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African American children respond differently to asthma medications

African Americans suffer asthma more often and more severely than Caucasian patients. However, clinical trials that have shaped treatment guidelines have included few African Americans. A new report demonstrates a shortcoming of that history. Researchers at National Jewish Health and their colleagues around the nation in the National Heart, Lung & Blood Institute's AsthmaNet report that African American children respond differently than African American adults and Caucasian adults and children to step-up therapies for inadequately controlled asthma.

"Asthma is a tremendously variable disease," said Dr Michael Wechsler, professor of medicine at National Jewish Health and first author on the study. "We need to more closely study subgroups of asthma patients, especially those disproportionately burdened by disease, such as African Americans."

The researchers evaluated 280 children, ages 5-11, and 294 adolescents/adults of African American ancestry whose asthma was inadequately controlled with low doses of inhaled corticosteroids. Treatment guidelines call for adding a long-acting beta agonist as the preferred step-up therapy. Researchers several medication strategies – adding long-acting beta agonists, increasing inhaled steroids alone and both increasing inhaled steroids and adding long-acting beta agonists.

The researchers measured response by evaluating several factors including exacerbations, asthma control days and lung function.

More adult African Americans responded better to adding long-acting beta agonists (49%) versus increasing inhaled steroids alone (28%). Caucasians have shown a similar response in previous trials. However, even numbers of African American children responded better to increasing the dose of inhaled corticosteroids along (46%) and adding long-acting beta agonists (46%).

"These results indicate that asthma treatment guidelines do not necessarily apply to African American children and that physicians should consider alternatives," said Wechsler. "We need to do a better job of understanding how different subgroups respond to asthma treatment."

The researchers also looked at several biological and genetic factors to determine if any could predict treatment response. However, they did not find that any biomarkers or percentage of African American ancestry was associated treatment response.

Background: Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.
Methods: We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.
Results: When quintupling the dose of fluticasone (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P=0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol–low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P=0.003]; salmeterol–medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P=0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.
Conclusions: In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA.

Michael E Wechsler, Stanley J Szefler, Victor E Ortega, Jacqueline A Pongracic, Vernon Chinchilli, John J Lima, Jerry A Krishnan, Susan J Kunselman, David Mauger, Eugene R Bleecker, Leonard B Bacharier, Avraham Beigelman, Mindy Benson, Kathryn V Blake, Michael D Cabana, Juan-Carlos Cardet, Mario Castro, James F Chmiel, Ronina Covar, Loren Denlinger, Emily DiMango, Anne M Fitzpatrick, Deborah Gentile, Nicole Grossman, Fernando Holguin, Daniel J Jackson, Harsha Kumar, Monica Kraft, Craig F LaForce, Jason Lang, Stephen C Lazarus, Robert F Lemanske, Dayna Long, Njira Lugogo, Fernando Martinez, Deborah A Meyers, Wendy C Moore, James Moy, Edward Naureckas, J Tod Olin, Stephen P Peters, Wanda Phipatanakul, Loretta Que, Hengameh Raissy, Rachel G Robison, Kristie Ross, William Sheehan, Lewis J Smith, Julian Solway, Christine A Sorkness, Lisa Sullivan-Vedder, Sally Wenzel, Steven White, Elliot Israel

[link url="https://www.nationaljewish.org/about/news/press-releases/2019/african-american-children-respond-differently-to-asthma-medications"]National Jewish Health material[/link]

[link url="https://www.nejm.org/doi/10.1056/NEJMoa1905560"]New England Journal of Medicine abstract[/link]

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