Pulmonary function and structure abnormalities in children and young adults with osteogenesis imperfecta point to intrinsic and extrinsic lung abnormalities

作者：Bernadette R. Gochuico, Mahin Hossain, Sara Talvacchio, Mei Xing G Zuo, Mark Barton, An Dang, Joan C. Marini · 发表于：Journal of Medical Genetics · 年份：2023 · DOI：10.1136/jmg-2022-109009 · 被引用次数：10 · 研究领域：Connective tissue disorders research、Child Abuse and Related Trauma、Dermatological and Skeletal Disorders

Purpose Pulmonary disease is the major cause of morbidity and mortality in osteogenesis imperfecta (OI). We investigated the contribution of intrinsic lung factors to impaired pulmonary function in children and young adults with OI types III, IV, VI. Methods Patients with type III (n=8), IV (n=21), VI (n=5), VII (n=2) or XIV (n=1) OI (mean age 23.6 years) prospectively underwent pulmonary function tests (PFTs) and thoracic CT and radiographs. Results PFT results were similar using arm span or ulnar length as height surrogates. PFTs were significantly lower in type III than type IV or VI OI. All patients with type III and half of type IV OI had lung restriction; 90% of patients with OI had reduced gas exchange. Patients with COL1A1 variants had significantly lower forced expiratory flow (FEF)25%–75% compared with those with COL1A2 variants. PFTs correlated negatively with Cobb angle or age. CT scans revealed small airways bronchial thickening (100%, 86%, 100%), atelectasis (88%, 43%, 40%), reticulations (50%, 29%, 20%), ground glass opacities (75%, 5%, 0%), pleural thickening (63%, 48%, 20%) or emphysema (13%, 19%, 20%) in type III, IV or VI OI, respectively. Conclusion Both lung intrinsic and extrinsic skeletal abnormalities contribute to OI pulmonary dysfunction. Most young adult patients have restrictive disease and abnormal gas exchange; impairment is greater in type III than type IV OI. Decreased FEF25%–75% and thickening of small bronchi walls indicate a critical role fo...