Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids
Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids
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DOI：
10.1016/j.jaci.2013.04.050
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发表时间：
2013-08-01
影响因子：
14.2
通讯作者：
Mishima, Michiaki
中科院分区：
文献类型：
--
作者：
Kanemitsu, Yoshihiro;Matsumoto, Hisako;Mishima, Michiaki
背景：Periostin是一种细胞外基质蛋白，在哮喘气道上皮下增厚中起重要作用，其血清水平反映了气道嗜酸性炎症。目的：探讨吸入糖皮质激素(ICS)治疗哮喘患者血清Periostin水平与肺功能下降的关系。方法：224例哮喘患者，平均年龄62.3岁，ICS治疗4年以上。评估了FEV1的年度变化，从ICS治疗开始后至少一年到登记或更晚的时间(平均每个人在8年内进行了16.2次测量)。在登记时，检查临床指标、包括血清Periostin和Periostin基因多态性在内的生物标记物。分析临床指标或生物标志物与每年FEV1下降30毫升或以上的相关性。结果：入选时血清骨膜蛋白水平高(<95 ng/毫升)、最高治疗步骤、较高的ICS每日剂量、因哮喘加重而入院的病史、合并症或鼻窦炎病史以及戒烟与每年FEV1下降30毫升或以上相关。多因素分析显示，高血清Periostin、最高治疗步骤和戒烟是下降的独立危险因素。Periostin基因多态性与血清Periostin水平升高(Rs3829365)和FEV1每年下降30mL或以上(Rs9603226)相关。结论：血清Periostin可作为ICS哮喘患者发生气流受限的有用生物标志物。
Background: Periostin, an extracellular matrix protein, contributes to subepithelial thickening in asthmatic airways, and its serum levels reflect airway eosinophilic inflammation. However, the relationship between periostin and the development of airflow limitation, a functional consequence of airway remodeling, remains unknown.Objective: We aimed to determine the relationship between serum periostin levels and pulmonary function decline in asthmatic patients on inhaled corticosteroid (ICS) treatment.Methods: Two hundred twenty-four asthmatic patients (average age, 62.3 years) treated with ICS for at least 4 years were enrolled. Annual changes in FEV1, from at least 1 year after the initiation of ICS treatment to the time of enrollment or later (average, 16.2 measurements over 8 years per individual), were assessed. At enrollment, clinical indices, biomarkers that included serum periostin, and periostin gene polymorphisms were examined. Associations between clinical indices or biomarkers and a decline in FEV1 of 30 mL or greater per year were analyzed.Results: High serum periostin levels (>= 95 ng/mL) at enrollment, the highest treatment step, higher ICS daily doses, a history of admission due to asthma exacerbation, comorbid or a history of sinusitis, and ex-smoking were associated with a decline in FEV1 of 30 mL or greater per year. Multivariate analysis showed that high serum periostin, the highest treatment step, and ex-smoking were independent risk factors for the decline. Polymorphisms of periostin gene were related to higher serum periostin levels (rs3829365) and a decline in FEV1 of 30 mL or greater per year (rs9603226).Conclusions: Serum periostin appears to be a useful biomarker for the development of airflow limitation in asthmatic patients on ICS.