The clinical and genetic features of COPD-asthma overlap syndrome.
The clinical and genetic features of COPD-asthma overlap syndrome.
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DOI：
10.1183/09031936.00216013
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Hersh CP
中科院分区：
文献类型：
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作者：
Hardin M;Cho M;McDonald ML;Beaty T;Ramsdell J;Bhatt S;van Beek EJ;Make BJ;Crapo JD;Silverman EK;Hersh CP
慢性阻塞性肺病和哮喘患者是一个重要但特征不明确的群体。copd -哮喘重叠的遗传决定因素尚未被研究。确定copd -哮喘重叠的临床特征和遗传危险因素。受试者为目前或曾经吸烟的非西班牙裔白人（NHW）或患有COPD的非裔美国人（AA）。重叠受试者报告在40岁之前有医生诊断的哮喘病史。我们比较了COPD和重叠受试者的临床和影像学特征。我们在NHW和AA人群中进行了全基因组关联研究（GWAS），并将这些结果合并到荟萃分析中。更多的女性和非裔美国人报告有哮喘病史。与单独患有COPD的受试者相比，重叠受试者有更严重和更频繁的呼吸恶化，更少的肺气肿和更大的气道壁厚。NHW GWAS在CSMD1 （rs11779254， P=1.57×10−6）和SOX5（rs95569785， P=1.61×10−6）中发现了snp， meta分析在GPR65 （rs6574978， P=1.18×10−7）中发现了与copd -哮喘重叠相关的snp。与单独COPD相比，重叠受试者有更多的加重，更少的肺气肿和更多的气道疾病，任何程度的肺功能损害。我们发现了与该综合征相关的新的遗传变异。copd -哮喘重叠是一个重要的综合征，可能需要不同的临床管理。
Individuals with COPD and asthma are an important but poorly characterized group. The genetic determinants of COPD-asthma overlap have not been studied. Identify clinical features and genetic risk factors for COPD-asthma overlap. Subjects were current or former smoking non-Hispanic whites (NHW) or African-Americans (AA) with COPD. Overlap subjects reported a history of physician-diagnosed asthma before the age of 40. We compared clinical and radiographic features between COPD and overlap subjects. We performed genome-wide association studies (GWAS) in the NHW and AA populations, and combined these results in a meta-analysis. More women and African Americans reported a history of asthma. Overlap subjects had more severe and more frequent respiratory exacerbations, less emphysema, and greater airway wall thickness compared to subjects with COPD alone. The NHW GWAS identified SNPs in CSMD1 (rs11779254, P=1.57×10−6) and SOX5(rs59569785, P=1.61×10−6) and the meta-analysis identified SNPs in the gene GPR65 (rs6574978, P=1.18×10−7) associated with COPD-asthma overlap. Overlap subjects have more exacerbations, less emphysema and more airway disease for any degree of lung function impairment compared to COPD alone. We identified novel genetic variants associated with this syndrome. COPD-asthma overlap is an important syndrome and may require distinct clinical management.