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轻度哮喘患者痰液 MUC5AC 和 MUC5B 水平的病理生理学相关性。

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

机构信息

Department of Respiratory Medicine, Kyoto University, Kyoto, Japan; Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University School of Medical Sciences, Aichi, Japan.

Department of Respiratory Medicine, Kyoto University, Kyoto, Japan; Department of Respiratory Medicine and Allergology, Kindai University Faculty of Medicine, Osaka, Japan.

出版信息

Allergol Int. 2022 Apr;71(2):193-199. doi: 10.1016/j.alit.2021.09.003. Epub 2021 Oct 13.

Abstract

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.

摘要

背景

气道黏液高分泌是哮喘的一个重要病理生理特征。MUC5AC 和 MUC5B 是气道中主要的分泌性聚合粘蛋白,它们的组成影响黏液的性质。尽管人们越来越认识到哮喘气道中 MUC5AC 和 MUC5B 的组成,但它们在人类中的病理生理相关性仍有待充分理解。

方法

在这项横断面研究中,我们前瞻性地招募了新转诊的未经类固醇治疗的轻度哮喘患者和健康对照者。我们比较了患者和对照组之间诱导痰中 MUC5AC 和 MUC5B 的水平。随后,我们评估了患者中 MUC5AC 和 MUC5B 水平与临床指标的相关性。使用酶联免疫吸附试验测量痰 MUC5AC 和 MUC5B 水平。

结果

患者(n=87)的痰 MUC5AC 和 MUC5B 水平明显高于对照组(n=22)(p=0.0002 和 p=0.006)。患者的痰 MUC5AC 与 MUC5B 比值高于对照组(p=0.07)。痰 MUC5AC 水平与呼气流量为 50ml/s 时的呼出气一氧化氮分数(Spearman's rho=0.29,p=0.006)、痰嗜酸性粒细胞比例(rho=0.34,p=0.0013)和气道敏感性(rho=0.39,p=0.0005)呈显著正相关。相比之下,痰 MUC5B 水平与气道敏感性呈显著正相关(rho=0.35,p=0.002),与气道反应性呈显著负相关(rho=-0.33,p=0.004)。

结论

在未经类固醇治疗的轻度哮喘患者中,痰 MUC5AC 增加与蛋白水平有关,并参与气道 2 型/嗜酸性粒细胞炎症和气道高反应性。

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