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.

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.