中性粒细胞炎症表型与哮喘中的全身炎症有关。

The neutrophilic inflammatory phenotype is associated with systemic inflammation in asthma.

机构信息

Centre for Asthma and Respiratory Diseases, University of Newcastle, and Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia.

出版信息

Chest. 2012 Jul;142(1):86-93. doi: 10.1378/chest.11-1838.

DOI:10.1378/chest.11-1838

PMID:22345378

Abstract

BACKGROUND

The role of systemic inflammation in asthma is unclear. The aim of this study was to compare systemic inflammation in subjects with stable asthma, categorized by airway inflammatory phenotype, with healthy control subjects.

METHODS

Adults with stable asthma (n = 152) and healthy control subjects (n = 83) underwent hypertonic saline challenge and sputum induction. Differential leukocyte counts were performed on selected sputum. Plasma high-sensitivity C-reactive protein (CRP), IL-6, and tumor necrosis factor-α levels and sputum IL-8 and neutrophil elastase levels were determined by enzyme-linked immunosorbent assay. Sputum IL-8 receptor α (IL-8RA) and IL-8 receptor β (IL-8RB) messenger RNA expression were determined by real-time polymerase chain reaction.

RESULTS

Subjects with asthma were classified as having nonneutrophilic asthma or neutrophilic asthma. The asthma (neutrophilic) group had increased systemic inflammation compared with the asthma (nonneutrophilic) and healthy control groups, with median (interquartile range) CRP levels of 5.0 (1.6-9.2), 1.8 (0.9-5.3), and 1.8 (0.8-4.1) mg/L (P = .011), respectively, and IL-6 levels of 2.1 (1.5-3.1), 1.4 (1.0-2.1), and 1.1 (0.8-1.5) pg/mL (P < .001), respectively. The proportion of subjects with elevated CRP and IL-6 levels was also higher in the asthma (neutrophilic) group. Sputum IL-8 and neutrophil elastase protein and IL-8RA and IL-8RB gene expression were significantly increased in the asthma (neutrophilic) group. In multiple regression analysis of subjects with asthma, sex, BMI, statin use, and percent sputum neutrophils were significant predictors of log(10)CRP. Sex, BMI, and %FEV(1) were significant predictors of log(10)IL-6.

CONCLUSIONS

Systemic inflammation is increased in patients with asthma with neutrophilic airway inflammation and associated with worse clinical outcomes. Systemic inflammation may contribute to the pathophysiology of neutrophilic asthma.

摘要

背景

系统性炎症在哮喘中的作用尚不清楚。本研究旨在比较稳定期哮喘患者（根据气道炎症表型分类）与健康对照者之间的系统性炎症。

方法

对 152 例稳定期哮喘患者和 83 例健康对照者进行高渗盐水激发和诱导痰检查。对选定的痰标本进行白细胞分类计数。采用酶联免疫吸附试验测定血浆高敏 C 反应蛋白（CRP）、IL-6 和肿瘤坏死因子-α水平，以及痰 IL-8 和中性粒细胞弹性蛋白酶水平。采用实时聚合酶链反应测定痰 IL-8 受体 α（IL-8RA）和 IL-8 受体 β（IL-8RB）信使 RNA 表达。

结果

将哮喘患者分为非中性粒细胞性哮喘或中性粒细胞性哮喘。与哮喘（非中性粒细胞性）和健康对照组相比，哮喘（中性粒细胞性）组患者存在全身性炎症增加，其 CRP 中位数（四分位距）水平分别为 5.0（1.6-9.2）、1.8（0.9-5.3）和 1.8（0.8-4.1）mg/L（P=.011），IL-6 水平分别为 2.1（1.5-3.1）、1.4（1.0-2.1）和 1.1（0.8-1.5）pg/mL（P<0.001），且 CRP 和 IL-6 水平升高的患者比例在哮喘（中性粒细胞性）组中也更高。哮喘（中性粒细胞性）组痰中 IL-8 和中性粒细胞弹性蛋白酶蛋白以及 IL-8RA 和 IL-8RB 基因表达均显著增加。在哮喘患者的多元回归分析中，性别、BMI、他汀类药物使用和痰中性粒细胞百分比是 log（10）CRP 的显著预测因子。性别、BMI 和 FEV（1）占比是 log（10）IL-6 的显著预测因子。