Cysteinyl leukotriene receptor-1 as a potential target for host-directed therapy during chronic schistosomiasis in murine model.

Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature female worms that are trapped in host's tissues, resulting in chronic Th2 driven fibrogranulmatous pathology. Although the disease can be treated with a relatively inexpensive drug, praziquantel (PZQ), re-infections remain a major problem in endemic areas. There is a need for new therapeutic drugs and alternative drug treatments for schistosomiasis. The current study hypothesized that cysteinyl leukotrienes (cysLTs) could mediate fibroproliferative pathology during schistosomiasis. Cysteinyl leukotrienes (cysLTs) are potent lipid mediators that are known to be key players in inflammatory diseases, such as asthma and allergic rhinitis. The present study aimed to investigate the role of cysLTR1 during experimental acute and chronic schistosomiasis using cysLTR1-/- mice, as well as the use of cysLTR1 inhibitor (Montelukast) to assess immune responses during chronic Schistosoma mansoni infection. Mice deficient of cysLTR1 and littermate control mice were infected with either high or low dose of Schistosoma mansoni to achieve chronic or acute schistosomiasis, respectively. Hepatic granulomatous inflammation, hepatic fibrosis and IL-4 production in the liver was significantly reduced in mice lacking cysLTR1 during chronic schistosomiasis, while reduced liver pathology was observed during acute schistosomiasis. Pharmacological blockade of cysLTR1 using montelukast in combination with PZQ reduced hepatic inflammation and parasite egg burden in chronically infected mice. Combination therapy led to the expansion of Tregs in chronically infected mice. We show that the disruption of cysLTR1 is dispensable for host survival during schistosomiasis, suggesting an important role cysLTR1 may play during early immunity against schistosomiasis. Our findings revealed that the combination of montelukast and PZQ could be a potential prophylactic treatment for chronic schistosomiasis by reducing fibrogranulomatous pathology in mice. In conclusion, the present study demonstrated that cysLTR1 is a potential target for host-directed therapy to ameliorate fibrogranulomatous pathology in the liver during chronic and acute schistosomiasis in mice.

Montelukast Influence on Lung in Experimental Diabetes.

Background and Objectives: The influence of montelukast (MK), an antagonist of cysLT1 leukotriene receptors, on lung lesions caused by experimental diabetes was studied. Materials and Methods: The study was conducted on four groups of six adult male Wistar rats. Diabetes was produced by administration of streptozotocin 65 mg/kg ip. in a single dose. Before the administration of streptozotocin, after 72 h, and after 8 weeks, the serum values of glucose, SOD, MDA, and total antioxidant capacity (TAS) were determined. After 8 weeks, the animals were anesthetized and sacrificed, and the lungs were harvested and examined by optical microscopy. Pulmonary fibrosis, the extent of lung lesions, and the lung wet-weight/dry-weight ratio were evaluated. Results: The obtained results showed that MK significantly reduced pulmonary fibrosis (3.34 ± 0.41 in the STZ group vs. 1.73 ± 0.24 in the STZ+MK group p < 0.01) and lung lesion scores and also decreased the lung wet-weight/dry-weight (W/D) ratio. SOD and TAS values increased significantly when MK was administered to animals with diabetes (77.2 ± 11 U/mL in the STZ group vs. 95.7 ± 13.3 U/mL in the STZ+MK group, p < 0.05, and 25.52 ± 2.09 Trolox units in the STZ group vs. 33.29 ± 1.64 Trolox units in the STZ+MK group, respectively, p < 0.01), and MDA values decreased. MK administered alone did not significantly alter any of these parameters in normal animals. Conclusions: The obtained data showed that by blocking the action of peptide leukotrienes on cysLT1 receptors, montelukast significantly reduced the lung lesions caused by diabetes. The involvement of these leukotrienes in the pathogenesis of fibrosis and other lung diabetic lesions was also demonstrated.

Eosinophilic granulomatosis with polyangiitis and its association with montelukast: a case-based review.

