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A systematic review on the off-label use of montelukast in atopic dermatitis treatment.
Chin, WK, Lee, SWH
International journal of clinical pharmacy. 2018;(5):963-976
Abstract
Background Atopic dermatitis (AD) is the most common form of eczema. As leukotriene mediators are involved in the inflammatory phase of atopic dermatitis, montelukast has been suggested as a possible therapy. Aim of the review To evaluate the safety and efficacy of montelukast off-label use for the treatment atopic dermatitis. Method A search was performed from database inception until March 2018 in six electronic databases for randomized-controlled-trials examining the use of montelukast for AD. Results Among 301 articles screened, 11 studies met the inclusion criteria and were included in the review. The study populations consist of paediatric and adult subjects with moderate-to-severe AD. Montelukast use was shown to improve symptoms such as pruritus in four studies. Another 2 studies reported that montelukast could improve symptoms similar to the standard regimen of topical steroid and oral antihistamine. However, five studies reported that montelukast had no effects in symptoms alleviation. The use of montelukast was associated with a similar safety profile to placebo and well-tolerated with minimal adverse effects. Conclusion There is limited evidence to suggest that the off-label use of montelukast is effective in treating moderate-to-severe AD. Further research with larger study populations employing standardized endpoint measuring instrument is warranted to further investigate the off-label use of montelukast in AD treatment. Until then, the use of conventional treatments including optimal daily skin hydration should remain the mainstay in the management of atopic dermatitis. In fact, for moderate-to-severe condition, steroid sparing immune-suppressants should still be used clinically until more effective and safer alternative is discovered.
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2.
Effect of montelukast on clinical score and cytokine levels of infants for clinically diagnosed acute bronchiolitis.
Tahan, F, Celik, S, Eke Gungor, H
Allergologia et immunopathologia. 2015;(4):376-82
Abstract
BACKGROUND Acute bronchiolitis comprises a major cause for morbidity in infants with viral infection which induces an immune inflammatory response that may produce long lasting harmful effects. Currently, there is no effective therapy for bronchiolitis. OBJECTIVE Our aim was to investigate the efficacy of five-day montelukast therapy in acute bronchiolitis management. METHODS The study included 50 infants with acute bronchiolitis. The infants with first episode of acute bronchiolitis were randomly assigned to receive daily montelukast dose of 4mg over five days after admission or no treatment. Plasma eotaxin, IL-4, IL-8 and IFN-gamma levels were evaluated before and after treatment by ELISA method. In the present study, the primary outcome measure was change in clinical severity score, whilst secondary outcome measures were changes in plasma eotaxin, IL-4, IL-8, IFN-gamma levels. RESULTS No significant differences was found in clinical severity score with five-day montelukast treatment (p>0.05, Mann-Whitney U test). There were no significant differences in plasma eotaxin, IL-4, IL-8, IFN-gamma levels between the groups (p>0.05 Mann-Whitney U test). There was significant decrease in plasma IFN-gamma levels following five-day montelukast treatment (p=0.027, Wilcoxon). There were no significant differences in plasma IL-4, IL-8, IFN-gamma levels between the groups after five-day montelukast treatment (p>0.05, Wilcoxon). There was significant increase in eotaxin levels after five-day montelukast treatment (p=0.009, Wilcoxon). CONCLUSION Our study showed that montelukast affected plasma IFN-gamma and eotaxin levels after five days of treatment. Further studies are needed to demonstrate effects of montelukast on chemokine levels in bronchiolitis.
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Cysteinyl leukotriene receptor-1 antagonists as modulators of innate immune cell function.
Theron, AJ, Steel, HC, Tintinger, GR, Gravett, CM, Anderson, R, Feldman, C
Journal of immunology research. 2014;:608930
Abstract
Cysteinyl leukotrienes (cysLTs) are produced predominantly by cells of the innate immune system, especially basophils, eosinophils, mast cells, and monocytes/macrophages. Notwithstanding potent bronchoconstrictor activity, cysLTs are also proinflammatory consequent to their autocrine and paracrine interactions with G-protein-coupled receptors expressed not only on the aforementioned cell types, but also on Th2 lymphocytes, as well as structural cells, and to a lesser extent neutrophils and CD8(+) cells. Recognition of the involvement of cysLTs in the immunopathogenesis of various types of acute and chronic inflammatory disorders, especially bronchial asthma, prompted the development of selective cysLT receptor-1 (cysLTR1) antagonists, specifically montelukast, pranlukast, and zafirlukast. More recently these agents have also been reported to possess secondary anti-inflammatory activities, distinct from cysLTR1 antagonism, which appear to be particularly effective in targeting neutrophils and monocytes/macrophages. Underlying mechanisms include interference with cyclic nucleotide phosphodiesterases, 5'-lipoxygenase, and the proinflammatory transcription factor, nuclear factor kappa B. These and other secondary anti-inflammatory mechanisms of the commonly used cysLTR1 antagonists are the major focus of the current review, which also includes a comparison of the anti-inflammatory effects of montelukast, pranlukast, and zafirlukast on human neutrophils in vitro, as well as an overview of both the current clinical applications of these agents and potential future applications based on preclinical and early clinical studies.
