Do pulmonary rehabilitation programmes improve outcomes in patients with COPD posthospital discharge for exacerbation: a systematic review and meta-analysis.

INTRODUCTION: Previous systematic reviews have provided heterogeneous and differing estimates for the efficacy of pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this review was to examine the efficacy of pulmonary rehabilitation programmes initiated within 3 weeks of hospital discharge following an exacerbation of COPD. METHODS: An update of a previous Cochrane review was undertaken using the Cochrane Airways Review Group Specialised Register. Searches were conducted from October 2015 to August 2023 for studies that initiated pulmonary rehabilitation within 3 weeks of hospital discharge. Studies assessing the impact of solely inpatient pulmonary rehabilitation were excluded. Forest plots were generated using a generic inverse variance random effects method. RESULTS: Seventeen studies were included. Posthospital discharge pulmonary rehabilitation reduced hospital re-admissions (OR 0.48, 95% CI 0.30 to 0.77, I2=67%), improved exercise capacity (6 min walk test, mean difference (MD) 57 m, 95% CI 29 to 86, I2=89%; incremental shuttle walk test, MD 43 m, 95% CI 6 to 79, I2=81%), health-related quality of life (St. George's Respiratory Questionnaire, MD -8.7 points, 95% CI -12.5 to -4.9, I2=59%; Chronic Respiratory Disease Questionnaire (CRQ)-emotion, MD 1.0 points, 95% CI 0.4 to 1.6, I2=74%; CRQ-fatigue, MD 0.9 points, 95% CI 0.1 to 1.6, I2=91%), and dyspnoea (CRQ-dyspnoea, MD 1.0 points, 95% CI 0.3 to 1.7, I2=87%; modified Medical Research Council Dyspnoea Scale, MD -0.3 points, 95% CI -0.5 to -0.1, I2=60%). Significant effects were not observed for CRQ-mastery, COPD assessment test, EuroQol-5 Dimension-5 Level and mortality. No intervention-related adverse events were reported. DISCUSSION: Pulmonary rehabilitation delivered posthospital discharge for exacerbation of COPD results in a reduction in hospital re-admissions and improvements in exercise capacity, health-related quality of life and dyspnoea in the absence of any intervention-related adverse events. TRIAL REGISTRATION NUMBER: CRD42023406397.

Pulmonary Rehabilitation for Adults with Chronic Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline.

Background: Despite the known benefits of pulmonary rehabilitation (PR) for patients with chronic respiratory disease, this treatment is underused. Evidence-based guidelines should lead to greater knowledge of the proven benefits of PR, highlight the role of PR in evidence-based health care, and in turn foster referrals to and more effective delivery of PR for people with chronic respiratory disease. Methods: The multidisciplinary panel formulated six research questions addressing PR for specific patient groups (chronic obstructive pulmonary disease [COPD], interstitial lung disease, and pulmonary hypertension) and models for PR delivery (telerehabilitation, maintenance PR). Treatment effects were quantified using systematic reviews. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to formulate clinical recommendations. Recommendations: The panel made the following judgments: strong recommendations for PR for adults with stable COPD (moderate-quality evidence) and after hospitalization for COPD exacerbation (moderate-quality evidence), strong recommendation for PR for adults with interstitial lung disease (moderate-quality evidence), conditional recommendation for PR for adults with pulmonary hypertension (low-quality evidence), strong recommendation for offering the choice of center-based PR or telerehabilitation for patients with chronic respiratory disease (moderate-quality evidence), and conditional recommendation for offering either supervised maintenance PR or usual care after initial PR for adults with COPD (low-quality evidence). Conclusions: These guidelines provide the basis for evidence-based delivery of PR for people with chronic respiratory disease.

Patient-related outcomes in patients referred to a respiratory clinic with persisting symptoms following non-hospitalised COVID-19.

Survivors of COVID-19 can present with varied and persisting symptoms, regardless of hospitalisation. We describe the ongoing symptoms, quality of life and return to work status in a cohort of non-hospitalised COVID-19 survivors with persisting respiratory symptoms presenting to clinic, who consented and completed patient-reported outcome measures. We identified fatigue, reduced quality of life and dysregulated breathing alongside the breathlessness. Those with co-existent fatigue had worse mood and quality of life and were less likely to have returned to normal working arrangements compared to those without fatigue. For non-hospitalised people with persisting symptoms following COVID-19 referred to a respiratory assessment clinic, there was a need for a wider holistic assessment, including return to work strategies.

