Airway remodelling in asthma, like vascular remodelling in atherosclerotic disease, is thought to occur in response to repeated inflammatory insults, and ultimately contributes to the pathophysiology of the disease. In asthma, these structural changes are many, and include thickening of the airway wall, associated with loss of epithelial organisation, goblet cell hyperplasia, subepithelial fibrosis, increased vascularisation, fibroblast and myofibroblast proliferation, and smooth muscle hyperplasia and/or hypertrophy. Several of these structural changes are increasingly thought to play a role in airway dysfunction in asthma1。
While the concept that most, if not all, components of airway wall remodelling develop as a result of ongoing inflammatory events seems entirely plausible, direct support for this is relatively sparse in asthma literature. Moreover, this is not an easy issue to address experimentally, as by the time patients present to their physician and are diagnosed with asthma, they usually display markers of airway remodelling processes similar to those in patients with long-standing asthma2。因此,一些研究人员转向动物模型,在长时间气道过敏原挑战期间,气道重塑的特定方面已被诱导。本期的一个这样的模型是European Respiratory Journal克里斯蒂等。3。该模型与其他几个模型相似,因为小鼠对卵蛋白(OVA)敏感,然后在几周的时间内与OVA挑战。该模型和其他类似模型的结果是,每种过敏原挑战都与炎症事件相似,类似于哮喘气道中的炎症事件,尤其是在疾病加剧期间发生的炎症事件。克里斯蒂(Christie等。3已经确认了自己和其他实验室的透水观察结果,这些观察结果重复过敏原挑战导致气道壁的结构变化以及气道高反应性。
克里斯蒂解决的具体问题等。3是通过与皮质类固醇氟替卡酮同时治疗可预防受到慢性过敏蛋白挑战的小鼠中观察到的重塑和功能变化。他们观察到,在过敏原挑战开始时开始的治疗可有效预防气道壁层粘连蛋白的增加,但有趣的是,无效防止气道高反应性。这一观察结果是,与皮质类固醇的伴随治疗能够显着减少气道墙重塑的一个方面,这与慢性过敏原挑战大鼠模型中先前的观察结果一致4。Interestingly, in that study, treatment was also effective at preventing airway hyperresponsiveness. Why this was not the case in the Christie等。3study is not clear, although as assessment of airway function was within 24 h of the most recent allergen challenge, it is not possible to say whether the observed dysfunction was secondary to the presence of inflammatory mediators or to structural abnormalities, or even an unrelated factor.
The results of the studies of Christie等。3还有Vanacker等。4, as well as previous observations that anti-leukotriene agents are capable of preventing allergen-induced airway wall structural changes5,指出一种潜在的哮喘管理方法。实际上,如果气道墙重塑的某些方面在功能上很重要,那么是否应该制定治疗策略来防止这种发展?这将与当前哮喘治疗的方法完全不同6。For one thing, this approach would require a screening process, where indices of airway remodelling are identified prior to the clinical manifestations of the disease. The reason for this is that, to date, available treatment strategies have minor effects on aspects of remodelling once established either in patients or animal models.
因此,我们正处于似乎重塑的某些方面可能在功能上很重要,并且可以通过早期引入适当的治疗来阻止这些重塑的发展,这可能是在没有疾病的临床证据的时候。再次类似于心血管疾病,这将类似于对无症状高血压的控制,以防止血管壁重塑和缺血性疾病的风险。但是,在我们进入这个阶段之前,需要进行大量研究。例如,尚不清楚哪些重塑事件需要定位;这种重塑是否在目标可行的时候发生;如何识别那些将朝着功能上重要的重塑迈进的个人(IE。we need a marker like hypertension, which may turn out to be genetic); and whether such intervention would have a clinically relevant outcome. This is not meant as a negative comment, rather a reflection that there is an increasing amount of information, such as that from the Christie等。3manuscript, that will have potentially major implications on how we view and manage asthma.
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