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Allergologia Et Immunopathologia 2022There is insufficient clarity regarding whether or not drugs used in asthma cause behavioral problems in children.
BACKGROUND
There is insufficient clarity regarding whether or not drugs used in asthma cause behavioral problems in children.
METHODS
A total of 155 individuals, categorized into an asthma group (n = 95) and a control group (n = 60), were enrolled in the current prospective controlled study. The asthma group consisted of patients receiving treatment (inhaled corticosteroids [ICS] or montelukast) for at least 1 month. Check Behavior Checklist (CBCL) for ages 1.5-5 scores for the asthma and controls were compared. The asthma group was divided into two subgroups based on prophylactic therapy received, ICS and montelukast, and these groups' CBCL scores were also compared.
RESULTS
The asthma group consisted of 95 children (ICS subgroup 45, montelukast subgroup 50) and the healthy control group of 60 cases. The mean total CBCL score was higher in the asthma group than in the control group (42 vs 32, respectively, P = 0.001). Internalization and externalization scores were also higher in the asthma group compared to the control group (P = 0.004 and P = 0.005, respectively). No significant difference was determined in terms of CBCL scores between the ICS and montelukast groups (P = 0.3). Montelukast was discontinued in one asthmatic child due to hallucination.
CONCLUSION
This study determined a higher rate of behavioral problems in preschool children with asthma compared to healthy children. In contrast to other studies in the literature, we determined no difference in terms of total CBCL, and internalization and externalization scores of children with asthma who received ICS and montelukast. Nevertheless, it should be kept in mind that montelukast may cause serious neuropsychiatric events such as hallucination.
Topics: Acetates; Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Child, Preschool; Cyclopropanes; Drug Therapy, Combination; Hallucinations; Humans; Infant; Problem Behavior; Quinolines; Sulfides
PubMed: 34965642
DOI: 10.15586/aei.v50i1.312 -
BMJ Open Jan 2022National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of...
BACKGROUND
National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of montelukast in children and young people (CYP).
OBJECTIVE
To systematically review evidence regarding deprescribing montelukast in CYP with established asthma.
DESIGN
Systematic review.
DATA SOURCES
Embase, Medline, PubMed and CINAHL were searched up to October 2020.
STUDY SELECTION
Eligible studies contained patients aged 0-18 years with a diagnosis of asthma, who had been administering montelukast before it was withdrawn. All reasons for withdrawal were included.
RESULTS
The search identified 197 papers. After deduplication, five papers were included (three randomised control studies and two cohort studies). Four studies observed the impact of montelukast withdrawal for 2 weeks, and one study for 8 weeks. The impact of withdrawal was measured in the studies using a combination of lung tests (eg, forced expiratory volume in 1 s (FEV1), fractional exhaled nitric oxide (FeNO)), asthma scoring methods and exercise challenges. Of the 17 domains in the Core Outcome Set for Clinical Trials in Childhood Asthma, eight outcomes were measured in at least one of the five studies, with all five studies measuring the outcome of 'Lung Function'. No significant differences were found between the montelukast and placebo groups following montelukast withdrawal. Significant differences between the comparator points within the test group were found in nine outcomes across four studies; FEV1/forced vital capacity, FEV1, forced expiratory flows (25%-75%), asthma score (study specific), maximum % fall in FEV1 and time to recovery (post exercise) significantly decreased whereas FEV1/bronchodilator response, FeNO and eNO significantly increased.
CONCLUSION
Only limited, contradictory and short-term effects of deprescribing montelukast in CYP with established asthma are presented in literature. Definitive studies determining clinical stability, and impact of deprescribing montelukast in CYP are imperative to improve the safety of asthma treatment in CYP.
PROSPERO REGISTRATION NUMBER
CRD42020213971.
Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Cyclopropanes; Deprescriptions; Forced Expiratory Volume; Humans; Infant; Infant, Newborn; Quinolines; Sulfides
PubMed: 35105629
DOI: 10.1136/bmjopen-2021-053112 -
Life Sciences Jul 2023Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1) that protects against inflammation and oxidative stress. However, the function of montelukast...
