montelukast and Chronic-Disease

Chronic urticaria (CU) is defined by episodes of urticaria with or without angioedema, which recur daily or nearly daily over more than 6 weeks. Sudden manifestations of CU with or without known causes are termed chronic spontaneous urticaria, which is differentiated from chronic inducible urticaria. The differential diagnoses of CU in childhood range from self-limiting dermatoses to severe systemic diseases. Further targeted steps are taken to detect potential trigger factors or underlying illnesses only if suspicion arises on anamnestic grounds and CU is best treated in accordance with international guidelines. First-line therapy consists of non-sedating H

Topics: Acetates; Angioedema; Child; Child, Preschool; Chronic Disease; Cyclopropanes; Cyclosporine; Diagnosis, Differential; Guideline Adherence; Histamine Antagonists; Humans; Infant; Long-Term Care; Omalizumab; Quinolines; Skin; Sulfides; Urticaria

This article describes the pathophysiology and management of postnasal drip (PND) with and without cough.. PND is a common complaint in primary care and ear-nose-throat offices, and is often, but not always, associated with chronic cough. Because it lacks objective testing and its symptoms can be vague and variable, PND has become a catch-all diagnosis for a variety of nasal and throat-related symptoms. Studies have shown that the traditional pathophysiology of PND related to sinonasal disease does not clearly lead to chronic cough and that the cough from PND may be related to an airway sensory hypersensitivity rather than actual irritation from inflamed nasal secretions.. The article summarizes the current recommendations on evaluation and management of PND as well as brings to discussion new therapies and hypothesis regarding its pathophysiology.

Topics: Acetates; Capsaicin; Chronic Disease; Cough; Cyclopropanes; Humans; Leukotriene Antagonists; Mucus; Nasal Mucosa; Quinolines; Rhinitis; Sensory System Agents; Sulfides; Viscosity

Topics: Acetates; Chronic Disease; Cyclopropanes; Humans; Leukotriene Antagonists; Nasal Polyps; Quinolines; Rhinitis; Sinusitis; Sulfides

Urticaria, by definition, is a disease presenting with wheals, angioedema or both. In patients with recurrent angioedema without wheals, urticaria needs to be distinguished from bradykinin-mediated angioedema, for example, hereditary angioedema or ACE inhibitor-induced angioedema.. Urticaria is comprised of acute and chronic forms. The latter group of chronic urticaria has many different subtypes needing partly different therapeutic approaches. However, all therapeutic approaches for symptomatic treatment center on reducing mast cell-mediator-release and preventing its effect.. The current guidelines recommend non-sedating, second generation H1-antihistamines (nsAHs) as the first-line treatment. If needed, nsAHs are to be used at higher doses (up to fourfold the standard dose), and Omalizumab, Montelukast or Cyclosporin A (not in preferred order) are recommended as third-line options. Many alternative treatments have been reported but not tested in randomized controlled trials. These include among others dapsone, H2-antihistamines, anticoagulants and methotrexate. Some therapies should no longer be used according to current guidelines, since studies have shown their inefficacy or because new safety concerns have emerged. This mainly refers to the formally propagated use of sedating antihistamines at night, which change REM-sleeping-patterns and learning curves and have been shown in head-to-head trials to not be superior in efficacy to non-sedating antihistamines.

Topics: Acetates; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Chronic Disease; Cyclopropanes; Cyclosporine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Histamine H1 Antagonists; Histamine Release; Humans; Omalizumab; Practice Guidelines as Topic; Quinolines; Sulfides; Treatment Outcome; Urticaria

Chronic idiopathic urticaria (CIU) is a disabling affliction that considerably limits patients' daily activities and interferes with sleep. Clinical studies have shown that histamine H1-receptor antagonists (antihistamines) are highly effective for inhibiting the hives/wheals and pruritus associated with CIU, as well as improving patients' quality of life. Desloratadine is a rapid-acting, once-daily, nonsedating selective H1-receptor antagonist/inverse receptor agonist with proven clinical efficacy in patients with CIU. It has 10-20 times the in vivo H1 receptor-binding affinity of loratadine, its parent compound, and 52-194 times the H1 receptor-binding affinity of cetirizine, ebastine, loratadine, and fexofenadine. Desloratadine displays linear pharmacokinetics after oral administration. Age and sex have no apparent effect on the drug's metabolism and elimination, and food does not affect its bioavailability or absorption. Desloratadine also exerts anti-inflammatory effects via mechanisms that are independent of H1-receptor antagonism. Results from randomized, double-blind, placebo-controlled studies of 6 weeks' duration in adults and adolescents with moderate-to-severe CIU indicate that desloratadine significantly minimizes the severity of pruritus, reduces the number and size of hives, and improves disease-impaired sleep and daily activities. Improvements were noted after a single dose of desloratadine and were maintained over 6 weeks of treatment. Desloratadine was safe and well tolerated in clinical trials of patients with CIU. The adverse effect profile of desloratadine in adults, as well as in children aged from 6 months to 11 years, is comparable to that of placebo. Evaluations of cognitive and psychomotor performance in adults indicate no impairment of function with dosages of desloratadine 5 mg/day. In conclusion, desloratadine is an important therapeutic option for prompt and enduring symptom relief in patients with moderate-to-severe CIU. In addition to efficacy and safety, desloratadine affords a convenient administration regimen, rapid onset of action, and an absence of drug-drug or drug-food interactions. Other important prescribing considerations are that, unlike all first-generation and some second-generation antihistamines, desloratadine is nonsedating at its clinically approved dosage and does not impair psychomotor function.

Topics: Acetates; Adolescent; Adult; Child; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Histamine H1 Antagonists, Non-Sedating; Humans; Infant; Leukotriene Antagonists; Loratadine; Quality of Life; Quinolines; Sulfides; Urticaria

Montelukast is a leukotriene receptor antagonist administered orally once daily for treatment of chronic asthma in adults and children. A comprehensive analysis of safety data from double-blind, randomized, placebo-controlled trials with montelukast has not been previously reported.. A pooled analysis of safety data from 11 multicentre, randomized, controlled montelukast Phase IIb and III trials and five long-term extension studies was performed. A total of 3386 adult patients (aged 15-85 years) and 336 paediatric patients (aged 6-14 years) were enrolled in the trials; 2031 adults received montelukast for up to 4.1 years, and 257 children received montelukast for up to 1.8 years. Summary statistics comparing incidences of adverse events among treatment groups were calculated.. The overall incidence of clinical and laboratory adverse events among montelukast-treated patients, both adult and paediatric, was similar to that among patients receiving placebo. There were no clinically relevant differences in individual adverse events, including infectious upper respiratory conditions and transaminase elevations, between montelukast and placebo groups. Discontinuations due to adverse events occurred with similar frequencies during placebo, montelukast and inhaled beclomethasone therapy. No dose-related adverse effects of montelukast were observed in adults treated with dosages as high as 200 mg per day (20 times the recommended dose) for 5 months. This tolerability profile montelukast observed in clinical trials has been generally reflected in the post-marketing safety experience seen to date.. These data indicate a tolerability profile for montelukast similar to placebo during both short-term and long-term administration, even at doses substantially higher than the recommended clinical dose of 10 mg once daily for adults and 5 mg once daily for children aged 6-14 years.

Topics: Acetates; Adolescent; Adult; Aged; Aged, 80 and over; Asthma; Child; Chronic Disease; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cyclopropanes; Double-Blind Method; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Multicenter Studies as Topic; Quinolines; Randomized Controlled Trials as Topic; Sulfides; Treatment Outcome

Topics: Acetates; Administration, Oral; Animals; Asthma; Chromones; Chronic Disease; Cyclopropanes; Humans; Leukotriene Antagonists; Leukotriene D4; Lung; Quinolines; Sulfides

The aim of this article is to review data on the efficacy and safety of montelukast in the treatment of children with asthma.. Available published literature, including published abstracts, is reviewed.. In patients aged 6 to 14 years with asthma (n = 27), montelukast 5mg demonstrated a significant decrease in exercise-induced bronchoconstriction 20 to 24 hours postdose after 2 days of treatment. For children with chronic asthma, only one study of the regular use of a leukotriene receptor antagonist has been published. The efficacy and safety of montelukast in children aged 6 to 14 years with asthma (n = 336) were studied during an 8-week, double-blind, placebocontrolled trial. There was a significantly greater improvement in forced expiratory volume in 1 second (FEV1) from baseline for the montelukast group (8.23%) compared with the placebo group (3.58%). There was a significant decrease in the use of a 3-agonist for symptom relief, as well as in the percentage of days and percentage of patients with asthma exacerbations. An asthma specific quality-of-life (QOL) questionnaire revealed a significant overall improvement in QOL and a significant improvement in the QOL domains for symptoms, activity and emotions in montelukast recipients. There was no significant difference between montelukast and placebo recipients in the frequency of adverse events, with the exception of allergic rhinitis, which was more prevalent in the placebo group. An open label follow-up of patients from the above study was undertaken. The effect of montelukast on FEV1 was consistent for up to 1.4 years, with the increase in FEV1 being not significantly different from that in a small control group treated with inhaled beclomethasone dipropionate. QOL remained significantly improved during the open treatment period.. Montelukast appears effective and safe for the treatment of children with asthma.

Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Asthma; Child; Chronic Disease; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; Sulfides

To examine the role of leukotriene-receptor antagonists (LTRAs) in management of asthma.. Most data were derived from randomized, double-blind, controlled trials.. Leukotrienes appear to have an important role in the pathophysiology of asthma, including airway inflammation. Leukotriene-receptor antagonists are effective in improving asthma control end points, such as allergen, ASA, and exercise challenge, in clinical models of asthma. In chronic asthma, LTRA administration reduces asthma symptoms and rescue beta 2-agonist use, changes that are paralleled by improvements in lung function. Both zafirlukast and montelukast decrease circulating levels of eosinophils and could have other useful anti-inflammatory properties. Administration of LTRAs allows doses of inhaled corticosteroids to be reduced. Currently available LTRAs are free of serious side effects and are available as oral formulations.. Leukotriene-receptor antagonists belong to a new class of asthma medication. While inhaled corticosteroids remain first-line therapy for managing chronic asthma, LTRAs should be considered for patients with ASA-sensitive asthma; as adjunct therapy when low to moderate doses of inhaled steroid alone provide incomplete control; or as adjunct therapy to allow reduction in doses of inhaled corticosteroids.

Topics: Acetates; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Bronchial Spasm; Chronic Disease; Cyclopropanes; Double-Blind Method; Humans; Indoles; Leukotriene Antagonists; Phenylcarbamates; Quinolines; Randomized Controlled Trials as Topic; Respiratory Therapy; Sulfides; Sulfonamides; Time Factors; Tosyl Compounds

Leukotriene receptor antagonists (LTRA) are a new class of drugs for asthma treatment, available in tablet form. Their unique mechanism of action results in a combination of both bronchodilator and anti-inflammatory effects. While their optimal place in asthma management is still under review, LTRA represent an important advance in asthma pharmacotherapy.

