practice (primary care), outpatient clinic (secondary care) and pulmonary rehabilitation (PR). Methods: In this randomized controlled trial 155 COPD patients, 102 males, median (IQR) age 62 (54-69) y, FEV 1 predicted 60 (40-75) % were assigned to a 12-weeks physical activity counseling program or usual care. Physical activity (pedometer (Yamax SW200) and metabolic equivalents), exercise capacity (six-minute walking distance) and quality of life (Chronic Respiratory Questionnaire and Clinical COPD Questionnaire) were assessed at baseline, after three and 15 months. Results: A significant difference between the counseling and usual care group in daily steps (803 steps, p=0.001) and daily physical activity (2214 steps+equivalents, p=0.001)) from 0-3 months was found in the total group, as well as in the outpatient (1816 steps, 2616 steps+equivalents, both p=0.007) and PR (758 steps, 2151 steps+equivalents, both p=0.03) subgroups. From 0-15 months no differences were found in physical activity. However, when patients with baseline physical activity>10000 steps per day (n=8), who are already sufficiently active, were excluded, a significant long term effect of the counseling program on daily physical activity existed in the total group (p=0.02). Differences in exercise capacity and quality of life were found only from 0-3 months, in the outpatient subgroup. Conclusion: Our PA counseling program effectively enhances PA level in COPD patients after three months. Sedentary patients at baseline still benefit after 15 months. ClinicalTrials.gov: registration number NCT

50 Effects of a physical activity counseling program in COPD Introduction Patients with COPD in general show a less active lifestyle than healthy subjects 1-6 which is already present in mild disease. 7 Low physical activity levels are clinically relevant in COPD as they are associated with lower quality of life 3, more frequent hospitalizations and higher mortality. 8 A downward circle of dyspnea induced physical inactivity and deconditioning is thought to be responsible for developing psychosocial problems such as depression and social isolation. 9 Up to now, several strategies have been proposed to increase physical activity in COPD, such as exercise training alone or in combination with a self-management program. 10,11 An alternative strategy to improve physical activity levels might be to aim at enhancing lifestyle physical activity instead of focusing on exercise training. The intensity level of lifestyle physical activities, such as walking, gardening and housekeeping in general is moderate, which makes it attractive for patients with COPD with reduced ventilatory capacity, because vigorous intensity often causes feelings of dyspnea and muscle fatigue. In this respect lifestyle physical activity is well assessed using pedometers or more sophisticated activity monitors, which can even be used as an intervention tool for increasing daily physical activity, showing positive results at least in patients with diabetes type II Inspired by these studies, we developed a pedometer-based physical activity counseling program using cognitive behavioral strategies 16, aiming at enhancement and incorporation of physical activities of moderate intensity in daily life. The counseling program has been studied in two pilot studies in two different COPD populations, namely patients from the outpatient clinic 17 and a patients following PR 18, and suggested an increase in physical activity after 3 months in the counseling group compared to usual care. 3 Our hypothesis for the current study is that the counseling program will result in an increase in physical activity in COPD patients, in the short as well as long term. This hypothesis was tested in three groups of COPD patients: patients from general practices (primary care), outpatient clinics (secondary care), and patients following a PR program. In the last group, the counseling program was additional to the conventional pulmonary rehabilitation program. Methods Study design The study design was randomized and controlled, as patients were assigned to a physical activity counseling program or usual care. Randomization was computerized and patients were allocated to counseling or usual care group in a 1:1 ratio, with minimization for age (< 60/ 60 years), FEV 1 (< 50/ 50 % predicted) and sex (male/female). Allocation was open to the researcher, counselor and patient. Patients were recruited from general practices (primary care), outpatient hospital clinics (secondary care) and a pulmonary rehabilitation centre (PR), all in the Netherlands, from 2007 till The last follow-up measurement was performed in December The study was approved by the medical ethical committee of the University Medical Center Groningen and all participating patients signed a written informed consent form. The trial was registered with ClinicalTrials.gov: registration number NCT

51 Chapter 3 Subjects Inclusion criteria were COPD according to the GOLD Guidelines and age between years. Excluded were patients with comorbidities which severely limited physical activity, such as severe orthopedic or neurological disorders or heart failure or having exacerbations or respiratory tract infections within two months prior to the study. Intervention Patients in the counseling group participated in a 12-weeks customized lifestyle physical activity counseling program designed to enhance physical activity in COPD patients, which is described in more detail elsewhere. 17,18 Lifestyle physical activity in our study comprised all activities in daily life, including leisure time, occupational and household activity. Patients were free to choose type, time point and location of activity to enhance their physical activity level. Patients received the physical activity counseling program in addition to usual care. Two trained exercise counselors performed all counseling. The individual counseling was predominantly based on principles of goal-setting and implementation of goals 16 and motivational interviewing techniques were used. Patients wore a pedometer all day during the intervention period, which was used for feedback and motivation. A diary was kept with steps taken and activities other than steps (e.g. cycling, swimming etc.) were noted as well. Patients in the counseling group attended 5 individual 30 minutes counseling sessions spread over 3 months. Counseling took place in the setting where patients were recruited. The usual care group received care appropriate to their health status. For the PR group usual care included a multidisciplinary PR program, which consisted of 9 weeks of exercise training, 3 sessions a week, with a duration of 1-2 hours per session. Training forms used to achieve increased exercise capacity were cycling, walking, swimming and sports. In addition, patients followed educational courses and received psychological and/or nutritional support if necessary. Measurements All measurements took place prior to the intervention (baseline), at the end of the intervention (3 months after baseline) and 15 months after baseline. In the PR group baseline meant prior to the intervention and prior to PR, as the physical activity counseling started together with PR. Lung function and bio-impedance were measured at baseline and 15 months after baseline. Primary outcome measure Physical activity was assessed in all patients in daily steps using a pedometer (Digiwalker SW-2000, Yamax; Tokyo Japan) and in daily physical activity. 19 The Compendium of physical activities of Ainsworth et al. was used to calculate metabolic equivalents for cycling, (cardio) fitness and swimming. 20,21 A step equivalent is defined as the physical activity with the energy expenditure of one step. At each measurement point patients from the counseling as well as the usual care group wore a pedometer during two weeks, from waking up until going to bed, and recorded number of steps per day and other activities (minutes per day) in a diary. The mean of the last week of steps was used for further analysis. Data were only used when at least 5 days of 7 were filled out. Secondary outcome measures. Spirometry was performed according to standardized guidelines (Jaeger MS-IOS). Fat free mass was measured with bioelectrical impedance analysis (Bodystat 1500). 22 Patients performed 50

52 Effects of a physical activity counseling program in COPD a six-minute walking distance (6MWD) test to measure submaximal exercise capacity. 23 General health status was assessed by the Short Form 36 (SF-36) and disease specific health status by the Clinical COPD Questionnaire (CCQ) and the Chronic Respiratory Questionnaire (CRQ) Fatigue was assessed by the Dutch Exertion and Fatigue Scale (DEFS). 27 Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS). 28 Self-efficacy was assessed by the Perceived Physical Ability Subscale (PPAS, Dutch version) (10 items) of the physical self-efficacy scale. 29 Intrinsic motivation for physical activity was assessed by the Self Regulation Questionnaire for Exercise (SRQ-E). 30 Statistical analyses Characteristics are shown as median (IQR) due to non-normal distribution of outcome variables. Sample size calculations for this two-armed study were based on changes in steps found in one of our pilot studies using an increase of 2000 steps/day (SD 4017 steps/day). 17 To have a two-sided significance of p<0.05 at a power of β= patients were needed. To compensate for expected drop-out 20% extra patients were included. Because of nonnormality of data, differences between counseling and usual care group were tested with a Mann-Whitney U test for 0-3 months and 0-15 months for the total group and subsequently for the three healthcare settings separately. To assess the associations between the different outcome measures Spearman s correlations were calculated between change scores of daily steps, daily physical activity, 6MWD, CRQ and CCQ in the counseling group. All statistical analyses were performed using Scientific Package of Social Sciences (SPSS) version P-values <0.05 were considered to be significant. 3 51

53 Chapter 3 Results In total 173 patients were screened and 155 were randomized. A detailed flow diagram of the study is shown in Figure 1, including information on reasons of dropout. The dropout rate from the counseling group (29.9%) did not differ significantly from that in the usual care group (27.6%). Baseline characteristics of the total group and the three subgroups are shown in Table 1. Patients in the PR group were significantly younger, less physically active, had a higher RV%TLC, and had worse sum score on the CRQ than patients in the primary care or secondary care group. Additionally, all the groups differed from each other in FEV 1 % predicted, FEV 1 % FVC, 6MWD and CCQ sum score. Table 2 shows the characteristics of the counseling and usual care group at different measurement points. Assessed for eligibility (n=173) Randomized (n=155) Excluded Not meeting inclusion criteria (n=18) Allocated to physical activity counseling (n=78) Received allocated intervention (n=76) Not received allocated intervention (n=2) - counselor not available Allocated to usual care (n=77) Received allocated intervention (n=77) 3 months Retained: n=65 Lost: n=13 (died n=1, personal reasons n=3, lack of motivation, n=7) Analyzed: n=65 3 months Retained: n=64 Lost: n=13 (died n=1, medical reasons n=5, personal reasons n=2, lack of motivation n=5) Analyzed: n=55, missing data n=9 15 months Retained: n=55 Drop out: n=10 (died n=3, medical reasons n=4, lack of motivation n=3) Analyzed: n=49, missing data n=6 15 months Retained: n=54 Drop out: n=10 (medical reasons n=3, lack of motivation n=7) Analyzed: n=48, missing data n=6 Figure 1. Flow Diagram: Short- and long-term effects of a physical activity counseling program in COPD 52

54 Effects of a physical activity counseling program in COPD Table 1. Baseline characteristics Total Primary care Secondary care PR (n=155) (n=48) (n=46) (n=61) Age (y) 1 62 (54-69) 65 (58-72) 68 (61-72) 54 (50-63) Sex (m/f) 102/53 32/16 34/12 36/25 Pack years (y) 33 (17-50) 30 (14-47) 37 (16-49) 31 (18-54) FEV 1 (%pred) 2 60 (40-75) 78 (66-95) 58 (40-69) 43 (28-58) FEV 1 (l) ( ) 2.36 ( ) 1.56 ( ) 1.24 ( ) FEV 1 %FVC, % 3 45 (34-59) 59 (52-65) 43 (33-54) 37 (28-53) RV%TLC, % 1 47 (41-54) 42 (39-49) 48 (38-53) 51 (45-61) GOLD stage (I-IV) 2 32/65/38/20 22/23/3/0 7/23/15/1 3/19/20/19 3 BMI (kg/m 2 ) 25.8 ( ) 25.8 ( ) 24.8 ( ) 26.4 ( ) FFMI (kg/m 2 ) ( ) 17.8 ( ) 17.7 ( ) 17.2 ( ) 6MWD (m) ( ) 519 ( ) 454 ( ) 378 ( ) HADS anxiety 5.0 ( ) 4.0 ( ) 5.0 ( ) 5.0 ( ) HADS depression ( ) 3.0 ( ) 4.0 ( ) 5.0 ( ) CRQ (86-118) 117 ( ) 111 (99-123) 86 (78-102) CCQ ( ) 0.75 ( ) 1.35 ( ) 2.3 ( ) Daily steps, n ( ) 5735 ( ) 4371 ( ) 2979 ( ) Daily physical activity, n # 6444 ( ) 7431 ( ) 5561 ( ) 6238 ( ) Data presented as median (IQR).1) PR is significantly (p < 0.05) different from primary and secondary care, 2) All healthcare groups are significantly different from each other, 3) Primary care is significantly different from secondary care and PR, 4) Primary care and PR are significantly different from each other. FEV 1 : forced expiration volume in 1 second; FVC: Forced Vital Capacity; RV: Residual Volume; TLC: Total Lung Capacity; GOLD: Global Initiative for Chronic Obstructive Lung Disease; BMI: body mass index; FFMI: fat free mass index; 6MWD: six minute walking distance; HADS: Hospital Anxiety and Depression Scale; CCQ: Clinical COPD Questionnaire; CRQ: Chronic Respiratory Questionnaire. # steps + metabolic equivalents 53

55 Chapter 3 Table 2. Characteristics of experimental vs. usual care group on the three measurement points of the study Baseline (n=155) 3 months (n=120) 15 months (n=101) Total group Counseling (n=78) Usual care (n=77) Counseling (n=65) Usual care (n=55) Counseling (n=50) Usual care (n=51) Daily steps (n) 4292 ( ) 4132 ( ) 5751 ( ) 4257 ( ) 4683 ( ) 4255 ( ) Daily physical activity (n) * 6563 ( ) 6238 ( ) 8239 ( ) 5592 ( ) 7513 ( ) 5450 ( ) 6MWD (m) 454 ( ) 450 ( ) 484 ( ) 453 ( ) 506 ( ) 468 ( ) CRQ 102 (86-118) 109 (87-119) 114 (96-126) 112 (91-122) 114 (94-129) 113 (89-129) CCQ 1.40 ( ) 1.35 ( ) 1.00 ( ) 1.20 ( ) 1.10 ( ) 1.30 ( ) Primary care (n=24) (n=24) (n=22) (n=18) (n=20) (n=18) Daily steps (n) 5961 ( ) 4785 ( ) 6540 ( ) 4757 ( ) 5542 ( ) 3751 ( ) Daily physical activity (n) * 8043 ( ) 6202 ( ) 8857 ( ) 5328 ( ) 8419 ( ) 5203 ( ) 6MWD (m) 508 ( ) 519 ( ) 550 ( ) 527 ( ) 547 ( ) 540 (486) CRQ 118 ( ) 116 ( ) 131 ( ) 121 ( ) 125 ( ) 121 ( ) CCQ 0.80 ( ) 0.70 ( ) 0.40 ( ) 0.70 ( ) 0.50 ( ) 0.50 ( ) 54

56 Effects of a physical activity counseling program in COPD Secondary care (n=23) (n=23) (n=21) (n=22) (n=20) (n=19) Daily steps (n) 4820 ( ) 4285 ( ) 5751 ( ) 4221 ( ) 4657 ( ) 4383 ( ) Daily physical activity (n) * 5816 ( ) 5536 ( ) 8685 ( ) 5726 ( ) 7428 ( ( ) 6MWD (m) 457 ( ) 444 ( ) 480 ( ) 445 ( ) 482 ( ) 448 ( ) CRQ 107 ( ) 114 (88-124) 111 (94-121) 106 (78-117) 112 ( ) 117 (98-130) CCQ 1.40 ( ) 1.20 ( ) 1.50 ( ) 1.40 ( ) 1.20 ( ) 1.30 ( ) PR (n=31) (n=30) (n=22) (n=15) (n=10) (n=13) Daily steps (n) 2276 ( ) 3668 ( ) 4138 ( ) 3852 ( ) 2731 ( ) 4724 ( ) Daily physical activity (n) * 5110 ( ) 7371( ) 6423 ( ) 5389 ( ) 4545 ( ) 7239 ( ) 6MWD (m) 395 ( ) 351 ( ) 419 ( ) 379 ( ) 409 ( ) 449 ( ) CRQ 86 (77-98) 90 (77-109) 101 (92-116) 100 (89-117) 77 (62-93) 80 (70-98) CCQ 2.15 ( ) 2.30 ( ) 1.75 ( ) 1.80 ( ) 3.10 ( ) 2.30 ( ) PR: Pulmonary Rehabilitation; 6MWD: six minute walking distance; CRQ: Chronic Respiratory Questionnaire; CCQ: Clinical COPD Questionnaire. * steps + metabolic equivalents 3 55

57 Chapter 3 Effects of physical activity counseling program Primary outcomes The changes in daily steps and daily physical activity, from 0-3 months and 0-15 months are presented in Table 3 and Figure 2 and 3. Daily steps and daily physical activity significantly increased after 3 months in the counseling group compared to usual care; subgroup analysis showed significant changes in the secondary care and PR groups. After 15 months a trend for increased physical activity level (p=0.062) was found in the total group but not in the subgroups. Figure 2a-d. Change in daily steps throughout the total study period for: a) total group, b) primary care, c) secondary care, d) pulmonary rehabilitation. * indicating a significant difference between counseling and usual care 56

58 Effects of a physical activity counseling program in COPD 3 Figure 3a-d. Change in daily physical activity throughout the total study period for: a) total group, b) primary care, c) secondary care, d) pulmonary rehabilitation. * indicating a significant difference between counseling and usual care When we excluded patients with a baseline daily steps level >10000/day, who can be considered to be sufficiently active already, a significant long term difference in daily physical activity, between counseling and usual care in the total group could indeed be demonstrated (p=0.017). (online Table 1) Secondary outcomes Overall, no significant changes in secondary outcome variables were found except for the improvements in 6MWD (p=0.049) and CRQ sum score (p=0.006) after 3 months in the secondary care group. (online Table 2) There were no significant correlations between changes in physical activity (daily steps and daily physical activity) and changes in 6MWD, CRQ, CCQ, neither for the total group (see online Table 3), nor for the subgroups. 57

59 Chapter 3 Table 3. Changes in daily physical activity after 3 and after 15 months Daily steps Daily physical activity * Total group Counseling Usual care p Counseling Usual care p 0-3 months 618 ( ) -185 ( ) ( ) -754 ( ) months 218 ( ) -201 ( ) ( ) -685 ( ) Primary care 0-3 months 537 ( ) 431 ( ) ( ) 528 ( ) months 157 ( ) 48 ( ) ( ) -576 ( ) Secondary care 0-3 months 1002 ( ) -814 ( ) ( ) ( months 1128 ( ) -217 ( ) ( ) -718 ( ) PR 0-3 months 547 ( ) -211 ( ) ( ) -849 ( ) months -569 ( ) ( ) ( ) ( ) Values are presented as median (IQR), change expressed as percentage of the initial value, p-value <0.05 printed bold. *steps + metabolic equivalents 58

60 Effects of a physical activity counseling program in COPD Discussion This study demonstrates that the physical activity counseling program effectively increased daily step count and daily physical activity after 3 months compared to usual care. The median difference between counseling and usual care was 803 steps (13 % increase in the counseling group, 4% decrease in usual care), and 2214 step equivalents, (22% increase in the counseling group, 12 % decrease in usual care). A trend for increased daily physical activity after 15 months was found in the total group (p=0.062); when patients with a baseline daily steps level >10000/day, who can be considered to be sufficiently physically active already, were excluded, the long term effect of the counseling on daily physical activity was statistically significant indeed. No effect was shown on exercise capacity and quality of life except for the change in 6MWD and CRQ scores after 3 months in the secondary care group. This group benefitted most as it showed the largest improvements (1816 daily steps and 2616 steps + step equivalents). Dropout rates were rather high, but did not differ from dropout from usual care. Physical activity counseling studies have demonstrated positive results in other disease populations Content and duration of the interventions differed, which may explain differences in effectiveness. Fibromyalgia patients were stimulated to achieve 30 minutes of moderate-intensity activity per day and reported a decrease in perceived functional deficits and pain and an increase in physical activity after 12 weeks that could not be maintained after 6 and 12 months. 31 A pedometer-based telephone intervention of 6 weeks in cardiac patients resulted in an increase in physical activity, which was still present after 6 months. 35 It is generally acknowledged that behavioral change programs are more likely to succeed when the intervention period is longer than 6 months. The Stages of Change model suggests that a person, who tries to change behavior, should start and stay in the action phase for about six months before entering the maintenance phase. 36 Two recent studies with longer intervention periods indeed showed sustained effects. A home-based program of 11 months aimed at integrating physical activity into daily routine supported by telephone calls compared to regular supervised exercise training and a control group of sedentary older subjects. 33 The lifestyle intervention group in this study showed improvements in physical activity, functional performance and cardiorespiratory fitness, directly after the intervention which were maintained after 12 months. 33,34 A 24 weeks pedometer-based intervention in diabetes type 2 patients resulted in an increased activity pattern, which was maintained after one year. 32 In COPD a six months period of PR was necessary to increase physical activity, although three months of rehabilitation was sufficient to improve exercise capacity and quality of life. 37 This also suggests that longer intervention periods are needed to improve physical activity in COPD patients. 3 In our study, significant changes in physical activity level between counseling and usual care group were shown in the secondary care group, and the PR group, whereas no significant change was found in the primary care group. We suggest that this difference is caused by differences in severity of disease between these three groups. A number of behavioral change theories, like the Health Belief Model, the Self Determination Theory and the Goal Setting theory, suggest that individuals are only motivated to change behavior, when they fear health consequences of an unhealthy lifestyle or expect benefits of behavioral change Patients with less severe disease, such as those in the primary care group, suffer less from their disease 59

61 Chapter 3 and it may therefore be less likely that they change their activity pattern. In addition these patients generally had already higher baseline physical activity levels, leaving less room for improvement than in patients with more severe disease, indicating that interventions aiming at physical activity are probably more beneficial in patients with more severe disease. The effects of the physical activity counseling program on physical activity were not well maintained after 15 months, though a clear trend was shown (p=0.062) towards positive effects. In line with that, when excluding patients with a baseline step level > 10000, who can be considered as sufficiently active already, a significant long term change in the counseling group compared to usual care was found. Our suggestion for the PR group that improvements in exercise capacity and muscle function, induced by PR, could be maintained in presence of a more active lifestyle after PR, was not proven. Our interpretation of these findings is that patients in the PR group had more severe COPD, making them more frail and susceptible to exacerbations greatly influencing their physical activity level. The high number of drop-outs (45% from the counseling arm of the study) in the PR group supports this explanation, but also hinders firm conclusions. For the secondary care group long term results were somewhat better but not significant. Apparently, maintaining an active lifestyle is much more challenging than starting it. Our physical activity counseling program had only limited effect on secondary outcomes, like the improvement of 6MWD and CRQ score in the secondary care group after 3 months. This may off course be due to type 1 errors, as this study was powered to detect relevant change in steps and not in quality of life or exercise capacity. However some other explanations are possible. In the primary care setting this absence of effect may be due to a higher baseline physical activity level, CRQ sum score and 6MWD (95% of predicted) in these patients, which leaves not much room for improvement. On the other hand, in the PR group, both treatment arms received physical training and psychosocial education, which may have limited the additional benefits of our physical activity counseling program on exercise capacity and quality of life. In general, an increase in physical activity might not easily be translated into additional improvements in quality of life and exercise capacity, which is supported by the weak and non-significant correlations between both in our study. On the other hand, exercising on moderate intensity, the intensity of most lifestyle physical activity, for 15 min/day or 90 min/ week already reduces all cause mortality with 14% and increased life expectancy with 3 years in the general population. 41 Every additional increase of 15 minutes of physical activity beyond this minimum of 15 min/day further reduced all cause mortality by 4%. Thus, the relationships between physical activity on the one hand, and quality of life, physical fitness and mortality on the other hand are not fully elucidated and further studies in the general population as well as in COPD are definitely needed. Our study design has particular strengths and weaknesses. A strong point is that a broad range of COPD patients was included, with three well-defined subgroups, which enables generalization of outcomes. Another strong point is that not only short term but also long term effects of a physical activity counseling program in COPD were studied: the absence of significant long term effects emphasizes the need for developing interventions for maintenance of beneficial effects of counseling such as in the present study. And finally the tool for intervention and measurement of the primary outcome variable, physical activity, was the same namely the pedometer, which obtains actual values of walking, an important form of physical activity. 60

62 Effects of a physical activity counseling program in COPD Some limitations should be mentioned. Firstly, the pedometer we used does not measure nonambulatory physical activity like cycling or swimming. We chose to calculate step equivalents from activities that could not be measured by the pedometer and were noted in activity diaries in minutes/day. 20,42 Secondly, usual care was not the same for all subgroups, as patients in the PR group additionally received PR. As the power calculation was based on a pilot study in which counseling was the single treatment, the power for this study would theoretically be lower. Despite this we found a significant short term effect of the counseling on physical activity. For clinical practice the results of our study show that pedometer based counseling is a useful tool in the treatment of COPD patients in various settings. It can be used as a single treatment option in less severe COPD patients, but also be part of a regular PR program, adjunct to exercise training and other psychosocial interventions. We suggest that more feedback moments over a longer period could make the intervention more effective in the long term. It has been demonstrated that adherence counseling after PR leads to maintenance of increases of daily activity, exercise adherence and exercise capacity after 1 year. 43 Furthermore, we suggest that in primary care patients should be selected more specifically for having low baseline physical activity, low exercise capacity and/or high motivation for physical activity. In developing other physical activity counseling programs modern tools for real time feedback may be used, such as sound or visual signals from a pedometer, accelerometer or smartphone. The feasibility of using an accelerometer and pedometer integrated into a mobile phone to support exercise training and physical activity has already been investigated in cardiac patients and the effects will be further investigated in a randomized controlled trial In conclusion, our study shows that a 12 weeks physical activity counseling program enhances physical activity level in COPD patients in the short term, which is maintained at 15 months in patients with baseline daily step count <10000 steps per day. The effects were most prominent in patients attending the outpatient clinic. Physical activity counseling might be used in various healthcare settings. 61