The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is well established. More recently, cases of immune-related adverse events ranging from inflammatory polyarthritis to necrotizing myositis in patients taking checkpoint inhibitors have been reported. However, data linking drugs to systemic vasculitis are scarce and at times debatable. Propylthiouracil, hydralazine, and minocycline have been associated with rare cases of ANCA-associated syndromes, including life-threatening pulmonary-renal syndromes and systemic polyarteritis nodosa-like diseases. Eosinophilic granulomatosis with polyangiitis (EGPA) has been reported in patients taking leukotriene inhibitors. Since the link between the use of leukotriene inhibitors and occurrence of EGPA remains highly controversial, we performed a literature review for cases of EGPA in patients taking montelukast without prior history of oral corticosteroid use. We found 24 cases, along with our own two cases described, making 26 cases in total. The mean age was 43 and a majority (18/26) were female. In majority of cases EGPA-like disease never relapsed after they were taken off leukotriene inhibitors suggesting a clear causal relationship between the use of these drugs and occurrence of eosinophil-rich systemic EGPA.

Efficacy of montelukast for adenoid hypertrophy in paediatrics: A systematic review and meta-analysis.

INTRODUCTION: Leukotrienes play a significant role in the pathogenesis of adenoid hypertrophy (A.H.). Therefore, we aimed to analyse the role of montelukast, a leukotriene receptor antagonist, alone or in combination with mometasone, a potent local intranasal steroid, for the treatment of A.H. METHODS: Participants were children with A.H. were treated with montelukast alone or montelukast and mometasone furoate. The main outcome measures were effect of montelukast on clinical symptoms of A.H. A literature review was conducted using online search engines, Cochrane Library, PubMed, Web of Science and Scopus, for randomized clinical trials assessing children with A.H. treated with montelukast alone or montelukast and mometasone furoate. Seven randomized clinical trials (RCTs) were included with 742 children. RESULTS: Our study reveals that montelukast alone or in combination with intranasal mometasone furoate significantly improves clinical symptoms of adenoid hypertrophy such as snoring, sleeping disturbance, mouth breathing and A/N ratio. Montelukast was superior to placebo in decreasing snoring (SMD = -1.00, 95% CI [-1.52, -0.49]), sleep discomfort (SMD = -1.26, 95% CI [-1.60, -0.93]), A/N ratio (MD = -0.11, 95% CI [-0.14, -0.09]) and mouth breathing (SMD = -1.36, 95% CI [-1.70, -1.02]). No difference was detected between montelukast and mometasone versus mometasone alone in snoring (SMD = -0.21, 95%CI [-0.69, 0.27]); however, the combination group was superior to the mometasone alone in mouth breathing (SMD = -0.46, 95% CI [-0.73, -0.19]). CONCLUSIONS: The limitation of studies included a small sample size, with an overall low to medium quality. Thus, further larger, higher-quality RCTs are recommended to provide more substantial evidence.

Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition.

BACKGROUND AND AIMS: The Glu504Lys polymorphism in the aldehyde dehydrogenase 2 (ALDH2) gene is closely associated with myocardial ischaemia/reperfusion injury (I/RI). The effects of ALDH2 on neutrophil extracellular trap (NET) formation (i.e. NETosis) during I/RI remain unknown. This study aimed to investigate the role of ALDH2 in NETosis in the pathogenesis of myocardial I/RI. METHODS: The mouse model of myocardial I/RI was constructed on wild-type, ALDH2 knockout, peptidylarginine deiminase 4 (Pad4) knockout, and ALDH2/PAD4 double knockout mice. Overall, 308 ST-elevation myocardial infarction patients after primary percutaneous coronary intervention were enrolled in the study. RESULTS: Enhanced NETosis was observed in human neutrophils carrying the ALDH2 genetic mutation and ischaemic myocardium of ALDH2 knockout mice compared with controls. PAD4 knockout or treatment with NETosis-targeting drugs (GSK484, DNase1) substantially attenuated the extent of myocardial damage, particularly in ALDH2 knockout. Mechanistically, ALDH2 deficiency increased damage-associated molecular pattern release and susceptibility to NET-induced damage during myocardial I/RI. ALDH2 deficiency induced NOX2-dependent NETosis via upregulating the endoplasmic reticulum stress/microsomal glutathione S-transferase 2/leukotriene C4 (LTC4) pathway. The Food and Drug Administration-approved LTC4 receptor antagonist pranlukast ameliorated I/RI by inhibiting NETosis in both wild-type and ALDH2 knockout mice. Serum myeloperoxidase-DNA complex and LTC4 levels exhibited the predictive effect on adverse left ventricular remodelling at 6 months after primary percutaneous coronary intervention in ST-elevation myocardial infarction patients. CONCLUSIONS: ALDH2 deficiency exacerbates myocardial I/RI by promoting NETosis via the endoplasmic reticulum stress/microsomal glutathione S-transferase 2/LTC4/NOX2 pathway. This study hints at the role of NETosis in the pathogenesis of myocardial I/RI, and pranlukast might be a potential therapeutic option for attenuating I/RI, particularly in individuals with the ALDH2 mutation.

