RATIONALE:Tuberculosis (TB) is a major worldwide cause of disability, with TB survivors experiencing a significant and often underrecognized burden, and approximately half going on to develop post-tuberculosis lung disease (PTLD). Pulmonary rehabilitation may offer effective disease management, but there is a lack of evidence in PTLD populations. OBJECTIVES:We aimed to determine the clinical and cost effectiveness of pulmonary rehabilitation for adults living with PTLD in Kyrgyzstan. METHODS:A single-blind randomized controlled trial, conducted March 2021 to June 2022 in Bishkek, Kyrgyzstan, compared supervised pulmonary rehabilitation to usual care for adults living with PTLD. Participants were randomized (1:1) to receive either usual care (control) or culturally adapted pulmonary rehabilitation (intervention), comprising individually prescribed and tailored exercise and self-management education. The primary outcome was change in maximal exercise capacity, measured by the incremental shuttle walking test (ISWT), from baseline to the end of 6 weeks of pulmonary rehabilitation, analyzed by intention-to-treat analysis. Secondary outcomes included health-related quality of life (HRQoL) and cost-effectiveness analysis. RESULTS:One hundred fourteen participants (mean ± SD, 43.3 ± 15.2 years; 57% male) received either supervised pulmonary rehabilitation or usual care. Compared with the control group, changes in exercise capacity and HRQoL from baseline were significantly greater in the intervention group (ISWT: 123.0 m [95% CI, 81.2-164.8 m], P <.001; EQ-5D-5L Visual Analogue Scale: 20.2 [95% CI 15.5-24.9], P <.0001). The intervention group saw a significant increase in quality-adjusted life-years (QALYs) over the control group (0.2 [95% CI, 0.1-0.2]). We calculated a total program cost of US$5686.5 (US$95 per patient who received pulmonary rehabilitation), giving a program cost, after adjusting for purchasing power, of US$2143.2 per QALY (95% CI, $1621.9-$2663.9). CONCLUSIONS:In adults with PTLD in Kyrgyzstan, a culturally adapted pulmonary rehabilitation program significantly improved exercise capacity and HRQoL compared with usual care and was both clinically and cost effective.

Purpose:Pulmonary rehabilitation (PR) is recommended internationally for individuals with chronic obstructive pulmonary disease (COPD), but there is limited evidence and practice of PR in Sri Lanka. Key challenges for PR such as poor accessibility, uptake and completion need to be addressed when designing and delivering new PR programmes. Accordingly, this study determined the feasibility and acceptability of culturally adapted PR for adults with COPD in Sri Lanka. Patients and Methods:A randomized controlled feasibility trial was conducted with 50 adults living with COPD in Colombo, Sri Lanka. A culturally adapted PR comprised a 6-week rolling programme with sessions conducted twice every week. Sessions involved endurance and resistance exercise training, education and cultural adaptations of nutritional support and group singing. The control group received usual care, which did not include any form of PR or exercise training. Feasibility was determined by uptake (≥60% of eligible participants consented) and completion (≥70% of recruited participants). Acceptability was explored by focus group discussions (FGDs) analysed thematically. Results:Seventy-nine eligible individuals (94% of screened) were referred in order to recruit 50 participants (63% uptake). The majority of participants in both intervention (72%, n=18) and control (64%, n=16) groups completed the study. Based on qualitative focus group discussions four themes emerged: (1) Increased knowledge following PR, including dispelling misbeliefs about COPD and improving medication adherence; (2) Perceived improvements in health following PR, including improved walking ability and reduced breathlessness (3) Enjoyment and benefits of cultural adaptations to PR, and (4) Challenges during PR, including adherence to exercise and travel requirements. Conclusion:Culturally adapted PR was feasible and acceptable to adults with COPD in Sri Lanka. A fully powered trial is warranted for evaluating clinical and cost-effectiveness of culturally adapted PR.

Integration of healthcare services for people with chronic respiratory disease (CRD) is proposed as a means to improve the delivery of evidence-based therapies, thereby improving outcomes, experience of care and reducing health inequalities. In this narrative review we define categories of integration interventions, present a structured assessment of the evidence supporting both horizontal and vertical integrated care models and case-finding in CRD, and describe the implications for the implementation and scaling of integrated care programmes in clinical practice. Our findings suggest better coordination of the provision of evidence-based interventions through horizontal integration can improve clinical outcomes in CRDs, including reducing episodes of unscheduled care. Vertical integration provided by different organisational units in healthcare systems can enhance delivery of evidence-based interventions but impact on longer-term outcomes is less clear. The available evidence, whilst providing support for integration, does not conclusively support a specific model of care or organisational structure. Careful attention is required to define components of integrated care interventions. Study duration and choice of outcomes are key to evaluating clinical and cost effectiveness in future trials.

