Effect of positive airway pressure therapy of obstructive sleep apnea on circulating Angiopoietin-2

Obstructive sleep apnea (OSA) has been identified as a possible contributor to interstitial lung disease. While positive airway pressure (PAP) is effective therapy for OSA, it causes large increases in lung volumes during the night that are potentially deleterious, analogous to ventilator-induced lung injury, although this has not been previously studied. The goal of this study was to assess the impact of PAP therapy on four biomarkers of alveolar epithelial and endothelial injury and extracellular matrix remodeling in patients with OSA. In 82 patients with moderate to severe OSA who were adherent to PAP therapy, surfactant protein D, osteopontin, angiopoietin-2, and matrix metalloprotease-7 were measured by ELISA in serum samples collected before and 3- to 6-months after initiation of PAP therapy. An increase in angiopoietin-2 level of 0.28 ng/mL following PAP therapy was observed (p = 0.007). This finding was replicated in an independent sample of OSA patients. No significant change was detected in surfactant protein D, osteopontin, or matrix metalloprotease-7. This finding raises concern for a possible adverse impact of PAP therapy on vascular endothelium. • Obstructive sleep apnea is associated with biomarkers of systemic inflammation. • CPAP did not reduce biomarkers of alveolar epithelial and endothelial injury. • Angiopoietin-2, a marker of endothelial injury and CVD risk, increased with CPAP. • Increased lung stretch due to CPAP may be associated with vascular inflammation. • This unexpected effect may limit the cardiovascular benefit of CPAP.