Importance of mucus burden and mucociliary impairment in asthma
Importance of mucus burden and mucociliary impairment in asthma
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粘液负荷和粘液纤毛损伤在哮喘中的重要性
DOI：
10.1016/j.jaci.2023.01.024
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发表时间：
2023
影响因子：
14.2
通讯作者：
Hirai Toyohiro
中科院分区：
文献类型：
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作者：
Nomura Natsuko;Matsumoto Hisako;Sunadome Hironobu;Oguma Tsuyoshi;Hirai Toyohiro
我们饶有兴趣地阅读了 Guntur 等人 1 题为“难治性中性粒细胞性哮喘和纤毛基因”的研究。本文表明，纤毛基因的失调和下调可能导致难治性哮喘（RA）的发生，特别是纤毛缺陷型 RA。纤毛缺陷的 RA 表现出 2 型和非 2 型炎症，以及亚临床感染的高风险，并在胸部计算机断层扫描 (CT) 上发现“粘液”、“支气管扩张/支气管扩张”或“树芽”。此外，考虑到S100A8激活气道上皮产生粘蛋白5AC，在RA中发现S100A8的上调，这可能导致粘液清除不良。他们的研究表明，必须充分认识粘液纤毛损伤和粘液负担在RA发展中的重要性。我们检查了胸部 CT 上的“树芽”模式与 rs2523870 的单核苷酸多态性之间的关联，rs2523870 是一种位于弥漫性全细支气管炎 (DPB) 风险基因（即染色体 6p21 上的 HCG22）附近的变体。 3、哮喘患者。树芽模式可能反映了细支气管炎的存在，是 DPB 的典型特征，DPB 是一种主要影响亚洲人的窦肺综合征 2，并且通常伴有支气管扩张、中性粒细胞性气道炎症和亚临床感染。 HCG22 的推定蛋白产物是一种分泌性粘蛋白，缺乏跨膜结构域，与具有几丁质结合能力的围营养蛋白 A 关系最密切。 3 值得注意的是，rs2523870 的次要 C 等位基因也是迟发性哮喘的风险等位基因。 4 本研究经京都大学医学伦理委员会批准（G0436）。
We read with interest the study by Guntur et al 1 titled “Refractory neutrophilic asthma and ciliary genes.” This article showed that the dysregulation and downregulation of ciliary genes may contribute to the development of refractory asthma (RA), particularly its subgroup cilium-deficient RA. The cilium-deficient RA showed both type 2 and non–type 2 inflammation and a high risk of subclinical infection with findings of “mucus,”“bronchiectasis/bronchial dilatation,” or “tree-in-bud” on chest computed tomography (CT). Furthermore, the upregulation of S100A8 was found in RA, which may contribute to poor mucus clearance, considering that S100A8 activates airway epithelium to produce mucin 5AC.Their study showed that the importance of mucociliary impairment and mucus burden in the development of RA must be well recognized. We examined the association between the “tree-in-bud” pattern on chest CT and a single-nucleotide polymorphism of rs2523870, a variant located near a risk gene of diffuse panbronchiolitis (DPB), that is, HCG22 on chromosome 6p21. 3, in patients with asthma. The tree-in-bud pattern, which may reflect the presence of bronchiolitis, is typically a feature of DPB, a sinopulmonary syndrome mainly affecting Asians, 2 and is often accompanied by bronchiectasis with neutrophilic airway inflammation and subclinical infection. The putative protein product of HCG22 is a secreted mucin that lacks a transmembrane domain and is most closely related to peritrophin A, which has chitin-binding ability. 3 Notably, the minor C allele of rs2523870 is also the risk allele for late-onset asthma. 4 This study was approved by the Kyoto University Medical Ethics Committee (G0436).