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Frontiers in Pharmacology 2022Epithelial-mesenchymal transition (EMT) of airway lung epithelial cells is considered a major driver of fibrosis and airway remodeling. Arsenic exposure is well known...
Epithelial-mesenchymal transition (EMT) of airway lung epithelial cells is considered a major driver of fibrosis and airway remodeling. Arsenic exposure is well known to cause the malignant transformation of cells, including those in the lung. Accumulating studies have shown that arsenic exposure is associated with chronic pulmonary diseases. However, clinical treatment for arsenic-induced pulmonary damage has not been well investigated. The therapeutic effects of montelukast and its combination with fluticasone on sodium arsenite-induced EMT changes in normal human bronchial cells were investigated. The cell migration ability was evaluated by Transwell and wound healing assays. EMT marker expression was determined by immunoblotting. Furthermore, the role of reactive oxygen species (ROS) generation in arsenic-induced EMT and the effect of montelukast on this process were determined by ROS inhibitor treatment and ROS measurement, respectively. Montelukast was effective at reducing arsenic-induced cell migration and mesenchymal protein (fibronectin, MMP-2, N-cadherin, β-catenin, and SMAD2/3) expression. Arsenic-induced ROS production was attenuated by pretreatment with montelukast. Treatment with the ROS inhibitor N-acetyl cysteine reduced arsenic-induced NF-kB phosphorylation and the mesenchymal protein expression, indicating that ROS production is critical for arsenic-induced EMT. In addition, combined treatment with montelukast and fluticasone reversed the inhibitory effects of montelukast on cell migration. The expression of fibronectin, MMP-2 induced by arsenic was further enhanced by the combination treatment compared with montelukast treatment only. This study demonstrated that montelukast is effective at reducing arsenic-induced EMT in human bronchial epithelial cells. Through the inhibition of arsenic-induced ROS generation and NF-kB activation, which is critical for arsenic-induced EMT, montelukast inhibited arsenic-induced cell migration and the expression of extracellular matrix proteins and several EMT-regulating transcription factors. The combination of fluticasone with montelukast reversed the inhibitory effect of montelukast on arsenic-induced EMT. This study provides therapeutic strategies and mechanisms for arsenic-induced pulmonary epithelial damage.
PubMed: 35517780
DOI: 10.3389/fphar.2022.877125 -
Clinical and Experimental Pediatrics Oct 2020
PubMed: 32882784
DOI: 10.3345/cep.2019.01662 -
Cureus Oct 2023Background Cough is one of the most common presenting complaints for physicians across the world, with the potential to result in a significant influence on one's daily...
Background Cough is one of the most common presenting complaints for physicians across the world, with the potential to result in a significant influence on one's daily life. It is typically categorized into acute cough (<3 weeks), subacute cough (three to eight weeks), and chronic cough (>8 weeks). The lack of specific treatment guidelines and evidence-based recommendations for resolving cough creates reasonable controversy in the medical field. This retrospective study aims to identify the clinical features of cough and evaluate the comparative efficacy between different anti-asthmatic treatment modalities in the urban city of Dubai, United Arab Emirates. Methods A retrospective cross-sectional study was performed on patients presenting to pulmonology or respiratory outpatient clinics with complaints of cough in the absence of any known history of chronic respiratory illness (e.g., asthma). Analysis was conducted via chi-squared and analysis of variance (ANOVA) testing. Results A total of 308 patients were eligible for inclusion, with 273 patients presenting for follow-up. Overall, patients with acute, subacute, and chronic coughs had similar clinical presentations, with no statistically significant differences noted. However, patients with pets were more likely to develop an acute cough (p = 0.04). Moreover, the follow-up outcomes of acute, subacute, and chronic cough were similar, with no significant statistical difference noted. Furthermore, patients receiving dual therapy using budesonide and montelukast, and patients receiving triple therapy using budesonide, montelukast, and tiotropium/ipratropium were most likely to gain complete relief of their symptoms, although triple therapy treatment was also associated with the highest rate of null improvement (p = 0.012). Additionally, chronic cough patients were more likely to be subject to higher C-reactive protein (CRP) levels in comparison to other cohorts (p = 0.26). Conclusion The comparative superiority of dual therapy using budesonide and montelukast, and triple therapy using budesonide, montelukast, and tiotropium/ipratropium were highlighted in this study. In the sparseness of specific treatment guidelines and evidence-based recommendations for cough, the use of anti-asthmatic therapy for cough patients has shown favorable results. Moreover, the lack of clinical differences between acute, subacute, and chronic cough may result in difficulties with the treatment of cough patients. To arrive at a valid conclusion, further comprehensive studies with larger and more diversified sample populations are encouraged.
