A 24 Month Observational Study of Infants 3-24 Months, Who Suffer an Acute Episode of Respiratory Infection and Wheezing Illness (BIOPA)

Respiratory BIOmarkers in Viral Wheezing That Predict Asthma

This study will identify infants between the age of 3 and 24 months of age who are experiencing one of their first acute respiratory infections with confirmed wheezing. Infants who are also confirmed to be wheezing and whose caregiver signs consent will be enrolled from a primary care clinic, emergency room or hospital.

Study Overview

• Status: Completed
• Conditions: Respiratory Tract Infections; Wheezing

Detailed Description

BACKGROUND: Respiratory virus infections are extremely common in young children. These infections typically lead to inflammation and constriction of the airways, which is termed bronchiolitis. Bronchiolitis is the leading cause of hospitalization for infants with respiratory infections, with an average of 120,000 children under the age of one hospitalized every year. Viral infection by Respiratory Syncytial Virus (RSV), rhinoviruses, or influenza viruses is thought to be by far the major driver of bronchiolitis. The children who need to be hospitalized with bronchiolitis have a drastically increased chance (about 45%) of developing chronic respiratory diseases such as wheezing or asthma. The disease of asthma affects children more than adults, and the Centers For Disease Control states that asthma is the most chronic condition among children under the age of 18, affecting more than 6 million (or 8.4%) children in the US. Due to this prevalence, asthma is the third leading cause of hospitalization among children under the age of 15 years, with the annual direct healthcare costs at ~$50 billion every year. The economic costs associated with parental lost productivity is another ~$6 billion every year. The American Lung Association states that asthma is also one of the leading causes of school absenteeism, with an estimated 13.8 million lost school days every year. While asthma can be managed with bronchodilator inhalers, there is not a single treatment designed to prevent or reverse asthma disease. Understanding how viral infection causes initial bronchiolitis and maintains the chronic inflammation that leads to asthma will lead to new treatments that prevent or reverse chronic lung diseases. This research has the potential to change everyday life for millions of children and their families in the US.

• Study Type: Observational
• Enrollment (Actual): 5

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 2 years (Child)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants will be offered enrollment into the study via Institutional Review Board-approved methods including review of newly hospitalized patients to Duke Children's Hospital, patients seen in the Duke Children's Hospital Emergency Room, and patients seen in a Duke Children's ambulatory clinics. Consent: The study will be explained to the participant and caregiver by trained study staff (Principal Investigator, Co-Investigator, research coordinator or research assistant).

Description

Inclusion Criteria:

• Documented informed consent from legal guardian prior to study procedures
• Age: 3-24 months at the time of visit 1
• Severe lower respiratory wheezing illness confirmed by auscultation requiring hospitalization or acute care (Emergency Department care or unscheduled ambulatory care)

Exclusion Criteria:

• No prior hospital admissions for wheezing illnesses
• No prior diagnosis of asthma or Reactive Airways Disease
• More than 1 prior episode of wheezing confirmed by auscultation
• No congenital or chronic disease which would negatively affect the conduct of the study (e.g. childhood cancer, cystic fibrosis, interstitial lung disease, prior aero-digestive surgery)
• No diagnosis of bronchopulmonary dysplasia
• No premature birth (gestational age < 32 weeks)
• Daily treatment with a daily asthma controller (e.g. Montelukast, inhaled corticosteroid)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Infants ages 3-24 months with respiratory infections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistent Asthma Phenotype (PAP)	Participants will be assessed for meeting criteria for the persistent asthma phenotype which will be defined as meeting any Asthma Predicative Indices plus abnormal lung pulmonary function testing by Impulse oscillometry (either from peripheral airway resistance or bronchodilator responsiveness).	Measured at 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total confirmed Respiratory tract infections as measured by nasal secretion sampling.		Up to 24 months
Pulmonary Function Testing (iPFT)	Impulse Oscillometry (IOS) simply requires the child to breathe in and out through a mouthpiece for 20-30 seconds. During breathing, a loudspeaker delivers a quiet pulse-shaped pressure-flow signal to the respiratory system. The overall respiratory system impedance (Z) is measured and reflects the resistive and viscoelastic forces of the respiratory system determined from the returning signal. Outcome data are reported as respiratory system resistance (R) and reactance (X) measured in centimeters of water per liter per second. Measurements from the 3 efforts for each outcome parameter will be averaged for the final result.	Measured at 24 months
Presence or absence of Loose Asthma Predictive Indices	Lose API is based on based on any wheezing in first 3 years of life plus, One of the following two: Parental asthma or child eczema, AND Two of the following three: eosinophilia, wheezing without colds, and allergic rhinitis.	24 months
Presence or absence of Strict Criteria for API	Strict API is measured based on Early Frequent wheezing in first 3 years of life plus, One of the following two: Parental asthma or child eczema, AND Two of the following three: eosinophilia, wheezing without colds, and allergic rhinitis.	24 months
Presence or absence of Modified API	Modified API is measured based on ≥4 wheezing episodes in a year plus, One of the following two: Parental asthma or child eczema or allergic sensitization to at least one aeroallergen, AND Two of the following three: eosinophilia, wheezing without colds, and allergic sensitization to milk, egg or peanuts.	24 months

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: The Hartwell Foundation
• Investigators: Principal Investigator: Jason Lang, MD, MPH, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Actual): June 16, 2020
• Study Completion (Actual): June 16, 2020

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: November 12, 2018
• First Posted (Actual): November 14, 2018

Study Record Updates

• Last Update Posted (Actual): November 25, 2020
• Last Update Submitted That Met QC Criteria: November 24, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Infections; Respiratory Tract Infections; Respiratory Sounds
• Other Study ID Numbers: Pro00100494

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No