Montelukast prevents mice against carbon tetrachloride- and methionine-choline deficient diet-induced liver fibrosis: Reducing hepatic stellate cell activation and inflammation.
AIMS
Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1) that protects against inflammation and oxidative stress. However, the function of montelukast in liver fibrosis remains unknown. In this study, we examined whether the pharmacological inhibition of CysLTR1 could protect mice against hepatic fibrosis.
MATERIALS AND METHODS
Carbon tetrachloride (CCl) and methionine-choline deficient (MCD) diet models were used in this study. The expression of CysLTR1 in liver were detected by RT-qPCR and Western blot analysis. Liver hydroxyproline levels, fibrotic genes expression, serum biochemical indexes and inflammatory factors were used to evaluate the effect of montelukast on liver fibrosis, injury, and inflammation. In vitro, we used the RT-qPCR and Western blot analysis to assess CysLTR1 in mouse primary hepatic stellate cell (HSC) and human LX-2 cell line. The role of montelukast on HSC activation and the underlying mechaisms were determined using RT-qPCR analysis, Western blot and immunostaining assays.
KEY FINDINGS
Chronic stimulation from CCl and MCD diet upregulated the mRNA and protein levels of CysLTR1 in the liver. Pharmacological inhibition of CysLTR1 by montelukast ameliorated liver inflammation and fibrosis in both models. Mechanistically, montelukast suppressed HSC activation by targeting the TGFβ/Smad pathway in vitro. The hepatoprotective effect of montelukast was also associated with reduced liver injury and inflammation.
SIGNIFICANCE
Montelukast suppressed CCl- and MCD-induced chronic hepatic inflammation and liver fibrosis. CysLTR1 might be a therapeutic target for treating liver fibrosis.
Topics: Mice; Humans; Animals; Carbon Tetrachloride; Methionine; Hepatic Stellate Cells; Signal Transduction; Liver Cirrhosis; Liver; Fibrosis; Racemethionine; Inflammation; Diet; Transforming Growth Factor beta1
PubMed: 37178864
DOI: 10.1016/j.lfs.2023.121772 -
Life Sciences Sep 2022Montelukast, a selective antagonist of type 1 cysteinyl-leukotriene receptors, has antioxidant and anti-inflammatory abilities. This study aimed to explore its...
AIMS
Montelukast, a selective antagonist of type 1 cysteinyl-leukotriene receptors, has antioxidant and anti-inflammatory abilities. This study aimed to explore its hepatoprotective impact against CCl-induced hepatotoxicity compared to a standard hepatoprotective agent, silymarin.
MAIN METHODS
Twenty-four albino mice were used in this study, CCl (1 mL/kg of 1:1 v/v CCl:olive oil) was singly injected in mice, and montelukast was administered in a dose of 10 mg/kg.
KEY FINDINGS
Results revealed that montelukast significantly improved CCl-induced alterations in both structure and function of the liver, verified respectively through histopathology and by the reduced levels of ALT, AST, ALP, and GGT upon comparison with CCl. Also, montelukast prevented the induction of oxidative stress via decreasing hepatic MDA content and enhancing GSH levels. Moreover, montelukast produced a profound decrease in the levels of hepatic NLRP3 and its adaptor protein, ASC, and a reduction in the pro-inflammatory markers, NF-κB, IL-1β, TNF-α, and IL-6. In addition, montelukast markedly reduced liver fibrosis, as illustrated by Masson Trichrome, and the decreased hepatic levels of TGF-β and α-SMA. Furthermore, montelukast efficiently decreased apoptosis as manifested by the decreased hepatic level of Caspase 3.
SIGNIFICANCE
Montelukast protected against CCl-induced hepatotoxicity via exerting antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic effects.
Topics: Acetates; Animals; Antioxidants; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Cyclopropanes; Inflammasomes; Liver; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Quinolines; Sulfides
PubMed: 35690106
DOI: 10.1016/j.lfs.2022.120707 -
International Immunopharmacology Feb 2022Levocetirizine, a third-generation antihistamine, and montelukast, a leukotriene receptor antagonist, exhibit remarkable synergistic anti-inflammatory activity across a...
