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MARC-43: Airway microbiome and age 6-year asthma phenotypes in a healthy infant cohort

Principal Investigator:
Carlos A. Camargo, MD, DrPH, Massachusetts General Hospital, Boston, MA

Co-investigators:
Elsie M. Taveras, MD, MPH, Massachusetts General Hospital, Boston, MA
Janice A. Espinola, MPH, Massachusetts General Hospital, Boston, MA
Kohei Hasegawa, MD, MPH, Massachusetts General Hospital, Boston, MA

External Co-investigators:
Cindy S. Bauer, MD, Phoenix Children's Hospital, Phoenix, AZ
Jonathan M. Mansbach, MD, MPH Children’s Hospital Boston, Boston, MA
Jonathan M. Spergel, MD, PhD, Children’s Hospital of Philadelphia, Philadelphia, PA
Michelle D. Stevenson, MD, MS, University of Louisville, Louisville, KY

Funding Source: National Institutes of Health (UG3 OD023253)

Purpose: (1) To investigate the relation of the airway microbiome to risk of childhood asthma among healthy infants; (2) To investigate the relation of longitudinal patterns of the airway microbiome (e.g., infancy, age 3 years, and age 6 years) to the risk of childhood asthma in a severe bronchiolitis cohort (MARC-35) and healthy cohort (MARC-43) combined.

Rationale: Childhood asthma remains at historically high levels, affecting ~7 million (9%) U.S. children. The disease is thought to result from a complex interplay between genetic predispositions and environmental exposures, including viral respiratory infections, such as bronchiolitis. Bronchiolitis is the leading cause of hospitalization in US infants, and small cohort studies indicate that 40-50% of infants hospitalized for bronchiolitis (severe bronchiolitis) will develop asthma. However, the underlying mechanism remains unclear. This major knowledge gap has hindered efforts to prevent asthma in this high-risk population. Progression from bronchiolitis to asthma is multi-factorial. Emerging evidence shows that the human microbiome contributes to airway immune response and asthma pathogenesis. To date, most microbiome research has focused on the gut; much less is known about the role of airway microbiome in asthma.

Procedure: This study will enroll healthy children age <1 year at hospital-affiliated outpatient practices. The study is coordinated by the EMNet Coordinating Center (Boston, MA). The study will be known to participants as the Childhood Microbiome study (or the CHIME study). MARC-43 is poised to serve as the “healthy controls” of MARC-35 and therefore undergoes data and specimen collection as well as follow-up similar to MARC-35. MARC-43 participants will have in-person visits at approximate ages of 1-, 2-, 3-, and 6-years in addition to telephone follow-up calls every 6 months. Study staff will collect nasal swabs, saliva swabs, fecal samples, and blood at various time points. Relevant medical records will be acquired by site researchers and EMNet staff from enrollment through age 6 years.

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