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Effect of cysteinyl leukotriene receptor antagonist on CD11b and CD23 expression in asthmatic children.
Gagro, A, Aberle, N, Rabatić, S, Ajduk, J, Jelacić, J, Dekaris, D
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2004;(6):939-44
Abstract
BACKGROUND Cysteinyl leukotrienes are potent pro-inflammatory mediators that contribute to the pathophysiologic features observed in allergic asthma. Inhibitors of leukotriene receptors represent novel therapy in asthma treatment. In addition to the protection from early asthmatic responses, these drugs have recently been shown to protect from late airway responses too. METHODS We studied the effect of treatment with an oral antagonist of cysteinyl leukotriene receptors on the increased expression of the low-affinity IgE receptor, CD23, on B cells, and of its ligands, CD11b and CD11c, on CD4(+) T cells and monocytes in peripheral blood of patients with allergic asthma. In this uncontrolled open-label study, 14 children with allergic asthma received montelukast, a cysteinyl leukotrine receptor antagonist, for a period of 6 weeks after demonstrating forced expiratory volume in 1 s (FEV(1)) of less than 80% of the predicted value. Samples of peripheral heparinized blood and sera were obtained before and after therapy completion. Three-colour immunofluorescence analysis was performed, and expression of CD11b and CD11c on CD4(+) T lymphocytes and monocytes as well as the expression of CD21 and CD23 on B cells were determined (n=12). Peripheral blood eosinophil count, changes in FEV(1) and peak expiratory flow rate (PEFR), asthma exacerbations, and as-needed use of beta-agonist were also monitored. RESULTS Montelukast improved FEV(1) and PEFR, and decreased peripheral eosinophil counts in all study patients. There was no significant change in the expression of CD21 and CD23 on B cells. The expression of CD11c on CD4(+) T cells and of both CD11b and CD11c on monocytes remained similar to the pretreatment expression. However, the percentage of CD11b(+)CD4(+) T lymphocytes significantly decreased after treatment with montelukast. This was accompanied by a significant decrease in the levels of total IgE. CONCLUSION The capacity of 6-week montelukast therapy to reduce the percentage of CD11b CD4(+) T cells might be a mechanism leading to the immune response modulation on this T cell subset interaction with CD23-expressing B cells and subsequent down-regulation of IgE synthesis.
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Anti-inflammatory effects of montelukast in mild cystic fibrosis.
Schmitt-Grohé, S, Eickmeier, O, Schubert, R, Bez, C, Zielen, S
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2002;(6):599-605
Abstract
BACKGROUND Immune-mediated inflammation contributes to progressive pulmonary damage in cystic fibrosis (CF). Sputum cysteinyl leukotriene levels, eosinophil cationic protein (ECP), and interleukin-8 (IL-8) are significantly related to disease severity. OBJECTIVE The aim of this study was to evaluate the anti-inflammatory and clinical effects of the cysteinyl leukotriene receptor antagonist montelukast in children with CF. METHODS A double-blind, randomized, crossover design was used. Patients received montelukast (6 to < or = 14 years, 5 mg; > 14 years, 10 mg) or placebo as a once-daily tablet for 21 days and then, after a washout period of at least 4 weeks, crossed over to receive the alternative treatment. Blood and native nasal fluid were taken on days 1 and 21 of each treatment block, and WBC count, ECP, and IL-8 were analyzed using a chemiluminescent immunometric assay. RESULTS Sixteen CF patients (10 boys, 6 girls; age, 5 to 18 years, median 9.5 years) completed the trial. There was a significant (P < or = 0.02) reduction of serum ECP (median reduction: montelukast 7.7 microg/L vs placebo 0.15 microg/L) and eosinophils (P < or = 0.027; median reduction: montelukast 85/microL vs placebo 0/microL). There was no significant change in nasal ECP, IL-8, or serum IL-8 after a 21-day course of montelukast. Clinical symptom scores did not change significantly. CONCLUSIONS Montelukast reduces eosinophilic inflammation in CF patients. Multicenter trials providing more patients to create more data to prove the hypothesis that montelukast is an effective tool to cut down disease severity in CF patients are needed.