Effect of budesonide combined with montelukast sodium on pulmonary function parameters and immunoglobulin levels in children with bronchial asthma

Background and aim: Bronchial asthma is a prevalent type of respiratory disease that affects a large proportion of pediatric patients. The purpose of this study is to further investigate the clinical effects of budesonide combined with montelukast sodium in treating bronchial asthma. Methods: Eighty-six children with bronchial asthma were equally divided into study and control groups via randomized double-blind controlled trial. The control group was treated with aerosol inhalation of budesonide combined with placebo, while the study group was treated with budesonide combined with montelukast sodium. Pulmonary function parameters, immunoglobulin, and recovery of related symptoms, along with the adverse reaction rate, were observed and compared between both groups. Results: Before treatment, there was no marked difference in pulmonary function parameters and immunoglobulin indexes between both groups (P > 0.05). All pulmonary function indicators and immunoglobulin indexes in both groups improved following therapy, with the study group outperforming the control group (P < 0.05). The recovery time of related symptoms in the study group was shorter than that in the control group (P < 0.05). The incidence of adverse reactions in both groups was compared, with notable differences (P < 0.05). Conclusion: Budesonide combined with montelukast sodium in the treatment of bronchial asthma has the value of clinical application and promotion (AU)

Combination of eudragit EPO with poloxamers for improved solubility and dissolution of Zafirlukast: An evaluation of solid dispersion formulations.

This study investigated the effect of solid dispersions (SD) on solubility and release of Zafirlukast (ZA) by physical mixture (PM), solvent evaporation (SE) and kneading method (KM) with Eudragit EPO (EPO) as binary component and Poloxamer 188 (P188) and Poloxamer 407 (P407) as ternary components. The binary and ternary systems caused an increase of 322 folds and 356 folds in aqueous solubility of ZA, respectively. Formulations were characterized for solubility, FTIR, PXRD, DSC, SEM and dissolution studies. P407 was found to be an excellent solubility booster in combination with EPO. It was concluded that solubility and dissolution rate of ZA increased significantly when SD of the ZA was prepared by solvent evaporation method (1:7 ratio) using 15% P407 as ternary component.

Comparative study evaluating antihistamine versus leukotriene receptor antagonist as adjuvant therapy for rheumatoid arthritis.

PURPOSE: Investigating the efficacy and safety of rupatadine (RUP) versus montelukast (MON) as adjuvant therapy for patients with rheumatoid arthritis (RA). METHODS: From December 2018 to December 2019, 75 patients with active RA were enrolled in this randomized double-blind placebo-controlled study. The patients were randomized into three groups (n = 25 in each group); methotrexate (MTX) group which received MTX 15-25 mg/week plus placebo tablet once daily; MTX/RUP group which received MTX plus RUP 10 mg once daily; and MTX/MON group which received MTX plus MON 10 mg once daily. The treatment duration was 3 months. At baseline and 3 months after treatment, blood samples were collected for the biochemical analysis of high-sensitivity C-reactive protein (hs-CRP), interleukins 8 and 17 (IL-8, IL-17), E-selectin, and clusterin (CLU) levels. Clinical and functional assessments using Disease Activity Score-CRP (DAS28-CRP) and Multidimensional Health Assessment Questionnaire (MDHAQ) were performed. RESULTS: Both RUP and MON produced clinical and functional improvements which were translated by significant improvements in DAS28-CRP score and MDHAQ. Rupatadine significantly reduced all measured parameters (P < 0.05) except for IL-17 and CLU. Montelukast significantly decreased all measured variables (P < 0.05) except for E-selectin. Interleukin-8 was positively correlated with IL-17 and CLU, while hs-CRP was positively correlated with E-selectin and body mass index (BMI). Both drugs were well tolerated; somnolence was the common side effect for RUP. No neuropsychiatric events were reported with MON. CONCLUSION: Rupatadine or montelukast may serve as a potential adjuvant therapy for patients with rheumatoid arthritis secondary to the preliminary evidence of efficacy and safety. ClinicalTrials.gov identifier NCT03770923, December 10, 2018.

