The Role of Microaspiration in Idiopathic Pulmonary Fibrosis

描述（由申请人提供）：特发性肺纤维化（IPF）是一种致命的弥漫性肺部疾病，没有有效的治疗方法。新出现的数据表明，微吸可能在IPF的发病机制和自然史中发挥作用。明确微吸与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：本建议的长期目标是确定微吸在指规数中的作用。目的1：确定IPF患者微吸的患病率。目的2：阐明IPF患者微吸的生物标志物。目的3：确定微吸对IPF患者疾病进展的影响。研究设计与方法：本研究纳入30名IPF患者的前瞻性队列研究。IPF患者微吸的发生率（Aim 1）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微吸的生物标志物（Aim 2）将通过食道功能研究（24小时pH监测和测压）、实验室检查、放射成像和调查来确定。微吸入对疾病进展的影响（目的3）将通过测量12个月内肺功能的变化和评估紧急医疗服务的使用率（计划外门诊就诊、急诊室就诊和住院）来确定。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。”该建议包括临床研究技能的高级培训，这将为未来作为独立临床研究人员的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）是一种没有任何已知治疗或治愈方法的致命疾病。确定微吸在IPF中的作用是很重要的，因为它可以导致有效的治疗选择。有效的治疗将大大提高IPF患者的生活质量和生存率。

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.