Physical activity and physical fitness in juvenile idiopathic arthritis Lelieveld, Otto

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1 University of Groningen Physical activity and physical fitness in juvenile idiopathic arthritis Lelieveld, Otto 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: 2010 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Lelieveld, O. (2010). Physical activity and physical fitness in juvenile idiopathic arthritis Groningen: s.n. 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 Physical Fitness in Juvenile Idiopathic Arthritis

3 Studies presented in this thesis were financially supported by: Beatrix Children s Hospital Foundation (Groningen, the Netherlands) Foundation for Beatrixoord Noord Nederland (Haren (Gr.), the Netherlands) OIM Orthopedie (Assen, the Netherlands) Printing of this thesis was financially supported by: Dutch Arthritis Association (Amsterdam, the Netherlands) Lode B.V. (Groningen, the Netherlands) Foundation for Beatrixoord Noord Nederland (Haren (Gr.), the Netherlands) Royal Dutch Society for Physical Therapy (KNGF) (Amersfoort, the Netherlands) Cover design: Davita Trip, Otto Lelieveld Lay-out: Otto Lelieveld Printed by Gildeprint Drukkerijen (Enschede, the Netherlands) ISBN (printed): ISBN (digital): Otto Lelieveld No part of this thesis may be reproduced, stored or transmitted in any way or by any means, without prior permission of the author.

4 Rijksuniversiteit Groningen Physical Activity and Physical Fitness in Juvenile Idiopathic Arthritis Proefschrift ter verkrijging van het doctoraat in de Medische Wetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. F. Zwarts, in het openbaar te verdedigen op woensdag 7 april 2010 om uur door Otto Theodorus Hendricus Maria Lelieveld geboren op 9 juli 1957 te Deventer

5 Promotores: Prof. dr. J.H.B. Geertzen Prof. dr. P.J.J. Sauer Copromotores: Dr. M.A. van Leeuwen Dr. E. van Weert Beoordelingscommissie: Prof. dr. J.G.S.J.S.M. Becher Prof. dr. P.J.M. Helders Prof. dr. W. Kuis

6 Paranimfen: Marieke Armbrust Inez de Graaf

7

8 Contents Chapter 1 Aim and introduction to the thesis 9 Chapter 2 Validity of the 6-minute walking test in juvenile idiopathic arthritis Arthritis & Rheumatism 2005; 53: Chapter 3 Aerobic and anaerobic exercise capacity in children with juvenile idiopathic arthritis Arthritis & Rheumatism 2007; 57: Chapter 4 Aerobic and anaerobic exercise capacity in adolescents with juvenile idiopathic arthritis Arthritis & Rheumatism 2007; 57: Chapter 5 Physical activity in adolescents with juvenile idiopathic arthritis Arthritis & Rheumatism 2008; 59: Chapter 6 Illness representations and the relationship with functional status in adolescents with juvenile idiopathic arthritis Submitted 71 Chapter 7 Promoting physical activity in children with juvenile idiopathic arthritis through an internet-based program: results of a pilot randomised controlled trial Arthritis Care & Research, in press 85 Chapter 8 Discussion, key findings and recommendations 101 Summary Nederlandse samenvatting Dankwoord

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10 Chapter 1 Aim and introduction to the thesis

11 Chapter 1 Introduction Juvenile idiopathic arthritis: a chronic disease Juvenile idiopathic arthritis (JIA) is a heterogeneous group of auto immune diseases that includes all forms of arthritis beginning before the age of 16 years, persisting for more than 6 weeks and of unknown origin 1-4. The main characteristic of JIA is arthritis due to inflammatory synovitis causing morning joint stiffness, swelling, decreased motion, pain, decreased muscle strength and muscle atrophy. The aim of current therapy is to induce and sustain remission of disease through the use of medication so that normal childhood activities, growth and development can be sustained 5, 6. Through medication the synovial inflammation caused by the derailed immune system is modified and eventually controlled leading to remission of the disease. Unfortunately no medication exists that achieve rapidly, consistently and long lasting remission of disease and therefore JIA patients can have intermittent periods of active and inactive disease 6, 7. Therefore JIA is a chronic disease affecting the child for extended periods of time and often for life. Long-term follow up studies over the last twelve years show that between 37 and 54% of adult JIA patients have active disease and between 2.5 and 37% have severe functional impairments 1, In the Netherlands it is estimated that between 2000 to 3000 children under the age of 16 years suffer from JIA. Chronic disease in perspective Children with a chronic disease are confronted with illness specific ailments. Furthermore, their chronic disease will induce changes in organ or body elements not primarily affected by the disease. Finally, a chronic disease will affect, through the physical domain, the psychological and social domain. Therefore, children with a chronic disease and their families have to deal with the impact of disease in many important life domains. Health is than not the mere absence or control of disease but a human condition with physical, social and psychological dimensions 17, 18. This view on health has created a higher awareness of the importance of function irrespective of the presence or absence of active disease. Assessment of function has become essential to reduce functional limitations and improve well-being 19. For this reason the World Health Organization has provided a unifying framework for classifying the consequences of (chronic) disease by the International Classification of Functioning, Disability and Health, abbreviated as ICF 20. The aim of the ICF is to provide a unified and standard framework and language for the description of health status and it is 10

12 Introduction based on a model of interactions among dimensions of human functioning at body, personal and societal levels whereby the role of the environment is clearly acknowledged 19, 20. The ICF conceptual framework is depicted in figure 1. Figure 1. International Classification of Functioning, Disability and Health conceptual framework Disorder or disease Body function & structure Activity Participation Environmental factors Personal factors In this framework function can be qualified in terms of capacity and performance 19, 20. Capacity is the child s ability to execute a task or action within a standardized environment while performance is defined as what an individual child does in his or her current environment 19, 20. Physical activity, physical fitness and health in chronic disease A chronic disease limits the child, direct and indirect in its (physical) activities leading to hypoactivity 21. Overprotection and ignorance of parents, teachers and even health professionals, fear towards activity, medication and social isolation are all possible contributing factors. Through a cascade of hypoactivity, deconditioning, detraining and increased and prolonged inactivity a vicious circle is unleashed causing disability (figure 2). 11

