Abstract
Objectives:To evaluate the dose effects of Recombinant human Club cell 10-kDa protein (rhCC10) on lung function in a well-characterized ovine model of acute respiratory distress syndrome (ARDS) induced by smoke inhalation injury (SII); specifically, the potential of rhCC10 protein to control the inflammatory response and protect pulmonary tissue and function following SII.Design:Randomized, controlled, prospective, and large animal translational studies.Setting:University large animal intensive care unit.Subjects:Thirty-six adult female sheep were surgically prepared and allocated into five groups (Sham (no SII), n = 6; 1 mg/kg/d CC10, n = 8; 3 mg/kg/d CC10, n = 7; 10 mg/kg/d CC10, n = 8; Control SII, n = 7).Interventions:All groups except the sham group were subjected to SII with cooled cotton smoke. Then, the animals were placed on a ventilator, treated with 1, 3, and 10 mg/kg/d of intravenous rhCC10 or vehicle, divided evenly into two administrations per day every 12 h, fluid resuscitated, and monitored for 48 h in a conscious state.Measurements and main results:The group treated with 10 mg/kg/d rhCC10 attenuated changes in the following variables: PaO2/FiO2 ratio, oxygenation index, and peak inspiratory pressure; neutrophil content in the airway and myeloperoxidase levels; obstruction of the large and small airways; systemic leakage of fluid and proteins, and pulmonary edema.Conclusions:In this study, high-dose rhCC10 significantly attenuated ARDS progression and lung dysfunction and significantly reduced systemic extravasation of fluid and proteins, normalizing fluid balance. Based on these results, rhCC10 may be considered a novel therapeutic option for the treatment of SII-induced ARDS.
Original language | English (US) |
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Pages (from-to) | 317-326 |
Number of pages | 10 |
Journal | Shock |
Volume | 53 |
Issue number | 3 |
DOIs | |
State | Published - Mar 1 2020 |
Keywords
- ARDS
- Burn
- CC10
- CC16
- CCSP
- Lung
- Mortality
- ROS
- SCGB1A1
- Secretoglobin 1A1
- Smoke inhalation
- Uteroglobin
ASJC Scopus subject areas
- Emergency Medicine
- Critical Care and Intensive Care Medicine