Native American Ancestry and Air Pollution Interact to Impact Bronchodilator Response in Puerto Rican Children with Asthma.

Objective: Asthma is the most common chronic disease in children. Short-acting bronchodilator medications are the most commonly prescribed asthma treatment worldwide, regardless of disease severity. Puerto Rican children display the highest asthma morbidity and mortality of any US population. Alarmingly, Puerto Rican children with asthma display poor bronchodilator drug response (BDR). Reduced BDR may explain, in part, the increased asthma morbidity and mortality observed in Puerto Rican children with asthma. Gene-environment interactions may explain a portion of the heritability of BDR. We aimed to identify gene-environment interactions associated with BDR in Puerto Rican children with asthma. Setting: Genetic, environmental, and psycho-social data from the Genes-environments and Admixture in Latino Americans (GALA II) case-control study. Participants: Our discovery dataset consisted of 658 Puerto Rican children with asthma; our replication dataset consisted of 514 Mexican American children with asthma. Main Outcome Measures: We assessed the association of pairwise interaction models with BDR using ViSEN (Visualization of Statistical Epistasis Networks). Results: We identified a non-linear interaction between Native American genetic ancestry and air pollution significantly associated with BDR in Puerto Rican children with asthma. This interaction was robust to adjustment for age and sex but was not significantly associated with BDR in our replication population. Conclusions: Decreased Native American ancestry coupled with increased air pollution exposure was associated with increased BDR in Puerto Rican children with asthma. Our study acknowledges BDR's phenotypic complexity, and emphasizes the importance of integrating social, environmental, and biological data to further our understanding of complex disease.

Racial/Ethnic-Specific Differences in the Effects of Inhaled Corticosteroid Use on Bronchodilator Response in Patients With Asthma.

American Thoracic Society guidelines recommend inhaled corticosteroid (ICS) therapy, plus a short-acting bronchodilator, in patients with persistent asthma. However, few prior studies have examined the efficacy of this combination in children of all racial/ethnic groups. We evaluated the association between ICS use and bronchodilator response (BDR) in three pediatric populations with persistent asthma (656 African American, 916 Puerto Rican, and 398 Mexican American children). The association was assessed using multivariable quantile regression. After adjusting for baseline forced expiratory volume in one second and use of controller medications, ICS use was significantly associated with increased BDR only among Mexican Americans (1.56%, P = 0.028) but not African Americans (0.49%, P = 0.426) or Puerto Ricans (0.16%, P = 0.813). Our results demonstrate that ICS augmentation is disproportionate across racial/ethnic groups, where improved BDR is observed in Mexican Americans only. This study highlights the complexities of treating asthma in children, and reinforces the importance of investigating the influence of race/ethnicity on pharmacological response.