Montelukast as a repurposable additive drug for standard-efficacy multiple sclerosis treatment: Emulating clinical trials with retrospective administrative health claims data.

BACKGROUND: Effective and safe treatment options for multiple sclerosis (MS) are still needed. Montelukast, a leukotriene receptor antagonist (LTRA) currently indicated for asthma or allergic rhinitis, may provide an additional therapeutic approach. OBJECTIVE: The study aimed to evaluate the effects of montelukast on the relapses of people with MS (pwMS). METHODS: In this retrospective case-control study, two independent longitudinal claims datasets were used to emulate randomized clinical trials (RCTs). We identified pwMS aged 18-65 years, on MS disease-modifying therapies concomitantly, in de-identified claims from Optum's Clinformatics® Data Mart (CDM) and IQVIA PharMetrics® Plus for Academics. Cases included 483 pwMS on montelukast and with medication adherence in CDM and 208 in PharMetrics Plus for Academics. We randomly sampled controls from 35,330 pwMS without montelukast prescriptions in CDM and 10,128 in PharMetrics Plus for Academics. Relapses were measured over a 2-year period through inpatient hospitalization and corticosteroid claims. A doubly robust causal inference model estimated the effects of montelukast, adjusting for confounders and censored patients. RESULTS: pwMS treated with montelukast demonstrated a statistically significant 23.6% reduction in relapses compared to non-users in 67.3% of emulated RCTs. CONCLUSION: Real-world evidence suggested that montelukast reduces MS relapses, warranting future clinical trials and further research on LTRAs' potential mechanism in MS.

Comparison of treatment efficacy of omega-3 fish oil and montelukast in ovalbumin-protease-induced allergic rhinitis model in rats.

OBJECTIVES: Montelukast is a well-known leukotriene receptor antagonist commonly used in treating allergic rhinitis and asthma. Omega-3 fatty acid is also known as an antiallergic and immunomodulator molecule. This study aimed to elucidate the efficacy of systemic montelukast and omega-3 fatty acid treatment in allergic rhinitis models in Wistar Hannover rats. METHODS: This research was conducted on 28 healthy Wistar Hannover rats weighing 250-350 g. After establishing the allergic rhinitis model, nasal symptoms were observed and scored, and the nasal mucosa of all rats was investigated histologically. Light microscopy was utilized to evaluate the degree of ciliary loss, goblet cell hyperplasia, vascular congestion, vascular proliferation, inflammatory cell infiltration, eosinophil infiltration, and hypertrophy in chondrocytes. RESULTS: As a result of the analysis of the data obtained from the study, it was determined that typical allergic rhinitis symptoms such as nasal scratching and sneezing were significantly reduced in the rats in the montelukast and omega-3 treated group, and these symptoms did not increase after repeated intranasal OVA-protease applications. Histological examinations after fish oil treatment did not reveal typical inflammatory changes in allergic rhinitis. None of the rats in the montelukast and omega-3 groups had any increase in goblet cells, whereas 14.3% of the rats in the control group and 28.6% of the rats in the allergic rhinitis group had mild increase. Last but not least, 71.4% of rats in the allergic rhinitis group had a moderate increase. The difference between the groups was statistically significant (p < 0.001). CONCLUSION: Regarding the outcomes of this research, it was observed that w-3 fatty acids had antiallergic effects, both histopathological and clinical, in the allergic rhinitis model. We believe that further randomized controlled trials incorporating larger cohorts are warranted to verify the use of omega-3 fatty acids in treating allergic rhinitis. The level of evidence of this article is Level 2.

The anti-seizure potential of cysteine leukotriene receptor antagonists: A systematic review of animal studies.

