https://doi.org/10.4081/monaldi.2026.4174
The diagnostic blind spot of spirometric staging in biomass-related non-smoking chronic obstructive pulmonary disease: a cross-sectional study of spirometry-diffusion discordance in a rural South Indian population
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Accepted: 15 September 2026
Published: 12 October 2026
Chronic obstructive pulmonary disease (COPD) is heterogeneous, yet severity is conventionally graded by spirometry [forced expiratory volume in 1 second (FEV1)] on the assumption that airflow limitation reflects parenchymal damage. Biomass-related non-smoking COPD (NS-COPD) is common in low- and middle-income countries. In this hospital-based cross-sectional study, we compared the physiological phenotypes of smoking COPD (S-COPD) and biomass-related NS-COPD and tested the concordance between Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric severity and diffusion-based gas-exchange impairment. A total of 91 stable COPD patients (S-COPD, n=54; NS-COPD, n=37) underwent post-bronchodilator spirometry, single-breath diffusing capacity of the lung for carbon monoxide (DLCO) with transfer coefficient (KCO), residual volume to total lung capacity ratio, and the 6-minute walk test; cohorts were stratified by exposure (>10 pack-years vs. >60 hour-years of biomass) and compared using the Student t-test and Fisher's exact test. Compared with smokers, non-smokers had higher DLCO (71.4±12.4 vs. 57.7±17.5% predicted; p<0.001) and KCO (0.95±0.19 vs. 0.71±0.22 mmol/min/kPa/L; p<0.001). All non-smokers with severe (GOLD 3) airflow limitation (8/8, 100%) retained normal or only mildly impaired diffusion [7/8 (87.5%) strictly normal], whereas 14/28 (50.0%) GOLD 3 smokers had impaired gas exchange [4/28 (14.3%) severe]. Non-smokers more often retained a normal DLCO [31/37 (83.8%) vs. 26/54 (48.1%); odds ratio 5.6, 95% confidence interval 2.0-15.5; p<0.001]. This difference persisted after multivariable adjustment for age, sex and body mass index (odds ratio 30.0, 95% confidence interval 2.5-358.5; p=0.007) and after further adjustment for FEV1 percent predicted (odds ratio 21.1, 95% confidence interval 1.6-282.7; p=0.021), indicating that the dissociation was not explained by these covariates or by the degree of airflow limitation itself. GOLD staging tended to overestimate parenchymal severity in biomass-related NS-COPD, in which airflow obstruction was largely uncoupled from gas-exchange loss, whereas in smokers the two were more tightly coupled. These cross-sectional, single-center findings, limited by a sex imbalance and the absence of imaging confirmation, support routine DLCO/KCO measurement to phenotype these patients and, where imaging is scarce, as a low-cost structural surrogate.
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Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2024 report). Available from: https://goldcopd.org/2024-gold-report/
Salvi SS, Barnes PJ. Chronic obstructive pulmonary disease in non-smokers. Lancet 2009;374:733-43. DOI: https://doi.org/10.1016/S0140-6736(09)61303-9
Jindal SK, Aggarwal AN, Gupta D, et al. Indian study on epidemiology of asthma, respiratory symptoms and chronic bronchitis in adults (INSEARCH). Int J Tuberc Lung Dis 2012;16:1270-7. DOI: https://doi.org/10.5588/ijtld.12.0005
Graham BL, Brusasco V, Burgos F, et al. 2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung. Eur Respir J 2017;49:1600016. DOI: https://doi.org/10.1183/13993003.00016-2016
Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report: GOLD executive summary. Am J Respir Crit Care Med 2017;195:557-82. DOI: https://doi.org/10.1164/rccm.201701-0218PP
