MEDIATORS OF MYOFIBROBLAST DIFFERENTIATION IN ARDS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There are 150,000 new cases of the Acute Respiratory Distress Syndrome (ARDS) annually in the US. Despite improvements in supportive care and ventilation strategies, the mortality is approximately 30%. The majority of deaths occur after the first week of mechanical ventilation and the inability to discontinue mechanical ventilation is due in part to development of fibroproliferative ARDS(fARDS) that is marked by mesenchymal cell activation. Recently, multiple reports have described the presence of myofibroblasts in fARDS. Myofibroblasts play an important role in extracellular matrix deposition and impaired lung compliance. In this investigation we will obtain expired gas analysis (i.e. metabolic cart), exhaled breath condensate (EBC) and bronchoalveolar lung lavage fluid from ARDS patients. We will also obtain the same measures from non-ARDS mechanically ventilated control patients, and fibrotic lung disease (FLD) control patients. The expired gas analysis will be used to estimate the dead space fraction in the ventilated patients and the EBC and BAL will be used determine if alveolar fluid contains factors that can induce myofibroblast differentiation. We will then determine if there is a relationship of myofibroblast induction by EBC and BALF and dead space fraction and important clinical outcomes (i.e. mortality, ICU-free days and vent-free days).