63 Chapter 3 References 1. Pita F, Troosters T, Spruit MA, Probst VS, Decramer M, Gosselink R. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 171: Schonhofer B, Ardes P, Geibel M, Kohler D, Jones PW. Evaluation of a movement detector to measure daily activity in patients with chronic lung disease. Eur Respir J 1997; 10: McGlone S, Venn A, Walters EH, Wood-Baker R. Physical activity, spirometry and quality-of-life in chronic obstructive pulmonary disease. COPD 2006; 3: Waschki B, Spruit MA, Watz H, Albert PS, Shrikrishna D, Groenen M, et al. Physical activity monitoring in COPD: Compliance and associations with clinical characteristics in a multicenter study. Respir Med 2012; 106: Shrikrishna D, Patel M, Tanner RJ, Seymour JM, Connolly BA, Puthucheary ZA, et al. Quadriceps wasting and physical inactivity in patients with COPD. Eur Respir J 2012; 40: Sandland CJ, Singh SJ, Curcio A, Jones PM, Morgan MD. A profile of daily activity in chronic obstructive pulmonary disease. J Cardiopulm Rehabil 2005; 25: Watz H, Waschki B, Meyer T, Magnussen H. Physical activity in patients with COPD. Eur Respir J 2009; 33: Garcia-Rio F, Rojo B, Casitas R, Lores V, Madero R, Romero D, et al. Prognostic value of the objective measurement of daily physical activity in COPD patients. Chest 2012;. 9. Global Strategy for the Diagnosis, Management and prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2010;. 10. Cindy Ng LW, Mackney J, Jenkins S, Hill K. Does exercise training change physical activity in people with COPD? A systematic review and meta-analysis. Chron Respir Dis 2012; 9: Effing T, Zielhuis G, Kerstjens H, van der Valk P, van der Palen J. Community based physiotherapeutic exercise in COPD self-management: a randomised controlled trial. Respir Med 2011; 105: Bravata DM, Smith-Spangler C, Sundaram V, Gienger AL, Lin N, Lewis R, et al. Using pedometers to increase physical activity and improve health: a systematic review. JAMA 2007; 298: Pitta F, Troosters T, Probst VS, Lucas S, Decramer M, Gosselink R. Potential consequences for stable chronic obstructive pulmonary disease patients who do not get the recommended minimum daily amount of physical activity. J Bras Pneumol 2006; 32: Pitta F, Troosters T, Probst VS, Spruit MA, Decramer M, Gosselink R. Quantifying physical activity in daily life with questionnaires and motion sensors in COPD. Eur Respir J 2006; 27: Vaes AW, Cheung A, Atakhorrami M, Groenen MT, Amft O, Franssen FM, et al. Effect of activity monitorbased counseling on physical activity and health-related outcomes in patients with chronic diseases: A systematic review and meta-analysis. Ann Med 2013; 45: Locke EA, Latham GP, Smith KJ. A theory of goal setting & task performance. Englewood Cliffs, N.J.: Prentice Hall; Hospes G, Bossenbroek L, Ten Hacken NH, van Hengel P, de Greef MH. Enhancement of daily physical 62

64 Effects of a physical activity counseling program in COPD activity increases physical fitness of outclinic COPD patients: results of an exercise counseling program. Patient Educ Couns 2009; 75: de Blok BM, de Greef MH, ten Hacken NH, Sprenger SR, Postema K, Wempe JB. The effects of a lifestyle physical activity counseling program with feedback of a pedometer during pulmonary rehabilitation in patients with COPD: a pilot study. Patient Educ Couns 2006; 61: Schneider PL, Crouter SE, Bassett DR. Pedometer measures of free-living physical activity: comparison of 13 models. Med Sci Sports Exerc 2004; 36: Ainsworth BE, Haskell WL, Leon AS, Jacobs DR,Jr, Montoye HJ, Sallis JF, et al. Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc 1993; 25: Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ, et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 2000; 32:S Kyle UG, Genton L, Mentha G, Nicod L, Slosman DO, Pichard C. Reliable bioelectrical impedance analysis estimate of fat-free mass in liver, lung, and heart transplant patients. JPEN J Parenter Enteral Nutr 2001; 25: ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166: van der Molen T, Willemse BW, Schokker S, ten Hacken NH, Postma DS, Juniper EF. Development, validity and responsiveness of the Clinical COPD Questionnaire. Health Qual Life Outcomes 2003; 1: Ware JE,Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: Guyatt GH, Berman LB, Townsend M, Pugsley SO, Chambers LW. A measure of quality of life for clinical trials in chronic lung disease. Thorax 1987; 42: Tiesinga LJ, Dassen TW, Halfens RJ. DUFS and DEFS: development, reliability and validity of the Dutch Fatigue Scale and the Dutch Exertion Fatigue Scale. Int J Nurs Stud 1998; 35: Snaith RP, Zigmond AS. The hospital anxiety and depression scale. Br Med J (Clin Res Ed) 1986; 292: Bosscher RJ, Laurijssen L, de Boer E. Measuring physical self-efficacy in old age. Percept Mot Skills 1993; 77: Ryan RM, Connell JP. Perceived locus of causality and internalization: examining reasons for acting in two domains. J Pers Soc Psychol 1989; 57: Fontaine KR, Conn L, Clauw DJ. Effects of lifestyle physical activity in adults with fibromyalgia: results at follow-up. J Clin Rheumatol 2011; 17: De Greef KP, Deforche BI, Ruige JB, Bouckaert JJ, Tudor-Locke CE, Kaufman JM, et al. The effects of a pedometer-based behavioral modification program with telephone support on physical activity and sedentary behavior in type 2 diabetes patients. Patient Educ Couns 2011; 84: Opdenacker J, Boen F, Coorevits N, Delecluse C. Effectiveness of a lifestyle intervention and a structured exercise intervention in older adults. Prev Med 2008; 46: Opdenacker J, Delecluse C, Boen F. A 2-year follow-up of a lifestyle physical activity versus a structured exercise intervention in older adults. J Am Geriatr Soc 2011; 59:

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66 Effects of a physical activity counseling program in COPD Supplementary Data online Table 1. Changes in daily physical activity after 3 and after 15 months without patients with > steps at baseline Daily steps Daily physical activity * Total group Counseling Usual care p Counseling Usual care p 0-3 months 676 ( ) -3 ( ) ( ) -601 ( ) months 255 ( ) 0 ( ) ( ) -644 ( ) Primary care 0-3 months 675 (4-1853) 342 ( ) ( ) 519 ( ) months 201( ) 38 ( ) ( ) -726 ( ) 0.06 Secondary care 0-3 months 1289 ( ) 34 ( ) ( ) -925 ( ) months 1436 ( ) 0 ( ) ( ) -526 ( ) PR 0-3 months 547 ( ) -198 ( ) ( ) -843 ( ) months -569 ( ) -759 ( ) ( ) -644 ( ) 0.91 Values are presented as median (IQR), change expressed as percentage of the initial value, p-value <0.05 printed bold. *steps + metabolic equivalents 3 65

67 Chapter 3 online Table 2. Changes in exercise capacity and quality of life after 3 and after 15 months 6MWD change CRQ change CCQ change Total group Counseling Usual care p Counseling Usual care p counseling usual care p 0-3 months 19.5 ( ) 6.0 ( ) (-2-15) 2 (-7-14) ( ) 0.00 ( ) months 22.8 ( ) 11.2 ( ) (-6-10) 2 (-5-12) ( ) 0.05 ( ) Primary care 0-3 months 10 ( ) 3.2 ( ) (-3-7) 5 ( ) ( ) ( ) months 20.3 ( ) 12.5 ( ) (-3-14) 13 (-1-15) ( ) ( ) Secondary care 0-3 months 23 (0-50.9) 3.5 ( ) (-6-11) -9 (-14--1) ( ) 0.10 ( ) months 24.7 (4-52.0) 16.8 ( ) (-4-10) 1 (-9-11) ( ) 0.20 ( ) PR 0-3 months 17.2 ( ) 24.5 ( ) (3-20) 8 (2-21) ( ) ( ) months 6.8 ( ) 9.7 ( ) (-16-1) -5 (-14-2) ( ) 0.30 ( ) Values are presented as median (IQR), p-value <0.05 printed bold. PR: Pulmonary Rehabilitation; 6MWD: six-minute walking distance; CRQ: Chronic Respiratory Questionnaire; CCQ: clinical COPD Questionnaire 66

68 Effects of a physical activity counseling program in COPD online Table 3. Spearman s correlations of change in daily steps and daily physical activity with change in 6MWD, CRQ, CCQ spearman s rho 6MWD p CRQ p CCQ p % 6MWD p % CRQ p % CCQ p daily steps daily physical activity * % daily steps % daily physical activity * MWD: six minute walking distance; CRQ: Chronic Respiratory Questionnaire; CCQ: Clinical COPD Questionnaire. * steps + metabolic equivalents 3 67

69

70 CHAPTER 4 Dropout from a physical activity counseling program in COPD: results from a a randomized controlled trial in three healthcare settings Wytske A. Altenburg, Linda Bossenbroek, Johan B. B. Wempe, Wim Wim P. Krijnen, P. Huib Huib A.M. A.M. Kerstjens, Kerstjens, Mathieu Mathieu H.G. de H.G. Greef, de Greef, Nick H.T. Nick ten H.T. Hacken ten Hacken Submitted

71 Chapter 4 Abstract Objective: Dropout frequently occurs in programs aiming at enhancing physical activity in chronic disorders. We investigated predictors of dropout in COPD patients participating in a physical activity program. Methods: Data from a randomized controlled trial on the effects of physical activity counseling was used retrospectively. 155 COPD patients were randomly assigned to either physical activity counseling (n=78) or usual care (n=77). Completers and dropouts were compared between 0-3 months and 3-15 months. Predictors of dropout between 0-3 months and 3-15 months were identified by logistic regression. Results: Total dropout rate was 29.7%. Between 0-3 months low motivation for physical activity and low mental status predicted dropout from counseling, whereas low motivation for physical activity predicted dropout from usual care. Between 3-15 months FEV 1 predicted dropout from counseling, whereas lower functional status predicted dropout from usual care. Conclusion: Short-term dropout was characterized particularly by motivational and psychological factors, whereas in long term this was related to diseases status (FEV 1, functional status). Healthcare practitioners might pay more attention to patients beliefs about and attitudes towards physical activity and healthy lifestyle, as well as to their physical capabilities before they start participating in a program. Trial Registration: ClinicalTrials.gov: NCT

72 Dropout from a physical activity counseling program in COPD Introduction In chronic obstructive pulmonary disease (COPD) low exercise capacity and low physical activity level are well-known problems. Patients enter a downward spiral of dyspnea, avoidance of physical activity and deconditioning. Importantly, decreased daily physical activity is already present in the early stages of disease. 1 These are important findings as regular physical activity has important benefits for everyday life. High daily physical activity level is associated with higher quality of life in COPD patients, and of note, so is increasing daily physical activity levels over time. 2 Therefore, there is a strong argument for enhancing physical activity in patients with COPD. 3 Different treatment strategies can be used to enhance physical activity level and exercise capacity. Recently, physical activity counseling programs have received more attention as a new way to enhance physical activity level in individuals with COPD. Physical activity counseling is, in contrast to pulmonary rehabilitation, accessible for a broad group of COPD patients. In healthy adults 4 and older adults with, or at higher risk for, cardiovascular disease 5 programs that include a behavioral treatment component, like physical activity counseling, have been shown to be more effective in promoting adherence than exercise training alone. Additionally, in sedentary subjects and obese women effects on physical activity and cardio respiratory fitness were found to be comparable with interventions using lifestyle physical activity enhancement and structured exercise. 6,7 Unfortunately, despite the use of cognitive behavioral treatment components in physical activity enhancement programs, studies have shown that subjects who participated in physical activity counseling programs may frequently drop out Reasons for dropping out from lifestyle physical activity counseling programs have been reported in different populations such as workers at risk for cardiovascular disease 11 and elderly with, or at risk for, cardiovascular disease 5. In elderly primary care patients, smoking was a significant predictor of non-adherence to a lifestyle physical activity program. 12 In addition, workers with cardiovascular disease participating in a lifestyle physical activity counseling program were also more likely to drop out if they smoked or were younger. 11 In a 3-month intervention study, stable COPD patients participating in a physical activity counseling program in a hospital outpatient clinic had a dropout rate of 10%, whereas those participating in a similar program in a pulmonary rehabilitation centre had a dropout rate of 24%. 13,14 Reasons for and predictive variables of dropout were not reported in these studies. The randomized controlled trial on physical activity counseling in COPD, from which data are used for the current analysis, was predominantly based on the goal-setting theory and selfdetermination theory. 15,16 Motivational interviewing techniques were used by the counselor, who together with the patient formulated achievable physical activity objectives. 17 This might prevent patients from dropping out because low adherence and dropout are likely to be more common when the aims of patients and the goals of the program differ. 18 Having a step goal and getting feedback in realizing this goal are considered to be the key predictors of increased physical activity in programs using a pedometer to enhance physical activity. 19 Despite the presence of these components in our physical activity counseling program, the dropout rate was considerable. Therefore it is of great interest to identify characteristics associated with 71

73 Chapter 4 dropout or successful completion of this program. Knowing the reasons for and predictors of dropout could help in identifying and supporting subjects at high risk for dropout. Therefore, we examined short- and long-term predictors of and reasons for dropout in COPD patients from our physical activity counseling program. In addition, predictors of dropout from the usual care group, who only attended measurement sessions, were examined as well, to investigate whether dropout predictors differed between participating in a counseling program or only participating in a control group. Methods Study design This study used data from a randomized controlled trial in which a 12-week physical activity counseling program was compared to usual care. 155 COPD patients were included and for each healthcare setting (general practice, outpatient clinic, pulmonary rehabilitation) patients were randomly assigned to experimental (counseling) or control (usual care) group. Randomization was computerized using minimization 20 for age (<60/ 60 years), forced expiration volume in one second (FEV 1 ; <50%/ 50 %, predicted) and sex (male/female). Allocation was open to the researcher, counselor and patient. Measurements were conducted prior to the intervention (baseline), at the end of the intervention (3 months) and after 15 months. Dropout predictors and reasons were assessed between 0-3 months (short-term) and 3-15 months (long-term). The local medical ethical committee of the University Medical Centre Groningen approved the study. Data were collected from The study was registered in ClinicalTrials.gov: NCT Participants Patients were recruited from general practices, outpatient hospital clinics and a pulmonary rehabilitation centre. Inclusion criteria were COPD diagnosis according to the Global Initiative for Chronic Obstructive Lung Disease Guidelines 21 and age between years. Exclusion criteria were comorbidities that severely limit physical activity and exacerbations or respiratory tract infections within the last two months. Patients were excluded when the pedometer did not count accurately, which was tested by checking the step count after taking 20 steps. Subjects had not been previously exposed to physical activity counseling. Patients who previously completed pulmonary rehabilitation were not excluded. All participating subjects signed a written informed consent form. Intervention The physical activity counseling group participated in a 12-week customized physical activity counseling program designed to enhance physical activity in COPD patients. 14 The physical activity counseling program was performed in addition to usual care, which for patients from the pulmonary rehabilitation setting was a multidisciplinary pulmonary rehabilitation program. The individual counseling was provided by a trained exercise counselor and was predominantly based on the principles of goal setting and implementation of goals. 15 The motivational interviewing technique was used as a counseling technique. 17 Patients in the counseling group attended five individual 30-minute counseling sessions spread over the first three months of the study. Counseling and usual care took place in the care setting where patients were recruited. A pedometer, worn all day during the intervention period, was used 72

74 Dropout from a physical activity counseling program in COPD for feedback and motivation. Patients kept a diary logging their steps and other activities (e.g. cycling, swimming). The usual care groups received care appropriate for their health status. For patients participating in the pulmonary rehabilitation centre, the pulmonary rehabilitation program consisted of 9 weeks of exercise training, 3 sessions a week, with duration of 1-2 hours per session. Training forms used to achieve increased exercise capacity were cycling, walking, swimming and sports. Patients in the counseling and the usual care group participated in three test sessions. In the counseling group the first and second measurement session, in which questionnaires were filled out and physical fitness was tested, were combined with the first and the fifth counseling session. Measurements Measurements were done prior to the intervention (baseline), at the end of the intervention (3 months) and after 15 months. Lung function and bio-impedance measurement, were assessed at baseline and after 15 months. The current study focused on predictors of and reasons for dropout from the physical activity counseling study. Only baseline measurements and data concerning reasons for dropout during the study were used. Clinical assessments Daily physical activity level was measured in steps per day using a pedometer (Digiwalker SW-200, Yamax; Tokyo Japan) and included step equivalents (using metabolic equivalents for cycling, conditioning exercise and swimming) Spirometry was performed according to standardized guidelines (Jaeger MS-IOS). 25 Patients performed a six-minute walking distance test according to international standards. 26 The chair stand test and arm curl test were used to measure muscle function. 27 For the 30-second chair stand test individuals are required to stand up from a standard chair (~ 43cm) to fully extended position as many times as possible with their arms folded across their chest. The number of repetitions achieved in 30 seconds is recorded. For the arm curl test individuals are required to make as many arm curls as possible in 30 seconds lifting a weight (2kg for women, 3kg for men). The individual was requested to turn the palm of the hand upwards while curling the arm through full range of motion and then return to full extension. The upper arm is maintained still against the body during the test. 4 Questionnaires Health status was measured with the Clinical COPD Questionnaire (CCQ) and Medical Outcomes Study (MOS) 36-item short form health survey (SF-36, Dutch version). 28,29 The Clinical COPD Questionnaire measures disease-specific health status and contains 10 items, with a sevenpoint Likert scale, evaluating symptoms, functional status and mental health. 28 A higher score indicates a lower health status. The Short Form-36 measures nine different general health components: physical functioning, social functioning, physical problems, emotional problems, mental health, vitality, bodily pain, general health perception and change in health status. 29 A higher score indicates a higher health status. Fatigue was measured with the Dutch Exertion and Fatigue Scale (DEFS) 30 which contains nine questions to be answered on a five-point Likert scale ranging from 0 (no) to 4 (yes). A higher score indicates a higher level of fatigue. Anxiety and depression were measured with the Hospital Anxiety and Depression Scale (HADS) which is a 14-item self-report screening scale. 31 It contains two seven-item scales: one for anxiety and one for depression both with a score range of A score <8 is considered 73

75 Chapter 4 to be normal, while a score 8 reflects psychological disturbances. Self-efficacy was measured with the Dutch version of the Perceived Physical Ability Subscale Questionnaire of the physical self-efficacy scale. 32 This questionnaire consists of 10 statements about physical fitness with five possible answers ranging from 0 (completely agree with) to 5 (completely disagree with). 32 A higher score indicates a higher self efficacy for physical activity. Intrinsic motivation for physical activity was measured with the Self Regulation Questionnaire for Exercise (SRQ-E). 33 This questionnaire deals with the reason why a person engages in physical activities and is based on the format of Ryan and Conell. 33 The responses represent external regulation, introjected regulation, identified regulation and intrinsic motivation. Reasons for dropout Reasons for dropout from the physical activity counseling study were divided into four categories: death, lack of motivation (e.g. not willing to come to follow-up appointment, refusing to be more physically active), medical reasons (COPD-related or other physical problems, medical conditions and comorbidities that limit physical activity) and personal reasons (e.g. marital or psychological problems). Dropouts were distinguished in short-term dropouts (between 0-3 months) and long-term dropouts (between 3-15 months). Data analysis Statistical analyses were performed using SPSS version 20.0 and R version A p<0.05 was considered statistically significant. Characteristics were expressed as mean and standard deviation (normally distributed variables), median and range (non-normally distributed variables) and percentages or numbers (nominal variables). Student s t-tests, Mann-Whitney U tests and χ 2 -tests were performed to indentify differences in characteristics of completers and dropouts at baseline. Differences in reasons for dropout were tested with the Fisher s exact test. Logistic regression analyses were performed for the counseling and the usual care group, analyzing the short and long term separately. Variables that showed significant differences in the univariate analyses were selected and entered in the logistic regression analyses. A backward minimum Akaike information criterion (AIC) procedure was used to select the best fitting combination of predictive variables. 34,35 Results Flow of participants A total of 155 COPD patients with a mean (SD) age of 61.9 (9.8) years and predicted FEV 1 of 59.4 (23.6) % were included (Figure 1 + online Table 1). Thirty of these patients had COPD GOLD-stage I, 64 GOLD-stage II, 39 GOLD-stage III and 20 GOLD-stage IV. Of these patients 109 completed the physical activity counseling study and 46 dropped out (29.7%). Two of these dropouts could not participate because of logistical reasons of the study team and those two patients were not taken into account in further analysis. Subjects who dropped out from the pulmonary rehabilitation setting, dropped out of physical activity counseling as well as pulmonary rehabilitation. Short-term dropout (0-3 months) was 16.6%, whereas long-term dropout (3-15 months) was 13.1%. Dropout rate in the counseling group did not differ significantly from dropout in the usual care group (27.6% vs. 29.9% respectively). 74

76 Dropout from a physical activity counseling program in COPD Reasons for dropout Reasons for dropout of the physical activity counseling study were lack of motivation (n=22), medical (n=12), personal (n=5) and death (n=5) (Figure 1). The distribution of reasons for dropout from the study was not significantly different between the counseling or usual care group (Fisher s exact=3.309, p=0.38). Assessed for eligibility (n=173) Randomized (n=155) Excluded Not meeting inclusion criteria(n=18) Allocated to physical activity counseling (n=78) Received allocated intervention (n=76) Not received allocated intervention (n=2) - counselor not available 3 months Retained: n=65 Lost: n=13 (died n=1, personal reasons n=3, lack of motivation, n=7) Allocated to usual care (n=77) Received allocated intervention (n=77) 3 months Retained: n=64 Lost: n=13 (died n=1, medical reasons n=5, personal reasons n=2, lack of motivation n=5) 4 15 months Retained: n=55 Drop out: n=10 (died n=3, medical reasons n=4, lack of motivation n=3) 15 months Retained: n=54 Drop out: n=10 (medical reasons n=3, lack of motivation n=7) Figure 1. Flow chart showing the selection of subjects for this study Differences between short-term completers and short-term dropouts. Short-term dropouts from physical activity counseling were significantly different from patients who completed the program, as dropouts had lower scores on the Self Regulation Questionnaire for exercise (p=0.01) which measures intrinsic motivation for physical activity and lower CCQ mental status scores (p=0.04) (Table 1). Short-term dropouts from the usual care group, who only underwent measurements and filled out questionnaires, showed a significant difference from patients who completed the study on the Self Regulation Questionnaire for exercise (p=0.05) (Table 1). 75

77 Chapter 4 Table 1. Baseline characteristics of short-term completers vs. short-term dropouts in counseling and usual care Counseling Usual care total n=153 Completer (n=65) Dropout (n=11) Completer (n=64) Dropout (n=13) Gender (male, %) a) Age, y 62 (10.4) 61 (10.2) (9.0) 60 (10.4) 0.40 Smoking status a) Smoker (%) Healthcare setting b) General practice Outpatient clinic Pulmonary rehabilitation FEV 1 (%pred) c) 60 (23.6) 54 (25.7) (24.3) 68 (21.6) 0.17 FEV 1 /FVC 0.47 (0.15) 0.39 (0.16) (0.15) 0.54 (0.11) 0.07 Body mass index (kg/m 2 ) c) 25.6 (4.88) 26.4 (3.85) (4.6) 28.6 (9.5) MWD (m) c) 443 (127.1) 393 (146.7) (124) 465 (157) 0.41 Steps/day d) 4798 ( ) 3144 ( ) ( ) 2503 ( ) 0.21 PA/day (steps+equivalents) d) 6614 ( ) 6416 ( ) ( ) 5651 ( ) 0.79 Chair stand test (repetitions) d) 10 (8-12) 10 (9-13) (8-12) 12 (9-15.5) 0.09 Arm curl test (repetitions) d) 15 ( ) 15 (10-18) (13-17) 17 ( ) 0.14 SRQ-E d) 10.6 ( ) 2.8 ( ) ( ) 7.6 ( ) 0.05 CCQ d) total 1.30 ( ) 2.10 ( ) ( ) 1.60 ( ) 0.95 symptoms 2.00 ( ) 2.88 ( ) ( ) 1.75 ( ) 0.86 functional status 1.00 ( ) 2.00 ( ) ( ) 1.00 ( ) 0.75 mental status 4) 0.00 ( ) 0.75 ( ) ( ) 0.00 ( )

