Exacerbation-prone asthma in the context of race and ancestry in Asthma Clinical Research Network trials

BackgroundMinority groups of African descent experience disproportionately greater asthma morbidity compared with other racial groups, suggesting that genetic variation from a common ancestry could influence exacerbation risk.ObjectiveWe evaluated clinical trial measures in the context of self-reported race and genetic ancestry to identify risk factors for asthma exacerbations.MethodsOne thousand eight hundred forty multiethnic subjects from 12 Asthma Clinical Research Network and AsthmaNet trials were analyzed for incident asthma exacerbations with Poisson regression models that included clinical measures, self-reported race (black, non-Hispanic white, and other), and estimates of global genetic African ancestry in a subgroup (n = 760).ResultsTwenty-four percent of 1840 subjects self-identified as black. Black and white subjects had common risk factors for exacerbations, including a history of 2 or more exacerbations in the previous year and FEV1 percent predicted values, whereas chronic sinusitis, allergic rhinitis, and gastroesophageal reflux disease were only associated with increased exacerbation risk in black subjects. In the combined multiethnic cohort, neither race (P = .30) nor percentage of genetic African ancestry as a continuous variable associated with exacerbation risk (adjusted rate ratio [RR], 1.26 [95% CI, 0.94-1.70; P = .13]; RR per 1-SD change [32% ancestry], 0.97 [95% CI, 0.78-1.19; P = .74]). However, in 161 black subjects with genetic data, those with African ancestry greater than the median (≥82%) had a significantly greater risk of exacerbation (RR, 3.06 [95% CI, 1.09-8.6; P = .03]).ConclusionBlack subjects have unique risk factors for asthma exacerbations, of which global African genetic ancestry had the strongest effect

Improving Quality of Acute Asthma Care in US Hospitals Changes Between 1999-2000 and 2012-2013

BackgroundLittle is known about the longitudinal change in the quality of acute asthma care for hospitalized children and adults in the United States. We investigated whether the concordance of inpatient asthma care with the national guidelines improved over time, identified hospital characteristics predictive of guideline concordance, and determined whether guideline-concordant care is associated with a shorter hospital length of stay (LOS).MethodsThis study was an analysis of data from two multicenter chart review studies of hospitalized patients aged 2 to 54 years with acute asthma during two time periods: 1999-2000 and 2012-2013. Outcomes were guideline concordance at the patient and hospital levels, and association of patient composite concordance with hospital LOS.ResultsThe analytic cohort for the comparison of guideline concordance comprised 1,634 patients: 834 patients from 1999-2000 vs 800 patients from 2012-2013. Over these 15 years, inpatient asthma care became more concordant at the hospital-level, with the mean composite score increasing from 74 to 82 (P < .001). However, during 2012-2013, wide variability in guideline concordance of acute asthma care remained across hospitals, with the greatest variation in provision of individualized written action plan at discharge (SD, 36). Guideline concordance was significantly lower in Midwestern and Southern hospitals compared with Northeastern hospitals. After adjusting for severity, patients who received care perfectly concordant with the guidelines had significantly shorter hospital LOS (-14% [95% CI, -23 to -4]; P = .009).ConclusionsBetween 1999 and 2013, the guideline concordance of acute asthma care for hospitalized patients improved. However, interhospital variability remains substantial. Greater concordance with evidence-based guidelines was associated with a shorter hospital LOS

Stress and Bronchodilator Response in Children with Asthma

RationaleStress is associated with asthma morbidity in Puerto Ricans (PRs), who have reduced bronchodilator response (BDR).ObjectivesTo examine whether stress and/or a gene regulating anxiety (ADCYAP1R1) is associated with BDR in PR and non-PR children with asthma.MethodsThis was a cross-sectional study of stress and BDR (percent change in FEV1 after BD) in 234 PRs ages 9-14 years with asthma. We assessed child stress using the Checklist of Children's Distress Symptoms, and maternal stress using the Perceived Stress Scale. Replication analyses were conducted in two cohorts. Polymorphisms in ADCYAP1R1 were genotyped in our study and six replication studies. Multivariable models of stress and BDR were adjusted for age, sex, income, environmental tobacco smoke, and use of inhaled corticosteroids.Measurements and main resultsHigh child stress was associated with reduced BDR in three cohorts. PR children who were highly stressed (upper quartile, Checklist of Children's Distress Symptoms) and whose mothers had high stress (upper quartile, Perceived Stress Scale) had a BDR that was 10.2% (95% confidence interval, 6.1-14.2%) lower than children who had neither high stress nor a highly stressed mother. A polymorphism in ADCYAP1R1 (rs34548976) was associated with reduced BDR. This single-nucleotide polymorphism is associated with reduced expression of the gene for the β2-adrenergic receptor (ADRB2) in CD4(+) lymphocytes of subjects with asthma, and it affects brain connectivity of the amygdala and the insula (a biomarker of anxiety).ConclusionsHigh child stress and an ADCYAP1R1 single-nucleotide polymorphism are associated with reduced BDR in children with asthma. This is likely caused by down-regulation of ADRB2 in highly stressed children