Treatment of IPF with Laparoscopic Anti-reflux Surgery

描述（由申请方提供）：特发性肺纤维化（IPF）是一种原因不明的慢性进行性肺病，在美国的患病率不断增加。据估计，今年将有10万美国人死于IPF，除了只有1%的人会接受肺移植外，没有FDA批准的治疗方法。在过去十年中，已经提出胃食管反流（格尔）和微抽吸在IPF进展中的潜在作用。胃酸反流和非胃酸反流可能都很重要，IPF患者的初步数据表明，腹腔镜胃底折叠术在减缓疾病进展方面的获益高于单独的药物抗酸剂治疗。在等待肺移植的IPF和其他形式的晚期肺病患者中安全地进行了腹腔镜胃底折叠术。这些数据为在IPF和相关GER患者中进行腹腔镜胃底折叠术试验提供了令人信服的论据。在临床建议中，我们假设腹腔镜胃底折叠术减少异常格尔将减缓IPF的进展（通过用力肺活量（FVC）测量）。为了解决这一假设，我们提出了以下目的：目的1：确定腹腔镜胃底折叠术对IPF患者48周内FVC变化的影响。 目的2：将IPF患者48周内酸和非酸反流事件的减少与FVC变化相关联。 目的3：确定腹腔镜胃底折叠术在IPF患者中的安全性。 目的4：探讨腹腔镜胃底折叠术在48周内对IPF关键次要终点的影响。 在辅助提案中，我们将通过使用血清、支气管肺泡灌洗液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，检验异常格尔有助于IPF中肺上皮细胞的促纤维化表型的假设。 临床研究

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