78 Dropout from a physical activity counseling program in COPD DEFS d) 3 (0-7) 4 (1-9) (1-7) 4.5 ( ) 0.59 HADS d) anxiety 5 ( ) 5 ( ) ( ) 6 ( ) 0.24 depression 4 ( ) 4 ( ) ( ) 5 (1.8-9) 0.34 LIVAS d) self efficacy total score 29 ( ) 29 ( ) ( ) 26 ( ) 0.36 SF-36 d) physical functioning 22 ( ) 23 ( ) ( ) 18.5 ( ) 0.35 social functioning 8 ( ) 9 (6.5-9) ( ) 9 ( ) 0.95 physical role limitation 6 ( ) 8 ( ) ( ) 5 ( ) 0.12 emotional role limitation 6 ( ) 6 (5.5-6) ( ) 6 ( ) 0.66 mental health 25 ( ) 22 ( ) ( ) 23- ( ) 0.29 vitality 15 ( ) 13 ( ) ( ) 14.5 ( ) 0.33 pain 55 ( ) 49 ( ) ( ) 46.5 ( ) 0.49 general health perception 13.5 ( ) 10 ( ) ( ) 14.5 ( ) 0.78 health change 3 ( ) 4 ( ) ( ) 3.5 ( ) 0.80 p<0.05 printed bold, a) numbers (%), b) numbers, c) mean (standard deviation), d) median (interquartile range) FEV 1 : Forced Expiratory Volume in one second; FVC: Forced Expiration Volume; 6 MWD: Six-minute Walking Distance; PA.: Physical Activity; SRQ-E: Self Regulation Questionnaire for Exercise; CCQ: Clinical COPD Questionnaire; DEFS: Dutch Exertion and Fatigue Scale; HADS: Hospital Anxiety and Depression Scale; LIVAS: Dutch version of the Perceived Physical Ability Subscale Questionnaire; SF 36: Dutch version of the Short Form

79 Chapter 4 Table 2. Baseline characteristics of long-term completers vs. long-term dropouts in counseling and usual care Counseling Usual care total n=153 Completer (n=55) Dropout (n=10) Completer (n=54) Dropout (n=10) Gender (male, %) a) Age, y 62 (10.4) 61 (10.6) (8.4) 57 (10.3) 0.03 Smoking status a) Smoker (%) Healthcare setting b) General practice 19 1 < <0.01 Outpatient clinic Pulmonary rehabilitation FEV 1 (%pred) c) 64 (21.7) 36 (20.3) < (24.1) 43 (20.0) 0.03 FEV 1 /FVC 0.49 (0.14) 0.33 (0.11) < (0.14) 0.40 (0.17) 0.18 Body mass index (kg/m 2 ) c) 25.8 (5.1) 24.3 (3.5) (4.4) 25.8 (5.6) MWD (m) c) 460 (120) 348 (126) < (112) 326 (139) <0.05 Steps/day d) 5126 ( ) 2319 ( ) ( ) 4000 ( ) 0.18 PA/day (steps+equivalents) d) 7033 ( ) 4454 ( ) ( ) 4942 ( ) 0.18 Chair stand test (repetitions) d) 10 (8.8-12) 8 ( ) (8-12) 7 (5-10) 0.03 Arm curl test (repetitions) d) 15 (12-18) 13 ( ) (13-17) 13 (9.5-18) 0.31 SRQ-E d) 10.5 ( ) 11 ( ) ( ) 11.8 ( ) 0.77 CCQ d) total 1.20 ( ) 2.10 ( ) ( ) 2.30 ( ) 0.01 symptoms 2.00 ( ) 2.50 ( ) ( ) 2.63 ( ) 0.03 functional status 1.00 ( ) 2.13 ( ) ( ) 2.63 ( ) 0.01 mental status 4) 0.00 ( ) 0.00 ( ) ( ) 0.00 ( )

80 Dropout from a physical activity counseling program in COPD DEFS d) 3 (0-6) 9 (4.3-9) < (1-6) 7.5 ( ) 0.01 HADS d) anxiety 5 ( ) 6 ( ) ( ) 5 ( ) 0.79 depression 4 ( ) 5 ( ) (2-6) 4.5 ( ) 0.86 LIVAS d) self efficacy total score 30 (26-36) 26 ( ) (25-35) 28 (19-38) 0.61 SF-36 d) physical functioning 23 (17-27) 14.5 ( ) < ( ) 17 ( ) 0.03 social functioning 8 (6-10) 7.5 (5-9.3) (7-10) 7.5 ( ) 0.16 physical role limitation 6 (4-8) 5 ( ) (5-8) 5.5 ( ) 0.10 emotional role limitation 6 (5-6) 6 ( ) (5-6) 6.0 ( ) 0.93 mental health 25 (21-27) 23.5 ( ) ( ) 26 (24-29) 0.21 vitality 15 (13-20) 15.5 ( ) ( ) 15.5 ( ) 0.32 pain 55 ( ) 49.5 ( ) (39-60) 60 ( ) 0.07 general health perception 15 (9-17) 10.5 ( ) ( ) 11 ( ) 0.21 health change 3 (3-4) 4.0 ( ) (3-4) 4 ( ) 0.08 p<0.05 printed bold, a) numbers (%), b) numbers, c) mean (standard deviation), d) median (interquartile range). FEV 1 : Forced Expiratory Volume in one second; FVC: Forced Expiration Volume; 6 MWD: Six-minute Walking Distance; PA.: Physical Activity; SRQ-E: Self Regulation Questionnaire for Exercise; CCQ: Clinical COPD Questionnaire; DEFS: Dutch Exertion and Fatigue Scale; HADS: Hospital Anxiety and Depression Scale; LIVAS: Dutch version of the Perceived Physical Ability Subscale Questionnaire; SF 36: Dutch version of the Short Form

81 Chapter 4 Differences between long-term completers and long-term dropouts. Long-term dropouts from physical activity counseling tended to be patients participating in the pulmonary rehabilitation setting. Dropouts had a significantly lower FEV 1 and FEV 1 /FVC ratio, lower six-minute walking distance and lower daily physical activity level. In addition, these patients had higher fatigue scores, lower SF-36 physical functioning and lower general health perception scores and higher SF-36 health change scores (Table 2). Long-term dropouts from the usual care group tended to be patients participating in the pulmonary rehabilitation setting. Dropouts had a significantly lower FEV 1, lower 6 MWD and scored lower on the chair stand test. In addition, these patients scored higher on symptoms, functional, and total score of the Clinical COPD Questionnaire, higher on the Dutch Exertion and Fatigue Scale and higher on Short Form-36 physical functioning score (Table 2). Predictors of dropout from the physical activity counseling and usual care group Logistic regression analyses showed that short-term dropout from the counseling group was significantly predicted by lower intrinsic motivation for physical activity (b=-0.302, p<0.01) and higher CCQ mental status scores (b=1.00, p=0.02), whereas in the usual care group low intrinsic motivation for physical activity was the only significant predictor of dropout (b-0.174, p=0.04) (Table 3). Long-term dropout from the counseling group was predicted by lower FEV 1 (b= , p<0.01) whereas in the usual care group higher CCQ functional status scores (b=0.832, p=0.01) predicted dropout. Lower age was not a significant predictor, but was kept in the model in order to correct for its effect (b=-0.074, p=0.11) (Table 3). Table 3. Predictors of dropout from counseling and usual care in the short and long term n completers/ dropouts predictor Coefficient (b) SE p deviance p OR (CI) counseling 72 64/8 SRQ-E < ( ) (short-term) CCQ mental ( ) usual care 73 63/10 SRQ-E ( ) (short-term) counseling (long-term) 59 50/9 FEV < ( ) usual care (long-term) 57 48/9 age ( ) CCQ functional ( ) SRQ-E: Self Regulation Questionnaire for Exercise; CCQ: Clinical COPD Questionnaire; FEV 1 : Forced Expiration Volume in one second 80

82 Dropout from a physical activity counseling program in COPD Discussion To our knowledge this is the first study that reports independent predictors of dropout from a physical activity counseling program for COPD patients. The dropout rates from the study were 16.6% in the short term (0-3 months) and 13.1% in the long term (3-15 months). Lower intrinsic motivation for physical activity and worse mental status were identified as predictors of shortterm dropout from counseling. Long-term dropout from counseling was predicted by a lower lung function. In usual care short-term dropout was predicted by a lower intrinsic motivation for physical activity and long-term dropout by a lower functional status. Low intrinsic motivation for physical activity was found to be a predictor of short-term dropout from counseling. In line with this, lack of motivation (in general) was also the commonest reason for dropout mentioned by participants. Although it seems logical that patients with a lower intrinsic motivation for physical activity more frequently drop out from a physical activity counseling program, there is not much research available in COPD patients. In other research fields however, there is consensus that intrinsic motivation in general has significant impact on the success of behavioral change programs dealing with lifestyle aspects such as smoking and drug addiction. 36,37 The question arises: why and how did patients motivation for physical activity already dwindle before they started participating in the study? In that perspective the Health Belief Model postulates that an individual is motivated for behavior change only when he feels at risk for severe health consequences resulting from his current behavior. 38 The decision to change is made by weighing the costs and benefits of the current behavior and may be influenced by increased perception of disease symptoms; health campaigns; or personal characteristics. 39 The inability to change unhealthy lifestyle behavior is addressed in the concept of self-efficacy, which is part of the Health Belief Model and relates to the belief of being capable of carrying out an intended behavioral change. Several studies have shown that low self-efficacy is associated with dropout and low attendance. 40,41 However, we found no evidence for differences in self-efficacy at baseline between completers and dropouts in our study. 4 Worse mental status at baseline was also predictive of short-term dropout from counseling, indicated by a higher score on the CCQ mental status scale. This scale of the CCQ contains two brief questions on how patients experience mental aspects accompanying their disease, such as feelings of anxiety or worries about dyspnea and feeling depressed. Possibly, these mental aspects interfere with the process of behavior change. A higher level of anxiety about experiencing dyspnea might restrain a patient from starting a more active lifestyle. Depressed feelings might influence patients motivation and make them give up more easy. In addition, the counseling program might have confronted patients with those feelings. Depending on their mental status and coping strategy this may have led to either empowerment and taking the opportunity to change physical activity behavior, or giving up because the psychological effort needed to change was more than they could take at that moment. In the long term, a lower lung function predicted dropout from counseling. This suggests that, in this behavior maintenance phase, worse disease status is more important than the psychological factors that have shown to play a role in the behavior change process. The predictive value of low lung function for long-term dropout may partly be explained by the 81

83 Chapter 4 fact that especially in this stage dropout rate from the pulmonary rehabilitation setting was relatively high. In our clinical experience, these patients have more severe COPD (online Table 1), have comorbidities, and suffer from related psychosocial problems. Indeed, these patients are confronted with rather high physical and psychosocial barriers that might have hindered them from sticking to a physical activity counseling program. Regarding the differences in predictors between short- and long-term dropout from physical activity counseling it has been shown that in the short term motivation and mental status, both psychological factors, are important in predicting dropout. Those factors are no longer relevant in long-term dropout, suggesting that those who are not motivated or experience too much psychological stress already dropout in an early stage. For patients who dropout in the long term mainly disease related physical factors restrain them from further participation in the counseling program, which is supported by the differences found between completers and dropouts in the counseling group in this stage (Table 2). This study shows low motivation for physical activity also predicted short-term dropout from usual care, although less strong. This means that low motivation for physical activity also influences dropout from just taking part in measurement sessions and filling out questionnaires. One might assume that patients participating in the current study, those in the usual care group as well as the counseling group initially had some motivation to change their physical activity behavior. All patients participated voluntarily in the study, and were aware of the goal of the study. Perhaps, the effort they had to make to either change their physical activity behavior, or to a lesser degree participate in measurement sessions, is too big for the patients with a lower initial motivation for physical activity. Lower functional status was predictive for long-term dropout from the usual care group, which is possibly related to the lower lung function found as predictor in the counseling group. In our study medical and motivational reasons were the most frequently reported reasons for dropout. To date, no publications exist focusing on dropout from physical activity counseling programs in patients with COPD. However, similar to findings in pulmonary rehabilitation studies medical reasons are one of the most important reasons for dropout in our study as well We found low motivation and low mental status to be predictive of short-term dropout. Low mental status might be comparable to being depressed which was mentioned as a predictor of dropout in one pulmonary rehabilitation study. 44 Lower FEV 1, predicting long term dropout in our study, might be linked to worse disease status which may also be true for low quadriceps force, higher number of pack years and lower fat free mass, which were found as predictors of dropout from two pulmonary rehabilitation studies. 42,44 It seems that although a patient s burden in pulmonary rehabilitation and physical activity counseling studies may differ, the reasons for and predictors of dropout show similarities. Strength of this study is that we collected many complementary demographic physiological and psychological data in a prospective randomized controlled trial in a broad group of COPD patients. Besides that, the predictors of dropout were collected not only from the counseling group but also from the usual care group. Hereby, we were able to unravel whether predictors of dropout were associated particularly with the intervention or whether the same predictors were found in the usual care group and thus could be seen as a study effect. 82

84 Dropout from a physical activity counseling program in COPD Some comments should also be made on the current analysis. Firstly, in this study patients recruited from a specialized pulmonary rehabilitation centre received more extensive treatment than patients recruited from general practice and hospital settings. Noteworthy, usual care in the pulmonary rehabilitation setting meant participating in a multidisciplinary program including structured exercise training. Secondly, we used a pedometer to measure physical activity. Although the pedometer we used is the preferred model, it is known to have reduced step count at low speed an in overweighed subjects. 46 We tested for this and excluded subjects in which the pedometer did not count accurately at the start of the study. Our study shows that not only physical but also psychological factors, especially in the behavior change phase of the program, influence whether a patient drops out of or completes the program. Therefore, we believe that for clinical practice and future research characterization of COPD patients at the start of an exercise or physical activity enhancement program should include more than just physical factors. Psychological components like motivation and selfefficacy for physical activity, patients beliefs about physical activity, and other lifestyle behavior should be assessed. In addition, information on prior exercise and physical activity behavior should be collected. 47 An attractive way to collect this information is through semi-structured interviews, in which reasons and barriers for physical activity can be categorized and thus can act as starting points for different treatment strategies. 48 To actively enhancing motivation before a counseling program actually starts a supportive intervention, a group opt-in session, before the start of a pulmonary rehabilitation program could be useful. 49 One study used such a session to introduce the concept of self-management presenting a fictional patient as an example, which resulted in higher program attendance. 49 Better characterization of patients and enhancing motivation before starting a counseling program may lead to more effective physical activity counseling. 4 In conclusion, low intrinsic motivation for physical activity and low mental status predict dropout from a physical activity counseling program in the short term, where behavior change is initiated. A lower lung function is predictive for dropout in the long term, where the new behavior should be maintained. We recommend that healthcare practitioners should pay more attention to the patients beliefs about and attitudes towards physical activity and healthy lifestyle, as well as to their physical capabilities before they start participating in a program. This might help to better tailor the counseling to the needs and skills of the patient. 83

85 Chapter 4 References 1. Watz H, Waschki B, Meyer T, Magnussen H. Physical activity in patients with COPD. Eur Respir J 2009; 33: Esteban C, Quintana JM, Aburto M, Moraza J, Egurrola M, Perez-Izquierdo J, et al. Impact of changes in physical activity on health-related quality of life among patients with COPD. Eur Respir J 2010; 36: Hartman JE, Boezen HM, de Greef MH, Bossenbroek L, ten Hacken NH. Consequences of physical inactivity in chronic obstructive pulmonary disease. Expert Rev Respir Med 2010; 4: Annesi JJ. Effects of a computer feedback treatment and behavioral support protocol on drop out from a newly initiated exercise program. Percept Mot Skills 2007; 105: Rejeski WJ, Brawley LR, Ambrosius WT, Brubaker PH, Focht BC, Foy CG, et al. Older adults with chronic disease: benefits of group-mediated counseling in the promotion of physically active lifestyles. Health Psychol 2003; 22: Dunn AL, Marcus BH, Kampert JB, Garcia ME, Kohl HW,3rd, Blair SN. Comparison of lifestyle and structured interventions to increase physical activity and cardiorespiratory fitness: a randomized trial. JAMA 1999; 281: Andersen RE, Wadden TA, Bartlett SJ, Zemel B, Verde TJ, Franckowiak SC. Effects of lifestyle activity vs structured aerobic exercise in obese women: a randomized trial. JAMA 1999; 281: Huisman S, de Gucht V, Maes S, Schroevers M, Chatrou M, Haak H. Self-regulation and weight reduction in patients with type 2 diabetes: a pilot intervention study. Patient Educ Couns 2009; 75: Toft UN, Kristoffersen LH, Aadahl M, von Huth Smith L, Pisinger C, Jorgensen T. Diet and exercise intervention in a general population--mediators of participation and adherence: the Inter99 study. Eur J Public Health 2007; 17: Huisman S, Maes S, De Gucht VJ, Chatrou M, Haak HR. Low goal ownership predicts drop-out from a weight intervention study in overweight patients with type 2 diabetes. Int J Behav Med 2010; 17: Groeneveld IF, Proper KI, van der Beek AJ, Hildebrandt VH, van Mechelen W. Factors associated with non-participation and drop-out in a lifestyle intervention for workers with an elevated risk of cardiovascular disease. Int J Behav Nutr Phys Act 2009; 6: Cooper TV, Resor MR, Stoever CJ, Dubbert PM. Physical activity and physical activity adherence in the elderly based on smoking status. Addict Behav 2007; 32: Hospes G, Bossenbroek L, Ten Hacken NH, van Hengel P, de Greef MH. Enhancement of daily physical activity increases physical fitness of outclinic COPD patients: results of an exercise counseling program. Patient Educ Couns 2009; 75: de Blok BM, de Greef MH, ten Hacken NH, Sprenger SR, Postema K, Wempe JB. The effects of a lifestyle physical activity counseling program with feedback of a pedometer during pulmonary rehabilitation in patients with COPD: a pilot study. Patient Educ Couns 2006; 61: Locke EA, Latham GP, Smith KJ. A theory of goal setting & task performance. Englewood Cliffs, N.J.: Prentice Hall;

86 Dropout from a physical activity counseling program in COPD 16. Deci EL RM. Intrinsic motivation and self-determination in human behavior. New York: Plenum Publishing Co.; Miller WR, Rollnick S. Motivational interviewing : preparing people to change addictive behavior. New York, NY etc.: The Guilford Press; Sivaraman Nair KP. Life goals: the concept and its relevance to rehabilitation. Clin Rehabil 2003; 17: Bravata DM, Smith-Spangler C, Sundaram V, Gienger AL, Lin N, Lewis R, et al. Using pedometers to increase physical activity and improve health: a systematic review. JAMA 2007; 298: Scott NW, McPherson GC, Ramsay CR, Campbell MK. The method of minimization for allocation to clinical trials. a review. Control Clin Trials 2002; 23: Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2007; 176: Schneider PL, Crouter SE, Bassett DR. Pedometer measures of free-living physical activity: comparison of 13 models. Med Sci Sports Exerc 2004; 36: Ainsworth BE, Haskell WL, Herrmann SD, Meckes N, Bassett DR,Jr, Tudor-Locke C, et al Compendium of Physical Activities: A Second Update of Codes and MET Values. Med Sci Sports Exerc 2011; 43: Ainsworth BE, Haskell WL, Leon AS, Jacobs DR,Jr, Montoye HJ, Sallis JF, et al. Compendium of physical activities: classification of energy costs of human physical activities. Med Sci Sports Exerc 1993; 25: Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl 1993; 16: ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166: Rikli RE, Jones CJ. Senior Fitness Test Manual. Champaign: Human Kinetics; van der Molen T, Willemse BW, Schokker S, ten Hacken NH, Postma DS, Juniper EF. Development, validity and responsiveness of the Clinical COPD Questionnaire. Health Qual Life Outcomes 2003; 1: Ware JE,Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: Tiesinga LJ, Dassen TW, Halfens RJ. DUFS and DEFS: development, reliability and validity of the Dutch Fatigue Scale and the Dutch Exertion Fatigue Scale. Int J Nurs Stud 1998; 35: Snaith RP, Zigmond AS. The hospital anxiety and depression scale. Br Med J (Clin Res Ed) 1986; 292: Bosscher RJ, Laurijssen L, de Boer E. Measuring physical self-efficacy in old age. Percept Mot Skills 1993; 77: Ryan RM, Connell JP. Perceived locus of causality and internalization: examining reasons for acting in two domains. J Pers Soc Psychol 1989; 57:

87 Chapter Akaike H. A new look at the statistical model identification. Automatic Control, IEEE Transactions on 1974; 19: Agresti A. Categorical Data Analysis. Third Edition ed. New York, USA: Wiley; O Toole TP, Pollini RA, Ford D, Bigelow G. Physical health as a motivator for substance abuse treatment among medically ill adults: is it enough to keep them in treatment? J Subst Abuse Treat 2006; 31: Curry SJ, Grothaus L, McBride C. Reasons for quitting: intrinsic and extrinsic motivation for smoking cessation in a population-based sample of smokers. Addict Behav 1997; 22: Becker MH. The Health Belief Model and Personal Health Behavior. 1974;. 39. Schofield I, Kerr S, Tolson D. An exploration of the smoking-related health beliefs of older people with chronic obstructive pulmonary disease. J Clin Nurs 2007; 16: McAuley E, Jerome GJ, Elavsky S, Marquez DX, Ramsey SN. Predicting long-term maintenance of physical activity in older adults. Prev Med 2003; 37: Oman RF, King AC. Predicting the adoption and maintenance of exercise participation using self-efficacy and previous exercise participation rates. Am J Health Promot 1998; 12: Fischer MJ, Scharloo M, Abbink JJ, van t Hul AJ, van Ranst D, Rudolphus A, et al. Drop-out and attendance in pulmonary rehabilitation: the role of clinical and psychosocial variables. Respir Med 2009; 103: O Shea SD, Taylor NF, Paratz JD. A predominantly home-based progressive resistance exercise program increases knee extensor strength in the short-term in people with chronic obstructive pulmonary disease: a randomised controlled trial. Aust J Physiother 2007; 53: Garrod R, Marshall J, Barley E, Jones PW. Predictors of success and failure in pulmonary rehabilitation. Eur Respir J 2006; 27: O Shea SD, Taylor NF, Paratz JD.... But watch out for the weather: factors affecting adherence to progressive resistance exercise for persons with COPD. J Cardiopulm Rehabil Prev 2007; 27:166,74; quiz Bassett DR,Jr, Ainsworth BE, Leggett SR, Mathien CA, Main JA, Hunter DC, et al. Accuracy of five electronic pedometers for measuring distance walked. Med Sci Sports Exerc 1996; 28: Rejeski WJ, Miller ME, King AC, Studenski SA, Katula JA, Fielding RA, et al. Predictors of adherence to physical activity in the Lifestyle Interventions and Independence for Elders pilot study (LIFE-P). Clin Interv Aging 2007; 2: Buman MP, Giacobbi PR,Jr, Yasova LD, McCrae CS. Using the constructive narrative perspective to understand physical activity reasoning schema in sedentary adults. J Health Psychol 2009; 14: Graves J, Sandrey V, Graves T, Smith DL. Effectiveness of a group opt-in session on uptake and graduation rates for pulmonary rehabilitation. Chron Respir Dis 2010; 7:

88 Dropout from a physical activity counseling program in COPD Supplementary data online Table 1. Baseline characteristics per healthcare setting General practice (n=48) Outpatient clinic (n=46) Pulmonary rehabilitation (n=61) Age, y 1 65 (58-72) 68 (61-72) 54 (50-63) Sex, m/f, n, (%) 32 (67)/16 (33) 34 (74)/12 (26) 36 (59)/25 (41) FEV 1, %pred 2 78 (66-95) 58 (40-69) 43 (28-58) FEV 1 %FVC, % 3 59 (52-65) 43 (33-54) 37 (28-53) RV%TLC, % 1 42 (39-49) 48 (38-53) 51 (45-61) GOLD stage, n (%) 2 I 22 (45) 7 (15) 3 (5) II 23 (48) 23 (50) 19 (31) III 3 (3) 15 (33) 20 (33) IV 0 (0) 1(2) 19 (31) BMI, kg/m ( ) 24.8 ( ) 26.4 ( ) 6MWD, m ( ) 454 ( ) 378 ( ) Daily steps ( ) 4371 ( ) 2979 ( ) Daily physical activity 7431 ( ) 5561 ( ) 6238 ( ) Dropout (0-3 months), n (%) 10 (21) 3 (7) 11 (19) Dropout (3-15 months), n (%) 1 (2) 3 (7) 16 (27) Data presented as median (IQR).1) The pulmonary rehabilitation group is significantly (p < 0.05) different from general practice and outpatient clinic, 2) All healthcare groups are significantly different from each other, 3) General practice group is significantly different from outpatient and pulmonary rehabilitation group. FEV 1 : forced expiration volume in 1 second; FVC: Forced Vital Capacity; RV: Residual Volume; TLC: Total Lung Capacity; GOLD: Global Initiative for chronic Obstructive Lung Disease; BMI: body mass index; 6MWD: six minute walking distance; HADS: Hospital Anxiety and Depression Scale; CCQ: Clinical COPD Questionnaire; CRQ: Chronic Respiratory Questionnaire. 4 87

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90 CHAPTER 5 A better response in exercise capacity after pulmonary rehabilitation in more severe COPD patients Wytske A. Altenburg, Mathieu H.G. de Greef, Nick H. T. ten Hacken, Johan B. Wempe Respiratory Medicine 2012 May; 106(5):

