Applicability of the Global Lung Initiative 2022 Spirometry Reference Equation Among Healthy Preschool-Aged Children...

The Global Lung Initiative (GLI) Global 2022 spirometry equations do not require race selection at the point of interpretation, but their applicability in Middle Eastern preschool populations remains uncertain. Therefore, the present study aims to assess the applicability of the GLI global (2022) (GLI-2022) reference equations in a large sample of healthy Jordanian preschool-aged children and compare them with historically labeled GLI-2012 Caucasian (GLI-C) and Other/Mixed (GLI-O) equations.

A cross-sectional study was conducted with 911 healthy children (461 boys, 450 girls; age range 3-6 years) recruited from various regions in Jordan. Anthropometric and spirometric data (FEV₁, FVC, FEV₁/FVC) were collected according to ATS/ERS standards. Race and ethnicity were not collected and were not used to assign equations. Instead, all participants were evaluated using each of the three equation sets. Z-Scores for each parameter were derived using the GLI-2022, GLI-C, and GLI-O equations. The validity of each equation set was evaluated by analyzing Z-score normality, performing regression analyses to detect residual bias from age and height, and assessing agreement in diagnostic classifications using Cohen's Kappa and Bland-Altman plots.

The GLI-C equations demonstrated the closest statistical fit, with mean FEV₁ and FVC Z-scores closely centered on zero for both boys and girls. In contrast, the GLI-2022 and GLI-O equations produced significantly positive mean Z-scores for FEV₁ and FVC in both sexes (p < 0.001), indicating a systematic overestimation of lung function. The GLI-2022 equations showed significant residual anthropometric bias, with Z-scores remaining dependent on height and/or age (p < 0.01). Furthermore, the results indicated that diagnostic agreement between equations was inconsistent.

The GLI-2022 race-neutral equations are not a suitable fit for preschool Jordanian children, and their use may lead to clinically significant misinterpretation of spirometric tests. These findings emphasize the critical need for population-specific reference equations for this population.