Determinants of Lung Fissure Completeness

RATIONALE: New advanced bronchoscopic treatment options for patients with severe COPD have led to increased interest for COPD phenotyping, including fissure completeness.

OBJECTIVES: We investigated clinical, environmental, and genetic factors contributing to fissure completeness in patients with and without COPD.

METHODS: We used data of 9926 participants of the COPDGene study who underwent chest computed tomography (CT). Fissure completeness was calculated from CT scans following quantitative CT analysis at baseline and five-year follow-up. The clinical and environmental factors 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 whites and African-Americans.

MEASUREMENTS AND MAIN RESULTS: African-Americans had significant higher fissure completeness than non-Hispanic whites for all three fissures (p<0.001). There was no change in fissure completeness between baseline and five-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 whites. In African-Americans, 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.

CONCLUSIONS: 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.