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Montelukast for Children with Obstructive Sleep Apnea: Results of a Double-Blind, Randomized, Placebo-Controlled Trial.
Kheirandish-Gozal, L, Bandla, HP, Gozal, D
Annals of the American Thoracic Society. 2016;(10):1736-1741
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Abstract
RATIONALE Obstructive sleep apnea (OSA) is highly prevalent in children and is usually treated by adenotonsillectomy. Nonsurgical therapies for OSA consist primarily of antiinflammatory approaches and have gained popularity, but their efficacy remains to be critically examined. OBJECTIVES To determine the effect of montelukast on pediatric OSA. METHODS A prospective randomized double-blind controlled trial of polysomnographically diagnosed OSA in children ages 2-10 years who were treated with either oral montelukast (4 or 5 mg daily) or placebo for 16 weeks. Adherence to the medication was ascertained using automated timed pill dispensers along with weekly telephonic reminders. MEASUREMENTS AND MAIN RESULTS Ninety-two children diagnosed with OSA were approached, and 64 (69.6%) agreed to participate. Of these, 57 (89.0%) completed the 16-week trial, 28 in the montelukast group and 29 in the placebo group. Age, sex, and percentage of obesity were similar in the two groups, as were initial apnea-hypopnea index (AHI) scores. Overall, intention-to-treat analyses revealed that beneficial effects occurred in 20 children receiving montelukast (71.4%), whereas only 2 (6.9%) of the children receiving placebo showed reductions in AHI score (P < 0.001). Indeed, AHI decreased from 9.2 ± 4.1/hour total sleep time (TST) to 4.2 ± 2.8/hour TST (P < 0.0001) in montelukast-treated children, whereas in children receiving placebo, the AHI did not change (from 8.2 ± 5.0/h TST before to 8.7 ± 4.9/h TST at completion of the trial). CONCLUSIONS When compared with placebo, montelukast for 16 weeks effectively reduced the severity of obstructive sleep apnea in children 2-10 years of age. These results support a therapeutic role for leukotriene modifiers in pediatric OSA provided that long-term trials confirm current findings. Clinical trial registered with www.clinicaltrials.gov (NCT 00599534).
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Urinary leukotriene E4/exhaled nitric oxide ratio and montelukast response in childhood asthma.
Rabinovitch, N, Graber, NJ, Chinchilli, VM, Sorkness, CA, Zeiger, RS, Strunk, RC, Bacharier, LB, Martinez, FD, Szefler, SJ, ,
The Journal of allergy and clinical immunology. 2010;(3):545-51.e1-4
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BACKGROUND A subset of children with asthma respond better to leukotriene receptor antagonists than to inhaled corticosteroids. Information is needed to identify children with these preferential responses. OBJECTIVE We sought to determine whether the ratio of urinary leukotriene E(4) (LTE(4)) to fractional exhaled nitric oxide (FE(NO)) delineates children with preferential responsiveness to montelukast compared with fluticasone propionate (FP) therapy. METHODS Data from 318 children with mild-to-moderate asthma enrolled in 2 National Heart, Lung, and Blood Institute Childhood Asthma Research and Education Network studies (Characterizing the Response to a Leukotriene Receptor Antagonist and an Inhaled Corticosteroid [CLIC] and the Pediatric Asthma Controller Trial [PACT]) were analyzed. The association between LTE(4)/FE(NO) ratios at baseline and improved lung function or asthma control days (ACDs) with montelukast and FP therapy was determined, and phenotypic characteristics related to high ratios were assessed. RESULTS LTE(4)/FE(NO) ratios were associated with a greater response to montelukast than FP therapy for FEV(1) measurements (2.1% increase per doubling of ratio, P = .001) and for ACDs per week (0.3-ACD increase, P = .009) in the CLIC study. In PACT the ratio was associated with greater ACD responsiveness to MT than FP therapy (0.6 ACD increase, P=.03) [corrected]. In a combined study analysis, LTE(4): FE(NO) ratios were associated with greater response to MT than FP therapy for FEV(1) (1.8% increase, P =.0005) and ACDs (0.4 increase, P =.001)[corrected].Children with LTE(4)/FE(NO) ratios at or above the 75th percentile were likely (P < .05) to be younger and female and exhibit lower levels of atopic markers and methacholine reactivity. CONCLUSION LTE(4)/FE(NO) ratios predict a better response to montelukast than FP therapy in children with mild-to-moderate asthma.
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Quality of life in patients with persistent allergic rhinitis treated with montelukast alone or in combination with levocetirizine or desloratadine.
Ciebiada, M, Ciebiada, MG, Kmiecik, T, DuBuske, LM, Gorski, P
Journal of investigational allergology & clinical immunology. 2008;(5):343-9
Abstract
BACKGROUND Persistent allergic rhinitis often impairs quality of life. OBJECTIVE We assessed the extent to which treating persistent allergic rhinitis with montelukast, desloratadine, and levocetirizine alone or in combination improved quality of life. METHODS A 32-week randomized, double-blind, placebo-controlled, crossover study was performed in 2 arms: 20 patients received montelukast 10 mg/d and/or desloratadine 5 mg/d or placebo; 20 patients received montelukast 10 mg/d and/or levocetirizine 5 mg/d or placebo. The treatment periods were separated by 2-week washout periods. Quality of life was assessed on the day before starting treatment and on the last day of each treatment period using the Rhinoconjunctivitis Quality of Life Questionnaire. Sleep problems were also assessed. RESULTS In the desloratadine plus montelukast arm, the mean (SEM) quality of life score before treatment was 3.1 (0.41). After placebo, this score was 2.16 (0.43), after desloratadine it was 1.79 (0.38), after montelukast it was 1.48 (0.37), and after montelukast plus desloratadine it was 1.59 (0.37). In the montelukast plus levocetirizine arm, the mean quality of life score before treatment was 2.58 (0.49). After placebo it was 1.78 (0.46), after levocetirizine it was 1.38 (0.42), after montelukast it was 1.36 (0.37), and after montelukast plus levocetirizine it was 1.26 (0.39). CONCLUSIONS Placebo, montelukast, desloratadine and levocetirizine significantly improved quality of life. Combining montelukast with either levocetirizine or desloratadine gave additional benefits in comparison to each agent alone and could be considered for patients whose quality of life is impaired by persistent allergic rhinitis.
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Efficacy of montelukast and loratadine as treatment for allergic rhinitis in children.
Watanasomsiri, A, Poachanukoon, O, Vichyanond, P
Asian Pacific journal of allergy and immunology. 2008;(2-3):89-95
Abstract
The objective of this study was to compare the effectiveness of montelukast combined with loratadine once daily to loratadine alone for a 2-week treatment course of allergic rhinitis in a randomized, double-blind placebo controlled trial which enrolled 115 children, 6- 15-years-old. The patients were randomly assigned to receive montelukast and loratadine (treatment group) or placebo and loratadine (control group). The primary outcome was the mean percent change of the total daytime nasal symptom scores (PDTS) and secondary outcomes were the mean percent changes of the nighttime nasal, daytime eye and composite symptom scores (PNTS, PES, PCS), as well as the nasal secretion, turbinate swelling and nasal congestion scores (PNSS, PTSS, PNCS). There were no significant differences in the PDTS of the 2 groups. The change in the night time nasal congestion score (PNTS-congestion) was higher in the treatment group, but not statistically significant (p = 0.077). Only the mean percent change in decreased turbinate swelling was significantly greater in the montelukast and loratadine group than the loratadine alone group (-22 +/- 7 vs. -1 +/- 5, p < 0.05).
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Real-life effectiveness of Singulair (montelukast) in 506 children with mild to moderate asthma.
Amirav, I
The Israel Medical Association journal : IMAJ. 2008;(4):287-91
Abstract
BACKGROUND Based on the outcome of several randomized controlled trials, the orally active leukotriene receptor antagonist montelukast (Singulair, Merck) has been licensed for treatment of asthma. The drug is favored for treating childhood asthma, where a therapeutic challenge has arisen due to poor compliance with inhalation therapy. OBJECTIVES To assess the efficiency of and satisfaction with Singulair in asthmatic children under real-life conditions. METHODS Montelukast was prescribed for 6 weeks to a cohort of 506 children aged 2 to 18 years with mild to moderate persistent asthma, who were enrolled by 200 primary care pediatricians countrywide. Four clinical correlates of childhood asthma--wheeze, cough, difficulty in breathing, night awakening--were evaluated from patients' diary cards. RESULTS Due to under-treatment by their physicians, almost 60% of the children were not receiving controller therapy at baseline. By the end of the study, which consisted of montelukast treatment, a significant improvement over baseline was noted in asthma symptoms and severity, as well as in treatment compliance. The participating pediatricians and parents were highly satisfied with the treatment. CONCLUSIONS The results of this extensive study show that the use of montelukast as monotherapy in children presenting with persistent asthma resulted in a highly satisfactory outcome for themselves, their parents and their physicians.
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Effect of montelukast on basophil releasability in patients with asthma.
