School of Medicine, Indiana University, Indianapolis, IN 46256, USA.
Int J Mol Sci. 2024 Sep 18;25(18):10043. doi: 10.3390/ijms251810043.
The prevalence of asthma exceeds 3% of the population. Asthma is observed to be more common in children following severe viral lower respiratory illnesses that affect ciliary function, but mechanisms linking ciliary function to asthma pathogenesis have been obscure. Recent data regarding primary ciliary dyskinesia (PCD) may help us to understand the association. Here, I will review what is known about the relationship between ciliary function and asthma. PCD is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33-mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Moreover, variants in genes that affect the function of cilia can be associated with poor lung function, even in the absence of PCD, and with increased asthma severity. The role of antigen stasis on the surface of dysfunctional airway cilia in the pathophysiology of asthma is a novel area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma.
哮喘的患病率超过 3%。哮喘在严重病毒性下呼吸道疾病后更为常见，这些疾病会影响纤毛功能，但将纤毛功能与哮喘发病机制联系起来的机制尚不清楚。最近关于原发性纤毛运动障碍（PCD）的数据可能有助于我们理解这种关联。在这里，我将回顾一下已知的纤毛功能与哮喘之间的关系。PCD 是由影响运动纤毛结构和功能的 50 多种不同基因的病理性变异引起的。在细胞水平上，大多数 PCD 患者共有的一个特征是上皮表面不能清除抗原和其他颗粒。抗原清除不良会导致促氧化剂途径激活和气道上皮损伤，这可能使 PCD 患者易患 DUOX1 和 IL33 介导的哮喘。继发性纤毛功能障碍，如病毒或吸烟引起的纤毛功能障碍，也可能导致哮喘的发生。此外，影响纤毛功能的基因变异即使在没有 PCD 的情况下也可能与肺功能下降相关，并与哮喘严重程度增加相关。表面功能失调的气道纤毛上的抗原停滞在哮喘发病机制中的作用是一个新的研究领域，因为特定的气道清除技术和其他治疗干预措施，如抗氧化剂，可能有助于预防哮喘的发生。
