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1.
Levocetirizine and montelukast in the COVID-19 treatment paradigm.
May, BC, Gallivan, KH
International immunopharmacology. 2022;:108412
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Abstract
Levocetirizine, a third-generation antihistamine, and montelukast, a leukotriene receptor antagonist, exhibit remarkable synergistic anti-inflammatory activity across a spectrum of signaling proteins, cell adhesion molecules, and leukocytes. By targeting cellular protein activity, they are uniquely positioned to treat the symptoms of COVID-19. Clinical data to date with an associated six-month follow-up, suggests the combination therapy may prevent the progression of the disease from mild to moderate to severe, as well as prevent/treat many of the aspects of 'Long COVID,' thereby cost effectively reducing both morbidity and mortality. To investigate patient outcomes, 53 consecutive COVID-19 test (+) cases (ages 3-90) from a well-established, single-center practice in Boston, Massachusetts, between March - November 2020, were treated with levocetirizine and montelukast in addition to then existing protocols [2]. The data set was retrospectively reviewed. Thirty-four cases were considered mild (64%), 17 moderate (32%), and 2 (4%) severe. Several patients presented with significant comorbidities (obesity: n = 22, 41%; diabetes: n = 10, 19%; hypertension: n = 24, 45%). Among the cohort there were no exclusions, no intubations, and no deaths. The pilot study in Massachusetts encompassed the first COVID-19 wave which peaked on April 23, 2020 as well as the ascending portion of the second wave in the fall. During this period the average weekly COVID-19 case mortality rate (confirmed deaths/confirmed cases) varied considerably between 1 and 7.5% [37]. FDA has approved a multicenter, randomized, placebo-controlled, Phase 2 clinical trial design, replete with electronic diaries and laboratory metrics to explore scientific questions not addressed herein.
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Montelukast's ability to fight COVID-19 infection.
Bozek, A, Winterstein, J
The Journal of asthma : official journal of the Association for the Care of Asthma. 2021;(10):1348-1349
Abstract
Montelukast can be effective in the treatment of SARS-CoV-2 infection.
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Montelukast and Coronavirus Disease 2019: A Scoping Review.
Sharifinejad, N, Sharafian, S, Salekmoghadam, S, Tavakol, M, Qorbani, M
Iranian journal of allergy, asthma, and immunology. 2021;(4):384-393
Abstract
Coronavirus disease 2019 (COVID-19) is an emerging worldwide issue, that has affected a large number of people around the world. So far, many studies have aimed to develop a therapeutic approach against COVID-19. Montelukast (MK) is a safe asthma controller drug, which is considered as a potential antiviral drug for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review has a systematic approach to investigate the reports on the use of MK as a part of treatment or a prophylactic agent in COVID-19. The search was conducted in PubMed, Web of Science, and Scopus databases and yielded 35 studies containing the influence of MK on SARS-CoV-2. Ultimately, MK appears to be worth being used as an adjuvant therapeutic and prophylactic drug against SARS-CoV-2. Nevertheless, more clinical trials are required to accurately investigate its effectiveness.
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Role of leukotriene pathway and montelukast in pulmonary and extrapulmonary manifestations of Covid-19: The enigmatic entity.
Al-Kuraishy, HM, Al-Gareeb, AI, Almulaiky, YQ, Cruz-Martins, N, El-Saber Batiha, G
European journal of pharmacology. 2021;:174196
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Abstract
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the responsible agent for the coronavirus disease 2019 (Covid-19), has its entry point through interaction with angiotensin converting enzyme 2 (ACE2) receptors, highly expressed in lung type II alveolar cells and other tissues, like heart, pancreas, brain, and vascular endothelium. This review aimed to elucidate the potential role of leukotrienes (LTs) in the pathogenesis and clinical presentation of SARS-CoV-2 infection, and to reveal the critical role of LT pathway receptor antagonists and inhibitors in Covid-19 management. A literature search was done in PubMed, Scopus, Web of Science and Google Scholar databases to find the potential role of montelukast and other LT inhibitors in the management of pulmonary and extra-pulmonary manifestations triggered by SARS-CoV-2. Data obtained so far underline that pulmonary and extra-pulmonary manifestations in Covid-19 are attributed to a direct effect of SARS-CoV-2 in expressed ACE2 receptors or indirectly through NF-κB dependent induction of a cytokine storm. Montelukast can ameliorate extra-pulmonary manifestations in Covid-19 either directly through blocking of Cys-LTRs in different organs or indirectly through inhibition of the NF-κB signaling pathway.