BACKGROUND:Post-TB lung disease (PTLD) causes significant disability in survivors of TB. Pulmonary rehabilitation (PR) may offer effective disease management but lacks high-quality evidence in this underrepresented population. RESEARCH QUESTION:Compared with usual care, does a 6-week PR program improve exercise capacity and health-related quality of life (HRQoL) cost-effectively in adults living with post-TB lung disease? STUDY DESIGN AND METHODS:We conducted a single-center randomized controlled trial with blinded outcome assessments, comparing PR vs usual care (UC) for adults in Kampala, Uganda with PTLD. Participants were randomized (1:1) to receive either PR or UC, with assessments at 6 weeks postintervention. The primary outcome was change in exercise capacity measured by the Incremental Shuttle Walk Test. Secondary outcomes included HRQoL, respiratory symptoms, psychological well-being, and cost-benefit analysis. A generalized linear mixed model was used for the primary efficacy analysis (intention-to-treat) and a difference-in-differences analysis for secondary outcomes (modified intention-to-treat). RESULTS:Between November 2020 and September 2022, 178 adults with PTLD were assessed for eligibility and 114 were randomized (mean age ± SD, 43.3 ± 15.2 years; 65 [57%] were male). The postintervention improvement in mean Incremental Shuttle Walk Test in the PR group was significantly greater than in the UC group, by 54.36 m (95% CI, 17.22-91.51 m; P = .004). We also observed significant improvements in HRQoL in PR compared with UC: COPD Assessment Test score, -3.6 (95% CI, -6.7 to -0.39; P = .015); and Clinical COPD Questionnaire total, -0.37 (95% CI, -0.68 to -0.06; P = .004). The EuroQol Visual Analog Scale and quality-adjusted life-years (QALYs) marginally improved in the PR group vs the UC group: 3.98 (95% CI, -2.05 to 10.02; P = .191) and 0.02 (95% CI, -0.02 to 0.05; P = .334), respectively. The average cost of PR was $6,468/QALY gained, equating to $20,000/QALY gained after adjusting for purchasing power (below the National Institute for Health and Care Excellence cost-effectiveness threshold). INTERPRETATION:In adults with PTLD, a 6-week PR program elicited clinically and statistically significant improvements in exercise capacity and HRQoL compared with UC, and was cost-effective. CLINICAL TRIAL REGISTRATION:ISRCTN Clinical Trial Registry; No.: ISRCTN18256843; URL: isrctn.com.

Background and objective Breathlessness is associated with higher rates of unplanned health service utilisation. We aimed to evaluate any associations between the severity of breathlessness limiting exertion (hereafter breathlessness), time between breathlessness recording and subsequent unplanned hospital admissions, and length of stay.Methods A retrospective cohort study of adults seen in general practice (UK Clinical Practice Research Datalink) with breathlessness (Medical Research Council (MRC) breathlessness scale; 1–5; 5 is most intense), no pre-existing cardio-respiratory disease and a subsequent unplanned hospital admission. Data from 2007 to 2017 were used. By intensity of breathlessness, time to first unplanned admission and hospital length of stay were evaluated, the latter using negative binomial regression.Results 103 917 adults had breathlessness scores recorded, of which 16 948 used MRC. 11 911 (70%) adults had a subsequent unplanned hospital admission (median (IQR) of 1538 days (846–2258)) later. More intense breathlessness was associated with higher age, higher body mass index and being a smoker/ex-smoker.Length of time between a first-recorded breathlessness score and the first unplanned hospital admission decreased significantly with higher MRC scores (MRC 1: 1167 days; MRC 5: 615 days).Negative binomial regression showed an association between higher MRC scores and an increased length of inpatient stay (p<0.001; Akaike information criterion=20 817), controlling for key demographic factors.Conclusion This is the first study to identify an association between recording breathlessness intensity and time to a person’s first unplanned hospital admission and longer inpatient length of stay. Future work must focus on whether interventions can change people’s health service use.

