哮喘联盟

   摘要
   基本原理：支气管平滑肌(BSM)质量增加是气道重构的关键特征，气道重构传统上是区分重症和非重症哮喘的特征。 BSM细胞增殖涉及重症哮喘患者中特殊的线粒体依赖的途径。然而，BSM重构及线粒体生物发生学在非重症哮喘中仍未被检测到。
   目的:我们目的是评价BSM质量的增加是否与非重症哮喘有关，以及其与线粒体和临床结果的关系。
   方法:我们登记了34例从未吸烟的非重症哮喘患者作为受试者。另外，我们募集了56例非重症患者和19 例重症哮喘患者作为对照组(COBRA 队列，Inserm)。表型鉴定通过问卷，特异反应性和肺功能测试，呼出一氧化氮测定和血液采集进行。支气管活检标本经免疫组织化学和电子显微镜分析。在BSM重构评价后，受试者仍被监测12个月。
   测量值和主要结果:我们鉴定出重构的特征(BSM 面积 > 26.6%) ，在非重症哮喘患者的亚组中BSM内线粒体数量增加。BSM线粒体的数量与BSM面积(r = 0.78; P < 0.001)成正相关。随访分析显示与低BSM患者相比，高BSM的哮喘患者其哮喘控制更差，，年急性加重率更高。
   结论:本研究揭示了BSM重构和线粒体生物发生学可能在非重症哮喘的自然进程中起到至关重要的作用。

 

（杨冬 审校）
Am J Respir Crit Care Med. 2015 Nov 5. [Epub ahead of print]
 

Bronchial Smooth Muscle Remodeling in Non-severe Asthma.
 

Girodet PO1, Allard B2,3, Thumerel M2,4,5, Begueret H6, Dupin I2,7, Ousova O2,8, Lassalle R9, Maurat E2,10, Ozier A11, Trian T12, Marthan R2,4,13, Berger P14,15.
 

Abstract
RATIONALE:Increased bronchial smooth muscle (BSM) mass is a key feature of airway remodeling that classically distinguishes severe from non-severe asthma. Proliferation of BSM cells involves a specific mitochondria-dependent pathway in severe asthmatic patients. However, BSM remodeling as well as mitochondrial biogenesis have not been examined in non-severe asthma.
OBJECTIVE:We aimed to assess whether an increase in BSM mass was also implicated in non-severeasthma, and its relationship with mitochondria and clinical outcomes.
METHODS:We enrolled 34 never smoker subjects, with non-severe asthma. Additionally, we recruited 56 non-severe and 19 severe asthmatics, as comparative groups (COBRA cohort, Inserm). A phenotypic characterization was performed using questionnaires, atopy and pulmonary function testing, exhaled nitric oxide measurement and blood collection. Bronchial-biopsy specimens were processed for immunohistochemistry and electron microscopy analysis. Following BSM remodeling assessment, participants were monitored over a 12 months period.
MEASUREMENTS AND MAIN RESULTS:We identified characteristic features of remodeling (BSM area > 26.6%) and increased mitochondrial number within BSM in a sub-group of non-severe asthmatics. The number of BSM mitochondria was positively correlated to BSM area (r = 0.78; P < 0.001). Follow-up analysis showed that asthmatics with high BSM had worse asthma control and higher rate of exacerbations per year as compared to low BSM patients.
CONCLUSION:This study reveals that BSM remodeling and mitochondrial biogenesis may play a critical role in natural history of non-severe asthma.
 

Am J Respir Crit Care Med. 2015 Nov 5. [Epub ahead of print]