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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 ?g twice a day) was compared with adding salmeterol (50 ?g twice a day) and doubling the fluticasone (to 100 ?g 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.).

SUBMITTER: Wechsler ME

PROVIDER: S-EPMC7026584 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Wechsler Michael E ME Szefler Stanley J SJ Ortega Victor E VE Pongracic Jacqueline A JA Chinchilli Vernon V Lima John J JJ Krishnan Jerry A JA Kunselman Susan J SJ Mauger David D Bleecker Eugene R ER Bacharier Leonard B LB Beigelman Avraham A Benson Mindy M Blake Kathryn V KV Cabana Michael D MD Cardet Juan-Carlos JC Castro Mario M Chmiel James F JF Covar Ronina R Denlinger Loren L DiMango Emily E Fitzpatrick Anne M AM Gentile Deborah D Grossman Nicole N Holguin Fernando F Jackson Daniel J DJ Kumar Harsha H Kraft Monica M LaForce Craig F CF Lang Jason J Lazarus Stephen C SC Lemanske Robert F RF Long Dayna D Lugogo Njira N Martinez Fernando F Meyers Deborah A DA Moore Wendy C WC Moy James J Naureckas Edward E Olin J Tod JT Peters Stephen P SP Phipatanakul Wanda W Que Loretta L Raissy Hengameh H Robison Rachel G RG Ross Kristie K Sheehan William W Smith Lewis J LJ Solway Julian J Sorkness Christine A CA Sullivan-Vedder Lisa L Wenzel Sally S White Steven S Israel Elliot E

The New England journal of medicine 20190901 13

<h4>Background</h4>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.<h4>Methods</h4>We conducted two prospective, random ...[more]

PMID: 31553835

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Project description:BackgroundFor children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking.MethodsWe randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%.ResultsA differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005).ConclusionsNearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.)

Project description:ContextAsymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. Untreated GER has been postulated to be a cause of inadequate asthma control in children despite inhaled corticosteroid treatment, but it is not known whether treatment with proton pump inhibitors improves asthma control.ObjectiveTo determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER.Design, setting, and participantsThe Study of Acid Reflux in Children With Asthma, a randomized, masked, placebo-controlled, parallel clinical trial that compared lansoprazole with placebo in children with poor asthma control who were receiving inhaled corticosteroid treatment. Three hundred six participants enrolled from April 2007 to September 2010 at 19 US academic clinical centers were followed up for 24 weeks. A subgroup had an esophageal pH study before randomization.InterventionParticipating children were randomly assigned to receive either lansoprazole, 15 mg/d if weighing less than 30 kg or 30 mg/d if weighing 30 kg or more (n = 149), or placebo (n = 157).Main outcome measuresThe primary outcome measure was change in Asthma Control Questionnaire (ACQ) score (range, 0-6; a 0.5-unit change is considered clinically meaningful). Secondary outcome measures included lung function measures, asthma-related quality of life, and episodes of poor asthma control.ResultsThe mean age was 11 years (SD, 3 years). The mean difference in change (lansoprazole minus placebo) in the ACQ score was 0.2 units (95% CI, 0.0-0.3 units). There were no statistically significant differences in the mean difference in change for the secondary outcomes of forced expiratory volume in the first second (0.0 L; 95% CI, -0.1 to 0.1 L), asthma-related quality of life (-0.1; 95% CI, -0.3 to 0.1), or rate of episodes of poor asthma control (relative risk, 1.2; 95% CI, 0.9-1.5). Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no treatment effect for lansoprazole vs placebo was observed for any asthma outcome. Children treated with lansoprazole reported more respiratory infections (relative risk, 1.3 [95% CI, 1.1-1.6]).ConclusionIn this trial of children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, compared with placebo, improved neither symptoms nor lung function but was associated with increased adverse events.Trial registrationclinicaltrials.gov Identifier: NCT00442013.

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

Publications

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

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