Impact of Different Spirometric Reference Equations on Diagnosing Respiratory Diseases in Iraqi Patients

Spirometry remains the cornerstone for diagnosing obstructive and restrictive lung disorders, yet the reference equation used to define “normal” function can significantly shift diagnostic outcomes, particularly in underrepresented populations. While the Global Lung Function Initiative (GLI) provides several equation sets, the implications of switching among them have not been fully explored in Middle Eastern populations. Therefore, the present study aimed to evaluate how diagnostic classification of respiratory disease changes when applying different GLI equations. This retrospective analysis included spirometric measures of 9,731 participants obtained at a specialized allergy and asthma center in Anbar, Iraq. The cohort comprised both patients and individuals examined for other purposes, with 4,341 males and 5,390 females, and a markedly sex-skewed smoking prevalence (28.4% in males vs. 1.6% in females). Predicted values, lower limits of normal (LLN), and z-scores were computed using the GLI Caucasian (GLI-C), GLI Other or Mixed (GLI-O), and the more recent race-neutral GLI equation (GLI-N). Diagnostic classifications for each equation were compared, stratified by sex and smoking status. GLI-C equations consistently yielded higher predicted values and more negative z-scores. The GLI-O identified more cases of obstruction, with the GLI-N producing the largest proportion of normal classifications. Reclassification was common, particularly from restrictive to normal categories. The agreement between equations ranged from 0.80 to 0.94. The choice of reference equations significantly affects spirometric interpretation among this Iraqi cohort. It is recommended that laboratories and clinics explicitly report, justify, and standardize the selected reference set, and prioritize prospective evaluations comparing GLI-N, GLI-O, and local equations with clinical correlates such as symptoms and outcomes to reduce misclassification across Middle Eastern populations.