Airway transcriptome networks for ozone and PM_2.5 exposure reveal distinct key drivers for children with asthma

Air pollution disproportionately affects individuals with asthma, triggering asthma exacerbations and morbidity. We hypothesized that children with and without asthma have distinct airway transcriptome networks associated with ozone and particulate matter ≤ 2.5 µm (PM_2.5) exposure.

We recruited children from the New York metropolitan area, mapped their air pollutant exposures, and collected nasal and bronchial samples for transcriptome and cellular profiling. We used causal network construction and key driver analyses to build airway transcriptome networks for ozone and PM_2.5 exposure.

The cohort included 307 children, including 167 (54.4%) with asthma and 140 (45.6%) without asthma. The mean age was 13.4 years (SD 4.4 years). Among children with asthma, the airway causal network and its key drivers represented pro-inflammatory adaptive immune processes. Six key driver transcripts for ozone (CLC, CPA3, FGL2, LGALS12, IL7R, HRH4) and three key driver transcripts for PM_2.5 (TNFRSF10C, FGL2, EVI2B) were identified. Nasal expression of CLC and CPA3 positively correlated with respective bronchial expression and bronchial eosinophil abundance. Bronchial expression of TNFRSF10C positively correlated with bronchial neutrophil abundance. In striking contrast, among healthy children, key drivers for the ozone network were enriched for DNA repair and immune regulation.

Children with and without asthma have very distinct causal networks and key drivers for ozone and PM_2.5 exposure. The identified key drivers represent high-yield targets for intervention and treatment of pollutant-exacerbated asthma.