91 Chapter 5 Abstract Purpose: Pulmonary rehabilitation (PR) has positive effects on exercise capacity in Chronic Obstructive Pulmonary Disease (COPD). However, not all COPD patients benefit from PR to the same extent. We investigated whether there is a patient profile, which is associated with the improvement in endurance exercise capacity. Methods: In this observational study, we included 102 COPD patients who followed PR (age 60 ± 10 (mean ± SD) years, FEV 1 %predicted 44±6 %, 54 men). Lung function, maximal incremental cycle testing (Wpeak, VO 2 peak, Δlactate), quadriceps force and incremental and endurance shuttle walk test (ISWT/ESWT) were performed at the start of PR. The ESWT was repeated after 7 weeks of PR. Results: Mean change in ESWT (ΔESWT) was 100±154 %. Four variables showed a statistically significant negative correlation with ΔESWT: FEV 1 %pred. (ρ=-0.20), Wpeak (ρ=-0.24), Δlactate (ρ=-0.33) and incremental shuttle walk test (ISWT) (ρ=-0.31). A cluster analysis identified two patient profiles: A profile with high ΔESWT, TLC and RV and low FEV 1, VO 2 peak, quadriceps force, Δlactate, HR peak % pred. and ISWT distance and a profile with low ΔESWT, TLC and RV and high FEV 1, VO 2 peak, quadriceps force, Δlactate, HR peak % pred. and ISWT distance. Conclusions: Single variables from lung function or exercise testing at baseline have limited predictive value for response to exercise training. However, patients with worse disease status (i.e. a combination of lower FEV 1, more hyperinflation, lower exercise capacity and worse quadriceps force) improve more in endurance exercise capacity. 90

92 Predictors of pulmonary rehabilitation outcome Introduction In patients with COPD strength and endurance exercise capacity are impaired. 1-4 Exercise capacity may be affected by many factors such as ventilatory limitation, dynamic hyperinflation and diminished oxygen uptake in the lung. 5 In addition, impaired exercise capacity could be caused by factors outside the lung, such as early lactate production 2,6-8, muscle dysfunction 1 and cardiovascular deconditioning (e.g. higher heart rate and lower stroke volume during exercise) 9,10, which may at least be partially induced by sedentary lifestyle due to dyspnea. 11 Pulmonary rehabilitation (PR) has beneficial effects on exercise-induced dyspnea, exercise capacity and daily physical activity level in COPD In addition, it is known in healthy subjects that exercise training can reverse the process of deconditioning and delays the anaerobic threshold during exercise. 17 Not all COPD patients benefit from PR to the same extent, as is shown in several studies The limiting factor in exercise may play a role in the response to PR. For instance, the presence of a marked ventilatory reserve is associated with improvement in exercise capacity after PR in two studies. 20,22 Besides that, the presence of cardiovascular limitation is associated with improvement in exercise capacity after PR as well. 19,20 Finally, reduced muscle strength is found to be associated with improvement in exercise capacity after PR. 18,20 These studies are, however, quite difficult to compare as they show differences in patient selection, rehabilitation program, outcome measures and statistical methods used In a well defined patient group we investigated whether a patient profile exists with a combination of variables instead of a single variable, which may predict the degree of improvement in endurance exercise capacity after PR. To reveal this profile, the cluster analysis technique was used. We hypothesized that patients with better lung function combined with more signs of deconditioning, e.g. high lactate production during maximal exercise testing and low peak exercise capacity show the largest improvement in endurance exercise capacity after PR. 5 Methods Design A post-hoc analysis was performed on data from patients participating in a PR program in a PR center. At baseline, standardized pulmonary function testing, maximal incremental cycle testing, and incremental and endurance shuttle walk tests (ISWT and ESWT) were performed. After seven weeks of exercise training the ESWT was repeated. Subjects In this study 102 COPD patients, who participated in the PR program of the Center for Rehabilitation of the University Medical Center Groningen, were included. Inclusion criteria were a diagnosis of COPD according to the GOLD guidelines and the capability of following an endurance exercise program and filling out questionnaires. Patients were free of exacerbations for at least six weeks. Excluded were patients with musculoskeletal disorders and malignant diseases which would interfere with exercise training. Both outpatients and inpatients were included. 91

93 Chapter 5 If necessary, patients were assigned to the inpatient PR program based on criteria such as travel distance, dependence in activities of daily life and nutritional status, in accordance with the ATS/ERS statement. 23 All patients consented to the scientific use of data from tests they performed. Pulmonary function testing Spirometry to determine FEV 1 and FVC was performed in the sitting position using a spirometer (Masterlab, Viasys Healthcare), and static lung volumes were determined with a bodyplethysmograph (Masterlab, Viasys Healthcare). Tests were performed following accepted standards. 24 Exercise testing Subjects performed a symptom-limited incremental cycle test (1-min increments of 5 or 10 W) to the limit of tolerance on an electromagnetically braked cycle ergometer (OxyconPro, Viasys Healthcare) after a 5-minute rest, followed by 1 min of unloaded pedaling. Peak work rate was defined as the highest work level reached and maintained at a pedaling frequency of 60 revolutions per minute for at least 30 s. Pulmonary oxygen uptake, pulmonary carbon dioxide output and minute ventilation were recorded using a mixing chamber. Heart rate was determined using the R-R interval from a 12-lead on-line electrocardiogram. Arterial blood was drawn from a line in the radial or brachial artery for the analysis of arterial oxygen tension, carbon dioxide tension and lactate, at rest, every 2 minutes during the test and 2 minutes after stopping (Rapidlab, Siemens). The change in lactate concentration from rest to the highest level, either at maximal work load or 2 minutes after stopping the test (Δlactate), was used for further analyses. Endurance exercise capacity was measured at the start of and after PR, using the endurance shuttle walk test (ESWT). The ESWT was developed as a standardized field test to assess endurance capacity using constant walking speeds and external regulation of pace. 25 This test is based on the incremental shuttle walk test (ISWT), which uses a 10m course and the walking speed is externally controlled by acoustic signals. 26 The patient is instructed to walk for as long as possible. Patients have to reach the end of the course in time before the audio signal; when they fail to do so, or when they indicate they are exhausted, the test is ended. This test was performed once at the start of PR. VO 2 peak can be predicted by the performance on ISWT with the equation: VO 2 peak (ml/min/kg) = (distance in meters). 27 For the ESWT a speed was used that corresponded with 85% of the VO 2 peak. The ESWT speed was read from a graph which related shuttle walking speeds to predicted VO 2 peak. 25 While the ISWT measures maximal exercise capacity in COPD patients, the ESWT is considered to better reflect the endurance exercise capacity. 25,27 The ESWT appears to be responsive to change after an intervention, perhaps even more than the ISWT and the six minute walking distance. 25,28 Quadriceps strength was measured with a handheld dynamometer (microfet), with the patient in sitting position, the knee at 90, and the leg vertical. 29 Pulmonary rehabilitation The exercise sessions in the PR program aimed at improving endurance exercise capacity. Training forms used to achieve increased endurance capacity were cycling, walking, swimming 92

94 Predictors of pulmonary rehabilitation outcome and sports, 3 sessions per week, 1-2 hours. All patients participated in all these exercise training modalities. The target of each training session was to achieve a training stimulus of 30 minutes at 60 to 70% of the peak work load achieved on maximal incremental cycle testing. In cycling, training intensity was based on work load, whereas in other training modalities the intensity was based on heart rate or Borg scores. The progression of the training load during the exercise program was individually tailored. In addition, subjects followed educational courses and received psychological and/or nutritional support if necessary. The program meets the criteria of the ACSM and ATS/ERS. 23,30,31 Statistical analysis Statistical analysis was performed using SPSS version A p-value below 0.05 (two-sided) was considered statistically significant. Means and standard deviations (SD) were calculated if the outcome variables were normally distributed. Normality was tested with the Kolmogorov- Smirnov or Shapiro-Wilks tests. Spearman s ρ was calculated because the primary outcome measure, percentage change in endurance shuttle walk test (ΔESWT), was not normally distributed. Discriminant analysis, method enter (meaning that all variables are taken into the model whether they contribute significantly or not) was performed to find predictors of improved endurance exercise capacity. The outcome variable ΔESWT was divided in two groups using the median. A K-means cluster analysis was used to find homogeneous groups with characteristic profiles showing different response to rehabilitation, measured with the ESWT. Cluster analysis is a data mining technique, in which all subjects are assigned to a predetermined number of relatively homogeneous subgroups. These groups are formed by comparing Euclidean distances between each subject, and each cluster centre in an interactive process. Within these groups the consistency of the variables is high. In this analysis we used the highest and lowest tertile of ΔESWT scores, because we opted for finding patient profiles which were associated with high or low improvement in endurance exercise capacity. 5 93

95 Chapter 5 Results In this study 102 COPD patients were included: 5 GOLD I, 28 GOLD II, 50 GOLD III and 19 GOLD IV patients. Characteristics of the total group are shown in Table 1. Table 1. Baseline patient characteristics (N= 102) Demographics Age (y) 60.2 ±10.4 Female / Male 48 / 54 BMI (kg/m 2 ) 27.3 ± 6.1 Pulmonary function FEV 1 (l) 1.27 ± 0.59 FEV 1 (% pred) 44.2 ± 15.9 TLC (% pred) ± 19.7 RV%TLC (%) 54.8 ± 10.3 Exercise tests ISWT (m) 233 ± 131 ESWT (m) 409 ± 350 ESWT (sec) 390 ± 274 Quadriceps force (N) 292 ± 82 Maximal incremental exercise testing Rest Peak exercise VO 2 peak (% pred) 54.5 ± 16.3 Wpeak (%pred) 41.5 ± 22.1 Wpeak (W) 53.8 ± 36.3 VO 2 (ml/min) ± ± HR (b/min) 88 ± ± 22 VE (l) 11.8 ± ± 15.2 PaCO 2 (kpa) 5.27 ± ± 1.02 PaO 2 (kpa) 9.38 ± ± 1.72 Lactate (mmol/l) 1.62 ± ± 2.50 Peak Borg score dyspnea 1 (0-3) 7 (5-9) Peak Borg score fatigue 0.5 (0-2) 7 (5-9) Values given as a mean ± sd or median (IQR) BMI: body mass index; FEV 1 : forced expiratory volume in one second; TLC: total lung capacity; RV: residual volume; ISWT: incremental shuttle walk test; ESWT: endurance shuttle walk test; VO 2: : oxygen uptake; Wpeak: peak work rate; HR: heart rate; VE: minute ventilation; PaCO 2 : carbon dioxide tension; PaO 2 : arterial oxygen tension 94

96 Predictors of pulmonary rehabilitation outcome The mean age of the patients was 60 ± 10 (mean ± SD) years, and the male/female ratio was almost equal. The number of missed exercise sessions was < 8%. Maximal exercise capacity was below normal values as shown by the decreased predicted peak workload (41.5% ± 22.1%) and predicted peak oxygen uptake (54.5% ± 16.3%). After 7 weeks of PR mean ΔESWT was 100% ± 154%, corresponding with an absolute ESWT distance improvement of 188 ± 446 meters and an improvement in ESWT time of 216 ± 418 seconds. Of all patients 24% improved between 10% and 50%, whereas 52% improved more than 50%. The correlations between various physiological factors and the ΔESWT are shown in Table 2. Four variables showed a weak but significant negative correlation with the ΔESWT: lactate, FEV 1 %pred, ISWT distance and Wpeak. Table 2. Correlations of initial measures with ΔESWT (Spearman s ρ ) Age (y) BMI (kg/m 2 ) FEV 1 (l) ΔESWT (%) FEV 1 (%pred) ρ = * TLC (% pred) RV% TLC (%) ISWT (m) ρ = * Quadriceps force (N) V O 2 peak (ml/min) Wpeak (W) ρ = * HR peak% predicted (%) Δlactate (mmol/l) ρ = * * p<.05, n.s.: non significant correlation BMI: body mass index; FEV 1 : forced expiratory volume in one second; TLC: total lung capacity; RV: residual volume; ISWT: incremental shuttle walk test; VO 2 peak: peak oxygen uptake; Wpeak: peak work rate; HR: heart rate; Δlactate: Change in lactate concentration before and after maximal incremental exercise testing n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. 5 Discriminant analysis (method enter) was used to further explore predictive factors for ΔESWT and we included the variables in the model which are currently known or suggested as predictors. In our final model Δlactate appeared to be the strongest contributing factor in the equation explaining 33% of the variance (Table 3). However, the model was not statistically significant (Wilk s Lambda = 0.888, p= 0.372) although 65.3 % of the patients were classified correctly. 95

97 Chapter 5 Table 3. Discriminant Analysis: Structure Matrix Canonical discriminant function coefficient Δlactate (mmol/) Wpeak (W) Quadriceps force (N) BMI (kg/m 2 ) FEV 1 (% pred) RV%TLC (%) TLC (%pred) Age (y) VO 2 peak (ml/min) HRpeak%predicted (%) Canonical correlation=.335, Wilks Lambda= 0.888, p=0.372 Patients classified correctly=65,3% Δlactate: Change in lactate concentration before and after maximal incremental exercise testing, Wpeak: peak work rate; BMI: body mass index; FEV 1 : forced expiratory volume in one second; RV: residual volume; TLC: total lung capacity; VO 2 peak: peak oxygen uptake; HR: heart rate. The K-means cluster analysis revealed the presence of two homogeneous groups, which were significantly different on several variables i.e. ΔESWT, FEV 1 %pred., TLC%pred., RV%TLC, Wpeak, quadriceps force, VO 2 peak, Δlactate, HRpeak%pred. and ISWT distance (Table 4). A high ΔESWT was associated with a patient profile with high TLC and RV%TLC and low FEV 1 %pred., Wpeak, VO 2 peak, HRpeak%pred., quadriceps strength, ISWT distance. A low ΔESWT was associated with a patient profile with low TLC and RV%TLC and high FEV 1 %pred, Wpeak, VO 2 peak, HRpeak%pred, quadriceps strength, ISWT distance. The clusters showed no significant differences for age and BMI. Discussion This study shows that four variables measured at the start of a PR program are correlated with the change in endurance exercise capacity after 7 weeks of exercise training in COPD: FEV 1 %pred., Wpeak, Δlactate and ISWT distance. As we expected, patients with lower Wpeak and ISWT distance improved more. However, opposite to what we expected, it appeared that lower values of FEV 1 and Δlactate correlate with a larger improvement in endurance exercise capacity after PR. In addition to this univariate analysis, the cluster analysis, used to detect patient profiles, shows that two homogeneous groups can be formed: a patient profile with a combination of worse lung function and exercise capacity, showing a larger improvement in endurance exercise capacity, and a patient profile with a combination of better lung function and exercise capacity, showing a substantially smaller improvement. 96

98 Predictors of pulmonary rehabilitation outcome Table 4. K-means cluster analysis: Cluster profile Final Cluster Centers ANOVA 1 (n=17) 2 (n=48) F p ΔESWT (%) FEV 1 (% pred) <0.001 TLC (% pred) RV%TLC (%) <0.001 Wpeak (W) <0.001 Quadriceps force (N) VO 2 peak (ml/min) <0.001 Δlactate (mmol/l) <0.001 HR peak (%predicted) ISWT (m) <0.001 Age (y) BMI (kg/m 2 ) ΔESWT: Change in endurance shuttle walk test percentage, before and after pulmonary rehabilitation; FEV 1 : forced expiratory volume in one second; TLC: total lung capacity; RV: residual volume; Wpeak: peak work rate; VO 2 peak: peak oxygen uptake; Δlactate: Change in lactate concentration before and after maximal incremental exercise testing; HR: heart rate; ISWT: incremental shuttle walk test; BMI: body mass index. A number of other investigators have examined whether the change in exercise capacity can be predicted Their results are equivocal and difficult to interpret. The differences in results may be due to differences in patient selection, outcome measures, intervention and statistical methods used to analyze the data. Garrod et al. studied a very heterogeneous group of COPD patients from primary and secondary care, who followed either outpatient or, for the most severe patients, home-based PR, for 7 weeks, twice a week for 1 h. 18 The 6MWD was the primary outcome measure for exercise capacity, and the minimal clinically important difference was used to determine if a patient was a responder. A logistic regression analysis was used and no predictors for the observed change in exercise capacity were found. 5 Plankeel et al. included non-oxygen dependent COPD patients following a 4-week PR program and found that the nature of limitation on maximal incremental exercise testing, whether it was cardiovasculary, ventilatory, both or none, did not predict the increase in endurance exercise capacity, measured with the 6MWD. 19 Interestingly, this study showed that the increase in VO 2 peak after PR was highest in subjects with no ventilatory limitation. Recently, Vagaggini et al. studied moderate to severe COPD patients who followed an 8-week outpatient PR program. 21 The effect of the PR program was measured with the 6MWD. Using a logistic regression analysis, they found that patients with BMI > 25 kg/m 2 and patients with PO 2 < 8 Kpa (60 mmhg) improved more in exercise capacity after PR. 97

99 Chapter 5 Troosters et al. studied moderate to severe COPD patients following a 12 week outpatient PR program. 20 They used a discriminant analysis to distinguish between responders and nonresponders. Responders were defined by having a 15% increase in maximal workload and/ or 25% increase in 6MWD. They found that responders had more ventilatory reserve and lower inspiratory and peripheral muscle strength. Zu Wallack et al studied pulmonary patients, of which 80% had a primary diagnosis of COPD, after a 6-week PR program. 22 The effect of the program was measured with the 12MWD. Using a regression analysis they showed that a combination of higher FEV 1 and low initial walking distance on 12MWD predicted improvement in exercise capacity. Together the above described results suggest that a worse functional status may be related to a larger improvement in endurance exercise capacity after exercise training. Our study adds to previous results by including a heterogeneous group of patients and using a different statistical approach, the cluster analysis. Besides that we think that the outcome measure in our study, the ESWT, is a sensitive measurement tool to assess changes in endurance capacity after PR, as it has shown to be responsive to change after an intervention. 28 We found a lower FEV 1 to be associated with a higher improvement in exercise capacity in contrast to some studies 19,20,22, which showed that patients with some ventilatory reserve improved the most after PR. However, the negative association we found between improvement in exercise capacity after PR and initial exercise testing is in line with other studies. 19,22 An explanation for the larger improvement of the patients with low initial exercise capacity in our study may be that these patients have entered a downward spiral of dyspnea, avoidance of physical activity, deconditioning and demotivation. 9 These deconditioned and demotivated patients may have a larger capacity for improvement than patients with more preserved exercise capacity and thus may show larger improvement after exercise training. The finding that patients with a lower lactate production improve more than patients with higher lactate production is confusing. The literature until now states that high lactate at maximal exercise testing is a reflection of poor (reversible) muscle and/or cardiac function thus possibly predicting a positive response to PR. 2,6,19 The maximal incremental cycle test in our study was symptom limited, and we believe that patients really reached their maximal value, reflected by high Borg scores on dyspnea and/or fatigue. That is why we expected higher lactate levels at low exercise levels, which reflect deconditioning, to be associated with larger improvement in endurance exercise capacity. However, it may be possible that in these severe COPD patients other aspects than aerobic capacity determine maximal work load or the change in walking distance. For instance, neuromuscular efficiency and psychological factors such as desensitization and self confidence may play a role. There are some limitations to our study. In contrast with many other studies, a considerable part of our patients followed an inpatient PR program in a specialized rehabilitation centre, thus including more severe patients, even those who are oxygen-dependent. This may limit the extrapolation of our results to less severe COPD patients. In our study we used data of a maximal incremental cycle test to characterize patients at the start of our PR program, and used an endurance walking test as a primary outcome measure of change in endurance capacity. The advantage of using a maximal incremental cycle test at the beginning of PR is 98

100 Predictors of pulmonary rehabilitation outcome that more variables can be measured, such as blood gases and lactate concentrations, and that EKG-recordings can easily be made to assess exercise safety. In addition, it is shown that the peak exercise response is not different for VO 2, tidal volume, respiratory frequency and heart rate between an incremental shuttle walking test and a maximal incremental cycle test. 32 Finally, we focused on endurance capacity as an outcome measure because we believe this is important for functioning in daily life. However, to be able to select patients that benefit from PR, changes in health related quality of life and healthcare utilization after PR should be investigated as well. In our opinion, the results of the current study are clinically relevant. Single variables from lung function or maximal incremental exercise testing at entry of PR are of limited value in predicting the response to exercise training. However, the cluster analysis shows that the more severe COPD patients, i.e. patients with worse lung function combined with worse exercise capacity seem to benefit more from PR, which provides a strong argument not to exclude these severely disabled patients from PR programs. We hypothesize that in these patients a downward spiral of dyspnea, avoidance of physical activity, deconditioning and demotivation exists. Therefore, we suggest that the role of lifestyle and psychological factors such as low activity pattern, demoralization and demotivation may particularly be important in these patients and should be investigated. In conclusion, COPD patients with worse disease status, i.e. lower FEV 1, more signs of hyperinflation, lower exercise capacity and worse quadriceps force improve more in endurance exercise capacity after PR and should not be excluded for treatment with PR. Acknowledgements The authors would like to acknowledge Wim P. Krijnen ( Hanze University, Institute for Life Science and Technology, Groningen, The Netherlands) for his contribution to the statistical analyses. 5 99

101 Chapter 5 References 1. Jobin J, Maltais F, Doyon JF, Leblanc P, Simard PM, Simard AA, et al. Chronic obstructive pulmonary disease: capillarity and fiber-type characteristics of skeletal muscle. J Cardiopulm Rehabil 1998; 18: Maltais F, Simard AA, Simard C, Jobin J, Desgagnes P, Leblanc P. Oxidative capacity of the skeletal muscle and lactic acid kinetics during exercise in normal subjects and in patients with COPD. Am J Respir Crit Care Med 1996; 153: Satta A, Migliori GB, Spanevello A, Neri M, Bottinelli R, Canepari M, et al. Fibre types in skeletal muscles of chronic obstructive pulmonary disease patients related to respiratory function and exercise tolerance. Eur Respir J 1997; 10: Whittom F, Jobin J, Simard PM, Leblanc P, Simard C, Bernard S, et al. Histochemical and morphological characteristics of the vastus lateralis muscle in patients with chronic obstructive pulmonary disease. Med Sci Sports Exerc 1998; 30: O Donnell DE. Ventilatory limitations in chronic obstructive pulmonary disease. Med Sci Sports Exerc 2001; 33:S Casaburi R, Patessio A, Ioli F, Zanaboni S, Donner CF, Wasserman K. Reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. Am Rev Respir Dis 1991; 143: Casaburi R. Skeletal muscle function in COPD. Chest 2000; 117:267S-71S. 8. Engelen MP, Schols AM, Does JD, Gosker HR, Deutz NE, Wouters EF. Exercise-induced lactate increase in relation to muscle substrates in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 162: MacIntyre NR. Mechanisms of functional loss in patients with chronic lung disease. Respir Care 2008; 53: Tiep BL. Disease management of COPD with pulmonary rehabilitation. Chest 1997; 112: Agusti AG, Noguera A, Sauleda J, Sala E, Pons J, Busquets X. Systemic effects of chronic obstructive pulmonary disease. Eur Respir J 2003; 21: Pulmonary rehabilitation American Thoracic Society. Am J Respir Crit Care Med 1999; 159: Lacasse Y, Guyatt GH, Goldstein RS. The components of a respiratory rehabilitation program: a systematic overview. Chest 1997; 111: Ries AL, Bauldoff GS, Carlin BW, Casaburi R, Emery CF, Mahler DA, et al. Pulmonary Rehabilitation: Joint ACCP/AACVPR Evidence-Based Clinical Practice Guidelines. Chest 2007; 131:4S-42S. 15. Pitta F, Troosters T, Probst VS, Langer D, Decramer M, Gosselink R. Are patients with COPD more active after pulmonary rehabilitation? Chest 2008; 134: Behnke M, Wewel AR, Kirsten D, Jorres RA, Magnussen H. Exercise training raises daily activity stronger than predicted from exercise capacity in patients with COPD. Respir Med 2005; 99:

102 Predictors of pulmonary rehabilitation outcome 17. Wagner PD. Determinants of maximal oxygen transport and utilization. Annu Rev Physiol 1996; 58: Garrod R, Marshall J, Barley E, Jones PW. Predictors of success and failure in pulmonary rehabilitation. Eur Respir J 2006; 27: Plankeel JF, McMullen B, MacIntyre NR. Exercise outcomes after pulmonary rehabilitation depend on the initial mechanism of exercise limitation among non-oxygen-dependent COPD patients. Chest 2005; 127: Troosters T, Gosselink R, Decramer M. Exercise training in COPD: how to distinguish responders from nonresponders. J Cardiopulm Rehabil 2001; 21: Vagaggini B, Costa F, Antonelli S, De Simone C, De Cusatis G, Martino F, et al. Clinical predictors of the efficacy of a pulmonary rehabilitation programme in patients with COPD. Respir Med 2009; 103: Zu Wallack RL, Patel K, Reardon JZ, Clark BA,III, Normandin EA. Predictors of improvement in the 12-minute walking distance following a six-week outpatient pulmonary rehabilitation program. Chest 1991; 99: Nici L, Donner C, Wouters E, Zuwallack R, Ambrosino N, Bourbeau J, et al. American Thoracic Society/ European Respiratory Society statement on pulmonary rehabilitation. Am J Respir Crit Care Med 2006; 173: Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl 1993; 16: Revill SM, Morgan MD, Singh SJ, Williams J, Hardman AE. The endurance shuttle walk: a new field test for the assessment of endurance capacity in chronic obstructive pulmonary disease. Thorax 1999; 54: Singh SJ, Morgan MD, Scott S, Walters D, Hardman AE. Development of a shuttle walking test of disability in patients with chronic airways obstruction. Thorax 1992; 47: Singh SJ, Morgan MD, Hardman AE, Rowe C, Bardsley PA. Comparison of oxygen uptake during a conventional treadmill test and the shuttle walking test in chronic airflow limitation. Eur Respir J 1994; 7: Eaton T, Young P, Nicol K, Kolbe J. The endurance shuttle walking test: a responsive measure in pulmonary rehabilitation for COPD patients. Chron Respir Dis 2006; 3: Schaubert KL, Bohannon RW. Reliability and validity of three strength measures obtained from community-dwelling elderly persons. J Strength Cond Res 2005; 19: Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc 2007; 39: Nelson ME, Rejeski WJ, Blair SN, Duncan PW, Judge JO, King AC, et al. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc 2007; 39:

