{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:06:26Z","timestamp":1791194786102,"version":"4.1.0"},"reference-count":33,"publisher":"BMJ","issue":"11","funder":[{"name":"Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["ZIA HD000408-38"],"award-info":[{"award-number":["ZIA HD000408-38"]}]},{"name":"Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["ZIA HD008830-15"],"award-info":[{"award-number":["ZIA HD008830-15"]}]},{"name":"Intramural Research Program of the National Human Genome Research Institute"},{"name":"Intramural Research Program of the National Heart, Lung, and Blood Institute"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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<jats:italic>COL1A1<\/jats:italic>variants had significantly lower forced expiratory flow (FEF)25%\u201375% compared with those with<jats:italic>COL1A2<\/jats:italic>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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%\u201375%\u2009and thickening of small bronchi walls indicate a critical role for small airways. Lung parenchymal abnormalities (atelectasis, reticulations) and pleural thickening were also detected. Clinical interventions to mitigate these impairments are warranted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03575221\">NCT03575221<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jmg-2022-109009","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T07:22:48Z","timestamp":1684308168000},"page":"1067-1075","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Pulmonary function and structure abnormalities in children and young adults with osteogenesis imperfecta point to intrinsic and extrinsic lung abnormalities"],"prefix":"10.1136","volume":"60","clinical-trial-number":[{"clinical-trial-number":"nct03575221","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03575221","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4727-8918","authenticated-orcid":false,"given":"Bernadette R","family":"Gochuico","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahin","family":"Hossain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara K","family":"Talvacchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Xing G","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Barton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4171-0493","authenticated-orcid":false,"given":"An Ngoc","family":"Dang Do","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-0950","authenticated-orcid":false,"given":"Joan C","family":"Marini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"2023102407401056000_60.11.1067.1","doi-asserted-by":"crossref","first-page":"17052","DOI":"10.1038\/nrdp.2017.52","article-title":"Osteogenesis imperfecta","volume":"3","author":"Marini","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"2023102407401056000_60.11.1067.2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.16.2.101"},{"key":"2023102407401056000_60.11.1067.3"},{"key":"2023102407401056000_60.11.1067.4","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.49.8.627"},{"key":"2023102407401056000_60.11.1067.5","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1002\/jbmr.2895","article-title":"Mortality and causes of death in patients with osteogenesis imperfecta: a register-based nationwide cohort study","volume":"31","author":"Folkestad","year":"2016","journal-title":"J Bone Miner Res"},{"key":"2023102407401056000_60.11.1067.6","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1080\/07853890.2021.1980819","article-title":"Pathophysiology of respiratory failure in patients with osteogenesis imperfecta: a systematic review","volume":"53","author":"Storoni","year":"2021","journal-title":"Ann Med"},{"key":"2023102407401056000_60.11.1067.7","doi-asserted-by":"crossref","unstructured":"Yonko EA , Emanuel JS , Carter EM , et al . Respiratory impairment impacts QOL in osteogenesis imperfecta independent of skeletal abnormalities. Arch Osteoporos 2020;15:153. doi:10.1007\/s11657-020-00818-0","DOI":"10.1007\/s11657-020-00818-0"},{"key":"2023102407401056000_60.11.1067.8","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1097\/00007632-199908150-00008","article-title":"Spinal deformity, pulmonary compromise, and quality of life in osteogenesis imperfecta","volume":"24","author":"Widmann","year":"1999","journal-title":"Spine"},{"key":"2023102407401056000_60.11.1067.9","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds183"},{"key":"2023102407401056000_60.11.1067.10","doi-asserted-by":"crossref","unstructured":"Baldridge D , Lennington J , Weis M , et al . Generalized connective tissue disease in Crtap-\/- mouse. PLoS One 2010;5:e10560. doi:10.1371\/journal.pone.0010560","DOI":"10.1371\/journal.pone.0010560"},{"key":"2023102407401056000_60.11.1067.11","doi-asserted-by":"crossref","first-page":"L592","DOI":"10.1152\/ajplung.00313.2019","article-title":"Respiratory defects in the CrtapKO mouse model of osteogenesis imperfecta","volume":"318","author":"Dimori","year":"2020","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2023102407401056000_60.11.1067.