Frequency and Functional Consequences of Low Appendicular Lean Mass and Sarcopenic Obesity in Patients with Asthma Referred for Pulmonary Rehabilitation.

INTRODUCTION: One of the most prominent extrapulmonary manifestations in patients with chronic respiratory disease is changes in body weight and composition. However, the frequency and functional consequences of low appendicular lean mass (ALM) or sarcopenic obesity (SO) in patients with asthma are largely unknown. Therefore, the aim of the current study was to assess the frequency and functional consequences of low appendicular lean mass index (ALMI) and SO in patients with asthma. METHODS: A retrospectively analyzed cross-sectional study was conducted in 687 patients with asthma (60% female, 58 ± 13 years, FEV1 76 ± 25% pred) referred for comprehensive pulmonary rehabilitation (PR). Body composition, pulmonary function, exercise capacity, quadriceps muscle function, and quality of life were assessed. Patients were classified as presenting low ALMI according to the 10th percentiles of age-sex-body mass index (BMI)-specific reference values and as having SO according to the diagnostic procedure proposed by the 2022 ESPEN/EASO consensus. In addition, clinical outcomes between patients with normal and low ALMI or with and without SO were compared. RESULTS: The frequency of patients classified as low ALMI was 19%, whereas 45% of the patients were obese. Among the obese patients, 29% had SO. In patients with normal weight, those with low ALMI were younger and had worse pulmonary function, exercise capacity and quadriceps muscle function than those with normal ALMI (all p < 0.05). Overweight patients with low ALMI presented poorer pulmonary function and quadriceps muscle function (both strength and total work capacity). In obese class I patients, those with low ALMI showed lower quadriceps strength and maximal oxygen uptake acquired during cardiopulmonary exercise testing. Both male and female patients with SO showed lower quadriceps muscle function and reduced maximal exercise capacity compared to non-SO asthma patients. CONCLUSION: Approximately one in five asthma patients presented low ALM when age-sex-BMI-specific ALMI cutoffs were applied. Obesity is common among patients with asthma referred for PR. Among the obese patients, a significant proportion presented SO. Low ALM and SO were associated with worse functional outcomes.

Inaccuracy of estimating peak work rate from six-minute walk distance in patients with COPD.

INTRODUCTION: The cardiopulmonary exercise test (CPET) and the 6-minute walk test (6MWT) are used to prescribe the appropriate training load for cycling and walking exercise in patients with chronic obstructive pulmonary disease (COPD). The primary aims were: (i) to compare estimated peak work rate (Wpeak(estimated)) derived from six existing Wpeak regression equations with actual peak work rate (Wpeak(actual)); and (ii) to derive a new Wpeak regression equation using six-minute walk distance (6MWD) and conventional outcome measures in COPD patients. METHODS: In 2906 patients with COPD, existing Wpeak regression equations were used to estimate Wpeak using 6MWD and a new equation was derived after a stepwise multiple regression analysis. RESULTS: The 6 existing Wpeak regression equations were inaccurate to predict Wpeak(actual) in 82% of the COPD patients. The new Wpeak regression equation differed less between Wpeak(estimated) and Wpeak(actual) compared to existing models. Still, in 74% of COPD patients Wpeak(estimated) and Wpeak(actual) differed more than (±) 5 watts. CONCLUSION: In conclusion, estimating peak work load from 6MWD in COPD is inaccurate. We recommend assessment of Wpeak using CPET during pre-rehabilitation assessment in addition to 6MWT.

Isokinetic testing of quadriceps function in COPD: feasibility, responsiveness, and minimal important differences in patients undergoing pulmonary rehabilitation.

