COMPARISON OF EFFECTS OF STRENGTH AND ENDURANCE TRAINING IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

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1 E1 Online Supplement for: COMPARISON OF EFFECTS OF STRENGTH AND ENDURANCE TRAINING IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE METHODS Subjects The study population consisted of patients with stable chronic obstructive pulmonary disease (COPD) (postbronchodilator FEV 1 < 70% of predicted with a reduced FEV 1 /FVC). The diagnosis of COPD was based on smoking history (> 20 pack-years) and pulmonary function tests showing irreversible bronchial obstruction defined by < 12% and < 200 ml increase of initial FEV 1 after administration of salbutamol (400 µg via a metered dose inhaler) (E1, E2). Most patients had been referred because of exercise intolerance, inability to perform activities of daily living, and exertional dyspnea. Subjects were in a clinically stable condition, aged between 40 and 80 years, with no history of a recent acute exacerbation episode. In all patients, drug management was considered to be optimal and was not modified during the exercise training program. Patients were excluded if they presented with unstable angina, peripheral vascular disease or joint-limiting mobility conditions, were unable to understand or complete questionnaires, or had other disorders likely to affect exercise performance. The research protocol for the study was approved by the ethics committee of our institution, and informed written consent was obtained for each participant. Study Design The training program conducted at our institution was developed in 3 alternate days each week for 12 weeks. Subjects were randomly assigned to endurance training alone, strength training alone, combined training modality (endurance and strength), or no training intervention (control group). Patients attended the hospital for 1 hour three times per week and were closely supervised by specialized personnel (chest physiotherapist, exercise physiologist, and respiratory physician). The duration of training sessions was 40 minutes plus a 10-minute warm-up and 10-minute cool off. Endurance training. The endurance training consisted of leg exercise on a calibrated ergocycle (Ergometer ZX1; Kettler Sport, Ense-Parsit, Germany) at a fixed pedaling speed (60 rpm) according to which it was possible to measure the actual work

2 E2 rate (W) achieved by the patient during each session. The physiotherapist was aware of the training intensity prescribed for each patient and encouraged him/her to reach it. The work rate corresponding to 70% of the peak work rate achieved during the baseline incremental exercise test was selected as the target training intensity. The criteria used to increase or decrease the intensity of the training session were those described by Maltais and associates (E3). Strength training. The strength training program included different exercises, which were performed with the following weight lifting procedures: (1) chest pull (mainly for strengthening of the latissimus dorsi); (2) butterfly (mainly for the pectoralis major muscle); (3) neck press (mainly for the triceps brachii and deltoid); (4) leg flexion (mainly for the biceps femoris and grastrocnemius); and (5) leg extension (mainly for the quadriceps femoris). The weight lifting exercises were performed with gymnastic apparatus (Fitness-Center Classic; Kettler Sport, Ense-Parsit, Germany). The patients performed four series of six to eight repetitions for each of the exercises included in the strength training program at a workload of 70 to 85% of the one repetition maximum (1 RM). This test was repeated each 2 weeks for new adjustments of the workload. Combined training modality. The combined endurance and strength modality consisted of half the endurance exercise of the endurance training group (20-minute cycling at the same intensity than in the endurance training) and half the strengthening exercise of the strength training group (two series of six to eight repetitions of the five weight lifting procedures). Evaluation Subjects were evaluated on 2 consecutive days at baseline, at the end of the 12-week training program, and at 12 weeks posttraining. Pulmonary function tests. Spirometry was measured with a pneumotachograph (CompactBody; Jaeger, Würzburg, Germany). Measures were performed according to the European Respiratory Society guidelines, and expressed as a percentage of reference values (E4). Static lung volumes were determined in a constant-volume whole-body plethysmograph (Jaeger, Würzburg, Germany). Normal values used were those of Goldman and Becklake for lung volumes (E5). Arterial blood was sampled at the radial artery while the patients breathed room air for at least 1 hour in the sitting position. Arterial oxygen tension (Pa ), arterial carbon dioxide tension (Pa O ), and ph were 2 CO 2

