Genetic Influences of Albuterol Response In Children With Bronchiolitis

Condition(s) targeted: Bronchiolitis

Phase: N/A

Status: Recruiting

Sponsored by: Connecticut Children's Medical Center

Official(s) and/or principal investigator(s):
Christopher L Carroll, MD, Principal Investigator, Affiliation: Connecticut Children's Medical Center

Overall contact:
Christopher L Carroll, MD, Phone: 860-545-9805, Email: ccarrol@ccmckids.org

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.

Official title: Genetic Influences of Albuterol Response In Children With Bronchiolitis

Study design: Case-Only, Prospective

Primary outcome: The primary end point is change in lung resistance following a single dose of inhaled b2-AR agonist therapy (albuterol).

Secondary outcome:

To assess the change in lung compliance following a single dose of inhaled b2-AR agonist therapy (albuterol)

To compare duration of mechanical ventilation and ICU hospital length of stay by genotype

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.

Minimum age: N/A. Maximum age: 2 Years. Gender(s): Both.

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

Christopher L Carroll, MD, Phone: 860-545-9805, Email: ccarrol@ccmckids.org

Connecticut Children's Medical Center, Hartford, Connecticut 06106, United States; Recruiting
Christopher L Carroll, MD, Phone: 860-545-9805, Email: ccarrol@ccmckids.org

Starting date: December 2007
Ending date: December 2010
Last updated: July 27, 2009