Concentration-dependent effects of tobacco smoke on airway inflammation and remodeling in asthmatic models.

Objective: This study aimed to investigate the effects of different concentrations of tobacco smoke on airway remodeling and airway inflammation in mouse models of asthma with distinct inflammatory phenotypes. Methods: Asthmatic mouse models were established, including an eosinophilic asthma (EA) model via ovalbumin (OVA) sensitization/challenge, a neutrophilic asthma (NA) model via OVA combined with lipopolysaccharide (LPS, 10μg) sensitization/challenge, and a mixed granulocytic asthma (MGA) model via OVA combined with LPS (0.1μg) sensitization/challenge. These mice were then exposed to tobacco environments at concentrations of 100 mg/m³ and 800 mg/m³. Body weight changes and clinical symptoms were observed and recorded. Levels of inflammatory factors (TNF-α, IFN-γ, IL-6, IL-12, MCP-1, and IL-10) in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Lung histopathological changes were assessed via hematoxylin and eosin (HE) staining, while bronchial goblet cell hyperplasia and mucus secretion were observed using periodic acid-Schiff (PAS) staining. Pulmonary fibrosis was assessed using Masson's trichrome staining. Result: Compared with the blank control group, mice in the EA, NA, and MGA model groups showed significantly reduced body weight growth rate (P < 0.001) and aggravated respiratory symptoms. Tobacco smoke exposure further exacerbated these symptoms in a concentration-dependent manner. Regarding inflammatory factors, the levels of pro-inflammatory factors (TNF-α, IFN-γ, IL-6, MCP-1, IL-12) in BALF were significantly elevated, while the level of the anti-inflammatory factor IL-10 was significantly decreased (P < 0.001) in the EA, NA, and MGA model groups. Tobacco smoke exposure significantly aggravated the airway inflammatory response in these different asthmatic models in a concentration-dependent manner. HE staining results demonstrated that tobacco smoke exposure worsened pathological injuries in the lung tissues of the different asthmatic models, including alveolar collapse, inflammatory cell infiltration, and epithelial cell necrosis, with the most severe damage observed in the 800 mg/m³ exposure group. PAS staining results revealed a significant increase in the percentage of goblet cells in the lung tissues of the different asthmatic models exposed to 800 mg/m³ tobacco smoke (P < 0.01, P < 0.05, and P < 0.01, respectively). Masson staining results showed that the degree of pulmonary fibrosis in mice from the EA model group, NA model group, and MGA model group exposed to an 800 mg/m³ tobacco environment was significantly increased (P < 0.001, P < 0.001, and P < 0.01, respectively). Conclusion: Tobacco smoke exposure exacerbates clinical symptoms, airway inflammation (by up-regulating pro-inflammatory factors and down-regulating the anti-inflammatory factor IL-10), and lung pathological damage in asthmatic mice in a concentration-dependent manner.