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

BACKGROUND: Minority 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. OBJECTIVE: We evaluated clinical trial measures in the context of self-reported race and genetic ancestry to identify risk factors for asthma exacerbations. METHODS: One 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). RESULTS: Twenty-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]). CONCLUSION: Black subjects have unique risk factors for asthma exacerbations, of which global African genetic ancestry had the strongest effect.

Susceptibility to exacerbations in Black adults with asthma.

OBJECTIVE: Exacerbations account for much of the morbidity in asthma. In a large intervention study, we sought to test the hypothesis that a Black adult exacerbation-prone phenotype - a group of Black people with asthma who are at high risk of repeat exacerbation within one year - exists in asthma independent of clinical control. METHODS: We analyzed exacerbation risk factors in 536 self-identified Black Americans with asthma eligible for, or on, Step 3 National Asthma Education and Prevention Program (NAEPP) therapy who participated in a randomized 6-18 month trial of tiotropium versus long acting beta agonist as add-on therapy to inhaled corticosteroids. Exacerbations were defined as events treated by oral or systemic corticosteroids. Clinical control was assessed by a validated asthma control questionnaire (ACQ5). RESULTS: Exacerbations became more likely with loss of clinical control. The mean baseline ACQs for exacerbators and non-exacerbators were 2.41 and 1.91, respectively (p < 0.001). The strongest independent factor associated with exacerbations across all ACQ levels was an exacerbation in the preceding year (adjusted OR 3.26; p < 0.001). The severity of prior exacerbations did not correlate with the likelihood of a future exacerbation. Lower baseline FEV1/FVC was also associated with increased risk of exacerbations. CONCLUSIONS: Even though exacerbations increase with loss of clinical control, an exacerbation susceptibility phenotype exists in Black adults with asthma, independent of clinical control. This phenotype requires precision therapeutic targeting.