Use Of Montelukast Research Articles

Clinical efficacy of antileukotriene therapy in children with acute bronchitis

Recurrent episodes of bronchial obstruction in preschool children are one of the important risk factors for the development of bronchial asthma.Purpose. The study aimed at investigating the clinical and immunological characteristics of children with acute bronchitis and to determine the clinical effectiveness of course anti-inflammatory therapy.Material and methods. The study was a single-center prospective cohort, including 1–5-year-old patients with acute bronchitis (main group, n = 109): a group with acute simple bronchitis (n = 34) and acute obstructive bronchitis (n = 75). Reference group: children of health group 2 (n = 29). Clinical and anamnestic and laboratory methods were used. Patients with a positive API (Asthma Predictive Index) were administered montelukast at a dose of 4 mg orally once a day for 3 months (control points at 1 and 3 months), reference patients received symptomatic therapy for respiratory infection. The end point of the study is the absence of bronchial obstruction. The effectiveness of the use of Montelukast was evaluated by calculating the clinical index, efficiency coefficient. Results. A statistically significant predominance of intoxication symptoms was found in patients with acute simple bronchitis (p = 0.02), signs of respiratory failure (p < 0.001), and peripheral eosinophilia — in children with acute obstructive bronchitis (p = 0.02). In etiology, rhinovirus significantly prevailed in patients with bronchial obstruction, and RS virus prevailed in patients with acute simple bronchitis (p = 0.02). The cytokine profile of patients with acute obstructive bronchitis is characterized by a decrease in the levels of macrophage inflammatory proteins (p = 0.01) and IL-8 (p = 0.048). A prolonged course of montelukast in children with a positive API significantly reduces the severity of subsequent acute respiratory infections, reduces the frequency of bronchial obstruction and the risk of bronchial asthma (p < 0.001).Conclusion. Evaluation of the results of montelukast therapy demonstrated clinical efficacy in patients with a positive API index.

Montelukast and Mental Health In Children Before and After Black Box Warning

In March 2020, the U.S. Food and Drug Administration (FDA) required a Black Box Warning for montelukast due to serious mental health side effects. We hypothesized that the warning would lead to an overall decrease in reports of mental health symptoms and disorders related to montelukast use among pediatric patients.

The Effect of Montelukast in Children with Asthma Predictive Index Negative Episodic Viral Wheezing

Background: The effectiveness of montelukast for wheezing in young children is not clear. We aimed to evaluate whether the use of montelukast in the treatment of wheezing affects the number of attacks in children aged 1 to 6 years. Methods: This is a single center study. It was conducted between August 2019-2020. Children with aged 0-6 years old with a wheezing complaint who applied to the pediatric allergy and immunology outpatient clinic were included in the study. Modified asthma predictive index of the patients were evaluated. It was classified as Episodic Viral Wheezing (EVW) or Multiple Trigger Wheezing (MTW) based on the type of wheezing. Montelukast treatment was started and the number of attacks was checked during five months. Results: The total of 141 children who applied with wheezing complaints were included in the study. The majority of the patients were boys (n = 99). The mean age of the children was 4.2 ± 1.5 years. The median number of attacks before treatment was 2 (2-3). In 2.8% of the patients, eczema, in 12.8% of them, rhinitis and in 26.7% of them, elevated eosinophils were detected. IgE levels were 148.25 ± 279.20 IU/mL. According to the number of attacks before treatment, there was a significant decrease in the number of attacks in followup (p < 0.001). Conclusion: In this study, montelukast has been shown to reduce the number of EVW attacks and we believe montelukast may be a potential treatment option for EVW in preschool children.

