Bronchiolitis is the #1 cause of hospitalization in US infants, with ~130,000 hospitalizations annually. Small cohort studies (n<210) suggest that 40-50% of infants hospitalized with bronchiolitis will later develop asthma. The greatest challenges for developing primary prevention strategies for this large group of children (indeed, all children) are the very early identification of modifiable risk factors and the heterogeneity of asthma. The 35th Multicenter Airway Research Collaboration (MARC-35) study (U01AI-087881; Camargo, PI) is a 17-center prospective cohort study that completed enrollment of 921 hospitalized infants with bronchiolitis in 2014. In this diverse cohort (53% African-American or Hispanic), investigators have collected biospecimens, including nasal swabs at the index hospitalization (median age 3 months) and at an age 3y exam (R01AI-114552; Camargo, PI). Follow-up data include biannual parent interviews and medical records to age 5 years, with ~90% follow-up to date. This UG3/UH3 application would: 1) extend the largest severe bronchiolitis cohort in the world (e.g., through an age 6y in-person exam to diagnose and phenotype asthma), and 2) build on our local MARC-43 cohort of 120 healthy infants by adding 600 healthy infants from four diverse sites (total n=720). Both cohorts undergo similar procedures (e.g., serial nasal swabs during early childhood). Our overarching hypothesis is that airway Moraxella abundance is associated with increased risk of childhood asthma, and our pilot data are supportive.
In Aim 1, we will investigate the relation of the airway microbiome in early infancy to risk of age 6y asthma among infants with severe bronchiolitis (MARC-35).
In Aim 2, we will do the same but among healthy infants (MARC-43).
In Aim 3, we will investigate the relation of longitudinal patterns of the airway microbiome (e.g., infancy, age 3y, age 6y) to risk of childhood asthma in the two cohorts combined. In a subset of 200 children (100 from each cohort), we will use whole genome shotgun (WGS) sequencing to examine the relations of bacterial species and metabolic potential in early infancy to risk of asthma. For all 3 Aims, we will examine if associations differ by asthma phenotype (e.g., allergic asthma). The investigators are NIH-funded researchers working in an outstanding research environment. The proposed project is innovative and, by providing a strong evidence base for the future development of targeted microbiome interventions, advances research on the primary prevention of asthma. Moreover, the two racially/ethnically-diverse cohorts will provide the ECHO Consortium with comprehensive data on demographics, development, environmental exposures, genetics, and outcomes from two already-harmonized, multicenter U.S. studies.

Public Health Relevance

In two racially/ethnically-diverse cohorts ? MARC-35 with 921 infants originally hospitalized with bronchiolitis, and MARC-43 with 720 healthy infants ? the investigators will examine the relation of nasal airway microbiome in early infancy to risk of developing childhood asthma. The project will advance the primary prevention of asthma and provide two already- harmonized, multicenter U.S cohorts for the ECHO Consortium.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Project #
1UG3OD023253-01
Application #
9262098
Study Section
Special Emphasis Panel (ZRG1-PSE-H (53)R)
Program Officer
Gillman, Matthew William
Project Start
2016-09-21
Project End
2018-08-31
Budget Start
2016-09-21
Budget End
2017-08-31
Support Year
1
Fiscal Year
2016
Total Cost
$1,752,088
Indirect Cost
$530,377
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
Hasegawa, Kohei; Jartti, Tuomas; Bochkov, Yury A et al. (2018) Rhinovirus Species in Children with Severe Bronchiolitis: Multicenter Cohort Studies in the US and Finland. Pediatr Infect Dis J :
Condella, Anna; Mansbach, Jonathan M; Hasegawa, Kohei et al. (2018) Multicenter Study of Albuterol Use Among Infants Hospitalized with Bronchiolitis. West J Emerg Med 19:475-483
Stewart, Christopher J; Hasegawa, Kohei; Wong, Matthew C et al. (2018) Respiratory Syncytial Virus and Rhinovirus Bronchiolitis Are Associated With Distinct Metabolic Pathways. J Infect Dis 217:1160-1169
Luna, Pamela N; Hasegawa, Kohei; Ajami, Nadim J et al. (2018) The association between anterior nares and nasopharyngeal microbiota in infants hospitalized for bronchiolitis. Microbiome 6:2
Forrest, Christopher B; Blackwell, Courtney K; Camargo Jr, Carlos A (2018) Advancing the Science of Children's Positive Health in the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) Research Program. J Pediatr 196:298-300
Hasegawa, K; Stewart, C J; Celedón, J C et al. (2018) Circulating 25-hydroxyvitamin D, nasopharyngeal airway metabolome, and bronchiolitis severity. Allergy 73:1135-1140
Hasegawa, Kohei; Pérez-Losada, Marcos; Hoptay, Claire E et al. (2018) RSV vs. rhinovirus bronchiolitis: difference in nasal airway microRNA profiles and NF?B signaling. Pediatr Res 83:606-614
Hasegawa, K; Piedra, P A; Bauer, C S et al. (2018) Nasopharyngeal CCL5 in infants with severe bronchiolitis and risk of recurrent wheezing: A multi-center prospective cohort study. Clin Exp Allergy 48:1063-1067
Hasegawa, Kohei; Stewart, Christopher J; Celedón, Juan C et al. (2018) Serum 25-hydroxyvitamin D, metabolome, and bronchiolitis severity among infants-A multicenter cohort study. Pediatr Allergy Immunol 29:441-445
Toivonen, Laura; Hasegawa, Kohei; Ajami, Nadim J et al. (2018) Circulating 25-hydroxyvitamin D, nasopharyngeal microbiota, and bronchiolitis severity. Pediatr Allergy Immunol 29:877-880

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