Defining Acute Exacerbations of Idiopathic Pulmonary Fibrosis

本K23提案的目的是允许我作为临床研究人员继续发展， 目标是成为间质性肺病研究的独立领导者。在指导下 Talmadge E.博士金纪念Michael A.马泰，并与指导网络的经验丰富的 临床和基础研究人员，我将获得必要的经验和技能，以实现这一目标。 我设计的研究方案涉及特发性肺动脉高压急性加重的定义 纤维化（IPF）在临床和生物学水平。IPF是间质性肺的一种常见和高度病态形式 疾病，其中急性加重是一个重要组成部分。发病率，原因和临床 急性加重意义仍然知之甚少。最近，NHLBI创建了IPF 临床研究网络（IPFNet），以进行大规模、精心设计的IPF干预性研究。通过 定位我的研究建议，以利用IPFNet的主题和基础设施，我计划实现 以下四个具体目标： 目的1：确定IPF急性加重的发生率和风险因素。 目的2：明确隐匿性病毒感染在IPF急性加重中的病因作用。 目的3：确定凝血功能紊乱在IPF急性加重中的作用。 目的4：证明IPF急性加重的预后意义。 为了实现这些目标，将从一名患者中收集临床数据、呼吸道分泌物和血液样本。 估计有150例IPF急性加重和适当控制的受试者。本研究提案 可以提供对急性加重的频率和原因的了解，提供证据， 设计预防和治疗的干预性试验。重要的是，这项研究提案还将有助于 培养我的职业发展目标，在开展前瞻性临床研究方面获得经验和专业知识 研究试验，掌握先进的生物统计技术，并发展多学科 临床和基础科学家之间的合作。这些技能将使我充分认识到 临床研究为基础生物学和医学知识提供信息。

The purpose of this K23 proposal is to allow for my continued development as a clinical researcher with the goal of becoming an independent leader in the investigation of interstitial lung disease. Under the mentorship of Dr. Talmadge E. King, Jr. and Dr. Michael A. Matthay, and with guidance from a network of experienced clinical and basic researchers, I will obtain the experience and skills necessary to achieve this goal. The research proposal I have designed involves defining acute exacerbations of Idiopathic Pulmonary Fibrosis (IPF) at a clinical and biological level. IPF is a common and highly morbid form of interstitial lung disease, of which acute exacerbations are an important component. The incidence, causes, and clinical significance of acute exacerbations remain poorly understood. Recently, the NHLBI has created the IPF Clinical Research Network (IPFNet) to allow for large-scale, well-designed interventional studies of IPF. By positioning my research proposal to take advantage of IPFNet subjects and infrastructure, I plan to achieve the following four specific aims: Aim 1: To determine the incidence of and risk factors for acute exacerbations ofIPF. Aim 2: To define the etiologic role of occult viral infection in acute exacerbations ofIPF. Aim 3: To determine the role of disordered coagulation in acute exacerbations ofIPF. Aim 4: To demonstrate the prognostic significance of acute exacerbations ofIPF. To achieve these aims, clinical data, respiratory secretions, and blood samples will be collected from an estimated 150 subjects with acute exacerbations of IPF and appropriate controls. This research proposal may provide insight into the frequency and causes of acute exacerbations,providing evidence upon which to design interventional trials of prevention and treatment. Importantly, this research proposal will also serve to foster my career development goals of gaining experience and expertise in conducting prospective clinical research trials, mastering sophisticated biostatistical techniques, and developing multidisciplinary collaborations among clinical and basic scientists. These skills will allow me to fully realize the power of clinical research to inform basic biology and advance medical knowledge.