Treatment of IPF with Laparoscopic Anti-reflux Surgery

描述（由申请人提供）：特发性肺纤维化（IPF）是一种病因不明的慢性进行性肺部疾病，在美国发病率不断上升。据估计，今年将有10万美国人死于IPF，除了只有1%的人会接受肺移植，目前还没有fda批准的治疗方法。在过去的十年中，胃食管反流（GER）和微误吸在IPF进展中的潜在作用已被提出。酸反流和非酸反流可能都很重要，来自IPF患者的初步数据表明，在减缓疾病进展方面，腹腔镜下盆底复制比单纯药物抗酸治疗更有益处。在IPF和其他形式的晚期肺部疾病等待肺移植的患者中，腹腔镜下的肺复盖术是安全的。这些数据为IPF和相关GER患者的腹腔镜手术提供了一个令人信服的论据。在临床建议中，我们假设通过腹腔镜下的强制肺活量（FVC）测量，减少异常GER将减缓IPF的进展。为了解决这一假设，我们提出以下目标：目的1：确定腹腔镜下扩底术对IPF患者48周内FVC变化的影响。目的2：将IPF患者48周内胃酸和非胃酸反流事件的减少与FVC的变化联系起来。目的3：探讨IPF患者腹腔镜下手术的安全性。目的4：探讨腹腔镜下扩底术对IPF患者48周内关键次要终点的影响。在辅助提案中，我们将通过使用血清、支气管肺泡灌洗和气道上皮细胞中的分子生物标志物来评估异常GER的存在和治疗的生物学相关性，来验证异常GER导致IPF肺上皮细胞纤维化表型的假设。

DESCRIPTION (provided by applicant): Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease of unknown cause and increasing prevalence in the United States. An estimated 100,000 Americans will die from IPF this year, and aside from lung transplantation, which only 1% will receive, there is no FDA-approved therapy. Over the last decade, a potential role for gastro-esophageal reflux (GER) and microaspiration in the progression of IPF has been suggested. Both acid and non-acid reflux are likely important, and preliminary data from IPF patients suggest an increased benefit of laparoscopic fundoplication over medical antacid therapy alone in slowing disease progression. Laparoscopic fundoplication has been safely performed in patients with IPF and other forms of advanced lung disease awaiting lung transplantation. These data provide a compelling argument for a trial of laparoscopic fundoplication in patients with IPF and associated GER. In the clinical proposal, we hypothesize that the reduction of abnormal GER with laparoscopic fundoplication will slow the progression of IPF as measured by the forced vital capacity (FVC). To address this hypothesis, we propose the following aims: Aim 1: To determine the impact of laparoscopic fundoplication on change in FVC over 48 weeks in IPF. Aim 2: To correlate the reduction in acid and non-acid reflux events with change in FVC over 48 weeks in IPF. Aim 3: To determine the safety of laparoscopic fundoplication in patients with IPF. Aim 4: To explore the impact of laparoscopic fundoplication on key secondary endpoints over 48 weeks in IPF. In the ancillary proposal, we will test the hypothesis that abnormal GER contributes to the profibrotic phenotype of lung epithelial cells in IPF by using molecular biomarkers in the serum, bronchoalveolar lavage, and airway epithelial cells to assess the biological relevance of the presence and treatment of abnormal GER. CLINICAL STUDY