Use Of Montelukast Research Articles

Time to Sustained Recovery Among Outpatients With COVID-19 Receiving Montelukast vs Placebo

The effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain. To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. This randomized clinical trial (Accelerating COVID-19 Therapeutic Interventions and Vaccines [ACTIV]-6) was conducted from January 27 through June 23, 2023, during the circulation of Omicron subvariants. Participants aged 30 years or older with confirmed SARS-CoV-2 infection and 2 or more acute COVID-19 symptoms for less than 7 days were included across 104 US sites. Participants were randomized 1:1 to receive montelukast, 10 mg once daily, or matched placebo for 14 days. The primary outcome was time to sustained recovery (defined as ≥3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of health care utilization events (hospitalization, urgent care clinic visit, emergency department visit, or death); COVID-19 clinical progression scale score; and difference in mean time unwell. A modified intention-to-treat approach was used for the analysis. Among 1250 participants who were randomized and received the study drug or placebo, the median age was 53 years (IQR, 42-62 years), 753 (60.2%) were female, and 704 (56.3%) reported receiving 2 or more doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [AHR], 1.02; 95% credible interval [CrI], 0.92-1.12; P = .63 for efficacy). Unadjusted median time to sustained recovery was 10 days (95% CI, 10-11 days) in both groups. No deaths occurred, and hospitalizations were reported for 2 participants (0.3%) in each group; the composite of health care utilization events was reported for 18 participants (2.9%) in the montelukast group and 18 (2.9%) in the placebo group (AHR, 1.01; 95% CrI, 0.45-1.84; P = .48 for efficacy). Five participants (0.4%) experienced serious adverse events (3 [0.5%] in the montelukast group and 2 [0.3%] in the placebo group). In this randomized clinical trial of outpatients with mild to moderate COVID-19, treatment with montelukast did not reduce duration of COVID-19 symptoms. These findings do not support the use of montelukast for the treatment of mild to moderate COVID-19. ClinicalTrials.gov Identifier: NCT04885530.

Risk of neuropsychiatric adverse events associated with montelukast use in children and adolescents: a population-based case-crossover study

PurposeMontelukast is used extensively in children and adolescents for allergic rhinitis and asthma. However, concerns have been raised regarding the increased risk of neuropsychiatric adverse events (NPAEs) associated with montelukast...

Exploring montelukast in dogs: A preliminary pharmacokinetic study following oral administration under fasted and fed conditions

This study investigates the pharmacokinetics (PK) of montelukast (MTK), a cysteinyl leukotriene receptor antagonist increasingly being considered in veterinary medicine. In dogs, MTK has found indications mainly for treating atopic dermatitis as an off-label use. Six male Labrador dogs underwent a single oral administration of MTK (40 mg/dog) in both fasted and fed conditions according to an open, single-dose, two-treatment, two-phase, cross-over design, with a washout period of one week. Blood was withdrawn to heparinized tubes at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 hr. MTK plasma concentrations were quantified using a validated HPLC method, and the data were analysed using PKanalix™ software with a non-compartmental approach.Concentrations remained quantifiable at 24 hr after administration, under both conditions. No significant differences were observed in the PK parameters between the fasted and fed states. MTK was relatively eliminated slowly, with t1/2 values of 8.10 and 7.68 hr after fasted and fed states, respectively. The attainment of maximum concentration (Cmax) occurred at a Tmax of 4 hr, with mean values of 1.98 μg/mL and 2.80 μg/mL under fasted and fed conditions, respectively. Given the unknown therapeutic range of MTK in dogs and the absence of controlled studies proving its efficacy in this species, further dosing adjustments and refinements should be considered based on both the current PK data and the need to establish an effective therapeutic range, if present. Future research should focus on efficacy studies, multiple-dose investigations, and pharmacodynamic assessments to evaluate the suitability of MTK use in dogs.