BACKGROUND: Emerging literature has suggested the antiepileptic activity of cysteine leukotriene receptor (CysLTR) antagonists in experimental animals of epilepsy. Leukotrienes are substances that cause inflammation and affect brain activity, blood flow, oxidation, and inflammation in the brain. These processes are related to epilepsy and its complications. CysLTR antagonists are drugs that prevent leukotrienes from working. They may be useful for treating epilepsy, especially for people who do not respond to other drugs. Therefore, the current study aims to systematically review the potential anti-seizure effect of CysLTR antagonists in experimental studies. METHOD: We systematically reviewed the online databases using online databases such as Google Scholar, science direct, and PubMed until December 2022 to identify experimental studies assessing the anti-seizure activity of CysLTR antagonists. The Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) was used to evaluate the risk of bias (RoB) of the included studies. RESULTS: Initially we identified 3823 studies. After screening using inclusion and exclusion criteria, 8 studies were finally included in the current study. All included studies, reported that CysLTR antagonists reduced the intensity of seizures in animal models of epilepsy. CONCLUSION: In conclusion, CysLTR antagonists could be a potential therapeutic approach for the treatment of epilepsy. However, further preclinical and clinical studies are required to confirm their efficacy, safety, and mechanism of anti-seizure activity.

Leukotriene antagonists reduce epileptic seizures-related hospitalization in older adult populations with allergic rhinitis or asthma: A population-based cohort study using the Shizuoka Kokuho database: The Shizuoka study.

OBJECTIVE: Managing the risk of epileptic seizures in older adults is increasingly important as the population ages. Leukotriene receptor antagonists (LTRAs) are commonly used to treat asthma or allergic rhinitis. Preclinical studies suggest that LTRAs have antiepileptic effects; however, few population-based etiological studies on this topic have been available. Our study explored whether LTRAs reduce hospitalization risk associated with epileptic seizures in older individuals with asthma or allergic rhinitis. METHODS: We conducted a new-user design analysis using the Shizuoka Kokuho database. We included all individuals aged 60-89 years who had at least one episode of allergic rhinitis or asthma during the study period. We compared individuals who newly started LTRAs with those who did not take LTRAs. Propensity score matching was used to balance the baseline characteristics of the participants. We compared the hazard ratios for seizure-related hospitalization between new LTRA users and non-users and performed subgroup analyses. RESULTS: Our matched cohorts consisted of 64 724 new users and non-users of LTRAs who were aged 60-89 years and had asthma or allergic rhinitis. During the observation period, 377 (0.58%) and 595 (0.92%) incidents were observed in the LTRA new-user and non-user groups, respectively. The hazard ratio for seizure-related hospitalization was 0.75 (95% confidence interval [CI]: 0.62-0.92) in the LTRA new-user group compared with the non-user group. Subgroup analysis revealed that the hazard ratio was weak in diabetic patients (1.31; 95% CI: 0.72-2.38). SIGNIFICANCE: This study indicated that LTRAs reduced seizure-related hospitalization in older adult patients with allergic rhinitis or asthma. We could not evaluate the severity and related diseases of epileptic seizures during LTRAs. Further studies, including observational studies, detailed multicenter prospective studies, and clinical trials, are needed to validate these findings. PLAIN LANGUAGE SUMMARY: This study examined if leukotriene receptor antagonists (LTRAs), commonly used for asthma or allergies, could lower seizure risk in older adults. Analyzing health records of 60-89 year-olds with asthma or allergies, we found a reduced rate of seizure-related hospitalizations in those starting LTRAs, though this was not as evident in diabetic patients. Our results suggest potential benefits of LTRAs in preventing seizures in older adults with respiratory issues, but further research is needed to confirm these findings.

Best step-up treatments for children with uncontrolled asthma: a systematic review and network meta-analysis of individual participant data.