13 Chapter 1 Figure 2. The relationship between chronic disease, hypoactivity and deconditioning ( Bar-Or 21 ) Chronic disease Overprotection Fear Medication Social isolation Ignorance Hypoactivity Deconditioning Disability Over the last decade physical activity (PA) and physical fitness (PF) are assessed in a number of chronic conditions and they are summarised in table 1. In these studies PF is expressed as aerobic (exercise) capacity, an important element of health related PF. These studies confirm the assumption of Bar-Or of reduced PA and PF in chronic disease. PA, PF and health are interrelated although their relationship is highly complex 17, To become and remain physically fit it is necessary to become physically active and to adopt a physically active lifestyle. PA can be described as all leisure and non-leisure body movements resulting in an increased energy output from the resting condition 25. PF is a physiologic state of well-being that allows one to meet the demands of daily living and that provides the basis for sport performance 26. Evidence for the health benefits of PA and PF is accumulating although conclusions are mostly based on prospective observational studies in adults 27. PA and PF are effective in the primary and secondary prevention of several chronic conditions 26, 28, 29. PA and PF are also associated with a reduction in all-cause mortality 26, 29, 30. There is evidence that in youth aged 6 to 18 years, PA controls body weight, reduces blood pressure in hypertensive youth, improves aerobic capacity, muscular strength, endurance and skeletal health, reduces anxiety and depression and improves self-concept 31. PA has also a positive 12

14 Introduction effect on academic performance, concentration, memory and classroom behaviour 31. For children with JIA and other chronic diseases it is recognised that they could take advantage of the same health benefits 32, 33. Table 1: Physical activity and aerobic capacity in children with chronic disorders compared to healthy controls* Smith Painter Study Chronic disease or disorder Number of Pre-term born children (< 32 weken, < 1000 gr) Dialysis and kidney transplant patients patients Aerobic capacity Physical activity 126 n.a. 40 Shaibi DM Type 2 13 Valerio DM Type n.a. Komatsu DM Type 1 72 n.a. Williams Asthma n.r. n.a. Henderson JIA 23 n.a. Takken JIA 144 n.a. Takken JDM 15 n.a. Nixon CF with normal lung function 30 Van Brussel ALL follow-up 102 n.a. Van Brussel ALL follow-up 13 n.a. Engelbert Hypomobility syndrome 19 Long Chronic pain 20 n.a. Takken OI Type 1 17 n.a. * Abbreviations: DM = diabetes mellitus; JIA = juvenile idiopathic arthritis; JDM = juvenile dermatomyositis; CF = cystic fibrosis; ALL = acute lymphatic leukemia; OI = osteogenesis imperfecta; = decreased compared to healthy controls; n.a. = not assessed; n.r. = narrative review Aims and outlines of the thesis The aim of this thesis is to measure PA and PF in children and adolescents with JIA and to determine the effects of a program to improve PA in children with JIA. The studies described in this thesis are focussed on the following topics. First a measurement tool is evaluated to 13

15 Chapter 1 measure aerobic capacity. Secondly aerobic and anaerobic capacity, PA and illness perceptions are measured in children and adolescents with JIA. Finally an intervention is designed and tested within a randomised controlled trial to improve PA and exercise capacity in patients with JIA. The thesis consists of the following chapters: In the first chapter the perspective of JIA as a chronic disease is described. Reduced PA and aerobic capacity is common in children with a chronic disease. In the second chapter we examine the validity of the 6-minute walking test as a simple and inexpensive measuring tool for aerobic capacity in children with JIA. In chapter 3 we describe the aerobic and anaerobic exercise capacity in children with JIA in comparison with healthy peers while in chapter 4 we do the same for adolescents with JIA. Chapter 5 describes PA in adolescents with JIA and these are compared with healthy age mates. In chapter 6 we describe the illness representations of adolescents with JIA and associations with functional status are explored. In chapter 7 we introduce a new interactive internet-based program for children with JIA and we examine the effectiveness of the intervention on PA and PF using a randomised controlled trial. In chapter 8 the general discussion can be found. References 1. Borchers AT. Juvenile idiopathic arthritis. Autoimmun Rev 2006; 5: Davidson J. Juvenile idiopathic arthritis: a clinical overview. Eur J Radiol 2000; 33: Jordan A. Juvenile idiopathic arthritis: the paediatric perspective. Pediatr Radiol 2006; 36: Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet 2007; 369: Haines KA. Juvenile idiopathic arthritis: therapies in the 21st century. Bull NYU Hosp Jt Dis 2007; 65: Wallace CA. Current management of juvenile idiopathic arthritis. Best Pract Res Clin Rheumatol 2006; 20: Wallace CA, Huang B, Bandeira M, Ravelli A, Giannini EH. Patterns of clinical remission in select categories of juvenile idiopathic arthritis. Arthritis Rheum 2005; 52: David J, Cooper C, Hickey L, Lloyd J, Dore C, McCullough C et al. The functional and psychological outcomes of juvenile chronic arthritis in young adulthood. Br J Rheumatol 1994; 33: Fantini F, Gerloni V, Gattinara M, Cimaz R, Arnoldi C, Lupi E. Remission in juvenile chronic arthritis: a cohort study of 683 consecutive cases with a mean 10 year followup. J Rheumatol 2003; 30: Flato B, Aasland A, Vinje O, Forre O. Outcome and predictive factors in juvenile rheumatoid arthritis and juvenile spondyloarthropathy. J Rheumatol 1998; 25: Flato B, Lien G, Smerdel A, Vinje O, Dale K, Johnston V et al. Prognostic factors in juvenile rheumatoid arthritis: a case-control study revealing early predictors and outcome after 14.9 years. J Rheumatol 2003; 30: Foster HE, Marshall N, Myers A, Dunkley P, Griffiths ID. Outcome in adults with juvenile idiopathic arthritis: a quality of life study. Arthritis Rheum 2003; 48: Koivuniemi R, Leirisalo-Repo M. Juvenile chronic arthritis in adult life: a study of long-term outcome in patients with juvenile chronic arthritis or adult rheumatoid arthritis. Clin Rheumatol 1999; 18: Minden K, Niewerth M, Listing J, Biedermann T, Bollow M, Schontube M et al. Long-term outcome in patients with juvenile idiopathic arthritis. Arthritis Rheum 2002; 46:

