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Introduction: Minimally important differences (MIDs) for common outcomes of pulmonary rehabilitation are well documented for people with chronic obstructive pulmonary disease (COPD). It is not known whether MIDs differ based on COPD disease characteristics. This study aimed to estimate MIDs for clinical outcomes of pulmonary rehabilitation dependent upon baseline characteristics., Methods: A database containing 2791 people with COPD was split into derivation (n=2245; age 66±9 years; 50% males; FEV 1 47±20% predicted) and comparator (n=546; age 66±9 years; 47% males; FEV 1 46±21% predicted) cohorts. MIDs were estimated using 0.5 x SD (symmetrically distributed) or 0.5 x IQR (non-symmetrically distributed) for: 6-minute walk test (6MWT), constant work rate test (CWRT), COPD assessment test (CAT), St. George's respiratory questionnaire (SGRQ), hospital anxiety and depression scale (HADS), and fat-free mass index (FFMI). MIDs were estimated based on baseline outcome scores, lung function, modified medical research council (mMRC) grade and FFMI., Results: MID estimates were comparable to previously reported values. MIDs for SGRQ domains (Symptom=8.7 points, Activity=7.1 points, Impact=8.1 points) and FFMI were produced (0.36kg/m 2 ). There was greater variation of change in 6MWT, SGRQ-activity, SGRQ-impact, HADS and FFMI on which the MIDs were determined when categorising for baseline values (all, p<0.05). Greater variation of change in 6MWT on which the MIDs were determined was evident with COPD disease severity grouping (p<0.05). The magnitude of change in 6MWT, CAT, CWRT, SGRQ-activity, and FFMI with baseline mMRC score categorisation resulted in greater variation on which the MIDs were determined (all, p<0.05). Baseline stratification for FFMI resulted in greater variation of change in CWRT (p<0.001) and HADS-depression (p = 0.043) on which MIDs were determined., Discussion: Findings suggest that baseline presentation should be considered for people with COPD when assessing the efficacy of pulmonary rehabilitation. However, clinical significance of the variation underpinning MIDs is yet to be determined., Competing Interests: Conflicts of interest The authors declare no conflicts of interest in relation to the production of this manuscript., (Copyright © 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Inspiratory muscle training (IMT) improves inspiratory muscle strength, exercise capacity and health status in patients with chronic obstructive pulmonary disease (COPD). However, there is no additional effect on top of comprehensive pulmonary rehabilitation (PR). It is unclear whether patients with different baseline degrees of static hyperinflation respond differentially to IMT as part of a PR program. Therefore, the aim was to study the effects of IMT as an add-on on PR after stratification for baseline degrees of static hyperinflation., Methods: In this single center retrospective study data were extracted between June 2013 and October 2020 of COPD patients who participated in a comprehensive PR program including IMT. IMT was performed twice daily, one session consisted of 3 series of 10 breaths and training intensity was set initially at a load of approximately 50% of patients' maximal static inspiratory mouth pressure (MIP). The primary outcome measure was MIP. Secondary outcomes were the distance achieved on the 6-min walk test (6MWD), endurance cycling exercise capacity at 75% of the peak work rate (CWRT) and disease-specific health status using the COPD assessment test., Results: 754 patients with COPD were screened for eligibility and 328 were excluded because of repeated PR programs, missing data or baseline residual volume (RV) > 350%. In total, 426 COPD patients were categorized into RV categories 50-130% (n = 84), 131-165% (n = 86), 166-197% (n = 86), 198-234% (n = 85) and 235-349% (n = 85). In the whole sample, MIP, endurance exercise capacity and health status improved significantly. The change in 6MWD was higher in the lowest baseline degree of static hyperinflation [+ 39 (9-92) m] compared with the baseline highest degree of static hyperinflation [+ 11 (- 18-54) m] (p < 0.05)., Conclusions: IMT as part of a PR program in patients with COPD with different baseline degrees improved MIP irrespective of the degree of static lung hyperinflation. Improvement in functional exercise capacity was significantly higher in the group with the lowest degree of static hyperinflation compared with the patients with the highest degree of static hyperinflation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aim: Patients with early-onset severe COPD are often female and characterized by severe emphysema. Extrapulmonary disease manifestations have not yet been investigated in this clinical phenotype. Therefore, this study aimed to study the physical and mental health profile of patients with early-onset severe COPD., Methods: This is a cross-sectional analysis including 1058 patients with COPD who were referred for pulmonary rehabilitation between July 2013 and August 2018. Based on a forced expiratory volume in 1 s (FEV 1 ) <50%predicted and age <55 years, 78 patients were identified having early-onset severe COPD. Using propensity score matching, these patients were matched to 