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Mast Cell Activation Syndrome and Mastocytosis: Initial Treatment Options and Long-Term Management.
Castells, M, Butterfield, J
The journal of allergy and clinical immunology. In practice. 2019;(4):1097-1106
Abstract
Patients with clonal mast cell activation syndromes (MCAS) including cutaneous and systemic mastocytosis (SM) may present with symptoms of mast cell activation, but in addition can have organ damage from the local effects of tissue infiltration by clonal mast cells. Patients with nonclonal MCAS may have chronic or episodic mast cell activation symptoms with an increase in serum tryptase and/or urinary metabolites of histamine, prostaglandin D2, and leukotrienes. Symptoms of MCAS and SM can be managed by blockade of mediator receptors (H1 and H2 antihistamines, leukotriene receptor blockade), inhibition of mediator synthesis (aspirin, zileuton), mediator release (sodium cromolyn), anti-IgE therapy, or a combination of these approaches. Acute episodes of mast cell activation require epinephrine, and prolonged episodes may be addressed with corticosteroids. Patients with clonal mast cell syndromes may need a reduction in the number of mast cells to prevent severe symptoms including anaphylaxis and/or progression to aggressive diseases.
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Asthma pharmacotherapy: an update on leukotriene treatments.
Trinh, HKT, Lee, SH, Cao, TBT, Park, HS
Expert review of respiratory medicine. 2019;(12):1169-1178
Abstract
Introduction: Asthma is a chronic inflammatory disease of the airways with a large heterogeneity of clinical phenotypes. There has been increasing interest regarding the role of cysteinyl leukotriene (LT) and leukotriene receptor antagonists (LTRA) in asthma treatment.Areas covered: This review summarized the data (published in PubMed during 1984-2019) regarding LTRA treatment in asthma and LTs-related airway inflammation mechanisms. Involvement of LTs C4/D4/E4 has been demonstrated in the several aspects of airway inflammation and remodeling. Novel pathways related to LTE4, the most potent mediator, and its respective receptors have recently been studied. Antagonists against cysteinyl leukotriene receptor (CysLTR) type 1, including montelukast, pranlukast and zafirlukast, have been widely prescribed in clinical practices; however, some clinical trials have shown insignificant responses to LTRAs in adult asthmatics, while some phenotypes of adult asthma showed more favorable responses to LTRAs including aspirin-exacerbated respiratory disease, elderly asthma, asthma associated with smoking, obesity and allergic rhinitis.Expert opinion: Further investigations are needed to understand the role of LTs in airway inflammation and remodeling of the asthmatic airways. There is a lack of biomarkers to predict responsiveness to LTRA, especially in adult asthmatics. Besides CysLTR1 antagonists, targets aiming other LT pathways should be considered.
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Question 2: Is there a role for Montelukast in the management of viral-induced wheeze in preschool children?
Burman, A
Archives of disease in childhood. 2018;(5):519-520
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Leukotriene receptor antagonists as maintenance or intermittent treatment in pre-school children with episodic viral wheeze.
Brodlie, M, Gupta, A, Rodriguez-Martinez, CE, Castro-Rodriguez, JA, Ducharme, FM, McKean, MC
Paediatric respiratory reviews. 2016;:57-9
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Leukotriene receptor antagonists as maintenance and intermittent therapy for episodic viral wheeze in children.
Brodlie, M, Gupta, A, Rodriguez-Martinez, CE, Castro-Rodriguez, JA, Ducharme, FM, McKean, MC
The Cochrane database of systematic reviews. 2015;(10):CD008202
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Abstract
BACKGROUND Episodic viral wheeze (EVW) associated with viral respiratory tract infections is a common reason for pre-school children to utilise health care resources and for carers to take time away from employment. About a third of children experience a wheezing episode before the age of five years. EVW therefore represents a significant public health problem. Many pre-school children only wheeze in association with viral infections and in such cases EVW appears to be a separate entity from atopic asthma. Some trials have explored the effectiveness of leukotriene receptor antagonists (LTRAs) as regular (maintenance) or episodic (intermittent) treatment in this context. OBJECTIVES To evaluate the evidence for the efficacy and safety of maintenance and intermittent LTRAs in the management of EVW in children aged one to six years. SEARCH METHODS We searched the Cochrane Airways Group register of trials with pre-specified terms. We performed additional searches by consulting the authors of identified trials, online trial registries of manufacturers' web sites, and reference lists of identified primary papers and reviews. Search results are current to June 2015. SELECTION CRITERIA We included randomised controlled trials with a parallel-group or cross-over (for intermittent LTRA only) design. Maintenance was considered as treatment for more than two months and intermittent as less than 14 days. EVW was defined as a history of at least one previous episode of wheezing in association with a viral respiratory tract infection in the absence of symptoms between episodes. As far as possible, relevant specific data were obtained from authors of studies that included children of a wider age group or phenotype. DATA COLLECTION AND ANALYSIS Two authors independently assessed studies for inclusion in the review and assessed risk of bias. The primary outcome was number of children with one or more viral-induced episodes requiring one or more treatments with rescue oral corticosteroids. We analysed combined continuous data outcomes with the mean difference and dichotomous data outcomes with an odds ratio (OR). MAIN RESULTS We identified five studies eligible for inclusion in the review (one investigated maintenance treatment, three intermittent therapy and one had both maintenance and intermittent treatment arms) these included 3741 participants. Each study involved oral montelukast and was of good methodological quality, but differed in choice of outcome measures thus limiting our ability to aggregate data across studies. Only primary outcome and adverse event data are reported in this abstract.For maintenance treatment, specific data obtained from a single study, pertaining to children with only an EVW phenotype, showed no statistically significant group reduction in the number of episodes requiring rescue oral corticosteroids