16 Introduction 15. Packham JC, Hall MA. Long-term follow-up of 246 adults with juvenile idiopathic arthritis: functional outcome. Rheumatology 2002; 41: Zak M, Pedersen FK. Juvenile chronic arthritis into adulthood: a long-term follow-up study. Rheumatology 2000; 39: Bouchard C. Physical activity, Fitness and Health: Overview of the Consensus Symposium. In: Quinney HA, Gauvin L, Wall TA, editors. Towards active living; Proceedings of the international conference on physical activity, fitness and health. Champaign, IL: Human Kinetics Publishers; Engel GL. The need for a new medical model: a challenge for biomedicine. Science 1977; 196: Lollar DJ, Simeonsson RJ. Diagnosis to function: classification for children and youths. J of dev and beh pediatrics 2005; 26: World Health Organisation. International Classification of Functioning, Disability and Health (ICF). Geneva, Switzerland: Bar-Or O. Children and exercise in a clinical context; a overview. Pediatric sports medicine. New York: Springer-Verlag; Boreham C. The physical activity, fitness and health of children. J Sports Sci 2001; 19: Ortega FB. Physical fitness in childhood and adolescence: a powerful marker of health. Int J Obes (Lond) 2008; 32: Rowland TW. Physical activity, fitness, and health in children: a close look. Pediatrics 1994; 93: Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep 1985; 100: Warburton DE. Health benefits of physical activity: the evidence. CMAJ 2006; 174: Blair SN. Is physical activity or physical fitness more important in defining health benefits? Med Sci Sports Exerc 2001; 33(6 Suppl):S379-S Macera CA. Major public health benefits of physical activity. Arthritis Rheum 2003; 49: U.S.Department of Health and Human Services. Physical Activity and Health; A Report of the Surgeon General. Atlanta: Centers for Disease Control and Prevention; Erikssen G. Changes in physical fitness and changes in mortality. The Lancet 1998; 352: Strong WB, Malina RM, Blimkie CJ, Daniels SR, Dishman RK, Gutin B et al. Evidence based physical activity for school-age youth. J Pediatr 2005; 146: Klepper SE. Exercise and fitness in children with arthritis: evidence of benefits for exercise and physical activity. Arthritis Rheum 2003; 49: Morris PJ. Physical activity recommendations for children and adolescents with chronic disease. Curr sports med reports 2008; 7: Smith LJ, van Asperen PP, McKay KO, Selvadurai H, Fitzgerald DA. Reduced exercise capacity in children born very preterm. Pediatrics 2008; 122:e287-e Painter P, Krasnoff J, Mathias R. Exercise capacity and physical fitness in pediatric dialysis and kidney transplant patients. Pediatr Nephrol 2007; 22: Shaibi GQ, Faulkner MS, Weigensberg MJ, Fritschi C, Goran MI. Cardiorespiratory fitness and physical activity in youth with type 2 diabetes. Pediatr Diabetes 2008; 9: Valerio G, Spagnuolo MI, Lombardi F, Spadaro R, Siano M, Franzese A. Physical activity and sports participation in children and adolescents with type 1 diabetes mellitus. Nutr Metab Cardiovasc Dis 2007; 17: Komatsu WR, Gabbay MA, Castro ML, Saraiva GL, Chacra AR, Barros Neto TL et al. Aerobic exercise capacity in normal adolescents and those with type 1 diabetes mellitus. Pediatr Diabetes 2005; 6: Williams B, Powell A, Hoskins G, Neville R. Exploring and explaining low participation in physical activity among children and young people with asthma: a review. BMC Fam Pract 2008; 9: Henderson CJ, Lovell DJ, Specker BL, Campaigne BN. Physical activity in children with juvenile rheumatoid arthritis: quantification and evaluation. Arthritis Care Res 1995; 8: Takken T, Hemel A, van der Net J, Helders PJ. Aerobic fitness in children with juvenile idiopathic arthritis: a systematic review. J Rheumatol 2002; 29: Takken T, Spermon N, Helders PJ, Prakken AB, van der Net J. Aerobic exercise capacity in patients with juvenile dermatomyositis. J Rheumatol 2003; 30: Nixon PA, Orenstein DM, Kelsey SF. Habitual physical activity in children and adolescents with cystic fibrosis. Med Sci Sports Exerc 2001; 33: van Brussel M, Takken T, Lucia A, van der Net J, Helders PJ. Is physical fitness decreased in survivors of childhood leukemia? A systematic review. Leukemia 2005; 19:

17 Chapter van Brussel M, Takken T, van der Net J, Engelbert RH, Bierings M, Schoenmakers MA et al. Physical function and fitness in long-term survivors of childhood leukaemia. Pediatr Rehabil 2006; 9: Engelbert RH, van Bergen M, Henneken T, Helders PJ, Takken T. Exercise tolerance in children and adolescents with musculoskeletal pain in joint hypermobility and joint hypomobility syndrome. Pediatrics 2006; 118:e690-e Long AC, Palermo TM, Manees AM. Brief report: using actigraphy to compare physical activity levels in adolescents with chronic pain and healthy adolescents. J Pediatr Psychol 2008; 33: Takken T, Terlingen HC, Helders PJ, Pruijs H, Van der Ent CK, Engelbert RH. Cardiopulmonary fitness and muscle strength in patients with osteogenesis imperfecta type I. J Pediatr 2004; 145:

18 Chapter 2 Validity of the 6-minute walking test in juvenile idiopathic arthritis Otto T.H.M. Lelieveld 1, Tim Takken 2, Janjaap van der Net 2, Ellen van Weert 1 1 Center for Rehabilitation, University Medical Center Groningen (UMCG), University of Groningen, Groningen, the Netherlands, 2 Department of Pediatric Physical Therapy & Exercise Physiology, University Hospital for Children and Youth Het Wilhelmina Kinderziekenhuis', University Medical Center Utrecht, Utrecht, the Netherlands Arthritis & Rheumatism (Arhritis Care & Research) Vol. 53, No.2, April 15, 2005, pp

19 Chapter 2 Abstract Objective To examine the validity of the 6-minute walking test (6-MWT) as a simple and inexpensive measuring tool for aerobic exercise capacity in children with juvenile idiopathic arthritis. Methods Patients participating in a randomized controlled trial on the effectiveness of an aquatraining program were selected for this study. In order to examine the consistency of the results, we took two independent samples of the study population. Walking distance was assessed with the 6-MWT and aerobic exercise capacity with symptom limited bicycle ergometry. Results In sample 1: 22 patients were included, 6 boys and 16 girls. Mean ± SD age was 8.2 ± 2.1 years. In sample 2: 21 patients were included, 5 boys and 16 girls. Mean ± SD age was 8.6 ± 2.0 years. Pearson s correlation between walking distance and absolute and relative peak oxygen uptake (VO 2peak ) were low to moderate. Conclusion Walking distance is a poor predictor of VO 2peak and it is concluded that the 6-MWT is not a valid measurement tool to measure aerobic exercise capacity.. 18

20 Validity of the 6-MWT in JIA Introduction Lower physical activity levels and decreased physical fitness levels have been reported in children with juvenile idiopathic arthritis (JIA) 1. Physical fitness includes 4 components: muscular endurance and strength, flexibility, body composition, and cardiorespiratory endurance or aerobic fitness 2. Cardiorespiratory endurance or aerobic fitness is most strongly associated with health benefits in the general population and is therefore the primary focus of most exercise programs 3,4. Children with JIA have a moderate to large impairment in aerobic fitness as represented by peak oxygen uptake (VO 2peak ) compared with healthy children 5. VO 2peak has been described as the golden standard for aerobic fitness and is frequently examined using symptom limited bicycle ergometry (SLBE) in combination with a metabolic cart to analyze respiratory gases 6. However, bicycle ergometry and metabolic measurements are not always feasible in pediatric patients. It may be difficult to motivate nonathletic children to an exhaustive effort, intensive exercise may pose a risk to children with cardiopulmonary or musculoskeletal disease, and metabolic measurements systems may not be available, particularly in a field setting 7. Therefore, there is need for simple and inexpensive measurement tools to measure aerobic fitness. The 6-Minute Walking Test (6- MWT), a simple and inexpensive measurement tool, is a good candidate 8. The 6-MWT is a self-paced and submaximal endurance test. In adult patients the 6-MWT has been widely used, most often in patients with pulmonary or cardiac diseases 9,10. Literature provides support for the reliability, validity, and responsiveness of the 6-MWT for a wide spectrum of adult individuals 9. In addition, the 6-MWT is described as easy to administer, better tolerated, and more reflective of activities of daily living than other walking tests and has therefore been described as the test of choice when using a functional walk test for clinical or research purposes 10. In pediatric patients, only 2 studies report the use of the 6- MWT 11,12. Gulmans et al found that for this group the 6-MWT is a valid and useful test to assess the exercise tolerance and endurance in children with cystic fibrosis 11. Nixon et al suggested that the 6-MWT might provide an alternative method for assessing functional exercise capacity in severely ill children 12. Despite these promising results, the validity of the 6-MWT in children with rheumatic disease has, to our knowledge, never before been examined. Validity refers to the question as to whether an instrument appears to measure what it purports to measure, i.e. endurance. In addition, validity indicates whether a variable can be correlated 19

21 Chapter 2 with the gold standard for cardiorespiratory endurance, i.e, VO 2peak. The aim of the present study was to examine the validity of the 6-MWT in children with JIA. Patients and methods Patients Patients participating in a randomized controlled trial (RCT) on the effectiveness of an aquatic training program were selected for this study 13. Eligible patients for the RCT were those with a diagnosis of JIA from a pediatric rheumatologist using European League Against Rheumatism and International League of Associations for Rheumatology Criteria 14, and had an age range of 5 to 12 years. Patients were recruited from the pediatric rheumatology outpatient clinics of the Beatrix Children s Hospital of the University Hospital Groningen and the Wilhelmina Children s Hospital of the University Medical Center Utrecht. All patients were receiving a local and/or systemic arthritis related therapy consisting of Non-Steroid Anti-Inflammatory drugs and/or disease modifying anti-rheumatic drugs and/or immunesuppressive drugs in the last six months prior to inclusion. Patients were excluded if they had minor surgery < 14 days prior to inclusion, or major surgery < 6 weeks prior to inclusion. Outcome measurements Walking distance was assessed with the 6-MWT, which was performed on an 8-meter track in a straight corridor. Patients were instructed to cover the largest possible distance in 6 minutes at a self-chosen walking speed. Turns were made on both ends of the 8-meter track. Standard encouragement was given: Keep going, You are doing well, and Everything is going well. Time was measured with a stopwatch. The patient was kept informed about the progress of the time. The total distance was calculated as the counted repetitions and multiplied by 8 meters. The total outcome of walking distance was taken for analysis. Aerobic capacity was assessed with SLBE using an electronically braked cycle ergometer (Lode Examiner; Lode BV, Groningen, the Netherlands). The seat height was adjusted to the patient's leg length. The workload was increased in constant increments during the exercise test until the patient stopped due to volitional exhaustion, despite strong verbal encouragement from the experimenters. Maximal effort occurred when 1 of 3 criteria was met: ratings of perceived exertion (RPE) of 10 on a scale from 1-10; heart rate (HR) >180 beats per minute; or a respiratory exchange ratio (RER) >