Eosinophilic Gastroenteritis: An Unusual Disease of Gastrointestinal Tract

Eosinophilic gastroenteritis (EGE) is a rare gastrointestinal disease characterized by generalized abdominal pain, nausea, vomiting, diarrhea, gastrointestinal bleeding and weight loss. The etiology and pathogenesis are not well understood and mostly based on case reports. Clinical presentation may vary depending on sites and depth of involvement of the gastrointestinal tract. The diagnosis is usually confirmed by histology that shows eosinophilic infiltration and the absence of secondary cause of eosinophilia.The authors present a case report of a 47-year-old woman that was diagnosed with dyslipidemia, obesity and allergic rhinitis. She had no significant family history. She was admitted in internal medicine department with 2 weeks of abdominal pain, nausea, vomiting, diarrhea and weight loss (> 10%). Further study revealed increased eosinophil count, normocytic anemia, elevated erythrocyte sedimentation rate and normal Ig E levels. Digestive endoscopic study was performed, and multiple biopsy specimens showed moderate eosinophilic infiltration in stomach and duodenal mucosa.The patient was started on prednisolone, with clinical improvement. Follow-up go the patient twenty years after the beginning of this treatment showed stabilization of clinical symptoms and laboratory tests.So, eosinophilic gastroenteritis is characterized by three criteria - presence of gastrointestinal symptoms, histologic evidence of eosinophilic infiltration and exclusion of other causes of tissue eosinophilia. The treatment is based on the severity of symptoms. Corticosteroids are the mainstay of therapy, so the usual dose of prednisolone/prednisone is 20-40 mg daily for two weeks with tapering thereafter. In the literature, the use of montelukast and biologic agents have been reported.

Comparison of Effect of Levocetirizine or Montelukast Alone and in Combination on Symptoms of Allergic Rhinitis

Objective. To determine the effect of levocetirizine, montelukast and the combination of both the drugs on symptoms of allergic rhinitis. Methods. Seventy-five patients with allergic rhinitis were randomly studied prospectively for a period of two weeks divided into three groups receiving either levocetrizine or montelukast or combination of both. The outcomes were measured by a visual analogue score for nasal and eye symptom during day-time and night-time. Results. All the three regimens were equally effective in improving the day-time symptoms, like sneezing and rhinorrhea. There was also no difference in the control of night-time and eye symptoms among the regimens. Conclusions. Montelukast, levocetirizine and their combination is equally effective in controlling symptoms, of allergic rhinitis. Thus, use of montelukast alone would be cost-effective and do avoid adverse effects of levocetirizine in combination therapy

Prescription Patterns of Asthma Preventers Among Children and Adolescents Between Australia and South Korea.

Purpose: Inhaled Corticosteroids (ICSs) and oral Leukotriene Receptor Antagonists (LTRAs) are commonly prescribed asthma preventers, however, concerns have been raised as to whether montelukast (LTRA) is associated with an increase in occurrences of neuropsychiatric side effects in children. Our study was conducted to observe prescribing patterns of asthma preventers among paediatric patients specifically focusing on ICSs and LTRAs between Australia and South Korea to see intercountry differences in the use of these medicines. Materials and Methods: The Health Insurance Review and Assessment Paediatric Patients Sample dataset for South Korea and data provided by Services Australia were used in the study. Paediatric patients aged between 3 and 19 with more than one dispensing of an asthma preventer and at least one reliever between 1 Jan 2018 and 31 December 2018 were selected. Prevalence per 1,00,000 persons and standardised prevalence were estimated. Results: A total of 3,58,470 patients (2,04,270 from South Korea and 1,54,200 from Australia) were included in the study. A higher prevalence of ICS-based inhalers was seen in Australia with 80.1% compared to 13.5% in South Korea. In addition, Australia showed a stronger tendency of prescribing high dose ICS-based inhalers compared to South Korea with 22.9% vs. 4.9%. In contrast, use of LTRAs was more prevalent in South Korea with 57.6% while in Australia, montelukast was the only LTRA dispensed at a proportion of 18.9%. Moreover, 29.9% of xanthines which are orally available preventers, were prescribed more frequently in South Korea compared to Australia (0.1%). Conclusion: Australia showed a tendency of prescribing ICS-based preventers whereas South Korea exhibited a preference towards the oral LTRAs. Given the potential risk of neuropsychiatric side effects among paediatric patients with montelukast, reasons for the high use of montelukast in South Korea should be investigated further.

