Efficacy of montelukast for adenoid hypertrophy in paediatrics: A systematic review and meta-analysis.

INTRODUCTION: Leukotrienes play a significant role in the pathogenesis of adenoid hypertrophy (A.H.). Therefore, we aimed to analyse the role of montelukast, a leukotriene receptor antagonist, alone or in combination with mometasone, a potent local intranasal steroid, for the treatment of A.H. METHODS: Participants were children with A.H. were treated with montelukast alone or montelukast and mometasone furoate. The main outcome measures were effect of montelukast on clinical symptoms of A.H. A literature review was conducted using online search engines, Cochrane Library, PubMed, Web of Science and Scopus, for randomized clinical trials assessing children with A.H. treated with montelukast alone or montelukast and mometasone furoate. Seven randomized clinical trials (RCTs) were included with 742 children. RESULTS: Our study reveals that montelukast alone or in combination with intranasal mometasone furoate significantly improves clinical symptoms of adenoid hypertrophy such as snoring, sleeping disturbance, mouth breathing and A/N ratio. Montelukast was superior to placebo in decreasing snoring (SMD = -1.00, 95% CI [-1.52, -0.49]), sleep discomfort (SMD = -1.26, 95% CI [-1.60, -0.93]), A/N ratio (MD = -0.11, 95% CI [-0.14, -0.09]) and mouth breathing (SMD = -1.36, 95% CI [-1.70, -1.02]). No difference was detected between montelukast and mometasone versus mometasone alone in snoring (SMD = -0.21, 95%CI [-0.69, 0.27]); however, the combination group was superior to the mometasone alone in mouth breathing (SMD = -0.46, 95% CI [-0.73, -0.19]). CONCLUSIONS: The limitation of studies included a small sample size, with an overall low to medium quality. Thus, further larger, higher-quality RCTs are recommended to provide more substantial evidence.

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.

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.

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.

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.

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.

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.

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.

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.

Corticosteroid reduction by addition of cetirizine and montelukast in biopsy-proven minimal-change nephrotic syndrome concomitant with allergic disorders.

Recent reports suggest helper T-cell abnormalities in minimal-change nephrotic syndrome (MCNS), which often complicate allergic disorders that show a similar helper T-cell profile with Th2/Th17 predominance. However, the effect of anti-allergy therapy on MCNS remains unknown. This retrospective study included 51 patients with biopsy-proven MCNS recruited between November 2012 and October 2015, with follow-up through November 2017. We analyzed relapse and temporal daily corticosteroid dose with and without co-administration of histamine H1 receptor antagonist, cetirizine, and cysteinyl-leukotriene receptor antagonist, montelukast, as well as between baseline and after follow-up. Thirteen patients were treated with cetirizine and montelukast in addition to conventional therapy, whereas 38 patients were treated by conventional therapy only, consisting of corticosteroids and immunosuppressants. To adjust for baseline clinical characteristics, a 1:1 propensity score-matched model was applied. The clinical characteristics of the two groups after matching were similar at baseline. The treatment group showed a significant reduction in the lowest daily dose of oral prednisolone throughout the entire treatment course after the study compared to that of baseline (p < 0.025), which was not observed in the control group (p = 0.37), and showed significantly higher percentage of patients establishing corticosteroid-free state for the first time throughout the entire treatment course by addition of cetirizine and montelukast compared to the control group (p < 0.025). The study shows, for the first time, the steroid sparing effect of cetirizine and montelukast in addition to conventional treatment in MCNS patients with concomitant allergies.

Zafirlukast in combination with pseudohypericin attenuates spinal cord injury and motor function in experimental mice.