22 Validity of the 6-MWT in JIA During the test the patients breathed through a face mask (Hans Rudolph Inc., Kansas City, MO) connected to a calibrated metabolic cart (Oxycon Champion; Jaeger, Mijnhart, Bunnik, The Netherlands). Expired gas was passed through a flow meter, an oxygen analyzer, and a carbon dioxide analyzer. The flow meter and gas analyzer were connected to a computer, which calculated breath-by-breath minute ventilation, oxygen consumption, carbon dioxide production, and RER from conventional equations. HR was measured continuously during the maximal exercise test by a bipolar electrocardiogram. RPE were recorded during exercise on a Borg CR-10 scale, in which 0 reflected no exertion and 10 maximal exertion. VO 2peak measured as the average value over the last 30 seconds during the maximal exercise test was taken for analysis. Joint status The number of affected joints of the lower extremities was determined. Tenderness and swelling were scored for the hip, knee, ankle, and toes. Tenderness was scored using a 2-point scale (1 = pain, and 2 = no pain.) Swelling was scored using a 4-point Likert scale (0 = no swelling, and 4 = severe swelling). The range of motion (ROM) was scored using the paediatric Escola Paulista de Medicina Range of Motion (pepm-rom) scale. Measurements were made using a goniometer and classification was done using a 4-point Likert scale (0 = no limitation and 4 = severe limitation) 15. Procedure Patients were selected from the RCT, but only patients who met the criteria of a maximal bicycle ergometry and a 6-MWT were included in the study. Therefore, patients who performed maximal during a graded exercise test to exhaustion (HR > 180, RER > 1.0) and patients who performed a 6-MWT were included to assess the validity of the 6-MWT. Additionally, to examine the consistency of the results, we took 2 independent samples of the study population. Samples were taken from the baseline measurements. Both groups consisted of different patients (i.e., none of the patients were included in both groups). Statistical analysis For statistical analysis the Statistical Package for Social Sciences (Version 10; SPSS, Chicago, IL) was used. Descriptive statistics were used for patient's characteristics of all samples and for walking distance and VO 2peak. Chi-square tests and independent t-samples 21

23 Chapter 2 were used to compare sample 1 and 2 on differences with respect to sex, age, and number of affected joints. Pearson's product-moment correlation coefficient (r) were performed to assess the relationship between VO 2peak and 6-MWT, in both independent samples. A Pearson correlation coefficient between 0.26 and 0.49 reflects poor agreement, those between 0.50 and 0.69 moderate agreement, and 0.70 high agreement 16. P values less than 0.05 were considered statistically significant. Results Patients/baseline characteristics There were 22 patients (6 boys, 16 girls) in sample 1. The mean ± SD age was 8.2 ± 2.1 years. There were 7 children with oligoarticular JIA, 12 with polyarticular JIA, and 3 children with systemic JIA. Seven children had no pain, swelling, or joint limitation in any of the measured lower extremity joints. Fifteen children had pain, swelling, and/or joint limitation in at least 1 of the lower extremity joints. There were 21 patients (5 boys, 16 girls) in sample 2. The mean ± SD age was 8.6 ± 2.0 years. Twelve of the children had oligoarticular JIA, and 9 polyarticular JIA. Nine children had no pain, swelling, or joint limitation in any of the measured lower extremity joints. Twelve children had pain, swelling, and/or joint limitation in at least 1 of the lower extremity joints (Table 1). Independent t-sample for age showed no difference between sample 1 and 2 (P = 0.54). Independent t-sample for number of affected joints showed no difference between sample 1 and 2 at the first (P = 0.72) and second (P = 0.17) baseline measurement. Chi-square test showed no differences in sample 1 and 2 with respect to sex ( 2 = 0.07, P = 0.80). The mean ± SD walking distance of the 6-MWT in sample 1 was 463 ± 63 meters. The mean ± SD absolute VO 2peak in this sample was 1.08 ± 0.30 liters/minute and mean ± SD relative VO 2peak was ± 5.58 ml/kg/minute bodyweight. The mean ± SD walking distance of the 6-MWT in sample 2 was 468 ± 57 meters. The mean ± SD absolute VO 2peak in sample 2 was 1.13 ± 0.29 liters/minute and the mean ± SD relative VO 2peak was ± 6.30 ml/kg/minute bodyweight. 22