Terapi <i>Montelukast </i>pada Asma

Asthma is a chronic inflammatory respiratory condition caused by various inflammatory mediators, including those from the arachidonic acid pathway, which serves as a precursor for leukotrienes and prostaglandins. Leukotriene receptor antagonists (LTRAs) have been approved since 1998 as a treatment for asthma. Montelukast is one of the LTRAs that is useful for asthma control, including cases that accompanied by allergic rhinitis. A daily dose of 5-10 mg is recommended for persistent asthma as the preferred controller. LTRAs are not recommended for acute asthma exacerbation due to their relatively slow onset, but they are beneficial in preventing exacerbations. They are also indicated for exercise-induced asthma (EIA), and can be taken 2 hours prior to exercise. Montelukast can be administered as monotherapy or added to LABA-ICS therapy. It is suitable for adults, children, and infants over 1 year of age, preferably taken at night to prevent symptoms in the early morning. Possible side effects include respiratory tract infections, abdominal pain, diarrhea, and neuropsychiatric disorders. Montelukast is considered safe for use during pregnancy and breastfeeding. Physicians should provide comprehensive education for patients regarding medication compliance and the potential risks of side effects. Regular daily use of montelukast is beneficial in preventing acute exacerbations in asthma patients.

Association and mechanism of montelukast on depression: A combination of clinical and network pharmacology study

BackgroundPost-marketing surveillance found montelukast use was associated with an increased risk of depression. However, results of observational studies are inconsistent. ObjectiveThis study aimed to assess whether montelukast exposure is associated with depression and elucidate the possible molecular mechanism. MethodWe conducted a cross-sectional study of 9508 adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2016. Multivariable regression was used to evaluate the association between montelukast exposure and depression. Network pharmacology was conducted to identify the mechanisms of montelukast on depression. ResultsMontelukast exposure had a higher prevalence of depression (37.4 %). In a multivariable logistic regression model adjusted for sociodemographic, behavioural, and health characteristics, montelukast exposure was associated with depression (odds ratio [OR]: 1.61; confidence interval [CI]: 1.18–2.19). Network pharmacology was identified 69 key targets of montelukast on depression. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested montelukast mainly works through multiple pathways in endocrine resistance, chemical carcinogenesis-receptor activation, estrogen signaling pathway, etc. LimitationsCross-sectional data. ConclusionsThe study implies a potential positive association between long-term montelukast exposure and depression through multi-faceted mechanisms. It is suggested that attention be given to the possibility of depression in patients undergoing prolonged montelukast therapy.

Expert opinion on the clinical use of a combination of antihistamines with leukotriene receptor antagonists in the management of allergic rhinitis in Indian settings

Background: Various clinical studies have reported that the combination of montelukast and levocetirizine was effective in alleviating residual symptoms and the improvement of quality of life associated with allergic rhinitis. However, there was a dearth of data regarding the prescription practice among clinical practitioners. So, this study aims to gather clinicians' opinion regarding the use of antihistamines, with a special focus on the combined use of antihistamines with leukotriene receptor antagonists for the management of AR in Indian settings. Methods: The multiple-response questionnaire-based survey involving 19 questions gathered information on current recommendations, clinical observations, clinical experience of specialists in AR management, and the use of montelukast with levocetirizine in routine settings. Results: Out of 388 participants, approximately 84% of respondents preferred a combination of antihistamines and leukotriene receptor antagonists for managing AR. Additionally, 36% stated that 26 to 50% of patients presenting to routine practice may require montelukast and antihistamine combination as treatment. Around 61% endorsed the combination of antihistamines with leukotriene receptor antagonists as the preferred AR treatment strategy. In long-term AR management, 65% of clinicians rated montelukast with levocetirizine as excellent, and 78% of respondents reported montelukast confers additive benefits when combined with antihistamines. Conclusions: The significant preference for the combined use of antihistamines and leukotriene receptor antagonists underscores their perceived efficacy in AR treatment. The combination of antihistamines with leukotriene receptor antagonists emerges as the favored strategy for managing AR.

