Determinants of Peripheral Muscle Strength and Activity in Daily Life in People With Bronchiectasis

Determinants of Peripheral Muscle Strength and Activity in Daily Life in People With Bronchiectasis Abstract Background Bronchiectasis is characterized by a progressive structural lung damage, recurrent infections and chronic inflammation which compromise the exertion tolerance, and may have an impact on skeletal muscle function and physical function. Objective The purpose of this study was to compare peripheral muscle strength, exercise capacity, and physical activity in daily life between participants with bronchiectasis and controls and to investigate the determinants of the peripheral muscle strength and physical activity in daily life in bronchiectasis. Design This study used a cross-sectional design. Methods The participants’ quadriceps femoris and biceps brachii muscle strength was measured. They performed the incremental shuttle walk test (ISWT) and cardiopulmonary exercise testing, and the number of steps/day was measured by a pedometer. Results Participants had reduced quadriceps femoris muscle strength (mean difference to control group = 7 kg, 95% CI = 3.8–10.1 kg), biceps brachii muscle strength (2.1 kg, 95% CI = 0.7–3.4 kg), ISWT (227 m, 95% CI = 174–281 m), peak VO2 (6.4 ml/Kg/min, 95% CI = 4.0–8.7 ml/Kg/min), and number of steps/day (3,332 steps/day, 95% CI = 1,758–4,890 steps/day). A lower quadriceps femoris strength is independently associated to an older age, female sex, lower body mass index (BMI), higher score on the modified Medical Research Council scale, and shorter distance on the ISWT (R2 = 0.449). Biceps brachii strength is independently associated with sex, BMI, and dyspnea (R2 = 0.447). The determinants of number of daily steps were dyspnea and distance walked in ISWT, explaining only 27.7% of its variance. Limitations Number of steps per day was evaluated by a pedometer. Conclusions People with bronchiectasis have reduced peripheral muscle strength, and reduced aerobic and functional capacities, and they also are less active in daily life. Modifiable variables such as BMI, dyspnea, and distance walked on the ISWT are associated with peripheral muscle strength and physical activity in daily life. Bronchiectasis is a chronic disease characterized by a permanent and abnormal anatomic distortion of the bronchi (thickening, herniation, or dilation) accompanied by inflammatory response in the lumen that contributes to recurrent lung infections.1 Pulmonary manifestations have been very well described in these individuals: persistent cough, daily sputum production, persistent infection, and impaired pulmonary function.2 However, it is reasonable to infer that extrapulmonary manifestations may occur in bronchiectasis because of its progressive nature, as explained by the persistence of infection, inflammation, and lung damage.3 Reduced exercise capacity,4,5 impaired health-related quality of life,6 and physical inactivity7 have already been described in people with bronchiectasis, but studies addressing these issues are scarce. One small study suggested that bronchiectasis may affect exercise capacity and quality of life, but it was not able to demonstrate a reduction in peripheral muscle strength.8 However, some aspects of that study are liable to criticism. Although the study participants had a reduced exercise capacity compared with controls, they reached approximately 90% of the predicted values on the 6-Minute Walk Test, which cannot be considered to be reduced functional capacity.9 Moreover, health status was assessed using the Leicester Cough Questionnaire, but cough is not the only symptom in people with bronchiectasis that may affect health-related quality of life. Therefore, the small sample size (n = 20) might have resulted in the underestimation of extrapulmonary manifestations of bronchiectasis and is unlikely to reflect the disease spectrum seen in bronchiectasis.8 The systemic consequences of other chronic respiratory disease, such as chronic obstructive pulmonary disease (COPD), are becoming better understood. Some abnormalities observed in COPD are shared by people with bronchiectasis, such as increased markers of systemic inflammation10 and oxidative stress,11 hypoxemia,12 increased arterial stiffness,13 and malnutrition.10 However, the possible systemic consequences of bronchiectasis have not been investigated in this population, especially in terms of exercise capacity, muscle force, and physical activity, which predict the prognosis in other chronic pulmonary diseases such as COPD.14–16 Based on the progressive pulmonary impairment associated with multiple exacerbations, systemic inflammation, and elevated oxidative stress, we hypothesized that people with bronchiectasis have impairment of skeletal muscle function and physical function. In addition, the predictors of peripheral muscle strength and physical activity in daily life have not been previously investigated in bronchiectasis and may contribute to indicate specific interventions for rehabilitation to improve the physical and functional performance. The primary aim of this study was to compare peripheral muscle strength, exercise capacity, and physical activity in daily life between participants with bronchiectasis and their peers who are healthy. The secondary aim was to investigate the determinants of the peripheral muscle strength and physical activity in daily life in people with bronchiectasis. Methods Study Design and Subjects This study uses a cross-sectional design, with a period of recruitment and assessments from March 2012 to December 2014. For the study, 168 adults diagnosed with bronchiectasis as confirmed using high-resolution computed tomography were consecutively recruited from the outpatient clinic of a tertiary university hospital. Participants with heart disease, COPD, or cystic fibrosis were excluded. Nineteen participants with bronchiectasis were excluded (Figure), rsulting in a sample size of 149 participants (95 women). An age- and sex-matched control group of participants (n = 51, 32 women) was recruited subsequently from the local community, being in the same season as the participants with bronchiectasis. The study was approved by the Human Research Ethics Committees from Universidade Nove de Julho (committee reference no. 921/11) and University of São Paulo (committee reference no. 451538), with written informed consent obtained from all participants. Figure. View largeDownload slide Flowchart protocol. Figure. View largeDownload slide Flowchart protocol. Assessments Spirometric tests were performed by using the CPX Ultima (MedGraphics Corporation, St Paul, Minnesota, USA). Technical procedures were those recommended by the American Thoracic Society and European Respiratory Society.17 Forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) are expressed as percentage of the normal values for the Brazilian population.18 A body composition analyzer (Tanita BC 554; Tanita Corporation of America, Arlington Heights, Illinois) was used to obtain the fat-free mass (FFM), and the FFM index was calculated. Nutritional depletion was considered when the FFM index was ≤15 kg/m2 for women and ≤16 kg/m2 for men.19 Peripheral muscle strength was measured by maximum voluntary isometric contraction (MVIC) of the biceps brachii and quadriceps femoris muscles. A load cell (EMG800C; EMG System, São José dos Campos, Brazil) was interfaced to a computer to record the MVIC. For both muscles, participants performed 3 MVIC repetitions, maintaining each one for 5 seconds, with a minute's rest between repetitions. The highest value from the 3 reproducible contractions (<5% variability among attempts) was considered for analysis. The quadriceps femoris measurement was made with the knee joint angle fixed at 90 degrees of flexion and hip joint angle set at 90 degrees of flexion; for the biceps brachii, the arm was positioned along the body, and the elbow joint angle was fixed at 90 degrees of flexion. Two incremental shuttle walking tests (ISWT) (30 minutes apart) were carried out according to previous description.20 to assess functional capacity. The greatest distance, in meters, was considered for analysis, and was also expressed as percentage of predicted.21 Cardiopulmonary exercise testing was performed as previously described,22 and oxygen uptake (peak VO2) was considered as aerobic capacity. Peak VO2 and peak workload were also expressed as percentages of predicted.23 Desaturation was considered to be a fall of ≥4% in SpO2.24 Physical activity in daily life (steps/day) was assessed by a pedometer (Yamax Power Walker, model PW-610; Yamax Corp, Tokyo, Japan), which was worn on the right pocket on the anterior surface of the pants for 5 consecutive weekdays. It was recommended that participants wear the pedometer as soon as they got dressed in the morning and used throughout the day, removing it only to shower and sleep. The first and last day's recordings were discarded, and the average of 3 days was considered for analysis.25 The number of steps per day less than 5000 was considered as “sedentary,” 5000 to 7499 as “low active,” 7500 to 9999 as “somewhat active,” and ≥10,000 as “active.”26 The modified Medical Research Council (mMRC) scale was used for assessment of dyspnea.27 Statistical Analysis The normality of the data was analyzed by the Shapiro-Wilk test. All variables presented a parametric distribution, except mMRC scores and the number of steps per day that presented a nonparametric distribution. Parametric data are presented as mean (SD), and nonparametric data are presented as median (interquartile range). Participants and participants who were healthy were compared using an unpaired t test for parametric data and the Mann-Whitney test for nonparametric data. Differences between groups are reported as mean difference and 95% CI. Comparisons between categorical variables were made by the Pearson chi-square statistic. A stepwise multiple regression analysis was used to investigate the determinants to peripheral muscle strength (quadriceps femoris and biceps brachii) and activity in daily life (number of steps/day) only in the group with bronchiectasis. The independent variables preselected for quadriceps femoris strength were age, sex, BMI, mMRC scores, FVC (% of predicted), FEV1 (% of predicted), ISWT (m), and number of steps. Except ISWT and number of steps, the same variables described for quadriceps femoris strength were used for biceps brachii strength. For the number of steps, the independent variables were age, sex, BMI, mMRC scores, FVC (% of predicted), FEV1 (% of predicted), ISWT (m), and quadriceps femoris strength. These independent variables were considered because they are representative of demographic and anthropometric characteristics, pulmonary and peripheral muscle function, and functional capacity. Probabilities for F-to-enter and F-to-remove were set in 0.05 and 0.10, respectively. The multicollinearity diagnostic for the stepwise regression analysis was done through