24 Validity of the 6-MWT in JIA Table 1. Baseline characteristics* Sample 1 (n = 22) Sample 2 (n = 21) No. male/female 6 /16 5 /16 Age, mean ± SD years 8.2 ± ± 2.0 JIA Type Oligoarticular Polyarticular Systemic Joint score *Except when indicated otherwise, values are the number. JIA = juvenile idiopathic arthritis. Number of joints with swelling, tenderness and/or joint limitation. Pearson's correlation coefficient (r) in sample 1 between walking distance and absolute VO 2peak was 0.43 (P = 0.05). Pearson's correlation coefficient between walking distance and relative VO 2peak in sample 1 was 0.41 (P = 0.06). Pearson's correlation coefficient in sample 2 between walking distance and absolute VO 2peak was 0.51 (P = 0.02). Pearson's correlation coefficient between walking distance and relative VO 2peak in sample 2 was 0.32 (P = 0.16) (Table 2). Post-hoc analysis We divided the patient population in 2 groups representing less extensive joint involvement and more extensive joint involvement. Therefore, we created a new dichotomous variable: joint involvement. Less extensive joint involvement (n = 20) represented those children with 0 or 1 joint of the lower extremity involved, and more extensive joint involvement (n = 23) represented those children with 2 joints involved. The less extensive group had a mean ± SD walking distance of 477 ± 14.3 meters while the more extensive group had a mean ± SD walking distance of 456 ± 11.6 meters. Although there was a 21-meter difference between the groups, independent samples tests showed no significant difference in walking distance between the 2 groups (P = 0.86). 23

25 Chapter 2 Table 2. Comparison of walking distance, absolute and relative VO 2peak, in samples 1 and 2* Sample 1 (n = 22) Sample 2 (n = 21) 6-MWD, meters 463 ± ± 57 VO 2peak, liters/minute 1.08 ± ± 0.29 VO 2peak, ml/kg/minute 35.4 ± ± 6.3 Pearson s correlation for 6-MWD and absolute VO 2peak Pearson s correlation for 6-MWD and relative VO 2peak *Except when indicated otherwise, values are mean ± SD. 6-MWD = 6-minute walking distance; VO 2peak = peak oxygen uptake. For sample 1, P = 0.05 and P = 0.06 for the comparison of the 6-MWD and absolute VO 2peak, and 6-MWD and relative VO 2peak, respectively. For sample 2, P = 0.02 and P = 0.16 for the comparison of the 6-MWD and absolute VO 2peak, and 6-MWD and relative VO 2peak, respectively. Discussion The aim of the present study was to determine the validity of the 6-MWT in children with JIA. The results of the study showed a statistically significant low to moderate correlation between walking distance and absolute VO 2peak in the first and second sample, suggesting a low to moderate validity of the 6-MWT. Furthermore, we found a low and a non-significant correlation between walking distance and relative VO 2peak in the first and second sample, respectively, indicating a low validity of the 6-MWT as indicator of VO 2peak in JIA patients. The differences in correlation between relative and absolute VO 2peak and walking distance are in accordance with observations made by Rowland 7. Rowland showed that both biologic maturation and body composition could profoundly affect the validity of VO 2peak per kilogram as an indicator of endurance fitness. Therefore VO 2peak is only useful as a marker in samples of children that are strictly homogeneous in terms of body fat as well as biologic maturity, which is not the case in our 2 samples. The same difference between absolute and relative VO 2peak is seen in the population of Gulmans et al 11 who also found a significant correlation between walking distance and absolute VO 2peak but a nonsignificant correlation between walking distance and relative VO 2peak. This also indicates a low validity of the 6-MWT as an indicator of VO 2peak in children with cystic fibrosis. The results of the present study were not in accordance with the high correlation of walking distance and relative VO 2peak in children with severe cardiorespiratory disease (Table 3). 24

26 Validity of the 6-MWT in JIA Table 3. Comparison of walking distance, absolute and relative VO 2peak in studies by Lelieveld (Sample 1, Sample 2), Gulmans et al (reference 11), and Nixon et al (reference 12)* Sample 1 n = 22 Sample 2 n = 21 Gulmans n = 15 Nixon n = 17 Group JIA JIA Moderate CF Severe CR Age, mean ± years 8.2 ± ± ± ± 2.6 Walking distance, mean ± meters 463 ± ± ± ± 143 Absolute VO 2peak 1.08 ± ± ± 0.50 Not reported Relative VO 2peak 35.4 ± ± ± ± 5.1 Pearson correlation for 6-MWD Not reported and absolute VO 2peak Pearson correlation for 6-MWD and relativevo 2peak * JIA = juvenile idiopathic arthritis; CF = cystic fibrosis; CR = cardiorespiratory disease; 6-MWD = 6 minute walking distance. For sample 1, P = 0.05 and P = 0.06 for the comparison of the 6-MWD and absolute VO 2peak, and 6-MWD and relative VO 2peak, respectively For sample 2, P = 0.02 and P = 0.16 for the comparison of the 6-MWD and absolute VO 2peak, and 6-MWD and relative VO 2peak, respectively For Gulmans et al, P < and P = not significant for the comparison of the 6-MWD and absolute VO 2peak, and 6-MWD and relative VO 2peak, respectively For Nixon et al, P = not reported and P < 0.05 for the comparison of the 6-MWD and absolute VO 2peak, and 6- MWD and relative VO 2peak, respectively These differences might be explained by disease-specific factors. In musculoskeletal diseases like JIA, endurance performance might be negatively influenced by joint status. This negative influence is more prominent during weight-bearing activities like walking compared with nonweight-bearing activities like cycling. In walking, the body weight has to be moved upwards and forwards, while in cycling the workload is provided by the wheel resistance and is therefore body-mass independent. In both samples of our study population, tenderness, swelling, and/or limited ROM in one or more lower extremity joints was generally present, indicating poor joint status. This poor joint status is also reflected in the low walking distance of the JIA group compared with the cystic fibrosis group. However, a post-hoc analysis in our study population indicated that more or less joint involvement does not have a significant influence on walking distance. Apparently, other factors such as coping strategy, kinesiophoby, development, or others may contribute to walking distance. We did not include these factors in our study, and we think it would be interesting to study these factors in the future. Gas exchange measurements during 6-MWT in children with JIA should elucidate the physiologic responses during this test in JIA patients. Disease-specific factors may also be present in the group with severe cardiorespiratory disease, but from a different origin. Mean relative VO 2peak values of 19.0 ml/kg/minute in this group indicate severely impaired cardiorespiratory function. With such severely impaired 25

