Clinical trial NCT00570297: Genetic Influences of Albuterol Response In Children With Bronchiolitis
Official title: Genetic Influences of Albuterol Response In Children With Bronchiolitis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Bronchiolitis
Keywords: Pediatric
Polymorphism, Genetic
Adrenergic beta-Agonists
Lead sponsor: Connecticut Children's Medical Center
Sponsor class: OTHER
Collaborators: name: UConn Health
First posted: 2007-12-10
Enrollment: 54
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children hospitalized in the intensive care unit with bronchiolitis

Brief summary: Bronchiolitis is a significant cause of morbidity and hospitalization in children, accounting for approximately 125,000 hospitalizations per year in the U.S. Recently, genetic variations of the β2-adrenergic receptor (β2-AR) have been shown to influence response to β2-AR agonist therapy in children with asthma. We suspect that genetic variations of the β2-AR also affect response to β2-AR agonist therapy in children with bronchiolitis.

Detailed description: Bronchiolitis is a significant cause of morbidity and hospitalization in children, accounting for approximately 125,000 hospitalizations per year in the U.S. Of these hospitalized children, 8% will require intensive care unit (ICU) admission and 67% of these children will require mechanical ventilation. Mortality in previously healthy children is generally low, however, in children with high-risk medical conditions such as prematurity or congenital heart disease, mortality can be as high as 3%. In addition, bronchiolitis infections are associated with long term respiratory problems including development of recurrent wheezing, airway hyperreactivity, and asthma.

Treatment for bronchiolitis is largely supportive. Despite four decades of clinical trials, there are no therapies demonstrated to be effective in shortening either hospitalization or ICU length of stay in children with bronchiolitis. The use of β2-adrenergic receptor (β2-AR) agonists has received the most attention from investigators, however the results of clinical trials have been contradictory and inconclusive.

Recently, investigators have shown that genetic factors have important influences on a patient's response to β2-AR agonists. Single nucleotide polymorphisms (SNP) at amino acid position 16 of the β2-AR gene are thought to be the most functionally relevant. A change at base 46 from adenine to guanine results in the amino acid sequence of the β2-AR containing a glycine (Gly), rather than an arginine (Arg), at amino acid position 16. Patients homozygous for Gly at this position (Gly/Gly) have been shown to have improved response to β2-AR agonist therapy when compared to children homozygous for Arginine (Arg/Arg) or heterozygous (Arg/Gly). The next most common polymorphism of the β2-AR gene, glutamine to glutamic acid at position 27 (Glu27Gln), may be associated with the development of asthma and airway hyperresponsiveness, but these relationships are less clear.

We believe that genetic factors also influence response to β2-AR agonist therapy in children with bronchiolitis. Specifically, we believe that β2-AR polymorphisms at amino acid position 16 affect response to acute β2-AR agonist therapy in children with bronchiolitis. Our hypothesis is that children with bronchiolitis who are homozygous for glycine at amino acid position 16 (Gly/Gly) will have improved response to inhaled β2-AR agonist therapy.

Eligibility criteria: Inclusion Criteria:

* Admission to the CCMC with a primary admission diagnosis of bronchiolitis.
* Age between 0 and 2 years.
* Intubated with cuffed endotracheal tube and mechanically ventilated for less than 72 hours.
* Receiving inhaled albuterol therapy

Exclusion Criteria:

* Congenital Heart Defect
* Immunodeficiency
* Pre-existing chronic lung disease, including asthma
* Receiving additional bronchodilator therapy (such as theophylline or ipratropium) or any therapy that would interfere with measuring pulmonary compliance or resistance
* Receiving Albuterol more frequently than every 4 hours

Primary outcomes:
measure: Change in lung resistance
timeFrame: Immediate
Secondary outcomes:
measure: Change in lung compliance
timeFrame: Duration of hospitalization
measure: Comparison by genotype
timeFrame: Duration of Hospitalization
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
Study officials:
affiliation: Connecticut Children's Medical Center
name: Christopher L Carroll, MD
role: PRINCIPAL_INVESTIGATOR
References: