Montelukast Treatment Research Articles

Influence of the Polymorphism C-509T in the TGFB1 Gene Promoter on the Response to Montelukast.

Transforming growth factor beta 1 (TGFB1) is a multifunctional cytokine with a key role in asthma airway inflammation and remodeling. Since elevated levels of this cytokine in airways might be associated with response to asthma therapy, the aim of this study was to investigate whether the presence of the polymorphism C-509T in the promoter of the TGFB1 gene is associated with response to montelukast. A group of 102 asthmatic patients was genotyped for the presence of the C-509T polymorphism by DNA sequencing and subjected to induced sputum sampling. Cells from sputum samples and BEAS 2B cells were treated with montelukast and endogenous TGFB1 expression was measured by quantitative real-time polymerase chain reaction. The promoter activity was analyzed by luciferase assays in BEAS 2B cells transfected with constructs carrying variants -509C and -509T of the TGFB1 gene promoter. After treatment with montelukast, the decrease in TGFB1 gene expression was greater for the -509TT genotype (58.9%) than for the -509CC and -509CT genotypes (49.6% and 31.8%, respectively) (P = 0.071). In BEAS 2B cells, expression of endogenous TGFB1 was reduced by about 27% after montelukast treatment, while luciferase activity of both promoter variants was increased after montelukast treatment (-509C allele: 48.3%, P = 0.060; and -509T allele: 100.5%, P = 0.062). A more intensive response was registered in the promoter containing the -509T allele, which had 135% higher activity than the -509C variant (P = 0.035). This study showed that the presence of the -509T allele in the TGFB1 promoter might modulate effects of montelukast on TGFB1 gene expression, but future studies are necessary, taking into consideration other genetic and nongenetic factors. It is of potential importance for clinical management of asthma to clarify the influence of the C-509T polymorphism on the response to treatment with montelukast.

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 με 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 με 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.

Montelukast reduces inhaled chlorine triggered airway hyperresponsiveness and airway inflammation in the mouse.

Cysteinyl leukotrienes (CysLTs) are pro-inflammatory lipid mediators that exacerbate disease state in several asthma phenotypes including asthma induced by allergen, virus and exercise. However, the role of CysLTs in irritant-induced airway disease is not well characterized. The purpose of the current study was to investigate the effect of montelukast, a CysLT1 receptor antagonist, on parameters of irritant-induced asthma induced by inhalation of chlorine in the mouse. BALB/c mice were exposed to chlorine in air (100ppm, for 5min). Montelukast (3mg·kg-1 ) or the vehicle (1% methylcellulose) was administered 24 and 1h prior to chlorine exposure and 1h prior to outcome measurements. Twenty-four hours after exposure, responses to inhaled aerosolized methacholine, cell composition and an array of cytokines/chemokines in bronchoalveolar lavage (BAL) fluid were measured. Neutralizing antibodies against IL-6 and VEGF were administered prior to exposures. Montelukast reduced chlorine -induced airway hyperresponsiveness (AHR) to methacholine in the peripheral lung compartment as estimated from dynamic elastance, but not in large conducting airways. Montelukast treatment attenuated chlorine-induced macrophage influx, neutrophilia and eosinophilia in BAL fluid. Chlorine exposure increased VEGF, IL-6, the chemokines KC and CCL3 in BAL fluid. Montelukast treatment prevented chlorine-induced increases in VEGF and IL-6. Anti-IL-6 antibody inhibited chlorine-induced neutrophilia and reduced AHR. Pre-treatment with montelukast attenuated chlorine-induced neutrophilia and AHR in mice. These effects are mediated, in part, via IL-6.

The prophylactic and therapeutic effects of montelukast on delayed neuropsychologic sequelae after acute carbon monoxide poisoning in rat model

Objective o investigate the prophylactic and therapeutic effects of montelukast, a cysteinyl leukotriene receptor-1 (CysLT1R) antagonist, on the delayed neuropsychological sequelae (DNS) in rat model of carbon monoxide (CO) poisoning and to explore the possible underlying mechanism. Methods A total of 90 rats were acclimated for one week prior to screening rat by Morris water maze test. Ten rats were randomly assigned to control group (Con group), and the remaining 80 rats were subjected to modified method of intraperitoneal injection of CO gas to establish animal model of acute CO poisoning, Thereafter, the survival rats randomized into CO poisoning group (Mod group), low-dose montelukast group (ML group), medium-dose montelukast group (MM group), high-dose montelukast group (MH group) (n=10 each). Montelukast was accordingly administered via intragastric tube at different intervals (30 min, 4 h and 12 h) after CO poisoning, and then montelukast was administered every 12 hours for 7 consecutive days. The rats of control group and Mod group received equal volume of normal saline instead at given intervals. Twenty-one days after CO exposure, the average escape latency was measured by Morris water maze test to screen DNS rats followed by H-E staining to observe the pathological changes of cortex and hippocampal CA1 region and TUNEL was used to assess the apoptosis of neurons in cortex and hippocampal CA1 region after rats sacrificed. Results All CO-exposed rats exhibited cognition function lowered, and the escape latency (seconds) in Mod group (43.3 ± 15.5), ML group (31.5 ± 13.2) and MH groups (30.1 ± 12.2) was significantly prolonged compared with Con group (12.1 ± 3.0) (P 0.05). Compared with Mod group, the escape latency in montelukast treatment groups was shortened, whereas the significant difference in escape latency only found between Mod group and MM group (P < 0.05). Except for Con group, DNS was evident in CO-exposed groups, and the numbers of DNS rats in Mod, ML, MM and MH groups were 8, 5, 1, 4, respectively, which made statistically significant differences to Con group (P< 0.05) except MM group. The DNS incidence in MM group was lower than that in Mod group (P < 0.05). Mod group exhibited severe histopathological injury to the brain, with evident apoptosis of neural cells, whereas in the groups with montelukast treatment, histopathological damage to the brain was mitigated and the number of apoptotic neuronal cells was diminished noticeably in MM group. Conclusion Montelukast can ameliorate the cognitive function of rats, decrease the incidence of DNS and reduce the apoptosis of neural cells as well as attenuate neuronal cell injury, thus exerting neuroprotection against DNS in rats with CO poisoning. Key words: Montelukast; Cysteinyl leukotriene receptor-1; Rat; Carbon monoxide poisoning; Delayed neuropsychologic sequelae; Morris water maze; Escape latency; Neuronal apoptosis

Effect of montelukast on progression of atherosclerosis

Objective: this study was undertaken to evaluate the effect of montelukast on the progression of atherosclerosis. Materials and methods: A total of 28 local domestic rabbits were assigned into four groups: Group I (normal control), Group II (atherogenic control), Group III (vehicle control),Group IV (montelukast 1.5 mg\kg daily). Blood samples were collected at the end of experiment (8 weeks) for measurement of serum triglycerides (TG), total cholesterol (TC), HDL-C, plasma high sensitive C-reactive protein (hsCRP), plasma malondialdehyde (MDA) and plasma reduced glutathione (GSH). Immunohistochemical analysis (VCAM-1, MCP-1, and TNF-α) and histopathologic assessment of aortic atherosclerotic changes were also performed.&#x0D; Results: Compared to NC, levels of lipid profile, atherogenic index, hsCRP, and MDA are increased while GSH were decreased in animals on atherogenic diet (p&lt; 0.05). Immunohistochemical analysis showed that aortic expression of VCAM 1, MCP-1, and TNF-α were significantly increased in AC group compared to NC group (p&lt;0.001). Histopathologic finding showed that animals on atherogenic diet have significant atherosclerotic lesion compared to NC group. Compared to AC group montelukast don’t have significant effect on lipid profile. Montelukast causes statistically significant reduction in hsCRP and MDA (p&lt;0.05). Montelukast treatment causes significantly increase the level of GSH. Montelukast treatment significantly reduced aortic expression of VCAM-1, MCP-1, and TNF-α (p&lt;0.005). Histopathologic examination of aortic arch showed that montelukast significantly reduced atherosclerotic lesion (p&lt;0.005).Conclusions: It thus can conclude that montelukast reduces lipid peroxidation, systemic inflammation and aortic expression of inflammatory markers used in this study and hence reduce the progression of atherosclerosis.

Montelukast treatment protects nigral dopaminergic neurons against microglial activation in the 6-hydroxydopamine mouse model of Parkinson's disease.