54 early-onset mild-to-moderate, 158 older severe and 103 older mild-to-moderate COPD patients based on FEV 1 %predicted, age and gender. An extensive panel of pulmonary and extrapulmonary disease markers (i.e. body composition, physical performance and mental health) was compared between these groups., Results: Pulmonary manifestations as well as physical and mental health were similar in patients with early-onset severe COPD compared to older severe patients, despite a mean age difference of 15.8 years. Remarkably, a high prevalence of depression was observed in early-onset severe COPD which was significantly higher compared to older severe patients (51.9 vs 32.7%, p = 0.029). In line with a large difference in FEV 1 (33.9 (25.1-41.5) vs 71.8 (61.3-85.4), p < 0.001), patients with early-onset severe COPD had lower exercise performance, indicated by a lower 6-min walking distance and peak work rate (mean difference 71.1 m, p = 0.001, and 25.9%predicted, p < 0.001, respectively), compared to patients with early-onset mild-to-moderate COPD. Interestingly, body composition and isokinetic muscle strength were not different between these comparable age groups., Conclusion: Pulmonary and physical health limitations are generally comparable between younger and older patients with severe airflow limitation, while more younger patients might have mental problems. These data suggest the need for early identification of subjects at risk for early-onset severe COPD., Competing Interests: Conflicts of interest FF reports grants and personal fees from Novartis, AstraZeneca and Chiesi and personal fees from GlaxoSmithKline, Boehringer, Mundipharma and TEVA, outside the submitted work. All other authors report no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Breathlessness is one of the most frequent symptoms in chronic obstructive pulmonary disease (COPD). COPD may result in disability, decreased productivity and increased healthcare costs. The presence of comorbidities increases healthcare utilization. However, the impact of breathlessness burden on healthcare utilization and daily activities is unclear. This study's goal was to analyze the impact of breathlessness burden on healthcare and societal costs. In this observational single-center study, patients with COPD were followed-up for 24 months after completion of a comprehensive pulmonary rehabilitation program. Every three months participants completed a cost questionnaire, covering healthcare utilization and impact on daily activities. The results were compared between participants with low (modified Medical Research Council (mMRC) grade <2; LBB) and high baseline breathlessness burden (mMRC grade ≥2; HBB). Healthcare costs in year 1 were €7302 (95% confidence interval €6476-€8258) for participants with LBB and €10,738 (€9141-€12,708) for participants with HBB. In year 2, costs were €8830 (€7372-€10,562) and €14,933 (€12,041-€18,520), respectively. Main cost drivers were hospitalizations, contact with other healthcare professionals and rehabilitation. Costs outside the healthcare sector in year 1 were €682 (€520-€900) for participants with LBB and €1520 (€1210-€1947) for participants with HBB. In year 2, costs were €829 (€662-€1046) and €1457 (€1126-€1821) respectively. HBB in patients with COPD is associated with higher healthcare and societal costs, which increases over time. This study highlights the relevance of reducing costs with adequate breathlessness relief. When conventional approaches fail to improve breathlessness, a personalized holistic approach is warranted.

Background: Cut offs for fat-free mass index (FFMI) and appendicular skeletal muscle mass index (ASMI) are available for diagnosing low muscle mass in patients with COPD. This study aimed to investigate: (1) the frequency of low muscle mass (FFMI and ASMI) applying different cut-offs and (2) the functional translation (clinical impact) of low muscle mass, in patients with COPD stratified into BMI categories., Methods: Patients with COPD were assessed regarding body composition, exercise capacity, quadriceps muscle strength, symptoms of anxiety and depression, dyspnea and quality of life upon referral to pulmonary rehabilitation. The proportion of patients with low muscle mass was compared among BMI categories. Clinical outcomes between patients with normal and low muscle mass within each BMI category were compared., Results: 469 patients with COPD were included for analyses. The frequency of patients classified as low FFMI varied significantly according to the choice of cut-off (32 to 54%; P < 0.05), whereas the frequency of patients with low ASMI was 62%. When applying age-gender-BMI-specific cut-offs, 254 patients (54%) were classified as low FFMI. The choice of the cut-off affected the frequency of patients with low muscle mass in all BMI categories. Overweight and obese patients with low muscle mass were more frequently males and presented worse pulmonary function, exercise capacity and muscle strength compared with overweight and obese patients with normal muscle mass., Conclusions: Approximately half of the overweight and obese patients with COPD have low muscle mass when applying age-gender-BMI-specific cut-offs. Low muscle mass is associated with worse functional outcomes in overweight and obese COPD patients.

