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.

A review of the therapeutic potential and possible mechanism of Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic stem cell transplantationLung and bone marrow transplantation are therapeutic modalities in chronic diseases of the lungs and the blood, 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 for BOS in lung transplant and graft-versus-host disease (GVHD) patients involving many immune components have been recognized. Cysteinyl leukotrienes are products of plasma membrane phospholipids that increase smooth muscle contraction, microvascular permeability, and airway mucus secretion. Montelukast is a highly selective cysteinyl leukotriene receptor blocker demonstrated to exert anti-inflammatory and anti-fibrotic effects. One area of interest for the use of montelukast is in lung transplant- or GVHD-associated BOS. In this article, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS. Finally, the possible relationship between cysteinyl leukotriene inhibition and BOS improvement will be discussed.

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.

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.

BACKGROUND: Montelukast, a selective leukotriene receptor antagonist, is a commonly prescribed allergy medication but its potential association with neuropsychiatric adverse events is concerning. OBJECTIVE: 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. METHODS: 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 ß2-agonists with montelukast or pranlukast and those not using leukotriene receptor antagonists (control group). RESULTS: 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. CONCLUSIONS: 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.

Montelukast influence on kidney in experimental induced diabetes mellitus.

Leukotrienes are important icosanoids group involved in a lot of normal and pathological states. Montelukast (MK) is a selective cysteinyl leukotriene receptor (Cys LT1) antagonist. Purpose. The purpose of the study is to observe the influence of MK on renal damage caused by experimental diabetes in rats. The experiment was carried out on four groups of adult male Wistar rats. Lot I was a witness and received 1.5ml of physiological saline ip. in unique dose on the first day of the experiment. Lots II and III have been caused experimental diabetes by streptozotocin (STZ) administration of 60mg/kg ip. in the unique dose. Lot III also received MK daily 10mg/kg/day daily 8weeks.Lot IV received only MK 10mg/kg/day daily 8 weeks. After eight weeks all animals were anesthetized and were sacrificed. The following pathological modifications were observed: tubular injury, glomerular hypertrophy and lesions, leukocytes infiltration. Obtained data showed that MK has significantly reduced the intensity of glomerular lesions (score 3.50+/-0.21 in STZ lot vs. 2.50+/-0.17 in STZ+MK lot p<0.01) and tubular damages. Renal interstitial leukocyte infiltration in animals with diabetes has been also reduced by MK. MK has a partially protective action against the lesions produced by experimental diabetes.

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.

Efficacy and safety of intravenous leukotriene receptor antagonists in acute asthma.

The incidence of bronchial asthma has increased substantially since recent decades in both children and adults. Moreover, the number of patients presenting with asthma exacerbation to the emergency department has also increased in several countries. Leukotrienes are inflammatory mediators that play an important role in bronchial asthma exacerbation. Leukotriene receptor antagonists reduce asthma exacerbation in chronic asthma; moreover, the current guidelines for asthma management recommend the use of oral leukotriene receptor antagonists for asthma control and reduce further exacerbation. However, data on the use of intravenous leukotriene receptor antagonists during acute asthma exacerbation are scarce. Nevertheless, currently available data revealed a trend of significant improvement of acute asthma and rapid reversal of airflow obstruction when administered during an acute asthma attack. This review aims to summarize currently available data on the use of intravenous leukotriene receptor antagonists in adult patients with acute asthma exacerbation.

New and promising type of leukotriene B4 (LTB4) antagonists based on the 1,4-benzodioxine structure.

New leukotriene B4 (LTB4) antagonists have been synthesized that can be considered as potential anti-inflammatory drugs. Structures containing the dioxygenated nucleus of 1,4-benzodioxine constitute a potential group of leukotriene B4 (LTB4) antagonists. The objective of this study was to access efficient and selective LTB4 antagonists as a way to elucidate the role of LTB4 in inflammatory processes and therefore allow the development of new types of structures based on 1,4-benzodioxine. Forty-one new 1,4-benzodioxine molecules substituted at different positions of the heterocyclic nucleus were synthesized to determine the minimum structural requirements by studying structure-activity relationships. Eighteen of them were tested in vitro and in vivo for their anti-inflammatory activity related to the antagonist character of LTB4. Pharmacological tests have shown satisfactory in vitro activity for compounds 24b, 24c and 24e with IC50's of 288, 439, 477 nM respectively. The results of the in vivo tests, carried out with the compound that presented greater activity in the in vitro tests 24b, have shown significant anti-inflammatory properties.

Psychiatric Adverse Effects of Montelukast-A Nationwide Cohort Study.

BACKGROUND: Recent observational studies suggest that the leukotriene receptor antagonist montelukast may have neuropsychiatric adverse effects; however, results are conflicting. OBJECTIVE: To assess whether montelukast exposure in adults with asthma is associated with onset of neuropsychiatric adverse events using data from the Danish nationwide health registers. METHODS: Individuals 18 years old or older with either 1 or more prescription redemption of inhaled corticosteroids or with at least 1 hospital contact with asthma as the main diagnosis between January 1, 2011, and December 31, 2018, were included. Montelukast exposure was assessed as a time-dependent variable. The 2 outcomes of interest were use of neuropsychiatric medicine including antidepressants, antipsychotics, anxiolytics, lithium, and medication used for attention-deficit/hyperactivity disorder (outcome 1), and hospital contacts with a neuropsychiatric diagnosis (outcome 2), within 90 days of exposure to montelukast. RESULTS: Initiation of montelukast was significantly associated with outcome 1: use of neuropsychiatric medicine (hazard ratio [95% confidence interval]) 1.14 [1.08-1.20]; P < .0001). In the assessment of outcome 2: hospital contacts with a neuropsychiatric diagnosis, a significant risk associated with montelukast initiation was found only in the youngest age groups (hazard ratio [95% confidence interval] 1.28 [1.12-1.47], P < .001 and 1.16 [1.02-1.31]; P < .05, for age group 18-29 y and 30-44 y, respectively). Age-stratified analyses showed that the risk of both outcomes increased with decreasing age, with the highest risk seen in patients aged 18 to 29 years. CONCLUSIONS: Among younger individuals, montelukast use was significantly associated with an increased risk of neuropsychiatric events such as use of neuropsychiatric medicine and hospital treatment. Clinicians should increase awareness of such adverse effects when prescribing montelukast.

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.

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.

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.

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)