Airway remodeling in asthma: New insights
Airway remodeling in asthma: New insights
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DOI：
10.1067/mai.2003.128
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发表时间：
2003-02-01
影响因子：
14.2
通讯作者：
Holgate, ST
中科院分区：
文献类型：
--
作者：
Davies, DE;Wicks, J;Holgate, ST
由于与西方生活方式相关的因素，哮喘在全球范围内的患病率正在增加。这种疾病的流行和慢性性质造成了巨大的经济负担。尽管在理解哮喘的炎症和免疫学成分方面取得了进展，但对哮喘肺中观察到的结构变化（气道重塑）的细胞和分子机制的理解相对较少。这些变化包括支气管平滑肌肥大、成纤维细胞转化为肌成纤维细胞和上皮下胶原沉积。哮喘患者气道重塑与支气管对不同触发因素的高反应性和肺功能长期下降的陡峭轨迹有关。直到最近，这些重塑变化一直被认为是继发性现象，在疾病过程的后期发展，作为持续炎症的结果。我们通过强调气道微环境（上皮间质营养单位）在哮喘发病中的重要性，讨论了哮喘发病机制的另一种观点。我们的建议是支持最近确定的ADAM 33作为哮喘易感基因，其表达是丰富的气道成纤维细胞和平滑肌，但缺乏T淋巴细胞或炎症细胞浸润的气道壁哮喘患者。（J Allergy Clin Immunol 2003;111：215-25.）。
Asthma is increasing in prevalence worldwide as a result of factors associated with a Western lifestyle. The prevalence and chronic nature of the disease represent significant economic burdens. Despite advances in understanding the inflammatory and immunologic components of asthma, there is relatively little understanding of the cellular and molecular mechanisms underlying the structural changes seen in the asthmatic lung (airway remodeling). These changes include hypertrophy of bronchial smooth muscle, transformation of fibroblasts to myofibroblasts, and deposition of subepithelial collagen. Airway remodeling is linked to bronchial hyperresponsiveness to diverse triggers and a steeper trajectory of long-term decrease in lung function in asthmatic patients. Until recently, these remodeling changes have been considered to be secondary phenomena, developing late in the disease process as a consequence of persistent inflammation. We discuss an alternative view of asthma pathogenesis by emphasizing the importance of the airway microenvironment (the epithelial mesenchymal trophic unit) in the origins of the disease. Our proposals are supported by the recent identification of ADAM33 as an asthma susceptibility gene, the expression of which is abundant in airway fibroblasts and smooth muscle but absent from T lymphocytes or inflammatory cells that infiltrate the airway wall in patients with asthma. (J Allergy Clin Immunol 2003;111:215-25.).