哮喘治疗对气道重构的影响:当前观点
2011/08/30
摘要
由气道损伤和修复导致的气道重构或气道壁结构改变,在哮喘的病理生理学中具有重要作用。气道重构主要表现为气道结构变化,包括支气管壁的细胞和分子组成成分、含量和排列的变化。这些结构变化包括上皮损伤、上皮下增厚/纤维化、气道平滑肌增生、杯状细胞肥厚和增生以及血管新生。过去,这些变化被认为是由于长期气道炎症所导致的。近期对婴儿和儿童进行的研究显示,气道重构与哮喘患者的炎症症状同时出现。尽管对于参与气道重构的关键细胞和分子机制研究有所进展,但关于哪些哮喘治疗或治疗间的相互作用最有可能调节这些过程,目前尚未完全清楚。此外,有关采取治疗措施调节重构的最佳时间,哪些组成部分可作为治疗靶点以及如何更好的监测干预措施对重构的影响,目前也仍不清楚。实际上,皮质激素吸入治疗一般认为对气道重构的影响有限。在那些研究与气道重构相关的新哮喘指标和表现型,以对新治疗措施(IgE单克隆抗体、IL-5单克隆抗体和TNF-α单克隆抗体)产生特异性疗效的研究中,结果显示皮质激素吸入治疗对患者有益。本综述将评价哮喘患者气道重构的发生过程以及哮喘治疗对该过程的影响。
(刘国梁 审校)
J Allergy Clin Immunol. 2011 Jul 11. [Epub ahead of print]
What effect does asthma treatment have on airway remodeling? Current perspectives.
Durrani SR, Viswanathan RK, Busse WW.
Source
Department of Medicine, Section of Allergy Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
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.
J Allergy Clin Immunol. 2011 Jul 11. [Epub ahead of print]
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哮喘患者支气管上皮屏障功能缺陷
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内毒素暴露和儿童期喘息和哮喘:对观察性研究的荟萃分析