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Background: The Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients' experience of physical activity. Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation., Objective: To test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries., Methods: We used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID., Results: We included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted). Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity. Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions. All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up. The MID was estimated to 6 for amount and difficulty scores and 4 for total score., Conclusions: The D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables., Competing Interests: Competing interests: JG-A reports other from AstraZeneca, other from Esteve, other from Chiesi, other from Menarini, outside the submitted work. SC-R reports personal fees from AstraZeneca, outside the submitted work. DE reports personal fees from Boehringer Ingelheim, outside the submitted work. NI reports personal fees from Almirall, outside the submitted work. NK reports personal fees from AstraZeneca, outside the submitted work. MIP reports personal fees from Philips, grants, personal fees and non-financial support from GSK, during the conduct of the study. MS reports personal fees from Chiesi, outside the submitted work. MT reports personal fees and other from GSK, outside the submitted work. TT reports grants from IMI-JU PROactive grant, during the conduct of the study; other from Boehringer Ingelheim, other from AZ Belgium, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Abnormalities of autonomic function have been reported in patients with chronic obstructive pulmonary disease (COPD). Our objectives were to identify determinants of abnormal heart rate recovery at 1 min (HRR 1 ) following completion of the 6-min walk test (6MWT) in COPD and to establish whether abnormal HRR 1 predicts acute exacerbations (AECOPD)., Methods: Hundred one COPD patients (FEV 1 (SD) 53 (19)  % predicted) were prospectively recruited in a multi-center study. HRR 1 after the 6MWT was evaluated as the difference between heart rate at the end of the test and 1 min into the recovery (HRR 1 ). Linear and logistic regression was used to identify predictors of HRR 1 and AECOPD, respectively. The best HRR 1 cut-off point to predict AECOPD was selected using the receiver operating characteristics (ROC) curves. The follow-up period was 12 months., Results: Distance covered during the 6MWT (m) and DLco (% predicted) were independently associated with HRR 1 (r 2  = 0.51, p = 0.001). Among several potential covariates, HRR 1 emerged as the most significant predictor of AECOPD (Odds ratio [OR], 0.91 per beat of recovery; 95% confidence interval [CI], 0.85-0.97; p = 0.02). The ROC analysis indicated that subjects with HRR 1 less than 14 beats (AUC, 0.71 [CI] 0.60-0.80; p = 0.0001) were more likely to suffer an exacerbation during the follow-up period (for HRR 1 , p = 0.004 [log-rank test])., Conclusions: HRR 1 after the 6MWT is an independent predictor factor for AECOPD. Further studies are warranted to examine the physiological mechanisms associating a delayed HRR and acute exacerbations in COPD patients.

Background: Guidelines have provided positive recommendations for pulmonary rehabilitation after exacerbations of chronic obstructive pulmonary disease (COPD), but recent studies indicate that postexacerbation rehabilitation may not always be effective in patients with unstable COPD., Objectives: To assess effects of pulmonary rehabilitation after COPD exacerbations on hospital admissions (primary outcome) and other patient-important outcomes (mortality, health-related quality of life (HRQL) and exercise capacity)., Search Methods: We identified studies through searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PEDro (Physiotherapy Evidence Database) and the Cochrane Airways Review Group Register of Trials. Searches were current as of 20 October 2015, and handsearches were run up to 5 April 2016., Selection Criteria: Randomised controlled trials (RCTs) comparing pulmonary rehabilitation of any duration after exacerbation of COPD versus conventional care. Pulmonary rehabilitation programmes had to include at least physical exercise (endurance or strength exercise, or both). We did not apply a criterion for the minimum number of exercise sessions a rehabilitation programme had to offer to be included in the review. Control groups received conventional community care without rehabilitation., Data Collection and Analysis: We expected substantial heterogeneity across trials in terms of how extensive rehabilitation programmes were (i.e. in terms of number of completed exercise sessions; type, intensity and supervision of exercise training; and patient education), duration of follow-up (< 3 months vs ≥ 3 months) and risk of bias (generation of random sequence, concealment of random allocation and blinding); therefore, we performed subgroup analyses that were defined before we carried them out. We used standard methods expected by Cochrane in preparing this update, and we used GRADE for assessing the quality of evidence., Main Results: For this update, we added 11 studies and included a total of 20 studies (1477 participants). Rehabilitation programmes showed great diversity in terms of exercise training (number of completed exercise sessions; type, intensity and supervision), patient education (from none to extensive self-management programmes) and how they were organised (within one setting, e.g. pulmonary rehabilitation, to across several settings, e.g. hospital, outpatient centre and home). In eight studies, participants completed extensive pulmonary rehabilitation, and in 12 studies, participants completed