Opportunities for correction of individual links of the pathogenesis of allergic rhinitis and bronchial asthma with assessment of the quality of life of patients

Introduction. One of the antileukotriene drugs for the treatment of bronchial asthma and allergic rhinitis with and without polyposis is montelukast. The presented article presents the results of the analysis of the effectiveness, safety and impact on the quality of life of patients, the use of the singular, in various forms of allergic rhinitis and associated comorbid conditions.Aim of the study. To assess the impact on the quality of life of patients, the effectiveness and safety of the use of montelukast in the complex therapy of patients with allergic rhinitis and comorbid diseases.Materials and methods.A simple, blind, randomized, controlled clinical trial involved 97 patients divided into 4 groups: patients with moderate allergic rhinitis; allergic rhinitis of moderate severity and bronchial asthma; severe allergic rhinitis and bronchial asthma; severe allergic rhinitis, bronchial asthma and polypous rhinosinusitis. In parallel with the comparison of drug tolerability, safety and clinical symptoms (rhinorrhea, nasal congestion, itching, sneezing, bronchopulmonary manifestations), the quality of life was assessed using a special SNOT-22 questionnaire.Results. The use of the antileukotriene drug montelukast in the complex therapy of allergic rhinitis and related comorbid conditions significantly improved the clinical symptoms and quality of life of patients over the entire period of treatment in all groups. There was an increase in the suppression of leukotriene-mediated effects when using montelukast, more in the group of people with allergic rhinitis and bronchial asthma, such as symptoms of the allergic triad, mucus hypersecretion, bronchospasm, eosinophilia, increased vascular permeability, etc.Conclusion. In the treatment of patients with allergic rhinitis and morbid conditions, Singular has demonstrated an inhibitory effect on cysteinyl leukotrienes, high bioavailability, good tolerability and safety.

Neuropsychiatric reactions with the use of montelukast.

### What you need to know A 13 year old boy was started on 5 mg montelukast daily in addition to low dose inhaled corticosteroids to treat his asthma. Within a few days, his mother noted that he was constantly arguing and wanted to hit and kick other people. He had not shown this behaviour earlier. At the time of prescribing, their doctor had asked for any history of psychiatric illnesses in their family, which they had none. The doctor had advised her to observe the child and report any changes in behaviour after starting the drug. Montelukast, used in patients with asthma or allergic rhinitis, is associated with a risk of neuropsychiatric adverse reactions (see box 1). These are uncommon and usually mild but can be worrisome and affect quality of life for patients and their families. Rarely, serious adverse reactions such as depression and suicide have been reported, mostly with prolonged use.8 Neuropsychiatric symptoms may be attributed to normal behavioural changes in children or to other conditions. Failure to recognise these adverse drug reactions early can result in serious harm to patients and their families. Box 1 ### Regulatory approval and safety warningsRETURN TO TEXT

Efficacy of montelukast in the management of COVID-19: double blind randomized placebo controlled trial