The leukotriene receptor antagonist montelukast in the treatment of non-alcoholic steatohepatitis: A proof-of-concept, randomized, double-blind, placebo-controlled trial.

Non-alcoholic fatty liver disease (NAFLD) is associated with fat accumulation in the liver which can progress into non-alcoholic steatohepatitis (NASH). There is no specific treatment strategy for NASH. In this context, this study aimed at evaluating the efficacy and safety of montelukast in the treatment of patients with NASH. In this randomized double-blind placebo-controlled study, 52 overweight/obese patients with NASH were randomized into group 1 (n = 26) which received montelukast 10 mg tablets once daily and group 2 (n = 26) which received placebo tablets once daily for 12 weeks. The fibro-scan was used to assess liver stiffness as a primary outcome at baseline and 12 weeks post-treatment. Furthermore, patients were assessed for biochemical analysis of liver aminotransferases, metabolic parameters, TNF-α, 8-hydroxy-2'-deoxyguanosine (8-OHdG), liver fibrosis biomarkers including hyaluronic acid (HA) and transforming growth factor beta-1 (TGF-ß1). Beck depression inventory questionnaire was used to report depressive symptoms. Data were statistically analyzed by paired and unpaired student's t-test, and Chi-square test. A total number of 44 patients completed the study. The two groups were statistically similar at baseline. After treatment and as compared to baseline data and placebo, montelukast showed a statistically significant improvement in liver stiffness, liver enzymes, metabolic parameters (except LDL-C), TNF-α, 8-OHdG, and liver fibrosis biomarkers (HA and TGF-ß1). Furthermore, montelukast was well tolerated and didn't provoke depression. In this proof-of-concept study, treatment with montelukast may represent a promising therapeutic strategy for patients with non-alcoholic steatohepatitis secondary to its efficacy and safety. Clinicaltrial.gov ID: NCT04080947.

Evaluation of efficiency and safety of combined montelukast sodium and budesonide in children with cough variant asthma: A protocol for systematic review and meta-analysis.

BACKGROUND: Cough variant asthma (CVA) is classified as a distinct form of asthma. As the primary or only symptom, cough is the leading cause for the most prevalent chronic cough among kids. The American College of Clinical Pharmacy, British Thoracic Society, and Chinese guidelines established for diagnosing and treating chronic cough in kids recommend inhaled corticosteroids, combined with leukotriene receptor antagonists when necessary. METHODS: We will conduct a comprehensive search in major databases using keywords to find studies related to the analysis of montelukast sodium and budesonide for treating CVA in kids. Two reviewers will independently assess the quality of the selected research articles and perform data extraction. Next, we will use the RevMan software (version: 5.3) to conduct the statistical analysis of the present study. RESULTS: This study will assess the efficacy and safeness of using montelukast sodium and budesonide to treat kids with CVA by pooling the results of individual studies. CONCLUSION: Our findings will provide vigorous evidence to judge whether montelukast sodium and budesonide therapy is an efficient form of therapy for CVA patients. ETHICS AND DISSEMINATION: Ethics approval is not needed for the present meta-analysis. OSF REGISTRATION NUMBER: May 17, 2021.osf.io/cuvjz (https://osf.io/cuvjz/).

A Randomized Trial of Comparing a Combination of Montelukast and Budesonide With Budesonide in Allergic Rhinitis.

