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

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

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

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.

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.

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.