Efficacy of unsupervised exercise in adults with obstructive lung disease: a systematic review and meta-analysis.

INTRODUCTION: The benefits of unsupervised exercise programmes in obstructive lung disease are unclear. The aim of this systematic review was to synthesise evidence regarding the efficacy of unsupervised exercise versus non-exercise-based usual care in patients with obstructive lung disease. METHODS: Electronic databases (MEDLINE, CINAHL, Embase, Allied and Complementary Medicine Database, Web of Science, Cochrane Central Register of Controlled Trials and Physiotherapy Evidence Database) and trial registers (ClinicalTrials.gov, Current Controlled Trials, UK Clinical Trials Gateway and WHO International Clinical Trials Registry Platform) were searched from inception to April 2020 for randomised trials comparing unsupervised exercise programmes with non-exercise-based usual care in adults with chronic obstructive pulmonary disease (COPD), non-cystic fibrosis bronchiectasis or asthma. Primary outcomes were exercise capacity, quality of life, mortality, exacerbations and respiratory cause hospitalisations. RESULTS: Sixteen trials (13 COPD, 2 asthma, 1 chronic bronchitis: 1184 patients) met the inclusion criteria. Only data on COPD populations were available for meta-analysis. Unsupervised exercise resulted in a statistically but not clinically significant improvement in the 6-Minute Walk Test (n=5, MD=22.0 m, 95% CI 4.4 to 39.6 m, p=0.01). However, unsupervised exercise did lead to statistically significant and clinically meaningful improvements in St. George's Respiratory Questionnaire (n=4, MD=-11.8 points, 95% CI -21.2 to -2.3 points, p=0.01) and Chronic Respiratory Disease Questionnaire domains (dyspnoea: n=4, MD=0.5 points, 95% CI 0.1 to 0.8 points, p<0.01; fatigue: n=4, MD=0.7 points, 95% CI 0.4 to 1.0 points, p<0.01; emotion: n=4, MD=0.5 points, 95% CI 0.2 to 0.7 points, p<0.01; mastery: unable to perform meta-analysis) compared with non-exercise-based usual care. DISCUSSION: This review demonstrates clinical benefits of unsupervised exercise interventions on health-related quality of life in patients with COPD. High-quality randomised trials are needed to examine the effectiveness of prescription methods.

Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.

Background: This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.Methods: Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.Results: The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions.Conclusions: The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.

Inflammatory responses to acute exercise during pulmonary rehabilitation in patients with COPD.

OBJECTIVE: Pulmonary rehabilitation is a cornerstone treatment in the management of chronic obstructive pulmonary disease (COPD). Acute bouts of exercise can lead to short bursts of inflammation in healthy individuals. However, it is unclear how COPD patients respond to acute bouts of exercise. This study assessed inflammatory responses to exercise in COPD patients at the start (phase 1) and end (phase 2) of pulmonary rehabilitation. METHODS: Blood samples were collected before and after an acute exercise bout at the start (phase 1, n = 40) and end (phase 2, n = 27) of pulmonary rehabilitation. The primary outcome was change in fibrinogen concentrations. Secondary outcomes were changes in CRP concentrations, total/differential leukocyte counts, markers of neutrophil activation (CD11b, CD62L and CD66b), and neutrophil subsets (mature, suppressive, immature, progenitor). RESULTS: Acute exercise (phase 1) did not induce significant changes in fibrinogen (p = 0.242) or CRP (p = 0.476). Total leukocyte count [mean difference (MD), 0.5 ± 1.1 (109 L-1); p = 0.004], neutrophil count [MD, 0.4 ± 0.8 (109 L-1); p < 0.001], and immature neutrophils (MD, 0.6 ± 0.8%; p < 0.001) increased post-exercise. Neutrophil activation markers, CD11b (p = 0.470), CD66b (p = 0.334), and CD62L (p = 0.352) were not significantly altered post-exercise. In comparison to the start of pulmonary rehabilitation (phase 2), acute exercise at the end of pulmonary rehabilitation led to a greater fibrinogen response (MD, 84 mg/dL (95% CI - 14, 182); p = 0.045). CONCLUSION: An acute bout of exercise does not appear to induce significant alterations in the concentrations of inflammatory mediators but can increase white blood cell subsets post-exercise. A greater fibrinogen response to acute exercise is seen at the end of pulmonary rehabilitation when compared to the start. Further research is required to understand the clinical context of these acute inflammatory responses to exercise.

