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More than 90% of chronic obstructive pulmonary disease (COPD)-related deaths occur in low- and middle-income countries; however, few studies have examined the illness experiences of individuals living with and providing treatment for COPD in these settings. This study characterizes illness representations for COPD in Nakaseke, Uganda from the perspectives of health care providers, village health teams and community members (CMs) with COPD. We conducted 40 in-depth, semi-structured interviews (16 health care providers, 12 village health teams and 12 CMs, aged 25-80 years). Interviews were analyzed using inductive coding, and the Illness Representations Model guided our analysis. Stakeholder groups showed concordance in identifying causal mechanisms of COPD, but showed disagreement in reasons for care seeking behaviors and treatment preferences. CMs did not use a distinct label to differentiate COPD from other respiratory illnesses, and described both the physical and social consequences of COPD. Local representations can inform development of adapted educational and self-management tools for COPD.

Rationale: Chronic obstructive pulmonary disease (COPD) is a prevalent and burdensome condition in low- and middle-income countries (LMICs). Challenges to better care include more effective diagnosis and access to affordable interventions. There are no previous reports describing therapeutic needs of populations with COPD in LMICs who were identified through screening. Objectives: To describe unmet therapeutic need in screening-detected COPD in LMIC settings. Methods: We compared interventions recommended by the international Global Initiative for Chronic Obstructive Lung Disease COPD strategy document, with that received in 1,000 people with COPD identified by population screening at three LMIC sites in Nepal, Peru, and Uganda. We calculated costs using data on the availability and affordability of medicines. Measurement and Main Results: The greatest unmet need for nonpharmacological interventions was for education and vaccinations (applicable to all), pulmonary rehabilitation (49%), smoking cessation (30%), and advice on biomass smoke exposure (26%). Ninety-five percent of the cases were previously undiagnosed, and few were receiving therapy (4.5% had shortacting β-agonists). Only three of 47 people (6%) with a previous COPD diagnosis had access to drugs consistent with recommendations. None of those with more severe COPD were accessing appropriate maintenance inhalers. Even when available, maintenance treatments were unaffordable, with 30 days of treatment costing more than a low-skilled worker's daily average wage. Conclusions: We found a significant missed opportunity to reduce the burden of COPD in LMIC settings, with most cases undiagnosed. Although there is unmet need in developing novel therapies, in LMICs where the burden is greatest, better diagnosis combined with access to affordable interventions could translate to immediate benefit. [ABSTRACT FROM AUTHOR]

Importance: Most of the global morbidity and mortality in chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries (LMICs), with significant economic effects.Objective: To assess the discriminative accuracy of 3 instruments using questionnaires and peak expiratory flow (PEF) to screen for COPD in 3 LMIC settings.Design, Setting, and Participants: A cross-sectional analysis of discriminative accuracy, conducted between January 2018 and March 2020 in semiurban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda, using a random age- and sex-stratified sample of the population 40 years or older.Exposures: Three screening tools, the COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE; range, 0-6; high risk indicated by a score of 5 or more or score 2-5 with low PEF [<250 L/min for females and <350 L/min for males]), the COPD in LMICs Assessment questionnaire (COLA-6; range, 0-5; high risk indicated by a score of 4 or more), and the Lung Function Questionnaire (LFQ; range, 0-25; high risk indicated by a score of 18 or less) were assessed against a reference standard diagnosis of COPD using quality-assured postbronchodilator spirometry. CAPTURE and COLA-6 include a measure of PEF.Main Outcomes and Measures: The primary outcome was discriminative accuracy of the tools in identifying COPD as measured by area under receiver operating characteristic curves (AUCs) with 95% CIs. Secondary outcomes included sensitivity, specificity, positive predictive value, and negative predictive value.Results: Among 10 709 adults who consented to participate in the study (mean age, 56.3 years (SD, 11.7); 50% female), 35% had ever smoked, and 30% were currently exposed to biomass smoke. The unweighted prevalence of COPD at the 3 sites was 18.2% (642/3534 participants) in Nepal, 2.7% (97/3550) in Peru, and 7.4% (264/3580) in Uganda. Among 1000 COPD cases, 49.3% had clinically important disease (Global Initiative for Chronic Obstructive Lung Disease classification B-D), 16.4% had severe or very severe airflow obstruction (forced expiratory volume in 1 second <50% predicted), and 95.3% of cases were previously undiagnosed. The AUC for the screening instruments ranged from 0.717 (95% CI, 0.677-0.774) for LFQ in Peru to 0.791 (95% CI, 0.770-0.809) for COLA-6 in Nepal. The sensitivity ranged from 34.8% (95% CI, 25.3%-45.2%) for COLA-6 in Nepal to 64.2% (95% CI, 60.3%-67.9%) for CAPTURE in Nepal. The mean time to administer the instruments was 7.6 minutes (SD 1.11), and data completeness was 99.5%.Conclusions and Relevance: This study demonstrated that screening instruments for COPD were feasible to administer in 3 low- and middle-income settings. Further research is needed to assess instrument performance in other low- and middle-income