Jones PW. Health status measurement in chronic obstructive pulmonary disease. Thorax 2001;56:880-7. DOI: https://doi.org/10.1136/thorax.56.11.880
Topalovic M, Exadaktylos V, Peeters A, et al. Computer quantification of airway collapse on forced expiration to predict the presence of emphysema. Respir Res 2013;14:131. DOI: https://doi.org/10.1186/1465-9921-14-131
Sheikh K, Coxson HO, Parraga G. This is what COPD looks like. Respirology 2016;21:224-36. DOI: https://doi.org/10.1111/resp.12611
Dal Negro RW, Turco P, Povero M. Sensitivity and specificity of various lung function parameters recommended for phenotyping COPD in clinical practice. Respir Med 2025;246:108256. DOI: https://doi.org/10.1016/j.rmed.2025.108256
Zavorsky GS, Barisione G, Gille T, et al. Enhanced detection of patients with previous COVID-19: superiority of the double diffusion technique. BMJ Open Respir Res 2025;12:e002561. DOI: https://doi.org/10.1136/bmjresp-2024-002561
Camp PG, Ramirez-Venegas A, Sansores RH, et al. COPD phenotypes in biomass smoke- versus tobacco smoke-exposed Mexican women. Eur Respir J 2014;43:725-34. DOI: https://doi.org/10.1183/09031936.00206112
Zhao D, Zhou Y, Jiang C, et al. Small airway disease: a different phenotype of early stage COPD associated with biomass smoke exposure. Respirology 2018;23:198-205. DOI: https://doi.org/10.1111/resp.13176
Mahesh PA, Jayaraj BS, Prabhakar AK, et al. Identification of a threshold for biomass exposure index for chronic bronchitis in rural women of Mysore district, Karnataka, India. Indian J Med Res 2013;137:87-94.
Holland AE, Spruit MA, Troosters T, et al. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur Respir J 2014;44:1428-46. DOI: https://doi.org/10.1183/09031936.00150314
Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J 2005;26:948-68. DOI: https://doi.org/10.1183/09031936.05.00035205
Stanojevic S, Kaminsky DA, Miller MR, et al. ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J 2022;60:2101499. DOI: https://doi.org/10.1183/13993003.01499-2021
Golpe R, Sanjuán López P, Cano Jiménez E, et al. Distribution of clinical phenotypes in patients with chronic obstructive pulmonary disease caused by biomass and tobacco smoke. Arch Bronconeumol 2014;50:318-24. DOI: https://doi.org/10.1016/j.arbr.2014.06.003
Olloquequi J, Jaime S, Parra V, et al. Comparative analysis of COPD associated with tobacco smoking, biomass smoke exposure or both. Respir Res 2018;19:13. DOI: https://doi.org/10.1186/s12931-018-0718-y
Lamprecht B, McBurnie MA, Vollmer WM, et al. COPD in never smokers: results from the population-based burden of obstructive lung disease study. Chest 2011;139:752-63. DOI: https://doi.org/10.1378/chest.10-1253
Agusti A, Bafadhel M, Beasley R, et al. Precision medicine in airway diseases: moving to clinical practice. Eur Respir J 2017;50:1701655. DOI: https://doi.org/10.1183/13993003.01655-2017
Smith BM, Kirby M, Hoffman EA, et al. Association of dysanapsis with chronic obstructive pulmonary disease among older adults. JAMA 2020;323:2268-80. DOI: https://doi.org/10.1001/jama.2020.6918
Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 2004;350:2645-53. DOI: https://doi.org/10.1056/NEJMoa032158
India State-Level Disease Burden Initiative CRD Collaborators. The burden of chronic respiratory diseases and their heterogeneity across the states of India: the Global Burden of Disease Study 1990-2016. Lancet Glob Health 2018;6:e1363-74.
Mannino DM, Buist AS. Global burden of COPD: risk factors, prevalence, and future trends. Lancet 2007;370:765-73. DOI: https://doi.org/10.1016/S0140-6736(07)61380-4
Rivera RM, Cosio MG, Ghezzo H, et al. Comparison of lung morphology in COPD secondary to cigarette and biomass smoke. Int J Tuberc Lung Dis 2008;12:972-7.
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