Clinical Outcomes and Inflammatory Responses of the Frequent Exacerbator in Pulmonary Rehabilitation: A Prospective Cohort Study.

Frequent exacerbators of Chronic Obstructive Pulmonary Disease (COPD) is a distinct clinical phenotype characterised by systemic inflammation. Study objectives were to determine clinical outcomes of pulmonary rehabilitation in frequent exacerbators and the impact this has on the key surrogate markers of this phenotype. Eighty-five mild-very severe COPD patients (FEV1 pred, 52 ± 18%) were categorised as frequent (≥2 exacerbations per year, n = 50) or infrequent exacerbators (≤1 exacerbation per year, n = 35). The primary outcomes were completion rates of pulmonary rehabilitation (clinical) and plasma fibrinogen (biological). Secondary outcomes were: incremental shuttle (ISWT) & endurance shuttle walk tests (ESWT), chronic respiratory disease questionnaire (CRQ), hospital anxiety and depression scale (HADS), plasma C-reactive protein (CRP), blood leukocyte counts, blood neutrophil activation (CD11b, CD62L, CD66b) and subsets (mature, immature, suppressive, progenitor). Fibrinogen and CRP concentrations were determined via ELISA's with neutrophil activation markers assessed using flow cytometry. Frequent exacerbators were less likely to complete pulmonary rehabilitation (44% vs 69%; p = 0.025). Both groups experienced improvements in ISWT (p < 0.001), ESWT (p < 0.001), all domains of the CRQ (p < 0.001) and Depression (p = 0.017). Pulmonary rehabilitation reduced resting concentrations of fibrinogen (frequent exacerbators = 12%, infrequent exacerbators = 4%, p = 0.033) and % of progenitor blood neutrophils (p = 0.015) in both groups, with reductions in total blood leukocyte (p = 0.018) and neutrophil counts (p = 0.018) also observed in frequent exacerbators. No significant reductions in CRP concentration (p = 0.937), neutrophil activation (CD11b, p = 0.553; CD62L, p = 0.070; CD66b, p = 0.317), or other neutrophil subsets (mature, p = 0.313; immature, p = 0.756; suppressive, p = 0.259) were observed. Frequent exacerbators of COPD were less likely to complete pulmonary rehabilitation, but those who complete experience similar benefits to infrequent exacerbators. Pulmonary rehabilitation may serve to have immune-modulatory properties for frequent exacerbators.

Development and validation of reference equations for dual-energy X-ray absorptiometry-derived measures of fat-free mass in adults aged 45-85 years: results from the Canadian Longitudinal Study on Aging.

Reference equations for fat-free mass (FFM) and lean soft tissue mass (LM) measures obtained from dual-energy X-ray absorptiometry (DEXA) are important for the interpretation of body composition. This study developed and validated reference equations for FFM and LM using DEXA from the Canadian Longitudinal Study on Aging. Reference equations were developed using data from a random population-based sample of ostensibly healthy and functionally independent adults aged 45-85 years. Reference equations for absolute (accounting for age, sex, height, and body mass) and height-adjusted aka index (accounting for age, sex, and body mass index) measures of FFM and LM were developed using quantile regression. Reference equations were respectively developed and validated in derivation (80%) and validation cohorts (20%). Reference equations were applied to symptomatic adults with self-reported chronic obstructive pulmonary disease (COPD) or heart disease to assess discriminant validity; and compared with other published equations to assess performance. Bland-Altman analyses and Lin's concordance correlation coefficients were utilised to assess agreement. Reference equations for 5th, 10th, 50th, 90th, and 95th percentiles were developed for DEXA-derived estimates of FFM and LM based on 1881 healthy participants (57% male) aged 55 [IQR: 50-61] years. Reference equations performed comparably in the validation cohort and discriminated reference values between ostensibly healthy adults and people with symptomatic COPD or heart disease. Previously published reference equations tended to over- or under-predict estimates of LM compared with the current reference equations. This study provides a comprehensive and validated set of reference equations for estimating and interpreting FFM and LM from DEXA in Canadian adults aged 45-85 years, although additional validation may be required for those >75 years.