the analysis of variance inflation factor (VIF), and none of the independent variables presented multicollinearity. Data were analyzed using SPSS, version 22.0 (SPSS Inc, Chicago, Illinois) statistical software. As the sample size has not been calculated previously, the power of the sample was calculated a posteriori (G*Power software; Universität Dusseldorf, Dusseldorf, Germany). The effect size was calculated using the Cohen test. The probability of a type I error was set at 5% (P < .05). Role of the Funding Source This study was supported by the São Paulo Research Foundation (FAPESP) (ref. no. 2013/0,1863–2, 2014/0,1902–0). The funder played no role in the conduct of this study. Results Participants with bronchiectasis were well matched to controls for age and body mass index (Tab. 1). As expected, there was difference in baseline characteristics for pulmonary function and dyspnea. Table 1. Baseline Characteristics of Participants With Bronchiectasis and Controlsa Characteristic  Men  P  Women  P    Bronchiectasis  Controls    Bronchiectasis  Controls    No. of participants  54  19  NA  95  32  NA  Age, y  39 (14)  34 (12)  .15  50 (13)  44 (15)  .10  BMI, kg/m2  23 (5)  24 (4)  .07  26 (6)  25 (4)  .55  FFM index, kg/m2  17.5 (2.0)b  18.2 (1.6)c  .29  16.2 (1.6)d  16.0 (1.3)e  .56  FVC, L  2.9 (1.0)  4.8 (0.6)  < .001  2.1 (0.7)  3.2 (0.5)  < .001  FVC, % predicted  70 (23)  101 (9)  < .001  70 (22)  99 (100)  < .001  FEV1, L  1.7 (0.9)  4.0 (0.5)  < .001  1.4 (0.6)  2.7 (0.5)  < .001  FEV1, % predicted  49 (25)  100 (7)  < .001  58 (24)  101 (12)  < .001  FEV1/FVC  0.58 (0.2)  0.85 (0.1)  < .001  0.67 (0.1)  0.85 (0.1)  < .001  mMRC, points  1.7 (1.4)  0 (0)  < .001  2.0 (1.2)  0 (0)  < .001  Characteristic  Men  P  Women  P    Bronchiectasis  Controls    Bronchiectasis  Controls    No. of participants  54  19  NA  95  32  NA  Age, y  39 (14)  34 (12)  .15  50 (13)  44 (15)  .10  BMI, kg/m2  23 (5)  24 (4)  .07  26 (6)  25 (4)  .55  FFM index, kg/m2  17.5 (2.0)b  18.2 (1.6)c  .29  16.2 (1.6)d  16.0 (1.3)e  .56  FVC, L  2.9 (1.0)  4.8 (0.6)  < .001  2.1 (0.7)  3.2 (0.5)  < .001  FVC, % predicted  70 (23)  101 (9)  < .001  70 (22)  99 (100)  < .001  FEV1, L  1.7 (0.9)  4.0 (0.5)  < .001  1.4 (0.6)  2.7 (0.5)  < .001  FEV1, % predicted  49 (25)  100 (7)  < .001  58 (24)  101 (12)  < .001  FEV1/FVC  0.58 (0.2)  0.85 (0.1)  < .001  0.67 (0.1)  0.85 (0.1)  < .001  mMRC, points  1.7 (1.4)  0 (0)  < .001  2.0 (1.2)  0 (0)  < .001  aData are presented as mean (SD) unless otherwise indicated. BMI = body mass index, FEV1 = forced expiratory volume in 1 second, FFM = fat-free mass, FVC = forced vital capacity, mMRC = modified Medical Research Council scale, NA = not applicable. bn = 30. cn = 12. dn = 48. en = 18. View Large The etiology of bronchiectasis was varied: 81 participants had idiopathic bronchiectasis. Thirteen had bronchiectasis due to primary ciliary dyskinesia; 8, due to gastroesophageal reflux disease; 6, due to Kartagener syndrome; 6, due to sequelae of tuberculosis; 6, due to pulmonary infection; 4, due to Mounier-Khun syndrome; 3, due to systemic lupus erythematosus; 3, due to common variable immunodeficiency; 2, due to α1-Antitrypsin deficiency; and the remainder due to other etiologies (ulcerative colitis, IgA deficiency, IgG2 deficiency, Bloom syndrome, Scimitar syndrome, Marfan syndrome, allergic bronchopulmonary aspergillosis, and ingestion of lye). Medications used by participants were as follows: long-acting bronchodilators (n = 103), short-acting bronchodilators (n = 39), antibiotics (n = 74), gastric protection drugs (n = 58), anti-inflammatory drugs (n = 52), antihypertensive medications (n = 20), analgesics (n = 8), vitamins (n = 4), and antiplatelet drugs (n = 2). The remainder (n = 39) were using other medications. The FFM index was evaluated in 78 participants with bronchiectasis (baseline characteristics did not differ from those of participants without measure of FFM index) and 30 control participants due the availability of the equipment during the development of the study. Twenty-five out of 78 participants (32%) presented with muscle depletion, whereas, in the control group, the prevalence was 20% (chi square = 0.554; P = .457). The distribution of participants according to the mMRC scale 0, 1, 2, 3, and 4 was 26, 28, 56, 14, and 25 participants, respectively. For the control group, all participants presented mMRC scores equal to 0. Participants with bronchiectasis had a reduced peripheral muscle strength compared with healthy controls for both biceps brachii and quadriceps femoris (Tab. 2). Functional capacity, represented by the distance walked in the ISWT, was significantly lower in participants with bronchiectasis (Tab. 2). In most participants (n = 61), the limiting symptom in the ISWT was dyspnea followed by dyspnea/fatigue with same score (n = 48) and fatigue (n = 40). Table 2. Peripheral Muscle Strength, Exercise Capacity, and Daily Physical Activity in Participants With Bronchiectasis and Controlsa Parameter  Bronchiectasis  Controls  Mean Difference (95% CI)  P  Effect Size  No. of participants  149  51  NA  NA  NA  Peripheral muscle force, kg            Biceps brachii strength  11.6 (4.3)b  13.7 (4.1)  2.1 (0.71 to 3.4)  .003  0.5  Quadriceps femoris strength  20.8 (9.2)b  27.7 (10.9)  7.0 (3.8 to 10.1)  < .001  0.67  Functional capacity            ISWT, m  451 (153)  679 (205)  227 (174 to 281)  < .001  1.27  SpO2 at peak, %  90 (6)  95 (5)  4.9 (3.1 to 6.6)  < .001  0.91  No. (%) of participants with desaturation  72 (48.3)          Dyspnea at end test  4.1 (2.4)  2.0 (2.0)  −2.1 (−2.8 to −1.4)  < .001  0.96  Fatigue at end test  3.7 (2.3)  2.7 (2.3)  −0.97 (−1.72 to −0.23)  .01  0.43  Cardiopulmonary exercise test            Peak VO2, mL·kg−1·min−1  17.6 (6.2)c  24.0 (7.4)  6.4 (4.0 to 8.7)  < .001  0.94  Peak workload, W  77 (39)  130 (51)  52.5 (38.8 to 66.1)  < .001  1.18  RER  1.23 (0.1)  1.16 (0.1)  0.07 (0.02 to 0.11)  .004  0.70  VE/MVV, %  69 (20)c  48 (12)  −20.7 (−26.7 to−14.7)  < .001  1.31  SpO2 at peak, %  93 (4)  96 (2)  3.4 (2.2 to 4.6)  < .001  1.00  No. (%) of participants with desaturation  41 (27.5)          Dyspnea at end test  5.1 (2.5)  3.6 (2.4)  −1.5 (−2.3 to −0.68)  < .001  0.61  Fatigue at end test  6.3 (2.3)  5.2 (2.8)  −1.2 (−2.3 to −0.68)  .003  0.43  Physical activity in daily lifeb            Steps/day during week  9164 (5348)d  12,440 (5255)  3276 (1571 to 4981)  < .001  0.62  Parameter  Bronchiectasis  Controls  Mean Difference (95% CI)  P  Effect Size  No. of participants  149  51  NA  NA  NA  Peripheral muscle force, kg            Biceps brachii strength  11.6 (4.3)b  13.7 (4.1)  2.1 (0.71 to 3.4)  .003  0.5  Quadriceps femoris strength  20.8 (9.2)b  27.7 (10.9)  7.0 (3.8 to 10.1)  < .001  0.67  Functional capacity            ISWT, m  451 (153)  679 (205)  227 (174 to 281)  < .001  1.27  SpO2 at peak, %  90 (6)  95 (5)  4.9 (3.1 to 6.6)  < .001  0.91  No. (%) of participants with desaturation  72 (48.3)          Dyspnea at end test  4.1 (2.4)  2.0 (2.0)  −2.1 (−2.8 to −1.4)  < .001  0.96  Fatigue at end test  3.7 (2.3)  2.7 (2.3)  −0.97 (−1.72 to −0.23)  .01  0.43  Cardiopulmonary exercise test            Peak VO2, mL·kg−1·min−1  17.6 (6.2)c  24.0 (7.4)  6.4 (4.0 to 8.7)  < .001  0.94  Peak workload, W  77 (39)  130 (51)  52.5 (38.8 to 66.1)  < .001  1.18  RER  1.23 (0.1)  1.16 (0.1)  0.07 (0.02 to 0.11)  .004  0.70  VE/MVV, %  69 (20)c  48 (12)  −20.7 (−26.7 to−14.7)  < .001  1.31  SpO2 at peak, %  93 (4)  96 (2)  3.4 (2.2 to 4.6)  < .001  1.00  No. (%) of participants with desaturation  41 (27.5)          Dyspnea at end test  5.1 (2.5)  3.6 (2.4)  −1.5 (−2.3 to −0.68)  < .001  0.61  Fatigue at end test  6.3 (2.3)  5.2 (2.8)  −1.2 (−2.3 to −0.68)  .003  0.43  Physical activity in daily lifeb            Steps/day during week  9164 (5348)d  12,440 (5255)  3276 (1571 to 4981)  < .001  0.62  aData are presented as mean (SD) unless otherwise indicated. ISWT = incremental shuttle walk test, MVV = maximal voluntary ventilation, NA = not applicable, RER = respiratory exchange rate, SpO2 = oxyhemoglobin saturation, VE = ventilation, VO2 = oxygen uptake. bn = 136. cn = 121. dn = 148 (1 participant did not record this item. View Large Twenty-eight out of 149 participants performed cardiopulmonary exercise testing without pulmonary gas exchange measurement because they needed oxygen supplementation during the test. Exercise tolerance was significantly lower in participants with bronchiectasis in both absolute values (Tab. 2) and percentage of predicted (Tab. 3). Unlike the ISWT, most participants stopped the cardiopulmonary exercise testing with a predominant symptom of fatigue (n = 88), dyspnea (n = 29), or dyspnea and fatigue in the same proportion (n = 32). For all variables in Table 2, the power of the sample ranged from 81% to 100%. Table 3. Functional and Exercise Capacities, Expressed as Percentage of Predicted Values, in Participants With Bronchiectasis and Controlsa Parameter  Bronchiectasis  Controls  Mean Difference (95% CI)  P  Effect Size  No. of participants evaluated  149  51  NA  NA  NA  Functional capacity            ISWT, % predicted  55 (16)  74 (15)  19 (14−25)  < .001  1.23  Peak HR, % of predicted maximum HR  78 (10)  84 (12)  5.9 (1.7−2.5)  < .001  0.55  Cardiopulmonary exercise test            Peak VO2, % predicted  62 (15)b  81 (17)  18.7 (13.6−23.9)  < .001  1.19  Peak workload, % predicted  65 (24)  94 (20)  29.5 (22.2−36.9)  < .001  1.46  Peak HR, % of predicted maximum HR  84 (9)  92 (12)  8.9 (5.7−12.1)  < .001  0.76  Parameter  Bronchiectasis  Controls  Mean Difference (95% CI)  P  Effect Size  No. of participants evaluated  149  51  NA  NA  NA  Functional capacity            ISWT, % predicted  55 (16)  74 (15)  19 (14−25)  < .001  1.23  Peak HR, % of predicted maximum HR  78 (10)  84 (12)  5.9 (1.7−2.5)  < .001  0.55  Cardiopulmonary exercise test            Peak VO2, % predicted  62 (15)b  81 (17)  18.7 (13.6−23.9)  < .001  1.19  Peak workload, % predicted  65 (24)  94 (20)  29.5 (22.2−36.9)  < .001  1.46  Peak HR, % of predicted maximum HR  84 (9)  92 (12)  8.9 (5.7−12.1)  < .001  0.76  aData are presented as mean (SD) unless otherwise indicated. HR = heart rate, ISWT = incremental shuttle walk test, NA = not applicable, VO2 = oxygen uptake. bn = 121. View Large In relation to physical activity in daily life, 32 (22%) participants were considered as “sedentary,” 29 (20%) as “low active,” 36 (24%) as “somewhat active,” and 51 (34%) as “active,” whereas, in the control group, the distribution was 1 (2%), 6 (12%), 10 (20%), and 34 (67%) participants, respectively (chi square = 19.740, P < .001). Stepwise regression analysis (Tab. 4) showed that age, sex, BMI, mMRC scores, and distance walked on the ISWT independently influenced quadriceps femoris strength, explaining 44.9% of its variance (P < .001). For biceps brachii strength, the determinants were sex, BMI, and dyspnea (R2 = 0.447, P < .001). The determinants of number of daily steps were dyspnea and distance walked on ISWT, explaining only 27.7% of