Although the main cause of degeneration of the nigrostriatal dopaminergic (DA) projection in Parkinson's disease (PD) is still controversial, many reports suggest that excessive inflammatory responses mediated by activated microglia can induce neurotoxicity in the nigrostriatal DA system in vivo. Montelukast, which plays an anti-inflammatory role, is used to treat patients with asthma. In addition, recent studies have reported that its administration could reduce neuroinflammatory activities, showing beneficial effects against various neuropathological conditions. These results suggest that montelukast may be a useful drug to alleviate inflammatory responses in PD, even though there are no reports showing its beneficial effects against neurotoxicity in the nigrostriatal DA system. In the present study, our results showed that treatment with montelukast could protect DA neurons against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity and its administration significantly attenuated the production of neurotoxic cytokines such as tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) from activated microglia in the substantia nigra (SN) and striatum following 6-OHDA treatment. Therefore, we suggest that montelukast can be used as a potential inhibitor of microglial activation to protect DA neurons in the adult brain against PD.

Treatment of chronic spontaneous urticaria with an inadequate response to H1-antihistamines: an expert opinion.

Chronic spontaneous urticaria (CSU) is characterized by the sudden, continuous or intermittent appearance of pruritic wheals (hives), angioedema, or both for six weeks or more, with no known specific trigger. The international EAACI/GA2LEN/EDF/WAO urticaria guideline advises standard-dose, second-generation H1-antihistamines as first-line therapy. However, H1-antihistamine treatment leads to absence of symptoms in fewer than 50% of patients. Updosing of second-generation H1-antihistamines (up to fourfold) as recommended by the EAACI/GA2LEN/EDF/WAO urticaria guideline as second-line therapy, can improve response, but many patients remain symptomatic. Definitions of response are often subjective and a consensus is needed regarding appropriate treatment targets. There is also an unmet need for biomarkers to assess CSU severity and activity and to predict treatment response. The EAACI/GA2LEN/EDF/WAO urticaria guideline recommends add-on omalizumab, ciclosporin A (CsA), or montelukast third-line treatment in patients with an inadequate response to high-dose H1-antihistamines. Omalizumab is currently the only licensed systemic biologic for use in CSU. Both omalizumab and CsA are effective third-line CSU treatments; montelukast appears to have lower efficacy in this setting. Omalizumab carries a label warning for anaphylaxis, although no cases of anaphylaxis were reported in the phase III trials of omalizumab in CSU and it is generally well tolerated in patients with CSU. Omalizumab arguably has a better safety profile than CsA.

The effect of montelukast on depression behaviour in rat forced swimming test

Objective: Montelukast (brand name: Singulair), which is used for treatment of chronic asthma, is a leukotriene receptor antagonist. The psychiatric side effects of montelukast use in asthma patients are controversial. The aim of this study is to examine the effect of montelukast treatment on depression behavior in both healthy and asthmatic rats. Method: 50 wistar albino female rats, of between 150 and 250 g in weight, were used in this study. The study was conducted with two groups: Group I: healthy group; including control, asthma, and montelukast-treated asthma subgroups (n=20) and Group II: asthmatic group including control, asthma, and montelukast-treated asthma subgroups (n=30). The bronchial asthma model was employed for all the rats in the asthmatic group. In this model, the animals were sensitized by giving ovalbumin intraperitoneally and they were also provoked by breathing ovalbumin. Montelukast was given to the rats intraperitoneally at a dose of 10 mg/kg for 10 days in montelukast-treated subgroups of both groups. A forced swimming test was used to determine the effect of montelukast treatment on depression behavior. Results: In the healthy rats (Group I), immobility time increased in montelukast-treated asthmatic rats compared to the control subgroup (p0.05). However, in this group (Group II), immobility time was higher in montelukast-treated asthmatic rats compared to saline treated asthmatic rats (p

Urinary cysteinyl leukotriene E4 level and therapeutic response to montelukast in children with mild obstructive sleep apnea.

