Shannon Joanne, Ernst Pierre, Yamauchi Yasuhiro, Olivenstein Ronald, Lemiere Catherine, Foley Susan, Cicora Leo, Ludwig Mara, Hamid Qutayba, Martin James G
Montreal Chest Institute, Respiratory Division of McGill University Health Centre, Montreal, QC, Canada.
Chest. 2008 Feb;133(2):420-6. doi: 10.1378/chest.07-1881. Epub 2007 Dec 10.
Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-gamma) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma.
Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry.
Subjects with severe asthma were more symptomatic, had a lower FEV(1), and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-gamma expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups.
Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.
一些关于重度哮喘的研究表明，炎症模式的持续或改变可能与疾病的严重程度相关。与中度哮喘患者相比，重度哮喘患者气道组织中与嗜酸性粒细胞和中性粒细胞炎症相关的主要细胞因子和趋化因子的表达是否存在差异尚未确定。本研究的目的是比较重度和中度哮喘患者气道组织中代表性的1型辅助性T（Th1）细胞因子（干扰素[IFN]-γ）和2型辅助性T细胞因子（白细胞介素[IL]-4、IL-5）以及与中性粒细胞和嗜酸性粒细胞相关的趋化因子（IL-8和嗜酸性粒细胞趋化因子）的表达模式。
对重度哮喘患者（n = 24）和中度哮喘对照组（n = 26）进行肺功能测定、诱导痰检测、呼出一氧化氮检测和支气管活检。通过免疫细胞化学检测气道壁上皮和上皮下感兴趣蛋白质的表达。
重度哮喘患者症状更明显，第一秒用力呼气容积（FEV₁）更低，痰液中性粒细胞增多（p = 0.007）和嗜酸性粒细胞增多（p = 0.001）。两组呼出一氧化氮水平相似。与中度哮喘相比，重度哮喘中IL-8和IFN-γ表达增加，IL-4表达降低（每项比较p < 0.001）。两组间嗜酸性粒细胞趋化因子和IL-5表达无差异。
重度哮喘患者痰液中中性粒细胞和嗜酸性粒细胞增多，气道细胞因子/趋化因子表达与中度哮喘患者不同。中性粒细胞增多可能由IL-8表达增加解释，但嗜酸性粒细胞增多的差异似乎与IL-5和嗜酸性粒细胞趋化因子表达无关。
