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Pakistan Journal of Medical Sciences 2020Our objective was to evaluate the effect of Montelukast on the symptoms of asthma and allergic rhinitis (AR), assess its effect on the individual quality of life (QoL),...
OBJECTIVES
Our objective was to evaluate the effect of Montelukast on the symptoms of asthma and allergic rhinitis (AR), assess its effect on the individual quality of life (QoL), and estimate the proportion of participants having adverse effects.
METHODS
This prospective, open-label study conducted at Dow University of Health Sciences, Ankle Saria Hospital and Sindh Government Hospital Liaquatabad, Karachi, from August 2018 to September 2019, included patients aged >18 years with a clinical diagnosis of Asthma, AR, or both. Patients were given a 10 mg Montelukast tablet each day and then called for follow-up in the fourth week, where the questions related to the improvement in the symptoms of asthma or AR were asked. Patients were also asked about the improvement in QoL and any adverse effects.
RESULTS
A total of 694 patients were registered of which 138(19.8%) had AR, 294(42.4%) had asthma, while 273(39.3%) had both. Mean age was 41.1±14.63 years and 352 (50.7%) were male and 342(49.3%) were females. On a follow-up visit, there was a sufficient improvement in 351 asthmatics (63.9%), and 288 patients with AR (70.1%) overall, strong or marked improvement in the day (n=342,62.3%) and night time (n=331,60.3%) asthma symptoms. Overall improvements in QoL were very good or good in 419 patients. Montelukast was well-tolerated here with adverse effects (like abdominal discomfort, fever, fatigue, headache, rash, and upper respiratory tract symptoms) seen in 125 patients (18.01%).
CONCLUSION
Montelukast was very effective in improving the symptoms and QoL of the individuals suffering from asthma and/or AR.
PubMed: 33235567
DOI: 10.12669/pjms.36.7.2657 -
Naunyn-Schmiedeberg's Archives of... Feb 2024The microbiome is increasingly implicated in playing a role in physiology and pharmacology; in this review, we investigate the literature on the possibility of bacterial... (Review)
Review
The microbiome is increasingly implicated in playing a role in physiology and pharmacology; in this review, we investigate the literature on the possibility of bacterial influence on the pharmacology of anti-asthmatic drugs, and the potential impact this has on asthmatic patients. Current knowledge in this area of research reveals an interaction between the gut and lung microbiome and the development of asthma. The influence of microbiome on the pharmacokinetics and pharmacodynamics of anti-asthmatic drugs is limited; however, understanding this interaction will assist in creating a more efficient treatment approach. This literature review highlighted that bioaccumulation and biotransformation in the presence of certain gut bacterial strains could affect drug metabolism in anti-asthmatic drugs. Furthermore, the bacterial richness in the lungs and the gut can influence drug efficacy and could also play a role in drug response. The implications of the above findings suggest that the microbiome is a contributing factor to an individuals' pharmacological response to anti-asthmatic drugs. Hence, future directions for research should follow investigating how these processes affect asthmatic patients and consider the role of the microbiome on drug efficacy and modify treatment guidelines accordingly.
Topics: Humans; Anti-Asthmatic Agents; Microbiota; Asthma; Lung; Bacteria
PubMed: 37650889
DOI: 10.1007/s00210-023-02681-5 -
Frontiers in Cellular and Infection... 2024Chronic obstructive pulmonary disease (COPD) is a prevalent condition that significantly impacts public health. Unfortunately, there are few effective treatment options...
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a prevalent condition that significantly impacts public health. Unfortunately, there are few effective treatment options available. Mendelian randomization (MR) has been utilized to repurpose existing drugs and identify new therapeutic targets. The objective of this study is to identify novel therapeutic targets for COPD.
METHODS
Cis-expression quantitative trait loci (cis-eQTL) were extracted for 4,317 identified druggable genes from genomics and proteomics data of whole blood (eQTLGen) and lung tissue (GTEx Consortium). Genome-wide association studies (GWAS) data for doctor-diagnosed COPD, spirometry-defined COPD (Forced Expiratory Volume in one second [FEV1]/Forced Vital Capacity [FVC] <0.7), and FEV1 were obtained from the cohort of FinnGen, UK Biobank and SpiroMeta consortium. We employed Summary-data-based Mendelian Randomization (SMR), HEIDI test, and colocalization analysis to assess the causal effects of druggable gene expression on COPD and lung function. The reliability of these druggable genes was confirmed by eQTL two-sample MR and protein quantitative trait loci (pQTL) SMR, respectively. The potential effects of druggable genes were assessed through the phenome-wide association study (PheWAS). Information on drug repurposing for COPD was collected from multiple databases.
