MARC-35: Prospective Cohort Study of Severe Bronchiolitis and Risk of Recurrent Wheezing

Investigators:
Carlos A. Camargo, MD, DrPH, Massachusetts General Hospital, Boston, MA
Michelle B. Dunn, MD, Children’s Hospital of Philadelphia, Philadelphia, PA
Haitham Haddad, MD, Rainbow Babies & Children’s Hospital, Cleveland, OH
Federico Laham, MD, MS, FAAP, Arnold Palmer Hospital, Orlando, FL
Charles G. Macias, MD, Baylor College of Medicine, Houston, TX
Jonathan M. Mansbach, MD, Children’s Hospital Boston, Boston, MA
Brian Pate, MD, The Children’s Mercy Hospital & Clinics, Kansas City, MO
Pedro A. Piedra, MD, Baylor College of Medicine, Houston, TX
Wayne G. Shreffler, MD, PhD, Massachusetts General Hospital, Boston, MA
Michelle D. Stevenson, MD, MS, University of Louisville, Louisville, KY
Richard T. Strait, MD, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
Stephen J. Teach, MD, MPH, Children’s National Medical Center, Washington, DC

Funding Source: National Institutes of Health (U01 AI087881)

Purpose: (1) To examine the association between (a) the infectious etiology of a child’s severe bronchiolitis, and (b) the severity of this illness, and the subsequent development of recurrent wheezing by age 3 years; (2) To examine the association between the level of serum 25-hydroxyvitamin D (25[OH]D) during severe bronchiolitis and the subsequent development of recurrent wheezing by age 3 years; (3) To combine these clinical and laboratory data to derive the wheezing index (WIND), a new clinical index that will identify children at higher risk of developing recurrent wheezing by age 3 years.

Rationale: Bronchiolitis is the most common cause of infant hospitalization in the US. Small cohort studies of children hospitalized with bronchiolitis have found that 20-60% of these children will develop recurrent wheezing of childhood; almost 50% will develop doctor-diagnosed asthma by age 6 years. Despite this strong association, it remains unclear which children with severe bronchiolitis (as defined by the need for hospitalization) will develop recurrent wheezing and eventually asthma. Indeed, no one has rigorously or effectively defined sub-groups of children with severe bronchiolitis who may respond differently to medications and/or have different clinical outcomes. As a result, lingering questions have followed other large studies designed to improve the treatment and understanding of children with severe bronchiolitis.

Procedure: This study will include children age <1 year hospitalized with severe bronchiolitis at 10 different EMNet hospitals.  The study will be coordinated by the EMNet Coordinating Center (Boston, MA). In brief, we will collect data for 2 consecutive years from November until April beginning in 2011.  During the hospitalization, we will collect clinical data, a NPA, blood, and a nasal swab.  The post-hospitalization follow-up involves phone calls, further collection of nasal swabs, and acquisition of medical records.  Researchers at each site will call the families 1-week post discharge. Subsequently, EMNet staff will conduct all phone calls – starting at approximately 3 weeks post-admission, and then from the age of 6 months every 6 months for approximately 5-6 years depending on age at enrollment. (Note: 1U01AI087881-01A1 will fund phone calls for first 4 years of study, then we will seek new funding for calls to age 6 years, as permitted per original consent form.  If new funding is not obtained, internal funds will be used to complete the study per protocol.)  A nasal swab will be collected by the parent/legal guardians 3 weeks after the date of index admission or by study personnel if the study participant is still hospitalized (clearance swab). Parent/legal guardians will also collect a nasal swab during the first summer after enrollment sometime in June, July, or August and 1 other time during the second year after enrollment (seasonal swab).  Additionally, until the child is age 3 years, the parent/legal guardian will collect a nasal swab each time the child has an outpatient, ED, or hospital visit related to an acute respiratory infection (ARI) called the ARI swab.  Relevant medical records will be acquired by site researchers and EMNet staff from enrollment until age 6 years. (Note: U01 1U01AI087881-01A1 will fund collection of medical records for first 4 years of study, then we will seek new funding for records to age 6 years, as permitted per original consent form.  If new funding is not obtained, internal funds will be used to complete the study per protocol.)

Site and patient data will come from multiple sources: site PI questionnaire (Site Form), study participant inclusion screening (Screening Form), hospital interview and chart review (Intake Form), family contact information (Contact Form), mother prenatal diet information (Maternal Pregnancy and Nutrition Form), inpatient chart review (Inpatient Form), readmission Intake Form, readmission inpatient form. Telephone interview one week after discharge (1-week Follow-Up Form), telephone interview three weeks after admission (3-week Follow-Up Form), telephone interview/online survey every 6 months from birth (6-month Follow-Up Form), assessment of severity of acute respiratory infection (ARI swab Form), assessment of potential worsening of ARI (ARI swab Follow-Up Form), assessment of wellness at three weeks after admission (Clearance Swab Form), assessment of wellness before seasonal swab collection (Seasonal Swab Form), review of medical records from birth, including HIPAA-approved medical release (Chart Review Form), parental allergy data collected during child medical record review (Parent Chart Review Form), protocol deviation form, and the adverse event case report form.