Background: Exercise limitation in COPD is multi-factorial. The contribution of cardiac function to exercise capacity is not clear., Methods: Potential determinants of the different constructs of exercise capacity (functional, peak and endurance exercise capacity using the 6-minute walk distance (6MWD), peak oxygen uptake (VO 2 peak) and peak work load, and sub-maximal constant work rate test (CWRT) cycle time, respectively) were analysed., Results: Data were collected in 516 people with COPD (56% male, age (mean ± SD) 64 ± 9 years, FEV 1 % predicted 49 ± 20%). Participants had reduced exercise capacity (6MWD 424 ± 124 m, 67 ± 18% predicted; VO 2 peak 1090 ± 414 ml/min, 66 ± 30% predicted; peak work load 70 ± 34 watts, 56 ± 27% predicted; CWRT cycle time (median (IQR)) 225 (169-328) seconds). Cardiac function measures, including echocardiography and N-terminal pro-brain natriuretic peptide level, were independently significantly correlated with exercise capacity. In multiple regression analyses adjusted for age and gender, 72% (p < 0.001) of the 6MWD variance could be explained, with the timed up-and-go test accounting for 32% of the variance. For VO 2 peak, 60% (p < 0.001) of the variance could be explained, with FEV 1 accounting for 30% of the variance. Quadriceps total work was a significant determinant of all exercise tests., Conclusions: Cardiac function is related to exercise capacity, however is not a primary determinant. Determinants of the different constructs of exercise capacity vary, but there is a strong relationship between quadriceps force and functional and endurance exercise performance, and between lung function and peak exercise capacity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference., Methods: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores., Main Outcomes: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points., Findings: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points., Conclusions: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed., (Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Objective: This study aims to investigate the association between exercise tolerance, pulmonary function and lower-limb muscle function in patients with lung cancer who underwent lung resection surgery in the previous year., Methods: Sixty-four patients (age: 67 ± 11 years, 66% males) performed a symptom-limited incremental cycle test to define peak oxygen consumption (VO 2 peak) and peak workload (Wpeak). The best of two 6-min walking distance (6MWD) tests was also included. Isometric quadriceps strength and isokinetic quadriceps endurance were measured. Post-bronchodilator spirometry, lung volumes and diffusing capacity of the lung for carbon monoxide (DL CO ) measurements were assessed. Univariate correlation analysis and multiple regression analyses were performed., Results: VO 2 peak, W peak and 6MWD showed moderate to strong correlations with quadriceps strength/endurance and DL CO while weak to moderate correlations were found with forced expiratory volume in 1 s (FEV 1 ) , functional residual capacity (FRC) and body weight. Multiple regression showed that peak isometric quadriceps strength (P < 0.001) and DL CO (P < 0.001) were significant predictors of VO 2 peak (explained variance R 2  = 0.67), while quadriceps endurance (P = 0.0015) and DL CO (P < 0.0001) were significant predictors of W peak (R 2  = 0.61). Quadriceps endurance capacity (P = 0.013), but not DL CO , significantly contributed to the 6MWD model (R 2  = 0.29)., Conclusion: We identified a strong significant relationship between peak aerobic capacity and quadriceps muscle function and lung diffusing capacity. 6MWD was significantly related to quadriceps muscle function but not to pulmonary function. These findings suggest that accurate assessment of lower-limb muscle strength has a role in the accurate interpretation of exercise tests and in selecting optimal candidates for resistance training interventions targeting the lower-limb muscles after resection surgery., (© 2017 Asian Pacific Society of Respirology.)

Objective: To systematically review the efficacy of advance care planning (ACP) interventions in different adult patient populations., Design: Systematic review and meta-analyses., Data Sources: Medline/PubMed, Cochrane Central Register of Controlled Trials (1966 to September 2013), and reference lists., Study Selection: Randomized controlled trials that describe original data on the efficacy of ACP interventions in adult populations and were written in English., Data Extraction and Synthesis: Fifty-five studies were identified. Study details were recorded using a predefined data abstraction form. Methodological quality was assessed using the PEDro scale by 2 independent reviewers. Meta-analytic techniques were conducted using a random effects model. Analyses were stratified for type of intervention: 'advance directives' and 'communication.', Main Outcomes and Measures: Primary outcome measures were completion of advance directives and occurrence of end-of-life discussions. Secondary outcomes were concordance between preferences for care and delivered care, knowledge of ACP, end-of-life care preferences, quality of communication, satisfaction with healthcare, decisional conflict, use of healthcare services, and symptoms., Results: Interventions focusing on advance directives as well as interventions that also included communication about end-of-life care increased the completion of advance directives and the occurrence of end-of-life care discussions between patients and healthcare professionals. In addition, interventions that also included communication about ACP, improved concordance between preferences for care and delivered care and may improve other outcomes, such as quality of communication., Conclusions: ACP interventions increase the completion of advance directives, occurrence of discussions about ACP, concordance between preferences for care and delivered care, and are likely to improve other outcomes for patients and their loved ones in different adult populations. Future studies are necessary to reveal the effective elements of ACP and should focus on the best way to implement structured ACP in standard care., (Copyright © 2014 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)