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.
Randomized, controlled, prospective, and large animal translational studies.
University large animal intensive care unit.
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).
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
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.
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