Antileukotriene has been used for alleviating disease severity in children with adenotonsillar hypertrophy (ATH) and mild obstructive sleep apnea (OSA). Previous study showed the relationship between urinary cysteinyl leukotriene E₄ (uLTE₄) level and therapeutic response to montelukast in asthmatic adults. However, this relationship has never been investigated in pediatric OSA. To determine the relationship between uLTE₄ level and therapeutic response to montelukast in children with ATH and mild OSA. Children aged 3-15 yrs who had ATH and mild OSA were enrolled. All had quality of life (assessed by Thai version OSA-18 QoL questionnaire) and uLTE₄ levels measured prior to start a 6-week course of montelukast treatment. Overnight polysomnography (PSG) and QoL reassessment were performed after completing the treatment. Those who demonstrated a large improvement of mean total QoL score or ≥ 50% decrease of obstructive apnea-hypopnea index (OAHI) after the treatment were defined as responders. Twenty-six children were enrolled (mean age 7.5 ± 2.9 yrs, 38.5% male). After 6-week course of montelukast, nine (34.6%) children showed significant improvement. The mean uLTE₄ level from the responders was higher comparing to the non-responders (2,952.56 ± 966.9 vs. 978.6 ± 460.8 pg/mg creatinine; p < 0.001). uLTE₄ level of ≥ 1,457 pg/mg creatinine had 100% sensitivity and 88.2% specificity in identifying the responders. We found the association between ULTE4 and therapeutic response to monteleukast. The uLTE₄ level of ≥ 1,457 pg/mg creatinine could predict the therapeutic response to montelukast in children who had ATH and mild OSA.

Effect of montelukast on markers of airway remodeling in children with asthma.

Asthma is a pathology characterized by chronic inflammation and remodeling of the airways. To evaluate the effect of montelukast treatment on markers of airway inflammation and remodeling in children with mild asthma and to evaluate if the administration of montelukast to children with mild asthma could inhibit the release of matrix metallopeptidase 9, matrix metallopeptidase 12, tissue inhibitor of metalloproteinase 1, transforming growth factor beta 1, C-peptide terminal procollagen type (PICP), and eosinophils count, which are markers of inflammation and remodeling in induced sputum. Thirty children with mild asthma were recruited. They were randomized into two groups: group A received montelukast and as needed beta-2-agonist for 8 weeks (T0-T1), whereas group B received placebo and as needed beta-2-agonist for 8 weeks. After 2 weeks of washout (T1-T2), they were reallocated for treatment according a crossover design (T2-T3). Tests for lung function, oral exhaled nitric oxide, and hypertonic saline solution-induced sputum level were performed at T0-T1-T2-T3. In the placebo group, the PICP mean (standard deviation [SD]) value at baseline was 2279.42 ± 2530.77 pg/mL and 1916.00 ± 2178.75 pg/mL after treatment. Patients treated with montelukast, in contrast, showed a baseline mean (SD) value of 2439.29 ± 2834.51 pg/mL and 1406.72 ± 1508.65 pg/mL after treatment. The difference between the mean pre- and posttreatment decrease of PICP in the two groups was statistically significant (delta -690.21 pg/mL [95% confidence interval, -1220.83 to -159.5844 pg/mL]; p = 0.011). The mean (SD) percentage of the eosinophil count in the placebo group was 3.11 ± 4.03% at baseline and 4.86 ± 5.83% after treatment. Patients treated with montelukast, in contrast, showed a percentage mean (SD) value at baseline of 4.51 ± 5.48% and, after treatment, of 3.06 ± 3.29%. The difference between the mean pre- and posttreatment decrease of the percentage eosinophil count in the two groups was statistically significant (delta -2.76% [95% confidence interval, -4.65 to -0.87%]; p = 0.004). This study investigated in vivo effects of montelukast on remodeling markers. The reduction of PICP levels and eosinophil count supported the hypothesis that montelukast can modulate collagen deposition in airways and reduce eosinophilic airway inflammation. Clinical Trials database clinicaltrials.gov (NCT00875082).

Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model

ObjectiveThe potency of acute montelukast treatment, a leukotriene receptor antagonist, has been demonstrated as tocolytic on in vitro myometrial contractility. This study assessed the ability of a 48h montelukast treatment to modify in vitro contractions under inflammatory conditions in a pregnant rat model. Study designPregnant Sprague-Dawley rats were injected intraperitoneally (gestational days 20–22) with lipopolysaccharides (LPS) 200μg/kg (4 treatments at 12h intervals) alone or combined with montelukast 10mg/kg/day or a saline solution for a 48h period. Uterine rings (n=72) were obtained by median laparotomy at day 22. Spontaneous contractile activities were compared using pharmacological compounds (oxytocin, nifedipine) along with assessment of contractile parameters. Myometrial subcellular fractions were also analyzed by Western blot to quantify oxytocin, cysteinyl leukotriene receptors and inflammation markers. ResultsIn in vitro experiments, the area under the curve, the amplitude and the duration of phasic contractions were significantly reduced following 48h of LPS+montelukast treatment comparatively to the LPS group. Moreover, in this same group, oxytocin (10−9–10−7M) largely decreased uterine sensitivity (p=0.04). Following LPS and montelukast treatment, the tocolytic effectiveness of nifedipine (10−9–10−7M) was increased (p<0.01). Western blot analysis confirmed the presence of type 1 CysLT receptors in all treated groups. Hence, montelukast treatment restored TNF-α and COX-2 basal levels. ConclusionOur results strongly suggest that montelukast treatment could facilitate a relative uterine quiescence by decreasing its sensitivity to uterotonic agent or by increasing tocolytic efficiency under proinflammatory conditions.

The beneficial effects of Montelukast against 2,3,7,8-tetrachlorodibenzo- p -dioxin toxicity in female reproductive system in rats.

To determine the toxic effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on reproductive system and the beneficial effects of Montelukast (ML) with histological and biochemical analysis. Rats were randomly divided into four equal groups (control, TCDD, ML and TCDD+ML). Tissue samples were collected on day 60 and oxidative status and histological alterations were analyzed. The results showed a significant increase in oxidative and histological damage on uterine and ovarian tissues. Otherwise, the oxidative and histological damages caused by TCDD were prevented with ML treatment. The toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on female reproductive system were reversed with Montelukast treatment. Therefore, we claimed that ML treatment might be useful for TCDD toxicity.

Psychiatrc symptoms induced by montelukast: A case report

Introduction Montelukast is a leukotrienes receptor antagonist, which is used, in chronic asthma, exercise induced broncoconstriction and allergic rhinitis treatment. Montelukast inhibates the proinflammatory cytokines and leukotriene is released from the specific cells. Leukotrienes cause mucus secretion, vasodilatation, broncoconstriction and eosinophilia. This case is about an asthma-diagnosed child who had acute disturbing behaviour and sleeping problems after using montelukast treatment. Case A 5 year-old boy assessed because of symptoms like breaking the rules, disturbing friends, self-harming, hyperactivity, distractability, insomnia and nightmares. In his history, when he was 9months old acute hyperactivity, yelling, naughtiness, insomnia, disturbing and self-harming behaviours occurred suddenly 24hours after intravenous montelukast treatment due to asthma crisis. While he was still using oral montelukast, his parents had cut off the treatment. After about 2months, there was decrease in the symptoms. After using montelukast, these kinds of misbehaviour occurred again in a week. The montelukast treatment was terminated controlled way under a pediatrician consultation. Turgay DSM-IV Based Distruptive Behaviour Disorders Screening and Rating Scale were completed by both of the parents in the first interview and after 2months of cutting off montelukast treatment. While comparing 2 scales and parents' anamnesis, we found that impulsivity, oppositional defiant, hyperactivity, distractability, breaking off the rules, irritability, insomnia and having nightmares reduced. Conclusion Montelukast can cause many psychiatric symptoms. In that case we found sleeping problems and disturbing behaviour caused or induced by montelukast treatment. As in that case, other drugs also can cause or enhance psychiatric symptoms. So it is important to assess the other drugs while assessing the diagnosis and the treatment.

Roflumilast combined with montelukast versus montelukast alone as add-on treatment in patients with moderate-to-severe asthma