Montelukast: results and prospects for applications in pediatric practice

The Centers for Disease Control and Prevention reports that more than 4 million children have been diagnosed with asthma. Currently, there is no treatment that could prevent the development of asthma or change its natural course over long-term follow-up. However, the disease can be controlled using treatments used in clinical practice. For persistent asthma in children aged 5 years and younger, low doses of inhaled glucocorticosteroids are recommended, as well as the administration of montelukast, a leukotriene receptor antagonist. In addition, montelukast is prescribed to patients with allergic rhinitis as an alternative to or in combination with oral antihistamines or nasal corticosteroids. Leukotrienes are lipid mediators that play a key role in acute and chronic inflammation and allergic diseases. They exhibit their biological effects by binding to specific G-protein-coupled receptors. Each subtype of the leukotriene receptor has unique functions and expression patterns. Leukotrienes play an important role in various allergic diseases, including bronchial asthma and allergic rhinitis. Montelukast is a cysteinyl leukotriene receptor-1 antagonist widely used to suppress the inflammatory response in asthma and allergic rhinitis. This review briefly summarizes the biology of leukotrienes and their receptors, recent developments in the field of antileukotriene drugs and the prospects for their different therapeutic applications. The role of antileukotriene drugs and key indications for the use of montelukast in the complex therapy of asthma and allergic rhinitis in children have been determined.

Promising Effects of Montelukast for Critically Ill Asthma Patients via a Reduction in Delirium.

Background: Montelukast (MTK), a potent antagonist of cysteinyl leukotriene receptor 1, has shown therapeutic promise for the treatment of neuropsychiatric disorders. Delirium, a common complication in critically ill patients, lacks effective treatment. This study aims to explore the impact of pre-intensive care unit (ICU) MTK use on in-hospital delirium incidence and, subsequent, prognosis in critically ill patients. Methods: A retrospective cohort study (n = 6344) was conducted using the MIMIC-IV database. After propensity score matching, logistic/Cox regression, E-value sensitivity analysis, and causal mediation analysis were performed to assess associations between pre-ICU MTK exposure and delirium and prognosis in critically ill patients. Results: Pre-ICU MTK use was significantly associated with reduced in-hospital delirium (OR: 0.705; 95% CI 0.497-0.999; p = 0.049) and 90-day mortality (OR: 0.554; 95% CI 0.366-0.840; p = 0.005). The association was more significant in patients without myocardial infarction (OR: 0.856; 95% CI 0.383-0.896; p = 0.014) and could be increased by extending the duration of use. Causal mediation analysis showed that the reduction in delirium partially mediated the association between MTK and 90-day mortality (ACME: -0.053; 95% CI -0.0142 to 0.0002; p = 0.020). Conclusions: In critically ill patients, MTK has shown promising therapeutic benefits by reducing the incidence of delirium and 90-day mortality. This study highlights the potential of MTK, beyond its traditional use in respiratory disease, and may contribute to the development of novel therapeutic strategies for delirium.

A review of the therapeutic potential of the cysteinyl leukotriene antagonist Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic-stem cell transplantation and its possible mechanisms.

Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in these patients is the development of bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms have been recognized for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving the TH-1 and TH-2 cells, NF-kappa B, TGF-b, several cytokines and chemokines, and cysteinyl leukotrienes (CysLT). Montelukast is a highly selective CysLT receptor antagonist that has been demonstrated to exert anti-inflammatory and anti-fibrotic effects in abundant experiments. One area of interest for the use of montelukast is lung transplants or GVHD-associated BOS. Herein, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS, and finally, the possible relationship between CysLTs antagonism and BOS improvement will be discussed.