27 Chapter 2 cardiorespiratory function even a submaximal endurance test will push a patient to maximal effort. This changes the character of the 6-MWT from submaximal to maximal, which can explain the high correlation between the 6-MWT and the SLBE. Therefore, in children with severe cardiorespiratory disease, the 6-MWT is a much better predictor of VO 2peak than in children with JIA. We can conclude that the 6-MWT seems to be a poor predictor of VO 2peak in children with JIA. Walking distance of the 6-MWT in children with JIA reflects more joint status than aerobic fitness. The 6-MWT might therefore be a possible instrument to measure walking ability in children with JIA in a field setting. References 1. Takken T. Studies on physical performance and functional ability in juvenile idiopathic arthritis [PhD thesis]. Utrecht, the Netherlands: Utrecht University; p Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep 1985; 100: NIH Consensus Development Panel on Physical Activity and Cardiovascular Health. Physical activity and cardiovascular health. JAMA 1996; 276: U.S. Surgeon General. Physical activity and health: a report of the Surgeon General. Washington (DC): U.S. Government Printing Office; Takken T, Hemel A, van der Net J, Helders PJ. Aerobic fitness in children with juvenile idiopathic arthritis: a systematic review. J Rheumatol 2002; 29: Shephard RJ, Allen C, Benade AJ, Davies CT, di Prampero PE, Hedman R, et al. The maximum oxygen intake: an international reference standard of cardiorespiratory fitness. Bull World Health Organ 1968; 38: Rowland TW. Developmental exercise physiology. Champaign (IL): Human Kinetics; p Singh G, Athreya BH, Fries JF, Goldsmith DP. Measurement of health status in children with juvenile rheumatoid arthritis. Arthritis Rheum 1994; 37: Sadaria KS, Bohannon RW. The 6-minute walk test: a brief review of literature. Clin Exerc Physiol 2001; 3: 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: Gulmans VA, van Veldhoven NH, de Meer K, Helders PJ. The six-minute walking test in children with cystic fibrosis: reliability and validity. Pediatr Pulmonol 1996; 22: Nixon PA, Joswiak ML, Fricker FJ. A six-minute walk test for assessing exercise tolerance in severely ill children. J Pediatr 1996; 129: Takken T, van der Net J, Kuis W, Helders PJ. Aquatic fitness training for children with juvenile idiopathic arthritis. Rheumatology (Oxford) 2003; 42: Hofer M, Southwood TR. Classification of childhood arthritis. Best Pract Res Clin Rheumatol 2002; 16: Len C, Ferraz MB, Goldenberg J, Oliveira LM, Araujo PP, Quaresma MR, et al. Pediatric Escola Paulista de Medicina Range of Motion Scale: a reduced joint count scale for general use in juvenile rheumatoid arthritis. J Rheumatol 1999; 26: Munro BH, Visintainer MA, Page EB. Statistical methods for health care research. Philadelphia: Lippincott Company; p

28 Chapter 3 Aerobic and anaerobic exercise capacity in children with juvenile idiopathic arthritis Marco van Brussel 1, Otto T. H. M. Lelieveld 2, Janjaap van der Net 1, Raoul H. H. Engelbert 1, Paul J. M. Helders 1, Tim Takken 1 1 Department of Pediatric Physical Therapy & Exercise Physiology, University Hospital for Children and Youth Het Wilhelmina Kinderziekenhuis', University Medical Center Utrecht, Utrecht, the Netherlands, 2 Center for Rehabilitation, University Medical Center Groningen (UMCG), University of Groningen, Groningen, the Netherlands Arthritis & Rheumatism (Arhritis Care & Research) Vol. 57, No.6, August 15, 2007, pp

29 Chapter 3 Abstract Objective To compare the aerobic and anaerobic exercise capacity of children with juvenile idiopathic arthritis (JIA) with healthy controls, to determine if there were differences based on disease onset type, and to examine the relationship between aerobic and anaerobic exercise capacity in children with JIA. Methods Sixty-two patients with JIA (mean ± SD age 11.9 ± 2.2 years, range ) participated in this study. Aerobic exercise capacity was measured using a cardiopulmonary exercise test. Anaerobic exercise capacity was measured using the Wingate Anaerobic Exercise Test (WAnT). Results All patients were able to perform the cardiopulmonary exercise test and WAnT without adverse events. On average, the maximal oxygen uptake (VO 2peak ) and VO 2peak/kg were 69.8% and 74.8%, respectively, of that predicted compared with healthy controls. Mean ± SD power was 66.7% ± 37.2% of that predicted compared with healthy children. Mean ± SD peak power was 65.5% ± 43.1% of that predicted compared with healthy children. There were significant differences between subgroups of JIA; the oligoarticular-onset group values did not significantly differ from healthy control values; the polyarticular rheumatoid factor positiveonset subgroup had the greatest impairment in both aerobic and anaerobic exercise capacity. The correlations of mean power and peak power with VO 2peak were r = and r = 0.697, respectively (P < 0.05). Conclusion This study demonstrates that both the aerobic and anaerobic exercise capacity in children with JIA are significantly decreased. The WAnT might be a valuable adjunct to other assessment tools in the followup of patients with JIA. 28