its variance. Table 4. Results of Multiple Regression Analysis (n = 149)a   Nonstandardized Coefficient (B)  Standardized Coefficient (β)  P  Adjusted R2  Quadriceps femoris strength        0.449  Constant  11.630  NA  .033    Age (y)  −0.172  −0.264  .001    Sex (women = 0/men = 1)  6.631  0.350  < .001    BMI (kg/m2)  0.48  0.290  < .001    mMRC (points)  −1.323  −0.182  .031    ISWT (m)  0.011  0.189  .047    Biceps brachii strength        0.447  Constant  6.443  NA  < .001    Sex (women = 0/men = 1)  5.254  0.596  < .001    BMI (kg/m2)  0.207  0.269  < .001    mMRC (points)  −1.040  −0.308  < .001    Steps/day        0.277  Constant  7791.81  NA  < .001    mMRC (points)  −1401.47  −0.325  .006    ISWT (m)  9.543  0.267  .006      Nonstandardized Coefficient (B)  Standardized Coefficient (β)  P  Adjusted R2  Quadriceps femoris strength        0.449  Constant  11.630  NA  .033    Age (y)  −0.172  −0.264  .001    Sex (women = 0/men = 1)  6.631  0.350  < .001    BMI (kg/m2)  0.48  0.290  < .001    mMRC (points)  −1.323  −0.182  .031    ISWT (m)  0.011  0.189  .047    Biceps brachii strength        0.447  Constant  6.443  NA  < .001    Sex (women = 0/men = 1)  5.254  0.596  < .001    BMI (kg/m2)  0.207  0.269  < .001    mMRC (points)  −1.040  −0.308  < .001    Steps/day        0.277  Constant  7791.81  NA  < .001    mMRC (points)  −1401.47  −0.325  .006    ISWT (m)  9.543  0.267  .006    aBMI = body mass index, ISWT = incremental shuttle walk test, mMRC = modified Medical Research Council scale, NA = not applicable. View Large Discussion Participants with bronchiectasis have lower biceps brachii and quadriceps femoris strength, reduced exercise tolerance, and a high prevalence of physical inactivity when compared with their peers who are healthy. To our knowledge, this is the first study to demonstrate that participants with bronchiectasis had significant reduction in muscle strength of the upper and lower limbs. A previous study examining peripheral muscle strength in bronchiectasis did not find reduction in quadriceps femoris strength.8 It is possible that the small sample size (n = 20) in the previous study8—comprising people who had less severity (FEV1 = 62.5 ± 20% of predicted, and mMRC score = 1.55 ± 0.60)—has resulted in an underestimation of the impairment of peripheral muscle strength in this population. Reduced quadriceps femoris force in our participants may be a consequence of chronic deconditioning, demonstrated by reduced aerobic capacity. We cannot rule out that skeletal muscle disuse28 could occur due to the systemic effects of bronchiectasis, since systemic inflammation,10 hypoxemia,5 oxidative stress,11 and muscle depletion10 have also been described in this population. The relationship among skeletal muscle dysfunction, exercise capacity, and inflammatory and oxidative markers has not yet been established in the literature and should be prospectively explored in people with bronchiectasis. In our study, the magnitude of the difference in quadriceps femoris force between participants and controls was larger than the magnitude of those observed for biceps brachii force (25% and 15%, respectively). It is interesting to note that in a study of participants with sarcoidosis,29 the difference in muscle strength for quadriceps femoris and handgrip in relation to participants who were healthy was quite similar to that observed in our study, considering absolute values of these outcomes (24% and 16%, respectively). The same has already been registered in participants with COPD whose quadriceps femoris strength was lower than pectoralis major30 and hand grip strength.31 This pattern—lower limb worse than upper limb—has been associated with a greater reduction in activity of the lower limbs.29 Reduced distance walked in the ISWT confirms a reduction in functional capacity in people with bronchiectasis. In the study by Ozalp et al,8 although participants walked a shorter distance than the control group in the 6-minute walk test, they showed no reduction in functional capacity, because this distance represented 91% of the predicted distance and also corresponded to 88% of the distance walked by the control group. In comparison with 2 previous studies32,33 that used ISWT and measured the dyspnea using the MRC scale, our participants are younger, display worse pulmonary function, and have higher scores on the mMRC scale. The combination of these characteristics could explain why our participants walked shorter distances. To our knowledge, this is the first time that cardiopulmonary exercise testing is described in a large number of participants with bronchiectasis who are representative of the spectrum of disease severity. This can be confirmed by the distribution of participants in different scores on the mMRC scale. Although our participants were younger than those in the study of Newall et al34 (44 years vs 61 years, respectively), with similar lung function (FEV1 = 52% and 59% of predicted, respectively), they displayed reduced aerobic capacity (peak VO2 = 62 ± 13 and 86% of predicted, respectively). Newall et al had their participants perform cardiopulmonary exercise testing on treadmill, which, per se, would determine a higher peak VO2 in relation to our study, in which a cycle ergometer was used. However, if the magnitude of the difference in peak VO2 between the Newall et al study and our study was exclusively due to type of ergometer, this difference would be 6% to 11%35 and not approximately 24% as observed. In another study,36 prior to a lung resection, 53 participants with bronchiectasis performed cardiopulmonary exercise testing on cycle ergometer, and they had a peak VO2 and peak workload higher than that observed in our participants (peak VO2 = 67.7 ± 17.1 vs 62 ± 16% of predicted, respectively; workload = 78.8 ± 23.8 vs 65 ± 24% of predicted, respectively). The large sample size in our study allowed us to include participants with a variety of functional impairments, which was more representative of a broad spectrum of the bronchiectasis population. In a previous study,5 we showed that physical activity in daily life (steps/day) was a predictor of the distance walked on ISWT. More recently, Bradley et al7 assessed physical activity in 55 participants (63 ± 10 years of age) with bronchiectasis (FVC = 94 ± 19% of predicted, and FEV1 = 76 ± 19% of predicted) using an accelerometer (ActiGraph, Pensacola, Florida). Compared with the Bradley et al study, our participants walked more in everyday life (6001 ± 2780 steps per day vs 9164 ± 5348 steps per day, respectively). In addition to differences in the instruments used for measuring physical activity in daily life between the Bradley et al study and ours, the characteristics of participants included in both studies differ substantially. Even though our participants performed higher number of steps per day in relation to participants in in that study, they walked 30% less in everyday life compared with controls; and about 41% of our participants were either “sedentary” or “low active,” which is similar to activity levels observed in adults with cystic fibrosis.37 This is the first study to investigate the determinants of peripheral muscle strength and physical activity in participants with bronchiectasis. Unlike the Bradley et al7 study, the distance walked on ISWT in our study was an independent predictor of physical activity. This finding confirms that not only the 6-Minute Walk Test but also the ISWT are representative of the level of activity required in everyday life. Bronchiectasis is a disease of a chronic and progressive nature, and people with this condition have to manage the progressive dyspnea that can induce sedentary behavior.7 This assertion proceeds once the dyspnea was a determinant of number of steps per day. Dyspnea was also a contributor to quadriceps femoris strength in the current study. Previous investigations have demonstrated a negative association between exercise capacity and the degree of dyspnea (based on mMRC scores),4,5,38 but this is the first time that dyspnea is also implicated with peripheral muscle strength in this population. Although stepwise regression models explained approximately half of the variation in peripheral muscle strength, we were able to explain only 27.7% of the variation in physical activity, illustrating the complex nature of physical activity in daily life where there may be physical, behavioral, and environmental contributors. Our data suggest that other variables as yet unmeasured—such as environmental, social, and personal factors—must be studied to understand the contributors to physical activity in bronchiectasis entirely. Limitations The current study naturally has some limitations. First, a reduced functional capacity, as evaluated using ISWT, might have been overestimated in our participants. In the study that determined the reference values for the Brazilian population,21 participants were permitted to run. The current study used the classical description of the ISWT, in which the test was interrupted when the patient, walking, did not complete a shuttle in time expected for 2 consecutive trials. Because of this methodological difference, even the controls showed a reduction of the distance walked on ISWT (74 ± 15%), and we have chosen to use the absolute values (m) of the ISWT in the multiple regression analysis. Second, this is a cross-sectional study, and we can only make statements about associations. A longitudinal study design would be more reliable to investigate whether the independent predictors established in the current study are the cause of reduced peripheral muscle strength and physical activity in daily life. Third, physical activity in daily life was assessed by the number of steps per day as measured by a pedometer, which might have underestimated the step count because the accelerometer is more accurate for this measure.39 However, the pedometer used in the current study has reproducible measurements and is a valid device for step counting during slow and fast walking.40 In addition, the pedometer does not record the wearing time by participants, which is a prerequisite for a valid physical activity measurement. It seems reasonable to assume, however, that the participants used the pedometer on average for 12 hours, as they were instructed to wear it from the time they woke up until bedtime. Finally, the use of BMI is not the best estimator for muscle mass. Our study may have important future clinical implications. We studied a younger bronchiectasis population that already had clinical and functional impairment, suggesting that early diagnosis may have a significant impact on improving the prognosis. Some of the determinants of the peripheral muscle strength and activity in daily life found in our study are modifiable, such as dyspnea, BMI, and distance walking on ISWT. Therefore, specific interventions to ameliorate exertional dyspnea and to improve nutritional status and aerobic capacity may have a positive impact on muscle function and physical