BACKGROUND: There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids (ICS) and international guidelines make different recommendations. We evaluated the pharmacological treatments to reduce asthma exacerbations and symptoms in uncontrolled patients age <18 years on ICS. METHODS: We searched MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, Web of Science, National Institute for Health and Care Excellence Technology Appraisals, National Institute for Health and Care Research Health Technology Assessment series, World Health Organization International Clinical Trials Registry, conference abstracts and internal clinical trial registers (1 July 2014 to 5 May 2023) for randomised controlled trials of participants age <18 years with uncontrolled asthma on any ICS dose alone at screening. Studies before July 2014 were retrieved from previous systematic reviews/contact with authors. Patients had to be randomised to any dose of ICS alone or combined with long-acting ß2-agonists (LABA) or combined with leukotriene receptor antagonists (LTRA), LTRA alone, theophylline or placebo. Primary outcomes were exacerbation and asthma control. The interventions evaluated were ICS (low/medium/high dose), ICS+LABA, ICS+LTRA, LTRA alone, theophylline and placebo. RESULTS: Of the 4708 publications identified, 144 trials were eligible. Individual participant data were obtained from 29 trials and aggregate data were obtained from 19 trials. Compared with ICS Low, ICS Medium+LABA was associated with the lowest odds of exacerbation (OR 0.44, 95% credibility interval (95% CrI) 0.19-0.90) and with an increased forced expiratory volume in 1 s (mean difference 0.71, 95% CrI 0.35-1.06). Treatment with LTRA was the least preferred. No apparent differences were found for asthma control. CONCLUSIONS: Uncontrolled children/adolescents on low-dose ICS should be recommended a change to medium-dose ICS+LABA to reduce the risk for exacerbation and improve lung function.

Heterogeneity of Treatment Response to Asthma.

The definition of asthma has evolved over the years with significant heterogeneity of the disease increasingly recognized. Complex gene and environment interactions result in different pheno-endotypes of asthma that respond differently to the same treatment. Multiple studies have revealed pharmacogenomic and endophenotypic factors that predict treatment response to standard therapies for asthma. Recent advances in biologic medications have enabled a more tailored approach to the care of patients with moderate to severe asthma, taking into consideration clinical traits and measurable biomarkers. This chapter will review heterogeneity in treatment response to different medication classes for asthma: inhaled and systemic corticosteroids, beta-2 agonists, leukotriene modifiers, muscarinic antagonists, macrolides, and biologics.

Basic clinical management of preschool wheeze.

Preschool wheeze is very common and often difficult to treat. Most children do not require any investigations; only a detailed history and physical examination to ensure an alternative diagnosis is not being missed; and the differential diagnosis, and hence investigation protocols for the child in whom a major illness is suspected, shows geographical variation. The pattern of symptoms may be divided into episodic viral and multiple trigger to guide treatment, but the pattern of symptoms must be re-assessed regularly. However, symptom patterns are a poor guide to underlying pathology. Attention to the proper use of spacers, and adverse environmental exposures such as tobacco smoke exposure, is essential. There are no disease-modifying therapies, so therapy is symptomatic. This paper reviews recent advances in treatment, including new data on the place of leukotriene receptor antagonists, prednisolone for acute attacks of wheeze, and antibiotics, based on new attempts to understand the underlying pathology in a way that is clinically practical.

Revisiting asthma pharmacotherapy: where do we stand and where do we want to go?

Several current guidelines/strategies outline a treatment approach to asthma, which primarily consider the goals of improving lung function and quality of life and reducing symptoms and exacerbations. They suggest a strategy of stepping up or down treatment, depending on the patient's overall current asthma symptom control and future risk of exacerbation. While this stepwise approach is undeniably practical for daily practice, it does not always address the underlying mechanisms of this heterogeneous disease. In the last decade, there have been attempts to improve the treatment of severe asthma, such as the addition of a long-acting antimuscarinic agent to the traditional inhaled corticosteroid/long-acting ß2-agonist treatment and the introduction of therapies targeting key cytokines. However, despite such strategies several unmet needs in this population remain, motivating research to identify novel targets and develop improved therapeutic and/or preventative asthma treatments. Pending the availability of such therapies, it is essential to re-evaluate the current conventional "one-size-fits-all" approach to a more precise asthma management. Although challenging, identifying "treatable traits" that contribute to respiratory symptoms in individual patients with asthma may allow a more pragmatic approach to establish more personalised therapeutic goals.

Highlights of the treatment of allergic rhinitis according to Chinese guidelines.

