Impact of Gender on Symptoms and Progression of IPF

描述(申请人提供)：这个K23奖项的目标是提供在终末期肺部疾病临床调查中发展独立研究生涯所需的候选资源，其中包括：(1)在纵向数据分析、非参数统计、缺失数据的处理以及以患者为中心的结果方面的重点额外教学培训；(2)有保护的时间获得进一步的临床试验实践经验，作为IPF CRN的研究实习生；以及(3)在Fernando J.Martinez博士和Kevin Flaherty博士的密切指导下，他们在IPF临床研究方面拥有丰富的经验并进行成功的指导。为了最大限度地实现这些目标，该研究计划不仅将寻求前瞻性地描述特发性肺纤维化(IPF)在生理进展、存活率和症状方面的性别差异，而且还将利用IPF CRN和肺组织研究联盟的临床和生物学数据来研究为什么会存在这些差异。回顾数据表明，患有特发性肺间质纤维化的男性进展更快，生存更差。初步数据表明，可测量的生物差异(肽、激素、松弛素)和生理差异(肺动脉收缩压)导致了疾病表型的性别差异。具体目标包括：(1a)通过生物和生理参数的基线比较确定男性和女性IPF的表型特征(1b)确定生物和生理参数之间的关系，以更好地了解IPF表型性别差异背后的机制；(2a)确定性别是否影响肺功能的纵向变化，并探索已知与性别有关的其他因素改善的贡献(2b)比较男性和女性的急性加重率(2c)前瞻性地确定女性是否独立于其他与性别相关的生物和生理参数而改善IPF的存活率；(3a)确定IPF女性的基线健康状况和症状测量，特别是焦虑和抑郁是否比男性更异常(3b)确定健康状况和症状测量的纵向行为是否存在性别差异。相关性(见说明)：这项研究有可能对公共卫生产生重大影响。这些结果不仅可以更好地预测IPF，更好地洞察性别在未来慢性肺部疾病研究设计中的作用，而且还将提供关键数据，可能导致IPF生物标记物的开发和治疗性临床试验。(摘要结束)

DESCRIPTION (provided by applicant): The goal of this K23 award is to provide the candidate resources needed to develop an independent research career in the clinical investigation of end stage lung disease including the following: (1) focused additional didactic training in the analysis of longitudinal data, nonparametric statistics, the handling of missing data, and patient centered outcomes; (2) protected time to gain further practical experience in clinical trial conduct as an investigative trainee of the IPF CRN; and, (3) close mentoring under both Drs. Fernando J. Martinez and Kevin Flaherty, individuals with extensive experience in IPF clinical research and successful mentoring. To maximize these goals the research plan will not only seek to prospectively describe gender differences in physiologic progression, survival, and symptoms in idiopathic pulmonary fibrosis (IPF) but also investigate why these differences might exist using clinical and biologic data from the IPF CRN and Lung Tissue Research Consortium. Retrospective data suggests that men with IPF progress more rapidly and experience worse survival. Preliminary data suggest that measurable biologic (peptide hormone relaxin) and physiologic (pulmonary artery systolic pressure) differences contribute to gender differences in disease phenotype. Specific aims include: (1a) characterize male and female IPF phenotypes through baseline comparison of biologic and physiologic parameters (1 b) determine the relationship between biologic and physiologic parameters to better understand mechanisms behind gender differences in IPF phenotype; (2a) determine if gender influences longitudinal change in pulmonary function and explore the contribution of other factors improves known to be associated with gender (2b) compare the rate of acute exacerbations between men and women (2c) determine prospectively whether female gender is associated with improved survival in IPF independent of other biologic and physiologic parameters associated with gender; (3a) determine whether baseline health status and symptom measures, particularly anxiety and depression, are more abnormal in women with IPF than men (3b) determine whether gender differences exist in the longitudinal behavior of health status and symptom measures. RELEVANCE (See instructions): This research has the potential for significant public health impact. The results could lead not only to better prognostication of IPF and improved insights into the role of gender in the design of future studies of chronic lung disease but will also provide key data that could lead to the both the development of a biomarker for IPF and a therapeutic clinical trial. (End of Abstract)