BACKGROUND: Isokinetic testing of peripheral muscle function is valid and reliable in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To evaluate whether and to what extent isokinetic testing of quadriceps function meets pre-defined test criteria in patients with COPD; to determine the response to pulmonary rehabilitation (PR), and to calculate minimal important differences (MIDs) of isokinetic quadriceps function. METHODS: Retrospective analysis of 2033 patients with COPD (age: 65±9 years, body mass index: 26±6 kg/m2, FEV1: 49±22% predicted) who followed a comprehensive PR program. Pre and post PR isokinetic quadriceps function was assessed with 30 maximal extension-flexion contractions at an angular speed of 90°/s on a computerized dynamometer. The chosen anchors were 6-min walk test and COPD assessment test. RESULTS: Pre PR, 27% of the patients performed the isokinetic test incorrectly. In male and female patients with a correct pre and post PR isokinetic test, peak torque (Δ=10±13 Nm or 9% and Δ=7±9 Nm or 10%, respectively) and total work (Δ=263±270 J or 14% and Δ=198±190 J or 15%, respectively) improved significantly. There was no change in work fatigue index following PR. Using distribution-based calculations, MID estimates for peak torque and total work ranged between 6-7 Nm and 97-135 J in males and between 4-5 Nm and 62-99 J in females. CONCLUSIONS: Based on the current test criteria, three in four patients with COPD performed the isokinetic quadriceps test correctly during baseline PR assessment. Furthermore, peak torque and total work, but not work fatigue index, were responsive to PR and sex-specific MIDs were established.

Impact of mild-to-moderate exacerbations on outcomes of neuromuscular electrical stimulation (NMES) in patients with COPD.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common among patients attending pulmonary rehabilitation (PR) and may compromise its outcomes. Neuromuscular electrical stimulation (NMES) seems one of the few exercise modalities that can actually be continued during AECOPD, due to its low burden on the impaired respiratory and cardiovascular system. However, the quality of evidence is low. The purpose of this study was to assess the impact of mild-to-moderate AECOPD on adherence/outcomes of a high-frequency (HF) or low-frequency (LF) NMES training program, as part of inpatient PR, in severely dyspneic, weakened individuals with COPD. 62 patients who received NMES as the sole supervised muscle training modality during an 8-week PR program (HF-NMES: n = 33; LF-NMES: n = 29) were analyzed retrospectively. 48.4% experienced ≥1 AECOPD during PR and were classified as exacerbators. Exacerbators completed 75 NMES sessions (interquartile range: 73-78) and were able to increase training intensity with 24 mA (15-39), while non-exacerbators completed 76 sessions (73-79) and increased training intensity with 35 mA (22-50), with no between-group differences (p = 0.474 and p = 0.065, respectively). The median change in 6-min walking distance, cycle endurance time, and isokinetic quadriceps strength and endurance did not differ between the exacerbation and non-exacerbation group. To conclude, the occurrence of mild-to-moderate AECOPD during a PR program primarily focused on NMES, does not affect adherence, intensity, and clinical outcomes in patients with severe COPD. Continuing NMES seems a feasible way to potentially counteract exacerbation-related lower-limb muscle dysfunction and improve outcomes of PR, with HF-NMES being the preferential muscle training modality.

Dietary supplementation with multiple micronutrients: no beneficial effects in pediatric cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) patients are subjected to increased oxidative stress due to chronic pulmonary inflammation and recurrent infections. Additionally, these patients have diminished skeletal muscle performance and exercise capacity. We hypothesize that a mixture of multiple micronutrients could have beneficial effects on pulmonary function and muscle performance. METHODS: A double-blind, randomized, placebo controlled, cross-over trial with a mixture of multiple micronutrients (ML1) was performed in 22 CF patients (12.9+/-2.5 yrs) with predominantly mild lung disease. Anthropometric measures, pulmonary function, exercise performance by bicycle ergometry, muscular strength and vitamins A and E were determined. RESULTS: Analysis was performed using the paired Student t-test comparing the change in each parameter during ML1 and placebo. Plasma vitamin E and A levels increased during ML1 when compared to placebo. However, no significant difference between the effect of the ML1 or placebo was observed neither for FEV1, FVC, anthropometry, nor for the parameters for muscle performance. CONCLUSIONS: The micronutrient mixture was not superior to placebo with respect to changes in pulmonary function or muscle performance in pediatric CF patients, despite a significant increase in plasma vitamin E concentrations.

No differences in physical activity in (un)diagnosed asthma and healthy controls.