OBJECTIVES/HYPOTHESIS: It is not unequivocally proven whether a combination of an intranasal corticosteroids (INSs) and a cysteinyl leukotriene receptor antagonist has greater efficacy than INSs in the treatment of seasonal allergic rhinitis (SAR). STUDY DESIGN: Single-center, randomized, open-label study. METHODS: Study subjects included 46 participants with SAR. Participants were randomized to receive budesonide (BD; 256 µg) plus montelukast (MNT; 10 mg) (BD + MNT) or BD alone (256 µg) for 2 weeks. Visual analog scale scores for five major symptoms of SAR, nasal cavity volume (NCV), nasal airway resistance (NAR), and fractional exhaled nitric oxide (FeNO) were assessed before and at the end of treatments. RESULTS: Both treatments significantly improved the five main SAR symptoms from baseline; however, BD + MNT produced significantly greater improvements in nasal blockage and nasal itching compared to BD alone. At baseline, the nasal blockage score was significantly correlated with NCV and NAR (r = -0.473, P = .002 and r = -0.383, P = .013, respectively). After 2 weeks of treatment, BD + MNT significantly improved NCV, but not NAR, to a greater level than BD. The number of patients with FeNO concentration ≥ 30 ppb at baseline was significantly decreased after BD + MNT treatment, but not after BD treatment. Similarly, BD + MNT treatment led to a significantly greater decrease in FeNO concentration than BD treatment. CONCLUSIONS: BD + MNT treatment may have an overall superior efficacy than BD monotherapy for patients with SAR, especially in improvement of nasal blockage, itching, and subclinical lower airway inflammation. Also, NCV and NAR could be used to assess nasal blockage more accurately. LEVEL OF EVIDENCE: 1b Laryngoscope, 131:E1054-E1061, 2021.

Pilot Study of Peak Plasma Concentration After High-Dose Oral Montelukast in Children With Acute Asthma Exacerbations.

Acute asthma exacerbations are primarily due to airway inflammation and remain one of the most frequent reasons for childhood hospitalizations. Although systemic corticosteroids remain the mainstay of therapy because of their anti-inflammatory properties, not all inflammatory pathways are responsive to systemic corticosteroids, necessitating hospital admission for further management. Cysteinyl leukotrienes (LTs) are proinflammatory mediators that play an important role in systemic corticosteroids non-responsiveness. Montelukast is a potent LT-receptor antagonist, and an intravenous preparation caused rapid, sustained improvement of acute asthma exacerbations in adults. We hypothesized that a 30-mg dose of oral montelukast achieves peak plasma concentrations (Cmax ), comparable to the intravenous preparation (1700 ng/mL) and would be well tolerated in 15 children aged 5 to 12 years with acute asthma exacerbations. After administration of montelukast chewable tablets, blood samples were collected at 0, 15, 30, 45, 60, 120, 180, and 240 minutes. Plasma was separated and frozen at -80°C until analysis for montelukast concentration using liquid chromatography- tandem mass spectrometry. Median time to Cmax (tmax ) was 3.0 hours. Six participants (40%) achieved Cmax of 1700 ng/mL or higher. However, there was high interindividual variability in peak plasma concentration (median Cmax of 1378 ng/mL; range, 16-4895 ng/mL). No participant had side effects or adverse events. Plasma concentrations from this pilot study support the design of a weight-based dose-finding study aimed at selecting an optimal dose for future clinical trials to assess the efficacy of high-dose oral montelukast in children with moderate to severe asthma exacerbations.

Montelukast, a cysteinyl leukotriene receptor antagonist, exerts local antinociception in animal model of pain through the L-arginine/nitric oxide/cyclic GMP/KATP channel pathway and PPARγ receptors.

OBJECTIVE: The leukotrienes are inflammatory mediators. In the present study, the analgesic role of local montelukast, a cysteinyl leukotriene receptor antagonist, and the possible involvement of L-arginine/NO/cGMP/KATP channel pathway and PPARγ receptors was assessed in the formalin test in rats. METHODS AND RESULTS: The local administration of montelukast into the hind paw produced dose-related analgesia during both phases of the formalin test. Furthermore, pre-treatment with L-NAME, methylene blue, and glibenclamide prevented montelukast (10 µg/paw)-induced antinociception in both early and late phases of the test. Moreover, the local L-arginine and diazoxide before the sub-effective dose of montelukast (3 µg/paw) produced an analgesic effect. Also, local GW-9662 blocked antinociception induced by montelukast plus pioglitazone (10 µg/paw). CONCLUSION: In conclusion, montelukast produced peripheral analgesia through PPARγ receptors and activation of the L-arginine/NO/cGMP/KATP channel pathway, with potential for a new topical analgesic drug.