Roflumilast, a selective phosphodiesterase 4 inhibitor, has been shown to provide modest improvements in lung function in patients with mild-to-moderate asthma, but its efficacy in patients with moderate-to-severe asthma has not been assessed. We hypothesized that this drug might provide benefit if combined with montelukast, a leukotriene receptor antagonist, in patients whose symptoms are uncontrolled by inhaled corticosteroids and long-acting β-agonists. We sought to examine the efficacy, safety, and mode of action of the addition of roflumilast and montelukast versus montelukast alone in patients with moderate-to-severe asthma. In a phase 2, randomized, double-blind, placebo-controlled, multiple-dose, 2-sequence, crossover study, 64 patients were randomized to receive 500μg of roflumilast plus montelukast followed by placebo plus 10mg of montelukast (sequence AB) or placebo plus 10mg of montelukast followed by 500μg of roflumilast plus 10mg of montelukast (sequence BA). All patients had a diagnosis of bronchial asthma inadequately controlled by at least a medium-dose inhaled corticosteroid plus a long-acting β-agonist. The analysis of FEV1 change from baseline to week 4 showed a statistically significant and clinically meaningful treatment difference of 100mL for roflumilast plus montelukast versus placebo plus montelukast. Also, improvements in patient-reported outcomes and a reduction in urinary leukotriene E4 levels were observed during roflumilast plus montelukast treatment compared with placebo plus montelukast treatment. Adverse events were consistent with the known safety profile of roflumilast. The combination of roflumilast with montelukast compared with montelukast alone improved lung function and asthma control in patients with moderate-to-severe asthma and deserves further study for this indication.

Montelukast versus Dexamethasone Treatment in a Guinea Pig Model of Chronic Pulmonary Neutrophilic Inflammation

Airway inflammation in chronic obstructive pulmonary disease (COPD) is refractory to corticosteroids and hence COPD treatment is hindered and insufficient. This study assessed the effects of oral treatment with Montelukast (10 and 30 mg/kg) or dexamethasone (20 mg/kg) for 20 days on COPD model induced by chronic exposure to lipopolysaccharide (LPS). Six groups of male guinea pigs were studied. Group 1: naïve group, group 2: exposed to saline nebulization. Groups 3, 4, 5, and 6: exposed to 9 nebulizations of LPS (30 μg/ml) for 1 hour, 48 hours apart with or without treatment with Montelukast or dexamethasone. Airway hyperreactivity (AHR) to methacholine (MCh), histopathological study and bronchoalveolar lavage fluid (BALF) as well as lung tissue analyses were performed 48 hours after the final exposure to LPS (day 20). LPS-induced pulmonary dysfunction was associated with increased neutrophil count, leukotriene (LT) B4, and tumor necrosis factor (TNF)-α in BALF. Moreover, there was an increase in malondialdehyde (MDA) level and a decrease in histone deacetylases(HDAC) activity in the lung tissue. Both Montelukast (10 or 30 mg /kg) and dexamethasone significantly reduced neutrophil count in BALF and inflammatory cells in lung parenchyma as well as TNF-α, and MDA levels. However, dexamethasone was more effective (p < 0.05). Montelukast, at a dose of 30 mg /kg, significantly reduced specific airway resistance after the 9th LPS exposure, attenuated AHR to MCh, decreased LTB4 and increased HDAC activity in comparison to dexamethasone. These results suggest that treatment with Montelukast can be useful in chronic airway inflammatory diseases including COPD poorly responsive to glucocorticoids.

Comparison of Oral Montelukast and Intranasal Fluticasone in Patients with Asthma and Allergic Rhinitis.

Even though the links between upper and lower airway had been of interest to clinicians since long back, it has not attracted the attention of the researchers till recent past. But the evidence is still far from conclusive, due to limited number of randomized controlled trials available on subjects with concomitant allergic rhinitis and asthma. This gap in the knowledge is even more conspicuous in Indian population. The current study is conducted with an objective of comparing the efficacy and tolerability of intranasal Fluticasone and oral Montelukast in treatment of allergic rhinitis and bronchial asthma. The study was a prospective randomized, single blinded, comparative, parallel group study, with two intervention groups conducted in a tertiary teaching hospital in Chennai, Southern India. One hundred and twenty patients diagnosed with concomitant diagnosis of allergic rhinitis and bronchial asthma was randomly allocated to either Fluticasone propionate aqueous nasal spray or oral Montelukast group. Out of total 120 subjects recruited, 108 subjects were included in the final analysis. The mean reduction in asthma and rhinitis symptom scores and improvement in PEFR was higher for Group A, compared to Group B during all the follow-up periods. No statistically significant difference was observed in proportion of subjects reporting exacerbations in the current study. Both the treatments were well tolerated. Addition of intranasal Fluticasone propionate to Salmeterol plus Fluticasone is beneficial in improving asthma control, allergic rhinitis control and lung functions as compared to oral Montelukast. Thereby the use of intranasal Fluticasone Propionate in comparison to oral Montelukast in control of Allergic Rhinitis is justified as per the significant improvement in outcome measures.