Background: Objective of the study was to determine the efficacy of montelukast in reducing the severity of COVID-19 symptoms using a double blinded randomized controlled trial.Methods: Parallel, double-blinded randomized controlled trial (RCT) with placebo as comparison to montelukast. All patients above the age of 14 years both males and females, admitted with a diagnosis of mild or moderate COVID-19 (on the basis of a positive reverse transcriptase polymerase chain reaction (RT-PCR) report) at our facility during the study period from 01 September 2020-31 January 2021) and excluding those having adverse reaction to montelukast or those not willing to participate, and pregnant and lactating females. Patients in the intervention arm were given tablet montelukast 10 mg OD HS from the day of admission for 10 days. The patients in the placebo group were given an identical appearing placebo at bedtime for 10 days from the day of admission. The rest of the treatment was given as per the standard operating procedure (SOP) of the institute with minor adjustments as per the treating team’s judgement. Primary outcome was progression of the disease to severe grade and secondary outcomes were discharge on or before day 10 from admission, admission to ICU, need for mechanical ventilation and in-hospital mortality.Results: A total of 94 patients were enrolled for the study. 90 patients, 45 in each arm were included in the final analysis. The baseline characteristics of the two arms including age, sex, comorbidities, severity at admission and treatment given apart from montelukast or placebo, were comparable with respect to these variables. This study did not find any improvement in primary outcome of progression to severe disease and secondary outcomes of intensive care unit (ICU) admission, mortality or need of mechanical ventilation, discharge on or by day 10 with the use of montelukast as compared to placebo in mild to moderate cases of COVID-19.Conclusions: There was no difference in primary or secondary outcomes with the use of Montelukast compared to placebo.

Risk Factors Associated With Health Care Utilization in Preschool Recurrent Wheezers in a Tropical Environment.

Introduction: The severity of wheezing episodes is related with the need for health services, but the factors associated with health care utilization in preschool recurrent wheezers in underdeveloped regions are unclear.Objective: To evaluate the factors associated with health care utilization in preschool recurrent wheezers in Cartagena, Colombia.Methods: One hundred twenty-seven recurrent wheezers (age 2–6 years old) who were admitted to the emergency room (ER) due to wheezing in a Pediatric reference hospital in Cartagena were included. Children were evaluated by means of questionnaires and classified according to the number of ER visits, need for hospitalization and history of intensive care unit (ICU) admission due to wheezing within the last year. Total serum IgE and specific IgE to house dust mite allergens (HDM) were measured by ImmunoCAP® and allergen sensitization was evaluated by skin prick tests (SPT).Results: The maternal report of nocturnal cough without fever in their children increased the risk to have ≥5 ER visits in the last year due to wheezing. The use of montelukast was negatively associated with hospitalization, while a history of pneumonia and lack of tap water, increased the risk of hospitalization due to wheezing. A history of bronchiolitis, family history of asthma, cohabiting with two or more siblings, passive exposure to smoke and lack of sewage facilities increased the risk of ICU admission due to wheezing. The presence of atopy evaluated by SPT reactivity, total IgE levels or specific IgE to HDM were not associated with health care utilization. We also found that seroprevalence of positive IgE (≥0.35 kU/L) was 27% to B. tropicalis and 20.3% to D. pteronyssinus but the prevalence of positive IgE sensitization to these allergens was below 2% and 8% when evaluated by SPT, respectively.Conclusions: Poverty indicators are associated with ICU admission in a group of preschool recurrent wheezers and should be considered as aggravating factors for wheezing. These factors must be systematically assessed in the medical approach in underdeveloped regions in the tropics. Nocturnal cough without fever is a symptom associated with frequent ER visits while atopy was not associated with health care utilization in preschool recurrent wheezers.

Age-related evolution of bronchial asthma in pediatric practice and approaches to improving prognosis

The main high-risk group for a diagnosis of bronchial asthma (BA) are children with recurrent obstructive bronchitis, complicated by a widespread form of acute respiratory viral infections. Basic therapy of BA is aimed at suppressing inflammation of the bronchial wall. In addition to inhaled glucocorticosteroids, the antileukotriene drug montelukast has a proven anti-inflammatory effect. This article discusses published work on the effect of montelukast on inflammation biomarkers in real clinical practice and remodeling of the bronchial wall in the experiment. A comparative study of the clinical efficacy of an antileukotriene drug and inhaled glucocorticosteroids in patients of different age groups and asthma phenotypes is presented. The use of montelukast in children at high risk of developing BA, with an indication for allergic rhinitis, is discussed. Presented current information on the risk of psychiatric AE against the background of using an antileukotriene drug. Literature review is illustrated by our own observation: a cohort of 127 patients was formed on the basis of the dispensary group of the City Allergy Cabinet of the Children’s City Polyclinic No. 44 in St. Petersburg in 2018, a prospective observation was conducted, which lasted 2 years. The inclusion criteria were age of 5 years to 5 years 11 months (5 ± 0.5 years) and an established diagnosis of mild BA. The patients were followed up for 2 years with evaluation of the change of basic therapy, control of the disease and functional indices achieved with therapy with the original drug montelukast. This observation showed high clinical efficacy of montelukast monotherapy in the group of preschool-age patients, which was expressed by a significant proportion of patients who had no exacerbations of BA for a year, a high score on the Asthma Control Test, statistically insignificant increase in forсed expiratory volume in 1 second after bronchodilator. Today Montelukast is a safe, effective and widely prescribed component of therapeutic regimen in patients with varying degrees of severity of bronchial asthma over the age of 2 years.