Assessing the risk of intentional self-harm in montelukast users: an updated Sentinel System analysis using ICD-10 coding

Background Montelukast prescribing information includes a Boxed Warning issued in March 2020 regarding neuropsychiatric adverse events. A previous Sentinel System study of asthma patients from 2000 to 2015 did not demonstrate an increased risk of intentional self-harm measured using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, with montelukast compared to inhaled corticosteroids (ICS). Methods Using a new user cohort study design, we examined intentional self-harm events in patients aged 10 years and older who were incident users of either montelukast or ICS as monotherapy, with a diagnosis of asthma, between October 1, 2015, to June 30, 2022, in the Sentinel System. We measured intentional self-harm using ICD-10-CM codes, which may have better accuracy for capturing suicide attempts than ICD-9-CM codes. We used inverse probability of treatment weighting to balance baseline covariates. We performed subgroup analyses by age group, sex, psychiatric history, and pre/post Boxed Warning era and conducted sensitivity analyses varying type of care setting of the outcome and exposure episode gaps. Results Among 752,230 and 724,855 patients in the montelukast and ICS exposure groups respectively, we found no association between montelukast use and self-harm compared to ICS use [Hazard Ratio (95% Confidence Interval): 0.96 (0.85, 1.08)]. This finding was consistent across all subgroups, and sensitivity analyses. Conclusion Our results cannot exclude other neuropsychiatric idiosyncratic reactions to montelukast. Compared to the previous Sentinel study, this study identified about double the rate of self-harm events, suggesting a greater sensitivity of ICD-10 codes for measuring self-harm than ICD-9.

The Effect of Oral Montelukast in Controlling Asthma Attacks in Children; A Randomized Double-blind Placebo Control Study

Oral Montelukast is recommended as maintenance therapy for persistent asthma, but there is controversy regarding its effectiveness in controlling asthma attacks. The present study was conducted to investigate the clinical efficacy of oral Montelukast for asthma attacks in children.
 This study was conducted as a double-blind placebo-controlled clinical trial on 80 children aged 1-14 years with asthma who were admitted to the emergency department of Bahrami Children's Hospital (Tehran, Iran) during one year. Patients were randomly divided into case and control groups. In addition to the standard asthma attack treatment, Montelukast was prescribed in the case group and placebo in the control group for one week. Patients were evaluated in terms of asthma attack severity score and oxygen saturation percentage (SpO2) in room air as primary outcomes 1, 4, 8, 24 and 48 hours after admission.
 In the first 48 hours, there was no significant difference in the score of asthma attack severity and SpO2 between the case and control groups. There was no significant difference between the groups in terms of length of hospitalization or number of admissions to the intensive care unit. None of the patients were re-hospitalized after discharge.
 The results of this study showed that the use of Montelukast along with the standard treatment of asthma attacks in children has no added benefit.

Meta-analysis of the relationship between montelukast use and neuropsychiatric events in patients with allergic airway disease

Use of montelukast, as a cause of neuropsychiatric events, in patients with asthma or allergic rhinitis is controversial, and comprehensive statistical analyses verifying this relationship remain lacking. To better understand the relationship between montelukast and neuropsychiatric events, it is vital to guide patients in the effective use of the drug, especially in children whose mothers are concerned about its side effects. In this study, randomized controlled trials (RCTs) investigating montelukast and neuropsychiatric events were retrieved from a literature search of the Medline (1966 to February 2023), Embase (1974 to February 2023), Web of Science, and other related databases. After screening, 18 RCTs were ultimately included in a meta-analysis to merge statistics, which demonstrated no significant increase in neuropsychiatric events compared with placebo. A similar pattern of adverse neuropsychiatric events was observed in patients grouped according to age, with headache being the most common adverse neuropsychiatric event. Overall, montelukast did not significantly increase neuropsychiatric events in patients with allergic rhinitis and/or asthma compared with placebo. Large-sample RCTs are needed to verify the association between neuropsychiatric events and montelukast use in children, and attention is also devoted to FDA warnings.

The Risk of Neuropsychiatric Adverse Events With Use of Leukotriene Receptor Antagonists in Patients With Asthma: Analysis of Korea’s National Health Insurance Sharing Service Database

