MEDIATORS OF MYOFIBROBLAST DIFFERENTIATION IN ARDS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在美国，每年有15万例急性呼吸窘迫综合征（ARDS）新发病例。 尽管支持性护理和通气策略有所改善，但死亡率仍约为30%。 大多数死亡发生在机械通气的第一周之后，并且不能停止机械通气部分是由于以间充质细胞活化为标志的纤维增生性ARDS（fARDS）的发展。 最近，多份报告描述了fARDS中肌成纤维细胞的存在。 肌成纤维细胞在细胞外基质沉积和肺顺应性受损中起重要作用。 在这项研究中，我们将获得呼出气体分析（即代谢车），呼出气冷凝液（EBC）和支气管肺泡肺灌洗液从ARDS患者。 我们还将从非ARDS机械通气对照患者和纤维化肺病（FLD）对照患者中获得相同的测量结果。 呼出气体分析将用于估计通气患者的死腔分数，EBC和BAL将用于确定肺泡液是否含有可诱导肌成纤维细胞分化的因子。 然后，我们将确定EBC和BALF诱导的肌成纤维细胞与死腔分数和重要临床结局（即死亡率、无ICU天数和无通气天数）之间是否存在关系。

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).