pulmonary rehabilitation ranging from not extensive to moderately extensive.Eight studies involving 810 participants contributed data on hospital readmissions. Moderate-quality evidence indicates that pulmonary rehabilitation reduced hospital readmissions (pooled odds ratio (OR) 0.44, 95% confidence interval (CI) 0.21 to 0.91), but results were heterogenous (I 2 = 77%). Extensiveness of rehabilitation programmes and risk of bias may offer an explanation for the heterogeneity, but subgroup analyses were not statistically significant (P values for subgroup effects were between 0.07 and 0.11). Six studies including 670 participants contributed data on mortality. The quality of evidence was low, and the meta-analysis did not show a statistically significant effect of rehabilitation on mortality (pooled OR 0.68, 95% CI 0.28 to 1.67). Again, results were heterogenous (I 2 = 59%). Subgroup analyses showed statistically significant differences in subgroup effects between trials with more and less extensive rehabilitation programmes and between trials at low and high risk for bias, indicating possible explanations for the heterogeneity. Hospital readmissions and mortality studies newly included in this update showed, on average, significantly smaller effects of rehabilitation than were seen in earlier studies.High-quality evidence suggests that pulmonary rehabilitation after an exacerbation improves health-related quality of life. The eight studies that used St George's Respiratory Questionnaire (SGRQ) reported a statistically significant effect on SGRQ total score, which was above the minimal important difference (MID) of four points (mean difference (MD) -7.80, 95% CI -12.12 to -3.47; I 2 = 64%). Investigators also noted statistically significant and important effects (greater than MID) for the impact and activities domains of the SGRQ. Effects were not statistically significant for the SGRQ symptoms domain. Again, all of these analyses showed heterogeneity, but most studies showed positive effects of pulmonary rehabilitation, some studies showed large effects and others smaller but statistically significant effects. Trials at high risk of bias because of lack of concealment of random allocation showed statistically significantly larger effects on the SGRQ than trials at low risk of bias. High-quality evidence shows that six-minute walk distance (6MWD) improved, on average, by 62 meters (95% CI 38 to 86; I 2 = 87%). Heterogeneity was driven particularly by differences between studies showing very large effects and studies showing smaller but statistically significant effects. For both health-related quality of life and exercise capacity, studies newly included in this update showed, on average, smaller effects of rehabilitation than were seen in earlier studies, but the overall results of this review have not changed to an important extent compared with results reported in the earlier version of this review.Five studies involving 278 participants explicitly recorded adverse events, four studies reported no adverse events during rehabilitation programmes and one study reported one serious event., Authors' Conclusions: Overall, evidence of high quality shows moderate to large effects of rehabilitation on health-related quality of life and exercise capacity in patients with COPD after an exacerbation. Some recent studies showed no benefit of rehabilitation on hospital readmissions and mortality and introduced heterogeneity as compared with the last update of this review. Such heterogeneity of effects on hospital readmissions and mortality may be explained to some extent by the extensiveness of rehabilitation programmes and by the methodological quality of the included studies. Future researchers must investigate how the extent of rehabilitation programmes in terms of exercise sessions, self-management education and other components affects the outcomes, and how the organisation of such programmes within specific healthcare systems determines their effects after COPD exacerbations on hospital readmissions and mortality.

Background and Objective: Exercise capacity decline is a predictor of mortality in patients with chronic obstructive pulmonary disease (COPD). Static pulmonary hyperinflation is a key determinant of exercise performance, but its effect on the longitudinal decline in exercise capacity remains unknown. We aimed to study the relationship between the inspiratory capacity-to-total lung capacity (IC/TLC) ratio and exercise capacity decline in COPD., Methods: We measured IC/TLC and other relevant clinical and functional variables in 342 clinically stable patients with COPD. The 6-min walk distance (6MWD) was determined at recruitment and after a mean ± SD of 1.7 ± 0.3 years. The annual rate of change in 6MWD was calculated. Multiple imputation to account for losses during follow up was implemented, and multivariate regression was used to analyze predictive factors of 6MWD decline., Results: Mean decline rate in the 6MWD was 21.9 ± 34.1 m/year. In the bivariate analysis, patients with lower levels of IC/TLC had greater 6MWD decline (-27.4 ± 42.5, -24.9 ± 36.5 and -13.4 ± 39.9 m/year in the first, second and third tertile of IC/TLC, respectively; P-for-trend = 0.018). From other potential risk factors considered, dyspnoea, health status, serum C-reactive protein and Borg dyspnoea score at the end of the exercise test were related to exercise capacity decline. In the multivariate regression model, only IC/TLC (β = 0.7 m/year per each percentage unit of IC/TLC; P = 0.007) and dyspnoea (mMRC ≥ 2) (β = -14.6 m/year; P = 0.013) were associated with the annual rate of 6MWD change., Conclusion: IC/TLC and dyspnoea in clinically stable patients with COPD predict their exercise capacity decline and may help to guide early therapeutic interventions., (© 2015 Asian Pacific Society of Respirology.)

