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.
This project seeks to understand the role of allergic disease in contributing to poor outcomes and disease progression in COPD. We will also determine whether the combination of sensitization and exposure to indoor allergens contributes to COPD morbidity, a question that has never been studied in COPD, despite strong associations in the population with asthma. Ultimately, this study will help to determine whether home environmental interventions to reduce allergen burden hold potential to reduce COPD morbidity, which could in turn inform COPD guidelines that currently do not provide guidance regarding individuals with COPD and concomitant allergic disease.