A Double-Blind, Randomized, Crossover Study to Compare the Effectiveness of Montelukast on Atopic Dermatitis in Korean Children.

PurposeSome studies report a role of leukotrienes in the pathogenesis of atopic dermatitis and suggest a rationale for the use of leukotriene receptor antagonist (LTRA) in the treatment of atopic dermatitis. This study aimed to evaluate the treatment effectiveness of montelukast in children with atopic dermatitis.MethodsFifty-four children between the ages of 2 and 6 years with moderate to severe atopic dermatitis were enrolled. Group A received montelukast for 8 weeks, followed by a crossover to 8 weeks of placebo after a 2-week washout period. Group B reversed the administration according to a randomized, double-blind, placebo-controlled, crossover design. The SCORing atopic dermatitis (SCORAD) index, urinary leukotriene E4 (LTE4), and eosinophil-derived neurotoxin (EDN) were assessed at every visit.ResultsForty-three patients (21 males) completed the study. Although the SCORAD index was decreased in both groups, there was no statistically significant difference between montelukast and placebo (-3.0±11.2 vs -5.7±11.3, P=0.43). The level of urinary LTE4 was decreased after taking montelukast when compared to placebo, but there was no statistically significant difference (-65.9±556.2 vs 87.7±618.3, P=0.26). The changes in urinary EDN after taking montelukast and placebo had no significant difference (37.0±1,008.6 vs -195.8±916.7, P=0.10). When analyzing SCORAD indices, urinary LTE4, and EDN, we could not prove the effectiveness of montelukast in the atopic, non-atopic or high ECP (ECP ≥15 µg/L) subgroups.ConclusionsThere was no statistically significant difference in clinical improvement or biomarkers between montelukast and placebo treatment. Therefore, conventional treatments with skin care and infection control might be more important strategies in the treatment of atopic dermatitis.

Efficiency of montelukast in control of atopic diseases at children of preschool age

The aim of study. To estimate clinical efficiency of the antagonist of the leukotriiene receptors - montelukast in control of atopic diseases at children of preschool age. Materials and methods. Open randomized comparative study of clinical efficiency of montelukast in parallel groups of children of preschool age having atopic diseases was conducted. Results. Inclusion of montelukast (singular) in basic therapy of children of preschool age, having atopic diseases, allowed to decrease the number of exacerbations of a bronchial asthma and allergic rhinitis and as well as the necessity of «emergency aid», when a dose of topical glucocorticosteroids reduced 1,9 times. Conclusion. Montelukast treatment showed high clinical efficiency and allowed to control symptoms of allergic rhinitis and bronchial asthma, when it was included in the basic therapy of atopic diseases at children of preschool age.

Leukotriene receptor antagonists as maintenance and intermittent therapy for episodic viral wheeze in children.

