Bronchiolitis is the most common cause of infant hospitalization in the US. Small cohort studies (n=51 to 206) suggest that 20-60% of children with severe bronchiolitis (as defined by the need for hospitalization) will develop recurrent wheezing of childhood. Despite this strong association, it remains unclear which children with severe bronchiolitis will develop recurrent wheezing. The proposed prospective multicenter cohort study has 3 specific aims to address this knowledge gap: 1) To examine the association between infectious etiology, illness severity, and CCL5 level and the development of recurrent wheezing by age 3 years. 2) To examine the association between the child's level of serum 25-hydroxyvitamin D [25(OH)D] and recurrent wheezing. 3) To combine these clinical and laboratory data to create a state-of-the-art childhood wheezing index (WIND) to identify children with severe bronchiolitis who are at higher risk of developing recurrent wheezing. This index would identify who might benefit from initiation of inhaled corticosteroids or other asthma control measures, as recommended by the 2007 NIH asthma guidelines. The research team is comprised of NIH-funded researchers who have led many multicenter studies in this area. Over a 2-year period, researchers at 10 hospitals will enroll 1,000 children age <1 year with severe bronchiolitis. Data collection for this cohort will include diaries, biannual interviews, and an annual review of relevant medical records. The study will use the Emergency Medicine Network, a clinical research collaboration that has completed >60 multicenter studies focusing on respiratory emergencies and public health. Site investigators will collect nasopharyngeal and blood samples;demographic, birth, nutritional, family, and environmental information;and clinical data from the parents and from primary care, emergency department, and inpatient settings. The study will have 80% power to detect a 1.3- to 1.8-fold difference in the development of recurrent wheezing for comparisons of children with rhinovirus bronchiolitis (vs. RSV or other pathogens), admitted to the intensive care unit (vs. regular ward), and with detectable (vs. not detectable) CCL5 in nasopharyngeal aspirate. Treating 25(OH)D as a continuous variable, the study will have 80% power to detect a 1.3-fold increase in the odds of recurrent wheezing for a 1 SD (19 nmol/L) increase in 25(OH)D. Study investigators estimate that WIND will have a positive predictive value of e85% to identify children with severe bronchiolitis who will develop recurrent wheezing. The study matches well with the 2009 NIH strategic plan for pediatric respiratory research, and has major public health implications.

Public Health Relevance

In a multicenter prospective cohort study of 1,000 children, a team of investigators will examine the association between two common pediatric conditions: bronchiolitis and recurrent wheezing of early childhood. The project matches well with NIH roadmap initiatives of utilizing clinical networks and focusing on early risk stratification. Specifically, the proposed cohort would improve the short- and long-term care of children with severe bronchiolitis, a condition that often leads to childhood asthma.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01AI087881-01A1
Application #
8206080
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Plaut, Marshall
Project Start
2011-09-01
Project End
2016-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
1
Fiscal Year
2011
Total Cost
$1,316,129
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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
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
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; Mansbach, Jonathan M; Ajami, Nadim J et al. (2017) Serum cathelicidin, nasopharyngeal microbiota, and disease severity among infants hospitalized with bronchiolitis. J Allergy Clin Immunol 139:1383-1386.e6
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, Kohei; Linnemann, Rachel W; Mansbach, Jonathan M et al. (2016) Household siblings and nasal and fecal microbiota in infants. Pediatr Int :
Mahato, Bisundev; Otero, Tiffany M N; Holland, Carrie A et al. (2016) Addition of 25-hydroxyvitamin D levels to the Deyo-Charlson Comorbidity Index improves 90-day mortality prediction in critically ill patients. J Intensive Care 4:40
Mansbach, Jonathan M; Hasegawa, Kohei; Henke, David M et al. (2016) Respiratory syncytial virus and rhinovirus severe bronchiolitis are associated with distinct nasopharyngeal microbiota. J Allergy Clin Immunol 137:1909-1913.e4
Quraishi, Sadeq A; McCarthy, Caitlin; Blum, Livnat et al. (2016) Plasma 25-Hydroxyvitamin D Levels at Initiation of Care and Duration of Mechanical Ventilation in Critically Ill Surgical Patients. JPEN J Parenter Enteral Nutr 40:273-8
Dumas, Orianne; Mansbach, Jonathan M; Jartti, Tuomas et al. (2016) A clustering approach to identify severe bronchiolitis profiles in children. Thorax 71:712-8

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