activities of daily life. Again, this is a cross-sectional study, and any supposition about interventions and their impact on the outcomes surveyed in this study must be interpreted with caution. In this context, our results support the necessity for further studies with pharmacological and nonpharmacological interventions that can benefit this population. People with bronchiectasis have reduced peripheral muscle strength and functional capacity, and they are less active in daily life compared with healthy age-matched controls. Functional capacity is an important determinant of peripheral muscle strength and activity in daily life. Future studies should evaluate whether it is possible to ameliorate these effects with pulmonary rehabilitation or other targeted interventions. Author Contributions Concept/idea/research design: Anne E. Holland, Rejane A. S. de Castro, Fernanda de Cordoba Lanza, Rodrigo A. Athanazio, Samia Z. Rached, Regina Carvalho-Pinto, Alberto Cukier, Rafael Stelmach, Simone D. Corso Writing: Anderson A. de Camargo, Jacqueline C. Boldorini, Anne E. Holland, Rodrigo A. Athanazio, Simone D. Corso Data collection: Anderson A. de Camargo, Jacqueline C. Boldorini, Rejane A. S. de Castro, Samia Z. Rached Data analysis: Anderson A. de Camargo, Jacqueline C. Boldorini, Rejane A. S. de Castro, Rafael Stelmach, Simone D. Corso Project management: Anderson A. de Camargo, Jacqueline Boldorini, Samia Z. Rached, Rafael Stelmach, Simone D. Corso Fund procurement: Fernanda Lanza, Rafael Stelmach Providing participants: Rejane A. S. de Castro, Rodrigo A. Athanazio, Samia Z. Rached, Regina Carvalho-Pinto, Alberto Cukier Providing facilities/equipment: Alberto Cukier, Rafael Stelmach Providing institutional liaisons: Rodrigo A. Athanazio, Samia Rached, Alberto Cukier, Rafael Stelmach Consultation (including review of manuscript before submitting): Fernanda de Cordoba Lanza, Rodrigo A. Athanazio, Samia Z. Rached, Regina Carvalho-Pinto, Alberto Cukier, Rafael Stelmach, Simone D. Corso Ethics Approval The study was approved by the Human Research Ethics Committees from Universidade Nove de Julho (ref. no. 921/11) and University of São Paulo (ref. no. 451538), with written informed consent obtained from all participants. Funding This study was funded by the São Paulo Research Foundation (FAPESP) (ref. no. 2013/01863-2, 2014/01902-0). Disclosures All authors completed the ICJME Form for Disclosure of Potential Conflicts of Interest and reported no disclosures relevant to this work. References 1 Lambrecht BN, GeurtsvanKessel CH. Pulmonary defence mechanisms and inflammatory pathways in bronchiectasis. Eur Respir Mon . 2011; 52: 11– 21. 2 Drain M, Elborn JS. Assessment and investigation of adults with bronchiectasis. Eur Resp Mon . 2011; 52: 32– 43. 3 Cole PJ. Inflammation: a two-edged sword −the model of bronchiectasis. Eur J Respir Dis Suppl . 1986; 147: 6− 15. Google Scholar PubMed  4 Koulouris NG, Retsou S, Kosmas E et al.   Tidal expiratory flow limitation, dyspnoea and exercise capacity in patients with bilateral bronchiectasis. Eur Respir J . 2003; 21: 743– 748. Google Scholar CrossRef Search ADS PubMed  5 de Camargo AA, Amaral TS, Rached SZ et al.   Incremental shuttle walking test: a reproducible and valid test to evaluate exercise tolerance in adults with non-cystic fibrosis bronchiectasis. Arch Phys Med Rehabil . 2014; 95( 5): 892– 899. Google Scholar CrossRef Search ADS PubMed  6 Wilson CB, Jones PW, O’leary CJ et al.   Validation of the St. George's respiratory questionnaire in bronchiectasis. Am J Respir Crit Care Med . 1997; 156: 536– 541. Google Scholar CrossRef Search ADS PubMed  7 Bradley JM, Wilson JJ, Hayes K et al.   Sedentary behaviour and physical activity in bronchiectasis: a cross-sectional study. BMC Pulm Med . 2015; 15( 1): 61. Google Scholar CrossRef Search ADS PubMed  8 Ozalp O, Inal-Ince D, Calik E et al.   Extrapulmonary features of bronchiectasis: muscle function, exercise capacity, fatigue, and health status. Multidiscip Respir Med . 2012; 7( 3): 1– 6. Google Scholar PubMed  9 Gosselink R, Troosters T, Decramer M. Exercise testing: why, which and how to interpret. Breath . 2004; 1( 2): 121– 129. Google Scholar CrossRef Search ADS   10 Olveira G, Olveira C, Gaspar I et al.   Fat-free mass depletion and inflammation in patients with bronchiectasis. J Acad Nutr Diet . 2012; 112( 12): 1999– 2006. Google Scholar CrossRef Search ADS PubMed  11 Olveira G, Olveira C, Dorado A et al.   Cellular and plasma oxidative stress biomarkers are raised in adults with bronchiectasis. Clin Nutr . 2013; 32( 1): 112– 117. Google Scholar CrossRef Search ADS PubMed  12 Öcal S, Portakal O, Öcal A et al.   Factors associated with pulmonary hypertension and long-term survival in bronchiectasis participants. Respir Med . 2016; 119: 109– 114. Google Scholar CrossRef Search ADS PubMed  13 Gale NS, Bolton CE, Duckers JM et al.   Systemic comorbidities in bronchiectasis. Chron Respir Dis . 2012; 9( 4): 231– 238. Google Scholar CrossRef Search ADS PubMed  14 Furlanetto KC, Donária L, Schneider LP, Lopes JR, Ribeiro M, Fernandes KB, Hernandes NA, Pitta F. Sedentary behavior is an independent predictor of mortality in participants with COPD. Respir Care . 2017; 62( 5): 579– 587. Google Scholar CrossRef Search ADS PubMed  15 Burtin C, Ter Riet G, Puhan MA et al.   Handgrip weakness and mortality risk in COPD: a multicentre analysis. Thorax . 2016; 71( 1): 86– 87. Google Scholar CrossRef Search ADS PubMed  16 Pinto-Plata VM, Cote C, Cabral H et al.   The 6-minute walk distance: chance over time and value as a predictor survival in severe COPD. Eur Respir J . 2004; 23( 1): 28– 33. Google Scholar CrossRef Search ADS PubMed  17 Pellegrino R, Viegi G, Brusasco V et al.   Interpretative strategies for lung function tests. Eur Respir J . 2005; 26( 5): 948– 968. Google Scholar CrossRef Search ADS PubMed  18 Pereira CAC, Sato T, Rodrigues SC. New reference values for forced spirometry spirometry in white adults in Brazil. J Pneumol . 2007; 33( 4): 397– 406. 19 Vermeeren M, Creutzberg E, Schols A et al.   Prevalence of nutritional depletion in a large out-patient population of patients with COPD. Respir Med . 2006; 100: 1349– 1355. Google Scholar CrossRef Search ADS PubMed  20 Singh SJ, Morgan MD, Scott S et al.   Development of a shuttle walking test of disability in patients with chronic airways obstruction. Thorax . 1992; 47( 12): 1019– 1024. Google Scholar CrossRef Search ADS PubMed  21 Probst VS, Hernandes NA, Teixeira DC et al.   Reference values for the incremental shuttle walking test. Respir Med . 2012; 106: 243– 248. Google Scholar CrossRef Search ADS PubMed  21 Dal Corso S, de Camargo AA, Izbicki M et al.   A symptom-limited incremental step test determines maximum physiological responses in patients with chronic obstructive pulmonary disease. Resp Med . 2013; 107: 1993– 1999. Google Scholar CrossRef Search ADS   23 Neder JA, Nery LE, Castelo A et al.   Prediction of metabolic and cardiopulmonary responses to maximum cycle ergometry: a randomised study. Eur Respir J . 1999; 14( 6): 1304– 1313. Google Scholar CrossRef Search ADS PubMed  24 Hadeli KO, Siegel EM, Sherrill DL et al.   Predictors of oxygen desaturation during submaximal exercise in 8,000 patients. Chest . 2001; 120: 88– 92. Google Scholar CrossRef Search ADS PubMed  25 Demeyer H, Burtin C, Van Remoortel H et al.   Standardizing the analysis of physical activity in patients with COPD following a pulmonary rehabilitation program. Chest . 2014; 146( 2): 318– 327. Google Scholar CrossRef Search ADS PubMed  26 Tudor-Locke C, Bassett DR Jr. How many steps/day are enough? Preliminary pedometer indices for public health. Sports Med . 2004; 34: 1– 8. Google Scholar CrossRef Search ADS PubMed  27 Bestall JC, Paul EA, Garrod R et al.   Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax . 1999; 54: 581– 586. Google Scholar CrossRef Search ADS PubMed  28 Maltais F, Decramer M, Casaburi R et al.  ; ATS/ERS Ad Hoc Committee on Limb Muscle Dysfunction in COPD. An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med . 2014; 189( 9): e15– e62. Google Scholar CrossRef Search ADS PubMed  29 Spruit MA, Thomeer MJ, Gosselink R et al.   Skeletal muscle weakness in patients with sarcoidosis and its relationship with exercise intolerance and reduced health status. Thorax . 2005; 60( 1): 32– 38. Google Scholar CrossRef Search ADS PubMed  30 Bernard S, LeBlanc P, Whittom F et al.   Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med . 1998; 158( 2): 629– 634. Google Scholar CrossRef Search ADS PubMed  31 Gosselink R, Troosters T, Decramer M. Peripheral muscle weakness contributes to exercise limitation in COPD. Am. J. Respir.Crit. Care Med.  1996; 153: 976– 980. Google Scholar CrossRef Search ADS PubMed  32 Lee AL, Hill CJ, Cecins N et al.   The short and long-term effects of exercise training in non-cystic fibrosis bronchiectasis − a randomised controlled trial. Respir Res . 2014; 15: 44. Google Scholar CrossRef Search ADS PubMed  33 Lee AL, Hill CJ, Cecins N et al.   Minimal important difference in field walking tests in non-cystic fibrosis bronchiectasis following exercise training. Respir Med . 2014; 108( 9): 1303– 1309. Google Scholar CrossRef Search ADS PubMed  34 Newall C, Stockley RA, Hill SL. Exercise training and inspiratory muscle training in patientes with bronchiectasis. Thorax . 2005; 60: 943– 948. Google Scholar CrossRef Search ADS PubMed  35 Neder JA, Nery LE. Teste de Exercício Cardiopulmonar [Cardiopulmonary exercise 
testing]. J Pneumol . 2002; 28( supl 3): s166-s206. Article in Portuguese. 36 Vallilo CC, Terra RM, de Albuquerque AL et al.   Lung resection improves quality of life of patients with symptomatic bronchiectasis. Ann Thorac Surg . 2014; 98: 1034– 1041. Google Scholar CrossRef Search ADS PubMed  37 Troosters T, Langer D, Vrijsen B et al.   Skeletal muscle weakness, exercise tolerance and physical activity in adults with cystic fibrosis. Eur Respir J . 2009; 33( 1): 99– 106. Google Scholar CrossRef Search ADS PubMed  38 Guan WJ, Gao YH, Xu G et al.   Six-minute walk test in Chinese adults with clinically stable bronchiectasis: association with clinical indices and determinants. Curr Med Res Opin . 2015; 31( 4): 843– 852. Google Scholar CrossRef Search ADS PubMed  39 O`Neill B, McDonough SM, Wilson JJ et al.   Comparing accelerometer, pedometer and a questionnaire for measuring physical activity in bronchiectasis: a validity and feasibility study? Respir Res . 2017; 18: 1– 10. Google Scholar CrossRef Search ADS PubMed  40 Sant’Anna T, Escobar VC, Fontana AD et al.   Evaluation of a new motion sensor in patients with chronic obstructive pulmonary disease. Arch Phys Med Rehabil . 2012; 93( 12): 2319– 2325. Google Scholar CrossRef Search ADS PubMed  © 2017 American Physical Therapy Association http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Physical Therapy Oxford University Press

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Oxford University Press
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© 2017 American Physical Therapy Association