103 Chapter Luxton N, Alison JA, Wu J, Mackey MG. Relationship between field walking tests and incremental cycle ergometry in COPD. Respirology 2008; 13:

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106 CHAPTER 6 Changes in the endurance shuttle walk test in COPD patients with chronic respiratory failure after pulmonary rehabilitation: the minimal important difference obtained with anchor- and distribution-based method. Wytske A. Altenburg, Marieke L. Duiverman, Nick H.T. ten Hacken, Huib A.M. Kerstjens, Mathieu H.G. de Greef, Peter J. Wijkstra, Johan B. Wempe Respiratory Research, February 2015, 16:27

107 Chapter 6 Abstract Background: Although the endurance shuttle walk test (ESWT) has proven to be responsive to change in exercise capacity after pulmonary rehabilitation (PR) for COPD, the minimally important difference (MID) has not yet been established. We aimed to establish the MID of the ESWT in patients with severe COPD and chronic hypercapnic respiratory failure following PR. Methods: Data were derived from a randomized controlled trial, investigating the value of noninvasive positive pressure ventilation added to PR. Fifty-five patients with stable COPD, GOLD stage IV, with chronic respiratory failure were included (mean (SD) FEV (12.0) % pred, age 62 (9) y). MID estimates of the ESWT in seconds, percentage and meters change were calculated with anchor based and distribution based methods. Six minute walking distance (6MWD), peak work rate on bicycle ergometry (Wpeak) and Chronic Respiratory Questionnaire (CRQ) were used as anchors and Cohen s effect size was used as distribution based method. Results: The estimated MID of the ESWT with the different anchors ranged from s, 76-82% and m. Using the distribution based method the MID was 144s, 61% and 137m. Conclusions: Estimates of the MID for the ESWT after PR showed only small differences using different anchors in patients with COPD and chronic respiratory failure. Therefore we recommend using a range of s, 76-82% or m as MID of the ESWT in COPD patients with chronic respiratory failure. Further research in larger populations should elucidate whether this cut-off value is also valid in other COPD populations and with other interventions. Trial registration: ClinicalTrials.Gov (ID NCT ). 106

108 Minimally important difference of the ESWT Background Patients with severe Chronic Obstructive Pulmonary Disease (COPD) have an impaired exercise capacity, which is frequently associated with lower physical activity level 1 and, importantly, with lower quality of life 2,3 and higher mortality 4. Therefore, enhancement of exercise capacity is an important goal of interventions such as pulmonary rehabilitation (PR) 5 and pharmacological treatment 6. Exercise capacity can be assessed by maximal and submaximal tests, which reflect different pathobiological properties like sufficient aerobic enzyme systems, muscle strength, cardiovascular fitness and motivation. Maximal exercise capacity is commonly assessed with incremental cycle ergometry or treadmill walking, but these tests are not very responsive to interventions such as medication 7 or exercise training 8. Field walking tests, such as the sixminute walking distance (6MWD) and endurance shuttle walk test (ESWT), might better reflect quality of life and activities of daily living, and therefore might be more relevant measurements in patients with severe COPD. The ESWT has a number of advantages compared to the 6MWD. Firstly, the ESWT has been shown to be very responsive to bronchodilation 9 and PR 10,11 and might be even more responsive to treatment than the 6MWD 11,12. Secondly, the ESWT is less affected by motivation and pacing ability of the patient than the 6MWD because gate speed is imposed. 13,14 Unfortunately, at this moment it is not clear which size of change in ESWT could be considered as clinically relevant. This is important for developing new studies, for weighing results of interventions, and for clinicians in evaluating provided care. Until now, only one study provided some information about the minimally important difference (MID) of the ESWT. 15 In that study, the MID was investigated after bronchodilation and PR using an anchor based (global rating of change) and distribution based method (half a standard deviation (SD) of the changes in ESWT time or distance). 15 The MID of the ESWT after treatment with salmeterol or ipratropium bromide was found to be seconds. The anchor based MID of the ESWT after 7 weeks of PR, however, was not determined. 6 For this study we used the Chronic Respiratory Questionnaire (CRQ), peak work rate (Wpeak) and 6MWD as anchors in combination with a distribution based method. Those anchors were chosen because they are accepted outcomes of pulmonary rehabilitation and all in some way reflect exercise capacity or quality of life. The aim of the current study is to determine the MID of the ESWT in patients with severe, hypercapnic COPD (GOLD IV) following PR with or without nocturnal non-invasive intermittent positive pressure ventilation (NIPPV). 107

109 Chapter 6 Methods Study population A total of 55 patients with stable COPD, GOLD stage IV, with chronic hypercapnic respiratory failure, were included in the current analyses. All these patients participated in a randomized controlled trial of which the results were published previously. 16,17 In this study the additional effect of NIPPV on the effects of PR was investigated. Seventy-two patients were included in the study, of which 56 patients completed the rehabilitation program of 12 weeks. Patients were assigned to rehabilitation with (n=32) or without NIPPV (n=24). Inclusion criteria were a stable clinical condition (no exacerbation in the four weeks prior to study participation), severe COPD (FEV 1 <50%pred), hypercapnia at rest (arterial carbon dioxide pressure PaCO 2 >6.0 kpa while breathing room air) and age between years. Exclusion criteria were the presence of cardiac or neuromuscular diseases limiting exercise tolerance, exposure to NIPPV or PR in the previous 18 months, or the presence of obstructive sleep apnoea syndrome (apnoea/ hypopnoea index 10/hour). The study was approved by the Medical Ethics Committee of the University Medical Centre Groningen and was registered at ClinicalTrials.Gov (ID NCT ). All patients gave written informed consent to participate. In the current analysis only patients that completed all measurements (31 in the PR group and 24 in the PR + NIPPV group) at the start and directly after the rehabilitation program were included. Study design At baseline lung function, exercise tolerance and quality of life were assessed. Thereafter patients started a 12 week period of rehabilitation with or without NIPPV. The rehabilitation program consisted of strength training, cycling, walking, inspiratory muscle training, education and psychological and/or nutritional support if necessary as described in detail elsewhere. 16,17 The exercise training sessions were on three days per week. NIPPV was initiated in the hospital to train the patients to use the ventilatory support during the night as long as possible with a minimum duration of 6 hours. The adjustment process of NIPPV and the patient compliance afterwards were described in detail in previous publications. 16,17 After the intervention period of 12 weeks measurements of exercise tolerance and quality of life were repeated. Apnea/ hypoapnea index was measured with overnight polygraphy prior to the study. Measurements All lung function measurements were performed after bronchodilation. Forced expiration volume in 1 second (FEV 1 ) and forced vital capacity (FVC) were assessed by spirometry according to ERS criteria. 18 Total lung capacity (TLC) and residual volume (RV) were measured by body plethysmography. 19 Cycle ergometer tests were performed after optimal bronchodilation. First, daytime resting arterial blood gases on room air were taken from all patients while lying (Rapid lab type 865, Siemens, USA). The incremental cycle ergometer test was performed using a 1-minute incremental protocol, using 5 Watt increments. Patients were seated on the bicycle, respired through a mouth piece and wore a nose clip during the test. Minute ventilation, tidal volume, breathing frequency and oxygen uptake were measured continuously (Oxycon Pro Viasys, Bilthoven, the Netherlands). Maximal workload (Wpeak) was defined as the highest work level reached and maintained for at least 30 seconds. 108

110 Minimally important difference of the ESWT The ESWT was performed on a 10 m long course at a speed corresponding with 85% of VO 2 peak, which was estimated from an earlier performed incremental shuttle walking test. 20 For both tests a practice walk was done during the run-in period of the study. Patients were instructed to walk as long as possible at the speed that was dictated by the auditory signal. The test was ended when a patient was more than 0.5 m away from the marker before the signal was given on two successive shuttles, or when he or she indicated to be exhausted. The 6MWD was assessed indoors on a 40 m long course. Patients used their usual walking aids and, if applicable, their usual ambulatory oxygen therapy during the test. The test assistant gave standardized encouragements every 30 seconds and told the patient after 2 and after 4 minutes that he/she was 2 and 4 minutes on his/her way. 21 All patients performed a practice test first, the results of which were discarded. During the walking tests supplemental oxygen was permitted, but conditions were the same at all tests. The walking tests were not stopped because of desaturation. Quality of life was assessed with the interviewed version of the Chronic Respiratory Questionnaire. 22 The CRQ is a widely used disease specific questionnaire which has shown to be reliable and valid in COPD patients. 23 Minimal important difference calculation methods and statistical analysis The minimal important difference can be estimated in various ways and generally a combination of methods is recommended. 24 In the current study we used both anchor based and distribution based methods. For the anchor based method we used three measures with an established MID: The 6MWD (25m) 25, Wpeak (4 Watt) 26,27 and the CRQ (10 points in total score) 28. Spearman s correlations between improved ESWT on the one hand and improved 6MWD, Wpeak and CRQ on the other hand had to be > 0.30 allowing linear regression analyses. There is no consensus on what an appreciable association between the outcome variable and the anchor should be. However, a correlation of 0.30 is considered to be the lower limit. 24,26,29 Afterwards, the MID of the ESWT was derived from substituting the MID of the anchors in the regression line of ESWT and anchor. A distribution-based method was used to compare the change in outcome variable with an arbitrary measure of variability, which in this study was the effect size, using the following equation: 0.5 *SD (ΔESWT). 6 The analyses were performed on pooled treatment groups as the separate analyses of the two treatment arms (PR or PR + NIPPV) showed similar associations, thereby increasing statistical power. The MID of the ESWT was expressed as change in time, percentage change from baseline (time or meters) and change in meters. All statistical analyses were performed using Scientific Package of Social Sciences (SPSS) version P-values <0.05 were considered to be significant. 109

111 Chapter 6 Results The baseline characteristics of the 55 COPD patients (42% female) are shown in Table 1. Table 1. Baseline characteristics (n=55) Age, y 62.0 (9) BMI, kg/m (6.1) FEV 1,l 0.84 (0.34) FEV 1 %pred, % 31.1 (12.0) FEV 1 /FVC, % 31.8 (9.2) TLC, l 7.27 (1.41) RV/TLC, % 63.9 (9.1) PO 2, kpa 8.14 (1.18) PCO 2, kpa 6.85 (0.73) Wpeak, W 28.1 (18.5) VO 2 peak, ml/min 250 (56) ISWT, m 160 (40-450) ESWT, m 240 ( ) ESWT, s 257 ( ) 6MWD, m 315 (80-615) CRQ total 80.3 (17.8) CRQ dyspnoea 16.7 (4.8) CRQ fatigue (4.5) CRQ emotion 31.5 (7.9) CRQ mastery 18.4 (5.0) Values or expressed as mean (SD) or median (range). BMI: body mass index; FEV 1 : forced expiration volume in 1 second; FVC: forced vital capacity; TLC: total lung capacity; RV: residual volume; Wpeak: peak work rate; ISWT: incremental shuttle walk test; ESWT: endurance shuttle walk test; 6MWD: six minute walking distance; CRQ: Chronic Respiratory Questionnaire Correlates of ESWT change with change in anchors For further analysis correlations >0.30 were used. These were shown for ESWT change in absolute time (ΔESWTs) and % change from baseline (ΔESWT%) with all three anchors, 6MWD, Wpeak and CRQ, and for ESWT change in meters (ΔESWTm) with the CRQ and Wpeak. (Table 2 and online Figure 1) The CRQ total score showed higher correlations with ESWT change than the CRQ subscales and therefore CRQ total score was used in the regression analysis. 110

112 Minimally important difference of the ESWT Table 2. Spearman s Correlation of ESWT with possible anchors ΔESWT (s) ΔESWT (%) ΔESWT (m) Wpeak, W CRQ total CRQ dyspnoea CRQ fatigue CRQ emotion CRQ mastery MWD, m Values printed bold p<0.05. Wpeak: peak work rate; CRQ: Chronic Respiratory Questionnaire; 6MWD: six minute walking distance; ΔESWT: change in endurance shuttle walking test Anchor based and distribution based estimates of the MID of the ESWT Table 3 shows the MID estimates and 95% confidence intervals (in seconds, percentage and meters) derived from the linear regression equations of ΔESWT and Δanchor. (online Table 1) The MID estimate of ESWTm using the 6MWD as an anchor was not calculated because ΔESWTm and Δ6MWD correlated <0.30. The MID estimates calculated with the distribution based method were 145s for ΔESWTs, 61.4% for ΔESWT% and 137m for ΔESWTm. Tabel 3. Anchor-based MID of ESWT (s and %) using CRQ and 6MWD anchor MID ESWT 95% CI MID ESWT (s) Wpeak CRQ MWD MID ESWT (%) Wpeak CRQ MWD MID ESWT (m) Wpeak CRQ Wpeak: peak work rate; CRQ: Chronic Respiratory Questionnaire; 6MWD: six minute walking distance; ΔESWT: change in endurance shuttle walking test 6 111

113 Chapter 6 Discussion In this population of patients with severe COPD and chronic hypercapnic respiratory failure, who followed PR (with or without NIPPV), we estimated the MID for the ESWT. Using three different anchors we found MID estimates ranging from s, 76-82% and m. The anchors Wpeak and 6MWD provided almost identical results. In contrast, the MID based on statistical variability of the effect size was somewhat lower: 61%, 145s and 137 m. All anchors used in our study meet the criteria of a good anchor. 24 These criteria, applied to this field, are firstly: the anchor should have an established MID derived from multiple high quality studies, including many well characterized COPD patients, using multiple methods, and agreeing about the final MID estimate. Secondly, the anchor should be derived from a comparable COPD population. Thirdly, the anchor should somehow reflect the perception of improved exercise capacity. Finally the anchor should correlate highly with changes in ESWT. The anchors used in this study will be discussed in this perspective. The first anchor was the Chronic Respiratory Questionnaire. The CRQ has a widely accepted MID of 10 points on the total score (or 0.5 per question), which has been estimated with different methods. 28,30,31 In addition, the CRQ has served as an anchor for establishing MID s of other measurement tools as well, such as the Hospital Anxiety and Depression Scale and the feeling thermometer. 32,33 Correlations of CRQ change and ESWT change showed rho values > 0.40 and the CRQ could therefore be used as an anchor. Although the CRQ does not reflect the exact same concept as the ESWT, it is a measure that reflects the patients perception of health status, which agrees with the MID concept. The second anchor was Wpeak. Two studies estimated the MID for Wpeak using anchor based or distribution based methods and expert opinions. Both studies suggest a MID of 4 Watt. 26,27 Correlations of Wpeak change and ESWT change showed rho values > 0.50 suggesting that Wpeak could be used as an anchor. In addition, Wpeak reflects exercise capacity as does the ESWT, and in both tests patients reach a similar peak performance. 34 The 6MWD also seems a suitable anchor as its MID has been established in different subgroups of COPD patients using different interventions including a PR intervention. We chose to use the MID of 25 m, based on two studies, one in a slightly milder COPD population (age 70 y, FEV 1 52% pred) after PR 25, and one in a more severe COPD population (age 66.4, FEV % pred), showing an MID of 26m after surgical lung volume reduction. 26 Another feature demonstrating the 6MWD to be a suitable anchor is that it reflects exercise capacity, as does the ESWT, though perhaps in a different way. Associations of 6MWD change with ESWT change were just high enough to use it as an anchor, therefore this estimation should be taken with some caution. On the other hand, the MID estimated using the 6MWD as anchor was very similar to the MID estimated using the CRQ and Wpeak. To verify the MID values found with the anchor based method we also used a distribution based method. The latter method should only be used complementary to an anchor based method as it does not fit with the primary aim of the MID concept, which is to indentify an effect size that is relevant in the perception of the patient. 24 In our study the distribution based 112

114 Minimally important difference of the ESWT method showed lower values for the MID than the anchor based method. It has been shown before that distribution based methods tend to underestimate the MID when based on a single study. 32 The MID values estimated with the CRQ, Wpeak and 6MWD were very close to one another (see Table 3). The MID estimated with the distribution based method was somewhat lower (144s, 61% and 137 m). In line with the literature we recommend to use MID values based on the anchor based method. 24 We prefer to use the MID estimates in seconds and %, and not meters as a change of 100 meters at a low speed has a different value in clinical perspective than a change of 100m at a high speed. The estimation of the MID of the ESWT after PR has been investigated in one other study in patients with less severe COPD (FEV 1 48% pred). In this study, global rating of change was used as an anchor, comprising of one question. To our opinion, the anchors in our study were suitable as well because the CRQ, 6MWD and to a lesser degree Wpeak, are outcome measures with an established MID and showed correlations >0.30 with ESWT change. However, we realize that our anchors might not reflect exactly the same construct as the ESWT. Pepin et al only used a distribution based method showing an MID of 186 seconds or 136%, because they decided that associations with the global rating of change were too low to be used to estimate an anchor based MID after PR. Though we studied a different population than Pepin, our anchor based MID was surprisingly similar to their distribution based estimate, at least for the change in ESWT (s). Of course we were very interested in how our results are in comparison to other PR intervention studies that used the ESWT as an outcome measure. Several studies were found and they all showed significant improvements in ESWT after intervention. 10, The studies included patients with quite similar mean age (60-75 years) and mean FEV 1 ( %predicted) and demonstrated mean ESWT improvements between seconds, % and meters. 10,35-39 These change values were consistent with our MID estimates (ranging from s, 76-82% and m). A major difference with the patients included in the present analysis is that the patients in the current analysis all suffered from chronic hypercapnic respiratory failure. Probably, the differences found in mean ESWT changes in these studies are due to differences in COPD population, study design and efficacy of the intervention. 6 A strong point of our study is that we used an anchor based method including three different anchors as well as a distribution based method to determine the MID of the ESWT. Another strong feature is that the correlations of the ESWT change with all anchors were above 0.30, allowing us to use the anchors in a meaningful way. A limitation of this study might be the relatively small number of patients in the study and the fact that this was a very specific group of COPD patients, namely those with severe COPD and chronic respiratory failure. Therefore, it might not be appropriate to generalize our results straight to the entire COPD population as the MID might differ between populations with other phenotypes and disease stages. A remark should also be made about the confidence intervals for the MID estimates we found, which were quite wide. This hinders firm conclusions. Another limitation of this study is that we did not use a global rating of change as an anchor to 113

115 Chapter 6 estimate the MID of the ESWT. For example by asking the patient the question: In comparison with your previous test, how would you rate your performance on the current test? Using a 7-point Likert scale to rate this performance. Conclusions In conclusion, in patients with severe hypercapnic COPD undergoing PR with or without NIPPV, the MID estimates for the ESWT ranged from s, 76-82% and m using different anchors (CRQ, Wpeak, 6MWD). Estimates of the MID of the ESWT using 6MWD and Wpeak as anchors provide almost identical results. This MID construct needs further validation in larger and different subgroups of COPD patients. Acknowledgements This study was funded by the Dutch Asthma Foundation. 114

116 Minimally important difference of the ESWT Referrences 1. Bossenbroek L, de Greef MH, Wempe JB, Krijnen WP, Ten Hacken NH. Daily physical activity in patients with chronic obstructive pulmonary disease: a systematic review. COPD 2011; 8: Stavem K, Boe J, Erikssen J. Health status, dyspnea, lung function and exercise capacity in patients with chronic obstructive pulmonary disease. Int J Tuberc Lung Dis 1999; 3: Mangueira NM, Viega IL, Mangueira Mde A, Pinheiro AN, Costa Mdo R. Correlation between clinical parameters and health-related quality of life in women with COPD. J Bras Pneumol 2009; 35: Cote CG, Pinto-Plata V, Kasprzyk K, Dordelly LJ, Celli BR. The 6-min walk distance, peak oxygen uptake, and mortality in COPD. Chest 2007; 132: Lacasse Y, Martin S, Lasserson TJ, Goldstein RS. Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. A Cochrane systematic review. Eura Medicophys 2007; 43: Liesker JJ, Wijkstra PJ, Ten Hacken NH, Koeter GH, Postma DS, Kerstjens HA. A systematic review of the effects of bronchodilators on exercise capacity in patients with COPD. Chest 2002; 121: Oga T, Nishimura K, Tsukino M, Hajiro T, Ikeda A, Izumi T. The effects of oxitropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease. A comparison of three different exercise tests. Am J Respir Crit Care Med 2000; 161: Plankeel JF, McMullen B, MacIntyre NR. Exercise outcomes after pulmonary rehabilitation depend on the initial mechanism of exercise limitation among non-oxygen-dependent COPD patients. Chest 2005; 127: Brouillard C, Pepin V, Milot J, Lacasse Y, Maltais F. Endurance shuttle walking test: responsiveness to salmeterol in COPD. Eur Respir J 2008; 31: Altenburg WA, de Greef MH, Ten Hacken NH, Wempe JB. A better response in exercise capacity after pulmonary rehabilitation in more severe COPD patients. Respir Med 2012; 106: Eaton T, Young P, Nicol K, Kolbe J. The endurance shuttle walking test: a responsive measure in pulmonary rehabilitation for COPD patients. Chron Respir Dis 2006; 3: Pepin V, Brodeur J, Lacasse Y, Milot J, Leblanc P, Whittom F, et al. Six-minute walking versus shuttle walking: responsiveness to bronchodilation in chronic obstructive pulmonary disease. Thorax 2007; 62: Solway S, Brooks D, Lacasse Y, Thomas S. A qualitative systematic overview of the measurement properties of functional walk tests used in the cardiorespiratory domain. Chest 2001; 119: Eiser N, Willsher D, Dore CJ. Reliability, repeatability and sensitivity to change of externally and selfpaced walking tests in COPD patients. Respir Med 2003; 97: Pepin V, Laviolette L, Brouillard C, Sewell L, Singh SJ, Revill SM, et al. Significance of changes in endurance shuttle walking performance. Thorax 2011; 66: Duiverman ML, Wempe JB, Bladder G, Vonk JM, Zijlstra JG, Kerstjens HA, et al. Two-year home-based nocturnal noninvasive ventilation added to rehabilitation in chronic obstructive pulmonary disease patients: a randomized controlled trial. Respir Res 2011; 12: Duiverman ML, Wempe JB, Bladder G, Jansen DF, Kerstjens HA, Zijlstra JG, et al. Nocturnal non-invasive ventilation in addition to rehabilitation in hypercapnic patients with COPD. Thorax 2008; 63:

117 Chapter Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al. Standardisation of spirometry. Eur Respir J 2005; 26: Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, et al. Standardisation of the measurement of lung volumes. Eur Respir J 2005; 26: Revill SM, Morgan MD, Singh SJ, Williams J, Hardman AE. The endurance shuttle walk: a new field test for the assessment of endurance capacity in chronic obstructive pulmonary disease. Thorax 1999; 54: Guyatt GH, Sullivan MJ, Thompson PJ, Fallen EL, Pugsley SO, Taylor DW, et al. The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J 1985; 132: Guyatt GH, Berman LB, Townsend M, Pugsley SO, Chambers LW. A measure of quality of life for clinical trials in chronic lung disease. Thorax 1987; 42: Wijkstra PJ, TenVergert EM, Van Altena R, Otten V, Postma DS, Kraan J, et al. Reliability and validity of the chronic respiratory questionnaire (CRQ). Thorax 1994; 49: Revicki D, Hays RD, Cella D, Sloan J. Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes. J Clin Epidemiol 2008; 61: Holland AE, Hill CJ, Rasekaba T, Lee A, Naughton MT, McDonald CF. Updating the minimal important difference for six-minute walk distance in patients with chronic obstructive pulmonary disease. Arch Phys Med Rehabil 2010; 91: Puhan MA, Chandra D, Mosenifar Z, Ries A, Make B, Hansel NN, et al. The minimal important difference of exercise tests in severe COPD. Eur Respir J 2011; 37: Sutherland ER, Make BJ. Maximum exercise as an outcome in COPD: minimal clinically important difference. COPD 2005; 2: Jaeschke R, Singer J, Guyatt GH. Measurement of health status. Ascertaining the minimal clinically important difference. Control Clin Trials 1989; 10: Hartman JE, Ten Hacken NH, Klooster K, Boezen HM, de Greef MH, Slebos DJ. The minimal important difference for residual volume in patients with severe emphysema. Eur Respir J 2012; 40: Redelmeier DA, Guyatt GH, Goldstein RS. Assessing the minimal important difference in symptoms: a comparison of two techniques. J Clin Epidemiol 1996; 49: Juniper EF, Guyatt GH, Willan A, Griffith LE. Determining a minimal important change in a diseasespecific Quality of Life Questionnaire. J Clin Epidemiol 1994; 47: Puhan MA, Frey M, Buchi S, Schunemann HJ. The minimal important difference of the hospital anxiety and depression scale in patients with chronic obstructive pulmonary disease. Health Qual Life Outcomes 2008; 6: Schunemann HJ, Griffith L, Jaeschke R, Goldstein R, Stubbing D, Guyatt GH. Evaluation of the minimal important difference for the feeling thermometer and the St. George s Respiratory Questionnaire in patients with chronic airflow obstruction. J Clin Epidemiol 2003; 56:

118 Minimally important difference of the ESWT 34. Hill K, Dolmage TE, Woon L, Coutts D, Goldstein R, Brooks D. Comparing peak and submaximal cardiorespiratory responses during field walking tests with incremental cycle ergometry in COPD. Respirology 2012; 17: Effing T, Zielhuis G, Kerstjens H, van der Valk P, van der Palen J. Community based physiotherapeutic exercise in COPD self-management: a randomised controlled trial. Respir Med 2011; 105: Dyer F, Callaghan J, Cheema K, Bott J. Ambulatory oxygen improves the effectiveness of pulmonary rehabilitation in selected patients with chronic obstructive pulmonary disease. Chron Respir Dis 2012; 9: Ringbaek T, Martinez G, Durakovic A, Thogersen J, Midjord AK, Jensen JE, et al. Vitamin d status in patients with chronic obstructive pulmonary disease who participate in pulmonary rehabilitation. J Cardiopulm Rehabil Prev 2011; 31: Leung RW, McKeough ZJ, Peters MJ, Alison JA. Short-form Sun-style t ai chi as an exercise training modality in people with COPD. Eur Respir J 2013; 41: McNamara RJ, McKeough ZJ, McKenzie DK, Alison JA. Water-based exercise in COPD with physical comorbidities: a randomised controlled trial. Eur Respir J 2013; 41:

119 Chapter 6 Supplementary data Online figure 1a-i. Scatterplots of change in ESWT versus change in anchor variable 118

120 Minimally important difference of the ESWT Online Table 1. Regression equations used to calculate MID values Constant B 95% CI B ΔESWT (s) MID ESWT = * MID CRQ MID ESWT = * MID 6MWD MID ESWT = * MID peak work rate ΔESWT (%) MID ESWT = * MID CRQ MID ESWT = * MID 6MWD MID ESWT = * MID peak work rate ΔESWT (m) MID ESWT = * MID CRQ MID ESWT = * MID peak work rate ESWT: endurance shuttle walk test; MID: minimally important difference; CRQ: chronic respiratory questionnaire; 6WD: six-minute walking distance. MID CRQ= 10 points, MID 6MWD= 25 meter, MID peak work rate= 4 Watt The numbers in the equations are rounded off by 2 decimal places. For the calculation of the MID s numbers were not rounded off (table 3)

121

122 CHAPTER 7 Summary and general discussion

123 Chapter 7 Summary and general Discussion In this thesis two main topics have been addressed: physical activity and physical fitness in patients with COPD. As detailed in Chapter 1 physical activity is defined as any bodily movement produced by skeletal muscles that requires energy expenditure. 1 And physical fitness can be defined as the ability to carry out daily tasks with vigor and alertness, without undue fatigue, and with ample energy to enjoy leisure time. Physical fitness can be divided into performance and health related fitness. 2 Both topics are important in patients with COPD. Physical activity level has been shown to be decreased even in early stages of the disease. 3 Low physical activity level has negative consequences in general and for COPD patients in particular. Physical fitness in this population is also decreased and loss of exercise tolerance and muscle strength negatively affect quality of life. Physical activity and physical fitness affect each other and can both be modified by interventions such as physical activity counseling and pulmonary rehabilitation (PR). Physical activity and physical fitness may also be affected by psychological variables and biological or environmental variables as has been described in the introduction of this thesis. This thesis focused on five research questions related to physical activity and physical fitness. Figure 1 shows in which chapters (2-6) the five research questions have been discussed. The figure shows how physical activity and physical fitness have a reciprocal interaction and can be modulated by interventions and psychological variables. Physical activity counseling Rehabilitation Interventions 4 3 Psychological variables 5 Interacting variables in COPD Physical activity 2 Physical fitness 6 Daily steps Daily physical activity HADS SRQ-E LIVAS ESWT 6MWD Measurement Tools Figure 1. Analytical model of variables interacting with physical activity and physical fitness in COPD. HADS: Hospital Anxiety and Depression Scale; SRQ-E: Self Regulation Questionnaire for Exercise; LIVAS: Lichamelijke vaardigheden schaal, Dutch version of the Perceived Physical Ability Subscale; ESWT: Endurance shuttle walk test; 6MWD: six minute walking distance. The numbers refer to the chapters in this thesis. 122

124 Summary and general discussion Physical activity in COPD Chapters 2, 3 and 4 dealt with physical activity in COPD patients. Three topics were addressed more specifically: - The relationship between daily physical activity, physical variables and psychological variables. Direct as well as indirect relationships between those variables were studied cross-sectionally. - The effects of a physical activity counseling intervention on physical activity level, exercise capacity and quality of life in patients from general practices, outpatient clinics and a PR centre. - The predictors of and reasons for drop-outs from a physical activity counseling study. To investigate these topics data from the COACH study, a randomized controlled trial, were used. In this trial COPD patients from all GOLD stages were recruited in three different settings: general practices, hospital outpatient clinics and a specialized PR centre. The counseling group received an intensive intervention period of 3 months in which 5 counseling sessions took place, followed by a follow up period of 12 months in which three additional counseling sessions were scheduled, including one phone call. The usual care group received care appropriate to their health status, which was a multidisciplinary PR program in the PR setting. The relationship between physical activity, physical fitness and psychological variables In chapter 2 the baseline data of the COACH study were used to investigate the associations of physical activity with variables reflecting functional capacity and psychological variables. In addition, we investigated whether these associations differed for patients with high or low functional status. Variables that correlated significantly with steps per day were included in a multiple linear regression model, which showed that the six minute walking distance (6MWD) and Saint George Respiratory Questionnaire (SGRQ) activity score together explained 37% of the variance of physical activity. However, in a multiple linear regression model containing only psychological variables the Dutch version of the perceived physical ability subscale (LIVAS), which measures self-efficacy, still explained a considerable 16% of the variance of physical activity. This led us to believe that the association of psychological variables with physical activity might be indirect and mediated by variables reflecting functional capacity. In a structural equations model this hypothesis was tested, and results suggested that indeed psychological variables indirectly explained physical activity through functional capacity variables. Besides that, we divided the population in patients with high and low functional status (based on the median 6 MWD) and calculated associations of physical activity with variables reflecting functional capacity and psychological variables within these two groups. In patients with a lower functional status physical activity was significantly associated with seven of the variables reflecting functional capacity (i.e. forced expiration volume in one second (FEV 1 ), 6MWD, Groningen Activity Restriction Scale (GARS) total score, SF-36 physical function, SGRQ activity, Clinical COPD Questionnaire (CCQ) function and Dutch Exertion and Fatigue Scale (DEFS)), whereas in patients with a higher functional status, physical activity was related to only four of these variables (i.e. 6 MWD, SGRQ activity, CCQ function and DEFS). In addition, in patients with a higher functional status a significant association existed between physical activity and two psychological variables (i.e. self-efficacy (LIVAS) and depression (HADS)), which was not found in patients with low functional status

125 Chapter 7 These results suggest an influence of psychological variables on someone s functional capacity. Using structural equations modeling we were able to show indirect relationships between groups of variables. Apparently variables such as motivation, self efficacy, anxiety and depression influence a persons functional capacity, which in turn influences the actual use of these capabilities expressed as daily physical activity. In addition, the analysis in the two subgroups suggests that psychological variables may play a more important role in physical activity in patients with high functional status, whereas variables reflecting functional capacity may be a more important determinant of physical activity in patients with low functional status. This cross sectional analysis of the COACH data showed, in line with other studies in COPD, that physical activity was significantly associated with variables reflecting functional capacity: higher physical activity level was associated with higher FEV 1 3-8, higher general quality of life (SF-36) 5,9, lower fatigue (DEFS) 10 and higher disease specific quality of life (SGRQ and CCQ) 7,8,11. The 6MWD, which explained the largest part of the variance in our multiple regression model, was also found to be a determining factor in three other studies. 4,5,11 In addition to the existing literature, we found that in COPD physical activity was negatively associated with disability (GARS), which has to our knowledge not been reported before. Regarding psychological variables in our study we found higher physical activity level to be associated with a higher self-efficacy, which is in accordance with two other studies in COPD. 5,8 Moreover, lower depressive symptoms were found to be associated with higher physical activity level, which was not found in two earlier studies. 3,9 Finally, and again, in addition to the existing literature we found that psychological variables might indirectly affect physical activity through variables reflecting functional capacity. The effects of a physical activity counseling program In chapter 3 we investigated the short- and long term effects of the COACH physical activity counseling program. In a population of 155 COPD patients from three healthcare settings a randomized controlled trial was performed aiming at increasing physical activity. The primary outcome measure of this study was physical activity level (steps/day and total activity/day), secondary outcome measures were quality of life (CRQ and CCQ) and exercise capacity (6MWD). Results show that steps/day and total activity/day increased significantly from 0-3 months in the counseling group compared to usual care in the total group (p=0.001) as well as in the outpatient clinic subgroup (p= 0.007) and the PR subgroup (p=0.03), but not in the general practice subgroup. After 15 months a nearly significant difference between counseling and usual care in the total group was found (p=0.062). When patients with a baseline physical activity level >10000 steps/day, who can be considered as sufficiently physically active, were excluded from the analysis, there was a significant long term positive effect of the counseling program (p=0.017) in the total group. With respect to secondary outcome measures significant changes in exercise capacity (6MWD) and quality of life (CRQ) were shown from 0-3 months only in the outpatient clinic group (p=0.049 for 6MWD, p=0.006 for CRQ). To our knowledge this was the first study that investigated the short term as well as the long term results of physical activity counseling in COPD. It is interesting that the physical activity counseling is not only assessed in patients in a PR setting, but also in the general practice and 124

126 Summary and general discussion outpatient clinic settings, thereby including a broad range of COPD patients. The COACH study confirmed short term results from two pilot studies 12,13 and added promising long term results. A higher physical activity level was maintained after 1 year follow up, at least in patients with a baseline step count <10000 steps/day. Indeed, some adjustments might be necessary to better tailor the program to the individual patient, which will be discussed below in the discussion and practical implications sections. It is generally acknowledged that behavioral change programs are more likely to succeed when the intervention period is longer than 6 months. The Stages of Change model suggests that a person, who tries to change behavior, starts and stays in the action phase for about six months before entering the maintenance phase. 14 Two recent studies with longer intervention periods indeed showed sustained effects on physical activity level in other populations In COPD a six months period of PR was necessary to increase physical activity, whereas three months of rehabilitation was sufficient to improve exercise capacity and quality of life. 18 This suggests that longer intervention periods indeed are needed to induce long-lasting changes in physical activity behavior. Predictors of and reasons for dropout from a physical activity counseling study In chapter 4 dropout from the COACH study was investigated. Drop out is a problem that frequently occurs in programs aiming at enhancement of physical activity level in patients with chronic disorders, whether or not as part of a clinical trial. 19,20 We investigated the reasons for and predictors of drop out of patients participating in a physical activity counseling study. Total dropout rate of the physical activity counseling study was 29.7%. Death, motivation, medical and personal reasons were identified as reasons for dropout. Motivation (n=22) and medical reasons (n=12) were the most prevalent reasons for dropout. Medical reasons were among the most important reasons for dropout from PR studies as well Although both treatment strategies may differ in their burden for the patients, the reasons for dropout may be similar. Regarding predictors of dropout, low intrinsic motivation for physical activity and low mental status at baseline predicted dropout from counseling in the short term (0-3 months). Lung function (FEV 1 ) predicted dropout from counseling in the long term (3-15 months). Only low motivation for physical activity predicted short term dropout from usual care, whereas lower functional status predicted long-term dropout from usual care. It seems that short term dropout is characterized more by psychological factors such as motivation and mental status, especially when a patient is participating in a physical activity behavior change program. In contrast, in long term dropout factors related to diseases status (FEV 1, functional status) play a more important role. 7 This study adds to the literature an analysis of dropout from physical activity counseling in COPD, which has not been reported before. There are some studies reporting on dropout from PR. In accordance with these studies we found medical reasons to be the most frequent reasons for dropout. Regarding predictors of dropout, low mental status was a predictor which might be similar to a PR study that found being depressed to predict dropout. 23 In addition, lower FEV 1, predicting long term drop out in our study, might be linked to worse disease status, which may also be the case for quadriceps force, higher number of pack years and lower fat free mass, which were found to be predictors of dropout in two PR studies. 21,23 125

127 Chapter 7 Discussion physical activity in COPD Together the results of the COACH study show that the role of psychological variables should not be underestimated in explaining physical activity behavior in COPD and therefore should not be overlooked in physical activity behavior change programs in this disease. Especially in patients with higher functional status these variables may play an important role as significant associations of physical activity with depression and self efficacy were shown. In addition, when we look at dropout, a psychological reason like lack of motivation is the most important reason of dropout. Moreover, intrinsic motivation for physical activity and low mental status at baseline predict dropout from a physical activity counseling program. Possibly, future studies should not only aim at improving physical activity level but also at modifying the psychological factors that either seem to influence this physical activity level, or lead to dropout from physical activity counseling. With regard to the applicability of the COACH counseling program we showed that the dropout rate was lowest in the outpatient clinic subgroup. The effects of counseling on physical activity level were the largest in this setting. This advocates for implementation of COACH particularly in patients from the outpatient clinic setting. Physical activity counseling in these patients might influence their disease progression. Adopting a physically active lifestyle in earlier disease stages might prevent patients from getting worse. Even when lung function decreases, patients can still benefit from the positive effects of their daily activity routine, as it prevents them from physical deconditioning. Moreover, it has been shown that in the general population being physically active on a moderate level has beneficial effects on hospital admission and mortality. 24 For the other two health care settings, general practice and PR, some alterations to the program or to the selection of patients might be necessary to make the program more effective. Such an alteration might be to offer more feedback moments over a longer period to increase the long term effects of the intervention. This might be especially important for patients in the PR group who were not able to maintain the higher physical activity level when they returned home again, and also dropped out more often. Other ways to improve the efficacy of our counseling program could be to introduce other or more intense feedback signals on physical activity. For example by offering patients real time feedback signals, such as sound or visual signals from a pedometer or accelerometer itself or integration of these devices in a smartphone (mhealth applications). When patients fail to achieve their goals a counselor can intervene early, e.g. by discussing the experienced barriers with a patient. Indeed, such applications have already been shown to be feasible in cardiac patients. 25 With regard to the lack of a positive effect in patients recruited from general practice we suggest this could be explained by several behavioral change theories. For instance, the Health Belief Model, the Self Determination Theory and the Goal Setting theory, suggest that individuals are only motivated to change behavior, when they fear health consequences of an unhealthy lifestyle or expect benefits of behavioral change When we apply these theories to our study population part of the patients in the general practice setting might not have been willing to change physical activity behavior, because they were not yet experiencing the limitations of their disease. Another explanation for the lack of a positive effect might be that these patients had higher baseline physical activity levels, which may have led to less room for 126

128 Summary and general discussion improvement. Nevertheless, we think the counseling program can still be worthwhile for COPD patients from the general practice setting, as intervening early in the disease might prevent these patients from getting worse in a later stage of their disease, when they start experiencing limitations. To be more effective, the counseling in this group might focus somewhat more on educating patients on the importance of a physically active lifestyle, thereby increasing patients motivation to keep or adopt a physically active lifestyle. Possibly, when patients in this setting are selected more specifically for having low baseline physical activity level, low exercise capacity and/or high motivation for physical activity the counseling can even be more effective. Besides the above suggested modifications to our counseling program, it might be necessary to develop programs with a different approach. For patients with low motivation for physical activity this may include more social support from family, friends, neighbors or other COPD patients acting as external motivation. Besides that, being physically active together with others gives the opportunity to learn from peers and often increases the experienced enjoyment of the activity. Social cognitive theory can be used to develop such interventions for COPD patients with low intrinsic motivation, as social support and enjoyment are factors mentioned to influence behavior in this theory, next to factors such as self-efficacy, goal setting and outcome expectations. 29 Physical fitness in COPD In Chapter 5 and 6 two different questions about the endurance shuttle walk test (ESWT), a measurement tool for endurance exercise capacity, were investigated: - Which variables explain the change in endurance exercise capacity in COPD patients, measured by the ESWT? Thereby insight was gained in whether there is a patient profile associated with improved exercise capacity after PR. - What is the clinically relevant change of the ESWT in a population of COPD patients with chronic respiratory failure? Variables explaining the change in endurance exercise capacity in COPD In chapter 5 the ESWT was used as primary outcome measure in an observational study investigating who benefits most of PR in terms of endurance exercise capacity. It has been shown before that PR has positive effects on exercise capacity in COPD. 30 However, not all COPD patients benefit from PR to the same extent. We included 102 COPD patients who followed PR (age 60 ± 10 (mean ± SD) years, FEV 1 % predicted 44 ± 6 %, 54 men). Lung function, maximal incremental cycle testing, quadriceps force and incremental and endurance shuttle walk test (ISWT/ESWT) were performed at the start of PR. The ESWT was repeated after 7 weeks of PR. A mean change in ESWT (ΔESWT) of 100±154 % was found. Four variables showed a statistically significant negative correlation with ΔESWT: FEV 1 % pred. (ρ=-0.20), peak work rate (ρ=-0.24), Δlactate (ρ=-0.33) and incremental shuttle walk test (ISWT) (ρ=-0.31). Further exploration of predictive variables for change in ESWT using a cluster analysis revealed the presence of 2 homogeneous groups which were significantly different on several variables: 1) a profile with high ΔESWT, TLC and RV and low FEV 1, VO 2 peak, quadriceps force, Δlactate, HR peak % pred. and ISWT distance, and 2) a profile with low ΔESWT, TLC and RV and high FEV 1, VO 2 peak, quadriceps force, Δlactate, HR peak % pred. and ISWT distance

129 Chapter 7 The study showed that single variables from lung function or exercise testing at baseline have limited predictive value for response to exercise training. However, patients with worse disease status (i.e. a combination of lower FEV 1, more hyperinflation, lower exercise capacity and worse quadriceps force) improve more in endurance exercise capacity. This is an important finding as many clinicians often hesitate to offer PR to COPD patients with a very severe disease status. The study also revealed that the ESWT showed a good responsiveness to change after PR. Existing literature on this topic suggests that a larger improvement in endurance exercise capacity may be related to worse functional status. 31,32 Our study adds to the existing literature the finding of a new patient profile that is a combination of clinical characteristics, rather than single variables to be related to larger improvements in endurance exercise capacity. The clinically relevant change of the ESWT In chapter 6 the minimally important difference (MID) of the ESWT in patients with severe COPD and respiratory failure undergoing PR was investigated. Although, the endurance shuttle walk test has proven to be responsive to changes in exercise capacity after PR for COPD, it is not clear yet which amount of change should be considered as clinically relevant. Data were derived from a randomized controlled trial, investigating the value of non invasive positive pressure ventilation added to PR. Fifty-five stable COPD patients, GOLD stage IV, with chronic respiratory failure were included, mean (SD) FEV (12.0) % pred, age 62 (9) y. The 6MWD, peak work rate and CRQ were used as anchors and Cohen s effect size was used as a distribution based method. The results of this study showed that the estimated MID of the ESWT is 186s, 76% or 154m with CRQ as anchor, 199s, 81% or 164m with peak work rate as anchor, and 199s or 82% with the 6MWD as anchor. Using the distribution based method the MID was 144s, 61% and 137m. The MID differed only slightly between the two anchor based methods used. Therefore we recommend using a change in ESWT ranging from s, 76-82% or m as MID in COPD patients with chronic respiratory failure. Further research should elucidate whether this cut-off value is also valid in other COPD populations and with other interventions. Discussion physical fitness in COPD We used the ESWT in two studies. Both studies have shown that the ESWT is a very feasible instrument to measure exercise capacity. In accordance with the literature the ESWT showed to be very responsive to changes in subjects following PR in both our studies. 33,34 In our opinion, these results are clinically relevant. Regarding predictors of this change in ESWT after PR, not one single variable from lung function or maximal incremental exercise testing at entry of PR predicts the response to exercise training, but an integrated patient profile seems more appropriate. Particularly the more severe COPD patients, i.e. patients with worse lung function combined with worse exercise capacity seem to benefit more from PR, which provides a strong argument not to exclude these severely disabled patients from PR programs. Although the ESWT has been shown to be responsive after PR in COPD patients, it was not clear yet whether a statistical change is clinically relevant. The MID of the ESWT has been investigated in one other study, that showed a smaller MID for the ESWT after pharmacological treatment with bronchodilators. 35 In that study a MID for the ESWT after PR was not estimated. The estimation of an MID may be influenced by many factors, e.g. the intervention, the population and the anchors and distribution based methods used. In this respect, our patient group was 128

130 Summary and general discussion rather small and specific. Taken together, it would be interesting to investigate whether the MID results from the current study can be confirmed in a larger and broader COPD population. Of course we were very interested in the implications of our newly defined MID for other PR studies. We identified four studies using the ESWT as outcome measure, all showing significant improvements in ESWT after intervention The four selected studies included patients with quite similar mean age (60-70 years) and mean FEV 1 ( %predicted) and demonstrated mean ESWT improvements between seconds and % A major difference with the patients included in our MID analysis is that the patients in our analysis all suffered from chronic hypercapnic respiratory failure. Probably, the differences found in mean ESWT changes in these studies are due to differences in COPD population, study design and efficacy of the intervention. Comparing the mean ESWT improvements of the four studies with our MID it can be acknowledged that a considerable proportion of the participants improved more than our MID. We realize that our newly defined MID is a construct that needs further validation in future studies, using different anchors and including different study populations. FUTURE PERSPECTIVES Implications for clinical practice Our physical activity counseling program can be used as a tool to enhance the self management of physical activity behavior in COPD patients. We think that the results from our physical activity counseling study have a number of possible implications for COPD patients and the healthcare practitioners treating these patients, such as GP s, pulmonary physicians, physical therapists and general practice/respiratory nurses across different healthcare settings. Firstly, enhancing awareness of COPD patients on the positive effects of physical activity is an important issue. Patients are often skeptic about being physically active or exercising because they experience dyspnea. However in the long term a more physically active lifestyle will show benefits. Although education on these positive effects theoretically plays an important role in this awareness process, self management, in this case of physical activity behavior, might even be more important. Patients can be made responsible for their own behavior by learning them strategies on starting to change their daily routines and implementing a more physically active lifestyle. Aspects of behavioral change theories such as goal-setting, and self-regulation might empower patients to take this responsibility and make a clear plan for themselves. Self management programs for COPD patients already exist, but till now aim mostly at medication and exacerbation control. Management of an active lifestyle should therefore have a more prominent role in self management programs and interventions. Also in clinical trials investigating self-management programs in COPD should include measures of behavior change such as changes in self efficacy and motivation besides measuring physical activity, exercise capacity, exacerbation and hospital admission rate Secondly, the question arises which healthcare practitioner is the most appropriate counselor, when this program would be implemented in the general management of COPD patients. In our opinion, the counselor should of course have specific knowledge on the medical aspects of COPD and the potential burden of this disease for the individual patient. Besides that, the counselor should be trained to perform the counseling according to the program, 129

131 Chapter 7 which includes the use of motivational interviewing techniques and strategies from several behavior change theories. This actually qualifies all health care practitioners involved in the treatment of a COPD patient as potential counselors. Still, we think that physical therapists and GP/respiratory nurses are the most appropriate healthcare practitioners to perform physical activity counseling. In general, physical therapists and GP/respiratory nurses have more time for individual patients, and they are more accessible for COPD patients. Moreover, these healthcare practitioners are experienced in monitoring patients over longer time periods. Besides that, counseling by a GP or pulmonary physician would be much more expensive, and therefore less cost-effective. Physical therapists and GP/respiratory nurses treat COPD patients in the different care settings. Ideally, the choice for counseling in a particular setting could depend on the individual preferences of the patient. But mostly, the choice is based on the actual treatment setting which has logistic advantages. For example, in patients with less severe disease counseling might work preventive and could be given by GP nurses, whom patients visit already for periodic lung function measurements, instructions on inhalation technique and exacerbation management. On the other hand, patients with more severe COPD who are already attending a supervised exercise training program in a primary care physical therapy centre might effectively be counseled on physical activity by their physical therapist in that particular setting. With regard to counseling in the tertiary healthcare setting some specific comments should be made. In our physical activity counseling study, the increase in physical activity level obtained in the intensive intervention period disappeared after 1 year follow up in this group. Nevertheless, we think that counseling might be appropriate in this group although some modifications from the initial program might be necessary as has been described before. Most important for these patients is the continuation of counseling in the home situation, either by phone calls of the PR physical therapist, or by face-to-face appointments with the physical therapist in the primary care setting to whom the patient is referred. Accurate transfer of information on physical activity behavior and plans, next to the usual information on exercise programs and test results, from the physical therapist in the PR setting to the physical therapist in the primary care setting should be warranted. The physical therapist can support patients to overcome (new) experienced barriers in the home situation that might occur when they lack the structure and the encouraging environment of a PR program. Thirdly, in our opinion it is important to make sure that COPD patients find their way to physical activity counseling programs. The doctors responsible for diagnosing and treating COPD patients, GP s and pulmonary physicians, should be well aware of the positive effects of physical activity. The question is how prescription of physical activity, possibly by means of a counseling program, can be improved. More evidence based data on the positive effects of regular physical activity might help to convince doctors in that perspective. The WHO states that non communicable diseases, including COPD, are largely preventable by effective interventions tackling the shared risk factors including physical activity. In another WHO document an overview of evidence on interventions targeting physical activity and/or diet in diverse populations is provided. (physical activity and diet, what works, WHO) It s important to be aware of the preventive effect of physical activity and realize that a COPD patient who is still functioning quite well in daily life should already pay extra attention to maintaining an active lifestyle, to prevent worsening of disease status. 130

