Evaluation of Salmeterol or Montelukast as Second-Line Therapy for Asthma Not Controlled With Inhaled Corticosteroids (original) (raw)
Related papers
Chest, 2000
We wished to evaluate whether the combination of a leukotriene receptor antagonist and long-acting  2-agonist might confer additive beneficial effects in terms of bronchoprotection and bronchodilatation, in mild to moderate asthmatic patients who were suboptimally controlled on inhaled corticosteroids alone. Methods: Twelve asthmatic patients were enrolled into a single-blind, placebo-controlled, crossover study, receiving additive therapy as either of the following: (1) montelukast alone, 10 mg (ML 10); (2) inhaled salmeterol alone, 50 g (SM 50); (3) ML 10 and SM 50 ; (4) ML 10 and inhaled salmeterol, 100 g (SM 100); or (5) placebo inhaler and tablet. Trough measurements were made of adenosine monophosphate (AMP) bronchial challenge (the provocative concentration of a drug [AMP] causing a fall of > 20% in FEV 1 [PC 20 ]) as the primary end point, and spirometry, following single doses of either placebo or active treatments (12 h after salmeterol, and 24 h after monteleukast, respectively). Results: Compared to placebo, all active treatments led to significant improvements (p < 0.05) in geometric mean AMP-PC 20 : placebo, 42 mg/mL; ML 10 , 106 mg/mL; SM 50 , 115 mg/mL; ML 10 and SM 50 , 183 mg/mL; and ML 10 and SM 100 , 247 mg/mL. The effects of montelukast and salmeterol were numerically additive, with ML 10 and SM 100 being significantly different (p < 0.05) from ML 10 alone. For mean FEV 1 and forced expiratory flow rate between 25% and 75% of vital capacity, there were significant differences (p < 0.05) between both combination therapies vs ML 10 alone. Conclusions: Our results suggest additive benefits of a single dose of a long-acting  2-agonist and leukotriene antagonist, in terms of bronchoprotection and bronchodilation. Further studies in more severe asthmatics are required to evaluate long-term clinical effects.
Respiratory Medicine, 2000
Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids represent a management challenge. Leukotrienes play a key role in asthma pathophysiology, and since pro-in¯ammatory leukotrienes are poorly suppressed by corticosteroids it seems rational to add a leukotriene receptor antagonist (LTRA) when a low to moderate dose of inhaled corticosteroids does not provide sucient disease control. Long acting 2 -agonist (LABA) treatment represents an alternative to LTRAs and both treatment modalities have been shown to provide additional disease control when added to corticosteroid treatment. To compare the relative clinical bene®ts of adding either a LTRA or a LABA to asthma patients inadequately controlled by inhaled corticosteroids, a randomized, double-blind, multi-centre, 48-week study will be initiated at approximately 120 centres throughout Europe, Latin America, Middle East, Africa and the Asia±Paci®c region in early 2000. The study will compare the oral LTRA montelukast with the inhaled LABA salmeterol, each administered on a background of inhaled¯uticasone, on asthma attacks, quality of life, lung function, eosinophil levels, healthcare utilization, and safety, in approximately 1200 adult asthmatic patients. The requirements for study enrolment include a history of asthma, FEV 1 or PEFR values between 50% and 90% of the predicted value together with !12% improvement in FEV 1 after -agonist administration, a minimum pre-determined level of asthma symptoms and daily -agonist medication. The study will include a 4-week run-in period, during which patients previously taking inhaled corticosteroids are switched to open-label¯uticasone (200 "g daily), followed by a 48-week doubleblind, treatment period in which patients continuing to experience abnormal pulmonary function and daytime symptoms are randomized to receive montelukast (10 mg once daily) and salmeterol placebo, or inhaled salmeterol (100 "g daily) and montelukast placebo. All patients will continue with inhaled¯uticasone (200 "g daily). During the study, asthma attacks, overnight asthma symptoms, and morning peak expiratory¯ow rate will be assessed using patient diary cards; quality of life will also be assessed using an asthma-speci®c quality-of life questionnaire. The results of this study are expected to provide physicians with important clinical evidence to help them make a rational and logical treatment choice for asthmatic patients experiencing breakthrough symptoms on inhaled corticosteroids.
