The association of allergic disease with clinical outcomes in COPD.

 描述（由申请方提供）：虽然特定致敏和暴露于过敏原的组合已被证明与哮喘的发病率相关，但是否存在COPD发病和进展风险较高的COPD个体的相似亚组仍不清楚。初步研究表明，COPD伴特应性的个体亚组具有更差的呼吸道症状和更差的横截面COPD结局。然而，COPD的过敏性亚表型及其与COPD进展的相关性的细节仍有待充分了解。在本申请中，我们计划在来自COPD遗传流行病学研究（COPDGene）的一组个体中研究COPD的过敏性亚表型及其与COPD进展的相关性。COPDGene是一项针对当前和既往吸烟者的正在进行的队列研究，旨在调查COPD发展和进展的风险因素和遗传决定因素。在本提案中，我们将进行一项辅助研究，旨在定义COPD的亚表型，包括过敏性疾病个体。[具体来说，我们将研究COPD基因参与者的整个队列中的临床过敏症状，然后关注600名中重度COPD患者中特异性致敏和全身过敏性炎症标志物的存在，并将这些特征与COPD的以患者为中心的纵向结果相关联。我们还将确定这些过敏性疾病特征是否改变了吸烟与COPD进展之间的已知关联。我们将在SPIROMICS研究中验证这些步骤的结果，以增强我们的发现的强度和普遍性。最后，我们将从[160]名COPD患者的家中收集沉降灰尘样本，以了解致敏和暴露于室内过敏原的组合是否与COPD发病率恶化相关。最终，从该应用程序中获得的信息将有助于了解目前知之甚少的COPD亚表型。此外，这些数据将对COPD的管理和未来对高危人群的环境和过敏原减少策略的测试产生影响。申请人是肺和重症监护医学以及临床流行病学的医生，已证明致力于发展临床研究事业。虽然她是在她的职业生涯早期，她已经表现出了很大的主动性，动力，和生产力在她正在进行的研究工作。该应用程序的结构允许候选人实现她的长期职业目标，成为一名独立的临床研究者，探索合并症在确定COPD结局中的作用，以改善COPD患者导向的结局。在短期内，该提案将允许申请人有专门的时间进行概述的研究项目，并进行免疫学，[环境健康科学]以及与该项目和未来研究计划相关的进一步定量方法的教学培训。[此外，我们希望从这项研究提案中产生的数据将成为R01申请的基础，该申请旨在研究专门的干预措施，以改善过敏性亚型COPD患者的结局，例如消除家庭过敏原。该申请人的职业发展计划包括结构化的指导方法，侧重于特定研究目标的教学课程，参加地方和国家会议，以及确定和定期评估职业里程碑。[自首次申请以来，候选人已被招聘到约翰霍普金斯大学的教师，她80%的时间用于发展她的研究事业。她还扩大了她的已发表和正在进行的项目清单，进一步表明对研究人员职业生涯的承诺。约翰霍普金斯大学提供的研究环境以及本申请中描述的导师团队将帮助Putcha博士成功完成她的职业生涯和研究目标。肺部和重症监护医学部和约翰霍普金斯大学在支持和协作环境中培养成功的年轻临床研究人员方面有着悠久的历史。COPDGene和SPIROMICS研究的现有结构，本申请的母研究，以及申请人与这些小组建立和正在进行的合作，将确保研究目标将在本奖项的时间范围内完成。我们已经组建了一支由具有多年生产研究经验和大量先前指导经验的教师组成的指导团队。在与本建议相关的研究领域，每个机构都有独特的、互补的优势。此外，辅导委员会的每一位成员都是申请人职业发展成为独立调查员的优秀榜样。

 DESCRIPTION (provided by applicant): While the combination of specific sensitizations and exposure to allergens have been shown to be associated with morbidity in asthma, whether there is a similar subgroup of individuals with COPD with higher risk for COPD morbidity and progression remains unclear. Preliminary studies suggest that a subgroup of individuals with COPD with atopy have worse respiratory symptoms and worse cross-sectional COPD outcomes. However, the specifics of the allergic sub-phenotype of COPD and its association with COPD progression remain to be fully understood. In this application, we plan to investigate the allergic sub-phenotype of COPD and its association with progression of COPD in a group of individuals from the Genetic Epidemiology of COPD study (COPDGene). COPDGene is an ongoing cohort study of current and former smokers which seeks to investigate the risk factors for and genetic determinants of COPD development and progression. In this proposal, we will conduct an ancillary study which seeks to define a sub-phenotype of COPD including individuals with allergic disease. [Specifically, we will study clinical allergic symptoms in the full cohort o participants of COPDGene, and then focus on the presence of specific sensitizations and markers of general allergic inflammation in 600 individuals with moderate to severe COPD and correlate these characteristics with patient-centered outcomes of COPD longitudinally. We will also determine whether these allergic disease characteristics modify the known association between smoking and COPD progression. We will validate our findings from these steps in the SPIROMICS study to lend strength and generalizability to our findings.] Finally, we will collect settled dust samples from the homes of [160] individuals with COPD to understand whether the combination of sensitization and exposure to indoor allergens is associated with worse COPD morbidity. Ultimately, the information gained from this application will contribute to understanding a sub-phenotype of COPD that is currently poorly understood. Additionally, these data will have implications for the management of COPD and future testing of environmental and allergen abatement strategies for at-risk individuals. The applicant, a physician in Pulmonary and Critical Care Medicine as well as Clinical Epidemiology, has demonstrated a dedication to developing a career in clinical research. Though she is early in her career, she has shown a great deal of initiative, motivation, and productivity in her ongoing research endeavors. This application is structured to allow the candidate to achieve her long-term career goal of becoming an independent clinical investigator exploring the role of comorbidities in determining COPD outcomes with the goal of improving patient-oriented outcomes in COPD. In the immediate timeframe, this proposal would allow the applicant dedicated time to conduct the outlined research project, as well as pursue didactic training in immunology, [environmental health sciences], and further quantitative methods relevant to this project and future research plans. [Additionally, we hope that the data generated from this research proposal will form the basis for an R01 application seeking to study specialized interventions to improve outcomes in patients with the allergic sub-type COPD such as home allergen abatement.] The career development plan for this applicant includes a structured approach to mentoring, didactic coursework focused on a specific research goal, participation in local and national meetings and identification and regular assessment of career milestones. [Since the initial application, the candidate has been recruited to the faculty at Johns Hopkins University with protection of 80% of her time for the development of her research career. She has also expanded her list of published and ongoing projects, showing further commitment to the career of a researcher.] The research environment provided by Johns Hopkins University as well as the mentorship team described in this application will assist in Dr. Putcha's successful completion of her career and research goals. The Division of Pulmonary and Critical Care Medicine and Johns Hopkins University have a long history of training successful young clinical researchers in a supportive and collaborative environment. The pre-existing structure of the COPDGene and SPIROMICS studies, the parent studies for this application, as well as the applicant's established and ongoing collaboration with these groups, will ensure that the study goals will be completed within the timeframe of this award. We have assembled a mentoring team of established faculty with many years of productive research experience and substantial prior mentoring experience. Each has distinct, complementary strengths in areas of research relevant to this proposal. In addition, each member of the mentoring committee serves as an excellent role model for the applicant's career development into an independent investigator.