哮喘和COPD急性加重风险预测因子:气道IL-1β与全身炎症
2015/12/31
摘要
背景:与哮喘和COPD频繁急性加重表型相关的固有炎症通路尚不清楚。本研究旨在探索气道先天免疫激活及全身炎症反应在预测哮喘和COPD急性加重方面的作用。
方法:这项前瞻性队列研究共纳入了152例受试者，其中63例为稳定期哮喘患者以及89例COPD患者，评估了受试者基线气道IL-1β、血清C反应蛋白（CRP）和IL-6水平，与其后续12个月内病情急性加重之间的相关性。同时对频繁（在随访期内有两次或两次以上急性加重）与非频繁急性加重组受试者的临床特点及其炎性生物标志物进行比较。采用多变量模型分析频繁急性加重表型与发作次数间的关系。采用路径分析法分析气道炎性反应、全身炎性反应与未来急性加重之间的关系。
结果：94例受试者经历了总共201次急性加重，其中，36.4%的受试者有两次或多次急性加重。COPD频繁加重组受试者基线时的血清IL-6水平、及其痰液内的IL-1β基因表达水平均较高。由过去急性加重通过IL-1β-全身炎症反应轴激活启动的路径，被确定为COPD患者未来发生急性加重的重要路径。而且，全身炎症反应也与哮喘急性发作风险增加具有相关性。
结论：气道IL-1β和全身炎症反应与COPD的频繁急性加重相关，并可能介导了患者过去与未来急性加重之间的恶性循环。因此，治疗策略旨在抑制这些炎性通路来减少COPD急性加重，值得进一步研究。
Airway IL-1β and Systemic Inflammation as Predictors of Future Exacerbation Risk in Asthma and COPD
Juan-juan Fu, MD , PhD ; Vanessa M. McDonald, PhD ; Katherine J. Baines, PhD ; and Peter G. Gibson, MBBS
CHEST 2015; 148 ( 3 ): 618 – 629
ABSTRACT
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-1β , 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-1β 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-1β -systemic inflamatory axis leading to future exacerbations in COPD. Systemic inflammation was also associated with increased exacerbation risk in asthma.
CONCLUSIONS: Airway IL-1β 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.
背景:与哮喘和COPD频繁急性加重表型相关的固有炎症通路尚不清楚。本研究旨在探索气道先天免疫激活及全身炎症反应在预测哮喘和COPD急性加重方面的作用。
方法:这项前瞻性队列研究共纳入了152例受试者，其中63例为稳定期哮喘患者以及89例COPD患者，评估了受试者基线气道IL-1β、血清C反应蛋白（CRP）和IL-6水平，与其后续12个月内病情急性加重之间的相关性。同时对频繁（在随访期内有两次或两次以上急性加重）与非频繁急性加重组受试者的临床特点及其炎性生物标志物进行比较。采用多变量模型分析频繁急性加重表型与发作次数间的关系。采用路径分析法分析气道炎性反应、全身炎性反应与未来急性加重之间的关系。
结果：94例受试者经历了总共201次急性加重，其中，36.4%的受试者有两次或多次急性加重。COPD频繁加重组受试者基线时的血清IL-6水平、及其痰液内的IL-1β基因表达水平均较高。由过去急性加重通过IL-1β-全身炎症反应轴激活启动的路径，被确定为COPD患者未来发生急性加重的重要路径。而且，全身炎症反应也与哮喘急性发作风险增加具有相关性。
结论：气道IL-1β和全身炎症反应与COPD的频繁急性加重相关，并可能介导了患者过去与未来急性加重之间的恶性循环。因此，治疗策略旨在抑制这些炎性通路来减少COPD急性加重，值得进一步研究。
(王程仕 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 2015; 148 ( 3 ): 618 – 629）
（CHEST 2015; 148 ( 3 ): 618 – 629）
Airway IL-1β and Systemic Inflammation as Predictors of Future Exacerbation Risk in Asthma and COPD
Juan-juan Fu, MD , PhD ; Vanessa M. McDonald, PhD ; Katherine J. Baines, PhD ; and Peter G. Gibson, MBBS
CHEST 2015; 148 ( 3 ): 618 – 629
ABSTRACT
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-1β , 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-1β 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-1β -systemic inflamatory axis leading to future exacerbations in COPD. Systemic inflammation was also associated with increased exacerbation risk in asthma.
CONCLUSIONS: Airway IL-1β 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.
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有关美国退伍军人哮喘与心理健康关系的全国性调查
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哮喘与身体质量指数和社会经济地位之间的关联：基于849 659名青少年的一项横断面研究