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0031-9023
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1538-6724
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10.1093/ptj/pzx123
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Abstract

Abstract Background Bronchiectasis is characterized by a progressive structural lung damage, recurrent infections and chronic inflammation which compromise the exertion tolerance, and may have an impact on skeletal muscle function and physical function. Objective The purpose of this study was to compare peripheral muscle strength, exercise capacity, and physical activity in daily life between participants with bronchiectasis and controls and to investigate the determinants of the peripheral muscle strength and physical activity in daily life in bronchiectasis. Design This study used a cross-sectional design. Methods The participants’ quadriceps femoris and biceps brachii muscle strength was measured. They performed the incremental shuttle walk test (ISWT) and cardiopulmonary exercise testing, and the number of steps/day was measured by a pedometer. Results Participants had reduced quadriceps femoris muscle strength (mean difference to control group = 7 kg, 95% CI = 3.8–10.1 kg), biceps brachii muscle strength (2.1 kg, 95% CI = 0.7–3.4 kg), ISWT (227 m, 95% CI = 174–281 m), peak VO2 (6.4 ml/Kg/min, 95% CI = 4.0–8.7 ml/Kg/min), and number of steps/day (3,332 steps/day, 95% CI = 1,758–4,890 steps/day). A lower quadriceps femoris strength is independently associated to an older age, female sex, lower body mass index (BMI), higher score on the modified Medical Research Council scale, and shorter distance on the ISWT (R2 = 0.449). Biceps brachii strength is independently associated with sex, BMI, and dyspnea (R2 = 0.447). The determinants of number of daily steps were dyspnea and distance walked in ISWT, explaining only 27.7% of its variance. Limitations Number of steps per day was evaluated by a pedometer. Conclusions People with bronchiectasis have reduced peripheral muscle strength, and reduced aerobic and functional capacities, and they also are less active in daily life. Modifiable variables such as BMI, dyspnea, and distance walked on the ISWT are associated with peripheral muscle strength and physical activity in daily life. Bronchiectasis is a chronic disease characterized by a permanent and abnormal anatomic distortion of the bronchi (thickening, herniation, or dilation) accompanied by inflammatory response in the lumen that contributes to recurrent lung infections.1 Pulmonary manifestations have been very well described in these individuals: persistent cough, daily sputum production, persistent infection, and impaired pulmonary function.2 However, it is reasonable to infer that extrapulmonary manifestations may occur in bronchiectasis because of its progressive nature, as explained by the persistence of infection, inflammation, and lung damage.3 Reduced exercise capacity,4,5 impaired health-related quality of life,6 and physical inactivity7 have already been described in people with bronchiectasis, but studies addressing these issues are scarce. One small study suggested that bronchiectasis may affect exercise capacity and quality of life, but it was not able to demonstrate a reduction in peripheral muscle strength.8 However, some aspects of that study are liable to criticism. Although the study participants had a reduced exercise capacity compared with controls, they reached approximately 90% of the predicted values on the 6-Minute Walk Test, which cannot be considered to be reduced functional capacity.9 Moreover, health status was assessed using the Leicester Cough Questionnaire, but cough is not the only symptom in people with bronchiectasis that may affect health-related quality of life. Therefore, the small sample size (n = 20) might have resulted in the underestimation of extrapulmonary manifestations of bronchiectasis and is unlikely to reflect the disease spectrum seen in bronchiectasis.8 The systemic consequences of other chronic respiratory disease, such as chronic obstructive pulmonary disease (COPD), are becoming better understood. Some abnormalities observed in COPD are shared by people with bronchiectasis, such as increased markers of systemic inflammation10 and oxidative stress,11 hypoxemia,12 increased arterial stiffness,13 and malnutrition.10 However, the possible systemic consequences of bronchiectasis have not been investigated in this population, especially in terms of exercise capacity, muscle force, and physical activity, which predict the prognosis in other chronic pulmonary diseases such as COPD.14–16 Based on the progressive pulmonary impairment associated with multiple exacerbations, systemic inflammation, and elevated oxidative stress, we hypothesized that people with bronchiectasis have impairment of skeletal muscle function and physical function. In addition, the predictors of peripheral muscle strength and physical activity in daily life have not been previously investigated in bronchiectasis and may contribute to indicate specific interventions for rehabilitation to improve the physical and functional performance. The primary aim of this study was to compare peripheral muscle strength, exercise capacity, and physical activity in daily life between participants with bronchiectasis and their peers who are healthy. The secondary aim was to investigate the determinants of the peripheral muscle strength and physical activity in daily life in people with bronchiectasis. Methods Study Design and Subjects This study uses a cross-sectional design, with a period of recruitment and assessments from March 2012 to December 2014. For the study, 168 adults diagnosed with bronchiectasis as confirmed using high-resolution computed tomography were consecutively recruited from the outpatient clinic of a tertiary university hospital. Participants with heart disease, COPD, or cystic fibrosis were excluded. Nineteen participants with bronchiectasis were excluded (Figure), rsulting in a sample size of 149 participants (95 women). An age- and sex-matched control group of participants (n = 51, 32 women) was recruited subsequently from the local community, being in the same season as the participants with bronchiectasis. The study was approved by the Human Research Ethics Committees from Universidade Nove de Julho (committee reference no. 921/11) and University of São Paulo (committee reference no. 451538), with written informed consent obtained from all participants. Figure. View largeDownload slide Flowchart protocol. Figure. View largeDownload slide Flowchart protocol. Assessments Spirometric tests were performed by using the CPX Ultima (MedGraphics Corporation, St Paul, Minnesota, USA). Technical procedures were those recommended by the American Thoracic Society and European Respiratory Society.17 Forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) are expressed as percentage of the normal values for the Brazilian population.18 A body composition analyzer (Tanita BC 554; Tanita Corporation of America, Arlington Heights, Illinois) was used to obtain the fat-free mass (FFM), and the FFM index was calculated. Nutritional depletion was considered when the FFM index was ≤15 kg/m2 for women and ≤16 kg/m2 for men.19 Peripheral muscle strength was measured by maximum voluntary isometric contraction (MVIC) of the biceps brachii and quadriceps femoris muscles. A load cell (EMG800C; EMG System, São José dos Campos, Brazil) was interfaced to a computer to record the MVIC. For both muscles, participants performed 3 MVIC repetitions, maintaining each one for 5 seconds, with a minute's rest between repetitions. The highest value from the 3 reproducible contractions (<5% variability among attempts) was considered for analysis. The quadriceps femoris measurement was made with the knee joint angle fixed at 90 degrees of flexion and hip joint angle set at 90 degrees of flexion; for the biceps brachii, the arm was positioned along the body, and the elbow joint angle was fixed at 90 degrees of flexion. Two incremental shuttle walking tests (ISWT) (30 minutes apart) were carried out according to previous description.20 to assess functional capacity. The greatest distance, in meters, was considered for analysis, and was also expressed as percentage of predicted.21 Cardiopulmonary exercise testing was performed as previously described,22 and oxygen uptake (peak VO2) was considered as aerobic capacity. Peak VO2 and peak workload were also expressed as percentages of predicted.23 Desaturation was considered to be a fall of ≥4% in SpO2.24 Physical activity in daily life (steps/day) was assessed by a pedometer (Yamax Power Walker, model PW-610; Yamax Corp, Tokyo, Japan), which was worn on the right pocket on the anterior surface of the pants for 5 consecutive weekdays. It was recommended that participants wear the pedometer as soon as they got dressed in the morning and used throughout the day, removing it only to shower and sleep. The first and last day's recordings were discarded, and the average of 3 days was considered for analysis.25 The number of steps per day less than 5000 was considered as “sedentary,” 5000 to 7499 as “low active,” 7500 to 9999 as “somewhat active,” and ≥10,000 as “active.”26 The modified Medical Research Council (mMRC) scale was used for assessment of dyspnea.27 Statistical Analysis The normality of the data was analyzed by the Shapiro-Wilk test. All variables presented a parametric distribution, except mMRC scores and the number of steps per day that presented a nonparametric distribution. Parametric data are presented as mean (SD), and nonparametric data are presented as median (interquartile range). Participants and participants who were healthy were compared using an unpaired t test for parametric data and the Mann-Whitney test for nonparametric data. Differences between groups are reported as mean difference and 95% CI. Comparisons between categorical variables were made by the Pearson chi-square statistic. A stepwise multiple regression analysis was used to investigate the determinants to peripheral muscle strength (quadriceps femoris and biceps brachii) and activity in daily life (number of steps/day) only in the group with bronchiectasis. The independent variables preselected for quadriceps femoris strength were age, sex, BMI, mMRC scores, FVC (% of predicted), FEV1 (% of predicted), ISWT (m), and number of steps. Except ISWT and number of steps, the same variables described for quadriceps femoris strength were used for biceps brachii strength. For the number of steps, the independent variables were age, sex, BMI, mMRC scores, FVC (% of predicted), FEV1 (% of predicted), ISWT (m), and quadriceps femoris strength. These independent variables were considered because they are representative of demographic and anthropometric characteristics, pulmonary and peripheral muscle function, and functional capacity. Probabilities for F-to-enter and F-to-remove were set in 0.05 and 0.10, respectively. The