3 E3 measured by means of an automated analyzer (ABL 300; Radiometer, Copenhagen, Denmark). Strength measurements. Weight lifting capacity was measured as the heaviest weight that could be lifted once throughout the complete range of movement (1 RM). Testing took place on 2 separate days, and the heaviest weight lifted was recorded as the pretraining value. In all cases, 1 RM values were determined for each of the exercises included in the strength training program. This test is used to assess patient s strength as well as to determine the workload of training. For each strength exercise, patients had to lift as much load as possible in only one attempt (four or five trials were generally required before the 1 RM was determined). The kilograms lifted were measured (E6, E7). Exercise test. Progressive exercise testing was performed to a symptom-limited maximum on a electronically braked cycle ergometer (Collins CPX GS/PLUS; Boston, MA). Patients began with a 3-minute period of unloaded pedaling at 60 rpm followed by 1-minute stepwise increments of 10 W. Subjects breathed through a low resistance two-way nonrebreathing valve (2700 series; Hans Rudolph, Kansas City, MO) with mouthpieces and noseclips in place. Minute ventilation and its components were measured with a pneumotachograph. The concentrations of expired O 2 and CO 2 were analyzed breath-by-breath with a zirconium dioxide-cell O 2 analyzer and an infrared CO 2 analyzer, respectively. These measures and the pneumotachograph flow signals were integrated electronically by a computerized system to yield 10-second averages of minute ventilation (VE), respiratory duty cycle (TI/Ttot), tidal volume (VT), respiratory rate (RR), oxygen uptake (VO 2 ), carbon dioxide output (VCO 2 ), and gas exchange ratio (R). Electrocardiographic monitoring for heart rate was carried out continuously as was monitoring of oxygen saturation (Sa O2 ) by a pulse oximeter (Biox 3700e; Ohmeda, Louisville, CO). The peak values for VO 2 and exercise work rate were related to the normal values (E8). Endurance test. A submaximal endurance cycling test was carried out on a calibrated cycle ergometer (Ergometer ZX1) at 70% of the maximum power output achieved during the baseline incremental exercise test. The same submaximal work rate was used throughout the study. The test was continued until the subject could no longer maintain the desired pedaling rate of 60 rpm, and time (in minutes) was then measured. Heart rate and oxygen saturation were monitored throughout exercise and during recovery.

4 E4 Shuttle walking test. We used the modified protocol of Singh and colleagues (E9). Patients were requested to walk between two cones placed 10 minutes apart. Walking speed increased progressively each minute. The instructions were standardized on a tape recording. The end point was determined when the patient was unable to maintain the required speed. Chronic breathlessness. The modified Baseline Dyspnea Index incorporates magnitude of task, magnitude of effort, and functional impairment (E10), and was used to generate an overall focal score of chronic activity-related breathlessness. Breathlessness was measured by an independent evaluator who was unaware of the purpose of the study and the patient s respiratory functional status. The same evaluator was kept for each subject throughout the study. Quality of life. Health-related quality of life was assessed using a Spanish validated version of the Chronic Respiratory Questionnaire (CRQ) (E11, E12). The CRQ measures health status and was specifically designed for assessment of change. It comprises four component scores: dyspnea, fatigue, emotional function and mastery, measured on a seven-point Likert scale. Statistical Analysis The sample size was calculated according to an improvement in submaximal exercise capacity (in minutes) greater than 20% in the exercise test, with a standard deviation of ± 10 minutes, α level of 0.05, β level of 0.20 (two-tailed test procedures), and assuming a loss percentage of 15%.The Kolmogorov-Smirnov test was used to assess the normal distribution of data. The analysis of variance (ANOVA) for repeated measures was applied for multiple comparisons between the groups (factor group and time ). Then, ANOVA for repeated measures was used for within-group comparisons (factor time ). A value of p < 0.05 was considered statistically significant. Values are reported as means ± standard deviation (SD).