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Asthma, Exercise-Induced; Chronic Disease; Cyclopropanes; Humans; Indoles; Leukotriene Antagonists; Phenylcarbamates; Quinolines; Sulfides; Sulfonamides; Tosyl Compounds

Topics: Acetates; Adolescent; Adult; Child; Chronic Disease; Cyclopropanes; Drug Evaluation; Drug Synergism; Drug Therapy, Combination; Female; Follow-Up Studies; Histamine H1 Antagonists; Humans; Indoles; Leukotriene Antagonists; Male; Middle Aged; Phenylcarbamates; Quinolines; Sulfides; Sulfonamides; Tosyl Compounds; Treatment Outcome; Urticaria

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.. Prospective, randomized, open-label trial.. 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.. 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.. These results suggest that the addition of montelukast to INCS should not be recommended in the treatment of postoperative CRSwNP patients.. 1b Laryngoscope, 1743-1751, 2018.

Topics: Acetates; Administration, Intranasal; Adrenal Cortex Hormones; Adult; Aged; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Endoscopy; Female; Follow-Up Studies; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Paranasal Sinuses; Postoperative Period; Prospective Studies; Quinolines; Rhinitis; Sinusitis; Sulfides; Treatment Outcome

Whether the fraction of exhaled nitric oxide (FeNO) measurement can predict the response to anti-inflammatory treatment in chronic cough is unknown.. To explore whether the effectiveness of treatment with 10 mg of montelukast or 20 mg of prednisolone in patients with chronic cough is predicted by FeNO level.. In this randomized, open-label, controlled pilot study conducted in the Clinical Trial Unit in Castle Hospital in the United Kingdom, 50 nonsmoking patients with a cough that lasted more than 8 weeks were sequentially enrolled in the study. Thirty patients with high FeNO levels (≥30 ppb) were randomized in a 1:1 ratio to receive 10 mg of montelukast or 20 mg of prednisolone for 2 weeks followed by 10 mg of montelukast for 2 weeks. Twenty patients with a low FeNO level (≤20 ppb) received 10 mg of montelukast. The primary objective was to determine the effectiveness of treatment on 24-hour cough counts.. The 24-hour cough counts decreased in both groups by approximately 50% (P < .005), indicating that FeNO did not predict treatment response. However, it was a good marker for eosinophilic inflammation with a high degree of correlation with blood and sputum eosinophilia (P < .001).. These results suggest that prior investigation may not predict response to anti-inflammatory treatment, which may be consequent on localized leukotriene-mediated inflammation.. ClinicalTrials.gov Identifier: NCT02479074.

Topics: Acetates; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Breath Tests; Chronic Disease; Cough; Cyclopropanes; Exhalation; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Nitric Oxide; Phenotype; Pilot Projects; Prednisolone; Quinolines; Sulfides; Treatment Outcome

Cysteinyl leukotriene (LT) has been proposed in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study sought to examine the expression of the LT receptor (LTR) in CRSwNP patients and evaluate the potential role of LTR antagonist (LTRA) in the management of eosinophilic CRSwNP (ECRS) patients.. Nasal polyps and uncinate process tissues were collected from 18 ECRS patients, 13 non-eosinophilic CRSwNP (non-ECRS) patients, and 16 control subjects. The messenger RNA (mRNA) and protein expression of LTR (cysteinyl leukotriene receptor 1 [CysLT1R] and cysteinyl leukotriene receptor 2 [CysLT2R]) was examined using quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, and Western blot analysis. Moreover, the effects of LTRA and steroids on total nasal symptom scores (TNSS) of uncontrolled ECRS patients were evaluated.. The mRNA and protein expression of CysLT1R and CysLT2R was significantly increased in polyp tissues compared with healthy controls (p < 0.05). Compared with the non-ECRS subset, the ECRS subset showed significantly increased expression of CysLT1R and CysLT2R, as well as leukotriene C4 (LTC4) and leukotriene D4 (LTC4) levels (p < 0.05). Moreover, combined LTRA and steroids significantly decreased TNSS more than steroids alone in uncontrolled ECRS patients (p < 0.01).. Our findings indicate that LTR was differentially expressed between ECRS and non-ECRS patients, and that LTRA may be used as an additional therapy for ECRS patients.

Topics: Acetates; Adult; Anti-Inflammatory Agents; Biomarkers; Blotting, Western; Budesonide; Case-Control Studies; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Eosinophils; Female; Humans; Leukotriene Antagonists; Leukotrienes; Male; Middle Aged; Nasal Polyps; Prospective Studies; Quinolines; Receptors, Leukotriene; Reverse Transcriptase Polymerase Chain Reaction; Rhinitis; Sinusitis; Sulfides; Treatment Outcome

Observational reports have linked vitamin D with chronic urticaria, yet no randomized controlled trial has been conducted.. To determine whether high-dose vitamin D supplementation would decrease Urticaria Symptom Severity (USS) scores and medication burden in patients with chronic urticaria.. In a prospective, double-blinded, single-center study, 42 subjects with chronic urticaria were randomized to high (4,000 IU/d) or low (600 IU/d) vitamin D3 supplementation for 12 weeks. All subjects were provided with a standardized triple-drug therapy (cetirizine, ranitidine, and montelukast) and a written action plan. Data on USS scores, medication use, blood for 25-hydroxyvitamin D, and safety measurements were collected.. Triple-drug therapy decreased total USS scores by 33% in the first week. There was a further significant decrease (40%) in total USS scores in the high, but not low, vitamin D3 treatment group by week 12. Compared with low treatment, the high treatment group demonstrated a trend (P = .052) toward lower total USS scores at week 12, which was driven by significant decreases in body distribution and number of days with hives. Beneficial trends for sleep quality and pruritus scores were observed with high vitamin D3. Serum 25-hydroxyvitamin D levels increased with high vitamin D3 supplementation, but there was no correlation between 25-hydroxyvitamin D levels and USS scores. There was no difference in allergy medication use between groups. No adverse events occurred.. Add-on therapy with high-dose vitamin D3 (4,000 IU/d) could be considered a safe and potentially beneficial immunomodulator in patients with chronic urticaria.. clinicaltrials.gov Identifier: NCT01371877.

Topics: Acetates; Adult; Aged; Cetirizine; Cholecalciferol; Chronic Disease; Cyclopropanes; Dietary Supplements; Disease Progression; Female; Humans; Male; Middle Aged; Prospective Studies; Quinolines; Ranitidine; Sulfides; Urticaria; Young Adult

Budesonide at 800 μg/d is generally suggested for treatment of nonasthmatic eosinophilic bronchitis (NAEB). In asthma, adjunctive therapy with montelukast has been shown to confer addictive anti-inflammatory effects to inhaled corticosteroid (ICS). However, whether such effects could be extrapolated to NAEB is not known.. To study the efficacy and tolerability of add-on therapy with montelukast as compared to double-dose ICS in suppressing airway eosinophilia and decreasing cough severity in NAEB.. In a randomized controlled trial, 26 nonsmoking, steroid-naïve NAEB patients presenting with chronic cough were treated with 800 μg/d budesonide or 400 μg/d budesonide plus montelukast 10 mg/d for 4 weeks. Cough visual analogue scale (CVAS) and eosinophil differential ratio in induced sputum (Eos) were monitored at baseline, Week 1, 2 and 4. Adverse events during treatment were recorded.. The two groups were comparable in age, gender distribution, cough duration, FEV(1)% predicted, FEV(1)/FEV ratio, baseline CVAS and geometric mean of Eos. Both regimens significantly reduced Eos and CVAS throughout the treatment course, with abrogation of sputum eosinophilia at end of therapy. There was no significant difference between the two groups in reduction of Eos and CVAS at all time points. Both regimens were well tolerated.. This preliminary study demonstrated that add-on montelukast might be an effective and well tolerated alternative to the generally suggested dose of ICS in treating steroid-naive NAEB, with suppression of eosinophilic inflammation, reduction of cough severity and sparing of ICS doses. (NCT01121016).

Topics: Acetates; Adult; Aged; Bronchitis; Bronchodilator Agents; Budesonide; Chronic Disease; Cough; Cyclopropanes; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Middle Aged; Pilot Projects; Pulmonary Eosinophilia; Quinolines; Sulfides; Treatment Outcome; Young Adult

The efficacy of oral montelukast in chronic asthma is well established. Montelukast is also an effective adjunctive therapy to inhaled corticosteroids (ICS) in asthma uncontrolled on ICS alone. Inhaled montelukast was recently shown to provide significant bronchodilation compared with placebo in patients with chronic asthma. The purpose of this study was to evaluate the efficacy of inhaled montelukast added to inhaled mometasone.. This was an 8-week, multicenter, randomized, double-blind, placebo-controlled study comparing once-daily inhaled montelukast 1 mg plus inhaled mometasone 220 μg (delivered by separate dry powder inhalers) with placebo plus inhaled mometasone 220 μg. Men and women aged 15-85 years with chronic asthma, forced expiratory volume in 1 second (FEV(1)) 50-80% of the predicted value, and β-agonist reversibility ≥12% were eligible. Patients were required to meet a minimum symptom threshold while receiving open-label inhaled mometasone during a 3-week prestudy/run-in period. Patients received blinded (montelukast vs. placebo) treatment for 2 weeks, entered a 1-week washout period, then crossed over to the other treatment for 2 weeks. The primary endpoint was the average change from baseline in FEV(1) over the 2-week treatment period. Secondary endpoints included daytime and nighttime symptom scores. Other endpoints included short-acting β-agonist (SABA) use, asthma exacerbations, asthma control, peak expiratory flow (PEF), and blood eosinophil count.. A total of 134 patients were randomized. For the primary endpoint, change from baseline in FEV(1), inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone (least squares mean 0.22 L vs. 0.17 L; p = .033 [two-sided at α = 0.05]). Inhaled montelukast plus inhaled mometasone was also significantly more effective than placebo plus inhaled mometasone in improving daytime asthma symptom scores (p = .005) and nighttime asthma symptom scores (p = .015), increasing the percentage of days with asthma control (p = .004), decreasing the percentage of days with asthma exacerbations (p ≤ .001), and decreasing the blood eosinophil count (p = .013). Differences were not significant on AM or PM PEF or SABA use, although the latter approached significance (p = .073). Both treatments were well tolerated.. Inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone in improving FEV(1), symptoms, asthma control, and blood eosinophil count.

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Chronic Disease; Confidence Intervals; Cross-Over Studies; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Linear Models; Male; Maximum Tolerated Dose; Middle Aged; Mometasone Furoate; Patient Compliance; Pregnadienediols; Quinolines; Reference Values; Risk Assessment; Severity of Illness Index; Spirometry; Sulfides; Treatment Outcome; United States; Young Adult

Antihistamines (AH) alleviate pruritus and decrease the incidence of hives in patients with chronic idiopathic urticaria (CU). However, some patients do not respond completely to this therapy. We hypothesized that some of them might benefit from the addition of leukotriene receptor antagonists (LA).. We screened patients diagnosed and treated for CU and selected those that had symptoms despite antihistamine treatment. In a double-blind crossover study, patients took the leukotriene antagonist montelukast (10 mg per day) or placebo. Efficacy was assessed by a symptom score.. In a group of 22 patients, the symptom score was not significantly different between periods using montelukast (48.8; 0-214) or placebo (68.5; 0-230). However in the subgroup of five patients with the most severe urticaria, defined as patients with symptom scores in the upper quartile at inclusion in the study, montelukast (41; 11 214) was superior to placebo (95.5; 48 230; p < 0.05), but only when using an in-house symptom score questionnaire and not when using a validated urticaria activity score questionnaire.. We showed that in patients with antihistamine-resistant CU the addition of montelukast significantly diminished symptoms in only a small minority of patients. However, response to add-on montelukast was seen in the subgroup of patients with particularly severe disease. To confirm this observation, a study with a larger group of patients is warranted.