Levocetirizine, a third-generation antihistamine, and montelukast, a leukotriene receptor antagonist, exhibit remarkable synergistic anti-inflammatory activity across a spectrum of signaling proteins, cell adhesion molecules, and leukocytes. By targeting cellular protein activity, they are uniquely positioned to treat the symptoms of COVID-19. Clinical data to date with an associated six-month follow-up, suggests the combination therapy may prevent the progression of the disease from mild to moderate to severe, as well as prevent/treat many of the aspects of 'Long COVID,' thereby cost effectively reducing both morbidity and mortality. To investigate patient outcomes, 53 consecutive COVID-19 test (+) cases (ages 3-90) from a well-established, single-center practice in Boston, Massachusetts, between March - November 2020, were treated with levocetirizine and montelukast in addition to then existing protocols [2]. The data set was retrospectively reviewed. Thirty-four cases were considered mild (64%), 17 moderate (32%), and 2 (4%) severe. Several patients presented with significant comorbidities (obesity: n = 22, 41%; diabetes: n = 10, 19%; hypertension: n = 24, 45%). Among the cohort there were no exclusions, no intubations, and no deaths. The pilot study in Massachusetts encompassed the first COVID-19 wave which peaked on April 23, 2020 as well as the ascending portion of the second wave in the fall. During this period the average weekly COVID-19 case mortality rate (confirmed deaths/confirmed cases) varied considerably between 1 and 7.5% [37]. FDA has approved a multicenter, randomized, placebo-controlled, Phase 2 clinical trial design, replete with electronic diaries and laboratory metrics to explore scientific questions not addressed herein.
Topics: Acetates; Adolescent; Adult; Aged; Aged, 80 and over; Cetirizine; Child; Child, Preschool; Cyclopropanes; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Retrospective Studies; SARS-CoV-2; Sulfides; Treatment Outcome; Young Adult; COVID-19 Drug Treatment
PubMed: 34942461
DOI: 10.1016/j.intimp.2021.108412 -
Asian Pacific Journal of Allergy and... Mar 2022Leukotriene receptor antagonists are recommended to treat asthma and allergic rhinitis. Although they had been used for a long time, recent studies have reported...
BACKGROUND
Leukotriene receptor antagonists are recommended to treat asthma and allergic rhinitis. Although they had been used for a long time, recent studies have reported neuropsychiatric adverse drug reactions are associated with montelukast.
OBJECTIVE
This study analyzed the adverse drug reactions of montelukast and pranlukast, which are the two most frequently prescribed leukotriene receptor antagonists, respectively in Korea.
METHODS
This study retrospectively reviewed ADRs of 5,426 montelukast and 1,146 pranlukast reported in the Korea Adverse Event Reporting System between January 2014 and December 2018.
RESULTS
When both drugs are classified by system organ class, the most adverse drug reactions were related to the gastro-intestinal system, followed by psychiatric events. The reported adverse drug reactions for both drugs were more common in women, and the ratio of adverse drug reactions to prescriptions was highest in the elderly. Women aged 19 to 64 years reported more than twice as many adverse drug reactions than men of the same age, and more than 5 times in insomnia.
CONCLUSIONS
When prescribing montelukast and pranlukast, attention would need to digestive and sleep disorders, especially women aged 19 to 64. After prescribing montelukast, physicians would need to pay more attention to agitation (5/396378 vs 0/82475), bad or vivid dreams (6/396378 vs 0/82475), anxiety (11/396378 vs 0/82475), depression (14/396378 vs 1/82475), tremor (53/396378 vs 7/82475), irritability (5/396378 vs 1/82475), insomnia (159/396378 vs 25/82475), and headache (68/396378 vs 10/82475), compared to when prescribing pranlukast. Further prospective research needs to elucidate the relationship between neuropsychiatric events and montelukast.
