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BMJ Open Jan 2022National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of...
BACKGROUND
National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of montelukast in children and young people (CYP).
OBJECTIVE
To systematically review evidence regarding deprescribing montelukast in CYP with established asthma.
DESIGN
Systematic review.
DATA SOURCES
Embase, Medline, PubMed and CINAHL were searched up to October 2020.
STUDY SELECTION
Eligible studies contained patients aged 0-18 years with a diagnosis of asthma, who had been administering montelukast before it was withdrawn. All reasons for withdrawal were included.
RESULTS
The search identified 197 papers. After deduplication, five papers were included (three randomised control studies and two cohort studies). Four studies observed the impact of montelukast withdrawal for 2 weeks, and one study for 8 weeks. The impact of withdrawal was measured in the studies using a combination of lung tests (eg, forced expiratory volume in 1 s (FEV1), fractional exhaled nitric oxide (FeNO)), asthma scoring methods and exercise challenges. Of the 17 domains in the Core Outcome Set for Clinical Trials in Childhood Asthma, eight outcomes were measured in at least one of the five studies, with all five studies measuring the outcome of 'Lung Function'. No significant differences were found between the montelukast and placebo groups following montelukast withdrawal. Significant differences between the comparator points within the test group were found in nine outcomes across four studies; FEV1/forced vital capacity, FEV1, forced expiratory flows (25%-75%), asthma score (study specific), maximum % fall in FEV1 and time to recovery (post exercise) significantly decreased whereas FEV1/bronchodilator response, FeNO and eNO significantly increased.
CONCLUSION
Only limited, contradictory and short-term effects of deprescribing montelukast in CYP with established asthma are presented in literature. Definitive studies determining clinical stability, and impact of deprescribing montelukast in CYP are imperative to improve the safety of asthma treatment in CYP.
PROSPERO REGISTRATION NUMBER
CRD42020213971.
Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Cyclopropanes; Deprescriptions; Forced Expiratory Volume; Humans; Infant; Infant, Newborn; Quinolines; Sulfides
PubMed: 35105629
DOI: 10.1136/bmjopen-2021-053112 -
Life Sciences Jul 2023Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1) that protects against inflammation and oxidative stress. However, the function of montelukast...
Montelukast prevents mice against carbon tetrachloride- and methionine-choline deficient diet-induced liver fibrosis: Reducing hepatic stellate cell activation and inflammation.
AIMS
Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1) that protects against inflammation and oxidative stress. However, the function of montelukast in liver fibrosis remains unknown. In this study, we examined whether the pharmacological inhibition of CysLTR1 could protect mice against hepatic fibrosis.
MATERIALS AND METHODS
Carbon tetrachloride (CCl) and methionine-choline deficient (MCD) diet models were used in this study. The expression of CysLTR1 in liver were detected by RT-qPCR and Western blot analysis. Liver hydroxyproline levels, fibrotic genes expression, serum biochemical indexes and inflammatory factors were used to evaluate the effect of montelukast on liver fibrosis, injury, and inflammation. In vitro, we used the RT-qPCR and Western blot analysis to assess CysLTR1 in mouse primary hepatic stellate cell (HSC) and human LX-2 cell line. The role of montelukast on HSC activation and the underlying mechaisms were determined using RT-qPCR analysis, Western blot and immunostaining assays.
KEY FINDINGS
Chronic stimulation from CCl and MCD diet upregulated the mRNA and protein levels of CysLTR1 in the liver. Pharmacological inhibition of CysLTR1 by montelukast ameliorated liver inflammation and fibrosis in both models. Mechanistically, montelukast suppressed HSC activation by targeting the TGFβ/Smad pathway in vitro. The hepatoprotective effect of montelukast was also associated with reduced liver injury and inflammation.
SIGNIFICANCE
Montelukast suppressed CCl- and MCD-induced chronic hepatic inflammation and liver fibrosis. CysLTR1 might be a therapeutic target for treating liver fibrosis.
Topics: Mice; Humans; Animals; Carbon Tetrachloride; Methionine; Hepatic Stellate Cells; Signal Transduction; Liver Cirrhosis; Liver; Fibrosis; Racemethionine; Inflammation; Diet; Transforming Growth Factor beta1
PubMed: 37178864
DOI: 10.1016/j.lfs.2023.121772 -
Life Sciences Sep 2022Montelukast, a selective antagonist of type 1 cysteinyl-leukotriene receptors, has antioxidant and anti-inflammatory abilities. This study aimed to explore its...
AIMS
Montelukast, a selective antagonist of type 1 cysteinyl-leukotriene receptors, has antioxidant and anti-inflammatory abilities. This study aimed to explore its hepatoprotective impact against CCl-induced hepatotoxicity compared to a standard hepatoprotective agent, silymarin.
MAIN METHODS
Twenty-four albino mice were used in this study, CCl (1 mL/kg of 1:1 v/v CCl:olive oil) was singly injected in mice, and montelukast was administered in a dose of 10 mg/kg.
KEY FINDINGS
Results revealed that montelukast significantly improved CCl-induced alterations in both structure and function of the liver, verified respectively through histopathology and by the reduced levels of ALT, AST, ALP, and GGT upon comparison with CCl. Also, montelukast prevented the induction of oxidative stress via decreasing hepatic MDA content and enhancing GSH levels. Moreover, montelukast produced a profound decrease in the levels of hepatic NLRP3 and its adaptor protein, ASC, and a reduction in the pro-inflammatory markers, NF-κB, IL-1β, TNF-α, and IL-6. In addition, montelukast markedly reduced liver fibrosis, as illustrated by Masson Trichrome, and the decreased hepatic levels of TGF-β and α-SMA. Furthermore, montelukast efficiently decreased apoptosis as manifested by the decreased hepatic level of Caspase 3.
SIGNIFICANCE
Montelukast protected against CCl-induced hepatotoxicity via exerting antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic effects.
Topics: Acetates; Animals; Antioxidants; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Cyclopropanes; Inflammasomes; Liver; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Quinolines; Sulfides
PubMed: 35690106
DOI: 10.1016/j.lfs.2022.120707 -
International Immunopharmacology Feb 2022Levocetirizine, a third-generation antihistamine, and montelukast, a leukotriene receptor antagonist, exhibit remarkable synergistic anti-inflammatory activity across a...
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.
Topics: Acetates; Adolescent; Adult; Aged; Aged, 80 and over; Cetirizine; Child; Child, Preschool; Cyclopropanes; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Retrospective Studies; SARS-CoV-2; Sulfides; Treatment Outcome; Young Adult; COVID-19 Drug Treatment
PubMed: 34942461
DOI: 10.1016/j.intimp.2021.108412 -
European Journal of Pharmacology Aug 2021Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the responsible agent for the coronavirus disease 2019 (Covid-19), has its entry point through interaction... (Review)
Review
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.
Topics: Acetates; COVID-19; Cyclopropanes; Cytokine Release Syndrome; Humans; Leukotriene Antagonists; Leukotrienes; Lung Diseases; Quinolines; Receptors, Leukotriene; Signal Transduction; Sulfides; COVID-19 Drug Treatment
PubMed: 34004207
DOI: 10.1016/j.ejphar.2021.174196 -
Biomedicine & Pharmacotherapy =... Oct 2016In order to verify the differences of effectiveness and safety between SAHs and Montelukast, and to find out potential uncared-for problems, we performed a systematic... (Comparative Study)
Comparative Study Meta-Analysis Review
PURPOSE
In order to verify the differences of effectiveness and safety between SAHs and Montelukast, and to find out potential uncared-for problems, we performed a systematic review and Meta-analysis to proceed a qualitative describe and quantitative assessment.
METHODS
We searched the databases of Pubmed, the Cochrane Library, Nature and Science as well as Wanfang data and CNKI from 2000 to March 2016, using key words "Montelukast SAH" or "H1-antihistamine Montelukast", or "Loratadine Montelukast", or "Desloratadine Montelukast", or "Levocetirizine Montelukast", or "Cetirizen Montelukast", or "Fexofenadine Montelukast". And also we included studies through relevant citations in related literature. Meta-analysis and bias of risk were performed. We analyzed Heterogeneity and publish bias as well.