Topics: Acetates; Chronic Disease; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Quinolines; Sulfides; Surveys and Questionnaires; Treatment Outcome; Urticaria

Chronic rhinosinusitis associated with asthma is often difficult to treat effectively with intranasal corticosteroids alone. Thus, the aim of this study was to evaluate the effectiveness of combination treatment with an intranasal corticosteroid and a leukotriene-receptor antagonist (montelukast) in reducing the size of nasal polyps.. The subjects of this study were 20 patients with chronic rhinosinusitis associated with adult-onset asthma, which was being treated with inhaled corticosteroids. All patients were treated with intranasal fluticasone propionate, 200 microg/day, and montelukast, 10 mg/day, for 1 year. The size of nasal polyps and the score of sinus shadows were assessed with nasal endoscopy and computed tomography (CT), respectively, before and after treatment. The peripheral blood eosinophil counts were also evaluated before and after treatment.. Nasal polyps were significantly smaller after both 6 months (p<0.01) and 12 months of treatment (p<0.01) than before treatment. The decrease in the shadow score was statistically significant after both 6 months (p<0.01) and 12 months of treatment (p<0.01). Significant reductions in peripheral blood eosinophil counts were also seen after both 6 months (p<0.05) and 12 months of treatment (p<0.01). A significant correlation was found between the rate of change in the peripheral blood eosinophil count and that in the CT score after both 6 months (r=0.578, p=0.012) and 12 months (r=0.625, p=0.007).. Combined treatment with intranasal fluticasone propionate and montelukast, for at least 1 year, is effective for chronic rhinosinusitis associated with adult-onset asthma.

Topics: Acetates; Administration, Intranasal; Adrenal Cortex Hormones; Adult; Aged; Androstadienes; Anti-Allergic Agents; Asthma; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Eosinophils; Female; Fluticasone; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Quinolines; Rhinitis, Allergic, Perennial; Sinusitis; Sulfides; Tomography, X-Ray Computed; Treatment Outcome

We conducted a prospective, randomized, placebo-controlled, double-blind study to determine if the leukotriene inhibitor montelukast is effective in eliminating persistent middle ear drainage in patients with otitis media with effusion (OME). Our study population was made up of patients aged 2 to 6 years who had had confirmed OME in one or both ears for at least 2 months. Patients were randomized to receive either placebo or 4 mg of montelukast daily for 1 month. The main outcome measure was clearance of middle ear effusion as demonstrated by otoscopy and tympanometry 1 month after the initiation of treatment. Our goal was to recruit 120 patients; however, an interim analysis was conducted after 38 patients had completed their regimen (19 patients in each group) when it became apparent that montelukast was not having any effect in clearing the effusions. Indeed, the OME had cleared in only 3 montelukast patients (15.8%) and 4 controls (21.1%); the difference was not statistically significant (p > 0.90). Based on this early trend, the study was terminated at this point. We conclude that montelukast appears to be no more effective than placebo in eliminating persistent middle ear effusion.

Topics: Acetates; Child; Child, Preschool; Chronic Disease; Cyclopropanes; Double-Blind Method; Humans; Leukotriene Antagonists; Otitis Media with Effusion; Quinolines; Sulfides; Treatment Failure

The efficacy of oral montelukast has been well established in asthma and allergic rhinitis in adults and children. The purpose of this study was to evaluate dose-related bronchodilation and tolerability of inhaled montelukast.. Randomized, double-blind, crossover, adaptive-design study comparing single-dose administration of inhaled montelukast versus placebo in patients age 15-65 years with chronic asthma (n = 68). Montelukast was delivered as a witnessed dose through dry powder inhaler at doses of 25, 250, or 1000 μg, and doses of 50, 100, and 500 μg could be used if needed based on a prespecified dose-response algorithm. Each administration was followed by a 4- to 7-day washout period before crossing over to the next treatment. The primary endpoint was the change from baseline in a forced expiratory volume in 1 second (FEV₁) over the first 4 hours after administration, calculated as a time-weighted average (ΔFEV₁ [0-4 hours]). Other endpoints included the onset and duration of bronchodilation and the effect of albuterol when added to inhaled montelukast.. Over 4 hours postdose, and compared with placebo (least-squares [LS] mean 0.03 L), inhaled montelukast 100 μg (0.13 L; p ≤ .001), 250 μg (0.10 L; p < .01), and 1000 μg (0.12 L; p ≤ .001) had significantly greater ΔFEV₁ (0-4 hours). At 24 hours postdose, inhaled montelukast 100 μg (0.10 L) and 1000 μg (0.09 L) had significantly greater bronchodilation compared with placebo (0.02 L; p < .05 vs. montelukast). Montelukast 1000 μg provided significant bronchodilation versus placebo within 20 minutes of administration (0.03 L vs. -0.05 L), whereas montelukast 100 μg provided significant bronchodilation relative to placebo within 2 hours of dosing (0.09 L vs. 0.01 L). Montelukast (pooled doses) plus albuterol was significantly more effective than montelukast plus placebo for ΔFEV₁ (0-90 minutes) (0.34 L vs. 0.15 L; p = .015). The tolerability of inhaled montelukast was similar to that of placebo. No serious adverse experiences were reported.. Inhaled montelukast provided significant bronchodilation compared with placebo as early as 20 minutes after the administration that persisted for 24 hours and provided additive bronchodilation to albuterol.

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Chronic Disease; Cross-Over Studies; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Forced Expiratory Volume; Humans; Least-Squares Analysis; Leukotriene Antagonists; Middle Aged; Quinolines; Sulfides; Young Adult

Chronic idiopathic urticaria (CIU) is often difficult to treat. Although histamine-releasing activity is detectable for up to 50% of CIU patients, antihistamine therapy provides only a limited response.. This study aimed to assess the clinical efficacy of combined leukotriene receptor antagonist (LRA) and H1 antihistamine, H1 and H2 antihistamine, and two H1 antihistamines as a synergistic therapeutic regimen for treating CIU compared with a matched placebo modality.. A total of 120 newly diagnosed adult patients were evaluated. Patients were single blinded and randomly assigned to one of four medication groups that received the following regimens for 4 weeks: Group A, combination of sedating H1 antihistamine and non-sedating H1 antihistamine; Group B, combination of H1 antihistamine and H2 antihistamine; Group C, combination of H1 antihistamine and LRA; and Group D, matched placebo medication. The primary measure of treatment efficacy was the daily urticaria activity score (UAS) of 'wheal and itch'. A positive therapeutic response was defined as a reduction to < 25% of baseline weekly UAS, while a relapse was a return to > 75% of baseline weekly UAS.. In all, 107 patients completed the trial medication. At the end of 4 weeks, the UAS score as a response to treatment was 23.3% for Group A, 63.3% for Group B, 53.3% for Group C, and no real change for the placebo treatment group.. The combination of LRA and H1 receptor antagonist is promising for CIU treatment and is reasonably well tolerated by patients. The combination of H1- and H2-receptor antagonists provided the greatest treatment efficacy by the measures used in this small study.

Topics: Acetates; Adolescent; Adult; Cetirizine; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Famotidine; Female; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Hydroxyzine; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Single-Blind Method; Sulfides; Urticaria; Young Adult

Loratadine added to montelukast has been suggested to improve endpoints of asthma.. This study investigated the additive effects of concomitant montelukast and loratadine when compared with montelukast, loratadine, and inhaled beclomethasone monotherapies in asthma. Methods. Patients (N = 406) were 15 to 65 years of age with a forced expiratory volume in 1 second (FEV(1))-predicted of 50% to 85%, FEV(1) reversibility > or = 15%, and a minimal level of daytime symptoms and beta -agonist use. This three-part 2X2 crossover-study consisted of two double-blind 6-week treatment periods where patients were administered once daily oral montelukast 10 mg, loratadine 10 mg, montelukast 10 mg + loratadine 10 mg, or twice daily inhaled beclomethasone 200 mu g. A subsequent 48-week extension study compared montelukast + loratadine with beclomethasone. The primary endpoint was the percentage change from baseline in FEV(1).. Over 6 weeks of double-blind treatment, significant improvements (p < 0.05) in the primary endpoint of FEV(1) were seen for montelukast + loratadine versus loratadine (least-square mean percentage-point difference of 5.8%), beclomethasone versus montelukast + loratadine (2.35%), montelukast versus loratadine (5.94%), and beclomethasone versus montelukast (4.65%); a numerical improvement (p = 0.054) was seen for montelukast + loratadine versus montelukast (1.60%). Significant improvements for montelukast + loratadine versus montelukast were seen in some secondary endpoints (evening peak expiratory flow, nocturnal asthma symptom score, nocturnal awakenings, and asthma-specific quality of life) but not others. Significant improvements in most endpoints except daytime asthma symptoms score were seen for montelukast + loratadine versus loratadine. In the extension study, both montelukast + loratadine and beclomethasone improved several endpoints. All treatments were generally comparable in the percentage of patients with clinical and laboratory adverse experiences.. In this study, the addition of loratadine to montelukast produced a small numerical, but not statistically significant, improvement in FEV(1) and, in general, no consistent improvement in other asthma endpoints. No improvement of montelukast + loratadine versus beclomethasone was seen in any endpoint.

Topics: Acetates; Adolescent; Adult; Aged; Anti-Allergic Agents; Asthma; Beclomethasone; Chronic Disease; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Loratadine; Male; Middle Aged; Quality of Life; Quinolines; Sulfides; Young Adult

Persistent allergic rhinitis often impairs quality of life.. We assessed the extent to which treating persistent allergic rhinitis with montelukast, desloratadine, and levocetirizine alone or in combination improved quality of life.. A 32-week randomized, double-blind, placebo-controlled, crossover study was performed in 2 arms: 20 patients received montelukast 10 mg/d and/or desloratadine 5 mg/d or placebo; 20 patients received montelukast 10 mg/d and/or levocetirizine 5 mg/d or placebo. The treatment periods were separated by 2-week washout periods. Quality of life was assessed on the day before starting treatment and on the last day of each treatment period using the Rhinoconjunctivitis Quality of Life Questionnaire. Sleep problems were also assessed.. In the desloratadine plus montelukast arm, the mean (SEM) quality of life score before treatment was 3.1 (0.41). After placebo, this score was 2.16 (0.43), after desloratadine it was 1.79 (0.38), after montelukast it was 1.48 (0.37), and after montelukast plus desloratadine it was 1.59 (0.37). In the montelukast plus levocetirizine arm, the mean quality of life score before treatment was 2.58 (0.49). After placebo it was 1.78 (0.46), after levocetirizine it was 1.38 (0.42), after montelukast it was 1.36 (0.37), and after montelukast plus levocetirizine it was 1.26 (0.39).. Placebo, montelukast, desloratadine and levocetirizine significantly improved quality of life. Combining montelukast with either levocetirizine or desloratadine gave additional benefits in comparison to each agent alone and could be considered for patients whose quality of life is impaired by persistent allergic rhinitis.

