The Mechanism of Airway Inflammation in Eosinophilic Bronchitis and Cough Variant Asthma

OBJECTIVE:To explore the characteristics of airway inflammatory cells, cytokines and inflammatory mediators in eosinophilic bronchitis (EB) and cough variant asthma (CVA) patients and to elucidate the underlying mechanism of distinct airway inflammation between EB and CVA. METHODS:This study included 15 patients with EB (EB group), 15 patients with cough variant asthma (CVA, CVA group), 14 patients with bronchial asthma (asthma group) and 14 healthy controls (healthy group). Percentage of eosinophils (EOS) in sputum induced by hypertonic saline was detected by FACS. The percentage of CD(69)(+) EOS stimulated by interleukin-5 (IL-5) and interferon γ (IFN-γ) was also detected by FACS. The expression of leukotriene C4 synthase (LTC4S) and prostaglandin-endoperoxide synthase-2 (PTGS2) mRNA in sputum was measured by real-time PCR and the concentration of leukotriene C4 (LTC4) and prostaglandin E2 (PGE2) in sputum was measured by ELISA. RESULTS:The percentage of EOS in induced sputum was 15.8 ± 3.2 (EB group), 13.0 ± 2.7 (CVA group) and 11.6 ± 4.5 (asthma group), respectively, which were significantly higher than 1.0 ± 0.4 in the healthy group. The difference was significant and the t value was 16.31, 15.23 and 14.21 respectively (P < 0.05). After stimulated by IL-5 and IFN-γ, the percentage of CD(69)(+) EOS in induced sputum was 1.5 ± 0.4 and 1.5 ± 0.5 (EB group), 1.4 ± 0.4 and 1.4 ± 0.3 (CVA group) and 1.42 ± 0.72 and 1.37 ± 0.46 (asthma group) respectively. There was no statistical significance between these 3 groups, but when compared with 0.4 ± 0.2 and 0.4 ± 0.1 in healthy group, the difference was significant (P < 0.05). The expression of IL-5 mRNA and protein in induced sputum of EB group, CVA group and asthma group were higher than the healthy group and the difference was all statistically different (P < 0.05), but there was no statistical significance between EB group, CVA group and asthma group. The expression of IFN-γ mRNA and protein in induced sputum of each group was not different when compared with healthy group (P > 0.05). The concentration of PGE2 in induced sputum of EB group was(839 ± 69) ng/L, which was higher than (33 ± 8) ng/L of CVA group, (25 ± 6) ng/L of asthma group and (24 ± 8) ng/L of healthy group (all P < 0.01). There was no statistical difference between CVA group, asthma group and healthy group. The expression of PTGS2 in induced sputum of EB group increased significantly; when compared with CVA group, asthma group and healthy group, the difference was significant (all P < 0.01). The concentration of LTC4 in induced sputum of EB group, CVA group and asthma group was all higher than the healthy group (all P < 0.05). The expression of LTC4S mRNA of EB group, CVA group and asthma group was also higher than the healthy group (all P < 0.05). The expression of LTC4S mRNA and LTC4 in the EB group was higher than that in the CVA group and the asthma group (P < 0.05). The value of LTC4/PGE2 in the CVA group and the asthma group was higher than that in the EB group (t = 8.7 and 13.1, P < 0.05). CONCLUSION:These data suggest that the difference in airway function observed in subjects with eosinophilic bronchitis and CVA (or asthma) may be due to the results of differences in PGE(2) production and an imbalance between the production of bronchoconstrictor LTC(4) and bronchoprotective PGE(2) lipid mediators.