控制不佳的哮喘患者抗病毒干扰素生成减少与中性粒细胞炎症及大剂量吸入激素相关
2016/12/27
背景：哮喘是一种异质性的慢性炎症疾病，其对抗呼吸道病毒如人鼻病毒（HRV）的宿主防御功能可能不正常。有一些研究报导哮喘患者合成干扰素Ⅰ（IFN）减少，而另一些研究认为哮喘患者合成干扰素相对正常，这目前是一个有争议的问题。
目的：本研究旨在检测一个大型队列控制不佳哮喘受试者的血循环中单个核细胞对HRV的应答，并确定在不同哮喘炎症表型中IFN-α和IFN-β的合成是否各不相同。
方法：符合条件的成人哮喘受试者（n=86）进行临床评估，痰诱导和静脉采血。由诱导痰细胞的分类计数决定哮喘炎症表型，并检测上清液中IL-1β水平。外周血单个核细胞（PBMCs）暴露于HRV血清型1b，用酶联免疫吸附法（ELISA）检测IFN-α、IFN-β的释放。
结果：受试者（平均年龄，59岁，过敏症，76%）哮喘控制均不理想（ACQ6，平均1.7分）。中性粒细胞型哮喘（n=12）HRV1b刺激PBMCs产生的IFN-α水平显著低于嗜酸粒细胞型哮喘（n=35）和寡粒细胞型哮喘（n=35）。诱导痰中性粒细胞比例及吸入激素剂量是预测暴露于HRV1b后IFN-α生成减少的两个独立因素。
结论：中性粒细胞性气道炎症和大剂量吸入激素的哮喘患者，其抗病毒I型干扰素的产生受损。该研究对明确控制不佳哮喘患者急性发作期，哪些患者对吸入性IFN治疗反应最好，迈出了重要一步。
Reduced Antiviral Interferon Production in Poorly Controlled Asthma is associated with Neutrophilic Inflammation and High-Dose Inhaled Corticosteroids
Jodie L. Simpson; Melanie Carroll; Ian A. Yang; Paul N. Reynolds, ; Sandra Hodge; Alan L. James; Peter G. Gibson; and John W. Upham
CHEST 2016; 149(3):704-713
METHODS: Eligible adults with asthma (n =86) underwent clinical assessment, sputum induction, and blood sampling. Asthma inflammatory subtypes were defined by sputum cell count, and supernatant assessed for IL-1β. Peripheral blood mononuclear cells (PBMCs) were exposed to HRV serotype 1b, and IFN-α and IFN-β release was measured by enzyme-linked immunosorbent assay.
RESULTS: Participants (mean age, 59 years; atopy, 76%) had suboptimal asthma control (mean asthma control questionnaire 6, 1.7). In those with neutrophilic asthma (n =12), HRV1b-stimulated PBMCs produced significantly less IFN-α than PBMCs from participants with eosinophilic (n = 35) and paucigranulocytic asthma (n =35). Sputum neutrophil proportion and the dose of inhaled corticosteroids were undependent predictors of reduced IFN-α production after HRV1b exposure.
CONCLUSIONS: Antiviral type I IFN production is impaired in those with neutrophilic airway inflammation and in those prescribed high doses of inhaled corticosteroids. Our study is an important step toward identifying those with poorly controlled asthma who might respond best to inhaled IFN therapy during exacerbations.
目的：本研究旨在检测一个大型队列控制不佳哮喘受试者的血循环中单个核细胞对HRV的应答，并确定在不同哮喘炎症表型中IFN-α和IFN-β的合成是否各不相同。
方法：符合条件的成人哮喘受试者（n=86）进行临床评估，痰诱导和静脉采血。由诱导痰细胞的分类计数决定哮喘炎症表型，并检测上清液中IL-1β水平。外周血单个核细胞（PBMCs）暴露于HRV血清型1b，用酶联免疫吸附法（ELISA）检测IFN-α、IFN-β的释放。
结果：受试者（平均年龄，59岁，过敏症，76%）哮喘控制均不理想（ACQ6，平均1.7分）。中性粒细胞型哮喘（n=12）HRV1b刺激PBMCs产生的IFN-α水平显著低于嗜酸粒细胞型哮喘（n=35）和寡粒细胞型哮喘（n=35）。诱导痰中性粒细胞比例及吸入激素剂量是预测暴露于HRV1b后IFN-α生成减少的两个独立因素。
结论：中性粒细胞性气道炎症和大剂量吸入激素的哮喘患者，其抗病毒I型干扰素的产生受损。该研究对明确控制不佳哮喘患者急性发作期，哪些患者对吸入性IFN治疗反应最好，迈出了重要一步。
(任慧玲 张红萍 王刚 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（CHEST 2016; 149(3):704-713）
（CHEST 2016; 149(3):704-713）
Reduced Antiviral Interferon Production in Poorly Controlled Asthma is associated with Neutrophilic Inflammation and High-Dose Inhaled Corticosteroids
Jodie L. Simpson; Melanie Carroll; Ian A. Yang; Paul N. Reynolds, ; Sandra Hodge; Alan L. James; Peter G. Gibson; and John W. Upham
CHEST 2016; 149(3):704-713
BACKGROUND: Asthma is a heterogeneous chronic inflammatory disease in which host defense against respiratory viruses such as human rhinovirus (HRV) may be abnormal. This is a matter of some controversy, with some investigators reporting reduced type I interferon (IFN) synthesis and others suggesting that type I IFN synthesis is relatively normal in asthma.
OBJECTIVE: The objective of this study was to examine the responsiveness of circulating mononuclear cells to HRV in a large cohort of participants with poorly controlled asthma and determine whether IFN-α and IFN-β synthesis varies across different inflammatory phenotypes.METHODS: Eligible adults with asthma (n =86) underwent clinical assessment, sputum induction, and blood sampling. Asthma inflammatory subtypes were defined by sputum cell count, and supernatant assessed for IL-1β. Peripheral blood mononuclear cells (PBMCs) were exposed to HRV serotype 1b, and IFN-α and IFN-β release was measured by enzyme-linked immunosorbent assay.
RESULTS: Participants (mean age, 59 years; atopy, 76%) had suboptimal asthma control (mean asthma control questionnaire 6, 1.7). In those with neutrophilic asthma (n =12), HRV1b-stimulated PBMCs produced significantly less IFN-α than PBMCs from participants with eosinophilic (n = 35) and paucigranulocytic asthma (n =35). Sputum neutrophil proportion and the dose of inhaled corticosteroids were undependent predictors of reduced IFN-α production after HRV1b exposure.
CONCLUSIONS: Antiviral type I IFN production is impaired in those with neutrophilic airway inflammation and in those prescribed high doses of inhaled corticosteroids. Our study is an important step toward identifying those with poorly controlled asthma who might respond best to inhaled IFN therapy during exacerbations.
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衰老对气道炎症和哮喘控制的影响
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