Joanne K. Fagan

Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial.

BACKGROUND The issue of whether regular use of an inhaled beta2-adrenergic agonist worsens airflow and clinical outcomes in asthma is controversial. Retrospective studies have suggested that adverse effects occur in patients with a genetic polymorphism that results in homozygosity for arginine (Arg/Arg), rather than glycine (Gly/Gly), at aminoacid residue 16 of the beta2-adrenergic receptor. However, the existence of any genotype-dependent difference has not been tested in a prospective clinical trial. METHODS Patients with mild asthma, not using a controller medication, were enrolled in pairs matched for forced expiratory volume in 1 s (FEV1) according to whether they had the Arg/Arg (n=37; four of 41 matches withdrew before randomisation) or Gly/Gly (n=41) genotype. Regularly scheduled treatment with albuterol or placebo was given in a masked, cross-over design, for 16-week periods. During the study, as-needed albuterol use was discontinued and ipratropium bromide was used as needed. Morning peak expiratory flow rate (PEFR) was the primary outcome variable. The primary comparisons were between treatment period for each genotype; the secondary outcome was a treatment by genotype effect. Analyses were by intention to treat. FINDINGS During the run-in period, when albuterol use was kept to a minimum, patients with the Arg/Arg genotype had an increase in morning PEFR of 23 L/min (p=0.0162); the change in patients with the Gly/Gly genotype was not significant (2 L/min; p=0.8399). During randomised treatment, patients with the Gly/Gly genotype had an increase in morning PEFR during treatment with regularly scheduled albuterol compared with placebo (14 L/min [95% CI 3 to 25]; p=0.0175). By contrast, patients with the Arg/Arg genotype had lower morning PEFR during treatment with albuterol than during the placebo period, when albuterol use was limited (-10 L/min [-19 to -2]; p=0.0209). The genotype-attributable treatment difference was therefore -24 L/min (-37 to -12; p=0.0003). There were similar genotype-specific effects in FEV1, symptoms, and use of supplementary reliever medication. INTERPRETATION Genotype at the 16th aminoacid residue of the beta2-adrenergic receptor affects the long-term response to albuterol use. Bronchodilator treatments avoiding albuterol may be appropriate for patients with the Arg/Arg genotype.

Characteristics and Correlates of Asthma Knowledge Among Emergency Department Users in Harlem

We constructed a questionnaire to assess asthma knowledge, assessed its psychometric properties, and examined its association with demographic characteristics, psychosocial factors, and disease severity and management in 375 adults following an asthma-related emergency department visit. Overall knowledge was poor but varied widely among respondents. Better knowledge was related to younger age, higher education, and less severe disease. Chance-orientated health locus of control and low self-esteem were associated with lower asthma knowledge. Better knowledge was associated with better disease management. We conclude that asthma education can lead to improved disease outcomes, and psychosocial factors need to be considered when designing interventions for asthma education.

Oral β2-Agonist Use by Preschool Children with Asthma in East and Central Harlem, New York

Although studies have documented underuse of controller medications and overuse of short-acting inhaled β2-agonist among children with persistent asthma in disadvantaged communities, the persistence of oral β2-agonist use in pediatric practice has not been studied since inhaled short-acting β2-agonists became widespread. We describe medications used to treat asthma among children 3 to 5 years of age at 10 Head Start and other subsidized preschool centers in East and Central Harlem, New York City. We interviewed 149 parents/guardians of children who were identified as having probable asthma based on physicians diagnosis, persistent symptoms, hospitalization, and medication use. We classified 86 of the 149 children (58%) as having current persistent asthma. Only 15 of them (17%) were reported to have used controller medications at least 5 days/week in the last 4 weeks—only 2 of whom used inhaled corticosteroids. By contrast, 53 children (62%) used oral β2-agonist in the last 4 weeks, often (72%) in conjunction with nebulized or inhaled short-acting β2-agonist. Use of oral β2-agonist was associated with more severe symptoms. This study documents the continued widespread use of oral β2-agonist for treatment of children in a low-income community with high prevalence of asthma.