PubMed: 38021559
DOI: 10.7759/cureus.47377 -
Experimental and Therapeutic Medicine Sep 2020Optimal treatment options for post-infectious bronchiolitis obliterans (PIBO) have not yet been established. The present study retrospectively analyzed the effect of...
Optimal treatment options for post-infectious bronchiolitis obliterans (PIBO) have not yet been established. The present study retrospectively analyzed the effect of budesonide, montelukast and azithromycin on treating PIBO in children <5 years old.. Based on treatment regimen, the cohort was divided into group A and group B. Group A received a combination of budesonide, montelukast and azithromycin for at least 3 months and group B received unconventional treatment (budesonide for nebulization intermittently, prednisone, montelukast and antibiotics if necessary) compared with standard treatment. Tidal pulmonary function and symptoms assessment were performed at diagnosis and after 3 months of therapy. There were no significant differences in the sex, age, pulmonary function and symptoms assessment between groups A and B at diagnosis. However, following 3 months of treatment, the time to peak tidal expiratory flow as a proportion of expiratory time, and volume to peak expiratory flow as a proportion of exhaled volume in group A were significantly higher compared with those in group B. The respiratory rate in group A was significantly lower compared with group B. The symptoms assessment score in group A was significantly higher compared with that of group B. In conclusion, the present study demonstrates that combination therapy with budesonide, montelukast and azithromycin improves pulmonary function and respiratory symptoms in PIBO children <5 years old. The present study was retrospectively registered on March 22, 2020 with register no. YY202003-008-HB03.
PubMed: 32765758
DOI: 10.3892/etm.2020.8983 -
Chinese Medical Journal Nov 2021Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of salmeterol/fluticasone compared with montelukast alone (or add-on therapy to fluticasone) in the treatment of bronchial asthma in children and adolescents: a systematic review and meta-analysis.
BACKGROUND
Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma.
METHODS
A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible.
RESULTS
Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC.
CONCLUSIONS
SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs.
PROSPERO REGISTRATION NUMBER
CRD42019133156.
Topics: Acetates; Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Albuterol; Anti-Asthmatic Agents; Asthma; Child; Cyclopropanes; Drug Therapy, Combination; Fluticasone; Humans; Quinolines; Salmeterol Xinafoate; Sulfides
PubMed: 34784306
DOI: 10.1097/CM9.0000000000001853 -
Frontiers in Pharmacology 2021Montelukast is a selective leukotriene receptor antagonist that is widely used to treat bronchial asthma and nasal allergy. To clarify the association between...
Montelukast is a selective leukotriene receptor antagonist that is widely used to treat bronchial asthma and nasal allergy. To clarify the association between montelukast and neuropsychiatric adverse events (AEs), we evaluated case reports recorded between January 2004 and December 2018 in the Food and Drug Administration Adverse Event Reporting System (FAERS). Furthermore, we elucidated the potential toxicological mechanisms of montelukast-associated neuropsychiatric AEs through functional enrichment analysis of human genes interacting with montelukast. The reporting odds ratios of suicidal ideation and depression in the system organ class of psychiatric disorders were 21.5 (95% confidence interval (CI): 20.3-22.9) and 8.2 (95% CI: 7.8-8.7), respectively. We explored 1,144 human genes that directly or indirectly interact with montelukast. The molecular complex detection (MCODE) plug-in of Cytoscape detected 14 clusters. Functional analysis indicated that several genes were significantly enriched in the biological processes of "neuroactive ligand-receptor interaction." "Mood disorders" and "major depressive disorder" were significant disease terms related to montelukast. Our retrospective analysis based on the FAERS demonstrated a significant association between montelukast and neuropsychiatric AEs. Functional enrichment analysis of montelukast-associated genes related to neuropsychiatric symptoms warrant further research on the underlying pharmacological mechanisms.
PubMed: 34987393
DOI: 10.3389/fphar.2021.764279 -
Medical Science Monitor : International... Mar 2015Montelukast is an antiinflammatory drug with an antioxidant property. In this study, we aimed to reveal whether montelukast has a preventive effect against seizures and...
