The goal of the proposed research is to use a prospective cohort of very low birthweight (VLBW) infants to determine the role of human rhinoviruses (HRV) in premature infant respiratory illnesses and subsequent asthma development.
The specific aims of this project are: 1) To define the incidence of symptomatic HRV infection among VLBW infants during the first year of life;2) To determine the prevalence of recurrent wheeze and asthma in children who were infected with HRV as infants;and 3) To elucidate viral and host factors associated with HRV respiratory disease severity in premature infants and subsequent asthma development. We present preliminary evidence that the novel HRVC group are associated with wheezing in VLBW infants, and that type III IFN-? is associated with HRV disease severity in these infants. There are currently no means to prevent asthma and thus the findings of this research are likely to improve human health. These findings might be generalizable to other patient populations and guide further studies to broaden the scope of impact. This will be the premise for a lifelong career in the study of the viral-asthma relationship, and will be the foundation for many other important future studies. The work proposed uses a unique combination of clinical and laboratory approaches to address these questions, and the knowledge gained from these studies will likely elucidate potential novel prevention and treatment strategies. I have the expertise, motivation, and leadership necessary to successfully complete the proposed work. My training in HRV research and asthma offer specific expertise in key areas for this application. I have learned to perform basic molecular diagnostics of real-time RT-PCR for viruses, carried out epidemiologic studies of HRV in young hospitalized children, and have performed viral sequencing to genotype HRV strains. I have applied this laboratory knowledge to large cohorts to describe some of the first statistically significant clinical differences in various HRV groups. The current application builds logically on my prior work to answer important questions in the area of HRV and asthma. I have laid the groundwork to pursue these studies effectively, and have the mentorship to guide me as I further my training and knowledge in biological pathogenesis hypothesis development, testing, and reporting. My primary research mentor and committee have demonstrated their commitment to my career as outlined in my biosketch and their letters. While I have had the opportunity to acquire skills that have helped me to pursue studies of viruses and asthma, I require further mentored research to equip myself with skills such as working with cohorts and investigation of pathogenetic hypotheses. This award will enhance my career development and optimize my chances for success in independent research.

Public Health Relevance

The goal of the proposed research is to continue/establish a prospective cohort of very low birthweight (VLBW) infants designed to determine the role of human rhinoviruses (HRV) in premature infant illness and subsequent asthma development in Argentina;and to investigate the role of the virus and host in this relationship.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AI091691-03
Application #
8429440
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Hauguel, Teresa M
Project Start
2011-03-01
Project End
2016-02-29
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
3
Fiscal Year
2013
Total Cost
$123,481
Indirect Cost
$7,739
Name
Vanderbilt University Medical Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Miller, E Kathryn; Avila, Pedro C; Khan, Yasmin W et al. (2014) Wheezing exacerbations in early childhood: evaluation, treatment, and recent advances relevant to the genesis of asthma. J Allergy Clin Immunol Pract 2:537-43
Linder, Jodell E; Kraft, David C; Mohamed, Yassir et al. (2013) Human rhinovirus C: Age, season, and lower respiratory illness over the past 3 decades. J Allergy Clin Immunol 131:69-77.e1-6
Miller, E Kathryn; Gebretsadik, Tebeb; Carroll, Kecia N et al. (2013) Viral etiologies of infant bronchiolitis, croup and upper respiratory illness during 4 consecutive years. Pediatr Infect Dis J 32:950-5
Miller, E Kathryn; Hernandez, Johanna Zea; Wimmenauer, Vera et al. (2012) A mechanistic role for type III IFN-ýý1 in asthma exacerbations mediated by human rhinoviruses. Am J Respir Crit Care Med 185:508-16
Miller, E Kathryn; Bugna, Jimena; Libster, Romina et al. (2012) Human rhinoviruses in severe respiratory disease in very low birth weight infants. Pediatrics 129:e60-7