Racial differences in biologic predictors of severe asthma: Data from the Severe Asthma Research Program

doi:10.1016/j.jaci.2010.08.049

Journal of Allergy and Clinical Immunology

Volume 126, Issue 6, December 2010, Pages 1149-1156.e1

https://doi.org/10.1016/j.jaci.2010.08.049 Get rights and content

Background

Biologic factors are known to contribute to asthma severity. It is unknown whether these factors differentially contribute to asthma severity in black compared with white subjects.

Objective

We sought to assess the extent to which racial disparities between black and white subjects with severe asthma are attributable to physiologic, immunoinflammatory, and sociodemographic variables.

Methods

Black and white asthmatic adults enrolled in a cross-sectional study focused on severe asthma were evaluated. Severe asthma was identified by using the American Thoracic Society definition. After initial univariable analyses, unconditional logistic regression models were used to estimate the probability of having severe asthma for black and white subjects.

Results

Differences in severe asthma in black compared with white subjects were observed. In univariable analysis IgE level was not associated with severe asthma in black or white subjects, whereas in multivariable analysis IgE level was significantly associated with severe asthma for black subjects (P = .014) but not for white subjects. The odds of having severe asthma more than doubled for black subjects with 2 or more family members with asthma (P = .026), whereas the odds of severe asthma for white participants with a strong family history of asthma decreased by almost half (P = .05). Atopy was negatively associated with severe asthma in both races in univariable analysis but remained significant only in black subjects, whereas comorbidities were associated with severe asthma in white subjects.

Conclusion

Biologic factors were distinctly associated with severe asthma only in black subjects. Studies that incorporate comprehensive evaluation of biologic factors associated with asthma might lead to the development of therapies that target biologic abnormalities in black subjects.

Section snippets

Subjects

The data in this study were obtained from subjects enrolled in SARP, a network established to identify and characterize subjects with severe asthma in relation to subjects with milder asthma to better understand mechanisms for their disease. The baseline characteristics of this population were recently published.⁴ SARP initially consisted of 8 funded sites: the University of Pittsburgh, the University of Virginia (subsites at Cleveland and Emory University), Brigham and Women’s Hospital,

General demographics

For more data on baseline demographics, see Table I. Of the 1391 total enrolled subjects in SARP, 916 met the inclusion criteria for this analysis. This analysis included only adult participants (≥18 years of age). Participants with a racial background classified as nonblack and nonwhite, as well as participants considered healthy (not asthmatic) were excluded (n = 475). There were more white (71%) than black (29%) participants. More female participants were included compared with male

Discussion

In this cross-sectional analysis of more than 900 black and white asthmatic subjects, striking differences were found in the factors associated with severe asthma. Although baseline FEV₁ percent predicted and GERD were important factors for both racial groups, biologic factors, including IgE levels, skin test reactivity, and family history, were distinctly associated with severe asthma in black subjects. Although socioeconomic factors almost certainly affect the high health care use and