PURPOSE OF REVIEW: This review aimed to introduce the pharmacotherapy of allergic rhinitis according to the 2022 updated Chinese guidelines. RECENT FINDINGS: Despite recent advances in basic and clinical research worldwide, pharmacotherapy remains a mainstream in allergic rhinitis treatment. Usually, the first-line drugs, involving intranasal corticosteroids, second-generation oral and intranasal H1-antihistamines, or leukotriene receptor antagonists, can achieve acceptable outcomes in the treatment of allergic rhinitis. The second-line drugs, such as oral corticosteroids, intranasal decongestants and intranasal anticholinergics, can assist in controlling severe symptoms, like nasal congestion/blockage and watery rhinorrhea. For those with moderate-to-severe allergic rhinitis, evidence-based stepwise strategies are suitable, in which the types and dosages of drugs are de-escalated or upgraded according to their therapeutic efficacy. Meanwhile, omalizumab, a novel biological agent, has burgeoned to satisfy the need of patients. SUMMARY: This review highlights the staples in Chinese guidelines about the pharmacotherapy for allergic rhinitis to better understand the guidelines and promote the clinical practice.

Can montelukast sodium be an alternative treatment in the treatment of interstitial cystitis?

Background: The leukotriene D4 receptors have been detected in human bladder detrusor myocytes, and they can play the role of interstitial cystitis etiology. Aim: Our study aims to explain the role of mast cells histologically and immunohistochemically in the pathogenesis and the effectiveness of montelukast that leukotriene D4 receptor antagonist in the treatment of interstitial cystitis. Subjects and Methods: Twenty-four Wistar albino adult female rats were used. Group 1 (n = 8): control (sham) group, Group 2 (n = 8): interstitial cystitis group, and Group 3 (n = 8): treatment group. Groups 2 and 3 rats were administered 75 mg/kg cyclophosphamide four times every three days intraperitoneally. The rats in the treatment group were started on montelukast sodium as 10 mg/kg, 1 × 1/day per orally after the last administration of cyclophosphamide and were given for 14 days. Mast cells in the bladder tissues were examined histologically, and the presence of IL-6, 8, VEGF, and TNF alpha was examined immunohistochemically. Results: Thin transitional epithelium, loose connective tissue, weak smooth muscle bundles, and signs of chronic inflammation were observed in the interstitial cystitis group. Regenerated transitional epithelium, intact basement membrane, compact lamina propia, thick smooth muscle bundles, and rare inflammatory cells were observed after the treatment with the montelukast. Mast cells were decreased in bladder tissue after treatment. IL-6, IL-8, VEGF, and TNF alpha levels were significantly decreased after treatment. Conclusions: We found that inflammatory mediators were significantly reduced after treatment with montelukast in the interstitial cystitis group. Montelukast can be used as an effective drug in the treatment of interstitial cystitis.

Use of Leukotriene-Receptor Antagonists During Pregnancy and Risk of Neuropsychiatric Events in Offspring.

This cohort study examines the association of the use of leukotriene-receptor antagonists during pregnancy with the risk of neuropsychiatric events in offspring.

Montelukast as a potential treatment for COVID-19.

INTRODUCTION: Montelukast is a leukotriene inhibitor that is widely used to treat chronic asthma and allergic rhinitis. The drug interferes with molecular signaling pathways produced by leukotrienes in a variety of cells and tissues throughout the human body that lead to tightening of airway muscles, production of aberrant pulmonary fluid (airway edema), and in some cases, pulmonary inflammation. AREAS COVERED: Montelukast has also been noted to have anti-inflammatory properties, suggesting it may have a role in the treatment of coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has been noted to induce misfiring of the immune system in some patients. A literature search of PubMed was performed to identify all relevant studies of montelukast and SARS-CoV-2 through 27 January 2023. EXPERT OPINION: Montelukast has been the subject of small studies of SARS-CoV-2 and will be included in a large, randomized, double-blind, placebo-controlled study of outpatients with COVID-19 sponsored by the United States National Institutes of Health known as Accelerating COVID-19 Therapeutic Interventions and Vaccines-6. This paper reviews what is known about montelukast, an inexpensive, well-tolerated, and widely available medication, and examines the rationale for using this drug to potentially treat patients with COVID-19.

Executive summary: Japanese guidelines for adult asthma (JGL) 2021.

