Factors predicting inhaled corticosteroid responsiveness in African American patients with asthma

Gould, Wendy; Peterson, Edward L.; Karungi, Gloria; Zoratti, Amanda; Gaggin, John; Toma, Ghazwan; Yan, Shaohua; Levin, Albert M.; Yang, James; Wells, Karen; Wang, Mingqun; Burke, Robert R.; Beckman, Kenneth B.; Popadic, Danijela; Land, Susan; Kumar, Rajesh; Seibold, Max A.; Lanfear, David E.; Burchard, Esteban G.; Williams, L. Keoki

doi:10.1016/j.jaci.2010.08.002

Cited by 36 publications

(43 citation statements)

References 51 publications

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“…Although differences within racial groups can further discriminate between differential ethnicities, specific phenotypes, and drug responsiveness (15,16), there has been little study of asthma therapies in study populations limited to African Americans or other ethnicities (17,18). However, data from the SMART study (a large multicenter trial examining safety of salmeterol) (3) and the current findings suggest that differential response to LABAs in African Americans exist.…”

Section: Discussionmentioning

confidence: 99%

“…However, adherence rates in the trials reported were high (87.5% and 91%, respectively, for African Americans and whites), and there was no difference in adherence rates between those who had treatment failures and those who did not (90% adherence in both), suggesting that differential adherence did not play a significant role. Although study populations are often racially admixed, self-identified racial and ethnic categories are crude descriptors of individual genetic ancestry; indeed, recent studies of African Americans suggest that fewer than 5% of self-reported African Americans get misclassified when race is analyzed using ancestry informative markers (15) and that genetic ancestry does not contribute to differences in response to asthma medications among African American patients with asthma (17).…”

Section: Table 3 Causes Of Treatment Failures In African Americans Amentioning

confidence: 99%

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Impact of Race on Asthma Treatment Failures in the Asthma Clinical Research Network

Wechsler

Castro

Lehman

et al. 2011

Am J Respir Crit Care Med

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Rationale: Recent studies suggest that people with asthma of different racial backgrounds may respond differently to various therapies. Objectives: To use data from well-characterized participants in prior Asthma Clinical Research Network (ACRN) trials to determine whether racial differences affected asthma treatment failures. Methods: We analyzed baseline phenotypes and treatment failure rates (worsening asthma resulting in systemic corticosteroid use, hospitalization, emergency department visit, prolonged decrease in peak expiratory flow, increase in albuterol use, or safety concerns) in subjects participating in 10 ACRN trials (1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003). Self-declared race was reported in each trial and treatment failure rates were stratified by race. ; mean age ¼ 32) were included in the analyses. At baseline, African Americans had fewer asthma symptoms (P , 0.001) and less average daily rescue inhaler use (P ¼ 0.007) than whites. There were no differences in baseline FEV 1 (% predicted); asthma quality of life; bronchial hyperreactivity; or exhaled nitric oxide concentrations. A total of 147 treatment failures were observed; a significantly higher proportion of African Americans (19.7%; n ¼ 46) experienced a treatment failure compared with whites (12.7%; n ¼ 101) (odds ratio ¼ 1.7; 95% confidence interval, 1.2-2.5; P ¼ 0.007). When stratified by treatment, African Americans receiving long-acting b-agonists were twice as likely as whites to experience a treatment failure (odds ratio ¼ 2.1; 95% confidence interval, 1.3-3.6; P ¼ 0.004), even when used with other controller therapies. Conclusions: Despite having fewer asthma symptoms and less rescue b-agonist use, African-Americans with asthma have more treatment failures compared with whites, especially when taking long-acting b-agonists.Keywords: asthma; long-acting b-agonist; African Americans; race; treatment failure Environmental and genetic factors have been shown to significantly influence response to medications in patients with asthma. Among these factors, it has been speculated that race contributes to differential response to pharmacologic therapies. In this regard, several studies have demonstrated that African Americans have worse asthma control than whites, and a disproportionately higher rate of asthma-related emergency department visits, hospitalizations, and deaths (1). Although genetic, environmental, and socioeconomic factors, including disparities in access to care and quality of care, have been implicated in these differential outcomes (2), it is also possible that there are inherent pathophysiologic or even pharmacogenomic differences between whites and African Americans that result in these discrepancies.Over the last few years, several reports have associated specific asthma therapies with adverse responses including lifethreatening asthma and asthma-related deaths, particularly among African Americans (3, 4). Because of these discrepancies in asthma control in patients with asthma of different rac...

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Section: Discussionmentioning

confidence: 99%

Section: Table 3 Causes Of Treatment Failures In African Americans Amentioning

confidence: 99%

Impact of Race on Asthma Treatment Failures in the Asthma Clinical Research Network

Wechsler

Castro

Lehman

et al. 2011

Am J Respir Crit Care Med

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show abstract

“…[4][5][6][7][8] The Salmeterol Multicenter Asthma Research Trial suggested that African American patients receiving the long-acting b 2 -adrenergic agonist (LABA) salmeterol had a significantly increased risk of combined respiratory-related death or life-threatening events. 6 Whether patients were taking inhaled corticosteroids (ICSs) concomitantly during that study is unclear, but baseline ICS use was reported by a smaller percentage of African American (38%) versus white (49%) patients.…”

mentioning

confidence: 99%

Long-term safety and asthma control measures with a budesonide/formoterol pressurized metered-dose inhaler in African American asthmatic patients: A randomized controlled trial

Brown

O’Brien

Martin

et al. 2012

Journal of Allergy and Clinical Immunology

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“…Gould et al 13 reasonably concluded that global genetic ancestry might not be responsible for the differences observed in the way African Americans respond to ICS therapy, but rather than dismiss the effect of genetic variation on ICS responsiveness altogether, they aptly note that this study does not rule out the potential for local genetic effects of ancestry. These findings are yet to be determined in SAPPHIRE and will likely be forthcoming.…”

mentioning

confidence: 88%

“…Importantly, Gould et al 13 have broken new ground in applying a novel tool in the complicated process of dissecting a particularly complicated phenotype, response to drug therapy, and this might ultimately shed new light on the underlying genetic mechanisms involved.…”

mentioning

confidence: 99%

Ancestry, ancestry-informative markers, asthma, and the quest for personalized medicine

Barnes¹

2010

Journal of Allergy and Clinical Immunology

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Factors predicting inhaled corticosteroid responsiveness in African American patients with asthma

Abstract: Background-African American patients suffer disproportionately from uncontrolled asthma. Treatment with an inhaled corticosteroid (ICS) is considered first-line therapy for persistent asthma.

Cited by 36 publications

References 51 publications

Impact of Race on Asthma Treatment Failures in the Asthma Clinical Research Network

Impact of Race on Asthma Treatment Failures in the Asthma Clinical Research Network

Long-term safety and asthma control measures with a budesonide/formoterol pressurized metered-dose inhaler in African American asthmatic patients: A randomized controlled trial

Ancestry, ancestry-informative markers, asthma, and the quest for personalized medicine

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