Topics: Acetates; Adolescent; Adult; Aged; Cetirizine; Chronic Disease; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Interactions; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Loratadine; Male; Middle Aged; Quality of Life; Quinolines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sulfides; Treatment Outcome

The non- or low-sedating H1 receptor antagonists represent the basic therapy for urticaria.. To test an alternative approach to patients unresponsive to conventional treatment.. A total of 22 patients with chronic urticaria unresponsive to conventional antihistamine treatment were enrolled for this study. They had uncontrolled urticaria even using multiple combinations of antihistamines on maximum doses and corticosteroids in short cycles (prednisone 20-40 mg, per os once a day, 3-7 days per month). Cutaneous biopsies of the urticaria lesions were taken. These findings were classified as: (I) a mixture of perivascular dermal inflammatory infiltrate composed of lymphocytes, monocytes and neutrophils and/or eosinophils; (II) inflammatory infiltrate composed chiefly of neutrophils; and (III) inflammatory infiltrate composed mainly of eosinophils. According to histology, the patients were submitted to one of the following therapeutic schemes: class A - antihistamine treatment plus dapsone; class B - colchicine or dapsone; class C - montelukast.. Four patients in class A, 08 in class B and seven in class C displayed complete control of urticaria after 12 weeks of treatment; one patient in class B and two in class C did not respond to treatment. Two years after discontinuation, 16 patients are still free of urticaria.. This study suggests an alternative approach for treating unresponsive chronic urticaria.

Topics: Acetates; Adult; Anti-Infective Agents; Chronic Disease; Colchicine; Cyclopropanes; Dapsone; Drug Therapy, Combination; Female; Histamine H1 Antagonists; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Sulfides; Tubulin Modulators; Urticaria

Topics: Acetates; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chronic Disease; Cyclopropanes; Graft vs Host Disease; Humans; Leukotriene Antagonists; Pilot Projects; Quinolines; Sulfides

Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma.. To determine whether montelukast is as effective as budesonide in controlling mild persistent asthma as determined by FEV(1).. Between November 2003 to October 2005, participants aged 5-15 years with recently diagnosed mild persistent asthma (n = 62) were randomized to oral montelukast (5 mg daily) [N(1) = 30] or inhaled budesonide (400 microg per day in two doses) [N(2) = 32] in a single center, double-blind study.. Baseline demographic and spirometric parameters were comparable. The median (95% confidence interval) percentage predicted FEV(1) was similar in the two groups after 12 weeks of treatment (budesonide: 76.70 (67.96-90.53%), montelukast: 75 (67.40-88.47)%; p = 0.44). There was similar improvement in spirometric parameters and clinical symptom scores in both the groups. There was no statistically significant difference between the groups in the need for rescue drugs as well as side effects reported by parents.. Montelukast is as effective as inhaled budesonide in the treatment of mild persistent asthma in children aged 5-15 years. Montelukast may be used as an alternative to low dose inhaled corticosteroids for management of mild persistent asthma.

Topics: Acetates; Administration, Inhalation; Adolescent; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Child; Child, Preschool; Chronic Disease; Cyclopropanes; Double-Blind Method; Female; Forced Expiratory Volume; Humans; India; Male; Quinolines; Sulfides

Montelukast has proven efficacy in the treatment of chronic asthma and seasonal allergic rhinitis, but it has not been evaluated in the subpopulation of asthmatic patients with seasonal asthma symptoms.. To determine the effectiveness of montelukast treatment in improving the control of asthma symptoms during the allergy season in patients with active asthma and seasonal aeroallergen sensitivity.. Adults with a history of chronic asthma who are also symptomatic during the allergy season and with skin test sensitivity to seasonal aeroallergens were enrolled in a randomized, parallel-group, multicenter study with a 1-week, single-blind, placebo run-in period followed by 3 weeks of double-blind treatment during the spring of 2004. After the run-in period, eligible patients were randomly assigned to receive either oral montelukast (10 mg) or placebo. Daytime and nighttime asthma symptom scores, beta-agonist use, and morning and evening peak expiratory flow rates were recorded daily using an electronic diary. The primary end point was mean change from baseline to week 3 in the daytime asthma symptom score.. Of 455 randomized patients, 433 completed the study. Compared with placebo, treatment with montelukast resulted in a significant improvement from baseline in the daytime asthma symptom score (-0.54 vs -0.34; P = .002) and in beta-agonist use, nighttime symptoms, and peak expiratory flow rates. Few patients in the montelukast and placebo groups discontinued study participation because of asthma (1.3% and 3.0%, respectively).. In patients with chronic asthma and seasonal aeroallergen sensitivity, montelukast treatment provided significant asthma control during the allergy season compared with placebo.

Topics: Acetates; Administration, Oral; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Logistic Models; Male; Middle Aged; Peak Expiratory Flow Rate; Quinolines; Rhinitis, Allergic, Seasonal; Sulfides

Many patients with chronic idiopathic urticaria are not sufficiently controlled with histamine H(1)-receptor antagonists. Leukotriene receptor antagonists have been reported to be effective for certain cases of urticaria, although their proper application remains to be established. To study the effectiveness of montelukast, a leukotriene receptor antagonist, for the treatment of chronic urticaria that was not controlled by histamine H(1)-receptor antagonists. Twenty-five patients with chronic idiopathic urticaria were treated with 10 mg of montelukast for one week or more, without changing any precedent treatment that they were using before the study including histamine H(1)-receptor antagonists. The effectiveness of montelukast for each patient was evaluated and compared with clinical features and/or backgrounds of the patients. Twelve patients, including six who had been treated with corticosteroids, were evaluated as "markedly improved" or "improved" following treatment with montelukast. There was no statistically significant relation of the effectiveness to the complications with non-steroidal anti-inflammatory drugs (NSAIDs) intolerance, mechanical urticaria, or reactions to autologous serum skin test. However, the patients for whom montelukast was effective were younger (33.2+/-16.3 years, mean +/- SD)(P<0.05, Mann-Whitney test) and their duration of illness shorter (15.9+/-18.3 months) (P<0.005, Mann-Whitney test) than those of patients for whom montelukast was ineffective (45.9+/-15.0 years, 89.6+/-71.7 months). Montelukast may be worth trying for patients with chronic idiopathic urticaria, when the condition is not sufficiently controlled with histamine H(1)-receptor antagonists.

Topics: Acetates; Adolescent; Adult; Aged; Child; Child, Preschool; Chronic Disease; Cyclopropanes; Drug Resistance; Female; Histamine H1 Antagonists; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Sulfides; Urticaria

This study is aimed to evaluate the efficacy and safety of montelukast, as monotherapy, in the treatment of chronic stable bronchial asthma in adults. This was a multicentre, open label, non-comparative, prospective, 4-week study. Eligible patients discontinued all anti-inflammatory medication (steroids, chromoglycate sodium) 2 weeks prior to starting therapy with montelukast (10 mg daily). The primary efficacy criteria were improvements in forced expiratory volume in one second (FEV1), peak exploratory flow rate (PEFR) after 4 weeks of therapy. Secondary efficacy criteria were improvement in the patients' symptoms (assessed on an ordinal scale), decrease in discomfort levels (scored on a scale of 0-100), change in peripheral eosinophil counts, decrease in total daily dose of inhaled beta2 agonist (salbutamol). A total of 148 patients, mean age (+/- SD) 40.21 +/- 13.70 years, were enrolled into the study. At the end of the study there were significant improvements in FEV1 and PEFR (29% and 28% increase respectively from baseline values, p<0.000001). The mean total daily dose of inhaled salbutamol decreased significantly from prestudy values of 461 +/- 332 microg/day to 161 +/- 207 microg/day (p<0.000001). The mean eosinophil counts fell from 5.80 +/- 4.90% (+/- SD) to 4.84 +/- 4.42% (+/- SD) (p=0.02). Symptom scores improved significantly as did subjective assessment of discomfort. A total of 29 (19.6%) adverse events were reported, all of which were of mild to moderate intensity. Monotherapy with montelukast significantly improved parameters of asthma control. It was well tolerated with no reports of serious or severe adverse events.

Topics: Acetates; Adult; Aged; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Middle Aged; Peak Expiratory Flow Rate; Prospective Studies; Quinolines; Sulfides; Treatment Outcome

Chronic urticaria (CU) is a common skin condition. It is frequently a disabling disease due to the persistency of clinical symptoms, the unpredictable course and negative influence on the quality of life.. The aim of this study is to determine whether montelukast, a LTD4 receptor antagonist, plus desloratadine, is more efficacious than desloratadine alone in the treatment of chronic urticaria.. A randomized, double-blind, placebo-controlled study was conducted on 81 patients with a diagnosis of CU. A 1-week single-blind placebo run-in period (baseline) was followed by a 6-weeks double blind active treatment period. The patients were randomized to receive the following treatment once daily: (a) oral desloratadine (5 mg) plus placebo; (b) desloratadine (5 mg) plus montelukast (10 mg); (c) oral placebo alone. The study ended after another 1-week single-blind placebo washout period.. The evaluable population thus consisted of 76 patients. Both desloratadine alone and desloratadine plus montelukast administered once daily yielded improvements with respect to the baseline assessment as regards pruritus, number of separate episodes, size and number of weals, visual analogue score and patients' quality of life and with respect to the placebo group both in the active treatment period and in the run-out period. However, desloratadine plus montelukast was shown to improve the symptoms and patients' quality of life significantly more than desloratadine alone, although it did not have a significant effect on the number of urticarial episodes.. The combination of desloratadine plus montelukast is effective in the treatment of CU. It may therefore be a valid alternative in patients with relatively mild CU, in view of its efficacy and the lack of adverse events.

