Sex-specific lung inflammation and mitochondrial damage in a model of electronic cigarette exposure in asthma

The prevalence of electronic cigarette (EC) use among adult with asthma has continued to increase over time, in part due to the belief of being less harmful than smoking. However, the extent of their toxicity and the involved mechanisms contributing to the deleterious impact of EC exposure on patients with preexisting asthma have not been delineated. In the present project, we tested the hypothesis that EC use contributes to respiratory damage and worsening inflammation in the lungs of patients with asthma. To define the consequences of EC exposure in established asthma, we used a mouse model with/without preexisting asthma for short-term exposure to EC aerosols. C57/BL6J mice were sensitized and challenged with a DRA (dust mite, ragweed, Aspergillus fumigates, 200 mu g/mL) mixture and exposed daily to EC with nicotine (2% nicotine in 30:70 propylene glycol: vegetable glycerin) or filtered air for 2 wk. The mice were evaluated at 24 h after the final EC exposure. After EC exposure in asthmatic mice, lung inflammatory cell infiltration and goblet cell hyperplasia were increased, whereas EC alone did not cause airway inflammation. Our data also show that mitochondrial DNA (mtDNA) content and a key mtDNA regulator, mitochondrial transcription factor A (TFAM), are reduced in asthmatic EC-exposed mice in a sex-dependent manner. Together, these results indicate that TFAM loss in lung epithelium following EC contributes to male-predominant sex pathological differences, including mitochondrial damage, inflammation, and remodeling in asthmatic airways.