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哮喘治疗对气道重塑有什么影响? 当前的观点。

What effect does asthma treatment have on airway remodeling? Current perspectives.

机构信息

Department of Medicine, Section of Allergy Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792, USA.

出版信息

J Allergy Clin Immunol. 2011 Sep;128(3):439-48; quiz 449-50. doi: 10.1016/j.jaci.2011.06.002. Epub 2011 Jul 12.

Abstract

Airway remodeling, or structural changes of the airway wall arising from injury and repair, plays an important role in the pathophysiology of asthma. Remodeling is characterized as structural changes involving the composition, content, and organization of many of the cellular and molecular constituents of the bronchial wall. These structural changes can include epithelial injury, subepithelial thickening/fibrosis, airway smooth muscle hyperplasia, goblet cell hypertrophy and hyperplasia, and angiogenesis. Historically, these changes are considered a consequence of long-standing airway inflammation. Recent infant and child studies, however, suggest that remodeling occurs in parallel with inflammation in asthmatic subjects. Despite advancements in the recognition of key cellular and molecular mechanisms involved in remodeling, there remains a paucity of information about which treatments or interactions are most likely to regulate these processes. Furthermore, it is unclear as to when is the best time to initiate treatments to modify remodeling, which components to target, and how best to monitor interventions on remodeling. Indeed, inhaled corticosteroids, which are generally considered to have limited influence on remodeling, have been shown to be beneficial in studies in which the dose and duration of treatment were increased and prolonged, respectively. Moreover, several studies have identified the need to identify novel asthma indices and phenotypes that correlate with remodeling and, as a consequence, might specifically respond to new therapies, such as anti-IgE, anti-IL-5, and anti-TNF-α mAbs. Our review will evaluate the development of remodeling in asthmatic subjects and the effects of treatment on these processes.

摘要

气道重塑,即气道壁结构因损伤和修复而发生的改变,在哮喘的病理生理学中起着重要作用。重塑的特征是结构变化,涉及支气管壁许多细胞和分子成分的组成、含量和组织。这些结构变化可包括上皮损伤、黏膜下增厚/纤维化、气道平滑肌增生、杯状细胞肥大和增生以及血管生成。从历史上看,这些变化被认为是长期气道炎症的结果。然而,最近的婴儿和儿童研究表明,在哮喘患者中,重塑与炎症同时发生。尽管在认识参与重塑的关键细胞和分子机制方面取得了进展,但对于哪些治疗或相互作用最有可能调节这些过程,仍知之甚少。此外,尚不清楚何时是开始治疗以改变重塑的最佳时机,应针对哪些成分进行治疗,以及如何最好地监测对重塑的干预措施。事实上,尽管吸入性皮质类固醇通常被认为对重塑的影响有限,但在分别增加和延长治疗剂量和持续时间的研究中,它们已被证明是有益的。此外,有几项研究确定了需要确定与重塑相关的新型哮喘指标和表型,并且作为结果,可能会对新型疗法(如抗 IgE、抗 IL-5 和抗 TNF-α mAb)有特异性反应。我们的综述将评估哮喘患者中重塑的发展以及治疗对这些过程的影响。

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