5 E5 References E1. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995;152:S77 S120. E2. Siafakas NM, Vermeire P, Pride NB, Paoletti P, Gibson J, Howard P, Yernault JC, Decramer M, Higenbottam T, Postma DS, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). A consensus statement of the European Respiratory Society (ERS). Eur Respir J 1995;8: E3. Maltais F, LeBlanc P, Jobin J, Bérubé C, Bruneau J, Carrier L, Breton MJ, Falardeau G, Belleau R. Intensity of training and physiologic adaptation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;155: E4. Quanjer PH. Standardized lung function testing. Bull Eur Physiopathol Respir 1983;19:7 44. E5. Goldman HI, Becklake MR. Respiratory function tests: normal values at median altitudes and the prediction of normal results. Am Rev Tuberc 1959;79: E6. Brown AB, McCartney N, Sale DG. Positive adaptation to weight-lifting training in the elderly. J Appl Physiol 1990;69: E7. Lillegard WA, Terrio JD. Appropriate strength training. Med Clin North Am 1994;78: E8. Jones NL. The interpretation of stage 1 exercise test results. In: Trumbold C, editor. Clinical Exercise Testing (3rd edition), Philadelphia: Saunders; p E9. Singh SJ, Morgan MDL, Scott S, Walters D, Hardman AE. Development of a shuttle walking test of disability in patients with chronic airways obstruction. Thorax 1992;47: E10. Stoller JK, Ferranti R, Feinstein AR. Further specification and evaluation of a new clinical index for dyspnea. Am Rev Respir Dis 1986;135: E11. Guyatt GH, Berman LB, Townsend M, Pugsley SO, Chambers LW. A measure of quality of live for clinical trials in chronic lung disease. Thorax 1987;42: E12. Güell R, Casan P, Sangenís M, Sentís J, Morante F, Borras JM, Guyatt G. Traducción española y validación de un cuestionario de calidad de vida en pacientes con enfermedad pulmonar obstructiva crónica. Arch Bronconeumol 1995;31:

6 E6 TABLE E1. PATIENT CHARACTERISTICS* Strenght Training (n = 17) Endurance Training (n = 16) Strength + Endurance (n = 14) Age, yr 66 ± 6 66 ± 8 60 ± 9 Sex, M/F 14/3 14/2 13/1 FVC, L 2.54 ± ± ± 0.55 FVC, % pred 72 ± ± ± 13 FEV 1, L 1.12 ± ± ± 0.4 FEV 1, % pred 40 ± ± ± 12 FRC, % 161 ± ± ± 34 TLC, % 113 ± ± ± 20 Pa O2, mm Hg 71 ± 7 65 ± ± 9 Pa CO2, mm Hg 44 ± 7 45 ± 7 44 ± 6 *Values are mean ± SD.

7 E7 TABLE E2. PHYSIOLOGICAL PARAMETERS AT PEAK EXERCISE BEFORE AND AFTER DIFFERENT TRAINING MODALITIES* Pretraining (t0) VO 2max (L/minute) VO 2max (% pred) Wmax (W) Wmax (% pred) VE max (L/minute) Strength 1.3 ± ± ± ± ± 15 Endurance 1.32 ± ± ± ± ± 8 Combined 1.26 ± ± 9 41 ± ± ± 8 End 12-week training (t1) Strength 1.43 ± ± ± ± ± 14 Endurance 1.48 ± ± ± ± ± 11 Combined 1.34 ± ± ± 9 33 ± ± 9 12-week posttraining (t2) Strength 1.3 ± ± ± ± ± 15 Endurance 1.41 ± ± ± 16 31± ± 13 Combined 1.24 ± ± ± ± ± 10 Changes t1 versus t0 Strength 0.13 ± ± 20 5 ± 12 4 ± ± 11.6 Endurance 0.15 ± ± ± 12 8 ± ± 8.2 Combined 0.08 ± ± 11 5 ± 17 4 ± ± 6 Changes t2 versus t1 Strength 0.14 ± ± 16 7 ± 8 5 ± ± 8.6 Endurance 0 ± ± 12 7 ± 11 6 ± 8 0 ± 2.9 Combined 0 ± ± 12 4 ± 7 2 ± ± 5.9 *Values are mean ± SD. p < 0.05 pre- versus end of 12-week training. p < 0.03 posttraining versus end of 12-week training. p = NS for all other within-group and between-group comparisons.