Montelukast, a selective leukotriene receptor antagonist, is a commonly prescribed allergy medication but its potential association with neuropsychiatric adverse events is concerning. To analyze Korea's National Health Insurance System claims records to identify the risk of neuropsychiatric adverse events in patients with asthma treated with montelukast. This retrospective population-based study analyzed the National Health Insurance claims records of the entire Korean population between 2008 and 2015. We compared the risk of neuropsychiatric adverse events among patients with asthma using inhaled corticosteroids and/or long-acting β2-agonists with montelukast or pranlukast and those not using leukotriene receptor antagonists (control group). There was no increased risk of the composite outcome of all measured neuropsychiatric adverse events in patients with asthma who were prescribed montelukast or pranlukast compared with those who were not. However, montelukast use was associated with an increased risk of hallucinations (inverse probability treatment weighting hazard ratio, 1.45; 95% CI, 1.07-1.96) and attention problems (inverse probability treatment weighting hazard ratio, 1.24; 95% CI, 1.01-1.52). Significant negative hazards for disorientation, anxiety, stress reactions, and somatic symptoms were observed in the montelukast group. When grouped by sex, the risk of hallucinations and attention problems was higher in men prescribed montelukast compared with the controls. We did not observe an increase in all neuropsychiatric adverse events in the leukotriene receptor antagonist-treated group; however, an increased risk of hallucinations and attention problems was observed in those taking montelukast, regardless of the medication administration period.

Evaluating the Association of Montelukast Use on Neuropsychiatry-Related Healthcare Utilization and Depression in COVID-19-Hospitalized Veterans: A Nationwide VA Observational Cohort Study.

Montelukast's new boxed warning for neuropsychiatric events questions its use in the setting of coronavirus disease 2019 (COVID-19) due to increased risk for new-onset psychiatric diagnoses. We aim to evaluate the impact of using montelukast in patients hospitalized with COVID-19 on neuropsychiatry-related healthcare utilization and depression. This retrospective nationwide observational cohort study using the Veterans Health Administration database included patients from January 1, 2020, through July 1, 2021. The treatment cohorts consisted of patients with and without montelukast use prior to COVID-19 hospitalization and matched using propensity score (PS) to two control cohorts: patients with COVID-19-related hospitalization without prior montelukast use and patients with prior montelukast use who were hospitalized for reasons other than COVID-19. The primary outcome of psychiatric hospitalizations at 90days and 180days and mental health visits at 180 days were compared using Poisson or negative binomial regression. Secondary outcomes of new-onset depression and new use of antidepressants were analyzed using multivariable logistic regression. After PS matching, a total of 415 patients were included in COVID-19 with and without montelukast matched cohort and 409 patients in montelukast with and without COVID-19-related hospitalization matched cohorts. For the primary outcomes, inpatient psychiatric hospitalization at 90days [incidence rate ratio (IRR) 95% CI 1.79 (1.36-2.36)] and 180 days [IRR 95% CI 1.79 (1.32-2.25)] and mental health visits at 180 days [IRR 95% CI 1.72 (1.45-2.03)] were significantly higher in the montelukast with COVID-19 hospitalization group compared with those hospitalized without COVID-19. No difference in primary outcomes were noted in patients hospitalized with COVID-19 with and without use of montelukast. No significant difference was found in the secondary outcomes between either comparator group. Patients with prior montelukast use who were hospitalized with COVID-19 appeared to have increased rate of neuropsychiatry-related healthcare utilization.

PSYCHIATRIC ADVERSE EFFECTS OF MONTELUKAST - A NATIONWIDE COHORT STUDY.

Recent observational studies suggest that the leukotriene receptor antagonist montelukast may have neuropsychiatric adverse effects, however, results are conflicting. To assess if montelukast exposure in adults with asthma is associated with onset of neuropsychiatric adverse events using data from the Danish nationwide health registers. Individuals ≥18 years with either ≥1 prescription redemption of inhaled corticosteroids (ICS) or with at least one 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 two 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. Initiation of montelukast was significantly associated with outcome 1: use of neuropsychiatric medicine (HR (95% CI) = 1.14 (1.08-1.20, p <0.0001). 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 (HR (95% CI) = 1.28 (1.12-1.47), p<0.001 and 1.16 (1.02-1.31), p<0.05, for age group 18-29 and 30-44, respectively). Age-stratified analyses showed that the risk of both outcomes increased with decreasing age, with the highest risk seen in patients aged 18-29. 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.