Montelukast's ability to fight COVID-19 infection.

Montelukast can be effective in the treatment of SARS-CoV-2 infection.

Comparing LAMA with LABA and LTRA as add-on therapies in primary care asthma management.

The Global Initiative for Asthma recommends a stepwise approach to adjust asthma treatment to the needs of individual patients; inhaled corticosteroids (ICS) remain the core pharmacological treatment. However, many patients remain poorly controlled, and evidence-based algorithms to decide on the best order and rationale for add-on therapies are lacking. We explore the challenges of asthma management in primary care and review outcomes from randomised controlled trials and meta-analyses comparing the long-acting muscarinic antagonist (LAMA) tiotropium with long-acting ß2-agonists (LABAs) or leukotriene receptor antagonists (LTRAs) as add-on to ICS in patients with asthma. In adults, LAMAs and LABAs provide a greater improvement in lung function than LTRAs as add-on to ICS. In children, results were positive and comparable between therapies, but data are scarce. This information could aid decision-making in primary care, supporting the use of add-on therapy to ICS to help improve lung function, control asthma symptoms and prevent exacerbations.

Airway mechanics after withdrawal of a leukotriene receptor antagonist in children with mild persistent asthma: Double-blind, randomized, cross-over study.

BACKGROUND: To determine the response of airway mechanics and the changes in asthma symptoms to stepping down of leukotriene receptor antagonist (LTRA) therapy. METHODS: Thirty children (mean age: 7.1 years) with mild, well-controlled, and persistent asthma who took LTRA as maintenance treatment were randomized into a double-blind, placebo-controlled, cross-over study. Each group received an LTRA (montelukast) or placebo daily for 2 weeks, followed by a 1-week washout period, and then the alternate treatment for 2 weeks. Spirometry and impulse oscillation system (IOS) measurements before and after four puffs of salbutamol inhalation, fractional exhaled nitric oxide (FeNO), and the childhood asthma control test (C-ACT) were evaluated at baseline, the end of placebo treatment, and the end of LTRA treatment. RESULTS: Changes of FEV1 /FVC (p = .113) and FEV1 (p = .109) from baseline to posttreatment did not differ significantly between the placebo and montelukast groups. In the placebo group, prebronchodilator (pre-) FEV1 /FVC was decreased (83% vs. 86%) and bronchodilator response (BDR) in FEV1 was diminished (10.7% vs. 6.4%) at posttreatment compared with baseline. However, the montelukast group had no significant changes in pre-FEV1 /FVC (p = .865) and BDR in FEV1 (p = .461). In addition, compared with the montelukast group, the placebo group showed no significant changes in Rrs5 (total airway resistance), Rrs5-20 (peripheral airway resistance), FeNO, and symptoms by the C-ACT. CONCLUSION: In children with well-controlled mild persistent asthma, changes in spirometry, IOS, FeNO, and C-ACT results did not differ between the placebo and montelukast groups within 2 weeks.

The efficacy of a leukotriene receptor antagonist in the treatment of human rectal aberrant crypt foci: a nonrandomized, open-label, controlled trial.

