Altered collagen I and premature pulmonary embryonic differentiation in patients with OI type II

Abstract

Pulmonary hypoplasia and respiratory failure are primary causes of death in patients with osteogenesis imperfecta (OI) type II. OI is a genetic skeletal disorder caused by pathogenic variants in genes encoding collagen type I. It is still unknown if the collagen defect also affects lung development and structure, causing lung hypoplasia in OI type II. The aim of this study was to investigate the intrinsic characteristics of OI embryonic lung parenchyma and to determine whether altered collagen type I may compromise airway development and lung structure. Lung tissue from nine fetuses with OI type II and six control fetuses, matched by gestational age, was analyzed for TTF‐1 and collagen type I expression by immunohistochemistry, to evaluate the state of lung development and amount of collagen. The differentiation of epithelium into type 2 pneumocytes during embryonic development was premature in OI type II fetuses compared to controls (p < 0.05). Collagen type I showed no significant differences between the two groups. However, the amount of alpha2(I) chains was higher in fetuses with OI and the ratio of alpha1(I) to alpha2(I) lower in OI compared to controls. Cell differentiation during lung embryonic development in patients with OI type II is premature and impaired. This may be the underlying cause of pulmonary hypoplasia. Altered cell differentiation can be secondary to mechanical chest factors or a consequence of disrupted type I collagen synthesis. Our findings suggest that collagen type I is a biochemical regulator of pulmonary cell differentiation, influencing lung development.

Bronchial obstruction in osteogenesis imperfecta can be detected by forced oscillation technique

“…Unlike previous studies where it was not possible to differentiate between a restrictive and an obstructive problem using FOT (36), our technique was able to assess the resistance, reactance, and the resonant frequency during both inspiration and expiration, giving insights in the respiratory function. Our findings provide support for the presence of obstructive lung disease in OI patients, as observed in four patients through standard PFTs and nearly all patients using FOT (16,32). These results are consistent with the recent Danish study that emphasized obstructive disease as a significant contributor to hospitalization, medical utilization, and mortality in patients with OI (29).…”

“…However, the Danish study linked respiratory-related deaths to chronic obstructive pulmonary disease (29). Our recent study on OI type II fetuses revealed intrinsic lung alterations, suggesting similar changes in other OI types (32). Our understanding of the mechanisms behind respiratory complications in OI remains limited.…”