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

Abstract

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...

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

“…Thus, individuals of African racial background appear to have less short-acting bronchodilator responsiveness to SABA, even after ICS therapy, compared with Mexican-Americans and Puerto-Ricans [205]. African-Americans suffering from asthma were reported to have more treatment failures compared with white Americans, particularly when taking LABAs [206]. There are currently on-going studies looking at the influence of race and b-adrenoceptor genotype on treatment responsiveness to b-adrenoreceptors.…”

Impact of Age and Sex on Response to Asthma Therapy

“…Detailed demographic and baseline data were collected and included age, sex, self-reported race, peak expiratory flows, FEV 1 , bronchial hyperresponsiveness, asthma symptoms, use of asthma rescue medication, and asthma quality-of-life scores. The primary dependent variable analyzed was asthma treatment failure as previously described (27), defined as any the following: an asthma exacerbation requiring oral corticosteroid or emergency room visit, worsening of lung function, increased use of asthma medication, or physician clinical judgment. To distinguish important differences across age groups, we separated the cohort at the 50th and 75th percentiles (aged 30 and 38).…”

“…It has previously been shown that race is important in predicting response to therapy (27,37). Specifically, black individuals have been shown to have an increased risk of treatment failures when treated with long-acting b-agonists and potentially an increased mortality when receiving long-acting b-agonist therapy alone (37).…”

Asthma phenotyping, therapy, and prevention: what can we learn from systems biology?

“…Even more prominent may be the effect of differences in phenotypes; patient groups with high symptom levels but low eosinophilic inflammation seem to have only moderate benefit from inhaled glucocorticoids (3). An issue in terms of therapy is also the retrospective observation that Americans with African ancestry showed greater deterioration when treated with long-acting β-agonists (45). There is a debate on whether treatment with this substance group alone without inhaled corticosteroids leads to increased mortality (46), and whether mutations in the β2-adrenoreceptor have an impact on the drug's effect on peak flow and disease symptoms (47).…”