The Genetics of Respiratory Failure in Bronchiolitis

Bronchiolitis is a potentially severe infection of the airway in infants and children, and among the most frequent diagnoses leading to pediatric intensive care unit admission in infants. This acute infection is caused by an array of viruses, but respiratory syncytial virus (RSV) is the most frequently implicated. The majority of infants hospitalized with bronchiolitis are previously healthy, and half of infants intubated and mechanically ventilated for respiratory failure due to RSV bronchiolitis have no previously identified risk factors. It is likely, therefore, that other factors, particularly genetic heterogeneity of the host, contribute to disease severity. However, no previous study has investigated the association of genetic variants with respiratory failure in children with bronchiolitis. Several categories of candidate genes have emerged as potentially important in the pathogenesis of the disease. Specifically, genetic polymorphisms of surfactants, pattern recognition receptors, receptor adhesion molecules, and cytokines have been examined. The aim is to evaluate these polymorphisms to determine their association with respiratory failure in a cohort of more severely ill children with bronchiolitis.

Study Overview

• Status: Completed
• Conditions: Bronchiolitis

Detailed Description

We propose to conduct a prospective observational study of infants and children admitted with bronchiolitis to determine if genetic polymorphisms in a number of likely candidate immune response related genes are positively associated with respiratory failure in this population. Respiratory failure will be defined as requiring intubation and mechanical ventilation. We plan to enroll two groups of children, those admitted to the ICU with respiratory failure due to bronchiolitis (cases) and those children admitted to the ward with less severe bronchiolitis infection (controls). In special circumstances, we will also enroll pairs of twins who are hospitalized with bronchiolitis (in the ICU or the ward), for whom either one or both twins do not meet inclusion criteria as a case or a control and/or for whom we are not able to obtain a DNA blood sample while hospitalized (twin inpatient population).

Demographic data, and data regarding the hospital treatments and course of these children will be collected. Blood, saliva or sputum for genotyping will also be obtained. If a patient enrolled as a control needs to be intubated, these children cannot be control patients, but instead would be considered cases.

We propose to compare a population of 100 children with respiratory failure due to bronchiolitis to a population of 100 children with bronchiolitis without respiratory failure. Clinical characteristics and genetic markers will be compared. We will also compare clinical characteristics and genetic markers of any twin pairs who are enrolled.

• Study Type: Observational
• Enrollment (Actual): 174

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Children hospitalized with bronchiolitis

Description

Inclusion Criteria, cases:

• admission to the ICU with a primary diagnosis of bronchiolitis
• endotracheally intubated and mechanically ventilated with respiratory failure due to bronchiolitis
• age less than 2 years

Exclusion Criteria, cases:

• pre-existing chronic disease including:

  1. bronchopulmonary dysplasia
  2. congenital heart disease
  3. immune deficiency
• requiring an additional venopuncture for blood collection for genotyping

Inclusion Criteria, controls:

• admission to the hospital with a primary diagnosis of bronchiolitis
• age less than 2 years

Exclusion Criteria, controls:

• pre-existing chronic disease including:

  1. bronchopulmonary dysplasia
  2. congenital heart disease
  3. immune deficiency
• requiring an additional venopuncture for blood collection for genotyping
• requiring non-invasive positive pressure ventilation or high flow nasal cannula
• requiring intubation and mechanical ventilation during the hospitalization

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Cases; Children hospitalized in the ICU with bronchiolitis
Controls; Children hospitalized in the general ward with bronchiolitis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Failure	The primary end point is respiratory failure.	2 years

Collaborators and Investigators

• Sponsor: Connecticut Children's Medical Center
• Collaborators: UConn Health
• Investigators: Principal Investigator: Christopher L Carroll, MD, MS, Connecticut Children's Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: November 9, 2010
• First Submitted That Met QC Criteria: January 5, 2011
• First Posted (Estimate): January 6, 2011

Study Record Updates

• Last Update Posted (Actual): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Pediatric
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Respiratory Insufficiency; Bronchiolitis
• Other Study ID Numbers: 10-097

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
• product manufactured in and exported from the U.S.: No