Kelly Margaret M, Chakir Jamila, Vethanayagam Dilini, Boulet Louis-Philippe, Laviolette Michel, Gauldie Jack, O'Byrne Paul M
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Chest. 2006 Sep;130(3):741-53. doi: 10.1378/chest.130.3.741.
Airway remodeling is believed to be important in the pathophysiology of asthma, and myofibroblasts are increased in the airways of asthmatic individuals 24 h after allergen challenge. Leukotriene receptor antagonists exert antiinflammatory activity in asthma, but it is unknown whether they influence indices of airway remodeling. In the present study, we evaluated the effect of montelukast on airway myofibroblasts following low-dose allergen challenge (LDAC).
Stable subjects with mild asthma were included in a two-center, randomized, parallel-group study. A 2-week run-in period was followed by LDAC and endobronchial biopsy. Subjects were then randomized to receive either montelukast, 10 mg/d, or placebo (n = 10 in each group) for 8 weeks in a double-blind manner; at the end of the treatment period, subjects underwent a second LDAC and endobronchial biopsy. The effect of treatment on myofibroblasts, fibroblasts, and inflammatory cells was examined using electron microscopy techniques.
Treatment with montelukast showed no significant difference by comparison with placebo but did show a significant within-group treatment-related decrease in airway wall myofibroblasts not seen in the placebo group. In addition, the montelukast-treated group also showed a significant within-group reduction in lymphomononuclear cells and increased neutrophils.
The results suggest that montelukast has an inhibitory effect on airway structural cells that play a key role in airway remodeling in allergic airway inflammation, and that montelukast may be a useful therapy to attenuate airway remodeling in asthma.
气道重塑被认为在哮喘的病理生理学中起重要作用，在变应原激发后24小时，哮喘患者气道中的肌成纤维细胞会增加。白三烯受体拮抗剂在哮喘中发挥抗炎活性，但它们是否影响气道重塑指标尚不清楚。在本研究中，我们评估了孟鲁司特对低剂量变应原激发（LDAC）后气道肌成纤维细胞的影响。
轻度哮喘稳定期患者纳入一项两中心、随机、平行组研究。经过2周的导入期后进行LDAC和支气管内活检。然后将受试者随机分为两组，以双盲方式分别接受10mg/d孟鲁司特或安慰剂治疗8周（每组10例）；在治疗期结束时，受试者接受第二次LDAC和支气管内活检。使用电子显微镜技术检查治疗对肌成纤维细胞、成纤维细胞和炎性细胞的影响。
与安慰剂相比，孟鲁司特治疗无显著差异，但确实显示出气道壁肌成纤维细胞在组内有与治疗相关的显著减少，而安慰剂组未见此现象。此外，孟鲁司特治疗组还显示组内淋巴细胞单核细胞显著减少，中性粒细胞增加。
结果表明，孟鲁司特对在过敏性气道炎症中气道重塑起关键作用的气道结构细胞具有抑制作用，孟鲁司特可能是减轻哮喘气道重塑的有效疗法。