BACKGROUND
Montelukast is an antiinflammatory drug with an antioxidant property. In this study, we aimed to reveal whether montelukast has a preventive effect against seizures and post-seizure oxidative stress in pentylenetetrazol (PTZ)-induced seizures in rats.
MATERIAL AND METHODS
Of the 48 male Sprague-Dawley rats used in the study, 24 were assigned to EEG recordings (group A) and 24 were assigned to behavioral studies (group B). In group A, the electrodes were implanted on dura over the left frontal cortex for EEG recording. After 10 days, in group A, i.p. saline, 25, 50, or 100 mg/kg montelukast+35 mg/kg PTZ was administered to the rats. EEG was recorded and spike percentage was evaluated. In group B, i.p. saline, 25, 50, or 100 mg/kg montelukast+70 mg/kg PTZ was administered to the rats. Racine's Convulsion Scale (RCS) and onset times of first myoclonic jerk (FMJ) was used to evaluate the seizures. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined in the brain tissue of animals.
RESULTS
Animals treated with 50 or 100 mg/kg montelukast had significantly lower RCS and significantly increased FMJ onset time compared to the saline-treated animals. Moreover, groups given 25, 50, or 100 mg/kg montelukast had significantly lower MDA and higher SOD levels compared to the saline-treated group. The differences were more pronounced in the 100 mg/kg montelukast-pretreated group (p<0.001).
CONCLUSIONS
Montelukast showed anticonvulsant action and led to amelioration of oxidative stress markers in PTZ-induced seizures in rats.
Topics: Acetates; Action Potentials; Animals; Brain; Cyclopropanes; Electroencephalography; Male; Malondialdehyde; Pentylenetetrazole; Quinolines; Rats, Sprague-Dawley; Seizures; Sulfides; Superoxide Dismutase; Time Factors
PubMed: 25803241
DOI: 10.12659/MSM.892932 -
Scientific Reports Feb 2024Preclinical and clinical data indicate that the 5-lipoxygenase pathway becomes activated in cardiovascular diseases suggesting an important role of CysLTs in...
Preclinical and clinical data indicate that the 5-lipoxygenase pathway becomes activated in cardiovascular diseases suggesting an important role of CysLTs in atherosclerosis and in its ischemic complications. This study aims to investigate the effects of montelukast, a CysLTR-1 antagonist, in a mouse model of myocardial infarction (MI). C57BL/6N female mice were subjected to coronary artery ligation and received montelukast (10 mg/kg/day, intraperitoneal) or vehicle. Montelukast exerted beneficial effects in the infarcted area, decreasing mRNA expression of inflammatory genes, such Il1β and Ccl2 (p < 0.05), at 48 h after MI, and reducing infarct size and preventing ischemic wall thinning (p < 0.05) at 4 weeks. Furthermore, montelukast counteracted maladaptive remodelling of whole heart. Indeed, montelukast reduced LV mass (p < 0.05) and remote wall thickening (p < 0.05), and improved cardiac pumping function, as evidenced by increased global ejection fraction (p < 0.01), and regional contractility in infarcted (p < 0.05) and in remote non-infarcted (p < 0.05) myocardium. Finally, montelukast prevented cardiomyocytes hypertrophy (p < 0.05) in remote myocardium, reducing the phosphorylation of GSK3β, a regulator of hypertrophic pathway (p < 0.05). Our data strongly demonstrate the ability of montelukast to contrast the MI-induced maladaptive conditions, thus sustaining cardiac contractility. The results provide evidences for montelukast "repurposing" in cardiovascular diseases and in particular in myocardial infarction.
Topics: Mice; Animals; Female; Ventricular Remodeling; Mice, Inbred C57BL; Myocardial Infarction; Myocardium; Acetates; Cyclopropanes; Quinolines; Sulfides
PubMed: 38337010
DOI: 10.1038/s41598-024-53936-x -
The Cochrane Database of Systematic... Mar 2015Bronchiolitis is an acute inflammatory illness of the bronchioles common among infants and young children. It is often caused by the respiratory syncytial virus (RSV).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiolitis is an acute inflammatory illness of the bronchioles common among infants and young children. It is often caused by the respiratory syncytial virus (RSV). Management of bronchiolitis varies between clinicians, reflecting the lack of evidence for a specific treatment approach. The leukotriene pathway has been reported to be involved in the pathogenesis of bronchiolitis. Leukotriene inhibitors such as montelukast have been used in infants and young children with bronchiolitis. However, the results from limited randomised controlled trials (RCTs) are controversial and necessitate a thorough evaluation of their efficacy for bronchiolitis in infants and young children.
OBJECTIVES
To assess the efficacy and safety of leukotriene inhibitors for bronchiolitis in infants and young children.
SEARCH METHODS
We searched CENTRAL (2014, Issue 5), MEDLINE (1946 to April week 4, 2014), EMBASE (1974 to May 2014), CINAHL (1981 to May 2014), LILACS (1982 to May 2014), Web of Science (1985 to May 2014), WHO ICTRP and ClinicalTrials.gov (6 May 2014).
SELECTION CRITERIA
RCTs comparing leukotriene inhibitors versus placebo or another intervention in infants and young children under two years of age diagnosed with bronchiolitis. Our primary outcomes were length of hospital stay and all-cause mortality. Secondary outcomes included clinical severity score, percentage of symptom-free days, percentage of children requiring ventilation, oxygen saturation, recurrent wheezing, respiratory rate and clinical adverse effects.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Collaboration methodological practices. Two authors independently assessed trial eligibility and extracted data, such as general information, participant characteristics, interventions and outcomes. We assessed risk of bias and graded the quality of the evidence. We used Review Manager software to pool results and chose random-effects models for meta-analysis.
MAIN RESULTS
We included five studies with a total of 1296 participants under two years of age hospitalised with bronchiolitis. Two studies with low risk of bias compared 4 mg montelukast (a leukotriene inhibitor) daily use from admission until discharge with a matching placebo. Both selected length of hospital stay as a primary outcome and clinical severity score as a secondary outcome. However, the effects of leukotriene inhibitors on length of hospital stay and clinical severity score were uncertain due to considerable heterogeneity between the study results and wide confidence intervals around the estimated effects (hospital stay: mean difference (MD) -0.95 days, 95% confidence interval (CI) -3.08 to 1.19, P value = 0.38, low quality evidence; clinical severity score on day two: MD -0.57, 95% CI -2.37 to 1.23, P value = 0.53, low quality evidence; clinical severity score on day three: MD 0.17, 95% CI -1.93 to 2.28, P value = 0.87, low quality evidence). The other three studies compared montelukast for several weeks for preventing post-bronchiolitis symptoms with placebo. We assessed one study as low risk of bias, whereas we assessed the other two studies as having a high risk of attrition bias. Due to the significant clinical heterogeneity in severity of disease, duration of treatment, outcome measurements and timing of assessment, we did not pool the results. Individual analyses of these studies did not show significant differences between the leukotriene inhibitors group and the control group in symptom-free days and incidence of recurrent wheezing. One study of 952 children reported two deaths in the leukotriene inhibitors group: neither was determined to be drug-related. No data were available on the percentage of children requiring ventilation, oxygen saturation and respiratory rate. Finally, three studies reported adverse events including diarrhoea, wheezing shortly after administration and rash. No differences were reported between the study groups.
AUTHORS' CONCLUSIONS
The current evidence does not allow definitive conclusions to be made about the effects of leukotriene inhibitors on length of hospital stay and clinical severity score in infants and young children with bronchiolitis. The quality of the evidence was low due to inconsistency (unexplained high levels of statistical heterogeneity) and imprecision arising from small sample sizes and wide confidence intervals, which did not rule out a null effect or harm. Data on symptom-free days and incidence of recurrent wheezing were from single studies only. Further large studies are required. We identified one registered ongoing study, which may make a contribution in the updates of this review.
Topics: Acetates; Bronchiolitis; Cyclopropanes; Humans; Infant; Length of Stay; Leukotriene Antagonists; Quinolines; Randomized Controlled Trials as Topic; Sulfides
PubMed: 25773054
DOI: 10.1002/14651858.CD010636.pub2 -
The Journal of Dermatological Treatment Dec 2024There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities.
BACKGROUND
There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities.
METHODS
We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines.
RESULTS
Of 212 patients, 108 (mean age 48.9 years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6 months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9 months (SD ± 3.2) and one quadruple therapy (2.1 months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria.
CONCLUSIONS
Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile.
Topics: Humans; Female; Middle Aged; Male; Hydroxychloroquine; Pilot Projects; Chronic Disease; Chronic Urticaria; Urticaria; Omalizumab; Histamine H1 Antagonists; Cyclosporine; Dapsone; Anti-Allergic Agents; Acetates; Cyclopropanes; Quinolines; Sulfides
PubMed: 38508226
DOI: 10.1080/09546634.2024.2329784