Interruption of intermittent hypoxia attenuates the severity of pulmonary fibrosis in male mice

Obstructive sleep apnoea (OSA) leading to chronic intermittent hypoxia (CIH) is a common comorbidity associated with idiopathic pulmonary fibrosis (IPF), a progressive fatal disease characterized by adverse lung remodeling and parenchymal stiffening. In the mouse model of lung fibrosis induced by intra-tracheal instillation (ITI) of bleomycin, we have previously shown that CIH exacerbates fibrosis, similar to pre-exposure to ITI. It has been suggested that correction of OSA and CIH with positive airway pressure may have a beneficial effect on the progression of fibrosis in IPF patients. Therefore, we designed this study to determine the benefits of stopping CIH in mice pre-exposed to CIH for 3 weeks prior to bleomycin ITI. Interruption of CIH exposure was associated with less diffuse lung fibrosis, reduced ratio of damaged area, alveolar destruction, collagen deposition, and fibrosis score. Interruption of CIH exposure significantly reduced macrophage density in fibrotic areas without significant changes in either lymphocyte or neutrophil density. In conclusion, this study demonstrates that early treatment of OSA-associated CIH can limit or reduce the development of severe forms of pulmonary fibrosis associated with a reduction in macrophage infiltrate and supports the beneficial effect of CIH exposure interruption on ongoing fibrosis severity.