Pathophysiological relevance of sputum MUC5AC and MUC5B levels in patients with mild asthma

Pathophysiological relevance of sputum MUC5AC and MUC5B levels in patients with mild asthma
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轻度哮喘患者痰 MUC5AC 和 MUC5B 水平的病理生理学相关性

DOI:
10.1016/j.alit.2021.09.003
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发表时间:
2022
影响因子:
6.8
通讯作者:
Niimi Akio
Niimi Akio
中科院分区:
医学2区
文献类型:
--
作者:
Tajiri Tomoko;Matsumoto Hisako;Jinnai Makiko;Kanemitsu Yoshihiro;Nagasaki Tadao;Iwata Toshiyuki;Inoue Hideki;Nakaji Hitoshi;Oguma Tsuyoshi;Ito Isao;Niimi Akio

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背景:气道粘液高分泌是哮喘的重要病理生理特征。MUC 5AC和MUC 5 B是气道中主要分泌的聚合粘蛋白,并且它们的组成影响粘液性质。尽管越来越多的赞赏MUC 5AC和MUC 5 B组合物在哮喘airways. Methods的病理生理学的相关性仍有待充分理解在human.Methods:在这个横断面研究中,我们前瞻性地招募了新提到的类固醇未治疗的轻度哮喘患者和健康对照。我们比较了患者和对照组诱导痰中MUC 5AC和MUC 5 B的水平。随后,我们评估了MUC 5AC和MUC 5 B水平与患者临床指标之间的相关性。结果:患者痰液MUC 5AC和MUC 5 B水平(n= 87)显著高于对照组(n= 22)(分别为p= 0.0002和p= 0.006)。患者的痰液MUC 5AC与MUC 5 B的比率倾向于高于对照组(p= 0.07)。痰液MUC 5AC水平与呼气流速为50 mL/s时呼出的一氧化氮分数(斯皮尔曼rho= 0.29,p= 0.006)、痰液嗜酸性粒细胞比例(rho= 0.34,p= 0.0013)和气道敏感性(rho= 0.39,p= 0.0005)显著正相关。相反,痰液MUC 5 B水平与气道敏感性显著正相关(rho= 0.35,p= 0.002),与气道反应性显著负相关(rho=-0.33,p= 0.004)。结论:痰液MUC 5AC蛋白水平升高,并参与轻度哮喘类固醇未治疗患者的气道2型/嗜酸性粒细胞炎症和气道高反应性。
Background: Airway mucus hypersecretion is an important pathophysiological feature of asthma. MUC5AC and MUC5B are the major secreted polymeric mucins in airways, and their compositions affect mucus properties. Despite the increasing appreciation of MUC5AC and MUC5B compositions in asthmatic airways, their pathophysiological relevance remains to be fully understood in humans.Methods: In this cross-sectional study, we prospectively enrolled newly referred steroid-untreated patients with mild asthma and healthy controls. We compared induced sputum MUC5AC and MUC5B levels between patients and controls. Subsequently, we assessed the correlation between MUC5AC and MUC5B levels and clinical indices in patients. Sputum MUC5AC and MUC5B levels were measured using enzyme-linked immunosorbent assays.Results: Sputum MUC5AC and MUC5B levels were significantly higher in patients (n= 87) than in controls (n= 22)(p= 0.0002 and p= 0.006, respectively). The ratio of sputum MUC5AC to MUC5B tended to be higher in patients than in controls (p= 0.07). Sputum MUC5AC levels significantly and positively correlated with fractional exhaled nitric oxide at expiratory flow of 50 mL/s (Spearman's rho= 0.29, p= 0.006), sputum eosinophil proportion (rho= 0.34, p= 0.0013), and airway sensitivity (rho= 0.39, p= 0.0005). By contrast, sputum MUC5B levels significantly and positively correlated with airway sensitivity (rho= 0.35, p= 0.002) and negatively correlated with airway reactivity (rho=-0.33, p= 0.004).Conclusions: Sputum MUC5AC is increased by protein levels and involved in airway type 2/eosinophilic inflammation and airway hyperresponsiveness in steroid-untreated patients with mild asthma.