Montelukast and Coronavirus Disease 2019: A Scoping Review

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.

Successful use of montelukast in eosinophilic gastroenteritis: a case report and a literature review

BackgroundEosinophilic gastrointestinal disorders, also known as eosinophilic gastroenteritis, are rare inflammatory conditions characterized by eosinophilic infiltration of different parts of the gastrointestinal tract, along with peripheral eosinophilia in most cases. Other known causes for gut eosinophilic infiltration must be excluded to confirm the diagnosis of eosinophilic gastroenteritis. Symptoms of the disorder depend on the affected gastrointestinal tract segment and depth of involvement. Treatment includes systemic glucocorticoids and/or dietary therapy with an empiric elimination diet. Second line therapies include the leukotriene receptor antagonist montelukast, and other anti-allergy drugs such as mast cell stabilizers (including cromolyn and the H1-antihistamine ketotifen), suplatast tosilate which is a selective Th-2 cytokines (IL-4 and IL-5) inhibitor, and the monoclonal anti-IgE antibody omalizumab. We report a case of eosinophilic gastroenteritis who was successfully treated and achieved remission with montelukast as an initial monotherapy. Upon extensive literature review, this represents the second reported adult case of eosinophilic gastroenteritis who responds to montelukast alone as a first line therapy.Case presentationA 49-year-old female presented with recurrent abdominal pain, vomiting, diarrhea and unexplained eosinophilia. She was diagnosed with eosinophilic gastroenteritis and was successfully treated with montelukast monotherapy. After 7 days of therapy, the patient responded well and had complete resolution of her gastrointestinal symptoms and peripheral eosinophilia. Patient remained in remission on follow-up after 12 months. We reviewed the literature for leukotriene antagonist use in the treatment of eosinophilic gastroenteritis and included the cases treated with the leukotriene antagonist montelukast as an initial therapy or as a second line therapy for refractory disease.ConclusionMontelukast may be an effective treatment for eosinophilic gastroenteritis, either alone or in combination with systemic steroids or ketotifen. Our patient is the second reported adult case of eosinophilic gastroenteritis who responded to montelukast alone as a first line therapy. Further studies and clinical trials are required to confirm efficacy compared to standard therapy.

Activity and Safety of Daratumumab Monotheray in Patients with Relapsed and Refractory Multiple Myeloma Requiring Dialysis: Preliminary Results of Spanish, Retrospective, Multicenter Trial