settings and to determine whether implementation is associated with improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: COPD is a leading cause of death globally, with the majority of morbidity and mortality occurring in low- and middle-income country (LMIC) settings. While tobacco-smoke exposure is the most important risk factor for COPD in high-income settings, household air pollution from biomass smoke combustion is a leading risk factor for COPD in LMICs. Despite the high burden of biomass smoke-related COPD, few studies have evaluated the efficacy of pharmacotherapy in this context. Currently recommended inhaler-based therapy for COPD is neither available nor affordable in most resource-limited settings. Low-dose theophylline is an oral, once-a-day therapy, long used in high-income countries (HICs), which has been proposed for the management of COPD in LMICs in the absence of inhaled steroids and/or bronchodilators. The Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD) trial investigates the clinical efficacy and cost-effectiveness of low-dose theophylline for the management of biomass-related COPD in a low-income setting.Methods: LODOT-BCOPD is a randomized, double-blind, placebo-controlled trial to test the efficacy of low-dose theophylline in improving respiratory symptoms in 110 participants with moderate to severe COPD in Central Uganda. The inclusion criteria are as follows: (1) age 40 to 80 years, (2) full-time resident of the study area, (3) daily biomass exposure, (4) post-bronchodilator FEV1/FVC below the 5th percentile of the Global Lung Initiative mixed ethnic reference population, and (5) GOLD Grade B-D COPD. Participants will be randomly assigned to receive once daily low-dose theophylline (200 mg ER, Unicontin-E) or placebo for 52 weeks. All participants will receive education about self-management of COPD and rescue salbutamol inhalers. We will measure health status using the St. George's Respiratory Questionnaire (SGRQ) and quality of life using the EuroQol-5D (EQ-5D) at baseline and every 6 months. In addition, we will assess household air pollution levels, serum inflammatory biomarkers (fibrinogen, hs-CRP), and theophylline levels at baseline, 1 month, and 6 months. The primary outcome is change in SGRQ score at 12 months. Lastly, we will assess the cost-effectiveness of the intervention by calculating quality-adjusted life years (QALYs) from the EQ-5D.Trial Registration: ClinicalTrials.gov  NCT03984188 . Registered on June 12, 2019 TRIAL ACRONYM: Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD). [ABSTRACT FROM AUTHOR]

Background: More than 90% of the morbidity and mortality from chronic respiratory disease occurs in low-income and middle-income countries (LMICs), with substantial economic impact. Preserved ratio impaired spirometry (PRISm) is a prevalent lung function abnormality associated with increased mortality in high-income countries. We aimed to conduct a post-hoc analysis of a cross-sectional study to assess the prevalence of, the risk factors for, and the impact of PRISm in three diverse LMIC settings., Methods: We recruited a random, age-stratified and sex-stratified sample of the population in semi-urban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda. Quality-assured post-bronchodilator spirometry was performed to American Thoracic Society standards and PRISm was defined as a forced expiratory volume in one second (FEV 1 ) of less than 80% predicted with a FEV 1 /forced vital capacity ratio of 0·70 or more. We used t tests and χ 2 analyses to assess the relationships between demographic, biometric, and comorbidity variables with PRISm. Multivariable logistic models with random intercept by site were used to estimate odds ratios (ORs) with 95% CIs., Findings: 10 664 participants were included in the analysis, with a mean (SD) age of 56·3 (11·7) years and an equal distribution by sex. The prevalence of PRISm was 2·5% in Peru, 9·1% in Nepal, and 16·0% in Uganda. In multivariable analysis, younger age (OR for each decile of age 0·87, 95% CI 0·82-0·92) and being female (1·37, 1·18-1·58) were associated with increased odds of having PRISm. Biomass exposure was not consistently associated with PRISm across sites. Individuals with PRISm had impairment in respiratory-related quality of life as measured by the St George's Respiratory Questionnaire (OR by decile 1·18, 95% CI 1·10-1·25)., Interpretation: The prevalence of PRISm is heterogeneous across LMIC settings and associated with age, female sex, and biomass exposure, a common exposure in LMICs. A diagnosis of PRISm was associated with worse health status when compared with those with normal lung function. Health systems in LMICs should focus on all spirometric abnormalities as opposed to obstruction alone, given the disease burden, reduced quality of life, and size of the undiagnosed population at risk., Funding: Medical Research Council., Competing Interests: Declaration of interests TS reports grants or contracts from the Australian Lung Health Initiative; consulting fees from Verona Pharmaceuticals; and a leadership or fiduciary role in board, society, committee, or advocacy groups for 4D Medical. OF-F reports a Global Emerging Leader Award grant from the Fogarty International Centre. JJM reports grant support and payments made to their institution from the Alliance for Health Policy and Systems Research, Bloomberg Philanthropies, FONDECYT via CIENCIACTIVA and CONCYTEC, the British Council, British Embassy, the Newton-Paulet Fund, the UK Department for International Development, the UK Medical Research Council, the Wellcome Global Health Trials partnership, the Fogarty International Center, Grand Challenges Canada, the International Development Research Center Canada, Inter-American Institute for Global Change