TY - JOUR
T1 - Step-up therapy in black children and adults with poorly controlled asthma
AU - NHLBI AsthmaNet
AU - Wechsler, Michael E.
AU - Szefler, Stanley J.
AU - Ortega, Victor E.
AU - Pongracic, Jacqueline A.
AU - Chinchilli, Vernon
AU - Lima, John J.
AU - Krishnan, Jerry A.
AU - Kunselman, Susan J.
AU - Mauger, David
AU - Bleecker, Eugene R.
AU - Bacharier, Leonard B.
AU - Beigelman, Avraham
AU - Benson, Mindy
AU - Blake, Kathryn V.
AU - Cabana, Michael D.
AU - Cardet, Juan Carlos
AU - Castro, Mario
AU - Chmiel, James F.
AU - Covar, Ronina
AU - Denlinger, Loren
AU - DiMango, Emily
AU - Fitzpatrick, Anne M.
AU - Gentile, Deborah
AU - Grossman, Nicole
AU - Holguin, Fernando
AU - Jackson, Daniel J.
AU - Kumar, Harsha
AU - Kraft, Monica
AU - LaForce, Craig F.
AU - Lang, Jason
AU - Lazarus, Stephen C.
AU - Lemanske, Robert F.
AU - Long, Dayna
AU - Lugogo, Njira
AU - Martinez, Fernando
AU - Meyers, Deborah A.
AU - Moore, Wendy C.
AU - Moy, James
AU - Naureckas, Edward
AU - Tod Olin, J.
AU - Peters, Stephen P.
AU - Phipatanakul, Wanda
AU - Que, Loretta
AU - Raissy, Hengameh
AU - Robison, Rachel G.
AU - Ross, Kristie
AU - Sheehan, William
AU - Smith, Lewis J.
AU - Solway, Julian
AU - Sorkness, Christine A.
N1 - Publisher Copyright:
Copyright © 2019 Massachusetts Medical Society.
PY - 2019/9/26
Y1 - 2019/9/26
N2 - 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 the addition of salmeterol than to an increase in the 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.
AB - 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 the addition of salmeterol than to an increase in the 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.
UR - http://www.scopus.com/inward/record.url?scp=85072686212&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1905560
DO - 10.1056/NEJMoa1905560
M3 - Article
C2 - 31553835
AN - SCOPUS:85072686212
SN - 0028-4793
VL - 381
SP - 1227
EP - 1239
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 13
ER -