Episodic viral wheeze (EVW) associated with viral respiratory tract infections is a common reason for pre-school children to utilise health care resources and for carers to take time away from employment. About a third of children experience a wheezing episode before the age of five years. EVW therefore represents a significant public health problem. Many pre-school children only wheeze in association with viral infections and in such cases EVW appears to be a separate entity from atopic asthma. Some trials have explored the effectiveness of leukotriene receptor antagonists (LTRAs) as regular (maintenance) or episodic (intermittent) treatment in this context. To evaluate the evidence for the efficacy and safety of maintenance and intermittent LTRAs in the management of EVW in children aged one to six years. We searched the Cochrane Airways Group register of trials with pre-specified terms. We performed additional searches by consulting the authors of identified trials, online trial registries of manufacturers' web sites, and reference lists of identified primary papers and reviews. Search results are current to June 2015. We included randomised controlled trials with a parallel-group or cross-over (for intermittent LTRA only) design. Maintenance was considered as treatment for more than two months and intermittent as less than 14 days. EVW was defined as a history of at least one previous episode of wheezing in association with a viral respiratory tract infection in the absence of symptoms between episodes. As far as possible, relevant specific data were obtained from authors of studies that included children of a wider age group or phenotype. Two authors independently assessed studies for inclusion in the review and assessed risk of bias. The primary outcome was number of children with one or more viral-induced episodes requiring one or more treatments with rescue oral corticosteroids. We analysed combined continuous data outcomes with the mean difference and dichotomous data outcomes with an odds ratio (OR). We identified five studies eligible for inclusion in the review (one investigated maintenance treatment, three intermittent therapy and one had both maintenance and intermittent treatment arms) these included 3741 participants. Each study involved oral montelukast and was of good methodological quality, but differed in choice of outcome measures thus limiting our ability to aggregate data across studies. Only primary outcome and adverse event data are reported in this abstract.For maintenance treatment, specific data obtained from a single study, pertaining to children with only an EVW phenotype, showed no statistically significant group reduction in the number of episodes requiring rescue oral corticosteroids associated with daily montelukast versus placebo (OR 1.20, 95% CI 0.70 to 2.06, moderate quality evidence).For intermittent LTRA, pooled data showed no statistically significant reduction in the number of episodes requiring rescue oral steroids in children treated with LTRA versus placebo (OR 0.77, 95% CI 0.48 to 1.25, moderate quality evidence). Specific data for children with an EVW phenotype obtained from a single study of intermittent montelukast treatment showed a small, but statistically significant reduction in unscheduled medical attendances due to wheeze (RR 0.83, 95% CI 0.71 to 0.98).For maintenance compared to intermittent LTRA treatment no data relating to the primary outcome of the review were identified.There were no other significant group differences identified in other secondary efficacy outcomes for maintenance or intermittent LTRA treatment versus placebo, or maintenance versus intermittent LTRA treatment. We collected descriptive data on adverse events as reported by four of the five included studies, and rates were similar between treatment and placebo groups.Potential heterogeneity in the phenotype of participants within and across trials is a limitation of the evidence. In pre-school children with EVW, there is no evidence of benefit associated with maintenance or intermittent LTRA treatment, compared to placebo, for reducing the number of children with one or more viral-induced episodes requiring rescue oral corticosteroids, and little evidence of significant clinical benefit for other secondary outcomes. Therefore until further data are available, LTRA should be used with caution in individual children. When used, we suggest a therapeutic trial is undertaken, during which efficacy should be carefully monitored. It is likely that children with an apparent EVW phenotype are not a homogeneous group and that subgroups may respond to LTRA treatment depending on the exact patho-physiological mechanisms involved.

Antileukotrienes in upper airway inflammatory diseases.

Leukotrienes (LTs) are a family of inflammatory mediators including LTA4, LTB4, LTC4, LTD4, and LTE4. By competitive binding to the cysteinyl LT1 (CysLT1) receptor, LT receptor antagonist drugs, such as montelukast, zafirlukast, and pranlukast, block the effects of CysLTs, improving the symptoms of some chronic respiratory diseases, particularly bronchial asthma and allergic rhinitis. We reviewed the efficacy of antileukotrienes in upper airway inflammatory diseases. An update on the use of antileukotrienes in upper airway diseases in children and adults is presented with a detailed literature survey. Data on LTs, antileukotrienes, and antileukotrienes in chronic rhinosinusitis and nasal polyps, asthma, and allergic rhinitis are presented. Antileukotriene drugs are classified into two groups: CysLT receptor antagonists (zafirlukast, pranlukast, and montelukast) and LT synthesis inhibitors (5-lipoxygenase inhibitors such as zileuton, ZD2138, Bay X 1005, and MK-0591). CysLTs have important proinflammatory and profibrotic effects that contribute to the extensive hyperplastic rhinosinusitis and nasal polyposis (NP) that characterise these disorders. Patients who receive zafirlukast or zileuton tend to show objective improvements in, or at least stabilisation of, NP. Montelukast treatment may lead to clinical subjective improvement in NP. Montelukast treatment after sinus surgery can lead to a significant reduction in eosinophilic cationic protein levels in serum, with a beneficial effect on nasal and pulmonary symptoms and less impact in NP. Combined inhaled corticosteroids and long-acting β-agonists treatments are most effective for preventing exacerbations among paediatric asthma patients. Treatments with medium- or high-dose inhaled corticosteroids, combined inhaled corticosteroids and LT receptor antagonists, and low-dose inhaled corticosteroids have been reported to be equally effective. Antileukotrienes have also been reported to be effective for allergic rhinitis.