To establish whether asthma affects physical activity levels in children (aged 7-10 years) we evaluated physical activity levels in children with undiagnosed asthma (UDA), diagnosed asthma (DA), and healthy controls (HCs). A cross-sectional community-based study was performed which included a parental questionnaire on their child's respiratory health, and testing of airway reversibility and bronchial hyperresponsiveness (BHR). DA was defined as the parents' confirmation of a physician's diagnosis of asthma in the past 12 months. UDA was defined by asthma symptoms combined with airway reversibility or BHR in children without a physician's diagnosis of asthma. Physical activity was measured during 5 days with an accelerometer and a diary, and with the habitual activity estimation scale which reviews the physical activity during the past 2 weeks. The final study population comprised 1,614 children of whom 81 (5%) had DA, 130 (8%) UDA, and 202 HCs. Baseline FEV(1) % was lowest in children with UDA (UDA FEV(1) 94% predicted, DA FEV(1) 98% predicted, HCs FEV(1) 100% predicted). Using the three methods, no differences were found in the physical activity between children with UDA, DA, and HCs. Childhood asthma does not appear to be associated with a decreased level of daily physical activity in our study population.

Aerobic exercise in adolescents with obesity: preliminary evaluation of a modular training program and the modified shuttle test.

BACKGROUND: Increasing activity levels in adolescents with obesity requires the development of exercise programs that are both attractive to adolescents and easily reproducible. The aim of this study was to develop a modular aerobic training program for adolescents with severe obesity, with a focus on variety, individual targets and acquiring physical skills. We report here the effects on aerobic fitness from a pilot study. Furthermore, we examined the feasibility of the modified shuttle test (MST) as an outcome parameter for aerobic fitness in adolescents with severe obesity. METHODS: Fifteen adolescents from an inpatient body weight management program participated in the aerobic training study (age 14.7 +/- 2.1 yrs, body mass index 37.4 +/- 3.5). The subjects trained three days per week for 12 weeks, with each session lasting 30-60 minutes. The modular training program consisted of indoor, outdoor and swimming activities. Feasibility of the MST was studied by assessing construct validity, test-retest reliability and sensitivity to change. RESULTS: Comparing pretraining and end of training period showed large clinically relevant and significant improvements for all aerobic indices: e.g. VO2 peak 17.5%, effect size (ES) 2.4; Wmax 8%, ES 0.8. In addition, a significant improvement was found for the efficiency of the cardiovascular system as assessed by the oxygen pulse (15.8%, ES 1.6). Construct validity, test-retest reliability and sensitivity to change of the MST were very good. MST was significantly correlated with VO2 peak (r = 0.79) and Wmax (r = 0.84) but not with anthropometric measures. The MST walking distance improved significantly by 32.5%, ES 2.5. The attendance rate at the exercise sessions was excellent. CONCLUSION: This modular, varied aerobic training program has clinically relevant effects on aerobic performance in adolescents with severe obesity. The added value of our aerobic training program for body weight management programs for adolescents with severe obesity should be studied with a randomized trial. This study further demonstrated that the MST is a reliable, sensitive and easy to administer outcome measure for aerobic fitness in adolescent body weight management trials.

Effects of anaerobic training in children with cystic fibrosis: a randomized controlled study.

BACKGROUND: Children's physical activity patterns are characterized by short-term anaerobic activities. Anaerobic exercise performance in children with cystic fibrosis (CF) has received little attention compared to aerobic performance. This study investigated the effects of anaerobic training in children with CF. DESIGN AND METHODS: Twenty patients were randomly assigned to the training group (TG) [11 patients; mean (+/- SD) age, 13.6 +/- 1.3 years; mean FEV(1), 75.2 +/- 20.7% predicted] or the control group (CG) [9 patients; mean age, 14.2 +/- 2.1 years; FEV(1), 82.1 +/- 19.1% predicted]. The TG trained 2 days per week for 12 weeks, with each session lasting 30 to 45 min. The training program consisted of anaerobic activities lasting 20 to 30 s. The control subjects were asked not to change their normal daily activities. Body composition, pulmonary function, peripheral muscle force, habitual physical activity, aerobic and anaerobic exercise performance, and quality of life were reevaluated at the end of the training program, and again after a 12-week follow-up period. RESULTS: Patients in the TG significantly improved their anaerobic performance, aerobic performance, and quality of life. No significant changes were seen in other parameters, and no improvements were found in CG. After the follow-up period, only anaerobic performance and quality of life in TG were significantly higher compared to pretraining values. CONCLUSIONS: Anaerobic training has measurable effects on aerobic performance (although not sustained), anaerobic performance, and health-related quality of life in children with CF. Therefore, anaerobic training could be an important component of therapeutic programs for CF patients.

Longitudinal determinants of peak aerobic performance in children with cystic fibrosis.

