Sex-specific modulation of lung function and transcriptome in neonate mice exposed to thirdhand electronic-cigarette aerosols.

backgroundVaping is increasingly prevalent among young adults at age for starting families. Thirdhand e-cigarette aerosols (THEA) are persistent residues that adhere to indoor surfaces and can resuspend in air. Since lung development continues after birth, infants from homes with adults who vape, are vulnerable to THEA exposures.

methodsNeonate mice were exposed to THEA with nicotine or nicotine + tobacco-flavoring from terrycloth and carpet for the first 21 days of life. We assessed broncho-alveolar lavage cytology, lung morphometry, gene expression, and intestinal microbiomes at 21 days. At 10 weeks, we evaluated lung function.

resultsWe showed that exposures to THEA during alveologenesis, a critical window of lung development, induced sex-specific alterations in pulmonary inflammatory and developmental trajectories. Females exhibited acute pulmonary neutrophilic inflammation with a resolving cytokine profile. In contrast, males exhibited upregulation of genes associated with pulmonary inflammation and epithelial mesenchymal transition, plus delayed lung development, leading to lung dysfunction in adulthood. Male gut microbiomes showed reduced abundance of taxa associated with xenobiotic biotransformation, suggesting host-microbial detoxification capacity as a target of THEA exposure.

conclusionLow-level of THEA exposures in early life can alter lung inflammation, structure, and function, increasing susceptibility to respiratory dysfunction later in life. IMPACT: Early-life exposures to nicotine and carbonyls from thirdhand e-cigarette aerosols (THEA) may induce alterations in lung alveologenesis and augment susceptibility to lung conditions later in life. Using a preclinical model of pediatric airways, we showed that THEA exposures caused neutrophilic inflammation in neonate female mice. In neonate male mice, THEA exposures led to alterations in lung structure, gene expression, and gut microbiome dysbiosis. Adult male mice exposed to THEA as neonates exhibited decline in lung function characteristic of obstructive pulmonary physiology.