multicollinearity diagnostic for the stepwise regression analysis was done through the analysis of variance inflation factor (VIF), and none of the independent variables presented multicollinearity. Data were analyzed using SPSS, version 22.0 (SPSS Inc, Chicago, Illinois) statistical software. As the sample size has not been calculated previously, the power of the sample was calculated a posteriori (G*Power software; Universität Dusseldorf, Dusseldorf, Germany). The effect size was calculated using the Cohen test. The probability of a type I error was set at 5% (P < .05). Role of the Funding Source This study was supported by the São Paulo Research Foundation (FAPESP) (ref. no. 2013/0,1863–2, 2014/0,1902–0). The funder played no role in the conduct of this study. Results Participants with bronchiectasis were well matched to controls for age and body mass index (Tab. 1). As expected, there was difference in baseline characteristics for pulmonary function and dyspnea. Table 1. Baseline Characteristics of Participants With Bronchiectasis and Controlsa Characteristic  Men  P  Women  P    Bronchiectasis  Controls    Bronchiectasis  Controls    No. of participants  54  19  NA  95  32  NA  Age, y  39 (14)  34 (12)  .15  50 (13)  44 (15)  .10  BMI, kg/m2  23 (5)  24 (4)  .07  26 (6)  25 (4)  .55  FFM index, kg/m2  17.5 (2.0)b  18.2 (1.6)c  .29  16.2 (1.6)d  16.0 (1.3)e  .56  FVC, L  2.9 (1.0)  4.8 (0.6)  < .001  2.1 (0.7)  3.2 (0.5)  < .001  FVC, % predicted  70 (23)  101 (9)  < .001  70 (22)  99 (100)  < .001  FEV1, L  1.7 (0.9)  4.0 (0.5)  < .001  1.4 (0.6)  2.7 (0.5)  < .001  FEV1, % predicted  49 (25)  100 (7)  < .001  58 (24)  101 (12)  < .001  FEV1/FVC  0.58 (0.2)  0.85 (0.1)  < .001  0.67 (0.1)  0.85 (0.1)  < .001  mMRC, points  1.7 (1.4)  0 (0)  < .001  2.0 (1.2)  0 (0)  < .001  Characteristic  Men  P  Women  P    Bronchiectasis  Controls    Bronchiectasis  Controls    No. of participants  54  19  NA  95  32  NA  Age, y  39 (14)  34 (12)  .15  50 (13)  44 (15)  .10  BMI, kg/m2  23 (5)  24 (4)  .07  26 (6)  25 (4)  .55  FFM index, kg/m2  17.5 (2.0)b  18.2 (1.6)c  .29  16.2 (1.6)d  16.0 (1.3)e  .56  FVC, L  2.9 (1.0)  4.8 (0.6)  < .001  2.1 (0.7)  3.2 (0.5)  < .001  FVC, % predicted  70 (23)  101 (9)  < .001  70 (22)  99 (100)  < .001  FEV1, L  1.7 (0.9)  4.0 (0.5)  < .001  1.4 (0.6)  2.7 (0.5)  < .001  FEV1, % predicted  49 (25)  100 (7)  < .001  58 (24)  101 (12)  < .001  FEV1/FVC  0.58 (0.2)  0.85 (0.1)  < .001  0.67 (0.1)  0.85 (0.1)  < .001  mMRC, points  1.7 (1.4)  0 (0)  < .001  2.0 (1.2)  0 (0)  < .001  aData are presented as mean (SD) unless otherwise indicated. BMI = body mass index, FEV1 = forced expiratory volume in 1 second, FFM = fat-free mass, FVC = forced vital capacity, mMRC = modified Medical Research Council scale, NA = not applicable. bn = 30. cn = 12. dn = 48. en = 18. View Large The etiology of bronchiectasis was varied: 81 participants had idiopathic bronchiectasis. Thirteen had bronchiectasis due to primary ciliary dyskinesia; 8, due to gastroesophageal reflux disease; 6, due to Kartagener syndrome; 6, due to sequelae of tuberculosis; 6, due to pulmonary infection; 4, due to Mounier-Khun syndrome; 3, due to systemic lupus erythematosus; 3, due to common variable immunodeficiency; 2, due to α1-Antitrypsin deficiency; and the remainder due to other etiologies (ulcerative colitis, IgA deficiency, IgG2 deficiency, Bloom syndrome, Scimitar syndrome, Marfan syndrome, allergic bronchopulmonary aspergillosis, and ingestion of lye). Medications used by participants were as follows: long-acting bronchodilators (n = 103), short-acting bronchodilators (n = 39), antibiotics (n = 74), gastric protection drugs (n = 58), anti-inflammatory drugs (n = 52), antihypertensive medications (n = 20), analgesics (n = 8), vitamins (n = 4), and antiplatelet drugs (n = 2). The remainder (n = 39) were using other medications. The FFM index was evaluated in 78 participants with bronchiectasis (baseline characteristics did not differ from those of participants without measure of FFM index) and 30 control participants due the availability of the equipment during the development of the study. Twenty-five out of 78 participants (32%) presented with muscle depletion, whereas, in the control group, the prevalence was 20% (chi square = 0.554; P = .457). The distribution of participants according to the mMRC scale 0, 1, 2, 3, and 4 was 26, 28, 56, 14, and 25 participants, respectively. For the control group, all participants presented mMRC scores equal to 0. Participants with bronchiectasis had a reduced peripheral muscle strength compared with healthy controls for both biceps brachii and quadriceps femoris (Tab. 2). Functional capacity, represented by the distance walked in the ISWT, was significantly lower in participants with bronchiectasis (Tab. 2). In most participants (n = 61), the limiting symptom in the ISWT was dyspnea followed by dyspnea/fatigue with same score (n = 48) and fatigue (n = 40). Table 2. Peripheral Muscle Strength, Exercise Capacity, and Daily Physical Activity in Participants With Bronchiectasis and Controlsa Parameter  Bronchiectasis  Controls  Mean Difference (95% CI)  P  Effect Size  No. of participants  149  51  NA  NA  NA  Peripheral muscle force, kg            Biceps brachii strength  11.6 (4.3)b  13.7 (4.1)  2.1 (0.71 to 3.4)  .003  0.5  Quadriceps femoris strength  20.8 (9.2)b  27.7 (10.9)  7.0 (3.8 to 10.1)  < .001  0.67  Functional capacity            ISWT, m  451 (153)  679 (205)  227 (174 to 281)  < .001  1.27  SpO2 at peak, %  90 (6)  95 (5)  4.9 (3.1 to 6.6)  < .001  0.91  No. (%) of participants with desaturation  72 (48.3)          Dyspnea at end test  4.1 (2.4)  2.0 (2.0)  −2.1 (−2.8 to −1.4)  < .001  0.96  Fatigue at end test  3.7 (2.3)  2.7 (2.3)  −0.97 (−1.72 to −0.23)  .01  0.43  Cardiopulmonary exercise test            Peak VO2, mL·kg−1·min−1  17.6 (6.2)c  24.0 (7.4)  6.4 (4.0 to 8.7)  < .001  0.94  Peak workload, W  77 (39)  130 (51)  52.5 (38.8 to 66.1)  < .001  1.18  RER  1.23 (0.1)  1.16 (0.1)  0.07 (0.02 to 0.11)  .004  0.70  VE/MVV, %  69 (20)c  48 (12)  −20.7 (−26.7 to−14.7)  < .001  1.31  SpO2 at peak, %  93 (4)  96 (2)  3.4 (2.2 to 4.6)  < .001  1.00  No. (%) of participants with desaturation  41 (27.5)          Dyspnea at end test  5.1 (2.5)  3.6 (2.4)  −1.5 (−2.3 to −0.68)  < .001  0.61  Fatigue at end test  6.3 (2.3)  5.2 (2.8)  −1.2 (−2.3 to −0.68)  .003  0.43  Physical activity in daily lifeb            Steps/day during week  9164 (5348)d  12,440 (5255)  3276 (1571 to 4981)  < .001  0.62  Parameter  Bronchiectasis  Controls  Mean Difference (95% CI)  P  Effect Size  No. of participants  149  51  NA  NA  NA  Peripheral muscle force, kg            Biceps brachii strength  11.6 (4.3)b  13.7 (4.1)  2.1 (0.71 to 3.4)  .003  0.5  Quadriceps femoris strength  20.8 (9.2)b  27.7 (10.9)  7.0 (3.8 to 10.1)  < .001  0.67  Functional capacity            ISWT, m  451 (153)  679 (205)  227 (174 to 281)  < .001  1.27  SpO2 at peak, %  90 (6)  95 (5)  4.9 (3.1 to 6.6)  < .001  0.91  No. (%) of participants with desaturation  72 (48.3)          Dyspnea at end test  4.1 (2.4)  2.0 (2.0)  −2.1 (−2.8 to −1.4)  < .001  0.96  Fatigue at end test  3.7 (2.3)  2.7 (2.3)  −0.97 (−1.72 to −0.23)  .01  0.43  Cardiopulmonary exercise test            Peak VO2, mL·kg−1·min−1  17.6 (6.2)c  24.0 (7.4)  6.4 (4.0 to 8.7)  < .001  0.94  Peak workload, W  77 (39)  130 (51)  52.5 (38.8 to 66.1)  < .001  1.18  RER  1.23 (0.1)  1.16 (0.1)  0.07 (0.02 to 0.11)  .004  0.70  VE/MVV, %  69 (20)c  48 (12)  −20.7 (−26.7 to−14.7)  < .001  1.31  SpO2 at peak, %  93 (4)  96 (2)  3.4 (2.2 to 4.6)  < .001  1.00  No. (%) of participants with desaturation  41 (27.5)          Dyspnea at end test  5.1 (2.5)  3.6 (2.4)  −1.5 (−2.3 to −0.68)  < .001  0.61  Fatigue at end test  6.3 (2.3)  5.2 (2.8)  −1.2 (−2.3 to −0.68)  .003  0.43  Physical activity in daily lifeb            Steps/day during week  9164 (5348)d  12,440 (5255)  3276 (1571 to 4981)  < .001  0.62  aData are presented as mean (SD) unless otherwise indicated. ISWT = incremental shuttle walk test, MVV = maximal voluntary ventilation, NA = not applicable, RER = respiratory exchange rate, SpO2 = oxyhemoglobin saturation, VE = ventilation, VO2 = oxygen uptake. bn = 136. cn = 121. dn = 148 (1 participant did not record this item. View Large Twenty-eight out of 149 participants performed cardiopulmonary exercise testing without pulmonary gas exchange measurement because they needed oxygen supplementation during the test. Exercise tolerance was significantly lower in participants with bronchiectasis in both absolute values (Tab. 2) and percentage of predicted (Tab. 3). Unlike the ISWT, most participants stopped the cardiopulmonary exercise testing with a predominant symptom of fatigue (n = 88), dyspnea (n = 29), or dyspnea and fatigue in the same proportion (n = 32). For all variables in Table 2, the power of the sample ranged from 81% to 100%. Table 3. Functional and Exercise Capacities, Expressed as Percentage of Predicted Values, in Participants With Bronchiectasis and Controlsa Parameter  Bronchiectasis  Controls  Mean Difference (95% CI)  P  Effect Size  No. of participants evaluated  149  51  NA  NA  NA  Functional capacity            ISWT, % predicted  55 (16)  74 (15)  19 (14−25)  < .001  1.23  Peak HR, % of predicted maximum HR  78 (10)  84 (12)  5.9 (1.7−2.5)  < .001  0.55  Cardiopulmonary exercise test            Peak VO2, % predicted  62 (15)b  81 (17)  18.7 (13.6−23.9)  < .001  1.19  Peak workload, % predicted  65 (24)  94 (20)  29.5 (22.2−36.9)  < .001  1.46  Peak HR, % of predicted maximum HR  84 (9)  92 (12)  8.9 (5.7−12.1)  < .001  0.76  Parameter  Bronchiectasis  Controls  Mean Difference (95% CI)  P  Effect Size  No. of participants evaluated  149  51  NA  NA  NA  Functional capacity            ISWT, % predicted  55 (16)  74 (15)  19 (14−25)  < .001  1.23  Peak HR, % of predicted maximum HR  78 (10)  84 (12)  5.9 (1.7−2.5)  < .001  0.55  Cardiopulmonary exercise test            Peak VO2, % predicted  62 (15)b  81 (17)  18.7 (13.6−23.9)  < .001  1.19  Peak workload, % predicted  65 (24)  94 (20)  29.5 (22.2−36.9)  < .001  1.46  Peak HR, % of predicted maximum HR  84 (9)  92 (12)  8.9 (5.7−12.1)  < .001  0.76  aData are presented as mean (SD) unless otherwise indicated. HR = heart rate, ISWT = incremental shuttle walk test, NA = not applicable, VO2 = oxygen uptake. bn = 121. View Large In relation to physical activity in daily life, 32 (22%) participants were considered as “sedentary,” 29 (20%) as “low active,” 36 (24%) as “somewhat active,” and 51 (34%) as “active,” whereas, in the control group, the distribution was 1 (2%), 6 (12%), 10 (20%), and 34 (67%) participants, respectively (chi square = 19.740, P < .001). Stepwise regression analysis (Tab. 4) showed that age, sex, BMI, mMRC scores, and distance walked on the ISWT independently influenced quadriceps femoris strength, explaining 44.9% of its variance (P < .001). For biceps brachii strength, the determinants were sex, BMI, and dyspnea (R2 = 0.447, P < .001). The determinants of number