BACKGROUND: Biosynthesis of leukotriene (LT) by arachidonic acid involves 5-lipoxygenase (5-LO) as an important precursor. Here, we evaluated the role of pseudohypericin (PHP) for its postulated 5-LO inhibitory activity along with a Cys-LT receptor antagonist zafirlukast (ZFL) against inflammatory response and tissue injury in mice. MATERIALS AND METHODS: The spinal injury was induced by two-level laminectomy of T6 and T7 vertebrae. The inflammation was assessed by histology, inflammatory mediators by enzyme-linked immunosorbent assay, apoptosis by Annexin-V, FAS staining, terminal deoxynucleoti-dyltransferase-mediated UTP end labeling (TUNEL) assay and expression of Bax and Bcl-2 by Western blot. Effect on motor recovery of hind limbs was evaluated for 10 days postinjury. RESULTS: The spinal injury resulted in tissue damage, apoptosis, edema, infiltration of neutrophils with increased expression of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2). The spinal tissue showed elevated levels of prostaglandin E2 (PGE2), and LTB4 and increased phosphorylation of injured extracellular signal-regulated kinase-1/2 (ERK1/2). The PHP, ZFL and combination decreased inflammation, tissue injury and infiltration of neutrophils. Treatment also decreased the levels of PGE2, phosphorylation of extracellular signal-regulated kinase-1/2 (pERK 1/2), LT, TNF-α and COX-2 with a marked reduction in apoptosis and improved the motor function. CONCLUSION: The present study confirmed 5-LO antagonist activity of PHP and established its neuroprotective role along with ZFL.

Oral Antihistamines Alone vs in Combination with Leukotriene Receptor Antagonists for Allergic Rhinitis: A Meta-analysis.

Objective To evaluate whether an adjuvant therapy of leukotriene receptor antagonists (LTRAs) based on oral H1-antihistamines (H1) can increase efficacy of allergic rhinitis (AR) treatment. Data Sources The search involved databases of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials, from inception up to September 23, 2017. Randomized controlled trials (RCTs) that compared efficacy of LTRAs + H1 vs H1 alone were eligible. Review Methods Pooled comparative effects were measured using weighted mean difference (WMD) and 95% confidence interval (CI). Subgroup analysis comparing seasonal vs perennial AR was prespecified to explore the source of heterogeneity. The evidence quality of each outcome was assessed by the GRADE approach. Results A total of 8 RCTs were included (n = 1886), and all measured outcomes used scaled scores. Compared with H1 alone, H1 + LTRAs were superior to improve overall daytime (WMD, -0.11; 95% CI, -0.19 to -0.03, high quality) and composite (WMD, -0.12; 95% CI, -0.23 to -0.01; low quality) nasal symptoms. Specifically, H1 + LTRAs had better efficacy against composite nasal rhinorrhea, sneezing, and daytime itching but not congestion. The effects were more pronounced in patients with perennial AR compared to those with seasonal AR. There were no significant differences in nighttime nasal symptoms and eye symptoms between the 2 groups. Conclusion The current evidence suggests that LTRAs + H1 can increase the therapeutic efficacy against daytime and composite nasal symptoms, including rhinorrhea, sneezing, and itching; however, it does not affect nighttime nasal symptoms and eye symptoms. The patients with perennial AR may benefit more from the combination therapy.

Clopidogrel but Not Prasugrel Significantly Inhibits the CYP2C8-Mediated Metabolism of Montelukast in Humans.

The oxidation of montelukast is mainly mediated by cytochrome P450 (CYP) 2C8, but other mechanisms may contribute to its disposition. In healthy volunteers, we investigated the effects of two widely used P2Y12 inhibitors on montelukast pharmacokinetics. Clopidogrel (300 mg on day 1 and 75 mg on day 2) increased the area under the plasma concentration-time curve (AUC) of montelukast 2.0-fold (90% confidence interval (CI) 1.72-2.28, P < 0.001) and decreased the M6:montelukast AUC0-7h ratio to 45% of control (90% CI 40-50%, P < 0.001). Prasugrel (60 mg on day 1 and 10 mg on day 2) had no clinically meaningful effect on montelukast pharmacokinetics. Our results imply that clopidogrel is at least a moderate inhibitor of CYP2C8, but prasugrel is not a clinically relevant CYP2C8 inhibitor. The different interaction potentials of clopidogrel and prasugrel are important to consider when antiplatelet therapy is planned for patients at risk for polypharmacy with CYP2C8 substrates.

