Genome-wide association study of short-acting β2-agonists. A novel genome-wide significant locus on chromosome 2 near ASB3.

Rationale: β2-Agonists are the most common form of treatment of asthma, but there is significant variability in response to these medications. A significant proportion of this responsiveness may be heritable.

Objectives: To investigate whether a genome-wide association study (GWAS) could identify novel pharmacogenetic loci in asthma.

Genetic predictors associated with improvement of asthma symptoms in response to inhaled corticosteroids.

Background: To date, genome-wide association studies (GWASs) of inhaled corticosteroid (ICS) response in asthmatic patients have focused primarily on lung function and exacerbations.

Objective: We hypothesized that GWAS analysis could identify novel genetic markers predicting a symptomatic response to ICSs.

Methods: We analyzed differences in asthma symptoms in response to ICSs in 124 white children from the Childhood Asthma Management Program (CAMP) trial using scores from diary cards.

Genome-wide association identifies the T gene as a novel asthma pharmacogenetic locus.

Rationale: To date, most studies aimed at discovering genetic factors influencing treatment response in asthma have focused on biologic candidate genes. Genome-wide association studies (GWAS) can rapidly identify novel pharmacogenetic loci.

Objectives: To investigate if GWAS can identify novel pharmacogenetic loci in asthma.

Predictors of symptoms are different from predictors of severe exacerbations from asthma in children.

Background: Asthma therapy is typically prescribed and titrated based on patient or parent self-report of symptoms. No longitudinal studies have assessed the relationship between symptoms and severe asthma exacerbations in children. The goal of our study was (1) to assess the association of asthma symptoms with severe asthma exacerbations and (2) to compare predictors of persistent asthma symptoms and predictors of severe asthma exacerbations.

Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study.

Background: Asthma exacerbations, most often caused by respiratory tract infections, are the leading causes of asthma morbidity and comprise a significant proportion of asthma-related costs. Vitamin D status might play a role in preventing asthma exacerbations.

Objectives: We sought to assess the relationship between serum vitamin D levels and subsequent severe asthma exacerbations.

Patterns of inhaled corticosteroid use and asthma control in the Childhood Asthma Management Program Continuation Study.

Background: Daily controller medication use is recommended for children with persistent asthma to achieve asthma control.

Objective: To examine patterns of inhaled corticosteroid (ICS) use and asthma control in an observational study of children and adolescents with mild-to-moderate asthma (the Childhood Asthma Management Program Continuation Study).

Methods: We assessed patterns of ICS use during a 12-month period (consistent, intermittent, and none) and asthma control (well controlled vs poorly controlled).

IL1B polymorphisms modulate cystic fibrosis lung disease.

Rationale: Variability in pulmonary disease severity is found in patients with cystic fibrosis (CF) who have identical mutations in the CF transmembrane conductance regulator (CFTR) gene. We hypothesized that one factor accounting for heterogeneity in pulmonary disease severity is variation in the family of genes affecting the biology of interleukin-1 (IL-1), which impacts acquisition and maintenance of Pseudomonas aeruginosa infection in animal models of chronic infection.

Methods: We genotyped 58 single nucleotide polymorphisms (SNPs) in the IL-1 gene cluster in 808 CF subjects from the University of North Carolina and Case Western Reserve University (UNC/CWRU) joint cohort.

Repeatability of response to asthma medications.

Background: Pharmacogenetic studies of drug response in asthma assume that patients respond consistently to a treatment but that treatment response varies across patients; however, no formal studies have demonstrated this.

Objective: To determine the repeatability of commonly used outcomes for treatment response to asthma medications: bronchodilator response, FEV(1), and PC(20).

Methods: The Childhood Asthma Management Program was a multicenter clinical trial of children randomized to receiving budesonide, nedocromil, or placebo.

Polymorphisms in IL12A and cockroach allergy in children with asthma.

Background: IL12A has been implicated in T-cell development and may thus influence the development of atopy and allergic diseases.

Methods: We tested for association between four linkage disequilibrium (LD)-tagging SNPs (rs2243123, rs2243151, rs668998, and rs17826053) in IL12A and asthma and allergy-related (serum total and allergen-specific IgE, and skin test reactivity [STR] to two common allergens) phenotypes in two samples: 417 Costa Rican children with asthma and their parents, and 470 families of 503 white children in the Childhood Asthma Management Program (CAMP). The analysis was conducted using the family-based association test (FBAT) statistic implemented in the PBAT program.