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Anti-inflammatory medications for the treatment of pediatric obstructive sleep apnea.
Kuhle, S, Urschitz, MS
Paediatric respiratory reviews. 2020;:35-36
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Efficacy of Montelukast in Allergic Rhinitis Treatment: A Systematic Review and Meta-Analysis.
Krishnamoorthy, M, Mohd Noor, N, Mat Lazim, N, Abdullah, B
Drugs. 2020;(17):1831-1851
Abstract
BACKGROUND In treating allergic rhinitis, montelukast has the potential to be used as an alternative or addition to an oral antihistamine or intranasal corticosteroid. OBJECTIVE The objective of this systematic review was to assess the effectiveness of montelukast in treating allergic rhinitis. METHODS An electronic literature search was performed using the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE from 1966 to 21 January 2019. The eligibility criteria were randomized controlled trials comparing montelukast with placebo or other standard treatments. The primary outcomes assessed were daytime nasal symptom score (DNS) and night-time nasal symptom score (NNS). The secondary outcomes assessed were composite nasal symptom score (CSS), daytime eyes symptom score (DES), and rhinoconjunctivitis quality-of-life questionnaires (RQLQ). The meta-analysis was conducted using Review Manager 5.3 software based on the random-effects model. RESULTS Fifteen studies of 10387 participants met the inclusion criteria. Montelukast was more effective than placebo in improving DNS (mean difference [MD] - 0.12, 95% confidence interval [CI] - 0.15 to - 0.08; p < 0.001), NNS (MD - 0.09, 95% CI - 0.13 to - 0.05; p < 0.001), CSS (MD - 0.08, 95% CI - 0.11 to - 0.06; p < 0.001), DES (MD - 0.17, 95% CI - 0.33 to - 0.02; p < 0.030), and RQLQ (MD - 0.34, 95% CI - 0.49 to - 0.20; p < 0.001). Oral antihistamine was superior to montelukast in improving DNS (MD 0.08, 95% CI 0.03-0.13; p = 0.002), CSS (MD 0.03, 95% CI - 0.02 to 0.07; p = 0.27), DES (MD 0.06, 95% CI 0-0.12; p = 0.040), and RQLQ (MD 0.03, 95% CI - 0.05 to 0.12; p = 0.430). Montelukast was superior to oral antihistamine in improving NNS (MD -0.03, 95% CI - 0.08 to 0.03; p = 0.330). Intranasal fluticasone spray was superior to montelukast in improving DNS (MD 0.71, 95% CI 0.44-0.99; p < 0.001) and NNS (MD 0.63, 95% CI 0.29-0.97; p < 0.001). Combined montelukast and oral antihistamine was superior to oral antihistamine in improving DNS (MD - 0.15, 95% CI - 0.27 to - 0.03; p = 0.010), NNS (MD - 0.16, 95% CI - 0.28 to - 0.05; p = 0.006), CSS (MD - 0.12, 95% CI - 0.25 to - 0.01; p = 0.070), DES (MD - 0.12, 95% CI - 0.30 to 0.06; p = 0.180), and RQLQ (MD - 0.10, 95% CI - 0.28 to 0.08; p = 0.290). Combined montelukast and OAH was superior to montelukast in improving DNS (MD 0.15, 95% CI 0.08-0.21; p < 0.001), NNS (MD 0.05, 95% CI - 0.09 to 0.19; p = 0.510), CSS (MD 0.1, 95% CI 0.03-0.17; p = 0.007), DES (MD 0.18, 95% CI 0-0.36; p = 0.050), and RQLQ (MD 0.07 95% CI - 0.15 to 0.29; p = 0.530). CONCLUSIONS Montelukast is more effective than placebo in treating the overall symptoms of allergic rhinitis while the combined therapy of montelukast and an oral antihistamine is superior to either montelukast or an oral antihistamine alone.