RESULT
Montelukast seems more effective in nighttime symptoms compare with SAHs (P=0.008, MD=-0.04, 95%CI: -0.08, -0.01). No significant difference was found between Montelukast and SAHs in CSS (P=0.10, MD=0.03, 95%CI: -0.01, 0.07). Montelukast and SAHs combined therapy was more effective than Montelukast DNSS (P=0.0006, MD=0.15, 95%CI: 0.07, 0.24) but not in CSS (P=0.04, MD=0.08, 95%CI: 0.00, 0.15; Bonferroni correction α=0.017).
CONCLUSION
Montelukast has a significant influence in improving patients' nasal symptoms quality of live but is not as effective as SAHs, and may have a slight advantage over SAHs in relieving nighttime symptoms significantly. Combined therapy is more effective in improving patients' day time symptom than Montelukast. Probably, patients might have a lower asthenia incidence rate when using Montelukas.
Topics: Acetates; Cyclopropanes; Drug Therapy, Combination; Histamine Antagonists; Humans; Placebos; Publication Bias; Quality of Life; Quinolines; Receptors, Histamine H1; Rhinitis, Allergic; Sulfides; Surveys and Questionnaires; Treatment Outcome
PubMed: 27522261
DOI: 10.1016/j.biopha.2016.08.003 -
The Journal of Allergy and Clinical... Jul 2023Recent observational studies suggest that the leukotriene receptor antagonist montelukast may have neuropsychiatric adverse effects; however, results are conflicting.
BACKGROUND
Recent observational studies suggest that the leukotriene receptor antagonist montelukast may have neuropsychiatric adverse effects; however, results are conflicting.
OBJECTIVE
To assess whether montelukast exposure in adults with asthma is associated with onset of neuropsychiatric adverse events using data from the Danish nationwide health registers.
METHODS
Individuals 18 years old or older with either 1 or more prescription redemption of inhaled corticosteroids or with at least 1 hospital contact with asthma as the main diagnosis between January 1, 2011, and December 31, 2018, were included. Montelukast exposure was assessed as a time-dependent variable. The 2 outcomes of interest were use of neuropsychiatric medicine including antidepressants, antipsychotics, anxiolytics, lithium, and medication used for attention-deficit/hyperactivity disorder (outcome 1), and hospital contacts with a neuropsychiatric diagnosis (outcome 2), within 90 days of exposure to montelukast.
RESULTS
Initiation of montelukast was significantly associated with outcome 1: use of neuropsychiatric medicine (hazard ratio [95% confidence interval]) 1.14 [1.08-1.20]; P < .0001). In the assessment of outcome 2: hospital contacts with a neuropsychiatric diagnosis, a significant risk associated with montelukast initiation was found only in the youngest age groups (hazard ratio [95% confidence interval] 1.28 [1.12-1.47], P < .001 and 1.16 [1.02-1.31]; P < .05, for age group 18-29 y and 30-44 y, respectively). Age-stratified analyses showed that the risk of both outcomes increased with decreasing age, with the highest risk seen in patients aged 18 to 29 years.
CONCLUSIONS
Among younger individuals, montelukast use was significantly associated with an increased risk of neuropsychiatric events such as use of neuropsychiatric medicine and hospital treatment. Clinicians should increase awareness of such adverse effects when prescribing montelukast.
Topics: Adult; Humans; Adolescent; Young Adult; Cohort Studies; Asthma; Leukotriene Antagonists; Acetates; Quinolines; Drug-Related Side Effects and Adverse Reactions; Anti-Asthmatic Agents
PubMed: 36948487
DOI: 10.1016/j.jaip.2023.03.010 -
Journal of the American Academy of... Mar 2018The role of leukotrienes and prostaglandins in development of atopy has been prototypically established in studies of asthma pathogenesis. Likewise, both in vitro and... (Review)
Review
The role of leukotrienes and prostaglandins in development of atopy has been prototypically established in studies of asthma pathogenesis. Likewise, both in vitro and in vivo studies of atopic dermatitis have demonstrated that these molecules maintain important pathophysiologic roles. Thus, it follows that targeted therapies against these molecules may be promising in management of atopic dermatitis. Montelukast has had questionable efficacy in patients with atopic dermatitis, whereas small pilots using zileuton did have some clinically significant improvement. There are several agents in development that target leukotrienes and/or prostaglandins as well, including OC000459, Q301, and ZPL-521. In atopic dermatitis, OC000459 did not demonstrate efficacy in clinical trials, and the efficacy of the other 2 agents remains to be seen. Should these medications prove promising, these topical agents may play a future role in chronic maintenance therapy and flare prophylaxis in atopic dermatitis, as antileukotriene therapy does in asthma.