Topics: Acetates; Administration, Oral; Adolescent; Adult; Aged; Chronic Disease; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Loratadine; Male; Middle Aged; Pruritus; Quality of Life; Quinolines; Severity of Illness Index; Sulfides; Treatment Outcome; Urticaria

H 1 -receptor antagonists are considered to be particularly effective in reducing pruritus, and they are therefore recommended as first-line treatment in patients with chronic idiopathic urticaria (CIU). Recently, antileukotriene receptors have been used in patients with CIU, either administered as monotherapy or combined with H 1 -receptor antagonists.. We compared the clinical efficacy of 5 mg of desloratadine administered once daily either as monotherapy or combined with a leukotriene antagonist, 10 mg of montelukast daily, and 10 mg of montelukast administered daily as monotherapy for the treatment of patients affected by CIU with placebo.. One hundred sixty patients aged 18 to 69 years (mean +/- SD, 43.9 +/- 13.4 years) with a history of moderate CIU were selected. A randomized, double-blind, double-dummy, placebo-controlled, parallel-group study design was used. Patients were treated with 5 mg of desloratadine once daily (n = 40), 10 mg of montelukast once daily (n = 40), 5 mg of desloratadine (n = 40) in the morning plus montelukast in the evening, or matched placebo (n = 40). Assessment of treatment efficacy was based on scores of daily cutaneous symptoms evaluated reflectively and instantaneously.. Only the group treated with desloratadine as monotherapy or as combined therapy concluded the whole study. Twenty-seven of the 40 patients in the montelukast group and 35 of the 40 patients in the placebo group discontinued the treatment. As reflective evaluation, all groups showed significant differences compared with the placebo group in terms of total symptom score, number of hives, and size of largest hive. In addition to the pruritus, only the groups treated with desloratadine as monotherapy or combined therapy showed significant differences compared with those receiving placebo, whereas there were no differences between the montelukast and placebo groups. Finally, no differences were found between the desloratadine group and the desloratadine plus montelukast group. The instantaneous evaluation demonstrated similar results regarding the desloratadine group and the desloratadine plus montelukast group versus the placebo group, whereas there were no significant differences between the group treated with montelukast alone and the placebo group for pruritus and size of largest hive. No differences were found between the group treated with desloratadine alone and the desloratadine plus montelukast group.. The results of this comparative study demonstrate that desloratadine is highly effective for the treatment of patients affected by CIU. In addition, the regular combined therapy of desloratadine plus montelukast does not seem to offer a substantial advantage with respect to desloratadine as monotherapy in patients affected by moderate CIU.

Topics: Acetates; Adolescent; Adult; Aged; Chronic Disease; Cyclopropanes; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Loratadine; Male; Middle Aged; Quinolines; Sulfides; Treatment Outcome; Urticaria

Chronic pancreatitis is a debilitating condition of which pain is a predominant feature, and, at present, only putative treatments, beyond analgesics, exist. Evidence suggests that leukotrienes may play a role in both acute and chronic pancreatitis and that cells involved in their signalling are implicated in both conditions and pain production in chronic pancreatitis. We thus performed a study of a cysteinyl leukotriene receptor antagonist of proven benefit in chronic asthma (montelukast sodium) in patients with chronic pancreatitis.. A double-blind, placebo-controlled crossover trial of daily montelukast sodium (10 mg), of 8 months' duration, was performed in those suffering from painful chronic pancreatitis. Daily visual analogue pain scores and analgesic diaries were completed throughout the trial, as were monthly quality-of-life questionnaires and blood taken for inflammatory markers. Visual analogue pain scores were the primary outcome measure.. In crossover analysis of mean visual analogue pain scores there was no significant difference between the groups (t = 1.51; P = 0.156). All baseline C-reactive protein results were 13 mg/l or less. Soluble tumor necrosis factor receptor results showed no significant difference pre- and post-treatment.. In both primary and secondary outcome measures there was no significant effect for the cysteinyl leukotriene receptor antagonist, montelukast sodium in chronic pancreatitis in humans.

Topics: Acetates; Adult; Aged; C-Reactive Protein; Chronic Disease; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Pain Measurement; Pancreatitis; Quinolines; Sulfides; Treatment Failure

We report a 4 yr follow up study of seven asthmatic children with chronic persistent asthma, high-residual volume and low-density areas at high-resolution computerized tomography after treatment with salmeterol and fluticasone. Improvement of lung function with disappearance of low-density areas in six patients after treatment with fluticasone and montelukast was obtained.

Topics: Acetates; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Child; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Fluticasone; Follow-Up Studies; Humans; Lung; Quinolines; Respiratory Function Tests; Salmeterol Xinafoate; Sulfides

Whether chronic dosing with montelukast confers benefit in patients with moderate to severe asthma remains to be fully established. A proof of concept study was performed evaluating putative benefits with montelukast in moderate persistent asthmatics who were taken off inhaled corticosteroids (ICS) and switched to salmeterol. The latter was done to dissociate the effects of montelukast from ICS.. Twenty moderate to severe persistent asthmatics completed a randomized double-blind crossover study. Subjects received montelukast 10 mg daily or placebo for 2 weeks each. This was preceded by a 2-week run-in when ICS were discontinued and salmeterol started, and used on a regular basis throughout the study. Measurements were made after run-in and after both randomized treatments.. There were no significant sequence effects for responses as to whether placebo or montelukast were given first or second. Methacholine PD20 values after run-in, first and second placebo were 63 micro g, 60 micro g and 64 micro g, respectively (corresponding to 2, 4 and 6 weeks of ICS washout, respectively). Lung function deteriorated pre vs post run-in, which was significant (P < 0.05) for FEF25-75 % predicted. Montelukast conferred significant (P < 0.05) improvements as change from post run-in compared with placebo in methacholine PD20, FEV1 % predicted, FEF25-75 % predicted, diurnal peak expiratory flow, symptoms and salbutamol use. For the primary outcome of methacholine PD20, this amounted to a 1.6-fold difference (95% CI 1.1, 2.5).. In moderate persistent asthmatics switched from taking ICS to salmeterol alone, adding montelukast conferred significant benefits on all parameters of asthma control. Further studies are indicated to evaluate whether montelukast exhibits additive effects to ICS/long-acting beta2-adrenoceptor agonist combination inhalers upon clinically important outcomes.

Topics: Acetates; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Double-Blind Method; Drug Evaluation; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Peak Expiratory Flow Rate; Quinolines; Sulfides; Treatment Outcome

Chronic idiopathic urticaria (CIU) might be refractory to standard therapies. For the patients with severe unremitting CIU who have failed to benefit from conventional therapy with antihistamines, other effective and safe therapeutic modalities are required.. A randomized, single-blind, placebo-controlled crossover study was conducted to evaluate the efficacy and safety of the new selective leukotriene antagonist montelukast sodium in the treatment of refractory CIU.. Thirty patients with refractory CIU were enrolled in the trial. After informed consent was obtained, patients were randomly assigned to 2 groups. The patients in group A received 10 mg/d montelukast and a nonsedating H(1) antihistamine (cetirizine) when needed for 6 weeks. After a 2-week washout period, they received placebo for 6 weeks and the same H(1) antihistamine as needed. Group B received the treatment vice versa. Improvement was monitored by using the self-estimated urticaria activity score, which is the sum of the wheal number score and the itch severity score, and the antihistamine counts used in each study period.. More significant decreases occurred in urticaria activity scores with montelukast therapy compared with those with placebo therapy (P <.001). H(1) antihistamine use was also significantly less frequent during the montelukast period (P <.001). There were no significant side effects with montelukast therapy.. The present study results suggest that montelukast might be an effective and safe therapeutic agent in the treatment of refractory CIU.

Topics: Acetates; Adult; Chronic Disease; Cross-Over Studies; Cyclopropanes; Female; Histamine H1 Antagonists; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Single-Blind Method; Sulfides; Urticaria

To compare the relative cost effectiveness of salmeterol (50 microg)/ fluticasone propionate (100 microg) with that of oral montelukast (10mg) as initial maintenance therapy in patients with persistent asthma uncontrolled on short-acting beta2-agonist therapy alone.. A cost-effectiveness analysis was performed based on effectiveness and resource utilisation data that was prospectively collected from a randomised, double-blind, double-dummy, 12-week trial.. Patients (>15 years of age) who had asthma for at least 6 months. Effectiveness measurements in this analysis included improvement in forced expiratory volume in 1 second (FEV(1)) and symptom-free days (SFDs). Cost of asthma drug treatment as well as costs related to an asthma exacerbation were used in the cost analysis. The study assumed a payer's perspective. All costs are in 2001 US dollars.. Of the 423 patients eligible for the study, 211 were randomised to salmeterol/fluticasone propionate and 212 to montelukast. Treatment with salmeterol/fluticasone propionate resulted in a significantly higher proportion of patients who achieved a 12% increase in FEV(1) (successful treatment) [salmeterol/fluticasone propionate: 71% vs montelukast: 39%; p < 0.001] and percentage of SFDs (salmeterol/fluticasone propionate: 46.8% vs montelukast: 21.5%; p < 0.001) compared with montelukast. The mean daily costs per successfully treated patient were lower in the salmeterol/fluticasone propionate group (US dollars 5.03, 95% CI US dollars 4.61 to US dollars 5.50) compared with the montelukast group (US dollars 8.25, 95% CI US dollars 6.98 to US dollars 9.93). Furthermore, per patient mean daily cost per SFD was lower with salmeterol/fluticasone propionate (US dollars 7.63, 95% CI US dollars 6.90 to US dollars 8.50) compared with montelukast (US dollars 14.89, 95% CI US dollars 12.36 to US dollars 17.98). Incremental cost-effectiveness ratios (ICERs) showed that the additional costs to achieve these benefits with salmeterol/fluticasone propionate were minimal. With regards to improvement in lung function, the ICER was US dollars 1.33 (95% CI US dollars 0.80 to US dollars 2.02) and with regards to SFD, the ICER was US dollars 1.69 (95% CI US dollars 1.01 to US dollars 2.48). Sensitivity analysis demonstrated the stability of the results over a range of assumptions.. From a third-party payer perspective, this analysis shows that based on increased efficacy and only a slight increase in cost, twice-daily treatment with salmeterol/fluticasone propionate is more cost effective than once-daily treatment with montelukast as initial maintenance therapy for persistent asthma. This finding complements the results of the clinical analyses indicating that treatment of both inflammation and bronchoconstriction with products such as salmeterol/ fluticasone propionate may be more cost effective as initial maintenance asthma therapy than the use of leukotriene modifiers such as montelukast.

Topics: Acetates; Adolescent; Adult; Aged; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cost-Benefit Analysis; Cyclopropanes; Double-Blind Method; Drug Combinations; Female; Fluticasone; Humans; Male; Middle Aged; Quinolines; Salmeterol Xinafoate; Sulfides

Asthma is a chronic disease characterized by inflammation and bronchoconstriction. Medications that are able to effectively treat both components are advantageous.. To compare the efficacy of an inhaled corticosteroid and a long-acting beta2-agonist combination product with a leukotriene antagonist for initial maintenance therapy in patients who were symptomatic while receiving short-acting beta2-agonists alone.. A 12-week, randomized, double-blind, double-dummy, multicenter study was conducted in 432 patients 15 years of age and older with persistent asthma who were symptomatic on short-acting beta2-agonists alone. Fluticasone propionate 100 microg and salmeterol 50 microg combination product (FSC) twice daily or montelukast 10 mg once daily was administered.. At endpoint, compared with montelukast, FSC significantly increased morning predose forced expiratory volume in 1 second (0.61 +/- 0.03 L vs 0.32 +/- 0.03 L), morning peak expiratory flow rate (peak expiratory flow rate; 81.4 +/- 5.9 L/minute vs 41.9 +/- 4.8 L/minute), evening peak expiratory flow rate (64.6 +/- 5.3 L/minute vs 38.8 +/- 4.7 L/minute), the percentage of symptom-free days (40.3 +/- 2.9% vs 27.0 +/- 2.7%), the percentage of rescue-free days (53.4 +/- 2.8% vs 26.7 +/- 2.5%), and the percentage of nights with no awakenings (29.8 +/- 2.5% vs 19.6 +/- 2.1%) (P < or = 0.011, all comparisons). At endpoint, FSC significantly reduced asthma symptom scores (-1.0 +/- 0.1 vs -0.7 +/- 0.1) and rescue albuterol use (-3.6 +/- 0.2 puffs/day vs -2.2 +/- 0.2 puffs/day) compared with montelukast (P < 0.001). At endpoint, patients treated with FSC also had a significantly greater improvement in quality of life scores and were more satisfied with their treatment compared with montelukast-treated patients (P < or = 0.001). Both treatments were well tolerated.. Initial maintenance therapy with FSC provides greater improvement in asthma control and patient satisfaction than montelukast.

