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.