Functional Recovery of Adults Following Acute COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to investigate the objective, functional recovery of patients more than 3 months after acute COVID-19 infection. METHODS: Comprehensive database searches of EMBASE, PubMed/MEDLINE, Cochrane COVID-19 Study Register, CINAHL, and Google Scholar in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were carried out until October 19, 2022. Data were extracted and agreed in duplicate. Data were narratively synthesized, and a series of meta-analyses were performed using the random-effects inverse variance method. RESULTS: One-hundred six papers covering 20,063 patients who were either hospitalized or not hospitalized with acute COVID-19 who were followed-up between 3 to 24 months were included. Percentage predicted 6-minute walk distance at 3 months to <5 months was 84.3% (95% CI = 79.2-89.3; n = 21; I2 = 98.3%) and 92.5% (95% CI = 89.8-95.3; n = 9; I2 = 94.5%) at ≥11 months. Cardiopulmonary exercise testing revealed percentage predicted peak oxygen consumption rate ($peak\dot{\mathrm{V}}{\mathrm{o}}_2$) at 3 months to <5 months was 77.3% (95% CI = 71.0-83.7; n = 6; I2 = 92.3%) and 95.4% (95% CI = 87.1-103.6; n = 2; I2 = 77.3%) at ≥11 months. Mean handgrip strength was greatest at ≥11 months at 31.16 kg (95% CI = 19.89-42.43; n = 2; I2 = 98.3%) of all time points. All analyses showed marked heterogeneity. CONCLUSION: Patients have reduced physical function more than 3 months after COVID-19 infection. Better physical function in multiple physical domains is found after a longer recovery time. IMPACT: Physical function as measured by the 6-minute walk test, hand grip strength, and cardiopulmonary exercise testing is reduced at 3 months after COVID-19 infection and can remain over 11 months of follow-up. This protracted recovery following acute COVID-19 infection supports the need to assess physical function at any clinical follow-up, and further research into rehabilitation programs and intervention for patients who have not recovered.

A fully automated pipeline for the extraction of pectoralis muscle area from chest computed tomography scans.

Background: Computed tomography (CT)-derived pectoralis muscle area (PMA) measurements are prognostic in people with or at-risk of COPD, but fully automated PMA extraction has yet to be developed. Our objective was to develop and validate a PMA extraction pipeline that can automatically: 1) identify the aortic arch slice; and 2) perform pectoralis segmentation at that slice. Methods: CT images from the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study were used for pipeline development. Aorta atlases were used to automatically identify the slice containing the aortic arch by group-based registration. A deep learning model was trained to segment the PMA. The pipeline was evaluated in comparison to manual segmentation. An external dataset was used to evaluate generalisability. Model performance was assessed using the Dice-Sorensen coefficient (DSC) and PMA error. Results: In total 90 participants were used for training (age 67.0±9.9 years; forced expiratory volume in 1 s (FEV1) 93±21% predicted; FEV1/forced vital capacity (FVC) 0.69±0.10; 47 men), and 32 for external testing (age 68.6±7.4 years; FEV1 65±17% predicted; FEV1/FVC 0.50±0.09; 16 men). Compared with manual segmentation, the deep learning model achieved a DSC of 0.94±0.02, 0.94±0.01 and 0.90±0.04 on the true aortic arch slice in the train, validation and external test sets, respectively. Automated aortic arch slice detection obtained distance errors of 1.2±1.3 mm and 1.6±1.5 mm on the train and test data, respectively. Fully automated PMA measurements were not different from manual segmentation (p>0.05). PMA measurements were different between people with and without COPD (p=0.01) and correlated with FEV1 % predicted (p<0.05). Conclusion: A fully automated CT PMA extraction pipeline was developed and validated for use in research and clinical practice.