Background There is a need to reduce delays to diagnosis for chronic breathlessness to improve patient outcomes.Objective To conduct a mixed-methods feasibility study of a larger cluster randomised controlled trial (cRCT) investigating a structured symptom-based diagnostic approach versus usual care for chronic breathlessness in primary care.Methods 10 general practitioner practices were cluster randomised to a structured diagnostic approach for chronic breathlessness including early parallel investigations (intervention) or usual care. Adults over 40 years old at participating practices were eligible if presenting with chronic breathlessness without an existing explanatory diagnosis. The primary feasibility outcomes were participant recruitment and retention rate at 1 year. Secondary outcomes included number of investigations at 3 months, and investigations, diagnoses and patient-reported outcome measures (PROMs) at 1 year. Semistructured interviews were completed with patients and clinicians, and analysed using thematic analysis.Results Recruitment rate was 32% (48/150): 65% female, mean (SD) age 66 (11) years, body mass index 31.2 kg/m2 (6.5), median (IQR) Medical Research Council dyspnoea 2 (2–3). Retention rate was 85% (41/48). At 3 months, the intervention group had a median (IQR) of 8 (7–9) investigations compared with 5 (3–6) investigations with usual care. 11/25 (44%) patients in the intervention group had coded diagnosis for breathlessness at 12 months compared with 6/23 (26%) with usual care. Potential improvements in symptom burden and quality of life were observed in the intervention group above usual care.Conclusions A cRCT investigating a symptom-based diagnostic approach for chronic breathlessness is feasible in primary care showing potential for timely investigations and diagnoses, with PROMs potentially indicating patient-level benefit. A further refined fully powered cRCT with health economic analysis is needed.

BACKGROUND: COPD is characterized by reduced exercise tolerance, and improving physical performance is an important therapeutic goal. A variety of exercise tests are commonly used to assess exercise tolerance, including laboratory and field-based tests. The responsiveness of these various tests to common COPD interventions is yet to be compared, but the results may inform test selection in clinical and research settings. RESEARCH QUESTION: What exercise test possesses the greatest sensitivity to change from before to after intervention in patients with COPD? STUDY DESIGN AND METHODS: One hundred fifty-four patients with symptomatic COPD were recruited and randomized (2:1:1) to 6 weeks of long-acting muscarinic antagonist, pulmonary rehabilitation (PR), or usual care. Before and after intervention, participants performed an incremental cycle exercise test and constant work rate cycle test (CWRCT), incremental shuttle walk test and endurance shuttle walk test (ESWT), 6-min walk test, and 4-m gait speed test. RESULTS: One hundred three participants (mean +/- SD age, 67 +/- 8 years; 75 male participants [73%]; FEV1, 50.6 +/- 16.8% predicted) completed the study. Significant improvements in the incremental cycle exercise test, CWRCT, incremental cycle exercise test, ESWT, and 6-min walk test results were observed after PR (P < .05), with the greatest improvements seen in the constant work rate protocols (percentages change: CWRCT, 42%; ESWT, 41%). INTERPRETATION: The ESWT and CWRCT seemed to be the most responsive exercise test protocols to long-acting muscarinic antagonist and PR therapy. The magnitude of change was much greater after a program of rehabilitation compared with bronchodilator therapy.

Background:Specialist intervention in COPD is often reactive, resulting in inequalities in the provision of care. A proactive approach, in which individuals with modifiable disease are identified from primary care records, may help to tackle this inequality in access. Aim:To estimate the prevalence of "treatable traits" in COPD in a primary care research database and to assess health service usage. Methods:We performed a secondary analysis of individuals with either 1) a primary care diagnosis of COPD or 2) obstructive spirometry and history of ever smoking in a large observational study recruiting individuals aged 40-69 years old in Leicestershire, UK. Spirometry, height, weight and smoking history were collected prospectively and linked to individuals' primary care records. "Treatable traits" were identified from primary care records (frequent exacerbations, current smoking, low body mass index, respiratory failure, severe breathlessness, potential suitability for lung volume reduction or psychological comorbidity). Differences in demographics and health usage between those with and without "treatable traits" were assessed. Results:In total, of the 347 individuals with COPD, 186 had at least one "treatable trait". Compared to those without treatable traits, individuals with treatable traits were younger (61 vs 64 years, p<0.001), had more severe airflow obstruction (FEV1 86% vs 94% predicted, p=0.002), higher eosinophil count (0.32 vs 0.27 cells/μL, p=0.04) and were more socioeconomically deprived (UK Indices of Multiple Deprivation decile 4.3 vs 5.8, p<0.001). Individuals with treatable traits had a higher annual primary care health usage (47 vs 30 visits per year, p=0.001). Referrals rates to specialist respiratory services were low in both groups. Conclusion:Treatable traits are common in COPD and can be identified from routinely collected primary care data. Treatable traits are associated with younger age and greater deprivation. These individuals pose a significant burden to primary care yet are rarely referred to specialist respiratory services.