PubMed: 35278057
DOI: 10.12932/AP-030821-1202 -
Sleep Medicine Feb 2021The efficacy and safety of montelukast in children with obstructive sleep apnea (OSA) remain controversial. Therefore, the aims of this systemic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The efficacy and safety of montelukast in children with obstructive sleep apnea (OSA) remain controversial. Therefore, the aims of this systemic review and meta-analysis are to verify this issue and further provide reference for clinical practice.
METHODS
Seven databases were searched for randomized controlled trials (RCTs) up to September 30, 2019. The literature screening and data extraction were performed by two independent researchers. Adverse reactions from trials were also recorded. Meta-analysis was performed and analyzed heterogeneity. Methodological and evidence quality were followed by to evaluate according to Cochrane handbook.
RESULTS
A total of 4 RCTs including 305 children with mild to moderate OSA were involved. Compared with placebo, we found that oral montelukast (OM) significantly improved polysomnography (PSG) monitoring parameters, typical and relevant symptoms including snoring and mouth breathing, and adenoid morphology in children with OSA. When compared with routine drugs, not only PSG monitoring parameters and adenoid morphology, but also sleep-disordered breathing (SDB)-related questionnaire scores were improved in patients with OSA treated by combination of OM and routine drugs. In addition, compared with single nasal spray of mometasone furoate, the present study also showed that OM combined with nasal spray of mometasone furoate significantly improved PSG monitoring parameters, symptoms of snoring and mouth breathing and reduced tonsil morphology in pediatric OSA. In terms of treatment safety, one study reported adverse reactions of OM such as headache, nausea and vomiting, while no adverse events were reported after OM treatment in another study.
CONCLUSION
As a classic leukotriene receptor antagonist, montelukast can be used to treat children with mild to moderate OSA in the short term and improve clinical characteristics. The promotion and application of OM in clinic is considered to be a noninvasive option to avoid surgical treatment.
Topics: Acetates; Adenoids; Child; Cyclopropanes; Humans; Quinolines; Sleep Apnea, Obstructive; Sulfides
PubMed: 33465554
DOI: 10.1016/j.sleep.2020.11.009 -
Journal of Thoracic Disease Nov 2021Outcomes after lung transplantation are limited by chronic lung allograft dysfunction (CLAD). The incidence of CLAD is high, and its clinical course tends to be... (Review)
Review
Outcomes after lung transplantation are limited by chronic lung allograft dysfunction (CLAD). The incidence of CLAD is high, and its clinical course tends to be progressive over time, culminating in graft failure and death. Indeed, CLAD is the leading cause of death beyond the first year after lung transplantation. Therapy for CLAD has been limited by a lack of high-quality studies to guide management. In this review, we will discuss the diagnosis of CLAD in light of the recent changes to definitions and will discuss the current clinical evidence available for treatment. Recently, the diagnosis of CLAD has been subdivided into bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). The current evidence for treatment of CLAD mainly revolves around treatment of BOS with more limited data existing for RAS. The best supported treatment to date for CLAD is the macrolide antibiotic azithromycin which has been associated with a small improvement in lung function in a minority of patients. Other therapies that have more limited data include switching immunosuppression from cyclosporine to tacrolimus, fundoplication for gastroesophageal reflux, montelukast, extracorporeal photopheresis (ECP), aerosolized cyclosporine, cytolytic anti-lymphocyte therapies, total lymphoid irradiation (TLI) and the antifibrotic agent pirfenidone. Most of these treatments are supported by case series and observational studies. Finally, we will discuss the role of retransplantation for CLAD.
PubMed: 34992842
DOI: 10.21037/jtd-2021-19 -
Plastic and Reconstructive Surgery Nov 2022Capsular contracture is the most common complication following breast augmentation. Recently, prophylaxis studies aiming to inhibit the release of profibrotic substances...
BACKGROUND
Capsular contracture is the most common complication following breast augmentation. Recently, prophylaxis studies aiming to inhibit the release of profibrotic substances to prevent capsular contracture have gained in importance. This study investigated the effects of cromolyn sodium, montelukast, and zafirlukast on capsular contracture in a rat model.
