Pulmonary Effects of Bronchial Segmental Endotoxin Instillation in Humans

我们将筛选最多58名健康志愿者，目标是招募最多48名受试者参与研究。 将研究两个队列。将在单个时间点对一个健康受试者队列进行支气管镜检查和BAL研究（最多n = 12）。这将提供肺细胞和血细胞，以在没有任何炎症刺激的情况下评估驻留肺细胞的免疫表型。将采用流式细胞术和细胞培养对细胞进行研究。 将在6 - 24小时的时间段内离体研究细胞相关和分泌的miRNA。 第二组受试者（n = 36）将在接受支气管镜节段性内毒素激发后进行研究。将在本次攻毒后6（n=12）、24（n=12）或48小时（n=12）进行BAL。参加第一个队列的受试者将有资格参加第二个队列，在其早期参与后间隔4周进行内毒素挑战。在这3个时间点用BAL获得的细胞将提供研究分泌的和细胞相关的miRNA的变化及其与特定细胞类型的关系的手段。 方案于2015年1月26日获得批准。我们于2015年6月18日招募了第一例受试者，迄今为止已完成了6项对照研究。该研究预计将于2016年秋季末开始研究的内毒素部分。

We will screen up to 58 healthy volunteers with the goal of enrolling up to 48 subjects to participate in the study. Two cohorts will be studied. One cohort of healthy subjects will be studied with bronchoscopy and BAL (up to n = 12) at a single time point. This will provide lung and blood cells to assess immunophenotypes of resident pulmonary cells in the absence of any inflammatory stimulus. The cells will be studied with flow cytometry and with cell culture. Cell-associated and secreted miRNA will be studied ex vivo over a 6 24 hour period. A second cohort of subjects (n = 36) will be studied after undergoing segmental endotoxin challenge with bronchoscopy. BAL will be performed at either 6 (n=12), 24 (n=12) or 48 hours (n=12) after this challenge. Subjects who participated in the first cohort will be eligible to participate in the 2nd cohort with endotoxin challenge after a 4-week interval from their earlier participation. The cells acquired with BAL at these 3 time points will provide a means to study changes in secreted and cell associated miRNA and their relation to specific cell types. The protocol was approved on 01/26/2015. We enrolled our first subject on 06/18/2015 and have completed six control studies to date.The study expects to initiate the endotoxin portion of the study by late fall 2016.