of daily steps were dyspnea and distance walked on ISWT, explaining only 27.7% of its variance. Table 4. Results of Multiple Regression Analysis (n = 149)a   Nonstandardized Coefficient (B)  Standardized Coefficient (β)  P  Adjusted R2  Quadriceps femoris strength        0.449  Constant  11.630  NA  .033    Age (y)  −0.172  −0.264  .001    Sex (women = 0/men = 1)  6.631  0.350  < .001    BMI (kg/m2)  0.48  0.290  < .001    mMRC (points)  −1.323  −0.182  .031    ISWT (m)  0.011  0.189  .047    Biceps brachii strength        0.447  Constant  6.443  NA  < .001    Sex (women = 0/men = 1)  5.254  0.596  < .001    BMI (kg/m2)  0.207  0.269  < .001    mMRC (points)  −1.040  −0.308  < .001    Steps/day        0.277  Constant  7791.81  NA  < .001    mMRC (points)  −1401.47  −0.325  .006    ISWT (m)  9.543  0.267  .006      Nonstandardized Coefficient (B)  Standardized Coefficient (β)  P  Adjusted R2  Quadriceps femoris strength        0.449  Constant  11.630  NA  .033    Age (y)  −0.172  −0.264  .001    Sex (women = 0/men = 1)  6.631  0.350  < .001    BMI (kg/m2)  0.48  0.290  < .001    mMRC (points)  −1.323  −0.182  .031    ISWT (m)  0.011  0.189  .047    Biceps brachii strength        0.447  Constant  6.443  NA  < .001    Sex (women = 0/men = 1)  5.254  0.596  < .001    BMI (kg/m2)  0.207  0.269  < .001    mMRC (points)  −1.040  −0.308  < .001    Steps/day        0.277  Constant  7791.81  NA  < .001    mMRC (points)  −1401.47  −0.325  .006    ISWT (m)  9.543  0.267  .006    aBMI = body mass index, ISWT = incremental shuttle walk test, mMRC = modified Medical Research Council scale, NA = not applicable. View Large Discussion Participants with bronchiectasis have lower biceps brachii and quadriceps femoris strength, reduced exercise tolerance, and a high prevalence of physical inactivity when compared with their peers who are healthy. To our knowledge, this is the first study to demonstrate that participants with bronchiectasis had significant reduction in muscle strength of the upper and lower limbs. A previous study examining peripheral muscle strength in bronchiectasis did not find reduction in quadriceps femoris strength.8 It is possible that the small sample size (n = 20) in the previous study8—comprising people who had less severity (FEV1 = 62.5 ± 20% of predicted, and mMRC score = 1.55 ± 0.60)—has resulted in an underestimation of the impairment of peripheral muscle strength in this population. Reduced quadriceps femoris force in our participants may be a consequence of chronic deconditioning, demonstrated by reduced aerobic capacity. We cannot rule out that skeletal muscle disuse28 could occur due to the systemic effects of bronchiectasis, since systemic inflammation,10 hypoxemia,5 oxidative stress,11 and muscle depletion10 have also been described in this population. The relationship among skeletal muscle dysfunction, exercise capacity, and inflammatory and oxidative markers has not yet been established in the literature and should be prospectively explored in people with bronchiectasis. In our study, the magnitude of the difference in quadriceps femoris force between participants and controls was larger than the magnitude of those observed for biceps brachii force (25% and 15%, respectively). It is interesting to note that in a study of participants with sarcoidosis,29 the difference in muscle strength for quadriceps femoris and handgrip in relation to participants who were healthy was quite similar to that observed in our study, considering absolute values of these outcomes (24% and 16%, respectively). The same has already been registered in participants with COPD whose quadriceps femoris strength was lower than pectoralis major30 and hand grip strength.31 This pattern—lower limb worse than upper limb—has been associated with a greater reduction in activity of the lower limbs.29 Reduced distance walked in the ISWT confirms a reduction in functional capacity in people with bronchiectasis. In the study by Ozalp et al,8 although participants walked a shorter distance than the control group in the 6-minute walk test, they showed no reduction in functional capacity, because this distance represented 91% of the predicted distance and also corresponded to 88% of the distance walked by the control group. In comparison with 2 previous studies32,33 that used ISWT and measured the dyspnea using the MRC scale, our participants are younger, display worse pulmonary function, and have higher scores on the mMRC scale. The combination of these characteristics could explain why our participants walked shorter distances. To our knowledge, this is the first time that cardiopulmonary exercise testing is described in a large number of participants with bronchiectasis who are representative of the spectrum of disease severity. This can be confirmed by the distribution of participants in different scores on the mMRC scale. Although our participants were younger than those in the study of Newall et al34 (44 years vs 61 years, respectively), with similar lung function (FEV1 = 52% and 59% of predicted, respectively), they displayed reduced aerobic capacity (peak VO2 = 62 ± 13 and 86% of predicted, respectively). Newall et al had their participants perform cardiopulmonary exercise testing on treadmill, which, per se, would determine a higher peak VO2 in relation to our study, in which a cycle ergometer was used. However, if the magnitude of the difference in peak VO2 between the Newall et al study and our study was exclusively due to type of ergometer, this difference would be 6% to 11%35 and not approximately 24% as observed. In another study,36 prior to a lung resection, 53 participants with bronchiectasis performed cardiopulmonary exercise testing on cycle ergometer, and they had a peak VO2 and peak workload higher than that observed in our participants (peak VO2 = 67.7 ± 17.1 vs 62 ± 16% of predicted, respectively; workload = 78.8 ± 23.8 vs 65 ± 24% of predicted, respectively). The large sample size in our study allowed us to include participants with a variety of functional impairments, which was more representative of a broad spectrum of the bronchiectasis population. In a previous study,5 we showed that physical activity in daily life (steps/day) was a predictor of the distance walked on ISWT. More recently, Bradley et al7 assessed physical activity in 55 participants (63 ± 10 years of age) with bronchiectasis (FVC = 94 ± 19% of predicted, and FEV1 = 76 ± 19% of predicted) using an accelerometer (ActiGraph, Pensacola, Florida). Compared with the Bradley et al study, our participants walked more in everyday life (6001 ± 2780 steps per day vs 9164 ± 5348 steps per day, respectively). In addition to differences in the instruments used for measuring physical activity in daily life between the Bradley et al study and ours, the characteristics of participants included in both studies differ substantially. Even though our participants performed higher number of steps per day in relation to participants in in that study, they walked 30% less in everyday life compared with controls; and about 41% of our participants were either “sedentary” or “low active,” which is similar to activity levels observed in adults with cystic fibrosis.37 This is the first study to investigate the determinants of peripheral muscle strength and physical activity in participants with bronchiectasis. Unlike the Bradley et al7 study, the distance walked on ISWT in our study was an independent predictor of physical activity. This finding confirms that not only the 6-Minute Walk Test but also the ISWT are representative of the level of activity required in everyday life. Bronchiectasis is a disease of a chronic and progressive nature, and people with this condition have to manage the progressive dyspnea that can induce sedentary behavior.7 This assertion proceeds once the dyspnea was a determinant of number of steps per day. Dyspnea was also a contributor to quadriceps femoris strength in the current study. Previous investigations have demonstrated a negative association between exercise capacity and the degree of dyspnea (based on mMRC scores),4,5,38 but this is the first time that dyspnea is also implicated with peripheral muscle strength in this population. Although stepwise regression models explained approximately half of the variation in peripheral muscle strength, we were able to explain only 27.7% of the variation in physical activity, illustrating the complex nature of physical activity in daily life where there may be physical, behavioral, and environmental contributors. Our data suggest that other variables as yet unmeasured—such as environmental, social, and personal factors—must be studied to understand the contributors to physical activity in bronchiectasis entirely. Limitations The current study naturally has some limitations. First, a reduced functional capacity, as evaluated using ISWT, might have been overestimated in our participants. In the study that determined the reference values for the Brazilian population,21 participants were permitted to run. The current study used the classical description of the ISWT, in which the test was interrupted when the patient, walking, did not complete a shuttle in time expected for 2 consecutive trials. Because of this methodological difference, even the controls showed a reduction of the distance walked on ISWT (74 ± 15%), and we have chosen to use the absolute values (m) of the ISWT in the multiple regression analysis. Second, this is a cross-sectional study, and we can only make statements about associations. A longitudinal study design would be more reliable to investigate whether the independent predictors established in the current study are the cause of reduced peripheral muscle strength and physical activity in daily life. Third, physical activity in daily life was assessed by the number of steps per day as measured by a pedometer, which might have underestimated the step count because the accelerometer is more accurate for this measure.39 However, the pedometer used in the current study has reproducible measurements and is a valid device for step counting during slow and fast walking.40 In addition, the pedometer does not record the wearing time by participants, which is a prerequisite for a valid physical activity measurement. It seems reasonable to assume, however, that the participants used the pedometer on average for 12 hours, as they were instructed to wear it from the time they woke up until bedtime. Finally, the use of BMI is not the best estimator for muscle mass. Our study may have important future clinical implications. We studied a younger bronchiectasis population that already had clinical and functional impairment, suggesting that early diagnosis may have a significant impact on improving the prognosis. Some of the determinants of the peripheral muscle strength and activity in daily life found in our study are modifiable, such as dyspnea, BMI, and distance walking on ISWT. Therefore, specific interventions to ameliorate exertional dyspnea and to improve nutritional status and