[Effects of epidermal growth factor receptor on airway inflammation in a rat asthmatic model].

OBJECTIVE: To explore the possible roles of epidermal growth factor receptor (EGFR) in the process of acute and chronic airway inflammation in a rat asthmatic model. METHODS: Forty-five Sprague-Dawley (SD) rats were randomly divided into control groups (subgroups A1, A2, A4), asthmatic groups (subgroups B1, B2, B4) and treatment groups (subgroups C1, C2, C4), with 5 mice in each subgroup. Mice in the asthmatic and treatment groups were exposed to OVA challenge for 1 week, 2 weeks and 4 weeks. Rats in the treatment groups received intraperitoneal injection of a tyrosine kinase inhibitor Genistein (Rongli China) with the dose of 20 mg/kg 1 hour before OVA exposure. Total cell counts and cell differentials in bronchoalveolar lavage fluid (BALF) were performed. A semi-quantified method of airway inflammation score was used to evaluate airway inflammation by hematoxylin-eosin (HE) staining. Expression of EGFR and tyrosine phosphorylation (EGFR activation) in airway epithelium at different times of OVA exposure were evaluated by immunohistochemical and immunofluorescence. All data were expressed as mean +/- SD. One-way ANOVA was used for comparison between 2 groups and post-hoc multiple comparisons of means were performed by using Least Significant Difference. RESULTS: (1) The total cell counts and cell differentials in the BALF of subgroups B1, B2 and B4 were higher than those of subgroups A1, A2 and A4. The total cell counts and eosinophils (EOS) in the BALF of subgroups C1, C2, and C4 [Total cells (48 +/- 6) x 10(5), (51 +/- 9) x 10(5), (57 +/- 12) x 10(5); EOS (2.5 +/- 0.5) x 10(5), (2.7 +/- 0.6) x 10(5), (2.6 +/- 0.5) x 10(5), respectively] decreased significantly as compared to those of subgroups B1, B2 and B4 [Total cells (70 +/- 10) x 10(5), (88 +/- 8) x 10(5), (72 +/- 10) x 10(5); EOS (5.6 +/- 0.8) x 10(5), (6.6 +/- 0.6) x 10(5), (4.3 +/- 0.4) x 10(5)], all P < 0.05. There was no significant difference in the counts of neutrophils and lymphocytes in BALF between the treatment groups and the asthmatic groups. The count of epithelial cells in group C1 [(2.5 +/- 0.5) x 10(5)] was lower than that in group B1[(4.9 +/- 0.7) x 10(5)], q = 4.671, P < 0.05. But that in group C4[(5.7 +/- 1.2) x 10(5)] was higher than that in group B4 [(4.3 +/- 0.4) x 10(5)], q = 4.012, P < 0.05. (2) The airway inflammation score in group C4(3.6 +/- 0.6) was less than that in group B4(5.1 +/- 0.6), q = 4.923, P < 0.05. The scores of group C1 and C2 were less than those of group B1 and B2, but the differences did not reach statistical significance. (3) The expression of EGFR and tyrosine phosphorylation in airway epithelium of the OVA sensitized subgroups were increased statistically as compared to the control subgroups (all P < 0.05). Genistein decreased tyrosine phosphorylation of EGFR in subgroups C1, C2 and C4[(3.12 +/- 0.24), (3.00 +/- 0.28), (2.69 +/- 0.54)] as compared to subgroups B1, B2 and B4[(3.69 +/- 0.43), (3.57 +/- 0.29), (4.46 +/- 0.47), respectively] (all P < 0.05). (4) There were positive correlations between expression and activation of EGFR in airway epithelium and total cell counts, EOS counts, neutrophil and lymphocyte counts in BALF, and airway inflammation scores (all P < 0.05). CONCLUSIONS: EGFR is involved in airway inflammation of asthmatic rats. Tyrosine kinase inhibitor Genistein inhibits acute and chronic airway inflammation in the asthmatic model.

[Evaluation of the clinical efficacy and the safety of salmeterol/fluticasone propionate accuhaler compared to budesonide turbuhalar in the control of adult asthma].

OBJECTIVE: To evaluate the efficacy and the safety of low dose salmeterol/fluticasone (SM/FP) combination therapy as compared to morate dose of budesonide (BUD) in the management of adult asthma. METHODS: A multicentre, randomised, open-label, parallel-group, 6-week treatment study was conducted. 398 patients (18 - 70 years) were given SM/FP (50/100 microg) twice daily via Accuhaler or BUD 400 microg twice daily via Turbuhaler. RESULTS: The morning and the evening peak expiratory flow (PEF) measurements both increased significantly (P < 0.01) in the SM/FP group, and the increase was greater than that in the BUD group. The significant benefit of SM/FP was evident from the first week. SM/FP led to a more significant reduction in the use of rescue medication and in the day- and night-time asthma symptom scores, as compared to budesonide. Both treatments were well tolerated, and the adverse reactions showed no significant difference between the two groups. CONCLUSIONS: Combination use of low doses of SM/FP is a better choice for the control of asthma. The addition of a low-dose long-acting beta(2) agonist is superior to the simple increase of the dosage of inhaled corticosteroids.

[Effect of tyrosine kinase inhibitors on airway remodeling in bronchial asthma].

OBJECTIVE: To investigate the effect of tyrosine kinase inhibitors (TKIs) on asthmatic rat airway remodeling. METHODS: The inhibitive effects of three TKIs (Genistein, jin-zhuan-ting and Tyrphostin AG1478) on proliferation of primary cultures of rat tracheal epithelial cells were assessed by MTT assay. Then, jin-zhuan-ting was adopted in the asthmatic rat model; immunohistofluorescene method was used to stain phosphorylated tyrosine (P-tyr) for disclosing the activation of EGFR; Sirius Red staining of submucosal collagen I and III was performed, and an analysis was made on the correlation between EGFR activation and collagen I and III deposition. RESULTS: All the three TKIs inhibited the growth of tracheal epithelial cells in a time and dose depending manner, and the inhibition rates among them showed no statistical differences; airway subepithelial collagen I and III deposition degrees were markedly elevated in asthmatic groups and jin-zhuan-ting reduced the deposition in a certain degree; EGFR activation (P-tyr) in airways epithelium of asthmatic groups was greatly increased in comparison with that of control groups, and it was evidently decreased in jin-zhuan-ting groups. Correlation analysis demonstrated that the amount of airway subepithelial collagen I and III was positively correlated to EGFR activation. CONCLUSION: TKIs may have preventive implications for asthmatic airway remodeling.