Introduction:Daratumumab (DARA) is a first-in-class, fully human IgG1 kappa MoAb that targets to a unique CD38 epitope in plasma cells and has been recently approved for patients with relapsed and refractory myeloma multiple (RRMM) that have received ≥3 prior lines of therapy including proteasome (IP) inhibitor and an immunomodulatory agent (IMiD). Based on pharmacokinetic analysis it is not necessary to adjust the dosage of DARA in patients with creatinine clearance 30-60 mL/min. However there are no published data available in patients with RRMM requiring dialysis.Aims:The objective of this retrospective, multicenter, open-label study is to report the safety and efficacy of DARA in patients with RRMM with end-stage renal failure requiring dialysis.Methods:The eligibility criteria to participate in this study included patients ≥18 years, documented progression of MM by IMWG criteria following the most recent therapy including a PI and an IMID or double-refractory to a PI and an IMID, ECOG performance status score 0-2, absence of chronic obstructive pulmonary disease or persistent asthma, and no prior exposure to anti-CD38 antibody therapy. Patients received DARA at the standard dose (16 mg/kg IV weekly for 8 weeks, then every 2 weeks for 16 weeks, and then every 4 weeks) until disease progression or unacceptable toxicity. Pre-medications with antihistamines, antipyretics and corticosteroids and post-infusion medications with corticosteroids were administered including the use of montelukast. Anti-viral prophylaxis was considered. Data on anti-MM activity and adverse events (AEs) including grade 3-4 AEs and infusion related reactions (IRRs) were collected.Results:The study, including eight Spanish centers is ongoing and we report here the preliminary results of the first eight patients included from January 2017 to July, 2017. There were 4 male and 4 female with a median age at the time of the beginning of DARA therapy of 63 years (range, 52 -71) and with a median time from diagnosis to initiation of DARA of 4.61 years (range, 1 - 6). MM was Bence Jones in 3 patients, IgA type in 2, IgD in 2, and IgG in 1 patient. Distribution of disease according to the International Stage System was: 5 patients were in stage II, 2 patients were in stage I, and the remaining patient was in stage III. The median number (range) of prior lines of therapy was 4 (2 -7); 37% of patients received >3 prior lines. All patients were double refractory to both a PI and IMiD, 2 patients were also refractory to carfilzomib, and 1 patient was triple refractory including pomalidomide. Four patients had received previous stem-cell transplant (3 autologous and 1 allogeneic).At the time of diagnosis, 2 out of the 8 patients had high-risk cytogenetics [1 patient with add(1q) and 1 with del(17p)]. Detailed patient characteristics with respect to baseline clinical features and laboratory parameters are provided in Table 1. In 6 patients, end-stage renal failure was myeloma-related (2 patients with acute renal injury at time of diagnosis), while the remaining 2 patients were already on dialysis at the time of MM diagnosis. The median time from the diagnosis of MM and the beginning of the dialysis was 5 years (range, 1-6). The median time on dialysis at study entry was 24 months (range, 8-97).The median (range) number of cycles of DARA administered was 4 (1-7). The overall response rate and the clinical benefit rate (stable disease or better) was 37.5% (1 VGPR and 2 PR) and 62.5%, respectively. No patient has become dialysis independent.With a median follow-up of 4 months, 2 patients have died because of disease progression (1 patient) and due to myeloma-related causes (1 patient) and one patient suffered disease progression. The remaining 5 patients are still alive with ongoing DARA treatment. Regarding safety, no patient discontinued treatment due to AEs and the most common non-hematological AEs included grade 1 or 2 IRRs observed only during the first cycle, (4 patients). Anemia (n=2, grade 2 and 3), thrombocytopenia (n=2, grade 1 and 2), and neutropenia (n=2, grade 1 and 4), were the hematological AEs most frequently observed.Conclusions:Although still preliminary, our data suggest that DARA monotherapy is an efficacious and safe therapeutic option for patients with RRMM and end-stage renal failure including dialysis. AE profile seems to be similar to that previously observed in patients with normal or moderately impaired renal function. [Display omitted] Disclosuresde la Rubia:Celgene: Other: Honoraria; Janssen: Other: Honoraria; Amgen: Other: Honoraria.

Is it always easy for children with mild asthma?