Asthma is characterized by chronic airway inflammation, variable airway narrowing, and sensory nerve irritation, which manifest as wheezing, dyspnea, chest tightness, and cough. Longstanding asthma may result in airway remodeling and become intractable. Despite the increased prevalence of asthma in adults, asthma-associated deaths have decreased in Japan (0.94 per 100,000 people in 2020). The goals of asthma treatment include the control of symptoms and reduction of future risks. A functional partnership between physicians and patients is indispensable for achieving these goals. Long-term management with medications and the elimination of triggers and risk factors are fundamental to asthma treatment. Asthma is managed via four steps of pharmacotherapy ("controllers"), ranging from mild to intensive treatments, depending on disease severity; each step involves daily administration of an inhaled corticosteroid, which varies from low to high dosage. Long-acting ß2 agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonists are recommended as add-on drugs. Allergen immunotherapy is a new option that is employed as a controller treatment. Further, as of 2021, anti-IgE antibody, anti-IL-5 and anti-IL-5 receptor α-chain antibodies, and anti-IL-4 receptor α-chain antibodies are available for the treatment of severe asthma. Bronchial thermoplasty can be performed for asthma treatment, and its long-term efficacy has been reported. Algorithms for their usage have been revised. Comorbidities, such as allergic rhinitis, chronic rhinosinusitis, chronic obstructive pulmonary disease, and aspirin-exacerbated respiratory disease, should also be considered during the treatment of chronic asthma. Depending on the severity of episodes, inhaled short-acting ß2 agonists, systemic corticosteroids, short-acting muscarinic antagonists, oxygen therapy, and other approaches are used as needed ("relievers") during exacerbation.

Adverse drug reactions affecting treatment adherence in first-line treatment of asthma: An observational study

Background: Asthma is the most common chronic lung disease among children. International guidelines recommend inhaled corticosteroids (ICS) as the first-line daily controller therapy for children with asthma and leukotriene receptor antagonists (LTRA) as the second alternative therapy. Adherence to treatment is the most significant component to optimize the benefits of therapy in asthma. Objective: This study aims to investigate the frequency of drug discontinuation due to adverse drug reactions (ADRs) that affect adherence to treatment in children with asthma or asthma and allergic rhinitis using LTRA or ICS as monotherapy. Methods: The subjects aged 4–18 years with asthma or asthma and allergic rhinitis and using montelukast or ICS as monotherapy were included in the study. They were evaluated in terms of ADRs affecting adherence to treatment in the first and third months of treatment. Results: A total of 468 cases, 356 of whom received montelukast monotherapy and 112 of whom received ICS treatment, with a mean age of 9.10 ± 3.08 (4–17) years, were included in the study. Males constituted 65.6% of the total cases (n = 307). In the first month of follow-up of the cases, it was observed that 4.8% (n = 17) of the patients in the montelukast group could not continue the treatment due to ADR. It was determined that the drug discontinuation rate in the montelukast group in the first month was significantly higher than in the ICS group (P = 0.016), and the risk of drug discontinuation due to ADR in the montelukast group was 1.333 (95% CI, 1.26–1.40) times higher. Conclusions: As a result, it was observed that the drug was discontinued due to ADR at a higher rate in children with asthma who received montelukast monotherapy compared to those who received ICS monotherapy (AU)

Montelukast Inhibits Lung Cancer Cell Migration by Suppressing Cysteinyl Leukotriene Receptor 1 Expression In vitro.

BACKGROUND: Lung cancer is a major threat to public health and remains difficult to treat. Repositioning of existing drugs has emerged as a therapeutic strategy in lung cancer. Clinically, low-dose montelukast has been used to treat asthma. OBJECTIVE: We evaluated the potential of using montelukast to treat lung cancer. METHODS: Migration was detected using wound-healing and Transwell assays, the expression of CysLT1 using western blotting, and subcellular localization of CysLT1 using immunofluorescence. CRISPR/Cas9 technology was used to further investigate the function of CysLT1. RESULTS: Subcellular localization staining showed that the CysLT1 distribution varied in murine and human lung cancer cell lines. Furthermore, montelukast suppressed CysLT1 expression in lung cancer cells. The treated cells also showed weaker migration ability compared with control cells. Knockout of CysLT1 using CRISPR/Cas9 editing in A549 cells further impaired the cell migration ability. CONCLUSION: Montelukast inhibits the migration of lung cancer cells by suppressing CysLT1 expression, demonstrating the potential of using CysLT1 as a therapeutic target in lung cancer.