8 E8 TABLE E3. EXERCISE PERFORMANCE AND MUSCLE STRENGTH BEFORE AND AFTER DIFFERENT TRAINING MODALITIES* Pretraining (t0) Shuttle Walking Test (m) Endurance Test (minute) Chest Pull Strength Measurements (kg) Butterfly Neck Press Leg Flexion Leg Extension Strength 457 ± ± ± ± 5 21± 5 15± 5 36± 13 Endurance 457 ± ± ± 8 19 ± 4 21 ± 4 15± 5 39 ± 8 Combined 434 ± ± ± ± 5 22 ± 4 17 ± 6 36 ± 11 End 12-week training (t1) Strength 561 ± ± ± 9 28 ± 6 30± 7 31± 6 55 ± 11 Endurance 501 ± ± ± 22 ± ± 6 20 ± 6 47 ± 9 Combined 493 ± ± ± 9 25 ± 6 30 ± 6 32 ± 5 55 ± week posttraining (t2) Strength 532 ± ± ± 8 23 ± 7 27 ± 6 27 ± 6 53 ± 13 Endurance 479 ± ± ± 9 22 ± 4 22 ± 4 22 ± 8 43 ± 14 Combined 498 ± ± ± 8 20 ± 5 26 ± 5 28 ± 5 51 ± 9 Changes t1 versus t0 Strength 104 ± ± ± 6 12 ± 4 8 ± 3 16 ± 5 19 ± 8 Endurance 39 ± ± ± 3 3 ± 6 1 ± 3 5 ± 4 8 ± 6 Combined 59 ± ± ± 7 9 ± 4 8 ± 5 14 ± 5 19 ± 5 Changes t2 versus t1 ** Strength 29 ± ± 13 3 ± 5 ± 3 4 ** 3 ± 4 3 ± 6 ** 2 ± 6 Endurance 49 ± ± ± 2 1 ± 2 0 ± 2 3 ± 8 2 ± 9 Combined 2 ± 97 8 ± ± 4 ± ± 4 ± 4 3 *Values are mean ± SD. Shuttle walking test: p < pre- versus end of 12-week training, p = NS for all other within- and between-group comparisons. Endurance test: p < 0.05 pre-versus end of 12-week training and pre- versus posttraining; p < endurance versus strength groups, and p < 0.01 combined modality versus strength. Strength test: p < 0.05 pre-versus end of 12-week training and pre- versus posttraining; p < strength versus endurance groups, and p < 0.01 combined modality versus endurance; ** p < 0.05 strength versus endurance groups and p < 0.05 combined modality versus endurance. 2 ± 5

9 E9 TABLE E4. CHANGES IN DYSPNEA AND HEALTH-RELATED QUALITY OF LIFE BEFORE AND AFTER DIFFERENT TRAINING MODALITIES* Pretraining (t0) Baseline Dyspnea Index (score) Magnitude of Task Magnitude of Effort Functional Impairment Chronic Respiratory Questionnaire (score) Dyspnea Fatigue Emotion Mastery Strength 1.6 ± ± ± ± ± ± ± 1.1 Endurance 2.1 ± ± ± ± ± ± ± 1.5 Combined 1.9 ± ± ± ± ± ± ± 1.3 End 12-week training (t1) Strength 2.1 ± ± ± ± ± ± ± 1 Endurance 2.4 ± ± ± ± ± ± ± 1.1 Combined 2.4 ± ± ± ± ± ± ± week posttraining (t2) Strength 2.1 ± ± ± ± ± 5.2 ± ± 1 Endurance 2.5 ± ± ± ± ± 5.1 ± ± Combined 2.6 ± ± ± ± ± ± ± 0.8 *Values as mean ± SD. p < 0.05 pre- versus end of 12-week training and pre- versus posttraining.