associated with daily montelukast versus placebo (OR 1.20, 95% CI 0.70 to 2.06, moderate quality evidence).For intermittent LTRA, pooled data showed no statistically significant reduction in the number of episodes requiring rescue oral steroids in children treated with LTRA versus placebo (OR 0.77, 95% CI 0.48 to 1.25, moderate quality evidence). Specific data for children with an EVW phenotype obtained from a single study of intermittent montelukast treatment showed a small, but statistically significant reduction in unscheduled medical attendances due to wheeze (RR 0.83, 95% CI 0.71 to 0.98).For maintenance compared to intermittent LTRA treatment no data relating to the primary outcome of the review were identified.There were no other significant group differences identified in other secondary efficacy outcomes for maintenance or intermittent LTRA treatment versus placebo, or maintenance versus intermittent LTRA treatment. We collected descriptive data on adverse events as reported by four of the five included studies, and rates were similar between treatment and placebo groups.Potential heterogeneity in the phenotype of participants within and across trials is a limitation of the evidence. AUTHORS' CONCLUSIONS In pre-school children with EVW, there is no evidence of benefit associated with maintenance or intermittent LTRA treatment, compared to placebo, for reducing the number of children with one or more viral-induced episodes requiring rescue oral corticosteroids, and little evidence of significant clinical benefit for other secondary outcomes. Therefore until further data are available, LTRA should be used with caution in individual children. When used, we suggest a therapeutic trial is undertaken, during which efficacy should be carefully monitored. It is likely that children with an apparent EVW phenotype are not a homogeneous group and that subgroups may respond to LTRA treatment depending on the exact patho-physiological mechanisms involved.
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Montelukast in paediatric asthma: where we are now and what still needs to be done?
Bush, A
Paediatric respiratory reviews. 2015;(2):97-100
Abstract
Leukotriene receptor antagonists were introduced as an entirely new concept in asthma therapy, which indeed they are. However, although an intellectually new concept, they have largely disappointed in clinical practice. A small minority of school age asthmatics may respond better to these medications as against inhaled corticosteroids as prophylactic therapy. In children not responding to low dose inhaled corticosteroids, the best add-on therapy is salmeterol, but a small number respond better to Montelukast. In pre-school wheeze, intermittent Montelukast may be an effective strategy in some children who wheeze just with viral colds, but the clinical trial data are controversial. Pre-schoolers with multiple trigger wheeze are probably best treated with inhaled corticosteroids. What is clear is that clinically, a higher proportion of children are prescribed Montelukast than would be predicted from the lterature to respond to the medication. No biomarker to predict response to Montelukast has reached clinical practice, so N of 1 clinical trials should be performed. It is important not to leave children on Montelukast if there is no convincing response to this treatment.
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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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Is montelukast indicated for treatment of chronic rhinosinusitis with polyposis?
Smith, TL, Sautter, NB
The Laryngoscope. 2014;(8):1735-6
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Impact of montelukast on asthma associated with rhinitis, and other triggers and co-morbidities.
Pacheco, Y, Freymond, N, Devouassoux, G
The Journal of asthma : official journal of the Association for the Care of Asthma. 2014;(1):1-17
Abstract
INTRODUCTION Rhinitis and other specific triggers or co-morbidities (tobacco exposure, excess weight, aspirin sensitivity or heredity factors) are frequently associated with uncontrolled asthma. Asthma associated with these exacerbating factors appears to be related to an increase in leukotriene-mediated inflammation. METHODS We reviewed the role of montelukast, a leukotriene receptor antagonist, in the treatment of asthma associated with these factors by using the PubMed database to search the English and French biomedical literature for articles describing randomized-controlled trials, large observational studies and reviews (published up to May 2012, inclusive). RESULTS Montelukast, either alone or in combination with other drugs, is an effective treatment against rhinitis-associated asthma. Montelukast also offers therapeutic benefits against exercise-induced asthma or in cases of asthma linked to tobacco exposure, excess weight or aspirin hypersensitivity. Thus, for some patients, montelukast may constitute an alternative to the gold-standard treatment of inhaled corticosteroids. Polymorphisms in several genes encoding proteins of the leukotriene signaling pathway may contribute to the variability in response to montelukast. CONCLUSIONS In conclusion, we have shown that montelukast treatment could be of particular benefit to subgroups of patients with asthma associated with rhinitis, exercise, tobacco exposure, being overweight or aspirin hypersensitivity.
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Role of leukotriene antagonists and antihistamines in the treatment of allergic rhinitis.
Cobanoğlu, B, Toskala, E, Ural, A, Cingi, C
Current allergy and asthma reports. 2013;(2):203-8
Abstract
Allergic rhinitis is the most common atopic disorder seen in ENT clinics. It is diagnosed by history, physical exam and objective testing. Patient education, environmental control measures, pharmacotherapy, and allergen-specific immunotherapy are the cornerstones of allergic rhinitis treatment and can significantly reduce the burden of disease. Current treatment guidelines include antihistamines, intranasal corticosteroids, oral and intranasal decongestants, intranasal anticholinergics, intranasal cromolyn, and leukotriene receptor antagonists. In the mechanism of allergic rhinitis, histamine is responsible for major allergic rhinitis symptoms such as rhinorrhea, nasal itching and sneezing. Its effect on nasal congestion is less evident. In contrast, leukotrienes result in increase in nasal airway resistance and vascular permeability. Antihistamines and leukotriene receptor antagonists are commonly used in the treatment of allergic rhinitis. The published literature about combined antihistamines and leukotriene antagonists in mono- or combination therapy is reviewed and presented.