RESEARCH: The goal of this proposal is to investigate the clinical and genetic predictors of childhood respiratory disease in former preterm infants. We hypothesize that bronchopulmonary dysplasia (BPD), poor somatic growth, smoke exposure, and genetic variants will be associated with reduced lung growth and obstructive lung disease in former preterm infants. Furthermore, network analysis will reveal shared biology between BPD, chronic obstructive pulmonary disease (COPD), and asthma.
The specific aims expand an existing patient registry, including over 780 former preterm infants with and without BPD who are followed at the Center for Healthy Infant Lung Development at Boston Children?s Hospital. This will include obtaining longitudinal lung function measures and survey data on smoke exposure, as well as initiating a DNA bank of buccal swab specimens. We will perform genome-wide genotyping, and examine specific associations with 48 single nucleotide polymorphisms (SNPs) known to be associated with COPD and lung function. We will leverage existing data from other populations with poor lung growth, and respiratory diseases including BPD, asthma, and COPD, to identify networks and pathways that may define lifelong susceptibility to reduced lung growth and obstructive lung disease, ultimately influencing prognosis, outcomes, and treatment response. This work will stimulate basic discoveries about the causes of BPD and COPD, and enable the translation of these discoveries into clinical practice. CANDIDATE: Lystra P. Hayden, MD, MMSc is a pediatric pulmonologist, Instructor of Pediatrics at Harvard Medical School (HMS) in the Division of Respiratory Disease of Boston Children?s Hospital (BCH) and an Associate Physician at the Channing Division of Network Medicine (CDNM) at Brigham and Women?s Hospital (BWH). She received a Master?s of Medical Science in Biomedical Informatics from HMS. At the CDNM she has been pursing epidemiologic and genomic investigations into the early origins of complex respiratory diseases, specifically COPD, with particular interest in the influences of smoke exposure, pneumonia, asthma and prematurity. Dr. Hayden plans to develop her career in the field of academic pediatric pulmonology as an independent researcher using genomics to elucidate the early origins of pulmonary disease with a focus on BPD, a population which may progress to future COPD patients. ENVIRONMENT: Dr. Hayden will perform her research and career development at the CDNM of BWH, and her clinical work, including subject recruitment, at The Center for Healthy Infant Lung Development in the Division of Respiratory Diseases at BCH. She will be mentored by Craig P. Hersh, MD, MPH, and Edwin K. Silverman, MD, PhD, both leaders in the field of COPD genetic epidemiology and experts in clinical research with excellent track records of mentoring young investigators towards independent research careers.
This project will improve understanding of how smoke exposure, growth, and genetics affect the development of lung disease following premature birth. This is an important area of research as an increasing number of younger and smaller premature infants are surviving into adulthood, many with respiratory disease due to poor lung development that may be similar to asthma and COPD. Genetic studies can help doctors identify who may develop lung disease, what their expected course is, and what the best treatments may be.
|Hayden, Lystra P; Cho, Michael H; Raby, Benjamin A et al. (2018) Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study. Respir Res 19:209|
|Hayden, Lystra P; Hardin, Megan E; Qiu, Weiliang et al. (2018) Asthma Is a Risk Factor for Respiratory Exacerbations Without Increased Rate of Lung Function Decline: Five-Year Follow-up in Adult Smokers From the COPDGene Study. Chest 153:368-377|