Systematic misclassification of lung function in Indian adolescents using GLI-2012 reference equations: evidence from the multicity APEAL cohort

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Background Accurate spirometric interpretation depends on appropriate reference equations. The Global Lung Function Initiative (GLI-2012) equations are widely used internationally, but South Asian populations were sparsely represented in their derivation and their applicability in Indian adolescents remains uncertain. Methods We performed a cross-sectional analysis of baseline data from the multicity Air Pollution Exposure on Adolescents’ Lungs cohort. Healthy, non-smoking school-going adolescents aged 11–14 years from Delhi, Mumbai, Bengaluru and Mysuru underwent spirometry using standardised American Thoracic Society/European Respiratory Society procedures. GLI-2012 z-scores for forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC were calculated using the Asian reference category. Fit was assessed using mean z-scores and the proportion below the lower limit of normal (LLN; z<−1.645). Results Among 4175 adolescents (2148 males), mean z-scores were −2.44 (SD 1.27) for FEV 1 , −1.34 (0.93) for FVC and −0.78 (1.11) for FEV 1 /FVC, all well outside the accepted ±0.5 range for adequate fit. Overall, 74.6% were below the LLN for FEV 1 , 36.8% for FVC and 19.3% for FEV 1 /FVC, compared with the expected 5% in a well-calibrated healthy population. The leftward shift in z-score distributions was consistent across sex, city, age, height and body mass index strata. Conclusion GLI-2012 equations, as currently applied in the absence of South Asian-specific references, demonstrated substantial calibration mismatch relative to this cohort of Indian adolescents and risk major overclassification of low lung function. Population-specific validation and recalibration are needed before routine clinical or epidemiological use in this population.