Annals of Allergy, Asthma & Immunology, 2004
Background: For patients whose asthma is uncontrolled with low-dose inhaled corticosteroids, addition of alternative therapy instead of increasing the steroid dose is recommended by current treatment guidelines. Objective: To compare montelukast, a once-daily leukotriene receptor antagonist, and salmeterol, a twice-daily, long-acting -agonist, concomitantly administered with inhaled fluticasone, according to the percentage of patients without an asthma attack for 1 year. Methods: A randomized, double-blind, double-dummy, multicenter study was conducted. Adult patients with moderate-tosevere persistent asthma (ages 14-73 years) receiving inhaled fluticasone (220 g/d) who remained symptomatic during a 4-week run-in period were randomized to the addition of salmeterol (84 g/d) or montelukast (10 mg/d) for 48 weeks. Results: Of the 1,473 randomized patients, 743 were randomized to montelukast and 730 to salmeterol; 1,059 patients completed the study. Eighty percent of patients in the montelukast group and 83.3% of patients in the salmeterol group remained attack free during the 48 weeks of treatment (relative risk, 1.20; 95% confidence interval, 0.96-1.49). Montelukast significantly reduced blood eosinophil counts compared with salmeterol, whereas salmeterol significantly increased prealbuterol forced expiratory volume in 1 second, asthma-specific quality of life, morning peak expiratory flow rate, and decreased nocturnal awakenings compared with montelukast. Differences between treatments were small, and both treatments were generally well tolerated. Conclusions: Addition of montelukast or salmeterol to an inhaled corticosteroid similarly protected most patients from experiencing an asthma attack during a 1-year period, but, based on noninferiority limits, the study was inconclusive with regard to a difference between treatment groups.
Respiratory Medicine, 2009
Background: Inhaled corticosteroid therapy suppresses nitric oxide levels (NO) of airway origin but not necessarily NO of alveolar or small airway origin. Systemic therapy with an oral anti-leukotriene agent may suppress NO production in distal airways and alveoli not reached by inhaled therapy. Methods: Adult patients with mild asthma were treated for 3 weeks with inhaled fluticasone 250 mg twice daily then with inhaled fluticasone plus oral montelukast 10 mg daily for 3 additional weeks. We monitored exhaled NO (eNO), spirometry, lung volumes, and asthma symptoms scores at baseline and at the end of each treatment period. In a subset of patients, we continued with montelukast monotherapy and repeated these measurements. Results: In the 18 patients studied, pulmonary function parameters and asthma symptom scores were not altered significantly from baseline by any therapy. The total eNO at baseline was 55 AE 35.3 ppb, dropping to 28.1 AE 15.3 ppb (p Z 0.005) after 3 weeks of fluticasone and to 23.5 AE 14 ppb (p Z 0.001 vs. baseline) after the addition of montelukast. The trend towards reduced total eNO with the combination therapy vs. monotherapy was not statistically significant. Alveolar eNO dropped from 4.2 AE 2.4 at baseline to 3.0 AE 1.5 (p Z 0.1) after fluticasone and then to 2.2 AE 0.9 (p Z 0.08 vs. baseline) after fluticasone plus montelukast, increasing then to 3.8 AE 1.8 after montelukast alone (p Z 0.6 vs. baseline). Conclusions: Leukotriene receptor antagonists administered systemically might decrease small airway/alveolar sites of inflammation when combined to inhaled corticosteroid therapy. ª a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / r m e d Respiratory Medicine (2009) 103, 296e300
CHEST Journal, 2003
Study objectives: Leukotriene receptor antagonists appear to exert anti-inflammatory activity in asthma. We undertook the present study to evaluate the effect of montelukast on levels of exhaled nitric oxide (ENO) and two inflammatory markers, hydrogen peroxide (H 2 O 2), and cysteinyl leukotrienes (cys-LTs), in the exhaled breath condensate of subjects with mild asthma. Patients: Twenty stable subjects with mild asthma (15 women and 5 men; mean [؎ SD] age, 34.8 ؎ 12.6 years) were included in the study. Intervention: A 1-week run-in period was followed by 2 weeks of treatment (with montelukast or placebo) that was administered in randomized, double-blind, crossover fashion. One week of washout followed each treatment arm. Results: Montelukast significantly reduced the levels of ENO from baseline (median, 52.5 parts per billion [ppb]; 25th to 75th percentile, 37.8 to 101.8 ppb) during the entire treatment period (ie, day 1 to day 14), with the effect measurable as early as day 1 (median, 45.9 ppb; 25th to 75th percentile, 29.3 to 92.5 ppb) and with the maximal effect being observed on day 7 (median, 35.7 ppb; 25th to 75th percentile, 27.6 to 66.6 ppb). The levels of ENO did not change significantly with placebo therapy. Montelukast improved symptom score and reduced peak expiratory flow (PEF) variability. Changes in PEF variability correlated positively with changes in ENO (r ؍ 0.46; p ؍ 0.04). No significant changes in FEV 1 or concentration of H 2 O 2 in the exhaled breath condensate were observed. Levels of cys-LTs were undetectable in the exhaled breath condensate. Conclusions: We concluded that montelukast reduces the levels of ENO in patients with mild asthma, a finding that is compatible with an anti-inflammatory effect of montelukast, and that ENO appears to be more sensitive in detecting this effect than FEV 1 and H 2 O 2 levels in the exhaled breath condensate.
