Impact of Gender on Symptoms and Progression of IPF

这个K23奖项的目标是提供候选人所需的资源，以开发一个独立的 在终末期肺部疾病的临床研究中的研究生涯包括以下内容：（1）专注于 在纵向数据分析、非参数统计、 缺失数据和以患者为中心的结局;（2）保护时间以获得进一步的实践经验， 作为IPF CRN的研究实习生进行临床试验;以及（3）在两位博士的密切指导下。 Fernando J. Martinez和Kevin Flaherty，在IPF临床研究方面具有丰富经验， 成功的指导。为了最大限度地实现这些目标，研究计划不仅要前瞻性地 描述特发性肺动脉高压患者的生理进展、生存率和症状的性别差异。 纤维化（IPF），但也研究为什么这些差异可能存在使用临床和生物学数据，从 IPF CRN和肺组织研究联盟。回顾性数据表明，IPF男性患者的进展 速度更快，生存率更差。初步数据表明，可测量的生物（肽 激素松弛素）和生理（肺动脉收缩压）差异有助于性别 疾病表型的差异。具体目标包括：（1a）表征男性和女性IPF表型 通过生物学和生理学参数的基线比较（1 B）确定 生物学和生理学参数，以更好地了解IPF性别差异背后的机制 表型;（2a）确定性别是否影响肺功能的纵向变化，并探索 已知与性别相关的其他因素的贡献改善（2b）比较急性 男性和女性之间的恶化（2c）前瞻性地确定女性性别是否与 IPF生存期改善，与其他生物和生理参数无关， （3a）确定基线健康状况和症状测量，特别是焦虑和 抑郁症在患有IPF的女性中比男性更异常（3b）决定性别差异是否 存在于健康状况和症状测量的纵向行为中。 相关性（参见说明）： 这项研究有可能对公共卫生产生重大影响。这些结果不仅可以带来更好的 IPF的说明和对性别在未来慢性疾病研究设计中的作用的更深入了解 但也将提供可能导致IPF生物标志物开发的关键数据 和临床治疗试验。

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.