RESULTS
A total of 31 potential druggable genes associated with doctor-diagnosed COPD, spirometry-defined COPD, and FEV1 were identified through SMR, HEIDI test, and colocalization analysis. Among them, 22 genes (e.g., MMP15, PSMA4, ERBB3, and LMCD1) were further confirmed by eQTL two-sample MR and protein SMR analyses. Gene-level PheWAS revealed that ERBB3 expression might reduce inflammation, while GP9 and MRC2 were associated with other traits. The drugs Montelukast (targeting the MMP15 gene) and MARIZOMIB (targeting the PSMA4 gene) may reduce the risk of spirometry-defined COPD. Additionally, an existing small molecule inhibitor of the APH1A gene has the potential to increase FEV.
CONCLUSIONS
Our findings identified 22 potential drug targets for COPD and lung function. Prioritizing clinical trials that target these identified druggable genes with existing drugs or novel medications will be beneficial for the development of COPD treatments.
Topics: Pulmonary Disease, Chronic Obstructive; Humans; Mendelian Randomization Analysis; Drug Repositioning; Quantitative Trait Loci; Genome-Wide Association Study; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38660492
DOI: 10.3389/fcimb.2024.1386506 -
Indian Journal of Otolaryngology and... Oct 2022There are many evidences showing diethylcarbamazine as a potential drug for the treatment of allergic rhinitis. This study evaluated the effectiveness of...
There are many evidences showing diethylcarbamazine as a potential drug for the treatment of allergic rhinitis. This study evaluated the effectiveness of diethylcarbamazine in the treatment of allergic rhinitis and compared it with montelukast and levocetirizine. This parallel double-blind randomized clinical trial was done in allergic rhinitis patients. Seven hundred and twelve participants who met the inclusion criteria and provided informed written consent were randomized and divided into 2 equal groups. Diethylcarbamazine 300 mg/day orally in divided doses was given to group A, and montelukast 10 mg and levocetirizine 5 mg/day orally at night for 21 days was given to group B. Primary outcomes were the change in symptoms, absolute eosinophil count, serum total IgE, phadiatop and response in skin prick from baseline to 21 days and 3 months after treatment. Secondary outcome was to compare it with montelukast and levocetirizine. The mean (SD) age of the patients was 33 (10.6) years, with 374 (52.5%) males and 338 (47.5%) females. There was statistically significant improvement in all the parameters in both groups. Improvement was better with diethylcarbamazine compared to montelukast and levocetirizine and the effects were sustained for 3 months in diethylcarbamazine group. The findings suggest that diethylcarbamazine is effective in the treatment of allergic rhinitis. It gives better control and is cost-effective than montelukast and levocetirizine. : https://www.ctri.nic.in Identifier: CTRI/2020/03/024145 registered on 20-03-2020.
PubMed: 36452711
DOI: 10.1007/s12070-020-02249-2 -
International Journal of Molecular... Dec 2023Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was...
Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was the only systemic treatment for TNBC, and the identification of actionable molecular targets might ultimately improve the prognosis for TNBC patients. We performed a genome-wide analysis of DNA methylation at CpG islands on a collection of one hundred ten breast carcinoma samples and six normal breast tissue samples using reduced representation bisulfite sequencing with the XmaI restriction enzyme (XmaI-RRBS) and identified a subset of TNBC samples with significant hypomethylation at the genes' CpG islands, including CpG dinucleotides covered with cg12853742 and cg21886367 HumanMethylation 450K microarray probes. Abnormal DNA hypomethylation of this region in TNBC compared to normal samples was confirmed by bisulfite Sanger sequencing. Gene expression generally anticorrelates with promoter methylation, and thus, the promoter hypomethylation detected and confirmed in our study might be revealed as an indirect marker of high expression using a simple methylation-sensitive PCR test. Analysis of RNA-seq expression and DNA methylation data from the TCGA dataset demonstrates that the expression of the and genes significantly negatively correlates with DNA methylation at both CpG sites cg12853742 (R = -0.4, = 2.6 × 10; R = -0.21, = 0.015) and cg21886367 (R = -0.45, = 7.3 × 10; R = -0.24, = 0.005), suggesting the upregulation of these genes in tumors with abnormal hypomethylation of their CpG island. Kaplan-Meier analysis using the TCGA-BRCA gene expression and clinical data revealed poorer overall survival for TNBC patients with an upregulated . To this day, only the leukotriene inhibitor LY255283 has been tested on an MCF-7/DOX cell line, which is a luminal A breast cancer molecular subtype. Other studies compare the effects of Montelukast and Zafirlukast (inhibitors of the cysteinyl leukotriene receptor, which is different from LTB4R/LTB4R2) on the MDA-MB-231 (TNBC) cell line, with high methylation and low expression levels of LTB4R. In our study, we assess the therapeutic effects of various drugs (including leukotriene receptor inhibitors) with the DepMap gene effect and drug sensitivity data for TNBC cell lines with hypomethylated and upregulated genes. LY255283, Minocycline, Silibinin, Piceatannol, Mitiglinide, 1-Azakenpaullone, Carbetocin, and Pim-1-inhibitor-2 can be considered as candidates for the additional treatment of TNBC patients with tumors demonstrating hypomethylation/upregulation. Finally, our results suggest that the epigenetic status of leukotriene B4 receptors is a novel, potential, predictive, and prognostic biomarker for TNBC. These findings might improve individualized therapy for TNBC patients by introducing new therapeutic adjuncts as anticancer agents.
