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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:144

Article

Grossman, Nicole L.¹  Ortega, Victor E.²  King, Tonya S.³  Bleecker, Eugene R.⁴  Ampleford, Elizabeth A.²  Bacharier, Leonard B.⁵  Cabana, Michael D.⁶  Cardet, Juan C.⁷  Carr, Tara F.⁸  Castro, Mario⁹  Denlinger, Loren C.¹⁰  Denson, Joshua L.¹¹  Fandino, Nicolas^12,13  Fitzpatrick, Anne M.¹⁴  Hawkins, Gregory A.¹⁵  Holguin, Fernando¹⁶  Krishnan, Jerry A.¹⁷  Lazarus, Stephen C.¹⁸  Nyenhuis, Sharmilee M.¹⁹  Phipatanakul, Wanda²⁰  Ramratnam, Sima K.²⁰  Wenzel, Sally²¹  Peters, Stephen P.²  Meyers, Deborah A.⁴  Wechsler, Michael E.¹¹ 

[1] Lahey Hosp & Med Ctr, Div Pulm & Crit Care, Dept Internal Med, Burlington, ON, Canada

[2] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27101 USA

[3] Penn State Univ, Sch Med, Dept Publ Hlth Sci, Hershey, PA USA

[4] Univ Arizona, Coll Med, Div Genet Genom & Precis Med, Dept Med, Tucson, AZ USA

[5] Washington Univ, Sch Med, Div Allergy Immunol & Pulm, Dept Pediat, St Louis, MO USA

[6] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA

[7] Univ S Florida, Morsani Coll Med, Div Allergy & Immunol, Deparment Internal Med, Tampa, FL USA

[8] Univ Arizona, Div Pulm Allergy Crit Care & Sleep Med, Dept Med, Tucson, AZ USA

[9] Univ Kansas, Div Pulm Dis & Crit Care Med, Dept Internal Med, Kansas City, KS USA

[10] Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA

[11] Natl Jewish Hlth, Div Pulm Crit Care & Sleep Med, Dept Med, Denver, CO USA

[12] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 1, 75 Francis St, Boston, MA 02115 USA

[13] Harvard Med Sch, Boston, MA 02115 USA

[14] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA

[15] Wake Forest Sch Med, Dept Biochem, Winston Salem, NC 27101 USA

[16] Univ Colorado, Anschutz Med Campus, Dept Med, Denver, CO USA

[17] Univ Illinois Hosp & Hlth Sci Syst, Dept Med, Chicago, IL USA

[18] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[19] Harvard Med Sch, Boston Childrens Hosp, Div Pediat Allergy & Immunol, Boston, MA USA

[20] Univ Wisconsin, Sch Med, Dept Pediat, Madison, WI 53706 USA

[21] Univ Pittsburgh, Sch Publ Hlth, Dept Environm & Occupat Hlth, Pittsburgh, PA 15260 USA

关键词: Exacerbations;    race;    ancestry;    admixture;    lung function;    genetics;    asthma;    black;    African American;    ethnic group;   

DOI  :  10.1016/j.jaci.2019.08.033

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free