BACKGROUND: Several cross-sectional studies in patients with cystic fibrosis (CF) have shown that nutritional status and lung function are important determinants of peak aerobic capacity (peak oxygen uptake [O(2)peak]). In order to account for individual changes, the aim of this study was to determine the longitudinal relationship of changes in nutritional status, lung function, and O(2)peak in children with CF. DESIGN AND METHODS: Fat-free mass (FFM), lung function, and O(2)peak were assessed in 65 children with CF at baseline (mean +/- SD age, 10.5 +/- 2.9 years; mean FEV(1), 92.6 +/- 20.5%) and again 2 years later. FFM was calculated using skinfold thickness, and O(2)peak was measured using an incremental treadmill test for children < 12 years old or an incremental cycle ergometry test for children > or =12 years old. Lung function was measured before the exercise test. RESULTS: Over the 2-year study period, an increase was found for absolute values of FFM (6.1 kg, p < 0.001), FEV(1) (229 mL, p < 0.001), and O(2)peak (240 mL, p < 0.001), while a decrease was found for predicted values of FEV(1) (- 8.9%, p < 0.001) and O(2)peak (- 4.4%, p < 0.05). DeltaO(2)peak over the 2-year period best correlated with DeltaFEV(1) (r = 0.619, p < 0.001) and to a lesser degree with DeltaFFM (r = 0.506, p < 0.001). Multiple regression analysis demonstrated that DeltaFEV(1) and DeltaFFM explained 47% of the variation of the DeltaO(2)peak over the 2-year period. CONCLUSIONS: Our results show that longitudinal changes in O(2)peak are associated with changes in lung function and to a lesser extent with changes in nutritional status in children with CF. Special consideration should be given to exercise training and nutritional intervention, which might improve long-term clinical outcome in children with CF.

Validation of the Dutch cystic fibrosis questionnaire (CFQ) in adolescents and adults.

BACKGROUND: This study assesses the reliability and validity of the Dutch version of a disease-specific measure of health-related quality of life (HRQOL) for adolescents and adults with CF (CFQ-14+). The 47-item CFQ-14+ covers nine domains, three symptom scales and one health perception scale. METHODS: To assess psychometric characteristics of the CFQ-14+, cross-sectional (homogeneity, discriminative and construct validity) and test-retest designs were used. Eighty-four adolescents and adults with CF (mean age: 21.4 years, range 14.0-46.5 years) and a wide range of lung function (mean FEV1: 59.9% predicted, range 15-121%) completed the questionnaire during a routine visit. RESULTS: Internal consistency was acceptable for most domains of the CFQ-14+ (alpha = 0.43-0.92) and test-retest reliability was high for all domain scores (0.72-0.98). Several domains of the CFQ-14+ were able to differentiate between individuals with varying disease severity and between nourished and malnourished patients. Construct validity of the questionnaire was fair, with moderate to strong correlation between physically orientated domains and pulmonary function (rs = 0.36-0.62). CONCLUSION: The results demonstrate that the CFQ-14+ questionnaire is a well-validated measure of HRQOL assessment in adolescents and adults with CF.

Anaerobic exercise in pediatric cystic fibrosis.

Anaerobic fitness is important for daily functioning of children with cystic fibrosis (CF). The aim of this study was to assess the determinants of anaerobic performance in CF. Anaerobic performance was measured in 39 children with CF (mean age, 13.2 +/- 1.8 (SD) years, forced expired volume in 1 sec (FEV(1)) 81.6 +/- 22.1% predicted), using a Wingate anaerobic test. Significant associations were found for peak power (PP) and mean power (MP) with fat-free mass (FFM) body weight, body mass index, maximal isometric muscle force, and aerobic capacity. Pulmonary function was correlated with anaerobic indices when controlled for FFM. Multiple regression analysis indicated that FFM and FEV(1) accounted for 82% and 86% of the variability in PP and MP, respectively. Patients with moderate CF (FEV(1) < 80%), as compared to mild CF (FEV(1) >/= 80%), had higher PP (difference = 85 W, 95% CI = 27-144 W) and MP (difference = 53 W, 95% CI = 42-63 W) at equivalent FFM. Our results indicate that FFM and pulmonary function are important determinants of anaerobic exercise performance in children with CF. With progression of pulmonary disease, anaerobic performance may be enhanced.