Dataset Information

Risk factors for montelukast treatment failure in step-down therapy for controlled asthma.

ABSTRACT: Leukotriene receptor antagonists including montelukast are an option for step-down therapy for mild asthmatics controlled on low-dose inhaled corticosteroids (ICS). Because some patients fail montelukast step-down therapy, it would be helpful for clinicians to be able to predict the risk of treatment failure.To determine patient characteristics associated with montelukast treatment failure and develop a clinical index to predict the risk of montelukast treatment failure.Using the 165 participants in the Leukotriene or Corticosteroid or Corticosteroid-Salmeterol Study (LOCCS) trial who were stepped down from low-dose ICS to montelukast, we determined associations between enrollment variables and treatment failure. We constructed a montelukast failure index to predict the risk of montelukast treatment failure during step-down. To assess its specificity for montelukast, index performance was evaluated in the other LOCCS treatment groups.Characteristics independently associated with montelukast treatment failure included age of asthma onset <10 years old (OR = 2.39; 95% CI = 1.17-5.02; p = .018), need for steroid burst in the last year (OR = 2.39; 95% CI = 1.13-5.09; p = .022), and pre-bronchodilator forced expiratory volume in 1 s (FEV(1)) (OR = 1.44 per 10% lower % predicted; 95% CI = 1.07-1.97; p = .016). A montelukast failure index was generated from these three variables (range: -5 to 7 points). Scores <0 predicted low risk (<0.20) of treatment failure, whereas scores >5 predicted high risk (>0.60) of treatment failure.Early asthma onset, worse asthma control in the last year, and lower pre-bronchodilator FEV(1) are associated with montelukast treatment failure. A montelukast failure index is proposed to quantify the risk of failure prior to treatment initiation.

SUBMITTER: Drummond MB

PROVIDER: S-EPMC4277696 | biostudies-other | 2011 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Risk factors for montelukast treatment failure in step-down therapy for controlled asthma.

Drummond M Bradley MB Peters Stephen P SP Castro Mario M Holbrook Janet T JT Irvin Charles G CG Smith Lewis J LJ Wise Robert A RA Sugar Elizabeth A EA

The Journal of asthma : official journal of the Association for the Care of Asthma 20111027 10

<h4>Background</h4>Leukotriene receptor antagonists including montelukast are an option for step-down therapy for mild asthmatics controlled on low-dose inhaled corticosteroids (ICS). Because some patients fail montelukast step-down therapy, it would be helpful for clinicians to be able to predict the risk of treatment failure.<h4>Objectives</h4>To determine patient characteristics associated with montelukast treatment failure and develop a clinical index to predict the risk of montelukast treat ...[more]

PMID: 22029858

Similar Datasets

Project description:Asthma guidelines suggest that therapy can be reduced once asthma is controlled. Despite these recommendations, asthmatic patients are seldom stepped down in clinical practice, and questions remain about when and how to reduce asthma therapy. The purpose of the present study was to evaluate lung function and asthma control in patients who were stepped down from the highest recommended dose of inhaled corticosteroid/long acting ?2 agonist combination therapy.This was a prospective, randomised, controlled, two-arm parallel group study. Asthmatic patients who were fully controlled with a high daily dose (1000/100??g) of fluticasone/salmeterol were randomly assigned to 6?months of open-label treatment with either 500/100??g fluticasone/salmeterol Diskus daily or 400/24??g extrafine beclomethasone/formoterol pMDI daily. The primary outcome was the change in morning peak expiratory flow (PEF) values between baseline and the end of treatment. The secondary outcomes included asthma control and exacerbation frequency.Four hundred twenty-two patients were included in the analysis. The PEF values remained above 95% of the predicted values throughout the study. The end-study morning PEF rates showed equivalence between the groups (difference between means, 2.49?L/min; 95% CI, -13.43 to 18.42). No changes from baseline were detected in PEF and forced expiratory volume in 1 second measured at the clinics, in the symptom scores or in the use of rescue medication. Asthma control was maintained in 95.2% of the patients at 6?months. No significant differences between the groups were detected in any other parameter, including exacerbation frequency and adverse events.Stepping down patients whose asthma is controlled with the highest recommended dose of fluticasone/salmeterol to either 500/100??g fluticasone/salmeterol daily or 400/24??g extra-fine beclomethasone/formoterol daily provides comparable maintenance of lung function and asthma control.clinicaltrials.gov NCT00497237.

