期刊
JCI INSIGHT
卷 7, 期 2, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.154573
关键词
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资金
- US Department of Defense Congressionally Directed Medical Research Program [W81XWH-18-1-0682]
- NIH/National Heart, Lung, and Blood Institute [R01-HL149422, R01-HL135849, K24-HL103836, F32-HL162230, T32-HL007085, TL1-TR002533]
- Colorado Clinical and Translational Sciences Institute [CO-M-21-5]
- Deutsche Forschungsgemeinschaft (German Research Foundation) [SFB 1449/B01]
This study investigated the mechanism and factors influencing lung injury in patients with acute respiratory distress syndrome, and found a close relationship between epithelial glycocalyx degradation and shedding of airspace glycosaminoglycans, suggesting a potential target for ARDS treatment and providing new predictive and monitoring methods for clinicians.
Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure yet has few pharmacologic therapies, reflecting the mechanistic heterogeneity of lung injury. We hypothesized that damage to the alveolar epithelial glycocalyx, a layer of glycosaminoglycans interposed between the epithelium and surfactant, contributes to lung injury in patients with ARDS. Using mass spectrometry of airspace fluid noninvasively collected from mechanically ventilated patients, we found that airspace glycosaminoglycan shedding (an index of glycocalyx degradation) occurred predominantly in patients with direct lung injury and was associated with duration of mechanical ventilation. Male patients had increased shedding, which correlated with airspace concentrations of matrix metalloproteinases. Selective epithelial glycocalyx degradation in mice was sufficient to induce surfactant dysfunction, a key characteristic of ARDS, leading to microatelectasis and decreased lung compliance. Rapid colorimetric quantification of airspace glycosaminoglycans was feasible and could provide point-of-care prognostic information to clinicians and/or be used for predictive enrichment in clinical trials.
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