35th Multicenter Airway Research Collaboration (MARC-35)

MARC-35 (also known as the WIND Study) is a multicenter, prospective cohort study of severe bronchiolitis and risk of recurrent wheezing. Please contact Dr. Carlos Camargo if you would like additional details.

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

Co-investigators:
Ari R. Cohen, MD, 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
Markus Boos, MD, PhD, Seattle Children’s Hospital, Seattle, WA
Juan C. Celedon, MD, DrPH, Children’s Hospital of Pittsburgh, Pittsburgh, PA
Nancy R. Inhofe, MD, University of Oklahoma/The Children’s Hospital at Saint Francis, Tulsa, OK
Sujit S Iyer, MD, Dell Children’s Medical Center of Central Texas, Austin, TX
Federico R. 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
Henry T. Puls, MD, The Children’s Mercy Hospital & Clinics, Kansas City, MO
Pedro A. Piedra, MD, Baylor College of Medicine, Houston, TX
Stephen C. Porter, MD, MSc, MPH, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
Jonathan M. Spergel, MD, PhD, Children’s Hospital of Philadelphia, Philadelphia, PA
Michelle D. Stevenson, MD, MS, University of Louisville, Louisville, KY
Stephen J. Teach, MD, MPH, Children’s National Medical Center, Washington, DC
Amy Thompson, MD, Alfred I. duPont Hospital for Children, Wilmington, DE
Ilana Waynik, MD, Connecticut Children’s Medical Center, Hartford, CT
Susan Wu, MD, Children’s Hospital of Los Angeles, Los Angeles, CA

Coordinating Center Staff

Steering Committee

Scientific Advisory Board

MARC-35 Site Locations

Funding Source: National Institutes of Health (U01 AI087881, R01AI114552, R01AI127507)

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 includes children age <1 year hospitalized with severe bronchiolitis at approximately 20 different hospitals. The study is coordinated by the EMNet Coordinating Center (Boston, MA). In brief, we collected data for up to 3 consecutive years from November until April beginning in 2011. During the hospitalization, we collected 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 called the families 1-week post discharge. Subsequently, EMNet staff 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: U01AI087881 funded phone calls for first 4 years of study; R01AI114552 will fund calls to age 6 years, as permitted per original consent form.)  A nasal swab was collected by the parent/legal guardians 3 weeks after the date of index admission or by study personnel if the study participant was still hospitalized (clearance swab). Parent/legal guardians also collected 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 collected 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: U01AI087881-01A1 funded collection of medical records for first 4 years of study; R01AI114552 will fund the collection of records to age 6 years, as permitted per original consent form.)

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.

Participants were invited to attend an age 3-year in-person exam. Age 6-year in-person exams are currently underway.

Introductory Video – English and Spanish

With children previously enrolled in MARC-35, MARC-35.5 will 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.

We will examine the relation of the airway microbiome to risk of childhood asthma and identify nasal airway microRNAs that are associated with asthma at age 6 years. We will derive asthma endotypes at age 6 years. This involves ongoing follow-up with the MARC-35 cohort, with an age 6-year in-person exam, and continued follow-up with telephone calls and chart reviews through age 9 years. General Training Presentation Manual of Procedures Visible Flexural Dermatitis Test Photographs (best viewed as slide show) Breath Sounds Reference Guide FeNO Instructional Video NIOX VERO User Manual Nasal Swab Collection Video (Note: this video was created for the baseline study, so for the age 6-year exam please only watch minutes 11:50 to 15:00 and ignore mention of pink VTM since we will be using normal saline) Saliva Specimen Collection Video (Note: created for The CHIME study so please ignore mention of a form being mailed to the study; you will be completing necessary documentation within the Research Exam Form) Stool Specimen Collection Video