Black Kids, Adults Respond Differently to Step-Up Asthma Tx

African-American children with poorly controlled asthma may not need to add a long-acting beta agonist (LABA) to treatment with an inhaled steroid, researchers reported.

In a study examining responses to step-up therapy in black adults and children with asthma not controlled with low-dose inhaled corticosteroids, just as many children responded to treatment escalation limited to higher inhaled steroid dosing alone, according to Michael E. Wechsler, MD, of National Jewish Health in Denver, and colleagues.

A step-up regimen limited to quadrupling the dosage of the inhaled corticosteroid fluticasone propionate elicited a superior response in 46%, which was the same percentage that saw a superior response to doubling the fluticasone dosage and adding salmeterol, they wrote in the New England Journal of Medicine.

The addition of the LABA salmeterol to inhaled steroid therapy was superior to escalating inhaled steroid among African-American adolescents and adults with poorly controlled asthma in the trial, the authors noted.

“In contrast to black adults and white persons of all ages, almost half the children who had at least one grandparent who identified as black and who had poorly controlled asthma had a superior response to an increased dose of an inhaled glucocorticoid over the addition of a LABA,” they wrote.

Adding a LABA to inhaled steroid treatment is considered the gold-standard step-up therapy in patients with poorly controlled asthma, but this recommendation is largely based on studies with few black participants, Wechsler told MedPage Today.

“We know that blacks with asthma are different,” he said. “They tend to have more exacerbations and more morbidity associated with asthma.”

Several prior retrospective studies have also suggested that African-American patients with poorly controlled asthma may not respond as well as white patients to the addition of a LABA to step-up treatment.

The Best African American Response to Asthma Drugs (BARDS) trial was designed to test this finding prospectively and to look for patient characteristics, biomarkers, and genomic variations predictive of response to step-up therapies, Wechsler said.

Separate prospective, randomized, double-blind trials were conducted in African-American adults and adolescents (ages ≥12) and in children (ages 5-11 years).

Participation was limited to patients who had at least one grandparent who identified as black with asthma that was not adequately controlled on low-dose inhaled corticosteroid therapy.

In the trial involving children, step-up strategies involved the doubling of the inhaled steroid to a dose of 100 μg, given twice daily (double fluticasone group); 100 µg of fluticasone and adding 50 µg of salmeterol twice a day (the salmeterol-double fluticasone group); quintupling the dose of fluticasone to 250 µg given twice a day (quadruple-fluticasone group); or quintupling the dose of fluticasone to 250 µg and adding 50 µg of salmeterol (salmeterol-quintuple-fluticasone group).

A composite measure that included asthma exacerbations, asthma control days, and lung function was used to compare the different treatment strategies.

In a comparison of outcomes among the quintuple-fluticasone group and the salmeterol-double fluticasone group, 46% of children in both groups experienced superior responses to the respective treatments (P=0.99).

The children in the BARDS trial responded to stepped increases in the dose of inhaled glucocorticosteroid. The authors reported that the increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children ages <8 years.

However, “[n]either the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments,” they stated, and Wechsler told MedPage Today that “we really need additional research to better understand this.”

“Our results are all the more striking in that in our parallel trial we confirmed that adolescent and adults who had at least one grandparent who identified as black had responses similar to those reported in white adults — that is, the addition of a LABA in adults was more likely to lead to superior responses in a larger group of patients than an increase in the dose of an inhaled glucocorticoid,” the researchers wrote.

“These findings suggest that data cannot be extrapolated from clinical trials involving mixed populations to specific subgroups, including those of different ages and races,” they added.

Wechsler noted that increasing inhaled steroid dosages without the addition of a LABA may be an appropriate step-up therapy approach among African-American children with poorly controlled asthma.

“These kids shouldn’t necessarily be treated with a LABA as first-line step-up therapy,” he said. “They are just as likely to respond better to increasing doses of inhaled corticosteroid.”