Defining Acute Exacerbations of Idiopathic Pulmonary Fibrosis

描述（由申请人提供）：此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疾病研究的独立领导者。在Talmadge E. King, Jr.博士和Michael a . Matthay博士的指导下，在经验丰富的临床和基础研究人员网络的指导下，我将获得实现这一目标所需的经验和技能。我设计的研究计划包括在临床和生物学水平上定义特发性肺纤维化（IPF）的急性加重。IPF是间质性肺疾病中一种常见且高发病率的形式，急性加重是其重要组成部分。急性加重的发生率、原因和临床意义仍然知之甚少。最近，NHLBI创建了IPF临床研究网络（IPFNet），以便对IPF进行大规模、精心设计的介入性研究。通过将我的研究计划定位为利用IPFNet的研究对象和基础设施，我计划实现以下四个具体目标：目标1：确定IPF急性加重的发生率和危险因素。目的2：明确隐匿病毒感染在IPF急性加重中的病原学作用。目的3：确定凝血障碍在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，将从大约150名IPF急性加重的受试者和适当的对照中收集临床数据、呼吸道分泌物和血液样本。本研究方案可深入了解急性发作的频率和原因，为设计预防和治疗的介入性试验提供证据。重要的是，这项研究计划也将有助于促进我的职业发展目标，即获得进行前瞻性临床研究试验的经验和专业知识，掌握复杂的生物统计技术，以及在临床和基础科学家之间开展多学科合作。这些技能将使我充分认识到临床研究在基础生物学和推进医学知识方面的力量。

DESCRIPTION (provided by applicant): 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 of IPF. Aim 2: To define the etiologic role of occult viral infection in acute exacerbations of IPF. Aim 3: To determine the role of disordered coagulation in acute exacerbations of IPF. Aim 4: To demonstrate the prognostic significance of acute exacerbations of IPF. 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.