Department of Pulmonary Diseases.
Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Am J Respir Crit Care Med. 2021 Oct 1;204(7):807-816. doi: 10.1164/rccm.202102-0260OC.
New advanced bronchoscopic treatment options for patients with severe chronic obstructive pulmonary disease (COPD) have led to increased interest for COPD phenotyping, including fissure completeness. We investigated clinical, environmental, and genetic factors contributing to fissure completeness in patients with and without COPD. We used data from 9,926 participants of the COPDGene study who underwent chest computed tomographic (CT) scans. Fissure completeness was calculated from CT scans after quantitative CT analysis at baseline and 5-year follow-up. Clinical and environmental factors, including sex, race, smoking, COPD, emphysema, maternal smoking during pregnancy and maternal COPD, were tested for impact on fissure completeness. Genome-wide association analyses were performed separately in non-Hispanic White subjects and African American subjects. African American subjects had significantly higher fissure completeness than non-Hispanic White subjects for all three fissures ( < 0.001). There was no change in fissure completeness between baseline and 5-year follow-up. For all fissures, no clinically relevant differences in fissure completeness were found for other clinical or environmental factors, including COPD severity. Rs2173623, rs264866, rs2407284, rs7310342, rs4904145, rs6504172, and rs7209556 showed genome-wide significant associations with fissure completeness in non-Hispanic White subjects. In African American subjects, rs264866, rs4904145 and rs6504172 were identified as significant associations. Rs2173623, rs6504172, and rs7209556 lead to WNT5A and HOXB antisense RNA expression, which play an important role during embryogenesis. Fissure completeness is genetically determined and not dependent on age, sex, smoking status, the presence and severity of COPD (including exacerbation frequency), maternal smoking during pregnancy, or maternal COPD.
新的针对严重慢性阻塞性肺疾病（COPD）患者的先进支气管镜治疗选择增加了对 COPD 表型的兴趣，包括裂隙完整性。我们研究了导致 COPD 患者和非 COPD 患者裂隙完整性的临床、环境和遗传因素。我们使用了 COPDGene 研究 9926 名参与者的数据，这些参与者接受了胸部计算机断层扫描（CT）扫描。裂隙完整性是通过基线和 5 年随访时的定量 CT 分析后的 CT 扫描计算得出的。临床和环境因素，包括性别、种族、吸烟、COPD、肺气肿、母亲怀孕期间吸烟和母亲 COPD，都被测试了对裂隙完整性的影响。全基因组关联分析分别在非西班牙裔白人和非洲裔美国人中进行。对于所有三条裂隙，非洲裔美国人的裂隙完整性明显高于非西班牙裔白人（<0.001）。在基线和 5 年随访之间，裂隙完整性没有变化。对于所有裂隙，其他临床或环境因素，包括 COPD 严重程度，对裂隙完整性没有明显的临床差异。在非西班牙裔白人中，rs2173623、rs264866、rs2407284、rs7310342、rs4904145、rs6504172 和 rs7209556 与裂隙完整性存在全基因组显著关联。在非洲裔美国人中，rs264866、rs4904145 和 rs6504172 被确定为显著关联。rs2173623、rs6504172 和 rs7209556 导致 WNT5A 和 HOXB 反义 RNA 表达，这在胚胎发生过程中发挥着重要作用。裂隙完整性是由遗传决定的，与年龄、性别、吸烟状态、COPD 的存在和严重程度（包括加重频率）、母亲怀孕期间吸烟或母亲 COPD 无关。