Research, the National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute of Mental Health, the Swiss National Science Foundation, the UK Research and Innovation (UKRI) Biotechnology and Biological Sciences Research Council, the UKRI Engineering and Physical Sciences Research Council, the UKRI Medical Research Council, the Wellcome Trust, and the World Diabetes Foundation; a contract from Health Action International; consulting fees from the Pan American Health Organization and Bloomberg Philanthropies; participation on data safety monitoring or advisory boards for the Nigeria Sodium Study, the Intensive care bundle with blood pressure Reduction in Acute Cerebral haemorrhage Trial, the Latin American Brain Health institute, Universidad Adolfo Ibáñez (Chile), Programa de Gastronomía, Facultad de Estudios Interdisciplinarios, Pontificia Universidad Católica del Perú, and the InterAmerican Heart Foundation; being Co-chair of the Independent Group of Scientists, 2023 Global Sustainable Development Report, UN; being a member of the Scientific Expert Committee, Global Data Collaborative for CV Population Health, the World Health Federation, Microsoft, and Novartis Foundation; being a member of the Scientific and Technical Advisory Committee for the Alliance for Health Policy and Systems Research, WHO; being a member of WHO's Technical Advisory Group on non-communicable disease-related research and innovation, Non-communicable Diseases Department, WHO; and being a member of the Advisory Scientific Committee, Instituto de Investigación Nutricional, Peru. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with varied clinical and pathophysiological characteristics. Although there is increasing evidence that COPD in low-income and middle-income countries may have different clinical characteristics from that in high-income countries, little is known about COPD phenotypes in these settings. We describe the clinical characteristics and risk factor profile of a COPD population in Uganda., Methods: We cross sectionally analysed the baseline clinical characteristics of 323 patients with COPD aged 30 years and above who were attending 2 national referral outpatient facilities in Kampala, Uganda between July 2019 and March 2021. Logistic regression was used to determine factors associated with spirometric disease severity., Results: The median age was 62 years; 51.1% females; 93.5% scored COPD Assessment Test >10; 63.8% modified medical research council (mMRC) >2; 71.8% had wheezing; 16.7% HIV positive; 20.4% had a history of pulmonary tuberculosis (TB); 50% with blood eosinophilic count >3%, 51.7% had 3 or more exacerbations in the past year. Greater severity by Global initiative for Chronic Obstructive Lung Disease (GOLD) stage was inversely related to age (aOR=0.95, 95% CI 0.92 to 0.97), and obesity compared with underweight (aOR=0.25, 95% CI 0.07 to 0.82). Regarding clinical factors, more severe airflow obstruction was associated with SPO 2 <93% (aOR=3.79, 95% CI 2.05 to 7.00), mMRC ≥2 (aOR=2.21, 95% CI 1.08 to 4.53), and a history of severe exacerbations (aOR=2.64, 95% CI 1.32 to 5.26)., Conclusion: Patients with COPD in this population had specific characteristics and risk factor profiles including HIV and TB meriting tailored preventative approaches. Further studies are needed to better understand the pathophysiological mechanisms at play and the therapeutic implications of these findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Low- and middle-income countries (LMICs) account for >90% of deaths and illness episodes related to COPD; however, this condition is commonly underdiagnosed in these settings. Case-finding instruments for COPD may improve diagnosis and identify individuals that need treatment, but few have been validated in resource-limited settings., Methods: We conducted a population-based cross-sectional study in Uganda to assess the diagnostic accuracy of a respiratory symptom, exposure and functional questionnaire in combination with peak expiratory flow for COPD diagnosis using post-bronchodilator FEV 1 /FVC z-score below the 5th percentile as the gold standard. We included locally relevant exposure questions and statistical learning techniques to identify the most important risk factors for COPD. We used 80% of the data to develop the case-finding instrument and validated it in the remaining 20%. We evaluated for calibration and discrimination using standard approaches. The final score, COLA (COPD in LMICs Assessment), included seven questions, age and pre-bronchodilator peak expiratory flow., Results: We analyzed data from 1,173 participants (average age 47 years, 46.9% male, 4.5% with COPD) with acceptable and reproducible spirometry. The seven questions yielded a cross-validated area-under-the-curve [AUC] of 0.68 (95% CI 0.61-0.75) with higher scores conferring greater odds of COPD. The inclusion of peak expiratory flow and age improved prediction in a validation sample (AUC=0.83, 95% CI 0.78-0.88) with a positive predictive value of 50% and a negative predictive value of 96%. The final instrument (COLA) included seven questions, age and pre-bronchodilator peak expiratory flow., Conclusion: COLA predicted COPD in urban and rural settings in Uganda has high calibration and discrimination, and could serve as a simple, low-cost screening tool in resource-limited settings., Competing Interests: Dr Robert A Wise reports personal fees from GSK, Novartis, AstraZeneca, Merck, Anapsysbio, Kikiksa, Kinevant, Galderma, Chimerx, and AbbVie, outside the submitted work. Professor John R Hursts report grants, personal fees, non-financial support from AstraZeneca, Boehringer Ingelheim, Chiesi, and Novartis  that make medicines to treat COPD, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2020 Siddharthan et al.)