Bronchiolitis is the #1 cause of infant hospitalization in the USA. Small cohort studies (n<210) suggest that 40-50% of hospitalized infants with bronchiolitis will develop childhood asthma. Unfortunately, it remains unclear which infants will develop asthma and this knowledge gap has hindered primary prevention efforts. The 35th Multicenter Airway Research Collaboration (MARC-35) study (U01 AI-87881; Camargo, PI) is a 17-center prospective cohort study that will complete enrollment of ~940 hospitalized infants with bronchiolitis (80% ward, 20% intensive care unit) in April 2014. In this diverse U.S. cohort (~52% African-American or Hispanic), site investigators have collected nasopharyngeal and blood samples (including DNA); extensive interview and survey data; and medical records from primary care, emergency department, and inpatient settings. Follow-up data include biannual parent interviews and annual review of medical records (~91% follow-up to date). For timing reasons, the primary outcome of the 5- year U01 grant is recurrent wheezing by age 3 years. However, all participants were consented for follow-up to age 6 years to permit ascertainment of asthma (as defined by doctor diagnosis, plus either asthma medication use or symptoms in past year); incident asthma at age 5 years is the primary outcome of this R01 ancillary application.
The Specific Aims address two risk factors for childhood asthma: 1) specific IgE, which preliminary data show in ~20% of MARC-35 infants; and 2) rhinovirus type C, a still-undefined subset (likely half) of the ~21% of infants with rhinovirus bronchiolitis.
Aim 3 examines the potential interaction between these two factors and incident asthma. Preliminary data (n=745) already show a strong interaction between infant specific-IgE and rhinovirus (not yet typed) and two available outcomes: risk of recurrent wheeze by age 12 months and use of inhaled corticosteroids by age 18 months (both Pinteraction<0.01). The R01 would provide funds to examine IgE sensitization longitudinally by testing serum specific IgE at age 42 months (3.5 years), rhinovirus typing by partial sequencing for rhinovirus samples from the index hospitalization, and continued follow-up with biannual telephone calls and annual chart reviews through age 5 years; these activities are not funded by the U01 grant. The application is time sensitive because of the new 42-month exam and follow-up after age 3 years. The study has >80% power for all aims. The investigators are NIH-funded researchers with international expertise in the field. The study advances research on the primary prevention of asthma, and matches well with the 2009 NIH strategic plan for pediatric respiratory research.

Public Health Relevance

In a 17-center prospective cohort study of ~940 infants originally hospitalized with bronchiolitis, who are being followed until the age of 3 years, investigators propose to add an in-person evaluation at age 3.5 years and to extend follow-up to age 5 years. These important changes will permit investigation, in a diverse U.S. cohort (~52% African-American or Hispanic), of the relation between two infant factors (specific IgE and rhinovirus type C bronchiolitis) and the development of asthma. The study is sufficiently large that it can test the hypothesis that infants with both risk factors (as compared to infants with neither) are at much higher risk of developing childhood asthma, a new finding that will advance efforts to prevent childhood asthma.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI114552-05
Application #
9604305
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Minnicozzi, Michael
Project Start
2014-12-01
Project End
2020-11-30
Budget Start
2018-12-01
Budget End
2020-11-30
Support Year
5
Fiscal Year
2019
Total Cost
Indirect Cost
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 :
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
Dumas, Orianne; Hasegawa, Kohei; Mansbach, Jonathan M et al. (2018) Severe bronchiolitis profiles and risk of recurrent wheeze by age 3 years. J Allergy Clin Immunol :
Hasegawa, Kohei; Stewart, Christopher J; Mansbach, Jonathan M et al. (2017) Sphingolipid metabolism potential in fecal microbiome and bronchiolitis in infants: a case-control study. BMC Res Notes 10:325
Hasegawa, Kohei; Linnemann, Rachel W; Mansbach, Jonathan M et al. (2017) Nasal Airway Microbiota Profile and Severe Bronchiolitis in Infants: A Case-control Study. Pediatr Infect Dis J 36:1044-1051
Stewart, Christopher J; Mansbach, Jonathan M; Wong, Matthew C et al. (2017) Associations of Nasopharyngeal Metabolome and Microbiome with Severity among Infants with Bronchiolitis. A Multiomic Analysis. Am J Respir Crit Care Med 196:882-891
Hasegawa, Kohei; Linnemann, Rachel W; Mansbach, Jonathan M et al. (2017) Household siblings and nasal and fecal microbiota in infants. Pediatr Int 59:473-481
Wu, Vickie; Abo-Sido, Nora; Espinola, Janice A et al. (2017) Predictors of successful telephone follow-up in a multicenter study of infants with severe bronchiolitis. Ann Epidemiol 27:454-458.e1
Hasegawa, K; Mansbach, J M; Ajami, N J et al. (2017) The relationship between nasopharyngeal CCL5 and microbiota on disease severity among infants with bronchiolitis. Allergy 72:1796-1800

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