哮喘联盟

   摘要
   背景：糖皮质激素是哮喘治疗的基石药物。但是，对于糖皮质激素在哮喘中的治疗获益是否仅基于其抗炎作用尚不十分清楚。糖皮质激素也可能具有改变气道平滑肌（ASM）的基因表达的作用。研究者假设，哮喘患者的支气管镜检结果可观察到口服糖皮质激素与安慰剂相比可能改变了ASM的基因表达。
   目的：首先，观察口服糖皮质激素14天后支气管镜检观察到的ASM转录特征的改变情况。其次，分析ASM转录特征的改变与肺功能间的相关性。
   方法：该项双盲干预研究共纳入了12例未使用激素的特异性哮喘患者。分别于口服糖皮质激素(n=6)或安慰剂(n=6)之前和14天后进行支气管活体组织检测。采用GS FLX+(454/Roche)法对激光切割的ASM的RAN序列(RNA-Seq)进行测定。采用信号网络分析（Ingenuity Pathway Analysis, IPA）软件分析基因网络。激光切开的呼吸道平滑肌的核糖核酸用GS FLX+进行排序(454/Roche)。通过信号路径分析识别基因网络。假定RNA-Seq阅读按负二项分布。当前样本量下的预估错误发现率约为3%。
   结果：口服强的松龙14天后，有15个基因发生明显改变。其中2个基因(FAM129A, SYNPO2)与气道高反应性相关(PC20: r=0.637, p=0.035; r=0.662, p=0.027)。通路分析显示：有3个基因网络与细胞功能，包括细胞生长、增殖和发育有关。
   结论：口服强的松龙改变了哮喘患者ASM层的转录情况。这表明，除抗炎特性之外，糖皮质激素也能影响ASM 的基因表达，这与改善呼吸道功能密切相关。
 

(林江涛 审校)
Am J Respir Crit Care Med. 2013 Mar 14. [Epub ahead of print]

 

Glucocorticoid-Induced Changes in Gene Expression of Airway Smooth Muscle in Patients with Asthma.
 

Yick CY, Zwinderman AH, Kunst PW, Grünberg K, Mauad T, Fluiter K, Bel EH, Lutter R, Baas F, Sterk PJ.

Source
Respiratory Medicine, Academic Medical Center, Amsterdam, Netherlands.

Abstract
BACKGROUND:Glucocorticoids are the mainstay of asthma therapy. However, it is unclear whether the benefits of glucocorticoids in asthma are merely based on anti-inflammatory properties. Glucocorticoids may also alter gene expression of airway smooth muscle (ASM). We hypothesized that the gene expression profile of the ASM layer in endobronchial biopsies of asthma patients alters by oral glucocorticoid therapy as compared to placebo.
OBJECTIVES:First, we investigated the change in ASM transcriptomic profile in endobronchial biopsies after 14 days of oral glucocorticoid therapy. Second, we investigated the association between changes in ASM transcriptomic profile and lung function.
METHODS:12 atopic steroid-free asthma patients were included in this double-blind intervention study. Endobronchial biopsies were taken before and after 14 days of oral prednisolone (n=6) or placebo (n=6). RNA of laser-dissected ASM was sequenced (RNA-Seq) using GS FLX+ (454/Roche). Gene networks were identified using Ingenuity Pathway Analysis. RNA-Seq reads were assumed to follow a negative binomial distribution. At the current sample size the estimated false discovery rate was approximately 3%.
RESULTS:15 genes were significantly changed by 14 days of oral prednisolone. 2 of these genes (FAM129A, SYNPO2) were associated with airway hyperresponsiveness (PC20: r=0.637, p=0.035; r=0.662, p=0.027). Pathway analysis revealed 3 gene networks that were associated with cellular functions including cellular growth, proliferation, and development.
CONCLUSION:Oral prednisolone changes the transcriptomic profile of the ASM layer in asthma. This indicates that in parallel to anti-inflammatory properties, glucocorticoids also exert effects on gene expression of ASM, which is correlated with improved airway function.

Am J Respir Crit Care Med. 2013 Mar 14. [Epub ahead of print]