Topics: Humans; Triple Negative Breast Neoplasms; Cell Line, Tumor; Epigenomics; Receptors, Leukotriene
PubMed: 38139172
DOI: 10.3390/ijms242417343 -
Frontiers in Pharmacology 2023Loratadine and montelukast are clinical first-line drugs in the treatment of allergic rhinitis (AR). However, there is no clear evidence of the efficacy of loratadine...
Loratadine and montelukast are clinical first-line drugs in the treatment of allergic rhinitis (AR). However, there is no clear evidence of the efficacy of loratadine combined with montelukast in the treatment of AR. This study aimed to evaluate the efficacy and safety of the loratadine-montelukast combination on AR. In this meta-analysis, searches were conducted on PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure (CNKI). The search terms included loratadine, montelukast, allergic rhinitis, and clinical trials. Meta-analyses were conducted using Rev Man 5.3 and Stata 15 statistical software. A total of 23 studies with 4,902 participants were enrolled. For the primary outcome, pooled results showed that loratadine-montelukast can significantly reduce total nasal symptom scores (TNSS), when compared with loratadine (SMD, -1.00; 95% CI, -1.35 to -0.65, < 0.00001), montelukast (SMD, -0.46; 95% CI, -0.68 to -0.25, < 0.0001), or placebo (SMD, -0.93; 95% CI, -1.37 to -0.49, < 0.00001). For secondary outcomes, pooled results showed that compared with loratadine, loratadine-montelukast can significantly improve nasal congestion, nasal itching, nasal sneezing, nasal rhinorrhea, and rhinoconjunctivitis quality of life questionnaires (RQLQ). Compared with montelukast, loratadine-montelukast can significantly improve nasal itching, and nasal sneezing. Compared with placebo, loratadine-montelukast can significantly improve nasal congestion, and RQLQ. Loratadine-montelukast combination is superior to loratadine monotherapy, montelukast monotherapy, or placebo in improving AR symptoms. Therefore, loratadine-montelukast combination can be an option for patients with moderate-severe AR or poorly response to monotherapy. Systematic review registration number: clinicaltrials.gov, identifier CRD42023397519.
PubMed: 37915414
DOI: 10.3389/fphar.2023.1287320 -
American Journal of Translational... 2021To investigate the impact of the asthma-exclusive nursing scheme on the treatment effect of asthma patients.
OBJECTIVE
To investigate the impact of the asthma-exclusive nursing scheme on the treatment effect of asthma patients.
METHODS
A total of 120 asthma patients treated in our hospital from January 2019 to June 2019 were included for the research, with 60 patients in Group A from January 2019 to March 2019, and 60 patients in Group B from April 2019 to June 2019. Montelukast combined with formoterol lyophilized powder was employed as the treatment for all patients. An asthma-exclusive nursing scheme was given to Group A, and conventional nursing was applied to Group B. The analysis and comparison of symptom relief time (SRT), pulmonary function indicators (PFI), 6-minute walking distance (6MWD), adverse drug reactions (ADRs), levels of inflammatory factors (LIF), and overall efficacy between the two groups were conducted.
RESULTS
After the treatment, Group A yielded a more promising outcome of SRT than Group B (P<0.001). Moreover, a notable increase of PFI and LIF of both groups of patients was observed, in which Group A garnered more promising results than Group B (P<0.001), and similar results were also demonstrated with regard to 6MWD (P<0.001). Neither abnormal metabolism in patients nor significant difference of ADRs between the two groups was detected (P>0.05). The overall efficacy and compliance rate of Group A were higher than those of Group B, and the 6-month recurrence rate was lower than that of Group B (P<0.05).
CONCLUSION
With the aid of an asthma-exclusive nursing scheme, montelukast combined with formoterol can safely and substantially optimize the PFI and LIF of asthma patients and enhance their exercise capacity, which is of application value in clinical practice.