Project description:BackgroundBiomarkers that can predict loss of asthma control among patients being considered for step-down therapy in well-controlled disease are lacking.ObjectiveTo evaluate whether baseline biomarkers of type 2 airway inflammation and/or serial measurement of fractional exhaled nitric oxide (Feno) predict loss of asthma control as therapy is stepped down.MethodsIn subanalyses of a multicenter randomized, double-blind, parallel 3-arm trial comparing strategies for step-down therapy in well-controlled asthma (Long-Acting Beta-Agonist Step-Down Study), we assessed whether baseline atopy as determined by serum aeroallergen allergy screening test (Phadiatop), baseline serum eosinophil peroxidase, or baseline or serial Feno measurements during follow-up predicted the time to loss of asthma control among participants. Loss of asthma control was defined in the study protocol. We analyzed these associations in adjusted models including all participants, after testing for interactions with assignment to each of the 3 treatment groups (continuation of stable dose of combination inhaled corticosteroid-long-acting beta-agonist, step-down of inhaled corticosteroid, or discontinuation of long-acting bronchodilator).ResultsFour hundred forty-seven of the 553 Long-Acting Beta-Agonist Step-Down Study participants who were randomized to 1 of 3 treatment arms and had at least 1 biomarker measurement were included in this analysis. At baseline, higher levels of Feno were significantly associated with greater levels of multiallergen IgE levels (P < .001), but not with serum eosinophil peroxidase (P = .742). Among all participants as a group, elevations in baseline biomarkers were not predictive of a higher risk of treatment failure. In addition, Feno levels measured serially at 6-week intervals demonstrated that compared with participants with low levels (<25 parts per billion), those with intermediate (25-50 parts per billion) and high (>50 parts per billion) levels did not have significantly increased likelihood of subsequent treatment failure (hazard ratios, 1.03 [95% CI, 0.59-1.78] and 1.29 [95% CI, 0.65-2.54], respectively). There were no significant interactions of treatment group and baseline biomarkers.ConclusionsIn patients with well-controlled asthma, neither baseline levels of type 2 airway inflammatory biomarkers nor serial measures of Feno are strong predictors of treatment failure.

Project description:BackgroundMorbidity 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.MethodsWe 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.ResultsWhen 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.ConclusionsIn 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.).

Project description:ObjectiveControl of airway inflammation is the cornerstone of asthma management. The aim of the present pilot study was to assess the effects of a leukotriene receptor antagonist (LTRA) added to a basic treatment of inhaled corticosteroids (ICS) and long-acting beta-agonist (LABA) on airway hyperresponsiveness, inflammation, and quality of life in well-controlled patients with asthma.Research design and methodsSeventeen patients (age 18-65, 11 women) with well-controlled asthma presenting airway hyperresponsiveness to mannitol and methacholine challenge were given add-on montelukast on a stable ICS + LABA for 4 weeks. Quality of life and selected parameters of airway inflammation were measured at baseline and at study end. (ClinicalTrials.gov (NCT01725360)).ResultsAdding montelukast to ICS + LABA resulted in an increase in mean FEV1 (+4.5%, p = 0.057), cumulated higher dose of mannitol (+32.5%, p = 0.023) and methacholine (+17.2%, 0.237) in the provocation test, lower airway reactivity with mannitol and methacholine (response dose ratio (RDR) -50.0%, p = 0.024 and -44.3%, p = 0.006, respectively), and improved airway sensitivity to mannitol and methacholine (+12.1%, p = 0.590 and +48.0%, p = 0.129 for PD15 and PD20 FEV1, respectively). Changes in inflammation parameters (blood eosinophil count, serum eosinophil cationic protein, and exhaled nitric oxide) were consistent with these findings. Asthma-related quality of life improved significantly in all domains and overall (from 5.3 at baseline to 6.1 at the final visit, p < 0.001). The main limitation was the absence of a control group.ConclusionThe consistency of the changes in airway hyperresponsiveness and inflammation as well as in quality of life observed with an add-on therapy with montelukast in well-controlled asthma patients during 4 weeks suggests that residual inflammation may represent an area for further improvement of asthma control to be explored in adequately powered randomized controlled trials.

Dataset Information

Risk factors for montelukast treatment failure in step-down therapy for controlled asthma.

Publications

Risk factors for montelukast treatment failure in step-down therapy for controlled asthma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets