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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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Leukotriene D4 inhalation challenge for predicting short-term efficacy of montelukast: a pilot study.
Guan, WJ, Shi, X, Zheng, JP, Gao, Y, Jiang, CY, Xie, YQ, Liu, QX, Zhu, Z, Guo, E, An, JY, et al
The clinical respiratory journal. 2015;(1):111-20
Abstract
INTRODUCTION The convenient measure to predict efficacy of leukotriene receptor antagonist is lacking. OBJECTIVES To determine if leukotriene D4 inhalation challenge predicts short-term efficacy of montelukast in asthma. METHODS In this open-labelled 28-day trial, 45 patients with asthma were allocated to leukotriene-sensitive and leukotriene-insensitive group to receive montelukast monotherapy (10 mg, once daily) based on the positive threshold of leukotriene D4 inhalation challenge test (4.800 nmol). Miscellaneous measurements comprised fractional exhaled nitric oxide, methacholine inhalation challenge, Asthma Control Test and Asthma Quality of Life Questionnaire. Peak expiratory flow was self-monitored throughout the treatment. End point assessments were performed 3 to 5 days after montelukast withdrawal. RESULTS Twenty-three patients in leukotriene-sensitive group and 10 leukotriene-insensitive group completed the study. Both groups differed neither in 28-day peak expiratory flow rate nor in maximal weekly peak expiratory flow (both P > 0.05). However, minimal weekly peak expiratory flow was significantly higher in leukotriene-insensitive group throughout the treatment course (all P < 0.05) except for week 1 (P > 0.05). Both groups did not differ statistically in the post-treatment improvement in forced expiratory volume in 1 s (FEV1 ) predicted% prior to inhalation challenge, fractional exhaled nitric oxide or the airway responsiveness to leukotriene D4 or methacholine (all P > 0.05). There was a marked increase in Asthma Control Test score and the symptom score of Asthma Quality of Life Questionnaire in both groups (both P < 0.05). The overall significance of Logistic regression model was unremarkable (P = 0.467). CONCLUSION Responsiveness to inhaled leukotriene D4 alone might not be sufficient to predict the short-term efficacy of montelukast monotherapy in patients with asthma.
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Desloratadine-montelukast combination improves quality of life and decreases nasal obstruction in patients with perennial allergic rhinitis.
Cingi, C, Oghan, F, Eskiizmir, G, Yaz, A, Ural, A, Erdogmus, N
International forum of allergy & rhinology. 2013;(10):801-6
Abstract
BACKGROUND The effects of desloratadine-montelukast combination on quality of life (QoL) and nasal airflow of patients with perennial allergic rhinitis (PAR) has not been reported. The objective of this work was investigate the efficacy of desloratadine-montelukast combination on nasal obstruction and health-related quality of life (HRQL) of patients with PAR. METHODS The patients with PAR (n = 40) were assessed using acoustic rhinometry (AcR) and Rhinoconjunctivitis QoL Questionnaire (RQLQ) before therapy. Desloratadine-montelukast fixed-dose combination treatment was applied to every patient once daily. The AcR and RQLQ score were reevaluated at the first and third months; and statistical comparison of pretreatment and posttreatment results was performed. RESULTS Nasal symptoms and signs such as itching, sneezing, discharge, congestion, and edema, and color change of turbinates have been decreased after treatment. In AcR, minimum cross-sectional area (MCA) measurements and volume results were increased after the treatment. Correlation was found between the volume results and nasal discharge and/or congestion in right nasal passages. In left nasal passages, statistical relation was observed between the MCA and itching and/or change of turbinate color (p < 0.05). A significant decrease in the overall RQLQ score was determined at the first and third months of therapy. The difference between scores at baseline and end of the first and third months for all domains was statically significant (p < 0.001). The treatment difference in change from the first month to the end of the third month was statistically significant (p < 0.05). CONCLUSION Desloratadine-montelukast combination therapy causes subjective and objective decrease in nasal obstruction, reduces the other symptoms of PAR and improves the disease-specific QoL.
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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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Abstract
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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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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Effects of montelukast on subjective and objective outcome measures in preschool asthmatic children.
Moeller, A, Lehmann, A, Knauer, N, Albisetti, M, Rochat, M, Johannes, W
Pediatric pulmonology. 2008;(2):179-86
Abstract
It is well accepted that control of airway inflammation is crucial for overall asthma control. Hence, efficient anti-inflammatory therapy is important for disease control. Therefore, we studied the effect of a treatment with montelukast on subjective and objective measures in preschool asthmatic children with insufficient control of airway inflammation, illustrated by increased fractional exhaled nitric oxide (FeNO). Thirty-one preschool children (2.5-5 years) were included in this study. Children with FeNO > or = 10 ppb at the first visit received montelukast 4 mg as a first line therapy or an add-on therapy to their baseline treatment (group 1). Therapy was not changed at first visit in children with FeNO < 10 ppb (group 2). Symptom scores, FeNO, lung function (forced oscillation, Rrs8Hz) and airway responsiveness to adenosine 5'-monophosphate (AMP) were assessed at visits 1 and 2 eight weeks apart. There was a significant decrease in FeNO (median [interquartile range]; 12.9 [3.7] vs. 7.6 [6.85] ppb, P = 0.011), Rrs8Hz (mean +/- SD; 10.03 +/- 3.1 vs. 8.72 +/- 2.43 hPa.s/L; P = 0.047) and symptom scores (2[2] vs. 1.5[2], P = 0.034) and a significant increase in the provocative AMP dose (2.65 +/- 2.1 vs. 4.54 +/- 1.05; P = 0.015) in group 1 but not in group 2. First line or add-on treatment of oral montelukast in preschool children with mild to moderate asthma and elevated FeNO, decreased levels of FeNO, improved airway responsiveness to AMP, lung function and symptom scores.
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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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Leukotriene receptor antagonists: a good choice in the treatment of premenstrual asthma?
Pasaoglu, G, Mungan, D, Abadoglu, O, Misirligil, Z
The Journal of asthma : official journal of the Association for the Care of Asthma. 2008;(2):95-9
Abstract
The aim of this study was to investigate the effects of leukotriene receptor antagonists (LTRAs) on the premenstrual exacerbation of asthma (PMA). Twenty-four female patients with mild asthma were enrolled in the study. Patients were followed for three menstrual cycles and separated into two groups based on whether they exhibit premenstrual worsening of asthma symptoms (n = 11) or not (n = 13). During the first month all were treated with only inhaled steroids (IS) (run-in period); during the second month they received IS plus placebo; and during the third month they were given IS plus montelukast. Furthermore, they were advised to use beta(2)-agonists as needed. Peak expiratory flow rate (PEFR) and symptom scores were recorded during the 3 months. Pulmonary function tests (PFT) and the levels of oestrogen, progesterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured a week before the beginning of the menstrual period. At the end of the 3-month period, it was observed that following therapy with montelukast, the patients with PMA showed significant improvement in PEFR variability and symptom scores when compared with the placebo group. Baseline FSH levels were higher, but FSH and other hormone levels and PFTs did not change in these groups. However, in the group without PMA there was no difference between the montelukast or placebo groups in PEFR variability, symptom scores, PFTs, and hormone levels. Based on the data in hand, it could be stated that LTRAs have ensured the control of symptoms and improved PEFR variability in patients with PMA by suppressing inflammation. We are of the view that LTRAs would be a right choice in the treatment of patients with PMA.
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The efficacy of montelukast and airway mast cell profiles in patients with cough variant asthma.
Kawai, S, Baba, K, Matsubara, A, Shiono, H, Okada, T, Yamaguchi, E
The Journal of asthma : official journal of the Association for the Care of Asthma. 2008;(3):243-50
Abstract
BACKGROUND Cough variant asthma (CVA) is characterized by chronic cough without apparent wheezing; its pathophysiology is considered to be similar to that of classic asthma. OBJECTIVE The clinical effects of montelukast, a cysteinyl-leukotriene receptor antagonist, on cough variant asthma were assessed, and the activation profile of airway mast cells was examined. METHODS Montelukast (10 mg/day) was given orally to 36 CVA patients (25 women and 11 men; median age, 37.5 years). Before treatment, the patients' bronchial mucosa underwent a biopsy with a fiberoptic bronchoscope. The biopsy specimens were double stained with anti-CD63 antibody and anti-human tryptase antibody. RESULTS After 2 weeks of montelukast treatment, cough symptoms improved in 22 patients (the effective group) but did not improve in 14 patients (the ineffective group); in the ineffective group, the symptoms disappeared 2 weeks after they were switched to fluticasone propionate (400 microg/day) inhalation therapy. In the effective group, the time interval from the onset of symptoms to the initiation of treatment was significantly shorter than in the ineffective group. The bronchial mucosa biopsy specimens showed that the proportion of CD63-positive cells in tryptase-positive mast cells was significantly higher in the effective group than in the ineffective group; although the total numbers of mast cells were not different between the two groups. CONCLUSION There is a subgroup of CVA patients in whom leukotrienes are closely involved in the pathogenesis of their chronic cough; activation of airway mast cells may be an essential feature in these patients.
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Association of IL-13 polymorphisms with leukotriene receptor antagonist drug responsiveness in Korean children with exercise-induced bronchoconstriction.
Kang, MJ, Lee, SY, Kim, HB, Yu, J, Kim, BJ, Choi, WA, Jang, SO, Hong, SJ
Pharmacogenetics and genomics. 2008;(7):551-8
Abstract
BACKGROUND IL-13 is a pivotal cytokine in allergic inflammation and bronchial hyperresponsiveness, and is known to influence leukotriene levels. OBJECTIVE We investigated whether IL-13 polymorphisms may be associated with clinical phenotypes and drug responsiveness to the leukotriene receptor antagonist (LTRA) in Korean asthmatic children with exercise-induced bronchoconstriction (EIB). METHODS We enrolled 242 normal controls and 374 patients with asthma. Of the asthmatic patients, 100 performed exercise challenge tests before and after receiving montelukast (5 mg/day) for 8 weeks and included 80 subjects in drug responsiveness analysis. We assessed IL-13 polymorphisms (-1512A/C, -1112C/T, +2044G/A) through PCR-restriction fragment length polymorphism analysis. RESULTS Significantly higher total IgE levels and maximum percent fall in forced expiratory volume in 1 s (FEV1) (%) after exercise challenge test were found in asthmatic patients carrying one or two copies of the IL-13 +2044A versus those homozygous for +2044G (P=0.011 and 0.040, respectively). We further noted a correlation of total IgE with maximum percent fall in FEV1 (%) in asthmatic patients, as well as a reverse correlation with improvement of maximum percent fall in FEV1 (%) after exercise challenge tests. Finally, we observed a significant association between responsiveness to montelukast and IL-13 -1112C/T polymorphism and the haplotype of IL-13 polymorphisms. CONCLUSION The IL-13 +2044G/A polymorphism may be associated with atopy and EIB severity in Korean children with EIB, and thus could potentially be considered as a disease-modifying gene. Moreover, the IL-13 -1112C/T polymorphism and the haplotype of IL-13 polymorphisms seem to be associated with LTRA drug responsiveness, and thus might prove useful as a target for modulation of LTRA drug responsiveness.