Background:Pulmonary rehabilitation (PR) is a key treatment for chronic obstructive pulmonary disease (COPD) recommended by all guidelines. However, programmes vary widely and the optimal combination of components to maximise benefits and efficiency remains unknown. We aimed to use the novel technique of component network meta-analysis (cNMA) to investigate the relative contribution of 1) exercise modality and intensity, 2) non-exercise components, 3) type of supervision, and 4) programme duration of PR for people with COPD. Methods:MEDLINE, EMBASE, CINAHL, and Cochrane databases searched in October 2023 with no date or language restrictions. We included randomised controlled trials (RCTs) which included an intervention involving exercise for people with COPD. We present outcomes of exercise capacity, breathlessness and health related quality of life (HRQoL). Screening and eligibility were assessed by two independent reviewers. cNMA, a technique developed to investigate complex interventions such as PR, was conducted to examine the contribution of single components within diverse multicomponent interventions controlling for cohort demographics. PROSPERO: CRD42022322058. Findings:We included 337 RCTs with 18,911 participants and 227 intervention components. In-person supervision enhanced gains in exercise capacity (Standardised mean difference (SMD) 0.41, 95% CrI 0.20; 0.63), HRQoL (0.43 95% CrI 0.19; 0.68) and breathlessness (0.31 95% CrI 0.04; 0.58) over exercise training alone with moderate to high certainty. Remote supervision increased gains in exercise capacity (0.40 95% CrI 0.08; 0.73) with trends towards improvements in HRQoL and breathlessness, with low certainty. Aerobic training appeared to be most effective for all outcomes at high or very high intensity but with low certainty. Addition of structured education did not improve any outcome. Psychological interventions led improvements in exercise capacity (0.37 95% CrI 0.01; 0.73, low certainty) and HRQoL (0.54 95% CrI 0.18; 0.91, moderate certainty). There was trend towards improvements in breathlessness with addition of breathing exercises (0.26 95% CrI -0.04; 0.56, low certainty). Programme duration did not impact outcomes. For outcomes of exercise capacity, HRQoL and breathlessness there were 60%, 63% and 59% studies at high risk of bias respectively. Interpretation:This large-scale analysis of over 300 randomised PR trials found the strongest effects for in-person supervised and prescribed aerobic exercise training with less certainty for the benefit of other commonly used PR components and delivery methods. Funding:This research was funded through a National Institute for Health and Care Research (NIHR) Applied Research Collaboration East Midlands grant (2.12) and carried out at the NIHR Leicester Biomedical Research Centre (BRC).

BACKGROUND:The impact of delays to diagnosis for individuals presenting with chronic breathlessness is unknown. We investigated the time to diagnosis after presenting with chronic breathlessness and associations with future unplanned hospitalisation and mortality. METHODS:A retrospective cohort study using the UK Clinical Practice Research Datalink involving adults with a first recorded code for breathlessness and no pre-existing cardiorespiratory disease. Adjusted Cox regression was used to investigate the associations with unplanned hospitalisation and mortality during all follow-up and within 2 years after the first code of breathlessness between those with and without a diagnosis, and using landmark analysis for time to diagnosis. RESULTS:66 909/101 369 (66%) of adults with a first recorded code for breathlessness received an explanatory diagnosis during a median 5 years of follow-up. 43 394 (43%) of adults received an explanatory diagnosis within 2 years and had a higher risk (HR (95% CI)) of unplanned hospitalisation (1.25, 1.19 to 1.31) and mortality (1.84, 1.42 to 2.38) in the subsequent 2 years compared with adults without a diagnosis. In those with a recorded diagnosis, waiting ≥6 months was associated with increased mortality (6-24 months: 3.33 (2.13 to 5.20); ≥24 months: 13.30 (8.98 to 19.80)). CONCLUSION:We describe better outcomes in adults coded for breathlessness without subsequent explanatory diagnoses. In adults with an explanatory diagnosis, waiting ≥6 months for a diagnosis was associated with reduced survival. Diagnostic pathways for chronic breathlessness need to differentiate between these two groups and achieve earlier diagnosis in those at higher risk.