Association of oral montelukast with reduced odds of developing exudative age-related macular degeneration.

This study was conducted to evaluate the association of oral montelukast, selective antagonism for cysteinyl leukotriene receptor 1, with reduced odds of exudative age-related macular degeneration (exAMD) development. This case-control study was conducted using Institutional Cohort Finder tool, and included 1913 patients with exAMD (ICD: H35.32 and 362.52) and 1913 age- and gender-matched control subjects without exAMD. Sub-analysis among 1913 exAMD and 324 non-exudative AMD was also conducted. A total of 47 (2.5%) exAMD cases were identified to have a history of oral montelukast use prior to exAMD diagnosis, compared to 84 (4.4%) controls. Montelukast usage was significantly associated with reduced odds of exAMD in the multivariable analysis (adjusted OR: 0.50, 95% CI: 0.31 - 0.80) as well as NSAID usage (adjusted OR: 0.69). Caucasian race, history of smoking, non-exudative macular degeneration in either eye were also found to have significant relationship with increased odds of exAMD. In the sub-analysis, montelukast usage showed significant association with reduced odds of developing exAMD from non-exudative AMD (adjusted OR: 0.53 95% CI: 0.29 - 0.97) as well as the presence of atopic disease (adjusted OR: 0.60). The study results suggested that oral montelukast is linked to reduced odds of exAMD development.

Efficacy and safety of montelukast adjuvant therapy in adults with cough variant asthma: A systematic review and meta-analysis.

Montelukast is a highly selective and specific cysteinyl leukotriene receptor antagonist used in the treatment of asthma. Whether montelukast as adjuvant therapy can significantly and safely treat adults with cough variant asthma (CVA) remains inconclusive. This meta-analysis systematically evaluated the efficacy and safety of montelukast as an adjuvant treatment for adults with CVA. Randomized controlled trials (RCTs) on montelukast combined with inhaled corticosteroids (ICS) and long-acting β2 agonists (LABAs) to treat CVA in adults, from inception to March 6, 2023, were retrieved from the CNKI, Wanfang, VIP, CBM, PubMed, Embase, Cochrane Library, and Web of Science databases and Clinical Trials website. Review Manager (version 5.4) and Stata (version 15.0) were used to conduct the meta-analysis. A total of 15 RCTs were ultimately included in the meta-analysis. It was established that montelukast as adjuvant therapy raised the total effective rate (RR = 1.20, 95% confidence interval [CI] [1.13, 1.27], P < 0.01) and improved the FEV1% (SMD = 0.91, 95% CI [0.40, 1.41], P < 0.01), PEF% (SMD = 0.63, 95% CI [0.38, 0.88], P < 0.01), FEV1 (SMD = 1.15, 95% CI [0.53, 1.77], P < 0.01), PEF (SMD = 0.64, 95% CI [0.42, 0.86], P < 0.01), and FEV1/FVC% (SMD = 0.76, 95% CI [0.51, 1.01], P < 0.01) and reduced the recurrence rate (RR = 0.28, 95% CI [0.15, 0.53], P < 0.01). The incidence of adverse reactions was higher in the montelukast auxiliary group compared to the control group but with no statistical difference (RR = 1.32, 95% CI [0.89, 1.96], P = 0.17). Existing evidence indicated that the use of montelukast as an adjuvant therapy had therapeutic efficacy superior to ICS + LABA alone for the treatment of adult patients with CVA. However, further research is needed, especially a combination of high-quality long-term prospective studies and carefully designed RCTs.