Topics: Acetates; Adult; Animals; Cyclopropanes; Dermatitis, Atopic; Female; Forecasting; Humans; Hydroxyurea; Leukotriene Antagonists; Male; Molecular Targeted Therapy; Prostaglandin Antagonists; Quinolines; Severity of Illness Index; Sulfides; Treatment Outcome
PubMed: 29248523
DOI: 10.1016/j.jaad.2017.12.021 -
Sleep Medicine Feb 2021The efficacy and safety of montelukast in children with obstructive sleep apnea (OSA) remain controversial. Therefore, the aims of this systemic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The efficacy and safety of montelukast in children with obstructive sleep apnea (OSA) remain controversial. Therefore, the aims of this systemic review and meta-analysis are to verify this issue and further provide reference for clinical practice.
METHODS
Seven databases were searched for randomized controlled trials (RCTs) up to September 30, 2019. The literature screening and data extraction were performed by two independent researchers. Adverse reactions from trials were also recorded. Meta-analysis was performed and analyzed heterogeneity. Methodological and evidence quality were followed by to evaluate according to Cochrane handbook.
RESULTS
A total of 4 RCTs including 305 children with mild to moderate OSA were involved. Compared with placebo, we found that oral montelukast (OM) significantly improved polysomnography (PSG) monitoring parameters, typical and relevant symptoms including snoring and mouth breathing, and adenoid morphology in children with OSA. When compared with routine drugs, not only PSG monitoring parameters and adenoid morphology, but also sleep-disordered breathing (SDB)-related questionnaire scores were improved in patients with OSA treated by combination of OM and routine drugs. In addition, compared with single nasal spray of mometasone furoate, the present study also showed that OM combined with nasal spray of mometasone furoate significantly improved PSG monitoring parameters, symptoms of snoring and mouth breathing and reduced tonsil morphology in pediatric OSA. In terms of treatment safety, one study reported adverse reactions of OM such as headache, nausea and vomiting, while no adverse events were reported after OM treatment in another study.
CONCLUSION
As a classic leukotriene receptor antagonist, montelukast can be used to treat children with mild to moderate OSA in the short term and improve clinical characteristics. The promotion and application of OM in clinic is considered to be a noninvasive option to avoid surgical treatment.
Topics: Acetates; Adenoids; Child; Cyclopropanes; Humans; Quinolines; Sleep Apnea, Obstructive; Sulfides
PubMed: 33465554
DOI: 10.1016/j.sleep.2020.11.009 -
International Journal of Pharmaceutical... 2020Asthma, which affects nearly 1 in every 12 people, is a large problem in the U.S. Asthma results in a cost of $56 billion dollars in various hospital bills and...
Asthma, which affects nearly 1 in every 12 people, is a large problem in the U.S. Asthma results in a cost of $56 billion dollars in various hospital bills and inconveniences. Many treatments of asthma use delivery methods (e.g., inhalers, tablets, capsules) that cannot be used by many patients if they have medical conditions that weaken their ability to inhale or swallow. This study's purpose was to examine the use of topically applied creams as a potential alternative to the use of conventional asthma medications. To test if a cream could work to treat asthma, a cream was developed with a drug normally taken orally that was combined with a cream base that was found most suitable to deliver the drug. The cream was then tested in-situ with mice as the test subject. The cream was applied to the backs of four groups of three mice for 0.5 hours, 1.5 hours, 5 hours, and 7 hours. Blood samples were taken after the respective times, and the quantity of the drug was analyzed in a mass spectrometer. The results showed that a cream delivered enough of an asthma drug to match the bioavailability of an average adult taking montelukast sodium. With this new delivery method, a cream can be used to treat asthma, which can also relieve the discomfort of asthma patients who are unable to use inhaled drugs and even possibly save lives of those unable to use traditional methods of delivery.
Topics: Adult; Animals; Asthma; Feasibility Studies; Humans; Mice; Ointments; Tablets
PubMed: 32196479
DOI: No ID Found