BACKGROUND: Leukotriene receptor antagonists (LTRAs) are broadly used for the management of allergic asthma and have recently been indicated to inhibit carcinogenesis and cancer cell growth. In colorectal cancer (CRC) chemoprevention studies, the occurrence of adenoma or CRC itself is generally set as the trial endpoint. Although the occurrence rate of CRC is the most confident endpoint, it is inappropriate for chemoprevention studies because CRC incidence rate is low in the general population and needed for long-term monitoring. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and darker in methylene blue staining than normal crypts, are regarded to be a fine surrogate biomarker of CRC. Therefore, this prospective study was designed to explore the chemopreventive effect of LTRA on colonic ACF formation and the safety of the medicine in patients scheduled for a poly resection as a pilot trial leading the CRC chemoprevention trial. METHODS: This study is a nonrandomized, open-label, controlled trial in patients with colorectal ACF and polyps scheduled for a polypectomy. Participants meet the inclusion criteria will be recruited, and the number of ACF in the rectum will be counted at the baseline colonoscopic examination. Next, the participants will be assigned to the LTRA or no treatment group. Participants in the LTRA group will continue 10 mg of oral montelukast for 8 weeks, and those in the no treatment group will be observed without the administration of any additional drugs. At the end of the 8-week LTRA intervention period, a polypectomy will be conducted to evaluate the changes in the number of ACF, and cell proliferation in the normal colorectal epithelium will be analyzed. DISCUSSION: This will be the first study to investigate the effect of LTRAs on colorectal ACF formation in humans. TRIAL REGISTRATION: This trial has been registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000029926 . Registered 10 November 2017.

The potential role of peak nasal inspiratory flow to evaluate active sinonasal inflammation and disease severity.

Although the pathophysiology of nasal polyposis is incompletely understood, rhinologists have seldom studied it with rhinomanometry or peak nasal inspiratory flow (PNIF) due to technical limitations and the perception that polyp size might impair reproducibility and the usefulness of recordings. The objective of this study is to assess how measures of rhinomanometry and PNIF relate to disease activity. Nineteen patients with polyps, 15 patients with chronic sinusitis without polyps and 11 negative controls were evaluated with active anterior rhinomanometry and PNIF. Sinusitis and polyp patients were re-evaluated after medical treatment. Polyp patients had the highest median Lund-Mackay score (14) and a median Johansen score of 1. PNIF and its variation after treatment were also lowest in this group (median 90 L/min before and after treatment; median variation of 0 L/min). Nasal resistance was similar between groups, and only correlated with Johansen score (Spearman = 0.517, p = 0.048) after treatment. Our study suggests that evaluating polyp patients using rhinomanometry and PNIF may provide useful and reproducible data. Several findings considered together suggest that polyp size is not the main determinant of nasal functional changes in these patients, warranting further studies to verify whether PNIF changes reflect sinus inflammation or merely airway obstruction.

Pharmacotherapeutic management of asthma in the elderly patient.

INTRODUCTION: Asthma is a heterogeneous syndrome with variable phenotypes. Reversible airway obstruction and airway hyper-responsiveness often with an atopic or eosinophilic component is common in the elderly asthmatic. Asthma chronic obstructive pulmonary disease overlap syndrome (ACOS), a combination of atopy-mediated airway hyper-responsiveness and a history of smoking or other environmental noxious exposures, can lead to some fixed airway obstruction and is also common in elderly patients. Little specific data exist for the treating the elderly asthmatic, thus requiring the clinician to extrapolate from general adult data and asthma treatment guidelines. AREAS COVERED: A stepwise approach to pharmacotherapy of the elderly patient with asthma and ACOS is offered and the literature supporting the use of each class of drugs reviewed. EXPERT OPINION: Inhaled, long-acting bronchodilators in combination with inhaled corticosteroids represent the backbone of treatment for the elderly patient with asthma or ACOS . Beyond these medications used as direct bronchodilators and topical anti-inflammatory agents, a stepwise approach to escalation of therapy includes multiple options such as oral leukotriene receptor antagonist or 5-lipoxygense inhibitor therapy, oral phosphodiesterase inhibitors, systemic corticosteroids, oral macrolide antibiotics and if evidence of eosinophilic/atopic component disease exists then modifying monoclonal antibody therapies.

Disagreement between guidelines regarding the third step of asthma drug therapy for school-age children.

