Airway IL-1β and Systemic Inflammation as Predictors of Future Exacerbation Risk in Asthma and COPD
Airway IL-1β and Systemic Inflammation as Predictors of Future Exacerbation Risk in Asthma and COPD
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DOI：
10.1378/chest.14-2337
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发表时间：
2015-09-01
期刊：
影响因子：
9.6
通讯作者：
Gibson, Peter G.
中科院分区：
文献类型：
--
作者：
Fu, Juan-juan;McDonald, Vanessa M.;Gibson, Peter G.
背景：哮喘和COPD频繁加重因子表型中涉及的先天炎症途径尚不清楚。本研究旨在探讨气道先天免疫激活和全身性炎症作为哮喘和COPD恶化的预测因素。方法：在这项前瞻性队列研究中，对152名稳定哮喘（n = 63）或慢性阻塞性肺病（n = 89）患者进行基线气道IL-1 β、血清c反应蛋白和IL-6的评估，并在随后的12个月内与病情恶化相关。临床特征和炎症生物标志物比较频繁（随访中两次或两次以上加重）和不频繁加重者。采用多变量模型分析频繁加重表型和加重频率。使用通径分析检查气道炎症、全身炎症和未来恶化之间的关系。结果：94名参与者共经历了201次急性发作，36.4%的参与者有两次或两次以上的急性发作。血清IL-6和痰中IL-1 β基因在基线时的表达在频繁加重的COPD患者中较高。通过IL-1 β -全身性炎症轴的激活，确定了先前加重引发的重要途径，从而导致COPD的未来加重。全身性炎症也与哮喘恶化风险增加有关。结论：气道IL-1 β和全身性炎症与慢性阻塞性肺病的频繁加重有关，并可能介导先前和未来加重之间的恶性循环。旨在减轻这些炎症途径以减少COPD恶化的治疗策略值得进一步研究。
BACKGROUND: The innate inflammatory pathways involved in the frequent exacerbator phenotypes of asthma and COPD are not well understood. This study aimed to investigate airway innate immune activation and systemic inflammation as predictors of exacerbations in asthma and COPD.METHODS: In this prospective cohort study, baseline airway IL-1 beta, serum C-reactive protein, and IL-6 were assessed in 152 participants with stable asthma (n = 63) or COPD (n = 89) and were related to exacerbations over the following 12 months. Clinical characteristics and inflammatory biomarkers were compared between the frequent (two or more exacerbations in the follow-up) and infrequent exacerbators. The frequent exacerbation phenotype and exacerbation frequency were analyzed with multivariable modeling. The relationships among airway inflammation, systemic inflammation, and future exacerbations were examined using path analysis.RESULTS: Ninety-four participants experienced a total of 201 exacerbations, and 36.4% had two or more exacerbations. Serum IL-6 and sputum gene expression of IL-1 beta at baseline were higher in the frequent exacerbators with COPD. Significant pathways initiated by previous exacerbations were identified as occurring through activation of the IL-1 beta-systemic inflammatory axis leading to future exacerbations in COPD. Systemic inflammation was also associated with increased exacerbation risk in asthma.CONCLUSIONS: Airway IL-1 beta and systemic inflammation are associated with frequent exacerbations and may mediate a vicious cycle between previous and future exacerbations in COPD. Treatment strategies aimed at attenuating these inflammatory pathways to reduce COPD exacerbations deserve further investigation.