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Genotype-phenotype correlations
Original research
Pulmonary function and structure abnormalities in children and young adults with osteogenesis imperfecta point to intrinsic and extrinsic lung abnormalities
  1. Bernadette R Gochuico1,
  2. Mahin Hossain1,2,
  3. Sara K Talvacchio3,
  4. Mei Xing G Zuo1,
  5. Mark Barton4,
  6. An Ngoc Dang Do3,
  7. Joan C Marini5
  1. 1Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
  2. 2Undergraduate Scholarship Program, Office of the Director, National Institutes of Health, Bethesda, Maryland, USA
  3. 3Office of the Clinical Director, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
  4. 4Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA
  5. 5Section on Heritable Disorders of Bone and Extracellular Matrix, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
  1. Correspondence to Dr Joan C Marini, Section on Heritable Disorders of Bone and Extracellular Matrix, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA; oidoc{at}helix.nih.gov

Abstract

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 for small airways. Lung parenchymal abnormalities (atelectasis, reticulations) and pleural thickening were also detected. Clinical interventions to mitigate these impairments are warranted.

Trial registration number NCT03575221.

  • respiratory tract diseases
  • phenotype
  • genetics, medical

Data availability statement

Data are available on reasonable request. Full data available on reasonable request.

https://doi.org/10.1136/jmg-2022-109009

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    Data availability statement

    Data are available on reasonable request. Full data available on reasonable request.

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    Footnotes

    • Contributors Conceptualisation: BRG, SKT, ANDD, JCM; data curation: BRG, MH, SKT, MXGZ, MB, ANDD, JCM; formal analysis: BRG, MH, SKT, ANDD, JCM; investigation: BRG, MH, SKT, MXGZ, MB, ANDD, JCM; methodology: BRG, MH, SKT, MB, ANDD, JCM; writing—original draft: BRG, JCM; writing—review and editing: BRG, MH, SKT, MXGZ, MB, ANDD, JCM; guarantor of overall content: JCM.

    • Funding This work is supported by the Intramural Research Programme of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (ZIA HD008830-15 and ZIA HD000408-38), the National Human Genome Research Institute and the National Heart, Lung, and Blood Institute.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.