Topics: Acetates; Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Middle Aged; Quinolines; Salmeterol Xinafoate; Sulfides

To compare the long-term effects of an inhaled corticosteroid with those of a leukotriene modifier on measures of clinical efficacy, subject preference, and safety in patients with persistent asthma.. Between November 17, 1998, and May 26, 2000, we conducted a multicenter, randomized, double-blind, double-dummy, parallel-group study of patients aged 15 years or older with persistent asthma. The patients were symptomatic while taking short-acting beta2-agonists alone and were treated with fluticasone propionate (88 microg [2 puffs of 44 microg] twice daily) or montelukast (10 mg/d) for 24 weeks. Measures of pulmonary function, asthma symptoms, albuterol use, nighttime awakenings, physician assessments of efficacy, patient satisfaction, asthma-related quality of life, and safety were evaluated.. A total of 522 patients were randomized to receive fluticasone or montelukast, and 395 patients completed the study. At end point, treatment with fluticasone significantly improved pulmonary function, asthma symptom scores, the percentage of symptom-free days, rescue albuterol use, and the number of nighttime awakenings due to asthma when compared with montelukast (P< or = .002, each comparison). Significantly more patients were satisfied with fluticasone therapy (83%) compared with montelukast therapy (66%) (P<.001), and fluticasone therapy was rated as effective by a significantly greater portion of physicians (67%) than was montelukast therapy (54%) (P<.001). Treatment with fluticasone significantly improved asthma-related quality-of-life measures compared with montelukast (P< or =.01). The incidence of asthma exacerbations was similar in the fluticasone (19 patients, 7%) and montelukast (21 patients, 8%) treatment groups, although slightly more patients in the montelukast group were withdrawn from the study because of asthma exacerbations (6% vs 4%, respectively).. Long-term treatment with a low dose of inhaled fluticasone is more effective than oral montelukast as first-line maintenance therapy for the treatment of persistent asthma.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Androstadienes; Anti-Allergic Agents; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Chronic Disease; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluticasone; Headache; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Patient Satisfaction; Quality of Life; Quinolines; Respiratory Tract Infections; Sleep Initiation and Maintenance Disorders; Sulfides; Treatment Outcome

Topics: Acetates; Adult; Aged; Chronic Disease; Cyclopropanes; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Sulfides; Terfenadine; Treatment Outcome; Urticaria

Leukotriene receptor antagonists have demonstrated clinical benefits in chronic asthma studies of up to 3 months in duration. The effects of these agents over extended periods of time have not been reported.. To describe the long-term effect of oral montelukast, a potent and specific cysteinyl leukotriene receptor antagonist, compared with inhaled corticosteroids in both adult and paediatric patients with chronic asthma.. Male and female patients with chronic, stable asthma (adults aged 15-85 years, children aged 6-14 years), who had completed double-blind, placebo-controlled clinical studies, participated in three extension studies with oral montelukast taken once daily (10 mg tablet for adults, 5 mg chewable tablet for paediatric patients) or inhaled corticosteroids (beclomethasone 200 microg twice daily for adults, beclomethasone 100 microg or equivalent three times daily for children). A double-blind adult extension study was 37 weeks in duration; open-label adult extension studies were 156 (adults) and 112 (paediatric) weeks in duration. A total of 436, 374, and 245 patients entered these extension studies, respectively.. Treatment with both montelukast and inhaled corticosteroids resulted in improvement in multiple parameters of asthma control. Improvements in daytime symptom scores were generally comparable among treatment groups. No tachyphylaxis to the effects of montelukast was evident. In the adult open-label study, however, the effect of beclomethasone on mean forced expiratory volume in 1 second (FEV1) gradually decreased from start of the study to the end of the follow-up treatment period.. Both montelukast and inhaled corticosteroids were effective in controlling mild to moderate chronic asthma; the relative effectiveness of montelukast and beclomethasone were similar in open-label conditions. The hypothesis, that clinical practice conditions (e.g., adherence) may have a significant impact on the effectiveness of these therapies, should be tested in future clinical trials.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Beclomethasone; Child; Chronic Disease; Cyclopropanes; Double-Blind Method; Eosinophils; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Leukocyte Count; Leukotriene Antagonists; Male; Middle Aged; Predictive Value of Tests; Quinolines; Sulfides; Time

Controlled trials suggest that leukotriene receptor antagonists can improve lung function and reduce requirement for oral or inhaled corticosteroids in patients with asthma. We aimed to assess whether montelukast, a leukotriene receptor antagonist, can improve symptoms or lung function in patients with chronic asthma with symptoms already taking corticosteroids.. We did a double-blind, placebo-controlled, crossover, randomised add-on study in which 100 patients with asthma and symptoms despite treatment with inhaled corticosteroids and additional therapy were given 10 mg montelukast sodium for 14 days in an outpatient clinic setting. Outcome measures were symptoms and peak flow diaries.. 72 patients had diary data for analysis. Compared with placebo, addition of montelukast did not result in any significant change in symptom scores (mean difference between the last 7 days of each treatment period 0.05; 95% CI --0.86 to 1.14), rescue inhaled beta(2) agonist use (mean difference in puffs per day 0.41; -0.29 to 0.57), or twice daily peak expiratory flow (PEF) measurements (mean difference in morning PEF 1.18 L/min; -14.29 to 17.14), and mean difference in evening peak flow (-0.50; -17.42 to 12.86). When treatment response was defined as a 15% or greater increase in mean peak flow readings, there were four responders to montelukast and seven responders to placebo.. Based on PEF data from our previous studies of a similar patient group we would have expected to detect changes of more than 5%. Used as additional therapy in a hospital outpatient clinic setting, montelukast did not provide such additional benefit in patients with moderate or severe asthma.

Topics: Acetates; Adrenergic beta-Agonists; Adult; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Chronic Disease; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Middle Aged; Peak Expiratory Flow Rate; Quinolines; Steroids; Sulfides

The cause and pathogenesis of chronic urticaria are still poorly understood. IgE-independent reactions, are common in adult patients with chronic urticaria, who have daily spontaneous occurrence of weals. H(1)-receptor antagonists (antihistamines) are the major class of therapeutic agents used in the management of urticaria and angioedema. Nevertheless, chronic urticaria is often difficult to treat and may not be controlled by antihistamines alone. It has been postulated that mediators other than histamine, such as kinins, prostaglandin and leukotrienes, may be responsible for some of the symptoms in urticaria which are not controlled by antihistamines. In this study, which was randomized double-blind, placebo-controlled, we compare the clinical efficacy and safety of montelukast (MT) 10 mg given once a day and cetirizine (CET) 10 mg given once a day with placebo (PLA), in the treatment of patients with chronic urticaria who have positive challenge to acetylsalicylic acid (ASA) and/or food additives.. A group of 51 patients, ranging in age from 15 to 71 years, with chronic urticaria and positive challenge to food additives and/or ASA, participated in this study for a period of 4 weeks, starting from a 3-day run-in. The assessment of the efficacy was based on scores of daily urticaria symptoms.. MT significantly increased the percentage of symptom-free days for hive and itch. Analysis of frequency distribution of urticaria scores for each symptom gave similar results (MT vs. CET and MT vs. PLA, P < 0.001). The interference with sleep due to their skin condition was also lower in the group treated with MT (P < 0.001). In addition, the median number of days without the rescue medication was significantly higher in the MT group (24 days) than both the CET and the PLA groups (18 days, P < 0.001, and 20 days, P < 0.001, respectively). Finally, a low incidence of adverse events was observed in this study.. The results of this comparative study demonstrate that montelukast orally administered once a day is very effective for the treatment of cutaneous symptoms in patients with chronic urticaria due to food additives and/or ASA.

Topics: Acetates; Adolescent; Adult; Aged; Aspirin; Cetirizine; Chronic Disease; Cyclopropanes; Double-Blind Method; Female; Food Additives; Food Hypersensitivity; Histamine H1 Antagonists; Humans; Incidence; Italy; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Sleep Stages; Sulfides; Treatment Outcome; Urticaria

The efficacy of montelukast, a leukotriene receptor antagonist, in treatment of mild asthma was evaluated.. Thirty children aged 6 to 14 years with mild persistent asthma (asthma history more than 12 months and > or = 15% FEV1 improvement after inhaled beta 2-agonist in the past, good control of asthma with inhaled cromolyn or budesonide in the last three months) were enrolled. The study included three periods (2 week's each): washout, placebo, and montelukast. Asthma symptoms score (range 0-5) and PEF were estimated twice daily by children. Spirometric parameters FEV1 and MEF50 were measured during three consecutive visits: on the day of study inclusion, on the last day of the placebo and montelukast period.. The mean value of asthma symptoms score was significantly lower during the montelukast period in comparison with placebo (p = 0.038). The mean PEF values were significantly higher during the montelukast vs. placebo period (p = 0.0091). Moreover, in the montelukast period, the mean PEF values in the second week were significantly higher than those in the first week (p = 0.003). The mean FEV1 predictive value in the last day of the montelukast period was higher, though not significantly, than on the day of study inclusion and on the last day of the placebo period. A similar change in mean MEF50 values was observed.. In children aged 6-14 years with mild persistent asthma, montelukast treatment significantly diminishes asthma symptoms and increases mean PEF values comparing to placebo.

Topics: Acetates; Adolescent; Asthma; Child; Chronic Disease; Cyclopropanes; Female; Humans; Leukotriene Antagonists; Male; Predictive Value of Tests; Quinolines; Spirometry; Sulfides; Treatment Outcome

Montelukast sodium, a potent, oral, specific leukotriene-receptor antagonist, has demonstrated clinical efficacy in the treatment of chronic asthma. Loratadine, a selective histamine type 1 (H(1))-receptor antagonist, has demonstrated antiallergic properties. Leukotriene-receptor antagonists given concomitantly with H(1)-receptor antagonists have been shown to have additive effects in the prevention of bronchospasm in antigen-challenge models.. To determine whether montelukast plus loratadine provides improved efficacy to montelukast alone in the treatment of chronic asthma.. The efficacy of montelukast alone vs montelukast-loratadine was studied in a 10-week, multicenter, randomized, double-blind, 2 x 2 crossover study. After a 2-week placebo run-in period, patients received montelukast sodium (10 mg) plus loratadine (20 mg), or montelukast sodium (10 mg) plus placebo once daily for 2 weeks. After a 2-week placebo washout period, patients were crossed over to receive 2 weeks of the other active treatment regimen, followed by another 2-week placebo washout period.. Montelukast given concomitantly with loratadine caused significant improvement in percentage of change from baseline in forced expiratory volume in 1 second (FEV(1)) compared with montelukast alone (13.86% vs 9.72%; P =.001). The average additional effect of loratadine (least square mean difference in percentage of change from baseline in FEV(1)) was 4.15% (95% confidence interval, 1.65%-6.65%). Key secondary end points (mean daily beta-agonist use, daytime and nighttime symptom scores, morning and evening peak expiratory flow rate, and the Patient Global Evaluation) all showed significant improvement with montelukast-loratadine (P<.05).. Montelukast-loratadine significantly improved end points of asthma control during a 2-week treatment period.