Pulmonary hypertension is a serious complication of chronic obstructive pulmonary disease (COPD) that currently has no established pharmacological treatment. This study aimed to assess whether concomitant treatment with sildenafil would enhance the results of pulmonary rehabilitation in patients with COPD and increased pulmonary arterial pressure (PAP). In this double-blind, randomised controlled trial patients received 20 mg sildenafil or placebo three times daily and underwent pulmonary rehabilitation for 3 months. The primary end-point was the gain in the cycle endurance time at a constant work-rate. Secondary end-points included performance in the incremental exercise test, 6-min walk distance and quality of life. 63 patients with severe COPD and moderately increased PAP were randomised. Cycle endurance time increased by 149 s (95% CI 26-518 s) in the sildenafil group and by 169 s (95% CI 0-768 s) in the placebo group (median change difference -7 s, 95% CI -540-244 s; p=0.77). Gains in the incremental exercise test, 6-min walk distance and quality of life at the end of the study did not differ between groups. Measurements of arterial oxygenation and adverse events were similar in both groups. In patients with severe COPD and moderately increased PAP, concomitant treatment with sildenafil does not improve the results of pulmonary rehabilitation in exercise tolerance.

Background: Pulmonary rehabilitation has become a cornerstone in the management of patients with stable Chronic Obstructive Pulmonary Disease (COPD). Systematic reviews have shown large and important clinical effects of pulmonary rehabilitation in these patients. However, in unstable COPD patients who have recently suffered an exacerbation, the effects of pulmonary rehabilitation are less established., Objectives: To assess the effects of pulmonary rehabilitation after COPD exacerbations on future hospital admissions (primary outcome) and other patient-important outcomes (mortality, health-related quality of life and exercise capacity)., Search Strategy: Trials were identified from searches of CENTRAL, MEDLINE, EMBASE, PEDRO and the Cochrane Airways Group Register of Trials. Searches were current as of March 2010., Selection Criteria: Randomized controlled trials comparing pulmonary rehabilitation of any duration after exacerbation of COPD with conventional care. Pulmonary rehabilitation programmes needed to include at least physical exercise. Control groups received conventional community care without rehabilitation., Data Collection and Analysis: We calculated pooled odds ratios and weighted mean differences (MD) using random-effects models. We requested missing data from the authors of the primary studies., Main Results: We identified nine trials involving 432 patients. Pulmonary rehabilitation significantly reduced hospital admissions (pooled odds ratio 0.22 [95% CI 0.08 to 0.58], number needed to treat (NNT) 4 [95% CI 3 to 8], over 25 weeks) and mortality (OR 0.28; 95% CI 0.10 to 0.84), NNT 6 [95% CI 5 to 30] over 107 weeks). Effects of pulmonary rehabilitation on health-related quality of life were well above the minimal important difference when measured by the Chronic Respiratory Questionnaire (MD for dyspnea, fatigue, emotional function and mastery domains between 0.81 (fatigue; 95% CI 0.16 to 1.45) and 0.97 (dyspnea; 95% CI 0.35 to 1.58)) and the St. Georges Respiratory Questionnaire total score (MD -9.88; 95% CI -14.40 to -5.37); impacts domain (MD -13.94; 95% CI -20.37 to -7.51) and for activity limitation domain (MD -9.94; 95% CI -15.98 to -3.89)). The symptoms domain of the St. Georges Respiratory Questionnaire showed no significant improvement. Pulmonary rehabilitation significantly improved exercise capacity and the improvement was above the minimally important difference (six-minute walk test (MD 77.70 meters; 95% CI 12.21 to 143.20) and shuttle walk test (MD 64.35; 95% CI 41.28 to 87.43)). No adverse events were reported in three studies., Authors' Conclusions: Evidence from nine small studies of moderate methodological quality, suggests that pulmonary rehabilitation is a highly effective and safe intervention to reduce hospital admissions and mortality and to improve health-related quality of life in COPD patients who have recently suffered an exacerbation of COPD.