Race-neutral GLI-2022 interpretation in GOLD-positive COPD: reclassification in a Jordanian clinical cohort
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Walid Al-Qerem1, Anan Jarab2, Khaled Al Oweidat3
1Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.
Background:
Diagnostic interpretation of chronic obstructive pulmonary disease (COPD) depends on the reference equation used to define airflow obstruction. This study examined how often race-neutral Global Lung Initiative (GLI-2022) lower-limit-of-normal (LLN) interpretation reclassified clinically confirmed COPD patients meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as non-obstructed. GLI-2012 Caucasian, GLI-2012 Other/Mixed, and local Jordanian equations were secondary comparators.
Methods:
This cross-sectional study included 845 patients aged ≥40 years with newly diagnosed, clinically confirmed COPD attending Jordan University Hospital, Amman, between August 2025 and March 2026. Diagnosis incorporated compatible symptoms, clinical history, post-bronchodilator FEV1/FVC <0.70, and additional investigations when clinically indicated. Patients with asthma or suspected asthma-COPD overlap were excluded. Predicted values, LLNs, and z scores were computed for each reference equation. Reclassification was examined across FEV1/FVC bands and using an adjusted bias-reduced logistic model.
Results:
Of 845 clinically confirmed COPD patients, 224 (26.5%) did not meet the GLI-2022 LLN criterion for airflow obstruction, compared with 262 (31.0%) using GLI-2012 Caucasian, 174 (20.6%) using GLI-2012 Other/Mixed, and 13 (1.5%) using the Jordanian equation. GLI-2022 classified 621 patients as obstructed (73.5%; 95% CI 70.4-76.4), and all three paired comparisons with GLI-2022 were statistically significant (exact McNemar p < 0.001). GLI-2022 reclassification increased from 2.8% at ages 40-49 years to 46.0% at ≥80 years and was concentrated in the post-bronchodilator FEV1/FVC 0.65-0.699 band.
Conclusion:
Over a quarter of patients with clinically confirmed COPD in this cohort did not meet the GLI-2022 LLN criterion for airflow obstruction. GLI-2022 LLN-negative status should not be used in isolation to negate a COPD diagnosis established through guideline-based clinical assessment.
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