A multicenter study to evaluate pulmonary function in osteogenesis imperfecta

Abstract

Pulmonary complications are a significant cause for morbidity and mortality in osteogenesis imperfecta (OI). However, to date, there have been few studies that have systematically evaluated pulmonary function in individuals with OI. We analyzed spirometry measurements, including forced vital capacity (FVC) and forced expiratory volume in the first second (FEV₁ ), in a large cohort of individuals with OI (n = 217) enrolled in a multicenter, observational study. We show that individuals with the more severe form of the disease, OI type III, have significantly reduced FVC and FEV₁ which do not follow the expected trends of the normal population. We also show that "normalization" of FVC and FEV₁ using general population data to generate percent predicted values underestimates the pulmonary involvement in OI. Within each subtype of OI, we used linear mixed models to find potential correlations between FEV₁ and FVC with the clinical variables including mobility, bisphosphonate use, and scoliosis. Our results are an important step in understanding the extent of pulmonary involvement in individuals with OI and for developing pulmonary endpoints for use in the routine patient care as well as in the investigation of new therapies.

Keywords: lung disease; osteogenesis imperfecta; pulmonary function; spirometry.

Figure 1:

Observed FVC and FEV₁ in type I collagen-related OI. Each dot represents observed FVC and FEV1 from the baseline visit of a single participant. The Lines represent the LOESS regression lines for each OI type. Whereas OI types I and IV demonstrate age-related increase in FVC and FEV₁, such changes are absent in OI type III.

Figure 2:

Predicted FVC and FEV₁ values were calculated using reference population data generated by Hankinson et al. Each dot represents predicted FVC and FEV₁ for a single participant. The lines represent the LOESS regression lines for control population and each OI type.