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15647-5"},{"key":"2023102407401056000_60.11.1067.13","unstructured":"Marini JC , Dang DA AN . Osteogenesis imperfecta. In: Feingold KR , Anawalt B , Boyce A , eds. Endotext. South Dartmouth (MA): MDText.com, Inc, 2000. Available: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK279109\/"},{"key":"2023102407401056000_60.11.1067.14","doi-asserted-by":"crossref","unstructured":"Garibaldi N , Besio R , Dalgleish R , et al . Dissecting the phenotypic variability of osteogenesis imperfecta. Dis Model Mech 2022;15:dmm049398. doi:10.1242\/dmm.049398","DOI":"10.1242\/dmm.049398"},{"key":"2023102407401056000_60.11.1067.15","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.trsl.2016.11.005","article-title":"Osteogenesis imperfecta: new genes reveal novel mechanisms in bone dysplasia","volume":"181","author":"Kang","year":"2017","journal-title":"Transl Res"},{"key":"2023102407401056000_60.11.1067.16","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1210\/endrev\/bnab017","article-title":"Osteogenesis imperfecta: mechanisms and signaling pathways connecting classical and rare OI types","volume":"43","author":"Jovanovic","year":"2022","journal-title":"Endocr Rev"},{"key":"2023102407401056000_60.11.1067.17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1210\/clinem\/dgab679","article-title":"Osteogenesis imperfecta: the impact of genotype and clinical phenotype on adiposity and resting energy expenditure","volume":"107","author":"Ballenger","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"2023102407401056000_60.11.1067.18","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201908-1590ST"},{"key":"2023102407401056000_60.11.1067.19","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3389\/fimmu.2018.00076","article-title":"The immunome in two inherited forms of pulmonary fibrosis","volume":"9","author":"El-Chemaly","year":"2018","journal-title":"Front Immunol"},{"key":"2023102407401056000_60.11.1067.20","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ymgme.2018.07.012","article-title":"Prolonged treatment with open-label pirfenidone in Hermansky-Pudlak syndrome pulmonary fibrosis","volume":"125","author":"O\u2019Brien","year":"2018","journal-title":"Mol Genet Metab"},{"key":"2023102407401056000_60.11.1067.21","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.180.2.1800513"},{"key":"2023102407401056000_60.11.1067.22","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1097\/CORR.0000000000001400","article-title":"Cardiopulmonary status in adults with osteogenesis imperfecta: intrinsic lung disease may contribute more than scoliosis","volume":"478","author":"Khan","year":"2020","journal-title":"Clin Orthop Relat Res"},{"key":"2023102407401056000_60.11.1067.23","doi-asserted-by":"publisher","DOI":"10.1378\/chest.97.2.315"},{"key":"2023102407401056000_60.11.1067.24","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.3.9805067"},{"key":"2023102407401056000_60.11.1067.25","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/cge.13440","article-title":"A multicenter study to evaluate pulmonary function in osteogenesis imperfecta","volume":"94","author":"Tam","year":"2018","journal-title":"Clin Genet"},{"key":"2023102407401056000_60.11.1067.26","doi-asserted-by":"crossref","unstructured":"Menzies-Gow A , Mansur AH , Brightling CE . Clinical utility of fractional exhaled nitric oxide in severe asthma management. Eur Respir J 2020;55:1901633. doi:10.1183\/13993003.01633-2019","DOI":"10.1183\/13993003.01633-2019"},{"key":"2023102407401056000_60.11.1067.27","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1038\/pr.2018.36","article-title":"Pulmonary and diaphragmatic pathology in collagen type I \u03b11 mutant mice with osteogenesis imperfecta","volume":"83","author":"Baglole","year":"2018","journal-title":"Pediatr Res"},{"key":"2023102407401056000_60.11.1067.28","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3544"},{"key":"2023102407401056000_60.11.1067.29","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201505-0942IM"},{"key":"2023102407401056000_60.11.1067.30","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-101142"},{"key":"2023102407401056000_60.11.1067.31","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1210\/jc.2016-3766","article-title":"Phenotypic spectrum in osteogenesis imperfecta due to mutations in TMEM38B: unraveling a complex cellular defect","volume":"102","author":"Webb","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"2023102407401056000_60.11.1067.32","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1038\/s41467-018-05369-0","article-title":"Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function","volume":"9","author":"Wyss","year":"2018","journal-title":"Nat Commun"},{"key":"2023102407401056000_60.11.1067.33","doi-asserted-by":"crossref","unstructured":"Locke BW , Lee JJ , Sundar KM . OSA and chronic respiratory disease: mechanisms and epidemiology. Int J Environ Res Public Health 2022;19:5473. doi:10.3390\/ijerph19095473","DOI":"10.3390\/ijerph19095473"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg-2022-109009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T14:42:37Z","timestamp":1698158557000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg-2022-109009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,16]]},"references-count":33,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,10,24]]},"published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1136\/jmg-2022-109009"],"URL":"https:\/\/doi.org\/10.1136\/jmg-2022-109009","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,16]]}}}