Lung Function Trajectory Using Race-Specific vs Race-Neutral Global Lung Function Initiative Coefficients
Authors: Darshali A. Vyas, Sophia Zhao, Peggy S. Lai, Josanna Rodriguez-Lopez, Eric P. Schmidt, Robert Brown, Kathryn A. Hibbert, Charles C. Hardin, Crystal M. North
Journal: JAMA Network Open (2025)

Importance The use of race-based coefficients in pulmonary function testing has led to the recent development of the race-neutral Global Lung Function Initiative (GLI) reference equation (hereafter GLI Global). The performance of GLI Global in comparison to race-adjusted coefficients (hereafter GLI 2012) has not been well characterized. Objective To compare the implications of GLI 2012 vs GLI Global reference equations for lung function trajectory. Design, Setting, and Participants This cohort study at Massachusetts General Hospital analyzed data of patients aged 18 to 95 years who completed spirometry testing between January 1, 1997, and December 31, 2020. Data analysis was performed from January 2023 to November 2024. Exposures GLI Global and GLI 2012 reference equations to define lung function. Main Outcomes and Measures Proportion of patients with recategorized lung function (FEV 1 and FVC) based on the 2 reference equations and their lung function trajectory over time. Lung function metrics included forced expiratory volume in the first second of expiration (FEV 1 ), forced vital capacity (FVC), and FEV 1 to FVC ratio. The z scores for FEV 1 and FVC were calculated using the GLI 2012 and GLI Global reference equations, with a score lower than −1.64 considered abnormal. Patients were categorized into 1 of 4 groups based on their z scores: normal to normal (normal z score on both equations); abnormal to normal (abnormal z score based on GLI 2012 equations but normal based on the GLI Global equation); normal to abnormal (normal z score on GLI 2012 equations but abnormal on the GLI Global equation); and abnormal to abnormal (abnormal z score on both equations). Results The sample included a total of 24 662 patients (988 Black [4.0%] and 22 297 White [90.4%] patients; 13 108 women [53.2%]) with a mean (SD) age of 57.6 (15.7) years who completed a median (IQR) of 3.0 (2.0-5.0) sets of spirometry over a median (IQR) of 2.6 (0.8-6.6) years between 1997 and 2020. Among Black patients, 190 (19.2%) had either their FEV 1 or FVC recategorized from normal to abnormal using the GLI Global reference equation. The subset of Black patients whose lung function was recategorized from normal to abnormal exhibited FEV 1 decline (−2.06%; 95% CI, −3.47% to −0.64%; P = .56) that was similar to decline in Black patients whose lung function was characterized as abnormal (−1.89%; 95% CI, −2.58% to −1.19%; P = .84) using both the GLI Global and GLI 2012 reference equations. Among White patients, 3348 (15.0%) had either their FEV 1 or FVC recategorized from abnormal to normal using the GLI Global equation. FEV 1 decline in these patients (−1.82%; 95% CI, −2.55% to −1.08%; P = .70) was similar to the decline in White patients with normal spirometry (−1.97%; 95% CI, −2.26% to −1.69%; P = .70) regardless of the reference equation used. Patterns in FVC trajectory among both Black and White participants were not consistent among participants whose spirometry was recategorized between normal and abnormal compared with those whose spirometry remained normal or remained abnormal regardless of the reference equation used. Conclusions and Relevance This cohort study found that Black patients whose lung function was recategorized from normal to abnormal using the GLI Global reference equation exhibited FEV 1 decline similar to that in Black patients whose lung function was classified as abnormal regardless of which equation was used. This finding suggests that a race-neutral approach to spirometry interpretation may allow a more accurate identification of lung pathology in Black patients.