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

ABSTRACT: 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.

SUBMITTER: Grossman NL

PROVIDER: S-EPMC6931257 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Grossman Nicole L NL Ortega Victor E VE King Tonya S TS Bleecker Eugene R ER Ampleford Elizabeth A EA Bacharier Leonard B LB Cabana Michael D MD Cardet Juan C JC Carr Tara F TF Castro Mario M Denlinger Loren C LC Denson Joshua L JL Fandino Nicolas N Fitzpatrick Anne M AM Hawkins Gregory A GA Holguin Fernando F Krishnan Jerry A JA Lazarus Stephen C SC Nyenhuis Sharmilee M SM Phipatanakul Wanda W Ramratnam Sima K SK Wenzel Sally S Peters Stephen P SP Meyers Deborah A DA Wechsler Michael E ME Israel Elliot E

The Journal of allergy and clinical immunology 20190911 6

<h4>Background</h4>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.<h4>Objective</h4>We evaluated clinical trial measures in the context of self-reported race and genetic ancestry to identify risk factors for asthma exacerbations.<h4>Methods</h4>One thousand eight hundred forty multiethnic subjects from 12 Asthma Clinical Research ...[more]

PMID: 31520679

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Project description:Background and objectivesChronic inflammatory airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), are complex syndromes with diverse clinical symptoms due to multiple pathophysiological conditions. In this study, using common and shared risk factors for the exacerbation of asthma and COPD, we sought to clarify the exacerbation-prone phenotypes beyond disease labels, and to specifically investigate the role of the IL4RA gene polymorphism, which is related to type 2 inflammation, in these exacerbation-prone phenotypes.MethodsThe study population comprised patients with asthma (n = 117), asthma-COPD overlap (ACO; n = 37) or COPD (n = 48) and a history of exacerbation within the previous year. Cluster analyses were performed using factors associated with both asthma and COPD exacerbation. The association of the IL4RA gene polymorphism rs8832 with each exacerbation-prone phenotype was evaluated by multinomial logistic analyses using non-asthma non-COPD healthy adults as controls (n = 1,529). In addition, the genetic influence of rs8832 was also examined in asthma patients with allergic rhinitis and no history of exacerbation (n = 130).ResultsTwo-step cluster analyses identified five clusters that did not necessarily correspond to the diagnostic disease labels. Cluster 1 was characterized by high eosinophil counts, cluster 2 was characterized by smokers with impaired lung function, cluster 3 was characterized by the presence of gastroesophageal reflux, cluster 4 was characterized by non-allergic females, and cluster 5 was characterized by allergic rhinitis and elevated total immunoglobulin E levels. A significant association with rs8832 was observed for cluster 5 (odds ratio, 3.88 (1.34-11.26), p = 0.013) and also for the type 2 exacerbation-prone phenotypes (clusters 1 and 5: odds ratio, 2.73 (1.45-5.15), p = 1.9 × 10-3).DiscussionOur results indicated that the clinical heterogeneity of disease exacerbation may reflect the presence of common exacerbation-prone endotypes across asthma and COPD, and may support the use of the treatable traits approach for the prevention of exacerbations in patients with chronic inflammatory airway diseases.

Dataset Information

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

Publications

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

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