Lack of long-term add-on effect by montelukast in postoperative chronic rhinosinusitis patients with nasal polyps.

OBJECTIVES/HYPOTHESIS: Eosinophils and mast cells are among the key cells in inflammatory diseases like chronic rhinosinusitis (CRS) and asthma. Leukotriene antagonists have proven to be effective in the treatment of asthma, but data about their efficacy in CRS are scarce, whereas data on montelukast as an add-on treatment to intranasal corticosteroids (INCS) in a postoperative setting are completely lacking. STUDY DESIGN: Prospective, randomized, open-label trial. METHODS: In this trial with long-term follow-up, we evaluated the efficacy of montelukast as an add-on treatment to INCS in postoperative CRS with nasal polyp (CRSwNP) patients. CRSwNP patients (N = 72) undergoing endoscopic sinus surgery were randomized in two arms for the postoperative treatment. One group (N = 36) received INCS in monotherapy, whereas the other group (N = 36) received INCS in association with montelukast for 1 year. The efficacy of montelukast with INCS was evaluated by assessing both subjective (total five-symptom score [T5SS]) and objective (nasal polyp score [NPS], Lund-Mackay [LMK] score, and subjective olfactometry [Barcelona Smell Test 24]) outcome parameters and compared with the gold standard of INCS in monotherapy. RESULTS: After 1 year of surgery, T5SS, NPS, and LMK score were significantly reduced in patients treated with either INCS or INCS plus montelukast, without significant differences between the two treatment arms. Improvement of smell loss by olfactometry was also observed with no differences between arms. Similar findings were observed at 3 and 6 months. CONCLUSIONS: These results suggest that the addition of montelukast to INCS should not be recommended in the treatment of postoperative CRSwNP patients. LEVEL OF EVIDENCE: 1b Laryngoscope, 1743-1751, 2018.

Antagonism of cysteinyl leukot-riene receptor 1 (cysLT1R) by montelukast regulates differentiation of MC3T3-E1 cells under overloaded mechanical environment.

Long-term exposure to overloaded mechanical environment induces bone fatigue damage symptoms and osteoblast damages. Montelukast is a selective cysteinyl leukot-riene receptor 1 (cysLT1R) antagonist, which has been used for the treatment of bronchial asthma in clinics. In the current study, we have identified a novel pharmacological role of montelukast by finding that it has protective properties against overload damage in osteoblastic MC3T3-E1 cells. Firstly, our results show that CysLT1R is expressed in MC3T3-E1 cells. Mechanical tensile strain of 5000-7000 µÎµ resulted in a significant upregulation of CysLT1R in osteoblastic MC3T3-E1 cells in an intensity dependent manner. Secondly, MTT assay indicates that loading with 5000 µÎµ mechanical strain inhibited cell proliferation, which was suppressed by montelukast treatment. Furthermore, montelukast promotes cell differentiation by increasing the expression of ALP and RUNX2. Alizarin Red S staining assay showed that montelukast abolished the inhibitory effects of overload mechanics on osteoblast mineralization. Mechanistically, the effect of montelukast on osteoblastic differentiation acted by activating the extracellular regulated protein kinases (ERK) pathway. The obtained results suggested that montelukast promotes proliferation and differentiation in osteoblasts exposed to overload mechanics.

The role of cysteinyl leukotrienes and their receptors in refractory nasal polyps.

Leukotriene signaling is essential in many diseases, including asthma, allergic rhinitis, atherosclerosis and inflammatory bowel disease. Nevertheless, the expression of cysteinyl leukotrienes (CysLTs) and its receptors (CYSLTRs) in different types of nasal polyps (NPs), and the role of their antagonist in the treatment of refractory chronic rhinosinusitis with nasal polyps (CRSwNP) are not well understood. The following study investigates the expression of CysLTs and CYSLTRs in different types of NPs, as well as the role of leukotriene receptor antagonist (montelukast) in refractory NPs. Our data showed that CysLTs and CYSLTRs were significantly elevated in CRSwNP group (p < 0.05), particularly in IL-5+NP patients, compared to patients with chronic rhinosinusitis but without NPs (CRSsNP) and the control group. Furthermore, montelukast have shown the ability to inhibit the expression of MUC5AC, TSLP, IL-4, IL-5, IL-13, and TGF-ß in NP explants after treatment with Staphylococcal Enterotoxins B (SEB). In addition, the patients treated by additional montelukast have better outcomes compared to those with INCS only. To conclude, our results demonstrate that the inhibition of CysLTs signaling by montelukast decreases the expression of cytokines and mucin in polyp explants, and in turn promotes the recovery in patients with refractory CRSwNP.