METHODS
Thirty female Wistar albino rats were randomly divided into five groups: control, sham, cromolyn sodium, montelukast, and zafirlukast. Intraperitoneal injections were administered daily to the sham (1 ml per day), cromolyn sodium (10 mg/kg per day), montelukast (10 mg/kg per day), and zafirlukast (1.25 mg/kg per day) groups 1 month before surgery. Miniature breast implants were then placed on the backs of the rats in each group. Injections were continued for the next 3 months. The rats were subsequently killed, and the capsules were harvested and assessed histopathologically. The histopathologic outcomes were acute inflammation status, inflammation severity, synovial metaplasia, foreign body reaction, mast cell count, and capsular thickness.
RESULTS
The cromolyn sodium, montelukast, and zafirlukast groups had less acute inflammation and lower mean inflammation severity scores, foreign body reaction occurrence, mast cell counts, and capsular thickness than the control and sham groups ( p < 0.05). These parameters were better in the cromolyn sodium group than in the montelukast and zafirlukast groups ( p < 0.05).
CONCLUSIONS
Cromolyn sodium appears to inhibit capsular contracture more efficiently than montelukast and zafirlukast. This report may be a pioneer study for the prophylactic use of cromolyn sodium in capsular contracture.
CLINICAL RELEVANCE STATEMENT
The prophylactic administration of cromolyn sodium appears to reduce capsular contracture more efficiently than that of montelukast and zafirlukast. This report might constitute a pioneer study for the prophylactic use of cromolyn sodium in capsular contracture.
Topics: Animals; Female; Rats; Breast Implants; Cromolyn Sodium; Foreign-Body Reaction; Implant Capsular Contracture; Leukotriene Antagonists; Rats, Wistar; Tosyl Compounds
PubMed: 35994348
DOI: 10.1097/PRS.0000000000009653 -
Children (Basel, Switzerland) Nov 2022Montelukast is a leukotriene receptor antagonist (LTRA) commonly prescribed for asthma, allergic rhinitis and sleep-related breathing disorders. Recently, some studies...
UNLABELLED
Montelukast is a leukotriene receptor antagonist (LTRA) commonly prescribed for asthma, allergic rhinitis and sleep-related breathing disorders. Recently, some studies have reported several adverse events, such as neuropsychiatric disorders and sleep disturbances, among children.
OBJECTIVE
To obtain more insight into the safety profile of montelukast for children with asthma, allergic rhinitis and sleep-related breathing disorders.
METHOD AND RESULTS
We retrospectively studied all adverse drug reactions to montelukast among 385 children 6 months or older in six tertiary centers over a two-year period. A total of 89.6% were asthmatic, 50% had allergic rhinitis and 13.6% had sleep-related breathing disorders; Singulair was the most common type of montelukast used (67.9%). This study reported a high prevalence of adverse drug reactions among 123 patients (31.9%), predominantly in those aged 4-9 years (52.8%), followed by adolescents (24.4%) and toddlers (22.8%). Two (ADRs) were reported in 9.8% of the children, while three or more were reported in 5.5%. Sleep disturbance was the most common (ADRs), affecting 15.1% of participants (overlap was common; 5.5% of children experienced sleep difficulties, 4.4% experienced sleep interruption and decreased sleep, and 1.82% experienced nightmares), followed by agitation (10.4%), pain (9.4%) and hyperactivity (6.8%). No serious (ADRs) were reported. Eleven percent of families faced difficulties in purchasing montelukast, and only 57% of families had insurance. Misconceptions were common (9.8% reported it to be a steroid, while 30.6% believed it to be a bronchodilator). Although 81% of the families believed it was an effective and preventive medication, 5.3% stopped the drug due to concern about side effects, especially agitation (3%) and nightmares (0.6%).
CONCLUSION
These data demonstrate that montelukast is effective, but the associated adverse neuropsychiatric drug reactions are more prevalent than those reported in the literature. In particular, sleep disturbance, agitation, pain and hyperactivity were observed. Pediatricians should be aware of such (ADRs). Misconceptions about montelukast are still common, and parental counseling and urgent epidemiological studies are needed to quantify the risk for management plans.
PubMed: 36421233
DOI: 10.3390/children9111783