Bronchial asthma is the most common chronic disease of children, the worst way is their quality of life. Compliance in the treatment of children is very important, since the actual effect of a drug is determined by both the effective drugs and patient adherence and correct use. A relevant test is the use of mild asthma, which is able to control bronchial hyperreactivity associated with exercise, cold air, and other nonspecific irritants (smoke, odors, etc.). Planning of baseline therapy for children with mild asthma aged 5 years old and younger is particularly problematic for paediatricians due to high incidences of acute respiratory viral diseases and viral-induced exacerbations of bronchial asthma among them. In these children, allergen-specific immunotherapy, long-acting B-agonists, the use of many metered-dose inhaled glucocorticosteroids. are not recommended.Montelukast, an oral antileukotriene drug, has advantages in the treatment of children with mild asthma with virus-induced exacerbations, with asthma of physical exertion and severe bronchial hyperreactivity, especially when combined with allergic rhinitis, as well as in special clinical cases, when parents refuse to use ICS for treatment children with mild asthma or inability to use them for some reason. The use of montelukast for mild asthma in children in the current context of the COVID-19 pandemic also has advantages that pediatricians can use when observing these children in the pediatric area, taking into account contraindications.

A Boxed Warning for Montelukast: The FDA Perspective

The U.S. Food and Drug Administration (FDA) became aware of postmarketing reports of neuropsychiatric adverse events with Singulair (montelukast) use in 2007. Over the years, the FDA has conducted reviews of the clinical trial safety data, focused analyses of postmarketing reports, and reviews of the published literature. These activities have resulted in successive labeling updates and public communications. However, there has been continued concern among stakeholders about the risk of neuropsychiatric events and the lack of awareness among prescribers and patients/caregivers. On the basis of these concerns, the FDA embarked on another comprehensive review and also conducted a new observational study using claims data in the Sentinel Distributed Database. In September 2019, the FDA held a public Advisory Committee meeting to discuss its review and solicit recommendations from the panel regarding labeling and communication strategies. After careful consideration of the available data and feedback received during the FDA Advisory Committee meeting, the FDA required a boxed warning and a revision specifically for the allergic rhinitis indication to reserve use of montelukast to patients who have an inadequate response or intolerance to alternative therapies. Based on benefit-risk considerations, the asthma indication was not changed. To provide insight into the process and rationale for the required labeling changes, we provide an overview of the decision-making framework we used.

Montelukast in hospitalized patients diagnosed with COVID-19

Objective Several therapeutic agents have been assessed for the treatment of COVID-19, but few approaches have been proven efficacious. Because leukotriene receptor antagonists, such as montelukast have been shown to reduce both cytokine release and lung inflammation in preclinical models of viral influenza and acute respiratory distress syndrome, we hypothesized that therapy with montelukast could be used to treat COVID-19. The objective of this study was to determine if montelukast treatment would reduce the rate of clinical deterioration as measured by the COVID-19 Ordinal Scale. Methods We performed a retrospective analysis of COVID-19 confirmed hospitalized patients treated with or without montelukast. We used “clinical deterioration” as the primary endpoint, a binary outcome defined as any increase in the Ordinal Scale value from Day 1 to Day 3 of the hospital stay, as these data were uniformly available for all admitted patients before hospital discharge. Rates of clinical deterioration between the montelukast and non-montelukast groups were compared using the Fisher’s exact test. Univariate logistic regression was also used to assess the association between montelukast use and clinical deterioration. A total of 92 patients were analyzed, 30 who received montelukast at the discretion of the treating physician and 62 patients who did not receive montelukast. Results Patients receiving montelukast experienced significantly fewer events of clinical deterioration compared with patients not receiving montelukast (10% vs 32%, p = 0.022). Our findings suggest that montelukast associates with a reduction in clinical deterioration for COVID-19 confirmed patients as measured on the COVID-19 Ordinal Scale. Conclusions Hospitalized COVID-19 patients treated with montelukast had fewer events of clinical deterioration, indicating that this treatment may have clinical activity. While this retrospective study highlights a potential pathway for COVID-19 treatment, this hypothesis requires further study by prospective studies.

Safety of anti-inflammatory drugs in children with asthma.