132 Summary and general discussion Fourthly, we have looked into the current healthcare guidelines on COPD in the Netherlands, and how physical activity and physical training are addressed in these guidelines. Several guidelines describe care for COPD patients such as the Richtlijn Ketenzorg COPD, the NHG standaard COPD for GP s, the Zorgstandaard COPD of the NVALT for pulmonary physicians and the KNGF richtlijn Chronisch Obstructieve Longziekten for physical therapists For physical training, patients in early stages of the disease are advised to participate in regular sports activities and more severe COPD patients can participate in disease specific training programs of which frequency, duration and intensity have been described. 43 Regarding physical activity, all guidelines mention the importance of physical activity and to advice patients to enhance their physical activity levels, but most guidelines do not mention for whom and in which setting enhancement of physical activity could be part of the treatment and which methods could be used. Physical activity is only shortly described in the NHG standard and the Richtlijn Ketenzorg as an advice for the patient. 40,41 The Zorgstandaard COPD adds to this physical activity advice that motivational interviewing techniques can be valuable in the physical activity behavior change process. 42 The KNGF-richtlijn is the only guideline providing some more information on how to enhance physical activity level, specifically for physical therapists. 43 In this guideline it is mentioned that patients should, during their training program, be encouraged to become more physically active. Physical therapists can use a problem solving approach and work together with the patient, supporting the patient to develop an active lifestyle. In this perspective, the physical therapist could use self-monitoring, goal-setting and evaluation, and five steps of behavior change. Although the KNGF guideline provides some direction on how to enhance physical activity it does not describe a structured program that can be used by physical therapists (or other health care practitioners) to enhance physical activity in all COPD patients in the different care settings. Fifthly, ideally physical activity counseling should be covered by health care insurance to make it accessible to all patients and lift the financial barriers to participate. As enhancement physical activity is already included in guidelines for COPD financing by health care insurance would be a logical next step. In this respect, it would be interesting to investigate the cost effectiveness of physical activity counseling compared to the current physical training programs patients for COPD patients which are already part of insured care. In our opinion, a structured physical activity counseling program might help to create uniformity in the way physical activity is enhanced in COPD patients and behavior change is initiated. A structured physical activity counseling program might also make the enhancement of physical activity more effective and easier to implement in health care practice. We think it is important to implement a structured physical activity enhancement program, as in our opinion physical activity advice might not be enough to empower COPD patients to change their physical activity behavior in the long term. Therefore, we think it would be very valuable to embed physical activity counseling as a treatment option within the integrated care programs being accessible as a treatment option across all healthcare settings and disease stages in the standard care for COPD patients. 7 Although some adjustment might be necessary to make the program more effective and better applicable in our healthcare practice, we think that our COACH physical activity counseling 131

133 Chapter 7 program could act as a starting point to implement structured physical activity counseling for COPD patients in clinical practice. Unfortunately, for implementation firstly into guidelines and secondly into medical practice and insured care, one positive trial, even if a careful randomized controlled trial, usually does not suffice. In a replication trial, use could be made of some of the above suggestions for further improvements. Some suggestions for future research have been described below. Future research In future research on physical activity counseling some topics might be addressed more specifically. With respect to the current counseling program it is interesting to: - Investigate the effect of more feedback moments during the follow-up period of the study, or adjusting the number of feedback moments to the need of the individual patient. - Monitor psychological variables, next to physical activity, physical fitness and health related quality of life, through time, and make these psychological variables target of the intervention as well. Especially variables such as self efficacy and motivation might be improved by the cognitive behavioral theories used in the counseling program. - Investigate whether physical activity counseling in earlier stages has a preventive effect, e.g. whether it prevents (part of) the disease progression or the decline in quality of life. - Investigate peoples ideas about physical activity counseling supported by ehealth/ mhealth applications because such applications are a rapidly evolving part of healthcare and might be useful tools to empower self management in COPD patients. Therefore ideas about apps in general and ideas about contents of an app for physical activity enhancement of all stakeholders should be mapped using qualitative research methods, such as semi-structured interviews and focus group interviews. - Develop an ehealth and/or mhealth application based on the information gathered in the qualitative research process and by integrating principles of behavioral change theories. Thereafter the feasibility of such an application could be investigated by comparing physical activity counseling with ehealth/mhealth support to physical activity counseling without ehealth/mhealth support, no counseling at all or ehealth/ mhealth counseling alone. 132

134 Summary and general discussion Referrences 1. WHO: Physical Activity. 2. Bouchard C SR. Physical activity, fitness, and health: International proceedings and consensus statement. 1994;. 3. Watz H, Waschki B, Meyer T, Magnussen H. Physical activity in patients with COPD. Eur Respir J 2009; 33: Pitta F, Troosters T, Spruit MA, Probst VS, Decramer M, Gosselink R. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 171: Belza B, Steele BG, Hunziker J, Lakshminaryan S, Holt L, Buchner DM. Correlates of physical activity in chronic obstructive pulmonary disease. Nurs Res 2001; 50: Schonhofer B, Ardes P, Geibel M, Kohler D, Jones PW. Evaluation of a movement detector to measure daily activity in patients with chronic lung disease. Eur Respir J 1997; 10: McGlone S, Venn A, Walters EH, Wood-Baker R. Physical activity, spirometry and quality-of-life in chronic obstructive pulmonary disease. COPD 2006; 3: Lemmens KM, Nieboer AP, Huijsman R. Designing patient-related interventions in COPD care: empirical test of a theoretical model. Patient Educ Couns 2008; 72: Moy ML, Matthess K, Stolzmann K, Reilly J, Garshick E. Free-living physical activity in COPD: assessment with accelerometer and activity checklist. J Rehabil Res Dev 2009; 46: Waschki B, Spruit MA, Watz H, Albert PS, Shrikrishna D, Groenen M, et al. Physical activity monitoring in COPD: Compliance and associations with clinical characteristics in a multicenter study. Respir Med 2012; 106: Garcia-Rio F, Lores V, Mediano O, Rojo B, Hernanz A, Lopez-Collazo E, et al. Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation. Am J Respir Crit Care Med 2009; 180: de Blok BM, de Greef MH, ten Hacken NH, Sprenger SR, Postema K, Wempe JB. The effects of a lifestyle physical activity counseling program with feedback of a pedometer during pulmonary rehabilitation in patients with COPD: a pilot study. Patient Educ Couns 2006; 61: Hospes G, Bossenbroek L, Ten Hacken NH, van Hengel P, de Greef MH. Enhancement of daily physical activity increases physical fitness of outclinic COPD patients: results of an exercise counseling program. Patient Educ Couns 2009; 75: Prochaska O, Redding CA, Evers KE. The transtheoretical model and stages of change. In: Glanz K, Rimer BK, Lewis FM, editors. Health behaviour and health education: theory, research and practice. : Jossey-Bass, San Fransisco; p. 99, De Greef KP, Deforche BI, Ruige JB, Bouckaert JJ, Tudor-Locke CE, Kaufman JM, et al. The effects of a pedometer-based behavioral modification program with telephone support on physical activity and sedentary behavior in type 2 diabetes patients. Patient Educ Couns 2011; 84: Opdenacker J, Boen F, Coorevits N, Delecluse C. Effectiveness of a lifestyle intervention and a structured exercise intervention in older adults. Prev Med 2008; 46:

135 Chapter Opdenacker J, Delecluse C, Boen F. A 2-year follow-up of a lifestyle physical activity versus a structured exercise intervention in older adults. J Am Geriatr Soc 2011; 59: Pitta F, Troosters T, Probst VS, Langer D, Decramer M, Gosselink R. Are patients with COPD more active after pulmonary rehabilitation? Chest 2008; 134: Toft UN, Kristoffersen LH, Aadahl M, von Huth Smith L, Pisinger C, Jorgensen T. Diet and exercise intervention in a general population--mediators of participation and adherence: the Inter99 study. Eur J Public Health 2007; 17: Huisman S, Maes S, De Gucht VJ, Chatrou M, Haak HR. Low goal ownership predicts drop-out from a weight intervention study in overweight patients with type 2 diabetes. Int J Behav Med 2010; 17: Fischer MJ, Scharloo M, Abbink JJ, van t Hul AJ, van Ranst D, Rudolphus A, et al. Drop-out and attendance in pulmonary rehabilitation: the role of clinical and psychosocial variables. Respir Med 2009; 103: O Shea SD, Taylor NF, Paratz JD. A predominantly home-based progressive resistance exercise program increases knee extensor strength in the short-term in people with chronic obstructive pulmonary disease: a randomised controlled trial. Aust J Physiother 2007; 53: Garrod R, Marshall J, Barley E, Jones PW. Predictors of success and failure in pulmonary rehabilitation. Eur Respir J 2006; 27: Wen CP, Wai JP, Tsai MK, Yang YC, Cheng TY, Lee MC, et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 2011; 378: Varnfield M, Karunanithi MK, Sarela A, Garcia E, Fairfull A, Oldenburg BF, et al. Uptake of a technologyassisted home-care cardiac rehabilitation program. Med J Aust 2011; 194:S Becker MH. The Health Belief Model and Personal Health Behavior. 1974;. 27. Ryan RM, Deci EL. Self-determination theory and the facilitation of intrinsic motivation, social development, and well-being. Am Psychol 2000; 55: Locke EA, Latham GP. Building a practically useful theory of goal setting and task motivation. A 35-year odyssey. Am Psychol 2002; 57: Bandura A. Self-efficacy: toward a unifying theory of behavioral change. Psychol Rev 1977; 84: Lacasse Y, Martin S, Lasserson TJ, Goldstein RS. Meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. A Cochrane systematic review. Eura Medicophys 2007; 43: Troosters T, Gosselink R, Decramer M. Exercise training in COPD: how to distinguish responders from nonresponders. J Cardiopulm Rehabil 2001; 21: Zu Wallack RL, Patel K, Reardon JZ, Clark BA,III, Normandin EA. Predictors of improvement in the 12-minute walking distance following a six-week outpatient pulmonary rehabilitation program. Chest 1991; 99: Pepin V, Brodeur J, Lacasse Y, Milot J, Leblanc P, Whittom F, et al. Six-minute walking versus shuttle walking: responsiveness to bronchodilation in chronic obstructive pulmonary disease. Thorax 2007; 62:

136 Summary and general discussion 34. Eaton T, Young P, Nicol K, Kolbe J. The endurance shuttle walking test: a responsive measure in pulmonary rehabilitation for COPD patients. Chron Respir Dis 2006; 3: Pepin V, Laviolette L, Brouillard C, Sewell L, Singh SJ, Revill SM, et al. Significance of changes in endurance shuttle walking performance. Thorax 2011; 66: Altenburg WA, de Greef MH, Ten Hacken NH, Wempe JB. A better response in exercise capacity after pulmonary rehabilitation in more severe COPD patients. Respir Med 2012; 106: Effing T, Zielhuis G, Kerstjens H, van der Valk P, van der Palen J. Community based physiotherapeutic exercise in COPD self-management: a randomised controlled trial. Respir Med 2011; 105: Dyer F, Callaghan J, Cheema K, Bott J. Ambulatory oxygen improves the effectiveness of pulmonary rehabilitation in selected patients with chronic obstructive pulmonary disease. Chron Respir Dis 2012; 9: Effing TW, Bourbeau J, Vercoulen J, Apter AJ, Coultas D, Meek P, et al. Self-management programmes for COPD: moving forward. Chron Respir Dis 2012; 9: Richtlijn Ketenzorg COPD, Stichting Ketenkwaliteit COPD. 2005;. 41. NHG-standaard COPD, samenvatting. 2007;. 42. Zorgstandaard COPD, Long Alliantie Nederland. 2013;. 43. KNGF-richtlijn Chronisch obstructieve longziekten. 2008;

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138 CHAPTER 8 Nederlandse samenvatting

139 Chapter 8 Introductie Definitie en impact van COPD Chronische obstructieve longziekten (COPD) vormen een belangrijk gezondheidsprobleem in Nederland met een prevalentie van 1,83% voor mannen 1,55% voor vrouwen. 1 Wereldwijd is COPD momenteel de vierde doodsoorzaak en er wordt verwacht dat dit in 2020 de derde zal zijn. 2 COPD is een aandoening die wordt gekarakteriseerd door een niet volledig omkeerbare luchtwegobstructie die in het algemeen progressief is en die wordt veroorzaakt door een abnormale ontstekingsreactie van de longen op schadelijke deeltjes of gassen. 3 De belangrijkste risicofactor voor het ontstaan van COPD is roken, actief en passief meeroken. Ook luchtvervuiling, blootstelling aan stof en chemicaliën en frequente lage luchtweg infecties in de kindertijd spelen een rol. 4 Pathofysiologie Er zijn verschillende pathologische processen die de fysiologische veranderingen en symptomen veroorzaken bij patiënten met COPD. Ontsteking en vernauwing van centrale en perifere luchtwegen leidt tot een verminderde mogelijkheid snel uit te ademen, meestal uitgedrukt als een verminderd geforceerd uitademingsvolume in 1 seconde (FEV1 ). Ook verlies van longweefsel draagt bij aan de verminderde luchtstroom en zuurstofopname. Perifere luchtwegobstructie en verminderde elasticiteit van de longen kunnen leiden tot het achterblijven van meer lucht in de longen dan normaal na uitademing (air trapping/ hyperinflatie) waardoor de inademingscapaciteit vermindert, en er minder ruimte is om nieuwe zuurstofrijke lucht in te ademen. Als gevolg hiervan ontstaat kortademigheid bij fysieke inspanning, waardoor het inspanningsvermogen beperkt wordt. Recent onderzoek richtte zich ook op de rol van systemische, dat wil zeggen in het hele lichaam aanwezige, ontsteking bij COPD. Ontstekingsstoffen in de bloedbaan dragen mogelijk bij aan verlies van spierweefsel en veroorzaken of verergeren gelijktijdig aanwezige andere ziekten zoals doorbloedingsstoornissen van de hartspier, hartfalen, botontkalking, diabetes mellitus, metabool syndroom en depressie. 3 Symptomen Belangrijke symptomen van COPD zijn chronisch hoesten, slijmproductie, kortademigheid en verminderd inspanningsvermogen. Patiënten komen vaak in een neerwaartse spiraal waarbij kortademigheid leidt tot het vermijden van fysieke activiteit, met een verminderde conditie als gevolg. Het inspanningsvermogen wordt beïnvloed door longgerelateerde factoren zoals ademhalingsbeperking, dynamische hyperinflatie of verminderde zuurstofopname in de longen. Daarnaast kunnen factoren buiten de longen zoals vroeg optredende melkzuurproductie in de spieren en vermindering van de cardiovasculaire conditie hier aan bijdragen. Deze factoren zijn deels te wijten aan de inactieve leefstijl van veel COPD-patiënten. Hoewel patiënten in een vroeg stadium van COPD nog niet altijd beperkingen ervaren in hun inspanningsvermogen, weten we dat het fysieke activiteitenniveau van deze patiënten (vanaf GOLD stadium II) lager is dan bij gezonde personen

140 Nederlandse samenvatting Fysieke activiteit en fysieke fitheid bij COPD Fysieke activiteit en fysieke fitheid zijn nauw met elkaar verbonden, maar niet geheel uitwisselbare concepten. Fysieke activiteit wordt gedefinieerd als: elke beweging van het lichaam waarbij krachtsinspanning van skeletspieren wordt geleverd en waar energieverbruik voor nodig is. 67 Fysieke fitheid kan worden gedefinieerd als: het vermogen om dagelijks taken uit te voeren met kracht en alertheid, zonder overmatige vermoeidheid en met voldoende energie om van vrije tijd te genieten. Gezondheidsgerelateerde fysieke fitheid geeft aan waar iemand toe in staat is in termen van kracht, uithoudingsvermogen en flexibiliteit. 8 De definitie van fysieke activiteit impliceert een gedragscomponent. Iemand heeft zelf de keuze om wel of niet gebruik te maken van een klein of groot gedeelte van zijn of haar beschikbare vermogen (fysiek fitheid). Zoals eerder genoemd is het fysieke activiteitenniveau van patiënten met COPD laag ten opzichte van gezonde personen. In verschillende studies werd een gemiddeld aantal stappen per dag gevonden van stappen terwijl dit voor gezonde personen stappen is Het fysieke activiteit niveau is daarnaast bij patiënten met COPD sterker verminderd dan bij patiënten met andere chronische ziekten. 16,17 Dit lage fysieke activiteitenniveau is bij patiënten met COPD gerelateerd aan een lagere longfunctie (FEV 1 ) 5,11,18-20, een lager maximaal inspanningsvermogen (VO 2 max) 19,21,22, lagere 6-minutenloopafstand 5,10,19-22, lagere kwaliteit van leven 11, lagere self-efficacy 20,23 en een hoger risico op overlijden al dan niet longgerelateerd Ook fysieke fitheid is verminderd bij patiënten met COPD. Dit komt tot uiting in een afname van inspanningsvermogen en spierkracht. Mogelijk spelen aan COPD gerelateerde factoren zoals systemische ontsteking en oxidatieve stress een rol hierin. 28 Daarnaast wordt ook het normale verouderingsproces gekarakteriseerd door een progressieve afname van skeletspierfunctie (sarcopenie). 29 Dit speelt extra bij patiënten met COPD, waarvan er veel al ouder zijn. Fysieke inactiviteit speelt een belangrijke rol in dit proces. Het lage fysieke activiteitenniveau en de snellere achteruitgang van fysieke fitheid bij patiënten met COPD benadrukt het belang van het stimuleren van fysieke fitheid en fysieke activiteit in deze doelgroep. Inspanningsvermogen is een maat voor fysieke fitheid. Hiervoor worden verschillende testen gebruikt. Hoewel maximale inspanningstesten op de loopband of fietsergometer vaak als gouden standaard worden gezien, zijn veldtesten zoals de 6-minuten-looptest, de incremental shuttle walk test en de endurance shuttle walk test (ESWT) goede alternatieven. Deze testen laten vaak een zelfde piekinspanning, gemeten in zuurstofopname, zien als maximale loopband- of fietsergometrietesten. 30,31 Daarnaast is duur inspanningscapaciteit mogelijk een meer relevante maat bij patiënten met COPD dan maximale inspanningscapaciteit omdat het de activiteiten van het dagelijks leven beter weerspiegelt. Twee veel gebruikte looptesten zijn de ESWT en de 6-minuten-looptest. Beide testen, maar met name de ESWT, blijken gevoelig voor verandering na revalidatie Het voordeel van de ESWT is dat het tempo is opgelegd, waardoor de test minder afhankelijk is van de motivatie en het vermogen om te temporiseren van de patiënt. Het is nog onduidelijk wat de klinisch relevante verandering is in de ESWT na revalidatie. Een minimale klinisch relevante verbetering wordt gedefinieerd als die verandering die nog net door een patiënt als zinvol en de moeite waard wordt ervaren en waarbij de patiënt de behandeling opnieuw zou overwegen als hij deze keuze opnieuw zou maken

141 Chapter 8 Het verbeteren en behouden van fysieke fitheid en fysieke activiteit Longrevalidatie is een belangrijke behandeloptie voor patiënten met COPD. 3 Longrevalidatieprogramma s zijn multidisciplinair en bevatten over het algemeen verschillende trainingsvormen zoals fietsen, wandelen, krachttraining en cardiofitness. Educatie is een vast onderdeel van longrevalidatie. Zo nodig kunnen aanvullende behandelingen op psychosociaal of voedingsgebied aangeboden worden. Het verbeteren van fysieke fitheid is een van de belangrijkste doelen van longrevalidatie. Een review van Lacasse laat zien dat er vele studies gedaan zijn naar de effecten van longrevalidatie. 38 Hieruit blijkt dat longrevalidatie de kwaliteit van leven en het inspanningsvermogen verbetert. De resultaten van longrevalidatie zijn goed op de korte termijn, maar kunnen vaak maar ten dele behouden worden op lange termijn. 39 Daarbij speelt uitval uit een trainingsprogramma, mede door gebrek aan motivatie, vaak een belangrijke rol. Gemiddeld is het percentage deelnemers dat een longrevalidatieprogramma, of een trainingsprogramma gericht op behouden van de effecten daarvan, volhoudt zo n 60%. 40 Een belangrijk probleem bij COPD-patiënten is om de gedragsverandering die tijdens de revalidatie is ingezet vast te houden in de thuissituatie. Programma s die gedragsmatige behandelcomponenten bevatten, zoals counseling gericht op het fysieke activiteitenniveau, zijn mogelijk effectief in het bestendigen van de effecten van longrevalidatie. Twee pilotstudies waarin een counseling programma gericht op meer bewegen in het dagelijks leven werd onderzocht laten positieve korte termijn veranderingen zien in fysieke activiteit, arm en beenkracht, kwaliteit van leven en intrinsieke motivatie. 41,42 Wat ook pleit voor gedragsmatige counseling is dat self-efficacy (het zelfvertrouwen om lichamelijk actief te worden) een voorspeller is van fysieke activiteit bij milde COPD. 43,44 Counseling kan de ervaren self-efficacy verhogen en daarmee patiënten helpen beter gebruik te maken van hun fysieke mogelijkheden. Een andere belangrijke reden om de mogelijkheden van een counseling programma gericht op meer bewegen in het dagelijks leven te onderzoeken is dat de kosten voor een dergelijk programma naar verwachting lager zijn dan die van een gestructureerd trainingsprogramma en dat counseling daarnaast ook voor een groter deel van de COPD-populatie toegankelijk zou kunnen zijn. Het counseling programma gericht op meer bewegen in het dagelijks leven (de COACHmethode) dat in dit gerandomiseerde onderzoek centraal staat, is gebaseerd op een aantal bekende principes uit verschillende gedragstheorieën. Er is gebruik gemaakt van de Stages of Change uit het Transtheoretische model door in de counseling de voordelen en barrières van de gedragsverandering te benoemen en mogelijke alternatieven te bespreken. 44 Hierdoor kan de patiënt het vertrouwen in zijn eigen mogelijkheden vergroten en beter keuzes maken voor zichzelf. Daarnaast is gebruik gemaakt van de Self Determination theorie. 45 Positieve feedback, sociale steun en empathie zijn vanuit deze invalshoek de middelen om de competentie, de sociale verbondenheid en de autonomie van de patiënten versterken, om zo de intrinsieke motivatie voor gedragsverandering te vergroten. Vanuit de Goal Setting theorie is gebruik gemaakt van het specifiek maken van doelen die uitdagend maar haalbaar zijn Ook wanneer een persoon achter zijn doel staat, anderen van het doel op de hoogte stelt en zichzelf een beloning in het vooruitzicht stelt, zouden mensen meer gemotiveerd zijn om de doelen te behalen. 140

142 Nederlandse samenvatting Er werd ook gebruik gemaakt van implementatie-intenties (Implementation Intention and Goal Attainment theorie), wat inhoudt dat personen heldere instructies voor zichzelf gebruiken om het doel te bereiken (als dan plannen). 49 Specifieke opdrachten gekoppeld aan bijvoorbeeld het tijdstip op de dag kunnen helpen om gedragsverandering op te nemen in de dagelijkse routine. Ook de Achievement Goal theorie maakt gebruik van als dan plannen en gaat hierbij uit van het verbeteren van competenties waarbij een belangrijke rol is weggelegd voor intrinsieke motivatie, adequaat gebruik van zelf regulatie strategieën, persisterend gedrag en een sterk gevoel van self-efficacy. 50,51 Er werd tijdens de counseling gebruik gemaakt van motivational interviewing-technieken zoals reflectief luisteren, open vragen stellen, samenvatten, bevestigen en ondersteunen. 52 De COACH-studie De COACH-studie, een gerandomiseerd onderzoek, is opgezet om de effecten van fysieke activiteiten counseling op fysiek activiteitenniveau, kwaliteit van leven en inspanningsvermogen te onderzoeken. Patiënten uit alle GOLD stadia zijn geïncludeerd en waren afkomstig uit 3 verschillende lijnen van de gezondheidszorg: de huisartsenpraktijk, het ziekenhuis (polikliniek) en een gespecialiseerd revalidatiecentrum. De intensieve interventieperiode duurde 3 maanden waarin 5 counseling gesprekken plaatsvonden. Daarna was er een followup periode van 12 maanden waarin nog 3 counseling gesprekken werden gepland, waarvan 1 telefonisch. In Figuur 1 en Tabel 1 is een overzicht te zien van het tijdschema van de studie en de counseling thema s. Counseling T1 + C1 C2 C3 C4 T2 + C5 C6 T3 + C7 T4 + C8 Arts vraagt patient voor deelname Wk 1 Wk 3 Wk 6 3 Wk 9 maanden 6 maanden 9 maanden 15 maanden Reguliere zorg T1 T2 T3 T4 8 T= meetmoment C= counseling sessie Figuur 1. Overzicht van de COACH-studie 141