Sade, K, Kivity, S, Fireman, E, Schwartz, Y, Kivity, S
The Israel Medical Association journal : IMAJ. 2005;(12):792-5
Abstract
BACKGROUND The anti-inflammatory effect of montelukast, a leukotriene receptor antagonist, in patients with bronchial asthma is not entirely clear. Basophils can release a variety of mediators, including histamine and leukotriens, which most likely play an active role in the late allergic response. OBJECTIVES To study the effect of montelukast (10 mg/day) on histamine and cysteinyl leukotriene release from basophils taken from 12 mild atopic asthmatic patients who took the drug for 4 weeks. METHODS Basophils were withdrawn at baseline, and after 48 hours, 1 week, and 4 weeks of therapy. Histamine was measured by a radioenzymatic method and leukotrienes by immunologic assay. Histamine and cysLT release was measured spontaneously and following stimulation with interleukin-3 and anti-immunoglobulin E. Spirometry and symptom score were measured before and during treatment. RESULTS During the treatment with montelukast there were no significant changes in spontaneous, IL-3 and anti-IgE-induced histamine release. cysLT release decreased significantly only after 4 weeks of treatment (from 2899 +/- 550 pg/ml at baseline to 2225 +/- 430 pg/ml at 4 weeks, P= 0.02). CONCLUSIONS Montelukast does not seem to affect the release of histamine from basophils but mildly inhibits the cysLT release seen after 4 weeks of treatment.
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Effects of montelukast on airway narrowing from eucapnic voluntary hyperventilation and cold air exercise.
Rundell, KW, Spiering, BA, Baumann, JM, Evans, TM
British journal of sports medicine. 2005;(4):232-6
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BACKGROUND Exercise induced bronchoconstriction (EIB) is common in elite athletes. Eucapnic voluntary hyperventilation (EVH) is a laboratory test recommended for the identification of EIB in athletes, secondary to a field exercise challenge. Montelukast attenuates EIB, but its protective effect against airway narrowing from EVH has not been investigated. OBJECTIVE To examine the effectiveness of montelukast after exercise and after EVH. METHODS A randomised, placebo controlled, double blind, crossover study was performed with 11 physically active EIB positive subjects (eight men, three women; mean (SD) age 22.8 (6.8) years). Six hours before each of the following challenges 10 mg montelukast or placebo was ingested: (a) a six minute, cold air (-3 degrees C) maximal effort work accumulation cycle ergometer exercise; (b) EVH, breathing 5% CO(2) compressed air at 85% maximal voluntary ventilation for six minutes. Spirometry was performed before and 5, 10, and 15 minutes after the challenge. At least 48 hours was observed between challenges. RESULTS No differences in forced expiratory volume in one second (FEV(1)) were found after the two challenges. Exercise and EVH resulted in falls in FEV(1) of 22.4 (18.0) and 25.6 (16.8) respectively. Falls in FEV(1) after montelukast were less than after placebo (10.6 (10.6) and 14.3 (11.3) after exercise and EVH respectively; p<0.05). Montelukast provided protection against bronchoconstriction (59% and 53%; p<0.05) for eight exercising subjects and 10 EVH subjects; no protection was afforded for three exercising and one EVH challenged subject. CONCLUSIONS Both exercise and EVH were potent stimuli of airway narrowing. A single dose of montelukast provided reasonable protection in attenuating bronchoconstriction from either exercise or EVH. The similar protection by montelukast suggests that EVH is a suitable laboratory surrogate for EIB evaluation.
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Failure of montelukast to reduce sputum eosinophilia in high-dose corticosteroid-dependent asthma.
Jayaram, L, Duong, M, Pizzichini, MM, Pizzichini, E, Kamada, D, Efthimiadis, A, Hargreave, FE
The European respiratory journal. 2005;(1):41-6
Abstract
Sputum eosinophilia is a sensitive predictor of benefit from corticosteroid treatment. Montelukast is a cysteinyl leukotriene antagonist, which also reduces sputum and blood eosinophils. The present study examined the possibility that montelukast has an added eosinophil-lowering effect in subjects with asthma who are corticosteroid responsive but relatively corticosteroid resistant. A total of 14 clinically stable adults with asthma requiring minimum treatment with a high-dose inhaled steroid or prednisone, with baseline sputum eosinophilia (> or =5%), were randomised to receive 4 weeks of 10 mg montelukast or placebo daily in a double-blind crossover trial. The primary outcome was the effect of treatment on the percentage of sputum eosinophils. Secondary outcomes were changes in the blood eosinophil count, symptoms, forced expiratory volume in one second, peak expiratory flow and the need for salbutamol. The median (interquartile range, i.e. 75th-25th centile) for sputum eosinophils at baseline was 15.7% (22). The effect of adding montelukast was not significantly different from that of placebo, sputum eosinophils being 9.3% (18.9) after montelukast and 11.3% (22.8) after placebo. No difference was detected on secondary outcomes. No crossover interactions were observed. In conclusion, the addition of montelukast to existing high-dose corticosteroid therapy in subjects with asthma with elevated sputum eosinophils does not provide additional attenuation of airway eosinophilia.
