E-Cigarette Nicotine Exposure Modulates Airway Inflammation in Experimental Allergic Asthma

Introduction: Asthma affects millions worldwide and is a major public health concern. Among factors that may contribute to asthma exacerbation, the growing use of electronic cigarettes has raised concerns because of their high nicotine content and the potential for nicotine exposure to worsen disease severity. This study investigated the role of nicotine from e-cigarettes in airway inflammation in a two-hit mouse model of allergic asthma. Methods: Female C57BL/6 mice (n = 7/group) were sensitised and challenged with saline (control) or ovalbumin to induce asthma, and concurrently exposed to ambient air or e-cig aerosol with or without nicotine for 1.5 h/day over 11 consecutive days. E-liquid contained synthetic nicotine (20 mg/mL) and propylene glycol/vegetable glycerine (1:1, v/v). Bronchoalveolar lavage (BAL) fluid and lungs were collected 24 h after the final exposure to assess leukocyte infiltration and quantify nicotine by LC–MS/MS. Ethics approval: CEUA-IOC (L-002/2020-A10). Results: Air-exposed asthmatic mice exhibited eosinophilic airway inflammation. Exposure to nicotine-containing e-cig aerosol further increased BAL leukocytes and shifted the inflammatory profile towards neutrophilia (17.2 ± 4.8 vs. 6.1 ± 1.9 × 10⁵ cells/BAL; p < 0.001). Asthmatic mice exposed to nicotine-containing aerosol also showed higher lung nicotine accumulation than non-asthmatic controls (28.4 ± 6.6 vs. 10.0 ± 2.7 ng/g; p < 0.01). Conclusion: Short-term exposure to nicotine-containing e-cig aerosol promoted nicotine accumulation in inflamed lungs and exacerbated airway inflammation, shifting the inflammatory phenotype from eosinophilic to neutrophilic. Prior investigations robustly indicate that neutrophilic asthma is associated with greater disease severity and reduced responsiveness to standard corticosteroid treatment, highlighting the potential risks of e-cig exposure for individuals with asthma. Financial Support: CAPES; FIOCRUZ.