aerobic capacity may have a positive impact on muscle function and physical activities of daily life. Again, this is a cross-sectional study, and any supposition about interventions and their impact on the outcomes surveyed in this study must be interpreted with caution. In this context, our results support the necessity for further studies with pharmacological and nonpharmacological interventions that can benefit this population. People with bronchiectasis have reduced peripheral muscle strength and functional capacity, and they are less active in daily life compared with healthy age-matched controls. Functional capacity is an important determinant of peripheral muscle strength and activity in daily life. Future studies should evaluate whether it is possible to ameliorate these effects with pulmonary rehabilitation or other targeted interventions. Author Contributions Concept/idea/research design: Anne E. Holland, Rejane A. S. de Castro, Fernanda de Cordoba Lanza, Rodrigo A. Athanazio, Samia Z. Rached, Regina Carvalho-Pinto, Alberto Cukier, Rafael Stelmach, Simone D. Corso Writing: Anderson A. de Camargo, Jacqueline C. Boldorini, Anne E. Holland, Rodrigo A. Athanazio, Simone D. Corso Data collection: Anderson A. de Camargo, Jacqueline C. Boldorini, Rejane A. S. de Castro, Samia Z. Rached Data analysis: Anderson A. de Camargo, Jacqueline C. Boldorini, Rejane A. S. de Castro, Rafael Stelmach, Simone D. Corso Project management: Anderson A. de Camargo, Jacqueline Boldorini, Samia Z. Rached, Rafael Stelmach, Simone D. Corso Fund procurement: Fernanda Lanza, Rafael Stelmach Providing participants: Rejane A. S. de Castro, Rodrigo A. Athanazio, Samia Z. Rached, Regina Carvalho-Pinto, Alberto Cukier Providing facilities/equipment: Alberto Cukier, Rafael Stelmach Providing institutional liaisons: Rodrigo A. Athanazio, Samia Rached, Alberto Cukier, Rafael Stelmach Consultation (including review of manuscript before submitting): Fernanda de Cordoba Lanza, Rodrigo A. Athanazio, Samia Z. Rached, Regina Carvalho-Pinto, Alberto Cukier, Rafael Stelmach, Simone D. Corso Ethics Approval The study was approved by the Human Research Ethics Committees from Universidade Nove de Julho (ref. no. 921/11) and University of São Paulo (ref. no. 451538), with written informed consent obtained from all participants. Funding This study was funded by the São Paulo Research Foundation (FAPESP) (ref. no. 2013/01863-2, 2014/01902-0). Disclosures All authors completed the ICJME Form for Disclosure of Potential Conflicts of Interest and reported no disclosures relevant to this work. References 1 Lambrecht BN, GeurtsvanKessel CH. Pulmonary defence mechanisms and inflammatory pathways in bronchiectasis. Eur Respir Mon . 2011; 52: 11– 21. 2 Drain M, Elborn JS. Assessment and investigation of adults with bronchiectasis. Eur Resp Mon . 2011; 52: 32– 43. 3 Cole PJ. Inflammation: a two-edged sword −the model of bronchiectasis. Eur J Respir Dis Suppl . 1986; 147: 6− 15. Google Scholar PubMed  4 Koulouris NG, Retsou S, Kosmas E et al.   Tidal expiratory flow limitation, dyspnoea and exercise capacity in patients with bilateral bronchiectasis. Eur Respir J . 2003; 21: 743– 748. Google Scholar CrossRef Search ADS PubMed  5 de Camargo AA, Amaral TS, Rached SZ et al.   Incremental shuttle walking test: a reproducible and valid test to evaluate exercise tolerance in adults with non-cystic fibrosis bronchiectasis. Arch Phys Med Rehabil . 2014; 95( 5): 892– 899. Google Scholar CrossRef Search ADS PubMed  6 Wilson CB, Jones PW, O’leary CJ et al.   Validation of the St. George's respiratory questionnaire in bronchiectasis. Am J Respir Crit Care Med . 1997; 156: 536– 541. Google Scholar CrossRef Search ADS PubMed  7 Bradley JM, Wilson JJ, Hayes K et al.   Sedentary behaviour and physical activity in bronchiectasis: a cross-sectional study. BMC Pulm Med . 2015; 15( 1): 61. Google Scholar CrossRef Search ADS PubMed  8 Ozalp O, Inal-Ince D, Calik E et al.   Extrapulmonary features of bronchiectasis: muscle function, exercise capacity, fatigue, and health status. Multidiscip Respir Med . 2012; 7( 3): 1– 6. Google Scholar PubMed  9 Gosselink R, Troosters T, Decramer M. Exercise testing: why, which and how to interpret. Breath . 2004; 1( 2): 121– 129. Google Scholar CrossRef Search ADS   10 Olveira G, Olveira C, Gaspar I et al.   Fat-free mass depletion and inflammation in patients with bronchiectasis. J Acad Nutr Diet . 2012; 112( 12): 1999– 2006. Google Scholar CrossRef Search ADS PubMed  11 Olveira G, Olveira C, Dorado A et al.   Cellular and plasma oxidative stress biomarkers are raised in adults with bronchiectasis. Clin Nutr . 2013; 32( 1): 112– 117. Google Scholar CrossRef Search ADS PubMed  12 Öcal S, Portakal O, Öcal A et al.   Factors associated with pulmonary hypertension and long-term survival in bronchiectasis participants. Respir Med . 2016; 119: 109– 114. Google Scholar CrossRef Search ADS PubMed  13 Gale NS, Bolton CE, Duckers JM et al.   Systemic comorbidities in bronchiectasis. Chron Respir Dis . 2012; 9( 4): 231– 238. Google Scholar CrossRef Search ADS PubMed  14 Furlanetto KC, Donária L, Schneider LP, Lopes JR, Ribeiro M, Fernandes KB, Hernandes NA, Pitta F. Sedentary behavior is an independent predictor of mortality in participants with COPD. Respir Care . 2017; 62( 5): 579– 587. Google Scholar CrossRef Search ADS PubMed  15 Burtin C, Ter Riet G, Puhan MA et al.   Handgrip weakness and mortality risk in COPD: a multicentre analysis. Thorax . 2016; 71( 1): 86– 87. Google Scholar CrossRef Search ADS PubMed  16 Pinto-Plata VM, Cote C, Cabral H et al.   The 6-minute walk distance: chance over time and value as a predictor survival in severe COPD. Eur Respir J . 2004; 23( 1): 28– 33. Google Scholar CrossRef Search ADS PubMed  17 Pellegrino R, Viegi G, Brusasco V et al.   Interpretative strategies for lung function tests. Eur Respir J . 2005; 26( 5): 948– 968. Google Scholar CrossRef Search ADS PubMed  18 Pereira CAC, Sato T, Rodrigues SC. New reference values for forced spirometry spirometry in white adults in Brazil. J Pneumol . 2007; 33( 4): 397– 406. 19 Vermeeren M, Creutzberg E, Schols A et al.   Prevalence of nutritional depletion in a large out-patient population of patients with COPD. Respir Med . 2006; 100: 1349– 1355. Google Scholar CrossRef Search ADS PubMed  20 Singh SJ, Morgan MD, Scott S et al.   Development of a shuttle walking test of disability in patients with chronic airways obstruction. Thorax . 1992; 47( 12): 1019– 1024. Google Scholar CrossRef Search ADS PubMed  21 Probst VS, Hernandes NA, Teixeira DC et al.   Reference values for the incremental shuttle walking test. Respir Med . 2012; 106: 243– 248. Google Scholar CrossRef Search ADS PubMed  21 Dal Corso S, de Camargo AA, Izbicki M et al.   A symptom-limited incremental step test determines maximum physiological responses in patients with chronic obstructive pulmonary disease. Resp Med . 2013; 107: 1993– 1999. Google Scholar CrossRef Search ADS   23 Neder JA, Nery LE, Castelo A et al.   Prediction of metabolic and cardiopulmonary responses to maximum cycle ergometry: a randomised study. Eur Respir J . 1999; 14( 6): 1304– 1313. Google Scholar CrossRef Search ADS PubMed  24 Hadeli KO, Siegel EM, Sherrill DL et al.   Predictors of oxygen desaturation during submaximal exercise in 8,000 patients. Chest . 2001; 120: 88– 92. Google Scholar CrossRef Search ADS PubMed  25 Demeyer H, Burtin C, Van Remoortel H et al.   Standardizing the analysis of physical activity in patients with COPD following a pulmonary rehabilitation program. Chest . 2014; 146( 2): 318– 327. Google Scholar CrossRef Search ADS PubMed  26 Tudor-Locke C, Bassett DR Jr. How many steps/day are enough? Preliminary pedometer indices for public health. Sports Med . 2004; 34: 1– 8. Google Scholar CrossRef Search ADS PubMed  27 Bestall JC, Paul EA, Garrod R et al.   Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax . 1999; 54: 581– 586. Google Scholar CrossRef Search ADS PubMed  28 Maltais F, Decramer M, Casaburi R et al.  ; ATS/ERS Ad Hoc Committee on Limb Muscle Dysfunction in COPD. An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med . 2014; 189( 9): e15– e62. Google Scholar CrossRef Search ADS PubMed  29 Spruit MA, Thomeer MJ, Gosselink R et al.   Skeletal muscle weakness in patients with sarcoidosis and its relationship with exercise intolerance and reduced health status. Thorax . 2005; 60( 1): 32– 38. Google Scholar CrossRef Search ADS PubMed  30 Bernard S, LeBlanc P, Whittom F et al.   Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med . 1998; 158( 2): 629– 634. Google Scholar CrossRef Search ADS PubMed  31 Gosselink R, Troosters T, Decramer M. Peripheral muscle weakness contributes to exercise limitation in COPD. Am. J. Respir.Crit. Care Med.  1996; 153: 976– 980. Google Scholar CrossRef Search ADS PubMed  32 Lee AL, Hill CJ, Cecins N et al.   The short and long-term effects of exercise training in non-cystic fibrosis bronchiectasis − a randomised controlled trial. Respir Res . 2014; 15: 44. Google Scholar CrossRef Search ADS PubMed  33 Lee AL, Hill CJ, Cecins N et al.   Minimal important difference in field walking tests in non-cystic fibrosis bronchiectasis following exercise training. Respir Med . 2014; 108( 9): 1303– 1309. Google Scholar CrossRef Search ADS PubMed  34 Newall C, Stockley RA, Hill SL. Exercise training and inspiratory muscle training in patientes with bronchiectasis. Thorax . 2005; 60: 943– 948. Google Scholar CrossRef Search ADS PubMed  35 Neder JA, Nery LE. Teste de Exercício Cardiopulmonar [Cardiopulmonary exercise 
testing]. J Pneumol . 2002; 28( supl 3): s166-s206. Article in Portuguese. 36 Vallilo CC, Terra RM, de Albuquerque AL et al.   Lung resection improves quality of life of patients with symptomatic bronchiectasis. Ann Thorac Surg . 2014; 98: 1034– 1041. Google Scholar CrossRef Search ADS PubMed  37 Troosters T, Langer D, Vrijsen B et al.   Skeletal muscle weakness, exercise tolerance and physical activity in adults with cystic fibrosis. Eur Respir J . 2009; 33( 1): 99– 106. Google Scholar CrossRef Search ADS PubMed  38 Guan WJ, Gao YH, Xu G et al.   Six-minute walk test in Chinese adults with clinically stable bronchiectasis: association with clinical indices and determinants. Curr Med Res Opin . 2015; 31( 4): 843– 852. Google Scholar CrossRef Search ADS PubMed  39 O`Neill B, McDonough SM, Wilson JJ et al.   Comparing accelerometer, pedometer and a questionnaire for measuring physical activity in bronchiectasis: a validity and feasibility study? Respir Res . 2017; 18: 1– 10. Google Scholar CrossRef Search ADS PubMed  40 Sant’Anna T, Escobar VC, Fontana AD et al.   Evaluation of a new motion sensor in patients with chronic obstructive pulmonary disease. Arch Phys Med Rehabil . 2012; 93( 12): 2319– 2325. Google Scholar CrossRef Search ADS PubMed  © 2017 American Physical Therapy Association

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Physical TherapyOxford University Press

Published: Mar 1, 2018

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