Step-up therapy in black children and adults with poorly controlled asthma

NHLBI AsthmaNet

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)1227-1239
Number of pages13
JournalNew England Journal of Medicine
Volume381
Issue number13
DOIs
StatePublished - Sep 26 2019
Externally publishedYes

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Asthma
Glucocorticoids
Therapeutics
Fluticasone
Hydrocortisone
Creatinine
Biomarkers
Morbidity
Lung
Salmeterol Xinafoate

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Step-up therapy in black children and adults with poorly controlled asthma. / NHLBI AsthmaNet.

In: New England Journal of Medicine, Vol. 381, No. 13, 26.09.2019, p. 1227-1239.

Research output: Contribution to journalArticle

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title = "Step-up therapy in black children and adults with poorly controlled asthma",
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 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.",
author = "{NHLBI AsthmaNet} and Wechsler, {Michael E.} and Szefler, {Stanley J.} and Ortega, {Victor E.} and Pongracic, {Jacqueline A.} and Vernon Chinchilli and Lima, {John J.} and Krishnan, {Jerry A.} and Kunselman, {Susan J.} and David Mauger and Bleecker, {Eugene R.} and Bacharier, {Leonard B.} and Avraham Beigelman and Mindy Benson and Blake, {Kathryn V.} and Cabana, {Michael D.} and Cardet, {Juan Carlos} and Mario Castro and Chmiel, {James F.} and Ronina Covar and Loren Denlinger and Emily DiMango and Fitzpatrick, {Anne M.} and Deborah Gentile and Nicole Grossman and Fernando Holguin and Jackson, {Daniel J.} and Harsha Kumar and Monica Kraft and LaForce, {Craig F.} and Jason Lang and Lazarus, {Stephen C.} and Lemanske, {Robert F.} and Dayna Long and Njira Lugogo and Fernando Martinez and Meyers, {Deborah A.} and Moore, {Wendy C.} and James Moy and Edward Naureckas and {Tod Olin}, J. and Peters, {Stephen P.} and Wanda Phipatanakul and Loretta Que and Hengameh Raissy and Robison, {Rachel G.} and Kristie Ross and William Sheehan and Smith, {Lewis J.} and Julian Solway and Sorkness, {Christine A.}",
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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.

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.

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JF - New England Journal of Medicine

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