Effects of oral montelukast on airway function in acute asthma
Respiratory Medicine, 2003
Montelukast, a specific cysteinyl leukotriene receptor antagonist, has been shown to improve pulmonary function within1h of ingestion.This study was undertaken to compare the effects on peakexpiratory flow rate (PEFR) of oral montelukast added to intravenous steroid, intravenous steroid alone and placebo during the 24 h period following administration.Seventyasthmatic patients (FEV 1 40^80% predicted and 15% improvement afterinhaled b agonist) were enrolled in a single blind study to receive oral montelukast (10 mg) plus intravenous prednisolone (1mg/kg), intravenous prednisolone (1mg/kg) or placebo in a randomised fashion.The patients received one of the above three groups of medication before any other treatments.This was immediately followed by the aerosol treatments of 100 mcg of terbutaline sulphate divided into three doses during1h as described in the consensus statement.Thereafter, patients were observed for 24 h to document the effects on PEFR,Borg dyspnoea score and need for rescue medication.The primary end point was percentage change atdifferenttime points. Secondary end points were Borg dyspnoea score and use of rescue medication.Compared with placebo, montelukast added to the prednisolone group and the prednisolone alone group had significant percentage change from baseline in PEFR in the entire 24 h period (Po0.05).The difference in PEFR between montelukast plus prednisolone group and prednisolone group favoured the montelukast plus prednisolone group but did not reach statistical significance.Furthermore, montelukast plus prednisolone group required lessinhaled short-acting b agonist than other two groups.The results of this study indicate that adding montelukast to steroid in acute asthma may have some additive improvement in lung functions.
Effect of montelukast on exhaled nitric oxide and nonvolatile markers of inflammation in mild asthma
Study objectives: Leukotriene receptor antagonists appear to exert anti-inflammatory activity in asthma. We undertook the present study to evaluate the effect of montelukast on levels of exhaled nitric oxide (ENO) and two inflammatory markers, hydrogen peroxide (H2O2), and cysteinyl. leukotrienes (cys-LTs), in the exhaled breath condensate of subjects with mild asthma. Patients: Twenty stable subjects with mild asthma (15 women and 5 men; mean [+/-SD] age, 34.8 +/- 12.6 years) were included in the study. Intervention: A 1-week run-in period was followed by 2 weeks of treatment (with montelukast or placebo) that was administered in randomized, double-blind, crossover fashion. One week of washout followed each treatment arm. Results: Montelukast significantly reduced the levels of ENO from baseline (median, 52.5 parts per billion [ppb]; 25th to 75th percentile, 37.8 to 101.8 ppb) during the entire treatment period (ie, day 1 to day 14), with the effect measurable as early as day I (median, 45.9 ppb; 25th to 75th percentile, 29.3 to 92.5 ppb) and with the maximal effect being observed on day 7 (median, 35.7 ppb; 25th to 75th percentile, 27.6 to 66.6 ppb). The levels of ENO did not change significantly with placebo therapy. Montelukast improved symptom score and reduced peak expiratory flow (PEF) variability. Changes in PEF variability correlated positively with changes in ENO (r = 0.46; p = 0.04). No significant changes in FEV1 or concentration of H2O2 in the exhaled breath condensate were observed. Levels of cys-LTs were undetectable in the exhaled breath condensate. Conclusions: We concluded that montelukast reduces the levels of ENO in patients with mild asthma, a finding that is compatible with an anti-inflammatory effect of montelukast, and that ENO appears to be more sensitive in detecting this effect, than FEV1 and H2O2 levels in the exhaled breath condensate
A Comparative Study of Montelukast and Salbutamol in Bronchial Asthma
International Journal of Scientific Research in Science and Technology, 2022