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Airway mechanics after withdrawal of a leukotriene receptor antagonist in children with mild persistent asthma: Double-blind, randomized, cross-over study.
Kim, JH, Lee, S, Shin, YH, Ha, EK, Lee, SW, Kim, MA, Yoon, JW, Baek, HS, Choi, SH, Han, MY
Pediatric pulmonology. 2020;(12):3279-3286
Abstract
BACKGROUND To determine the response of airway mechanics and the changes in asthma symptoms to stepping down of leukotriene receptor antagonist (LTRA) therapy. METHODS Thirty children (mean age: 7.1 years) with mild, well-controlled, and persistent asthma who took LTRA as maintenance treatment were randomized into a double-blind, placebo-controlled, cross-over study. Each group received an LTRA (montelukast) or placebo daily for 2 weeks, followed by a 1-week washout period, and then the alternate treatment for 2 weeks. Spirometry and impulse oscillation system (IOS) measurements before and after four puffs of salbutamol inhalation, fractional exhaled nitric oxide (FeNO), and the childhood asthma control test (C-ACT) were evaluated at baseline, the end of placebo treatment, and the end of LTRA treatment. RESULTS Changes of FEV1 /FVC (p = .113) and FEV1 (p = .109) from baseline to posttreatment did not differ significantly between the placebo and montelukast groups. In the placebo group, prebronchodilator (pre-) FEV1 /FVC was decreased (83% vs. 86%) and bronchodilator response (BDR) in FEV1 was diminished (10.7% vs. 6.4%) at posttreatment compared with baseline. However, the montelukast group had no significant changes in pre-FEV1 /FVC (p = .865) and BDR in FEV1 (p = .461). In addition, compared with the montelukast group, the placebo group showed no significant changes in Rrs5 (total airway resistance), Rrs5-20 (peripheral airway resistance), FeNO, and symptoms by the C-ACT. CONCLUSION In children with well-controlled mild persistent asthma, changes in spirometry, IOS, FeNO, and C-ACT results did not differ between the placebo and montelukast groups within 2 weeks.
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Effect of montelukast combined with methylprednisolone for the treatment of mycoplasma pneumonia.
Wu, H, Ding, X, Zhao, D, Liang, Y, Ji, W
The Journal of international medical research. 2019;(6):2555-2561
Abstract
OBJECTIVE To study the effect of the leukotriene receptor agonist montelukast combined with methylprednisolone on inflammatory response and peripheral blood lymphocyte subset content in children with mycoplasma pneumonia. METHODS Seventy-four children were enrolled and randomly divided into a standard treatment group and a montelukast plus methylprednisolone group. Serum levels of inflammatory cytokines and corresponding cytokines of T lymphocyte subsets were measured, and peripheral blood was collected to determine the T cell subset content. RESULTS At 3 days and 7 days after treatment, serum MCP-1, PCT, ICAM-1, CXCL8, CRP, IFN-γ, and IL-17 levels and peripheral blood Th1 and Th17 content were significantly decreased in both groups, while serum IL-4 and TGF-β levels and peripheral blood Treg and Th2 content were significantly increased. However, serum MCP-1, PCT, ICAM-1, CXCL8, CRP, IFN-γ, and IL-17 levels and peripheral blood Th1 and Th17 content were significantly lower while serum IL-4 and TGF-β levels and peripheral blood Treg and Th2 content were significantly higher in the montelukast plus methylprednisolone group compared with the control group. CONCLUSION Montelukast combined with methylprednisolone for the treatment of mycoplasma pneumonia can inhibit inflammatory responses and regulate levels of Th1/Th2 and Th17/Treg cells.
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Combination therapy with montelukast and loratadine alleviates pharyngolaryngeal symptoms related to seasonal allergic rhinitis.
Imoto, Y, Takabayashi, T, Sakashita, M, Tokunaga, T, Morikawa, T, Ninomiya, T, Okamoto, M, Narita, N, Fujieda, S
The journal of allergy and clinical immunology. In practice. 2019;(3):1068-1070.e3
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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.