Topics: Acetates; Adolescent; Adult; Aged; Asthma; Chronic Disease; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Histamine H1 Antagonists; Humans; Leukotriene Antagonists; Loratadine; Male; Middle Aged; Quinolines; Sulfides

To determine the ability of montelukast, a leukotriene receptor antagonist, to allow tapering of inhaled corticosteroids in clinically stable asthmatic patients.. Double blind, randomised, placebo controlled, parallel group study. After a single blind placebo run in period, during which (at most) two inhaled corticosteroids dose decreases occurred, qualifying, clinically stable patients were allocated randomly to receive montelukast (10 mg tablet) or matching placebo once daily at bedtime for up to 12 weeks.. 23 academic asthma centres in United States, Canada, and Europe.. 226 clinically stable patients with chronic asthma receiving high doses of inhaled corticosteroids (113 randomised to montelukast and 113 to placebo).. Every 2 weeks, the inhaled corticosteroids dose was tapered, maintained, or increased (rescue) based on a standardised clinical score.. Last tolerated dose of inhaled corticosteroids.. Compared with placebo, montelukast allowed significant (P=0. 046) reduction in the inhaled corticosteroid dose (montelukast 47% v placebo 30%; least square mean difference 17.6%, 95% confidence interval 0.3 to 34.8). Fewer patients on montelukast (18 (16%) v 34 (30%) placebo, P=0.01) required discontinuation because of failed rescue.. Montelukast reduces the need for inhaled corticosteroids among patients requiring moderate to high doses of corticosteroid to maintain asthma control.

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Aged; Asthma; Chronic Disease; Cyclopropanes; Double-Blind Method; Drug Administration Schedule; Female; Glucocorticoids; Humans; Leukotriene Antagonists; Lung; Male; Middle Aged; Quinolines; Single-Blind Method; Sulfides

The primary objective of this study was to determine whether montelukast, an oral leukotriene receptor antagonist, provides additional clinical benefit to the effect of inhaled corticosteroids. A total of 642 patients with chronic asthma (FEV(1) 50 to 85% of predicted value and at least a predefined level of asthma symptoms) incompletely controlled with inhaled beclomethasone, 200 microg twice daily using a spacer device, during the 4-wk run-in period were randomly allocated, in a double-blind, double-dummy manner to one of four treatment groups: (1) montelukast 10 mg plus continuing inhaled beclomethasone; (2) placebo tablet plus continuing inhaled beclomethasone; (3) montelukast 10 mg and inhaled placebo (after blind beclomethasone removal); and (4) placebo tablet and inhaled placebo (after blind beclomethasone removal). The primary endpoints were FEV(1) and daytime asthma symptoms score. Montelukast provided significant (p < 0.05) clinical benefit in addition to inhaled beclomethasone by improving FEV(1), daytime asthma symptom scores, and nocturnal awakenings. Blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control, demonstrating that patients received clinical benefit from inhaled corticosteroids. Blind removal of beclomethasone in the presence of montelukast resulted in less asthma control but not to the level of the placebo group. All treatments were well tolerated; clinical and laboratory adverse experiences were generally similar to placebo treatment in this study. In conclusion, montelukast provided additional asthma control to patients benefitting from, but incompletely controlled on, inhaled beclomethasone.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Beclomethasone; Chronic Disease; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Single-Blind Method; Sulfides

Leukotrienes are important mediators of asthma by causing bronchoconstriction, mucous secretion, and increased vascular permeability. Studies using compounds that block leukotrienes have demonstrated improvement in asthma control in adults and adolescents, but children younger than 12 years, for whom asthma is the most common chronic disease, have not been studied.. To determine the clinical effect of montelukast, a leukotriene receptor antagonist, in 6- to 14-year-old children with asthma.. Eight-week, multicenter, randomized, double-blind study.. Forty-seven outpatient centers at private practices and academic medical centers in the United States and Canada.. A total of 336 children with forced expiratory volume in 1 second (FEV1) between 50% to 85% of the predicted value, at least 15% reversibility after inhaled beta-agonist administration, a minimal predefined level of daytime asthma symptoms, and daily beta-agonist use. Concomitant inhaled corticosteroids at a constant daily dose were used by 39% of patients receiving montelukast and 33% receiving placebo.. After a 2-week placebo run-in period, patients received either montelukast (5-mg chewable tablet) or matching-image placebo once daily at bed-time for 8 weeks.. Morning FEV1 percent change from baseline.. Mean morning FEV1 increased from 1.85 L to 2.01 L in the montelukast group and from 1.85 L to 1.93 L in the placebo group. This represents an 8.23% (95% confidence interval [CI], 6.33% to 10.13%) increase from baseline in the montelukast group and a 3.58% (95% CI, 1.29% to 5.87%) increase from baseline in the placebo group (P<.001 for montelukast vs placebo).. Montelukast improves morning FEV1 in 6- to 14-year-old children with chronic asthma.

Topics: Acetates; Adolescent; Adrenergic beta-Agonists; Analysis of Variance; Anti-Asthmatic Agents; Asthma; Child; Chronic Disease; Cyclopropanes; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides

The leukotrienes are known to be important mediators of bronchial asthma. The ability of montelukast, a potent and selective CysLT1 leukotriene receptor antagonist, to cause a dose-related improvement in chronic asthma was investigated in a placebo-controlled, multicentre, parallel-group study. After a two week placebo run-in period, chronic asthmatic patients with a forced expiratory volume in one second (FEV1) 40-80% predicted with > or = 15% increase (absolute value) after beta2-agonist were randomly assigned to one of four treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the evening) for a three week, double-blind treatment period. For patient-reported end-points (daytime symptom score, use of as needed inhaled beta2 agonist, asthma-specific quality of life) and frequency of asthma exacerbations, montelukast 10 and 50 mg caused similar responses, superior to 2 mg and significantly (p<0.05; linear trend test) different from placebo. All three doses caused improvements in FEV1 and morning and evening peak expiratory flow rate (PEFR) that were significantly (p<0.05) different from placebo. Differences (least square mean) between the pooled 10 and 50 mg montelukast treatment groups and placebo were: 7.1% change from baseline in FEV1, 19.23 L x min(-1) in morning PEFR, -0.29 in daytime asthma symptom score (absolute value), and -0.82 in beta2-agonist use (puff x day(-1)). The incidence of adverse experiences was neither dose-related nor different between montelukast and placebo treatments. We conclude that montelukast causes a dose-related improvement in patient-reported asthma end-points over the range 2-50 mg. Montelukast causes benefit to chronic asthmatic patients by improving asthma control end-points.

Topics: Acetates; Adolescent; Adult; Aged; Asthma; Chronic Disease; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Middle Aged; Peak Expiratory Flow Rate; Quality of Life; Quinolines; Spirometry; Sulfides

Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Double-Blind Method; Humans; Leukotriene Antagonists; Placebos; Quinolines; Sulfides; Time Factors

Cysteinyl leukotrienes mediate signs and symptoms of asthma. In a double-blind, placebo-controlled, crossover study, a new potent and specific cysteinyl leukotriene (LTD4) receptor antagonist, montelukast (MK-0476), was evaluated for tolerability and clinical efficacy in patients with chronic asthma (receiving and not receiving inhaled corticosteroids).. Twenty-nine nonsmoking patients with asthma (15 treated concomitantly with inhaled corticosteroids) with FEV1 percent predicted values between 50% to 80% received MK-0476, 200 mg, or placebo three times daily for 10 1/3 days (31 doses) in a random, crossover manner, after a 2-week, open, baseline period. Comparisons in FEV1 (mean percent change from baseline after the first and last dose), mean daily daytime asthma and nocturnal awakening scores, and mean daily beta-agonist use were made between treatment periods.. Montelukast, compared with placebo, caused improvements in FEV1 (mean percentage point difference of the percentage change from baseline) 3 and 4 hours after dosing on day 1 (hour 3, 9.0%; 95% confidence interval [CI] 0.53, 18.72; hour four, 10.9%; 95% CI -0.25, 20.20) and day 11 (hour 3, 14.0%; 95% CI 0.76, 31.43; hour 4, 13.4%; 95% CI 1.24, 28.83). Reductions were observed in mean daily beta-agonist use (1.0 puff/day [95% CI -1.61, -0.26]), mean daytime symptom scores, and nocturnal awakenings over the 10 1/3 day treatment period. There were no important differences between the groups receiving and those not receiving inhaled corticosteroids. Montelukast was well tolerated with no serious clinical adverse events reported.. In this study Montelukast, 200 mg, administered three times daily for 10 1/3 days, compared with placebo, was generally well tolerated and resulted in significant improvement in chronic asthma, irrespective of the presence of inhaled corticosteroids.

Topics: Acetates; Adolescent; Adrenal Cortex Hormones; Adult; Asthma; Chronic Disease; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Administration Schedule; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Leukotriene D4; Male; Membrane Proteins; Middle Aged; Quinolines; Receptors, Leukotriene; Sulfides

Delayed pressure urticaria (DPU) is a rare form of chronic inducible urticaria (CIndU) when it manifests alone. Treatment of DPU is disappointing owing to the lack of response to antihistamines, even when up-dosing. In addition, the absence of randomized clinical trials and the low number of patients included in the studies mean that there is little scientific evidence for the validity of omalizumab in DPU.. Objectives of the study were to perform a real-world study of the effectiveness and safety of omalizumab in DPU patients without chronic spontaneous urticaria or other forms of CIndU and to describe their clinical and diagnostic features.. We performed an ambispective observational study of 14 patients with DPU who did not respond to 2 or more second-generation H1-antihistamines in an up-dosing regimen and/or corticosteroids, montelukast, or cyclosporine. Treatment was initiated with omalizumab 300 mg every 4 weeks. We recorded the following: age, time to diagnosis, previous treatment, diagnostic testing (mean time threshold after removing the stimulus and duration of the lesions), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D dimer, total IgE, antithyroid peroxidase (anti-TPO) antibodies, and the Urticaria Control Test (UCT) score before and after the first dose. We evaluated the efficacy of omalizumab according to the Urticaria Control Test score. We analyzed the time to complete or satisfactory response after the first dose (superfast) and its adverse effects.. Women accounted for 64.28% patients. The mean age at diagnosis was 43.64 (±13.78) years. The time to diagnosis was 4.53 (±5.54) years. The mean time threshold after removing the stimulus was 4.18 h (±2.75). The mean duration of lesions after testing was 32.42 (±13.8) hours. High ERS values (>20.0 mm/h) were detected in 50% of patients. CRP was >0.5 mg/dL in 42.85% and D dimer levels were high (>500.0 ng/mL) in 3/10 patients. Anti-TPO level was normal in 100% of patients. Total IgE was >100 IU/mL in 6/8 patients. Medium UCT levels before treatment with omalizumab were 3.07 (±2.40), reaching 15.28/16 (±1.72) after the first dose of omalizumab. All 14 patients responded superfast, and none experienced an adverse reaction.. Despite the limitation of a low sample size in this real-life study, our findings suggest that omalizumab is a rapid, effective, and safe treatment for patients with DPU refractory to antihistamines in an up-dosing regimen. We recommend omalizumab for patients who do not respond to up-dosing antihistamines and montelukast.

