Traffic-related air pollution induces non-allergic eosinophilic airway inflammation and cough hypersensitivity in guinea-pigs.
BACKGROUND:The pathogenesis and pathophysiology of eosinophilia-related chronic cough such as non-asthmatic eosinophilic bronchitis and cough variant asthma are still not clear. OBJECTIVE:This study is to examine the potential role of traffic-related air pollution (TRAP) in eosinophilic inflammation and cough responses. METHODS:Non-sensitized guinea-pigs were exposed to TRAP in an urban traffic tunnel or kept in a filtered air environment for 7 or 14 days. Reflexive cough was measured using citric acid and allyl isothiocyanate (AITC) challenges, respectively. Spontaneous cough counting was determined using audio recording and a waveform analysis. Airway inflammation was evaluated using differential cells in bronchoalveolar lavage fluid (BALF) and lung histopathology. To further elucidate the relationship between airway inflammation and cough hypersensitivity, a subgroup of those exposed for 14 days received a dexamethasone treatment. RESULTS:Compared to reflexive cough count (mean (95% confidence interval) in 10 minutes) provoked by the AITC challenge for the unexposed animals (3.1 (1.7-4.5)), those were increased significantly following both the 7-day (12.0 (6.8-17.2), P < 0.01) and the 14-day (12.0 (6.4-17.6), P < 0.01) TRAP exposure. The effect provoked by the citric acid challenge was more profound following the 14-day exposure (26.0 (19.5-32.5) vs 3.8 (1.5-6.0) for the control, P < 0.001). TRAP exposures enhanced spontaneous cough events, caused a significant increase of eosinophils and neutrophils in BALF and resulted in a dramatic eosinophilic infiltration in submucosal layer of trachea and bronchus, which can be inhibited significantly by dexamethasone treatment. CONCLUSIONS & CLINICAL RELEVANCE:TRAP exposures induced cough hypersensitivity and non-allergic eosinophilic inflammation of airways in guinea-pigs. This study highlights the potential mechanisms of eosinophilia-related chronic cough that can be induced by traffic-related air pollution.
Fang, Z; Huang, C; Zhang, JJ; Xie, J; Dai, S; Ge, E; Xiang, J; Yao, H; Huang, R; Bi, X; Wang, B; Zhong, N; Lai, K
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