Asthma is a chronic inflammatory airway disease resulting in airflow obstruction, which in part can become irreversible to conventional therapies, defining the concept of airway remodeling. The introduction of biologics in severe asthma has led in some patients to the complete normalization of previously considered irreversible airflow obstruction. This highlights the need to distinguish a “fixed” airflow obstruction due to structural changes unresponsive to current therapies, from a “reversible” one as demonstrated by lung function normalization during biological therapies not previously obtained even with high-dose systemic glucocorticoids. The mechanisms by which exposure to environmental factors initiates the inflammatory responses that trigger airway remodeling are still incompletely understood. Alarmins represent epithelial-derived cytokines that initiate immunologic events leading to inflammatory airway remodeling. Biological therapies can improve airflow obstruction by addressing these airway inflammatory changes. In addition, biologics might prevent and possibly even revert “fixed” remodeling due to structural changes. Hence, it appears clinically important to separate the therapeutic effects (early and late) of biologics as a new paradigm to evaluate the effects of these drugs and future treatments on airway remodeling in severe asthma.

中文翻译：

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严重哮喘的生物制剂和气道重塑

哮喘是一种慢性炎症性气道疾病，会导致气流阻塞，这在一定程度上对传统疗法来说是不可逆转的，定义了气道重塑的概念。在严重哮喘中引入生物制剂已使一些患者完全恢复了以前认为不可逆的气流阻塞。这突出表明需要区分由于结构变化对当前疗法无反应而导致的“固定”气流阻塞与生物疗法期间肺功能正常化所证明的“可逆”气流阻塞，即使使用高剂量全身性糖皮质激素也无法实现。暴露于环境因素引发引发气道重塑的炎症反应的机制仍未完全了解。Alarmins 代表上皮衍生的细胞因子，可启动导致炎症性气道重塑的免疫事件。生物疗法可以通过解决这些气道炎症变化来改善气流阻塞。此外，生物制剂可能会阻止甚至可能恢复由于结构变化引起的“固定”重塑。因此，将生物制剂的治疗效果（早期和晚期）分开作为评估这些药物和未来治疗对严重哮喘气道重塑的影响的新范例在临床上似乎很重要。