The Genetics of Respiratory Failure in Bronchiolitis
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Bronchitis, Pulmonary |
| Therapuetic Areas: | Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | Any - 2 |
| Updated: | 7/19/2018 |
| Start Date: | November 2010 |
| End Date: | October 2020 |
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.
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.
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.
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.
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
We found this trial at
1
site
282 Washington St
Hartford, Connecticut 06106
Hartford, Connecticut 06106
(860) 545-9000
Phone: 860-545-9805
Connecticut Children's Medical Center Connecticut Children’s Medical Center is a nationally recognized, 187-bed not-for-profit children’s...
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