Inhaled corticosteroids (ICS) are widely used as the first-line treatment of asthma. When the disease is not controlled by standard doses of ICS, other anti-inflammatory drugs should be considered. The aim of this report is to review the main adverse events induced by anti-inflammatory drugs in children with asthma and discuss possible actions to prevent or mitigate these effects. Proper interpretation of ICS safety studies requires knowledge of the pharmaceutical properties and delivery device systems of the different ICS available. Genetic variants affecting susceptibility to corticosteroid-induced adrenal suppression were found in children and adults who use ICS to treat their asthma. There is evidence of the association between montelukast use and neuropsychiatric events. Benefits of ICS, properly prescribed and used, outweigh their potential adverse effects. There is substantial evidence that the combination of ICS with long-acting beta2 agonists is safe for asthmatic children. Awareness of the potential risks of neuropsychiatric events in children taking montelukast should inform the clinicians' prescribing practices. Omalizumab is generally well-tolerated, but the evidence on the safety of other biologic agents in children is scanty. The risk of systemic adverse events with anti-inflammatory drugs must be balanced against the risks of uncontrolled asthma and/or frequent oral steroid use.

Practice, self-confidence and understanding of pediatric obstructive sleep apnea survey among pediatricians.

Pediatricians play an important role in the screening, diagnosis and management of childhood obstructive sleep apnea (OSA). This study used a questionnaire to explore the knowledge, self-confidence and general practices of childhood OSA among Thai pediatricians. This was a descriptive cross-sectional survey study, using a newly developed questionnaire; including: 21 knowledge items, 4 self-confidence items, questions regarding OSA screening, number of OSA cases per month and OSA management. A total of 307, convenient pediatricians; from different types of hospitals across all regions of Thailand, participated in this study. The median, total knowledge score was 19 (range 14‒21). Two-thirds of the respondents felt confident/extremely confident in their ability to identify and manage children with OSA. The average number of OSA cases reported by pediatricians was 5.9 cases per month. During a general medical check-up, 86.6% of the respondents did not routinely ask about OSA symptoms. Significant odds ratios (ORs) for the use of montelukast, as the first-line drug for OSA in young children, were observed in pediatric allergists and pulmonologists (adjusted OR 2.58, 95% CI 1.11-6.01 and adjusted OR 2.20, 95% CI 1.2-4.02) (P = 0.008), respectively, compared to general pediatricians and other sub-specialties. Pediatricians had a high level of overall OSA knowledge, and good self-confidence in identifying and managing children with OSA. However, a low recognition rate and unawareness of OSA screening were observed.

The Leukotriene Receptor Antagonist Montelukast as a Potential COVID-19 Therapeutic.

The emergence and global impact of COVID-19 has focused the scientific and medical community on the pivotal influential role of respiratory viruses as causes of severe pneumonia, on the understanding of the underlying pathomechanisms, and on potential treatment for COVID-19. The latter concentrates on four different strategies: (i) antiviral treatments to limit the entry of the virus into the cell and its propagation, (ii) anti-inflammatory treatment to reduce the impact of COVID-19 associated inflammation and cytokine storm, (iii) treatment using cardiovascular medication to reduce COVID-19 associated thrombosis and vascular damage, and (iv) treatment to reduce the COVID-19 associated lung injury. Ideally, effective COVID-19 treatment should target as many of these mechanisms as possible arguing for the search of common denominators as potential drug targets. Leukotrienes and their receptors qualify as such targets: they are lipid mediators of inflammation and tissue damage and well-established targets in respiratory diseases like asthma. Besides their role in inflammation, they are involved in various other aspects of lung pathologies like vascular damage, thrombosis, and fibrotic response, in brain and retinal damages, and in cardiovascular disease. In consequence, leukotriene receptor antagonists might be potential candidates for COVID-19 therapeutics. This review summarizes the current knowledge on the potential involvement of leukotrienes in COVID-19, and the rational for the use of the leukotriene receptor antagonist montelukast as a COVID-19 therapeutic.