Respiratory health outcomes following co-exposure to subchronic high temperature, episodic wildfire smoke exposure, and high-cholesterol diet

BACKGROUND: Increased ambient temperature alongside concomitant heatwaves and wildfire smoke imperil human health. We examined whether long-term episodic exposure to wildfire smoke induced greater respiratory injury/inflammation in male rats subchronically housed at elevated temperature or consuming unhealthy, cholesterol-rich diets. Respiratory effects of wildfire eucalyptus smoke exposure (WFES; ∼7mg/m3 particulate matter) were assessed 2h and 24h post-exposure in rats housed at 22 °C (room temperature; RT) consuming normal diet (ND) and exposed to filtered air (FA) or WFES for 1h. METHODS: To determine effects of ongoing exposure, 4-5-week-old rats were subchronically housed at RT or high temperature (HT; 30-31°C) and fed ND or high-cholesterol (2%) diet (HCD). Rats were episodically exposed to FA or WFES 1h/d, 1d/wk, for 12-13wk. 48h after final exposure, bronchoalveolar lavage fluid (BALF) lung injury and inflammation, gene expression, and lung/nasal pathology were assessed. RESULTS: Acute WFES exposure increased BALF markers of lung injury and neutrophilic inflammation. Subchronic HT resulted in >30% lower weight gain and decreased body fat relative to RT; effects were greater in episodically WFES-exposed rats. Whole body plethysmography revealed HT-induced changes in breathing parameters; WFES exacerbated these effects. Small effects were observed on BALF markers of lung injury/inflammation, consistent with minimal pathological findings in lung and nasal cavity. All three stressors, individually and in combination, inhibited gene expression of proteins involved in glucocorticoid-mediated regulation of neuroendocrine stress response and peripheral homeostatic physiology. CONCLUSION: These findings suggest functional impairment at HT, exacerbated by WFES, linked to dysregulation of stress without affecting structural integrity of respiratory tract.