With the help of a routine clinical case, we highlighted the difference between two of the best asthma guidelines available at the time regarding therapeutic suggestions for the so-called "third step" for school-age asthmatic children. We have analyzed the scientific evidence that each of the two guidelines brings to support their position. Finally, we have motivatedly solved the clinical scenario. However, the question of disagreement between two guidelines remains unresolved. This can lead to unjustified differences in the management of schoolchildren with persistent asthma.

Post hoc analysis of initial treatments and control status in the INITIAL study: an observational study of newly diagnosed patients with asthma.

BACKGROUND: The 12-week, multicentre, observational INITIAL study (NCT02143739) assessed asthma severity in newly diagnosed Chinese patients. METHODS: Post hoc analysis of medication combinations prescribed per routine clinical practice at baseline, and the impact on control levels evaluated using 2012 vs 2018 Global Initiative for Asthma (GINA) criteria. RESULTS: In total, 4491 patients were included in the analysis. At baseline, intermittent, mild, moderate and severe asthma was reported in 3.9, 12.0, 22.6 and 61.6% of patients, respectively. Most patients (90.2%) were prescribed inhaled corticosteroid/long-acting ß2 agonist (ICS/LABA). ICS/LABA plus ≥1 additional medication(s) was prescribed to 66.7% of patients, with leukotriene receptor antagonist (LTRA, 54.7%) being the most common additional medication. Distribution of ICS/LABA vs ICS/LABA+LTRA was comparable in patients with intermittent (3.2% vs 3.0%), mild (11.5% vs 9.7%), moderate (21.2% vs 19.9%) and severe asthma (64.1% vs 67.4%). Control levels among patients using ICS/LABA+LTRA vs ICS/LABA were comparable using GINA 2012 and lower using GINA 2018 criteria. The proportion of patients using ICS/LABA+LTRA vs ICS/LABA with intermittent, mild, moderate and severe asthma controlled at Week 12 (using GINA 2012) were 78.1% vs 80.0, 86.5% vs 85.8, 78.5% vs 71.3, and 59.6% vs 61.8%, respectively. Using GINA 2018 criteria proportions were 86.8% vs 95.9, 86.1% vs 93.2, 82.1% vs 85.3, and 71.9% vs 77.6%, respectively. CONCLUSIONS: Asthma control was not improved by adding LTRA to ICS/LABA and may have been unnecessary for some newly diagnosed patients. These findings were irrespective of the GINA criteria (2012 vs 2018) used and baseline severity.

Radioprotective effects of montelukast, a selective leukotriene CysLT1 receptor antagonist, against nephrotoxicity induced by gamma radiation in mice.

PURPOSE: In this study, we evaluated the renal protective effects of montelukast (MLK) against ionizing radiation (IR) induced nephrotoxicity in mice. MATERIALS AND METHODS: Radioprotective effects of MLK were assessed by biochemical analysis including measurements of kidney malondialdehyde (MDA), reduced glutathione (GSH), and serum creatinine and urea levels. Besides, for further evaluation of protective effects of MLK on renal system, 99m Tc-dimercaptosuccinic acid (DMSA) has been applied. The total antioxidant capacity of MLK was measured by using 1,1-diphenyl-2-picryl hydrazyl radical reagents and compared with butylated hydroxyl toluene standard antioxidant. RESULTS: The biochemical evaluation revealed that better results have been achieved for the groups administered with MLK than the only radiation group. Besides only IR-treated mice group, those treated with MLK demonstrated a significant decrease in urea and creatinine levels. Statistically, significant differences of MDA and SHG levels (P < .05) were found between the radiation group and MLK plus IR-treated group. Also, 99m Tc-DMSA kidney uptake value (%ID/g) was observed lower for MLK plus IR-treated mice group than only radiation-treated mice group. CONCLUSIONS: According to our findings, MLK has a potential role to be used as a renal protective agent against gamma radiation in radiotherapy.