Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.
Administration, Inhalation
Adolescent
Adrenergic beta-2 Receptor Agonists
/ administration & dosage
Adult
Black or African American
Asthma
/ drug therapy
Bronchodilator Agents
/ administration & dosage
Child
Child, Preschool
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Drug Combinations
Female
Fluticasone
/ administration & dosage
Glucocorticoids
/ administration & dosage
Humans
Male
Prospective Studies
Salmeterol Xinafoate
/ administration & dosage
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
26 09 2019
26 09 2019
Historique:
entrez:
26
9
2019
pubmed:
26
9
2019
medline:
8
10
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.).
Sections du résumé
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.).
Identifiants
pubmed: 31553835
doi: 10.1056/NEJMoa1905560
pmc: PMC7026584
mid: NIHMS1553135
doi:
Substances chimiques
Adrenergic beta-2 Receptor Agonists
0
Bronchodilator Agents
0
Drug Combinations
0
Glucocorticoids
0
Salmeterol Xinafoate
6EW8Q962A5
Fluticasone
CUT2W21N7U
Banques de données
ClinicalTrials.gov
['NCT01967173']
Types de publication
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1227-1239Subventions
Organisme : NHLBI NIH HHS
ID : K08 HL118128
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL098075
Pays : United States
Organisme : NIAID NIH HHS
ID : K23 AI125785
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL098115
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10HL098075
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002378
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL064313
Pays : United States
Investigateurs
Michael E Wechsler
(ME)
Stanley J Szefler
(SJ)
Victor E Ortega
(VE)
Jacqueline Pongracic
(J)
Vernon Chinchilli
(V)
John J Lima
(JJ)
Jerry A Krishnan
(JA)
Susan J Kunselman
(SJ)
David Mauger
(D)
Eugene R Bleecker
(ER)
Leonard B Bacharier
(LB)
Avraham Beigelman
(A)
Mindy Benson
(M)
Kathryn Blake
(K)
Michael Cabana
(M)
Juan Carlos Cardet
(JC)
Mario Castro
(M)
James F Chmiel
(JF)
Ronina Covar
(R)
Loren Denlinger
(L)
Emily DiMango
(E)
Anne M Fitzpatrick
(AM)
Deborah Gentile
(D)
Nicole Grossman
(N)
Fernando Holguin
(F)
Daniel Jackson
(D)
Monica Kraft
(M)
Craig LaForce
(C)
Stephen C Lazarus
(SC)
Robert F Lemanske
(RF)
Dayna Long
(D)
Njira Lugogo
(N)
Fernando Martinez
(F)
Deborah A Meyers
(DA)
Wendy C Moore
(WC)
James Moy
(J)
Edward Naureckas
(E)
J Tod Olin
(JT)
Stephen P Peters
(SP)
Wanda Phipatanakul
(W)
Loretta Que
(L)
Hengameh Raissy
(H)
Rachel Robison
(R)
Kristie Ross
(K)
William Sheehan
(W)
Lewis J Smith
(LJ)
Julian Solway
(J)
Christine A Sorkness
(CA)
Lisa Sullivan Vedder
(LS)
Sally Wenzel
(S)
Steve White
(S)
Elliot Israel
(E)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Massachusetts Medical Society.
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