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. 2024 Dec 4;19(1):455.
doi: 10.1186/s13023-024-03452-y.

Lung function in adult patients with osteogenesis imperfecta: a cohort study

Alexandra Lenoir #  1 , Bérengère Aubry-Rozier #  2 , Aline Bregou  3 , Elena Gonzalez Rodriguez  4 , Célia Paquier  5 , Joëlle Tanniger  5 , Mohamed Faouzi #  6 , Romain Lazor #  7   8
Affiliations

Lung function in adult patients with osteogenesis imperfecta: a cohort study

Alexandra Lenoir et al. Orphanet J Rare Dis. .

Abstract

Background: Osteogenesis imperfecta (OI) is a rare hereditary bone disease resulting from a defect in collagen synthesis or processing, leading to bone fragility, frequent fractures and skeletal deformities. OI is associated with increased respiratory morbidity and mortality, but the mechanisms of lung involvement are poorly understood, and there are no data on the natural history of lung function. We studied lung function over time in a cohort of adult OI patients at one center.

Methods: We used data from OI patients aged 15 and above followed up at the Lausanne university hospital between 2012 and 2023 with available pre-bronchodilator spirometry. Associations between spirometric measurements at first visit and clinical characteristics were studied through linear regression. Changes of spirometric variables over time were analysed through mixed linear regression. Models were adjusted for age, sex, height and OI type (Sillence classification).

Results: Among 46 subjects, 24% had impaired spirometry at baseline, with similar distribution between restrictive (8.7%), obstructive (8.7%) and mixed (6.5%) ventilatory patterns. At first visit, higher age was associated with lower FEV1 (β = -0.019 l, p = 0.014) and lower FEV1/FVC (β = -0.175%, p = 0.012). A history of asthma was associated with higher FEV1 (β = 0.636 l, p = 0.028) and FVC (β = 0.834 l, p = 0.010). At first visit, FEV1 (β = -0.750 l, p = 0.006) and FVC (β = -0.859 l, p = 0.004) was lower in individuals with OI Sillence types 3, 4 or 5 compared to type 1. Over a mean follow-up of 3.4 years, smokers had a greater decline of FEV1/FVC compared to non-smokers (β = -6.592%, p = 0.007). Individuals with a mutation in the gene COL1A2 had 740 ml lower FVC compared to those with a mutation in COL1A1 (p = 0.037). After adjustment for sex, age, height and OI type, FEV1 increased by 26 ml (95% CI 8; 45) or 1.28%pred (0.51; 2.05) and FVC increased by 25 ml (95% CI 8; 43) or 0.93%pred (0.31; 1.55) per year of follow-up.

Conclusions: An increase of FEV1 and FVC over time was observed in OI patients after adjustment for other variables, suggesting that the defective collagen synthesis may impact the pulmonary interstitium and lead to increased lung compliance and hyperinflation, in contrast to skeletal deformities, which reduce the thoracic volume. Lung function changes in OI thus result from the interplay of several mechanisms.

Keywords: Cohort studies; Lung diseases/physiopathology; Osteogenesis imperfecta; Spirometry.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of canton Vaud, Switzerland (CER Vaud 2018–01673). Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Change in FEV1 over time in adult patients with osteogenesis imperfecta
Fig. 2
Fig. 2
Change in FVC over time in adult patients with osteogenesis imperfecta
Fig. 3
Fig. 3
Change in FEV1/FVC over time in adult patients with osteogenesis imperfecta
See this image and copyright information in PMC

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