Persistent exposure to second-hand smoke and asthma endotypes in a study of Puerto Rican youth

Abstract

Background: Little is known about second-hand smoke (SHS) exposure and asthma endotypes in children and adolescents.

Objective: To evaluate the relation between exposure to SHS and asthma endotypes in Puerto Rican youth.

Methods: Longitudinal study of 337 Puerto Rican youths with (n = 173) and without (n = 164) asthma who completed a first visit at ages 6 to 14 years and a second visit at ages 9 to 20 years. Exposure to SHS was defined as: in early life only, at school age only (at either study visit only), and persistent (in early life and at school age). On the basis of nasal epithelial expression of 8 "signature genes" for T_H2 and T_H17 immunity, 3 asthma endotypes were identified at the second visit: T_H2-high, T_H17-high, and T_H2-low/T_H17-low. Percent (%) predicted lung function was calculated using GLI-2021 equations. Gene Ontology (Gene Ontology Consortium) pathway enrichment analysis was used to characterize endotype-associated pathways.

Results: In a multivariable analysis, youths with persistent SHS exposure had 2.2 times higher odds of T_H17-high asthma (95% CI = 1.01-4.71) and 2.6 times higher odds of T_H2-low/T_H17-low asthma (95% CI = 1.15-5.91) than controls without SHS exposure. Among participants with T_H2-low/T_H17-low asthma, youths with persistent SHS exposure had 6.6% to 13.7% significantly lower %predicted forced expiratory volume in 1 second (FEV₁) and %predicted FEV₁/forced vital capacity than those never exposed to SHS. Mitochondrial and oxidative stress pathways were revealed to underlie the estimated effects of SHS exposure.

Conclusion: In Puerto Rican youths, persistent SHS exposure was associated with T_H17-high and T_H2-low/T_H17-high asthma, and with lower FEV₁ and FEV₁/forced vital capacity in participants with T_H2-low/T_H17-high asthma.