Beta2-adrenergic receptor polymorphisms in African American children with status asthmaticus.

BACKGROUND: The beta2-adrenergic receptor plays a central role in the bronchodilator response to beta2-agonists in patients with asthma. Genetic polymorphisms within the gene coding for this receptor influence responsiveness of the receptor. A number of these polymorphisms differ in frequency in the African American and white populations. OBJECTIVE: To determine the frequency of specific beta2-adrenergic receptor polymorphisms in African American children with status asthmaticus and to examine whether a specific genotype is associated with the clinical response to therapy. DESIGN: Cohort of African American children diagnosed with status asthmaticus. SETTING: Tertiary care children's hospital. PATIENTS: A total of 31 African American children with status asthmaticus. INTERVENTION: Blood samples were obtained from children at admission. Genotypes were determined by polymerase chain reaction amplification and restriction enzyme digestion. MAIN OUTCOME MEASURES: The requirement for admission to the pediatric intensive care unit, need for mechanical ventilation, institution of various therapies, and length of stay. RESULTS: The genotypes of the polymorphic sites at amino acid positions 16 and 27 in the beta2-adrenergic receptor were determined. There were no significant differences between the various genotypes in the percentage of children requiring pediatric intensive care unit admission, mechanical ventilation, terbutaline treatment, or length of stay. However, in children heterozygous for Glu at position 27 of the beta2-adrenergic receptor, the percentage of patients requiring aminophylline treatment, in addition to beta2-agonist therapy, was significantly higher than that seen in patients homozygous for Gln at that position (5/10 [50%] vs. 1/21 [5%], respectively; p = .002). CONCLUSIONS: African American children with status asthmaticus who have the Gln/Glu genotype at amino acid position 27 of the beta2-adrenergic receptor may benefit from aminophylline treatment in addition to beta2-agonist therapy.

Socioeconomic variation in asthma hospitalization: excess utilization or greater need?

OBJECTIVE: To assess the hypothesis that higher incidence of severe acute asthma exacerbation, not lower severity threshold for admission, explains the difference between the asthma hospitalization rates of inner-city and suburban children. METHODS: All 2028 asthma hospitalizations between 1991 and 1995 for children (aged >1 month and <19 years) dwelling in Rochester, New York, were analyzed. ZIP codes defined residences as inner-city, other urban, or suburban. Based principally on the worst oxygen saturation (SaO2) during the first 24 hours of hospitalization, severity was examined by hospital record review (n = 443) of random samples of inner-city, other urban, and suburban asthma admissions. RESULTS: Large inner-city/suburban differences were noted in many sociodemographic attributes, and there was also a distinct, stepwise gradient in risk factors in moving from the suburbs to other urban areas and to the inner city. Racial and economic segregation was particularly striking. Black individuals accounted for 62% of inner-city births versus <3% in the suburbs. Medicaid covered 65% of inner-city births, whereas Medicaid covered only 6% of suburban births. The overall asthma hospitalization rate was 2.04 admissions/1000 child-years. Children <24 months old, those most commonly hospitalized for asthma, were fourfold more likely to be hospitalized (OR: 3.97, 95% CI: 3. 44-4.57) than children between the ages of 13 and 18 years. The hospitalization rate of asthma in boys was almost twice the rate of asthma in girls. The greatest gender difference was observed among children who were <24 months old. For these children, the rate for boys was 6.10/1000 child-years compared with 2.65/1000 child-years for girls (OR: 2.31, 95% CI: 1.95-3.03). This gender difference diminished gradually in older age groups to the extent that there was no difference among girls and boys between the ages of 13 and 18 years (males, 1.12/1000 child-years vs females, 1.09/1000 child-years). Based on worst SaO2 values, mild (worst SaO2 >/=95%), moderate (90%-94%), and severe (<90%) admissions constituted 10.3%, 41.9%, and 47.7% of all hospitalizations, respectively. Although rates within the community followed a distinct geographic pattern of suburban (1.05/1000 child-years) < other urban (2.99/1000 child-years) < inner-city (5.21/1000 child-years), the proportions of admissions with low severity did not vary among areas. Likewise, the proportions of admissions that were severe (SaO2 <90%) were not significantly different (44.8, 45.7, and 52.1% for suburban, other urban, and inner-city areas, respectively). The distributions of asthma severity, measured by the duration of frequent nebulized bronchodilator treatments and the length of hospital stay, were also similar among children from different socioeconomic areas. CONCLUSION: The marked socioeconomic and racial disparity in Rochester's asthma hospitalization rates is largely attributable to higher incidence of severe acute asthma exacerbations among inner-city children; it signals greater need, not excess utilization. Both adverse environmental conditions and lower quality primary care might explain the higher incidence. Interventions directed at the environment offer the possibility of primary prevention, whereas primary care directed at asthma is focused on secondary prevention, principally on improved medication use. Higher hospitalization rates cannot be assumed to identify opportunities for cost reduction. The extent to which our observations about asthma hold true under other conditions and in other communities warrants systematic attention. Knowledge of when higher rates signal excess utilization and when, instead, they signify greater needs should guide equitable national health policy.