Human airway branch variation and chronic obstructive pulmonary disease
Human airway branch variation and chronic obstructive pulmonary disease
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DOI：
10.1073/pnas.1715564115
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发表时间：
2018-01-30
影响因子：
11.1
通讯作者：
Barr, R. Graham
中科院分区：
文献类型：
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作者：
Smith, Benjamin M.;Traboulsi, Hussein;Barr, R. Graham
吸烟以外的慢性阻塞性肺疾病（COPD）的易感性尚不完全清楚，尽管已知与COPD相关的几种遗传变异可调节气道分支发育。我们证明，在体内中央气道分支变异存在于26.5%的一般人群中，是不变的超过10年，并表现出强烈的家族聚集。最常见的气道分支变异与两个队列（n = 5，054）中的COPD相关，具有较大的中央气道分叉密度和整个肺的肺气肿。第二种最常见的气道分支变异与吸烟者的COPD相关，所有肺叶的气道管腔都较窄，并且与FGF 10基因内的遗传多态性相关。我们的结论是，中央气道分支的变化，很容易检测到的计算机断层扫描，是一个生物标志物的广泛改变肺结构的遗传基础，并代表了慢性阻塞性肺疾病的易感因素。
Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts (n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung. The second most common airway branch variant is associated with COPD among smokers, with narrower airway lumens in all lobes, and with genetic polymorphisms within the FGF10 gene. We conclude that central airway branch variation, readily detected by computed tomography, is a biomarker of widely altered lung structure with a genetic basis and represents a COPD susceptibility factor.