Effect of Montelukast on Treatment of Coronavirus Pneumonia (COVID-19): A Systematic Review

Background: The coronavirus disease 2019 (COVID‐19) exhibits the most important global public health emergency. Montelukast (MTL), a prototype cysteinyl leukotriene receptor antagonist, is commonly considered in the therapy of exercise- and aspirin-induced asthma. The purpose of this study was to present a systematic review of the literature on the effectiveness of MTL against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and exuberant immune activation in COVID‐19 disease. Methods: PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched from the database on August 15, 2021and updated on November 19, 2022. Two reviewers independently screened articles, appraised methodological quality, and extracted the data. Results: A total of 118 related reports were recognized after eliminating duplicates. Of these, 30 references were screened based on titles and abstracts. After removing unrelated studies, 20 studies were included in the full-text review and evaluated for appropriateness. Finally, eight studies fitting the inclusion criteria for data extraction were selected. One of them was a prospective, randomized, controlled, and single-blinded study, three were open-label randomized or non-randomized controlled clinical trials, two were retrospective studies, and two were case series or comparative studies. A total of 1083 patients infected with COVID-19 infection (999 adults and 84 children) were examined on the effectiveness of MTL on symptom severity as well as hospitalization length. The results of the mentioned studies showed a low risk of clinical deterioration in the MTL group. In addition, the length of hospital stay was low in the treatment group compared to the standard management. Conclusion: MTL as a potential adjuvant therapy in COVID-19 may improve lung injury, inflammation, and symptoms. Moreover, the use of MTL could decrease the severity and mortality of COVID-19. Additional well-designed randomized controlled trials are necessary to approve the role of MTL in SARS-CoV-2 prevention or COVID-19 symptoms improvement.

Montelukast Attenuates Retraction of Expanded Flap by Inhibiting Capsule Formation around Silicone Expander through TGF-β1 Signaling.

Tissue expansion has tremendous applications in plastic surgery, but flap retraction provides insufficient tissue for use. Inspired by the use of montelukast to suppress capsular contracture, the authors investigated the effects of montelukast on capsule formation around the expander and retraction of the expanded scalp of the rat. Thirty-six male Sprague-Dawley rats were randomly divided into control and montelukast groups. In each group, 12 expanded flaps with or without capsules were harvested for histologic and molecular analysis; the six remaining expanded flaps were transferred to repair defects. Myofibroblast and transforming growth factor-β1 expression in the capsule was determined using immunofluorescence. Capsule ultrastructure was observed using transmission electron microscopy. Related protein expression in the capsules was detected using Western blot analysis. A comparison of control and montelukast groups revealed that areas of the harvested expanded flaps with capsules were greater (2.04 ± 0.11 cm 2 versus 2.42 ± 0.12 cm 2 , respectively; P = 0.04); the retraction rate decreased (41.3% ± 2.16% versus 28.13% ± 2.17%, respectively; P < 0.01). However, the increased areas and decreased retraction disappeared after capsule removal. The number of myofibroblasts declined. Thin, sparse collagen fibers were observed in the capsules. The expression of COL1, COL3, TGF-β1, EGR1, and phosphorylated ERK1/2 in the capsules decreased. Furthermore, the recipient area repaired by the transferred expanded flap was increased from 4.25 ± 0.39 cm 2 to 6.58 ± 0.31 cm 2 ( P < 0.01). Montelukast attenuates retraction of the expanded flap by inhibiting capsule formation through suppressing transforming growth factor-β1 signaling. This study provides novel insights into a method for increasing the area of the expanded flap.

β2-Adrenoreceptor Agonists, Montelukast, and Parkinson Disease Risk.

This study was undertaken to examine the association between montelukast use, β2-adrenoreceptor (β2AR) agonist use, and later Parkinson disease (PD). We ascertained use of β2AR agonists (430,885 individuals) and montelukast (23,315 individuals) from July 1, 2005 to June 30, 2007, and followed 5,186,886 PD-free individuals from July 1, 2007 to December 31, 2013 for incident PD diagnosis. We estimated hazard ratios and 95% confidence intervals using Cox regressions. We observed 16,383 PD cases during on average 6.1 years of follow-up. Overall, use of β2AR agonists and montelukast were not related to PD incidence. A 38% lower PD incidence was noted among high-dose montelukast users when restricted to PD registered as the primary diagnosis. Overall, our data do not support inverse associations between β2AR agonists, montelukast, and PD. The prospect of lower PD incidence with high-dose montelukast exposure warrants further investigation, especially with adjustment for high-quality data on smoking. ANN NEUROL 2023;93:1023-1028.