Mechanical ventilation is usually required for saving lives in critically ill patients; however, it can cause ventilator-induced lung injury (VILI). As VEGF-secreting Ly6C^high monocytes are involved in VILI pathogenesis, we investigated whether cyclooxygenase-2 (COX-2) activity regulates the recruitment of VEGF-secreting Ly6C^high monocytes during VILI. The clinically relevant two-hit mouse model of VILI, which involves the intravenous injection of lipopolysaccharide prior to high tidal volume (HTV)-mechanical ventilation, was used in this study. To investigate the role of COX-2 in the recruitment of VEGF-secreting Ly6C^high monocytes during VILI, celecoxib, which is a clinical COX-2 inhibitor, was administered 1 h prior to HTV-mechanical ventilation. Pulmonary vascular permeability and leakage, inflammatory leukocyte infiltration, and lung oxygenation levels were measured to assess the severity of VILI. HTV-mechanical ventilation significantly increased the recruitment of COX-2-expressing Ly6C^high, but not Ly6C^low, monocytes. Celecoxib significantly diminished the recruitment of Ly6C^high monocytes, attenuated the levels of VEGF and total protein in bronchoalveolar lavage fluid, and restored pulmonary oxygenation during VILI. Our findings demonstrate that COX-2 activity is important in the recruitment of VEGF-secreting Ly6C^high monocytes, which are involved in VILI pathogenesis, and indicate that the suppression of COX-2 activity might be a useful strategy in mitigating VILI.

In patients of very severe obstructive sleep apnea (OSA) with confined framework, reducing volume is difficult to achieve a postoperative apnea-hypopnea index (AHI) qualifying the classical surgical success. However, a higher AHI with a larger part of hypopneas may have similar or even less severity of oxygen (O₂) desaturation, compared to a lower index mostly made of apneas. Here, in 27 consecutive enrolled patients, we show that besides the improvement of mean AHI, the multilevel surgery increased hypopnea in AHI from 29.1% to 77.3%, and improves postoperative O₂ saturation by reducing desaturation frequency (mean desaturation index decreased from 62.5 to 24.4 events/h) and level (mean oxyhemoglobin saturation of pulse oximetry (SpO₂) desaturation cut down from 10.0 to 5.8%). The mean SpO₂ improved from 92.3% to 94.7%, and the improvement was positively related to the proportion increase of hypopnea/AHI. The results suggest that the non-framework surgery could help patients with very severe OSA whose AHIs are ≥60 events/h in terms of improving postoperative O₂ saturation. Due to the improvement also presented in those not qualified as classical surgical success, further studies are needed to clarify the connection between O₂ desaturation and various consequences to reconsider defining a surgical success.