30 Exercise capacity in children with JIA Introduction Children with juvenile idiopathic arthritis (JIA) are believed to have a lower aerobic capacity, anaerobic capacity, and functional ability, which means that they have more problems in performing daily activities compared with healthy children 1. These lower parameters could lead to a more inactive lifestyle. Nonetheless, the manifestations of the disease such as chronic joint pain and stiffness, synovitis, and deformity are also thought to aggravate an inactive lifestyle 2,3. The aerobic capacity in children with JIA has been studied extensively in recent years Most of these studies suggest that patients with JIA have impairment in aerobic fitness 13, but little is known about the anaerobic capacity of children with JIA 10, Anaerobic capacity is important because most daily activities performed by children are anaerobic in nature. In a study by Takken et al 15, a large association between anaerobic physical fitness and functional ability demonstrated the importance of anaerobic physical fitness for children with JIA. Malleson et al 10 compared anaerobic fitness of a group of children with chronic arthritis with that of healthy controls and found no significant differences between mean peak anaerobic power for patients and controls; however, the mean values for both controls and patients were significantly lower than reported values for healthy children 10. Fan et al 16 and Wessel et al 17 studied children with JIA during a 50-meter run and found reduced sprint ability compared with healthy peers. Fisher et al 18 found that children with JIA could improve muscle strength significantly after an exercise training program, without increase in disease signs and symptoms. The current evidence base for anaerobic exercise capacity is small and is derived from findings in small cohorts. In the current study, we aimed to increase the evidence basis for both aerobic and anaerobic exercise capacity and their interrelationship. We therefore studied 1) the aerobic and anaerobic exercise capacity of a large cohort of patients with JIA and compared these with healthy controls, 2) if there were differences in aerobic and anaerobic exercise capacity in children with JIA based on disease onset type, and 3) the relationship among aerobic and anaerobic exercise capacity in children with JIA. 29

31 Chapter 3 Patients and methods Patients Sixty-two patients with JIA participated in this study. The patients were recruited from the pediatric rheumatology outpatient clinic of the Wilhelmina Children's Hospital and were diagnosed with JIA according to the International League of Associations for Rheumatology (ILAR) criteria 19. Thirty-six patients had polyarticular-onset JIA (29 rheumatoid factor negative and 7 rheumatoid factor positive), 11 patients had oligoarticular-onset JIA, 8 patients were classified as having extended oligoarticular-onset JIA, and 7 patients were classified as having systemic-onset JIA. Fifteen patients in the cohort were off medication. Of the remaining patients, 41 patients were receiving nonsteroidal antiinflammatory drugs, 28 were receiving disease-modifying antirheumatic drugs, 6 were receiving corticosteroids, and 7 were receiving biologic agents (biologic response modifiers). Disease onset and duration were assessed by retrospective analysis of patients' files. During the tests, 35 patients had active disease, 12 patients were in clinical remission and taking medication, and 15 patients were in clinical remission and off medication, according to criteria developed by Ruperto and Martini 20. All tests and measurements of the patients were performed on the same day, with enough resting time between the aerobic and anaerobic exercise tests. Informed consent was obtained from the parents and/or from the children if they were >12 years of age. The Medical Ethics Committee of the University Medical Center Utrecht approved all study procedures. Anthropometry The children's body mass and height were determined using an electronic scale and a stadiometer, respectively. Body mass index (BMI) was calculated as body mass (kg)/height (m 2 ). The BMI of the included children was compared with reference values of healthy Dutch children 21 and with international cutoff points for BMI for overweight and obese children 22. Subcutaneous adiposity was determined from skinfold measurements using Harpenden skinfold calipers (British Indications, St. Albans, Hertfordshire, UK). Measurements were obtained in triplicate at 7 sites (at the right side of the body): triceps, biceps, subscapular, suprailiac, mid-abdominal, medial calf, and thigh in accordance with the American College of Sports Medicine guidelines 23. The sum of the 7 skin folds was used as an index for subcutaneous fat according to methods described by Pollack et al

32 Exercise capacity in children with JIA Joint status Joint status was assessed by the number of tender and swollen joints. Tenderness and swelling were scored for the following joints: temporomandibular, sternoclavicular, shoulder, elbow, wrist, metacarpophalangeal and fingers, knee, ankle, metatarsophalangeal, and toes. Joint mobility was scored on the Pediatric Escola Paulista de Medicina Range of Motion Scale (pepmrom) 25. The pepmrom measures mobility in children with JIA based on the evaluation of joint range of motion. Ten joint movements (cervical spine [rotation], shoulder [abduction], wrist [flexion and extension], thumb [flexion metacarpophalangeal], hip [internal and external rotation], knee [extension], and ankle [dorsiflexion and plantar flexion]) were examined using a goniometer and were classified on a 4-point Likert scale ranging from 0 to 3 (0 = no limitation and 3 = severe limitation). The final score was calculated as the sum of the joint score of each movement divided by 10, providing a final range of scores for joint movement from 0 to 3. Functional ability The Childhood Health Assessment Questionnaire (CHAQ) was adapted by Sing et al 26 from the Stanford Health Assessment Questionnaire for use in patients ages 1-19 years, and measures functional status. A Dutch version was translated and validated 27. The CHAQ is a pediatric multidimensional questionnaire, which measures the child's ability in performing functions included in 8 areas (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities) for a total item number of 30. Respondents are directed to note only those difficulties caused by arthritis. Each question is scored from 0 to 3 (0 = able to do with no difficulty, 1 = able to do with some difficulty, 2 = able to do with much difficulty, 3 = unable to do). The question with the highest score within each domain determined the score for that domain. Whenever aids or assistance were required, the score for that domain was increased to a minimum of 2. The mean of the scores on the 8 domains provided the CHAQ disability scale (range 0-3, with 0 denoting no disability and 3 denoting severe disability). The CHAQ also incorporates a double-anchored, horizontal, 10-cm visual analog scale for the assessment of the child's overall well-being and a visual analog scale for the assessment of the intensity of the child's pain. 31