Sex-Stratified Correlates of Pulmonary Function in Mexican Children and Adolescents (6-17 Years) with Asthma: An Exploratory Analysis of HDL Cholesterol, BMI, and Pubertal Stage.

Background/Objectives: Pubertal maturation encompasses hormonal, somatic, and metabolic alterations that may influence pulmonary function in children with asthma. We evaluated the correlates of pulmonary function in pediatric asthma using sex-stratified analyses of pubertal stage, BMI z-score, asthma control (ACQ-6), and HDL cholesterol levels on FEV1, FVC, and the FEV1/FVC ratio (% predicted, NHANES III). Methods: A cross-sectional study was conducted with 118 children and adolescents with asthma (74 males and 44 females). The Tanner stages were categorized as pre-/early (I-II), mid (III), and late (IV). No participant had reached Tanner stage V at recruitment, and the reference category was composed predominantly of Tanner II participants; therefore, the pubertal contrast reflected early- versus mid-/late-pubertal physiology rather than a strictly prepubertal-versus-pubertal comparison. We performed hierarchical linear regression with bias-corrected and accelerated bootstrap inference (5000 replicates) for each sex and for all participants combined, complemented by a formal sex × predictor interaction test. Results: Mid- and late puberty were independently associated with reduced FEV1% and FVC% (β -0.25 to -0.31), without affecting the FEV1/FVC ratio. Sex-stratified analyses were exploratory and identified apparently divergent predictor sets by sex: in males, the pubertal stage was significant in FEV1% and FVC% (β -0.30 to -0.42), whereas the BMI z-score diminished the FEV1/FVC ratio (β = -0.274). In females, FEV1% was associated with HDL-c (β = 0.463), BMI z-score (β = 0.429), and ACQ-6 score (β = -0.306); the female FEV1/FVC% model showed a substantial apparent effect (Cohen's f2 = 0.508), with ACQ-6 score and HDL-c as primary associated variables. The formal sex × predictor interaction test in the combined sample, however, did not reach statistical significance (ΔR2 = 0.037; p = 0.178), indicating that the sex-differential patterns observed in the stratified models were not confirmed as effect modifications. Conclusions: Sex-stratified exploratory analyses in this pediatric asthma cohort identified apparently divergent patterns of associations in males and females; however, the formal interaction test was not statistically significant, indicating that these stratified differences were not confirmed and require validation in adequately powered prospective cohorts. These findings identify HDL-c, body composition, and symptom control as candidate correlates of pulmonary function, with potential sex-related differences warranting further investigation.