143 Chapter 8 Tabel 1. Thema s van counseling sessies Activatie: 3 maanden Counseling 1 : motivatie voor fysieke activiteit Counseling 2 : persoonlijk beweegdoel: fase 1 Counseling 3 : verleggen van grenzen Counseling 4 : persoonlijk beweegdoel: fase 2 Counseling 5 : consolidatie, vaststellen persoonlijke beweegnorm Consolidatie: 12 maanden Counseling 6 (tel) Counseling 7 Counseling 8 : consolidatie : terugvechten als het beweegniveau is afgenomen : evaluatie van het nieuwe beweegniveau, aanpassen van het persoonlijke beweegdoel Onderzoeksthema s In dit proefschrift is een aantal onderwerpen beschreven dat gerelateerd is aan fysieke activiteit en fysieke fitheid bij patiënten met COPD. Mogelijke relaties tussen fysieke activiteit, fysiek fitheid, psychologische variabelen, longrevalidatie en counseling van fysieke activiteiten zijn te zien in figuur 2. De getallen in de figuur corresponderen met de hoofdstukken van dit proefschrift. Fysieke activiteiten counseling Revalidatie Interventies 4 3 Psychologische variabele 5 Gerelateerde factoren bij COPD Fysieke activiteit 2 Fysieke fitheid 6 Stappen Dagelijkse fysieke activiteit HADS SRQ-E LIVAS ESWT 6MWD Meetinstrumenten Figuur 2. Analytisch model van variabelen die wederzijds samenhangen met fysieke activiteit en fitheid bij patiënten met COPD. HADS: Hospital Anxiety and Depression Scale; SRQ-E: Self Regulation Questionnaire for Exercise; LIVAS: Lichamelijke vaardigheden schaal, Dutch version of the Perceived Physical Ability Subscale; ESWT: Endurance shuttle walk test; 6MWD: six minute walking distance. 142

144 Nederlandse samenvatting Belangrijkste bevindingen van dit proefschrift Fysieke activiteit In Hoofdstuk 2, 3 en 4 worden de resultaten van de COACH studie beschreven. In deze studie zijn onderzocht: - De relatie tussen fysieke variabelen, psychologische variabelen en dagelijkse fysieke activiteit. Directe en indirecte relaties tussen deze variabelen zijn cross-sectioneel onderzocht (Hoofdstuk 2) - Het effect van de COACH-interventie op fysieke activiteit, inspanningsvermogen en kwaliteit van leven bij patiënten met COPD uit de huisartsenpraktijk, de poli van de longarts en een revalidatiecentrum (Hoofdstuk 3) - De redenen en voorspellers van uitval uit de COACH studie (Hoofdstuk 4) De relatie tussen fysieke activiteit, fysieke fitheid en psychologische variabelen In hoofdstuk 2 zijn de relaties tussen fysieke activiteit, functionele capaciteit en psychologische variabelen beschreven. Daarnaast werd onderzocht of deze relaties verschillen tussen patiënten met een hoge en een lage functionele status (gemeten met de 6 minuten looptest). Een regressiemodel waarin variabelen werden opgenomen die significant gecorreleerd waren met fysieke activiteit, toonde aan dat de 6-minuten looptest en de kwaliteit van leven (gemeten met de Saint George Respiratory Questionnaire (SGRQ)) samen 37% van de variantie in fysieke activiteit verklaarden. Als in het regressiemodel uitsluitend psychologische variabelen zoals bijvoorbeeld self-efficacy werden opgenomen, bedroeg de proportie verklaarde variantie van fysieke activiteit 16%. Mogelijk is de invloed van psychologische factoren indirect gerelateerd aan fysieke activiteit via de functionele variabelen. Path-analyse laat inderdaad zien dat psychologische variabelen direct gerelateerd zijn aan functionele variabelen en indirect aan het fysieke activiteitenniveau. Bij patiënten met een lage functionele status (lage 6-minuten loopafstand) was fysieke activiteit geassocieerd met zeven variabelen die functionele capaciteit weerspiegelen (FEV 1, 6 minuten looptest, Groningen Activiteiten Restrictie schaal (GARS), Short Form 36 fysiek functioneren, SGRQ, Clinical COPD Questionnaire (CCQ) en Dutch Exertion and Fatigue scale (DEFS)) en met geen van de psychologische factoren. Bij patiënten met een hoge functionele status was fysieke activiteit geassocieerd met 4 variabelen die functionele capaciteit weerspiegelen en aan twee psychologische factoren, self-efficacy en depressie. Deze resultaten suggereren dat psychologische variabelen, zoals motivatie, self-efficacy, angst en depressie de functionele capaciteit van een COPD-patiënt beïnvloeden en daarmee indirect het fysiek activiteitenniveau. Uit de subgroep analyse blijkt dat psychologische factoren het fysieke activiteitenniveau vooral beïnvloeden bij patiënten met een hogere functionele status terwijl functionele capaciteit het fysieke activiteitenniveau vooral beïnvloedt bij patiënten met een lagere functionele status. 8 In overeenstemming met bestaande literatuur vonden we dat een hoger fysieke activiteitenniveau gerelateerd is aan een hogere FEV 1 5,11,18-20,23, hogere kwaliteit van leven (zowel generiek als ziekte specifiek) 10,11,20,21,23 en lagere vermoeidheid 13. Daarnaast vonden we dat een hoger fysiek activiteitenniveau was gerelateerd aan self-efficacy, dit werd ook gevonden in twee andere studies. 20,23 De 6 minuten looptest werd ook in andere studies als verklarende factor gevonden

145 Chapter 8 In aanvulling op de bestaande literatuur vonden we dat een hoog fysiek activiteitenniveau was gerelateerd aan een hogere zelfredzaamheid. In tegenstelling tot eerdere studies bij COPDpatiënten vinden we een significante relatie tussen een hoger fysiek activiteitenniveau en lagere score op depressieve symptomen. 5,10 De effecten van het counseling programma gericht op fysieke activiteiten (COACH) In hoofdstuk 3 zijn de effecten van het counseling programma COACH beschreven. Dit counseling programma richt zich op het meer bewegen in het dagelijks leven door middel van leefstijlactiviteiten zoals wandelen, fietsen en tuinieren. Om de effectiviteit van dit counseling programma te onderzoeken is een gerandomiseerd gecontroleerd onderzoek uitgevoerd, waarin 155 patiënten met stabiel COPD, verdeeld over een controlegroep (usual care) en experimentele groep (counseling), zijn geïncludeerd. De primaire uitkomstmaat was fysieke activiteit, secundaire uitkomstmaten waren kwaliteit van leven en inspanningsvermogen. Van 0 tot 3 maanden verbeterde de fysieke activiteit zowel in stappen als in totale fysieke activiteit significant in de counseling groep ten opzichte van de usual care groep. Dit gold voor de totale groep en de patiënten die deelnamen via de polikliniek van het ziekenhuis of het revalidatiecentrum, maar niet voor patiënten die deelnamen via de huisartsenpraktijk. Na 15 maanden was dit effect niet significant (meer) voor de totale groep. Het effect was na 15 maanden wel significant groter als actieve patiënten, die bij de start van het onderzoek al meer dan stappen zetten, uit de analyse werden gelaten. De secundaire uitkomstmaten zoals inspanningscapaciteit en kwaliteit van leven lieten alleen een significante verbetering van de counselingroep ten opzichte van usual care zien in de groep patiënten die deelnam aan de COACH interventie via de polikliniek van het ziekenhuis en dan alleen in de periode van 0 tot 3 maanden. Voor zover ons bekend is dit de eerste studie die zowel de effecten van counseling bij COPDpatiënten op korte en lange termijn heeft onderzocht. Daarnaast is het interessant dat niet alleen patiënten uit de revalidatie setting maar ook patiënten uit de huisartsenpraktijk en de polikliniek van het ziekenhuis hebben deelgenomen. Hiermee is een brede groep patiënten geïncludeerd. De COACH-studie heeft de korte termijn resultaten uit de pilot-studies 41,42 bevestigd en daar een veelbelovend lange termijn resultaat aan toegevoegd. Uitval uit de COACH studie In hoofdstuk 4 is de uitval uit de COACH studie beschreven. Van alle patiënten die deelnamen viel 29,7 % uit. Als redenen voor uitval werden gebrek aan motivatie, medische redenen, persoonlijke redenen en overlijden, gecategoriseerd. De meest voorkomende redenen waren gebrek aan motivatie (47,8 % van de uitvallers) en medische redenen (26,1 %). Uitval uit het counseling programma wordt op korte termijn (0-3 maanden) voorspeld door een lage mentale status en een lage motivatie voor fysieke activiteit op baseline. Op langere termijn (3-15 maanden) is dit een lagere longfunctie. Uitval uit de usual care groep wordt op korte termijn alleen voorspeld door lage motivatie voor fysieke activiteit en op lange termijn door een lager functionele status. 144

146 Nederlandse samenvatting De resultaten suggereren dat uitval op korte termijn meer bepaald wordt door psychologische factoren, met name als patiënten een gedragsveranderings-programma volgen. Uitval op langere termijn wordt meer bepaald door ziekte gerelateerde factoren. Uitval uit een counseling programma gericht op meer bewegen in het dagelijks leven, is niet eerder uitgebreid beschreven bij COPD-patiënten. In overeenstemming met studies die uitval beschrijven uit longrevalidatieprogramma s vonden we dat medische redenen een vaak voorkomende reden van uitval zijn De voorspellers voor uitval uit het counseling programma (lage motivatie voor fysieke activiteit en lage score op mentale gezondheid) zijn eveneens vergelijkbaar met die van longrevalidatie studies waarin onder andere depressie als voorspeller van uitval wordt aangetoond. 55 We vonden dat een lage FEV 1 voorspellend was voor uitval op langere termijn, hetgeen mogelijk gerelateerd is aan een slechtere ziekte status. Dit geldt mogelijk ook voor een lage quadriceps kracht, een hoog aantal pakjes sigaretten per jaar en een lage vetvrije massa, factoren die als voorspeller van uitval aangetoond werden in twee longrevalidatiestudie s. 53,55 Fysieke fitheid Hoofdstuk 5 en 6 richten zich op een specifieke uitkomstmaat van fysieke fitheid, namelijk de ESWT. In deze studies is onderzocht: - Welke variabelen verklaren de verandering in duurvermogen bij patiënten met COPD. Hiermee kan wellicht een patiëntenprofiel opgesteld worden dat qua duurvermogen goed reageert op longrevalidatie. (Hoofdstuk 5) - Wat is het minimaal klinisch relevante verschil van de ESWT in een populatie van COPD-patiënten met chronisch respiratoir falen. (Hoofdstuk 6) Variabelen die de verandering in duurvermogen na revalidatie verklaren bij COPD-patiënten In deze studie werden 102 COPD-patiënten geïncludeerd die een longrevalidatieprogramma volgden. Voor de start van de revalidatie werden longfunctie testen, fietsergometrie, quadricepskracht, ISWT en ESWT getest. Na 7 weken werd de ESWT herhaald. Het gemiddelde verschil (SD) in de verandering van de ESWT was 100% (154). FEV 1 %pred, peak work rate, delta lactaat en ISWT, waren significant gerelateerd aan de verandering in ESWT. Een clusteranalyse laat zien dat er 2 homogene groepen kunnen worden onderscheiden die significant verschillen op bepaalde kenmerken: 1) een patiëntenprofiel met een hoge delta ESWT, TLC en RV en een lage FEV 1, VO2max, quadricepskracht, delta lactaat, Hfmax%pred en ISWT afstand en 2) een patiëntenprofiel met lage delta ESWT, TLC en RV en een hoge FEV 1, VO 2 max, quadricepskracht, delta lactaat, Hfmax%pred en ISWT afstand. 8 De studie laat zien dat op zichzelf staande variabelen van longfunctie of inspanningstesten een beperkte voorspellende waarde hebben voor de respons op fysieke training. Onze studie laat in aanvulling op bestaande literatuur zien dat patiënten met een slechtere ziekte status, dat wil zeggen een combinatie van lagere FEV 1, meer hyperinflatie, lage inspanningscapaciteit en quadricepskracht relatief meer verbeteren in duur vermogen, gemeten met de ESWT. Dit is relevant voor de dagelijkse praktijk omdat er nog wel eens geaarzeld wordt om patiënten met een zeer slechte ziekte status te verwijzen voor longrevalidatie. 145

147 Chapter 8 Het klinisch relevante verschil van de ESWT In hoofdstuk 6 is het klinisch relevante verschil van de ESWT onderzocht bij patiënten met ernstig COPD en respiratoir falen die een revalidatieprogramma volgden. Er werden 55 patiënten met stabiel COPD GOLD IV en respiratoir falen geïncludeerd voor deze analyse. Deze patiënten namen deel aan een gerandomiseerde studie naar de waarde van non invasieve positieve druk beademing in aanvulling op longrevalidatie. De 6-minuten looptest, de CRQ en de piekbelasting bij fietsergometrie werden gebruikt als ankers om het klinisch relevante verschil te bepalen en Cohens effects size als distibutiemaat. De klinisch relevante verschillen berekend met de verschillende ankers lagen dicht bij elkaar: 186s, 76% of 154m met CRQ als anker, 199s, 81% of 164m met peak work rate als anker, en 199s of 82% met de 6MWD als anker. Op basis van Cohens effect size werd het minimale klinisch relevante verschil iets lager geschat 144s, 61% of 137m. We raden aan een verandering met een variatie van s, 76-82% of m te gebruiken als minimale klinisch relevant verschil. Verder onderzoek zal moeten uitwijzen of deze waarden ook te gebruiken zijn in andere COPD-populaties of bij andere interventies. Het klinisch relevante verschil van de ESWT is onderzocht in één andere studie, waar een kleiner verschil klinisch relevant werd bevonden, echter de interventie betrof hier geen revalidatie maar een farmacologische verbetering van de longfunctie. 56 Praktische implicaties Het onderzochte counseling programma kan gebruikt worden als middel om het zelfmanagement van beweeggedrag van COPD-patiënten te vergroten. De resultaten van dit onderzoek kunnen implicaties hebben voor de verschillende betrokkenen bij de zorg voor COPD-patiënten. Achtereenvolgens zullen de implicaties voor de patiënt, de zorgverleners en op maatschappelijk niveau, besproken worden. Bij patiënten is het belangrijk om het bewustzijn van de positieve effecten van bewegen te vergroten. Patiënten zijn vaak terughoudend wat betreft bewegen en trainen vanwege de kortademigheid die zij ervaren. Aandacht voor het veranderen van het beweeggedrag als onderdeel van zelfmanagement speelt hierin mogelijk een belangrijke rol. Patiënten worden zo meer verantwoordelijk gemaakt voor hun eigen gedrag en leren strategieën aan om dagelijkse routines te veranderen en een fysiek actievere leefstijl toe te passen. Er zijn al wel zelfmanagement programma s voor COPD-patiënten, maar de meeste richten zich vooral op de medicamenteuze kant. Daarnaast zou wat ons betreft het counseling programma gericht op meer bewegen in het dagelijks leven een plaats kunnen krijgen in de reguliere zorg. Hiervoor moet goed gekeken worden welke zorgverlener deze counseling het beste uit kan voeren. Een counselor moet voldoende kennis hebben van de medische aspecten van COPD en de ziektelast die de aandoening met zich meebrengt. Daarnaast zou een counselor geschoold moeten zijn om motivational interviewing toe te passen en de strategieën van de verschillende gedragsveranderingstheorieën te gebruiken. Wij denken dat fysiotherapeuten, praktijkondersteuners en longverpleegkundigen het meest geschikt zijn om de counseling uit 146

148 Nederlandse samenvatting te voeren. Zij zijn laagdrempelig toegankelijk voor patiënten en hebben meer tijd voor een individuele patiënt dan bijvoorbeeld de huisarts of longarts. Daarnaast zijn deze zorgverleners gewend om patiënten te ondersteunen bij het monitoren van hun gedrag. De keuze voor een bepaalde zorgverlener hangt af van de voorkeur van de patiënt en de beschikbare mogelijkheden. Zo kan een patiënt met mild COPD wellicht het best gecounseld worden door de praktijkondersteuner, die immers de patiënt toch veelal periodiek ziet in het kader van longfunctie-testen, inhalatie-instructies en exacerbatiemanagement. Patiënten met ernstiger COPD die een trainingsprogramma volgen bij een eerstelijns fysiotherapeut zouden misschien juist het best door de fysiotherapeut gecounseld kunnen worden. Het is naar onze overtuiging belangrijk dat patiënten met COPD hun weg vinden naar counseling programma s die gericht zijn op meer bewegen. De artsen die COPD-patiënten begeleiden moeten op de hoogte zijn van de positieve effecten van fysieke activiteit. Meer evidence based data over de positieve effecten van dagelijkse fysieke activiteit kan dit bevorderen. De World Health Organisation laat in een overzicht zien dat er interventies zijn die op korte termijn effectief zijn in het verhogen van fysieke activiteit bij verschillende doelgroepen. Deze interventies zijn ook van invloed zijn op het verbeteren van fysieke fitheid. Ook noemt de World Health Organisation het van belang om bij chronische ziekten, zoals COPD, de risicofactoren aan te pakken. Een laag fysieke activiteitenniveau is één van deze risicofactoren waarop interventies kunnen worden gericht. 57 Tenslotte dienen de behandelaren van COPD-patiënten zich te realiseren dat een COPD-patiënt die fysiek nog goed functioneert in zijn dagelijks leven al extra aandacht moet besteden aan een actieve leefstijl om verergering van de ziekte te voorkomen. Tenslotte hebben we gekeken naar de plaats van stimuleren van fysieke activiteit binnen de huidige zorg voor COPD-patiënten. De Nederlandse zorgrichtlijnen voor COPD, de NHG standaard COPD, de Richtlijn Ketenzorg, de Zorgstandaard COPD en de KNGF-richtlijn COPD beschrijven fysieke activiteit, maar de meeste richtlijnen beschrijven niet voor wie en in welke setting verbeteren van fysieke activiteitenniveau onderdeel zou kunnen zijn van de behandeling In de NHG standaard COPD en de Richtlijn Ketenzorg wordt fysieke activiteit alleen kort beschreven als een advies voor de patiënt. 58,59 De Zorgstandaard COPD voegt hier aan toe dat motivational interviewing technieken waardevol kunnen zijn bij het gedragsveranderingsproces dat nodig is om het beweeggedrag te veranderen. 60 De KNGFrichtlijn COPD is de enige richtlijn die meer informatie geeft over hoe fysieke activiteit gestimuleerd zou kunnen worden. 61 Patiënten zouden tijdens hun trainingsprogramma, gestimuleerd moeten worden om meer fysiek actief te zijn. Fysiotherapeuten kunnen hiervoor een probleemoplossende benadering gebruiken en samen met de patiënt werken aan een actievere leefstijl. Hiervoor zou de fysiotherapeut zelf-monitoring, het stellen en evalueren van doelen en de vijf stappen van gedragsverandering kunnen gebruiken. Echter de richtlijn beschrijft geen gestructureerd programma dat geïmplementeerd kan worden door fysiotherapeuten in de verschillende lijnen van de zorg. 8 Het zou goed zijn als er geld wordt vrijgemaakt om verder te onderzoeken voor welke patiënten het COACH-programma het meest effectief is in verbetering van kwaliteit van leven en afname van gezondheidszorgconsumptie. Een volgende stap zou dan vergoeding van counseling door de zorgverzekeraar kunnen zijn. 147

149 Chapter 8 Het COACH-programma zou kunnen helpen om meer uniformiteit te creëren in de manier waarop mensen met COPD gestimuleerd worden om het fysieke activiteitenniveau te verbeteren en hoe deze gedragsverandering kan worden geïnitieerd. Naar ons idee is het belangrijk om een counseling programma gericht op meer bewegen in het dagelijks leven te implementeren in de zorg, omdat het een krachtiger middel is om het beweeggedrag van COPD-patiënten te verbeteren dan het geven van alleen een beweegadvies. Mogelijk kan counseling gericht op meer bewegen in het dagelijks leven een waardevolle toevoeging zijn op de reguliere ketenzorg, waar het een behandeloptie kan zijn binnen alle lijnen van de zorg en ziekte stadia van COPD. Toekomstige onderzoeksonderwerpen Vervolgonderzoek kan zich mogelijk richten op: - Het verbeteren van de resultaten van de COACH-interventie door meer frequente feedbackmomenten door de beweegcounselor of het aanpassen van feedbackmomenten aan de (tijdelijke) behoefte van de patiënt tijdens de follow-up fase van het counselen van beweeggedrag van COPD-patiënten. - Vastleggen, monitoren en beïnvloeden van psychologische factoren die van invloed zijn op het fysieke activiteitenniveau van de patiënt en de veranderingen hierin tijdens een counseling programma. - Het preventieve effect van fysieke activiteiten counseling in vroege stadia van de ziekte. - De mogelijkheden van ehealth en mhealth toepassingen bij fysieke activiteitencounseling. 148

150 Nederlandse samenvatting Referenties WHO: Chronic Obstructive Pulmonary Disease. 3. Global Strategy for the Diagnosis, Management and prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2010;. 4. WHO: Chronic Obstructive Pulmonary Disease. 5. Watz H, Waschki B, Meyer T, Magnussen H. Physical activity in patients with COPD. Eur Respir J 2009; 33: WHO: Physical Activity. 7. WHO: Physical Activity. 8. Bouchard C SR. Physical activity, fitness, and health: International proceedings and consensus statement. 1994;. 9. Pitta F, Takaki MY, Oliveira NH, Sant'anna TJ, Fontana AD, Kovelis D, et al. Relationship between pulmonary function and physical activity in daily life in patients with COPD. Respir Med 2008; 102: Moy ML, Matthess K, Stolzmann K, Reilly J, Garshick E. Free-living physical activity in COPD: assessment with accelerometer and activity checklist. J Rehabil Res Dev 2009; 46: McGlone S, Venn A, Walters EH, Wood-Baker R. Physical activity, spirometry and quality-of-life in chronic obstructive pulmonary disease. COPD 2006; 3: Camillo CA, Pitta F, Possani HV, Barbosa MV, Marques DS, Cavalheri V, et al. Heart rate variability and disease characteristics in patients with COPD. Lung 2008; 186: Waschki B, Spruit MA, Watz H, Albert PS, Shrikrishna D, Groenen M, et al. Physical activity monitoring in COPD: Compliance and associations with clinical characteristics in a multicenter study. Respir Med 2012; 106: Watz H, Waschki B, Boehme C, Claussen M, Meyer T, Magnussen H. Extrapulmonary effects of chronic obstructive pulmonary disease on physical activity: a cross-sectional study. Am J Respir Crit Care Med 2008; 177: Troosters T, Sciurba F, Battaglia S, Langer D, Valluri SR, Martino L, et al. Physical inactivity in patients with COPD, a controlled multi-center pilot-study. Respir Med 2010; 104: Tudor-Locke C, Washington TL, Hart TL. Expected values for steps/day in special populations. Prev Med 2009; 49: Arne M, Janson C, Janson S, Boman G, Lindqvist U, Berne C, et al. Physical activity and quality of life in subjects with chronic disease: chronic obstructive pulmonary disease compared with rheumatoid arthritis and diabetes mellitus. Scand J Prim Health Care 2009; 27: Schonhofer B, Ardes P, Geibel M, Kohler D, Jones PW. Evaluation of a movement detector to measure daily activity in patients with chronic lung disease. Eur Respir J 1997; 10: Pitta F, Troosters T, Spruit MA, Probst VS, Decramer M, Gosselink R. Characteristics of physical activities in daily life in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 171:

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153 Chapter Fischer MJ, Scharloo M, Abbink JJ, van 't Hul AJ, van Ranst D, Rudolphus A, et al. Drop-out and attendance in pulmonary rehabilitation: the role of clinical and psychosocial variables. Respir Med 2009; 103: O'Shea SD, Taylor NF, Paratz JD. A predominantly home-based progressive resistance exercise program increases knee extensor strength in the short-term in people with chronic obstructive pulmonary disease: a randomised controlled trial. Aust J Physiother 2007; 53: Garrod R, Marshall J, Barley E, Jones PW. Predictors of success and failure in pulmonary rehabilitation. Eur Respir J 2006; 27: Pepin V, Laviolette L, Brouillard C, Sewell L, Singh SJ, Revill SM, et al. Significance of changes in endurance shuttle walking performance. Thorax 2011; 66: WHO. Interventions on diet and physical activity: what works. 58. Richtlijn Ketenzorg COPD, Stichting Ketenkwaliteit COPD. 2005;. 59. NHG-standaard COPD, samenvatting. 2007;. 60. Zorgstandaard COPD, Long Alliantie Nederland. 2013;. 61. KNGF-richtlijn Chronisch obstructieve longziekten. 2008;. 152

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155