PubMed: 34540017
DOI: No ID Found -
Montelukast induces beneficial behavioral outcomes and reduces inflammation in male and female rats.Frontiers in Immunology 2022Accumulative data links inflammation and immune dysregulation to the pathophysiology of mental disorders; little is known regarding leukotrienes' (LTs) involvement in...
BACKGROUND
Accumulative data links inflammation and immune dysregulation to the pathophysiology of mental disorders; little is known regarding leukotrienes' (LTs) involvement in this process. Circumstantial evidence suggests that treatment with leukotriene modifying agents (LTMAs) such as montelukast (MTK) may induce adverse neuropsychiatric events. Further methodic evaluation is warranted.
OBJECTIVE
This study aims to examine behavioral effects, as well as inflammatory mediator levels of chronic MTK treatment in male and female rats.
METHODS
Depression-like phenotypes were induced by exposing male and female rats to a chronic unpredictable mild stress (CUMS) protocol for four weeks. Thereafter, rats were treated (intraperitoneally) once daily, for two weeks, with either vehicle (dimethyl sulfoxide 0.2 ml/rat) or 20 mg/kg MTK. Following treatment protocols, behavioral tests were conducted and brain regions were evaluated for inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and prostaglandin (PG) E2.
RESULTS
Overall, MTK did not invoke negative behavioral phenotypes (except for an aggression-inducing effect in males). Numerous positive behavioral outcomes were observed, including reduction in aggressive behavior in females and reduced manic/hyperactive-like behavior and increased sucrose consumption (suggestive of antidepressant-like effect) in males. Furthermore, in control males, MTK increased IL-6 levels in the hypothalamus and TNF-α in the frontal cortex, while in control females it generated a robust anti-inflammatory effect. In females that were subjected to CUMS, MTK caused a prominent reduction in TNF-α and IL-6 in brain regions, whereas in CUMS-subjected males its effects were inconsistent.
CONCLUSION
Contrary to prior postulations, MTK may be associated with select beneficial behavioral outcomes. Additionally, MTK differentially affects male vs. female rats in respect to brain inflammatory mediators, plausibly explaining the dissimilar behavioral phenotypes of sexes under MTK treatment.
Topics: Acetates; Animals; Anti-Inflammatory Agents; Antidepressive Agents; Cyclopropanes; Depression; Dimethyl Sulfoxide; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Male; Prostaglandins; Quinolines; Rats; Sucrose; Sulfides; Tumor Necrosis Factor-alpha
PubMed: 36148246
DOI: 10.3389/fimmu.2022.981440 -
Molecules (Basel, Switzerland) Feb 2022Copper oxide nanoparticles (CuO NPs) were synthesized through the coprecipitation method and used as nanocarriers for etoricoxib (selective COX-2 inhibitor drug) and...
Synthesis of Copper Oxide-Based Nanoformulations of Etoricoxib and Montelukast and Their Evaluation through Analgesic, Anti-Inflammatory, Anti-Pyretic, and Acute Toxicity Activities.
Copper oxide nanoparticles (CuO NPs) were synthesized through the coprecipitation method and used as nanocarriers for etoricoxib (selective COX-2 inhibitor drug) and montelukast (leukotriene product inhibitor drug) in combination therapy. The CuO NPs, free drugs, and nanoformulations were investigated through UV/Vis spectroscopy, FTIR spectroscopy, XRD, SEM, and DLS. SEM imaging showed agglomerated nanorods of CuO NPs of about 87 nm size. The CE1, CE2, and CE6 nanoformulations were investigated through DLS, and their particle sizes were 271, 258, and 254 nm, respectively. The nanoformulations were evaluated through in vitro anti-inflammatory activity, in vivo anti-inflammatory activity, in vivo analgesic activity, in vivo anti-pyretic activity, and in vivo acute toxicity activity. In vivo activities were performed on albino mice. BSA denaturation was highly inhibited by CE1, CE2, and CE6 as compared to other nanoformulations in the in vitro anti-inflammatory activity. The in vivo bioactivities showed that low doses (5 mg/kg) of nanoformulations were more potent than high doses (10 and 20 mg/kg) of free drugs in the inhibition of pain, fever, and inflammation. Lastly, CE2 was more potent than that of other nanoformulations.
Topics: Acetates; Analgesics; Anti-Infective Agents; Anti-Inflammatory Agents; Chemistry Techniques, Synthetic; Copper; Cyclopropanes; Drug Compounding; Etoricoxib; Metal Nanoparticles; Quinolines; Spectrum Analysis; Structure-Activity Relationship; Sulfides
PubMed: 35209221
DOI: 10.3390/molecules27041433 -
Frontiers in Molecular Biosciences 2020The 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... (Review)
Review
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 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.
PubMed: 33392263
DOI: 10.3389/fmolb.2020.610132