Considering a huge burden of chronic respiratory diseases (CRDs) in India, there is a need for locally relevant Pulmonary rehabilitation (PR) services. This cross-sectional survey was aimed to explore the interest, needs and challenges among various stakeholders for PR in Pune city, India. At the outpatient respiratory medicine department of a multi-speciality hospital in Pune, India, 403 eligible people with CRDs were invited to participate in the survey, of which 370 (92%) responded and agreed to participate. (220 males, mean ± SD age 56 ± 15 years). Out of the 370, 323 (87%) people with CRDs were keen to attend PR. In a multiple selection question, there was inclination towards paper-based manuals home-based (70%) and web-based (84%) programs. 207 healthcare providers (HCPs), including physicians, pulmonologists and physiotherapists involved in the care of people living with CRDs across Pune city were invited to participate in the survey. Out of the 207, (80%) of the HCPs believed that PR was an effective management strategy and highlighted the lack of information on PR and need for better understanding of PR (48%) and its referral process. The surveyed stakeholders are ready to take up PR, identifying specific needs around further knowledge of PR, modes of delivery, and referral processes, that could potentially feed the development of relevant PR programs in the Indian healthcare settings.

Background There are known delays to diagnosis for diseases which commonly present with chronic breathlessness, but the subsequent impact is unknown. For adults presenting with breathlessness, we investigated the time taken to achieve an explanatory diagnosis, and associations with unplanned hospitalisation and mortality.Methods A retrospective cohort study using the UK CPRD was conducted involving adults with a first-recorded code for breathlessness and no pre-existing cardiorespiratory disease. We documented whether an explanatory diagnosis was recorded after the first code of breathlessness within two years and during all follow-up, and the time to diagnosis. Cox regression (adjusted) was used to investigate the associations with unplanned hospitalisation and mortality.Results 101369 adults were included with a first-recorded code for breathlessness. After two-years, 43394 (43%) adults received a recorded explanatory diagnosis and had a higher risk of unplanned hospitalisation (1.25 [1.19-1.31]) and mortality (2.06 [1.60-2.65]) compared to adults without a diagnosis. Overall, 66909 (66%) adults received a recorded diagnosis during a median of 5-years follow-up. Adults that received a recorded diagnosis after ≥6 months had worse outcomes of unplanned hospitalisation (6-24 months: 1.01 [0.94-1.08]; ≥24 months: 1.13 [1.06-1.20]) and mortality (6-24 months: 3.38 [2.21-5.18]; ≥24 months: 10.80 [7.46-15.70]).Conclusion We describe a sub-group of adults coded for breathlessness but without an explanatory diagnosis with better outcomes. However, in adults with an explanatory diagnosis waiting beyond six months was associated with worse outcomes. Diagnostic pathways for chronic breathlessness need to differentiate between these two groups and achieve earlier diagnosis in those at higher risk.What is already known on this topic? What this study adds How this study might affect research, practice or policy ### Competing Interest StatementKK is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and the NIHR Leicester Biomedical Research Centre (BRC).### Funding StatementUK is funded by a National Institute for Health Research (NIHR) Biomedical Research Council (BRC) / Leicester Precision Medicine Institute (LPMI) Studentship. RAE is funded by a NIHR Clinician Scientist Fellowship CS-2016-16-020. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This study was approved by Independent Scientific Advisory Committee for Medicines and Healthcare products Regulatory Agency database research (Protocol Number = 20_075). This study is based in part on data from the Clinical Practice Research Datalink obtained under licence from the UK Medicines and Healthcare products Regulatory Agency.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesThe study uses data from the Clinical Practice Research Datalink (CPRD). CPRD does not allow the sharing of patient-level data.

Background Chronic obstructive pulmonary disease (COPD) is characterised by reduced exercise tolerance and improving physical performance is an important therapeutic goal. A variety of exercise tests are commonly used to assess exercise tolerance, including laboratory and field-based tests. The responsiveness of these tests to common COPD interventions is yet to be compared, but may inform test selection in clinical and research settings. Research Question What exercise test possesses the greatest sensitivity to change pre- to post-intervention in patients with COPD? Study Design and Methods 154 patients with symptomatic COPD were recruited and randomised (2:1:1) to six weeks of long-acting muscarinic antagonist (LAMA), pulmonary rehabilitation (PR), or usual care (UC). Pre- and post-intervention, participants performed a ramp-incremental and constant work rate cycle ergometer exercise test (ICET and CWRCT), incremental and endurance shuttle walk test (ISWT and ESWT), six-minute walk test (6MWT), and a four metre gait speed test (4MGS). Results 103 participants (67 ± 8 y; 75 [73%] males; FEV1: 50.6 ± 16.8 % predicted) completed the study. Significant improvements in the ICET, CWRCT, ISWT, ESWT, and 6MWT were observed following PR (p<0.05), with the greatest improvements seen in the constant work rate protocols (% change: CWRCT: 42%; ESWT: 41%). Interpretation The ESWT and CWRCT appeared to be the most responsive exercise test protocols to LAMA and PR. The magnitude of change was much greater after a programme of rehabilitation compared to bronchodilator therapy.