Literature DB >> 31553835

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.

Michael E Wechsler1, Stanley J Szefler1, Victor E Ortega1, Jacqueline A Pongracic1, Vernon Chinchilli1, John J Lima1, Jerry A Krishnan1, Susan J Kunselman1, David Mauger1, Eugene R Bleecker1, Leonard B Bacharier1, Avraham Beigelman1, Mindy Benson1, Kathryn V Blake1, Michael D Cabana1, Juan-Carlos Cardet1, Mario Castro1, James F Chmiel1, Ronina Covar1, Loren Denlinger1, Emily DiMango1, Anne M Fitzpatrick1, Deborah Gentile1, Nicole Grossman1, Fernando Holguin1, Daniel J Jackson1, Harsha Kumar1, Monica Kraft1, Craig F LaForce1, Jason Lang1, Stephen C Lazarus1, Robert F Lemanske1, Dayna Long1, Njira Lugogo1, Fernando Martinez1, Deborah A Meyers1, Wendy C Moore1, James Moy1, Edward Naureckas1, J Tod Olin1, Stephen P Peters1, Wanda Phipatanakul1, Loretta Que1, Hengameh Raissy1, Rachel G Robison1, Kristie Ross1, William Sheehan1, Lewis J Smith1, Julian Solway1, Christine A Sorkness1, Lisa Sullivan-Vedder1, Sally Wenzel1, Steven White1, Elliot Israel1.   

Abstract

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. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).
Copyright © 2019 Massachusetts Medical Society.

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Year:  2019        PMID: 31553835      PMCID: PMC7026584          DOI: 10.1056/NEJMoa1905560

Source DB:  PubMed          Journal:  N Engl J Med        ISSN: 0028-4793            Impact factor:   91.245


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