Current asthma drug therapy is highly effective, having evolved from naturally occurring substances via logical pharmaceutical developments. Pharmacology has played an important role in the development of asthma drugs, and several key experimental findings have been published in this journal. Understanding the pharmacology of effective drug therapies has also taught us a lot about the mechanisms underlying asthma. 2-Adrenoceptor agonists, which evolved from catecholamines in the adrenal medulla, are the most effective bronchodilators, whereas corticosteroids, which evolved from catecholamines in the adrenal cortex, are by far the most effective controllers of the underlying inflammatory process in the airways. A combination inhaler containing a long-acting 2-agonist and a corticosteroid - an improved form of adrenal gland extract - is the current "gold standard" of asthma therapy. Theophylline, a dietary methyl xanthine, and chromoglycate, a plant-derived substance, have both been widely utilized in the treatment of asthma, but their molecular mechanisms are still unknown. Pharmacology has been crucial in enhancing natural products to create effective, long-lasting, and secure asthma medications, but it has faced difficulties in developing new classes of anti-asthma treatments. Leukotriene antagonists, the only brand-new type of anti-asthma therapy established in the previous 30 years, are less efficient than currently available medications. Corticosteroids are less successful than new, more focused medicines that target particular cytokines, but more focused medications run the risk of having side effects that may not be tolerable. Pharmacology, not molecular genetics, appears to be the most likely direction for future advancements in asthma treatment.
Thorax, 2008
Objective: To systematically review the evidence for the medium to long term benefits and risks of montelukast as add-on therapy to inhaled corticosteroids (ICS) in comparison with placebo and active controls in mild to moderate asthma. Data sources: Medline, Embase, Cochrane Register of Controlled Trials, reference lists of retrieved articles, clinical trial registries and study results databases. Review methods: Systematic review of randomised controlled trials (duration >12 weeks) in adolescents and adults comparing montelukast/ICS versus ICS monotherapy or montelukast/ICS versus active control/ICS. Metaanalyses were conducted where feasible. The main focus was on clinical outcomes (eg, exacerbations). Adverse events were also assessed. Results: 13 studies meeting all of the inclusion criteria were identified: 7 studies, including constant or tapered doses of ICS, compared montelukast/ICS with ICS monotherapy. Six studies compared add-on montelukast with an add-on active control (salmeterol). Overall, the data indicated that montelukast/ICS was clinically more effective than ICS monotherapy. The ICS sparing potential of montelukast was clearly demonstrated in one study. Montelukast/ICS and ICS monotherapy showed similar safety profiles. In the active controlled studies, montelukast/ICS was clinically less effective than salmeterol/ICS in the 12 week trials (pooled proportion of patients with >1 exacerbation: p = 0.006). However, separate analysis of active controlled 48 week trials showed comparable proportions for patients with >1 exacerbation in both groups. Conclusions: Montelukast as add-on therapy to ICS improves control of mild to moderate asthma compared with ICS monotherapy. Although the addition of salmeterol to ICS is clinically as effective as or even more effective than the addition of montelukast, montelukast may have a better long term safety profile and offer a treatment alternative for asthma patients.
Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial
European Respiratory Journal, 1999
Leukotrienes are pro-inflammatory mediators which may contribute to tissue, sputum, and blood eosinophilia seen in allergic and inflammatory diseases, including asthma. Montelukast is a cysteinyl leukotriene 1 (CysLT 1 ) receptor antagonist which improves asthma control; the aim of this study was to investigate its effect on induced sputum eosinophils.