The Role of Microaspiration in Idiopathic Pulmonary Fibrosis

描述（由申请方提供）：特发性肺纤维化（IPF）是一种无有效治疗的一致致死性弥漫性肺部疾病。新出现的数据表明，微抽吸可能在IPF的发病机制和自然史中发挥作用。确定微抽吸和IPF之间的关系可能具有重要的病理生物学和治疗意义。目标和目的：本提案的长期目标是确定微抽吸在IPF中的作用。目的1：确定IPF患者中微抽吸的患病率。目的2：阐明IPF患者微抽吸的生物标志物。目的3：确定微抽吸对IPF疾病进展的影响。研究设计和方法：该提案涉及一个前瞻性确定的30例IPF受试者队列。将通过测量支气管肺泡灌洗液中的胃蛋白酶水平来确定IPF中微抽吸的患病率（目的1）。将使用食管功能研究（24小时pH监测和测压）、实验室检查、放射学成像和调查确定IPF中微抽吸的生物标志物（目的2）。将通过测量12个月内肺功能的变化和评估紧急医疗护理使用率（计划外门诊访视、急诊室访视和住院）来定义微抽吸对疾病进展的影响（目标3）。该提案与NHLBI的使命直接相关：“支持新研究人员的研究培训和职业发展，以开展与肺部疾病诊断相关的临床研究。“这项建议包括临床研究技能的高级培训，这将为未来作为一名独立的临床研究人员取得成功提供必要的技能。研究与公共卫生的相关性：特发性肺纤维化（IPF）是一种致死性疾病，没有任何已知的治疗或治愈方法。确定微抽吸在IPF中的作用很重要，因为它可能导致有效的治疗选择。有效治疗将显著改善IPF患者的生活质量和生存期。

DESCRIPTION (provided by applicant): Idiopathic pulmonary fibrosis (IPF) is a uniformly fatal diffuse lung disease with no effective treatment. Emerging data suggest that microaspiration may play a role in the pathogenesis and natural history of IPF. Defining the relationship between microaspiration and IPF could have major pathobiological and therapeutic implications. Objectives and Aims: The long-term objective of this proposal is to define the role of microaspiration in IPF. Aim 1: To determine the prevalence of microaspiration in patients with IPF. Aim 2: To elucidate biomarkers of microaspiration in patients with IPF. Aim 3: To define the impact of microaspiration on disease progression in IPF. Research Design and Methods: This proposal involves a prospectively identified cohort of 30 subjects with IPF. The prevalence of microaspiration in IPF (Aim 1) will be determined by measuring pepsin levels in bronchoaveolar lavage fluid. Biomarkers for microaspiration in IPF (Aim 2) will be identified using esophageal function studies (24h pH monitoring and manometry), laboratory tests, radiological imaging, and survey. The impact of microaspiration on disease progression (Aim 3) will be defined by measuring changes in pulmonary function over 12 months and assessing rates of urgent medical care use (unscheduled clinic visit, emergency room visit, and hospitalization). This proposal is directly relevant to the mission of the NHLBI: "supporting research training and career development of new researchers to enable conduct of clinical research related to diagnosis of lung disease." This proposal includes advanced training in clinical research skills that will provide the necessary skills for future success as an independent clinical researcher. Relevance of Research to Public Health: Idiopathic pulmonary fibrosis (IPF) is a fatal disease without any known treatment or cure. Defining the role of microaspiration in IPF is important because it could lead to effective treatment options. Effective treatment will substantially improve the quality of life and survival of those patients suffering with IPF.