General Management Principles of the Pregnant Woman.

Pregnancy is a dynamic process that consists of profound physiological changes mediated by hormonal, mechanical, and circulatory pathways. Understanding of changes in physiology is essential for distinguishing abnormal and normal signs and symptoms in a pregnant patient. These physiological changes also have important pharmacotherapeutic considerations for a pregnant patient. Although there are limited data to guide decisions regarding medications and diagnostic procedures in pregnancy, a careful review of risks should be balanced with review of risk of withholding a medication or procedure. Interventional pulmonary procedures can be safely performed in pregnant women while keeping in mind the maternal anatomic and physiologic changes. Furthermore, management of a maternal cardiopulmonary arrest requires important modifications in patient positioning and intravenous access to ensure adequate efficacy of chest compressions, circulation, and airway management. This review will provide an overview of maternal physiologic changes with a focus on cardiopulmonary physiology, pharmacotherapeutic considerations, diagnostic and interventional pulmonary procedures during pregnancy, and cardiopulmonary resuscitation in pregnancy.

LTB4 and montelukast in transplantation-related bronchiolitis obliterans in rats.

BACKGROUND: Lung transplantation is the only effective treatment for end-stage lung diseases. Bronchiolitis obliterans, which is known as non-infectious chronic lung allograft dysfunction (CLAD) in the new classification, is the greatest threat to long-term survival after lung transplantation. This study investigated the role of leukotriene B4 (LTB4) and montelukast in transplantation-related bronchiolitis obliterans and discussed the pathophysiological significance of LTB4 in chronic rejection. METHODS: Rats were randomly divided into an experimental group (montelukast), a positive control group (dexamethasone), and a blank control group (normal saline solution; NS). Each piece of trachea removed from a F344 rat was transplanted into a Lewis rat through a 5-mm incision at the episternum by subcutaneous embedding. The recipients were treated with gastric lavage with 3 mg/kg · d montelukast suspension, 1 mg/kg · d dexamethasone, and 1 mL/kg · d NS, respectively, in each group. On Day 28, peripheral blood was drawn to measure the white blood cell counts and plasma LTB4 levels. The donor specimens were stained by H-E and Masson, and their organizational structure and extent of fibrosis were visually assessed. The measurement data were compared using one-way analysis of variance, and the categorical data were compared using the chi-square test. A P value of less than 0.05 was considered to indicate statistical significance. RESULTS: The white blood cell counts of the montelukast, dexamethasone, and NS groups were (16.0 ± 4.2) × 109/L, (19.5 ± 11.6) × 109/L, and (25.8 ± 3.6) × 109/L; no statistical significance was found (P = 0.101). The concentrations of LTB4 were 2230 ± 592 pg/mL, 1961 ± 922 pg/mL, and 3764 ± 1169 pg/mL, and statistical significance was found between the NS group and each of the others (P = 0.009). The percentages of tracheal occlusion were 73.6% ± 13.8%, 23.4% ± 3.2%, and 89.9% ± 11.3%, and statistical significance was found among the three groups (P = 0.000). CONCLUSIONS: The study established a model to simulate bronchiolitis obliterans after clinical lung transplantation. Oral administration of montelukast reduced plasma LTB4 levels in rats and played a preventive role against tracheal fibrosis after transplantation. This suggests that LTB4 may be involved in bronchiolitis obliterans after pulmonary transplantation. This study indicates a new direction for research into the prevention and treatment of bronchiolitis obliterans after lung transplantation.