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Short-term effects of montelukast in stable patients with moderate to severe COPD.
Celik, P, Sakar, A, Havlucu, Y, Yuksel, H, Turkdogan, P, Yorgancioglu, A
Respiratory medicine. 2005;(4):444-50
Abstract
This study aims to investigate the possibility of additional value of leukotriene receptor antagonist (LTA) on dyspnea score, arterial blood gases (ABG), pulmonary function tests (PFTs), and quality of life (St. George QoL) in chronic obstructive pulmonary disease (COPD) patients. In this randomized, prospective, single-blind, and controlled study, 117 non-reversible COPD patients defined by global initiative for chronic obstructive lung disease (GOLD) criteria were randomized to receive ipratropium bromide, formoterol and montelukast (n:58, montelukast group) or ipratropium bromide and formoterol (n:59, control group) after a 2-week run-in period. There was no significant demographic difference between the two groups (P>0.05). Baseline ABG, PFT, visual analoque scores (VAS), and QoL scores were obtained and at first month and second month, PFT, VAS, and QoL scores were repeated and ABG was obtained at second month and the values were compared with baseline values. As the result of the comparison, there was significant increase in vital capacity, FVC, FEV1, VAS, and PaO2 parameters (P<0.05), and a significant decrease in the QoL scores (P<0.05) in the montelukast group. These parameters did not show any difference in the control group (P>0.05). Sputum samples that could be obtained in 24 of the COPD patients were evaluated and in the montelukast group, there was a decrease in neutrophilic activity after treatment (n:13) (P:0.059). These results suggest that LTA that is used additionally in routine treatment protocol can produce additive improvement on PFT, dyspnea score and especially QoL in patients with stable COPD and for these reasons, LTA may be taken into account when there is need for an additional anti-inflammatory treatment in COPD patients.
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Effects of single or combined histamine H1-receptor and leukotriene CysLT1-receptor antagonism on nasal adenosine monophosphate challenge in persistent allergic rhinitis.
Lee, DK, Jackson, CM, Soutar, PC, Fardon, TC, Lipworth, BJ
British journal of clinical pharmacology. 2004;(6):714-9
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BACKGROUND The effects of single or combined histamine H(1)-receptor and leukotriene CysLT(1)-receptor antagonism on nasal adenosine monophosphate (AMP) challenge in allergic rhinitis are unknown. OBJECTIVE We elected to study the effects of usual clinically recommended doses of fexofenadine (FEX), montelukast (ML) and FEX + ML combination, compared with placebo (PL), on nasal AMP challenge in patients with persistent allergic rhinitis. METHODS Twelve patients with persistent allergic rhinitis (all skin prick positive to house dust mite) were randomized in a double-blind cross-over fashion to receive for 1 week either FEX 180 mg, ML 10 mg, FEX 180 mg + ML 10 mg combination, or PL, with nasal AMP challenge performed 12 h after dosing. There was a 1-week washout period between each randomized treatment. The primary outcome measure was the maximum percentage peak nasal inspiratory flow (PNIF) fall from baseline over a 60-min period after nasal challenge with a single 400 mg ml(-1) dose of AMP. The area under the 60-min time-response curve (AUC) and nasal symptoms were measured as secondary outcomes. RESULTS There was significant attenuation (P < 0.05) of the mean maximum percentage PNIF fall from baseline after nasal AMP challenge vs. PL, 48; with FEX, 37; 95% confidence interval for difference 2, 20; ML, 35 (4, 22); and FEX + ML, 32 (7, 24). The AUC (%.min) was also significantly attenuated (P < 0.05) vs. PL, 1893; with FEX, 1306 (30, 1143); ML, 1246 (214, 1078); and FEX + ML, 1153 (251, 1227). There were no significant differences for FEX vs. ML vs. FEX + ML comparing either the maximum or AUC response. The total nasal symptom score (out of 12) was also significantly improved (P < 0.05) vs. PL, 3.3; with FEX, 2.1 (0.3, 2.0); ML, 2.0 (0.5, 1.9); and FEX + ML, 2.5 (0.1, 1.4). CONCLUSION FEX and ML as monotherapy significantly attenuated the response to nasal AMP challenge and improved nasal symptoms compared with PL, while combination therapy conferred no additional benefit.