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Several mechanisms could explain the differences in asthma presentation. Evidence of ethnic differences in the biological predictors in severe asthma from the United States and an association between exacerbation frequency and African genetic ancestry support a genetic contribution.7,8 However, disentangling genetic effects from environmental factors among often more disadvantaged Black and underrepresented ethnic populations remains difficult,9 and other researchers reported that substantial racial disparities in health care use rates are largely or completely mediated by socioeconomic and environmental exposure variables such as income and housing conditions.5,10-12
Understanding the effects of ethnicity in severe asthma is important for optimal personalized patient care.
To assess ethnic differences in disease control, exacerbations, biological phenotype, and treatment in severe asthma in the United Kingdom.
We compared demographics, type 2 biomarkers, lung function, asthma control, medications, and health care use between White and underrepresented ethnic group patients in the UK Severe Asthma Registry (UKSAR) and Optimum Patient Care Research Database (OPCRD).
A total of 3637 patients (665 from the underrepresented ethnic group) were included from UKSAR and 10,549 (577 from the underrepresented ethnic group) from OPCRD. Patients in the underrepresented ethnic group had higher levels of uncontrolled disease when measurements were made using the asthma control questionnaire in UKSAR (odds ratio [OR] = 1.47; 95% confidence interval [CI], 1.12-1.93) and the Royal College of Physicians 3 Questions in OPCRD (OR = 1.82; 95% CI, 1.27-2.60). Although exacerbation rates were similar, patients in the underrepresented ethnic group were more likely to have recently attended the emergency department (OR = 1.55; 95% CI, 1.26-1.92) or to have been hospitalized (OR = 1.31; 95% CI, 1.07-1.59) owing to asthma. Inflammatory biomarkers were consistently higher in the underrepresented ethnic group, including blood eosinophils in OPCRD (ratio = 1.12; 95% CI, 1.05-1.20) and in UKSAR blood eosinophils (ratio = 1.16; 95% CI, 1.06-1.27), FeNO (ratio = 1.14; 95% CI, 1.04-1.26), and IgE (ratio = 1.70; 95% CI, 1.47-1.97). Patients in the underrepresented ethnic group were more likely to be atopic in the UKSAR (OR = 1.32; 95% CI, 1.07-1.63) and OPCRD (OR = 1.67; 95% CI, 1.26-2.21), and less likely to be using maintenance oral corticosteroids at referral (OR = 0.75; 95% CI, 0.61-0.92).
Severe asthma patients from underrepresented ethnic groups presented with a higher disease burden and were more likely to attend the emergency department. They had a distinct phenotypic presentation and differences in medicine use, with higher levels of type 2 biomarkers.
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We found an association between self-identified black race and progression from AD to asthma. Conversely, Asian or Pacific Islander race was associated with progression from AD to IgE-mediated food allergy, and white race was associated with progression from AD to AR. Genome-wide association study of trajectory groups identified risk loci associated with progression from AD to asthma (rs60242841) and from AD to AR (rs9565267, rs151041509, and rs78171803). Consistent with our epidemiologic associations, rs60242841 was more common in individuals of African ancestry than in individuals of European ancestry, whereas rs9565267 and rs151041509 were more common in individuals of European ancestry than in individuals of African ancestry.
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We sought to determine associations between black and white patients and asthma-related health care use, accounting for complex relationships.
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Black patients had greater odds of ED use over 1 year (odds ratio, 2.19; 95% CI, 1.43-3.35) but also differed in the majority (>50%) of baseline variables measured. After statistical balancing of the racial groups, the difference between black and white patients with respect to ED use no longer reached the level of significance. Instead, in secondary analyses black patients were less likely to see an outpatient physician for asthma management (adjusted odds ratio, 0.57; 95% CI, 0.38-0.85).
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The prevalences of comorbidities in patients with difficult-to-control asthma in our study are in line with those reported in the Belgian Severe Asthma Registry for anxiety/depression (around 30%), but not for obesity (47% vs 17.8% in our study), which might be explained by differences in life style factors (diet and exercise) between the Belgian and Dutch population. This study also showed a lower prevalence of gastroesophageal reflux (39% vs 62%),22 and also other cohort studies in severe or difficult-to-control asthma found varying prevalences of between 30% and 64%.23-26 This wide variation in prevalences is probably due to differences in how this comorbidity was diagnosed (prescription-based in our study vs doctor's diagnosed in other studies).
Difficult-to-control asthma is associated with significant medical and financial burden. Comorbidities are known to contribute to uncontrolled asthma. Better insight into the prevalence, nature, and risk factors of comorbidities may optimize treatment strategies in patients with difficult-to-control asthma and decrease disease burden.
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: Supported by Clinical and Translational Research Center funding: UL1 RR024153 (National Center for Research Resources). Grant support: HL69116, HL69130, HL69155, HL69167, HL69170, HL69174, HL69349, HL091762, M01 RR02635, M01 RR03186, M01 RR007122-14, 1UL1RR024153, 1UL1RR024989, 1UL1RR024992, 1UL1RR025011.

: Disclosure of potential conflict of interest: E. Bleecker has served as an advisor/consultant for Aerovance, AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Merck, Novartis, Pfizer, and Wyeth and has received research support from Aerovance, Amgen, AstraZeneca, Boehringer-Ingelheim, Centocor, Ception, Genentech, GlaxoSmithKline, Novartis, Pfizer, Wyeth, and the National Institutes of Health (NIH). W. Busse is on the advisory board for Altair, Amgen, Centocor, GlaxoSmithKline, Merck, Pfizer, Wyeth, and Johns & Johnson; is a consultant for AstraZeneca, Boehringer-Ingelheim, Novartis, TEVA, and GlaxoSmithKline; is a speaker for Merck; and has received research support from the NIH/National Institute of Allergy and Infectious Diseases (NIAID), the NIH/National Heart, Lung, and Blood Institute (NHLBI), Novartis, AstraZeneca, GlaxoSmithKline, MedImmune, and Ception. M. Castro is a consultant for Electrocore, NKTT, Schering-Plough, Asthmatx, and Cephalon; is on the advisory board for Genentech; is a speaker for AstraZeneca, Boehringer-Ingelheim, Pfizer, Merck, and GlaxoSmithKline; has received research support from Asthmatx, Amgen, Ception, Genentech, MedImmune, Merck, Novartis, the NIH, and GlaxoSmithKline; and has received royalties from Elsevier. K. F. Chung is a consultant for Gilead, is on the advisory board for Merck and GlaxoSmithKline, and has received research support from MRC UK, Asthma UK, and Wellcome Trust. S. Wenzel has served as a consultant for Merck and GlaxoSmithKline and as an advisory board member for Amira. The rest of the authors have declared that they have no conflict of interest.

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Asthma and lower airway diseaseRacial differences in biologic predictors of severe asthma: Data from the Severe Asthma Research Program

Background

Objective

Methods

Results

Conclusion

Section snippets

Subjects

General demographics

Discussion

J Allergy Clin Immunol

Clin Chest Med

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

Chest

Ann Allergy Asthma Immunol

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Chest

J Allergy Clin Immunol

J Allergy Clin Immunol

Asthma and lower airway disease
Racial differences in biologic predictors of severe asthma: Data from the Severe Asthma Research Program