Topics: Acetates; Adrenal Cortex Hormones; Adult; Anti-Allergic Agents; C-Reactive Protein; Chronic Disease; Chronic Urticaria; Cyclopropanes; Cyclosporins; Female; Histamine Antagonists; Humans; Immunoglobulin E; Middle Aged; Omalizumab; Peroxidases; Quinolines; Sulfides; Treatment Outcome; Urticaria

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.. 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.. 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.. Our findings will provide vigorous evidence to judge whether montelukast sodium and budesonide therapy is an efficient form of therapy for CVA patients.. Ethics approval is not needed for the present meta-analysis.. May 17, 2021.osf.io/cuvjz (https://osf.io/cuvjz/).

Topics: Acetates; Administration, Inhalation; Asthma; Budesonide; Child; Chronic Disease; Cough; Cyclopropanes; Drug Therapy, Combination; Glucocorticoids; Humans; Leukotriene Antagonists; Meta-Analysis as Topic; Quinolines; Randomized Controlled Trials as Topic; Sulfides; Systematic Reviews as Topic; Treatment Outcome

Chronic lung allograft dysfunction (CLAD) is a major cause of post‒lung transplant mortality, with limited medical treatment options. In this study we assessed the association of montelukast treatment with pulmonary function and outcome in lung transplant recipients with progressive CLAD.. We performed a retrospective study of all lung transplant recipients transplanted between July 1991 and December 2016 at our center and who were treated for at least 3 months with montelukast for progressive CLAD, despite at least 3 months of prior azithromycin therapy. Main outcome parameters included evolution of pulmonary function and progression-free and overall survival.. A total of 153 patients with CLAD (115 with bronchiolitis obliterans syndrome and 38 with restrictive allograft syndrome) were included, of whom 46% had a forced expiratory volume in 1 second (FEV. Montelukast was associated with a significant attenuation in rate of FEV

Topics: Acetates; Adult; Allografts; Chronic Disease; Cyclopropanes; Cytochrome P-450 CYP1A2 Inducers; Female; Follow-Up Studies; Forced Expiratory Volume; Graft Rejection; Humans; Lung Transplantation; Male; Middle Aged; Postoperative Period; Quinolines; Retrospective Studies; Sulfides; Transplant Recipients

Topics: Acetates; Anti-Inflammatory Agents; Antimalarials; Cetirizine; Chronic Disease; Cyclopropanes; Diphenhydramine; Drug Resistance; Histamine Antagonists; Humans; Hydroxychloroquine; Infant; Male; Quinolines; Ranitidine; Skin; Sulfides; Urticaria

The rationale of this study is that, treatment of asthmatic Guinea pig with combined administration of Montelukast sodium and Green Tea Extract (GTE) as a single capsule will mitigate the inflammatory injury in the airways and weaken the asthmatic response. Recent patents for the treatment of asthma researched a polyphenolic alternatives for antiasthmatic combination therapy, especially for those patients who remains unresponsive or poorly responsive for current asthma therapy (US7232585B2). Synergistic activity of green tea polyphenols and therapeutic, prophylatic agents are also reported in some recent patents (US20120172423A1, US20150320696A1). The present work is therefore aimed, to study the effect of Montelukast Sodium capsules coformulated with GTE on oxidative stress markers including Malondialdehyde (MDA), Glutathione (GSH) in different organs and Oxygen Radical Absorbance Capacity (ORAC) assay in plasma.. Guinea pigs were placed in histamine chamber and exposed to an aerosol challenge of 0.2% w/v histamine dihydrochloride in distilled water using pressurized air driven nebulizer at a pressure of 0.05 MPa-0.106 MPa for one week. After that, they were divided in to four groups of three each; control, asthmatic control, asthmatic treated with marketed preparation and asthmatic received developed capsules. After oral administration of formulations for three days, pigs were scarificed and oxidative stress markers level including cytoarchitectural manifestation in tissues was studied.. In comparison with the healthy control group, MDA level of the asthmatic animal liver and lung was found to be elevated as 0.059 ± 0.031(p < 0.002) and 0.802 ± 0.310 (p < 0.005) respectively, whereas GSH level was declined as 13.223 ± 1.485 (p < 0.0001) in liver and 3.037 ± 0.282 (p < 0.0004) in lung tissues. TAC of asthmatic animal plasma was low as 2.132 ± 0.986 mM Trolox Eq/L (p < 0.009). The level of these biomarkers reverts back towards normal after treatment with marketed and developed formulation, although treatment with developed formulation was more efficacious since it was coformulated with GTE, which acts as an adjuvant for the management of inflammatory disease like asthma.. It is contemplated that, use of GTE as an adjuvant to anti leukotriene drug played a significant role in asthma management by reducing oxidant injury. Since, studies in animals do not directly translate to human biology, further multi-control studies with better sampled patient population and more number of patients are needed.

Topics: Acetates; Administration, Oral; Animals; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Drug Combinations; Female; Glutathione; Guinea Pigs; Histamine; Liver; Lung; Male; Malondialdehyde; Oxidative Stress; Oxygen Radical Absorbance Capacity; Patents as Topic; Plant Extracts; Quinolines; Sulfides; Tea

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.

Topics: Acetates; Animals; Bronchoalveolar Lavage Fluid; Chronic Disease; Cyclopropanes; Dexamethasone; Disease Models, Animal; Glucocorticoids; Guinea Pigs; Histone Deacetylases; Inflammation; Leukocyte Count; Leukotriene Antagonists; Leukotriene B4; Lipopolysaccharides; Lung; Male; Malondialdehyde; Neutrophils; Pulmonary Disease, Chronic Obstructive; Quinolines; Respiratory Hypersensitivity; Sulfides; Tumor Necrosis Factor-alpha

Montelukast is used in the treatment of allergic rhinitis and asthma. It has been used as adjuvant therapy in patients with chronic rhinosinusitis (CRS), but its effectiveness has not been evaluated. This study evaluates the efficacy of adjuvant leukotriene receptor antagonism in CRS and subtypes.. Retrospective review of collected data at a tertiary-referral institution. We identified all patients who were prescribed montelukast postoperatively and had a lapse in therapy for at least 1 month (n = 50), so that the patients themselves serve as their own control group. Twenty-item Sino-Nasal Outcomes Test (SNOT-20) scores and Lund-Kennedy endoscopy scores were obtained for each patient. Scores were compared with and without montelukast using Wilcoxon signed rank test. The analysis was controlled for changes in other medications.. Fifty-two therapy lapses were identified in 50 patients. Twenty-seven patients had eosinophilic CRS with polyps (eCRSwNP), 8 had Samter's triad (ST), and 15 had allergic fungal sinusitis (AFS). Overall mean follow-up was 46.5 months. Overall, SNOT-20 scores and endoscopy scores were significantly lower with montelukast (p < 0.005 for both). On subgroup analysis, SNOT-20 scores were significantly improved for patients with eCRSwNP and AFS (p < 0.001 and p = 0.001, respectively). Endoscopy scores were significantly improved for patients with eCRSwNP (p = 0.044). Outcomes approached, but did not reach, significance for patients with ST (p = 0.123 for SNOT-20 and p = 0.146 for endoscopy). There was also significant improvements in patients with asthma.. The addition of montelukast as postoperative therapy may be beneficial for patients with eCRSwNP and AFS.

Topics: Acetates; Adolescent; Adult; Aged; Asthma; Chronic Disease; Cyclopropanes; Eosinophils; Female; Follow-Up Studies; Humans; Leukotriene Antagonists; Male; Middle Aged; Postoperative Complications; Quinolines; Retrospective Studies; Rhinitis; Rhinoplasty; Sinusitis; Sulfides; Treatment Outcome; Young Adult

Cysteinyl leukotrienes and their receptors have been shown to be involved in the generation of neuropathic pain. We performed this study to determine the antagonistic effect of montelukast, a cysteinyl leukotrienes receptor antagonist, on neuropathic pain and its underlying mechanism.. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in rats. After CCI, rats were repeatedly administered montelukast (0.5, 1.0, and 2.0 mg/kg intraperitoneal, once daily) for a period of 14 days. Mechanical withdrawal threshold and thermal withdrawal latency were assessed before surgery and on days 1, 3, 5, 7, and 14 after CCI. The levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the spinal cord were determined by enzyme-linked immunosorbent assay. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) and activation of nuclear factor-kappaB (NF-κB) were assessed by Western blot. The expression of astrocyte marker glial fibrillary acidic protein and microglia marker Iba-1 and the coexpression of p-p38MAPK and Iba-1 or NF-κB and Iba-1 were observed by immunofluorescent staining.. The CCI group displayed significantly decreased mechanical withdrawal threshold and thermal withdrawal latency on days 1, 3, 5, 7 and 14 compared with sham groups (P <0.05, P < 0.0001), which were markedly increased by montelukast (P < 0.05, P < 0.01, P <0.0001). After administration with montelukast for 14 days, as biological markers of inflammation, the levels of IL-1β (P < 0.0001), IL-6 (P = 0.001 for low dosage, P < 0.0001 for middle and high dosages), and TNF-α (P =0.002, 0.001, < 0.0001 for low, middle, and high dosage, respectively) in the spinal cord were lower than those in the CCI group. Western blot analysis demonstrated that montelukast reduced the elevated expression of p-p38 MAPK (P =0.006, 0.015, < 0.0001 for low, middle, and high dosage, respectively) and NF-κB (P < 0.0001) in the spinal cord induced by CCI. Immunofluorescent staining showed that montelukast could inhibit CCI-induced activation of microglia but not astrocytes in the spinal cord. In addition, montelukast (2.0 mg/kg) significantly decreased the number of p38MAPK and Iba-1 or NF-κBp65 and Iba-1 double-positive cells.. These results suggest that montelukast could effectively attenuate neuropathic pain in CCI rats by inhibiting the activation of p38MAPK and NF-κB signaling pathways in spinal microglia.

Topics: Acetates; Animals; Astrocytes; Blotting, Western; Chronic Disease; Constriction, Pathologic; Cyclopropanes; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Hot Temperature; Interleukins; Leukotriene Antagonists; Male; Microglia; Neuralgia; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Physical Stimulation; Protein Kinase Inhibitors; Quinolines; Rats; Rats, Sprague-Dawley; Spinal Cord; Sulfides; Tumor Necrosis Factor-alpha

Bronchiolar Clara cells play a critical role in lung homoeostasis. The main goal of this study was to evaluate the effects of chronic allergy on these cells and the efficacy of budesonide (BUD) and montelukast (MK) in restoring their typical phenotypes after ovalbumin-induced chronic allergy in mice. Chronic allergy induced extensive bronchiolar Alcian blue-periodic acid-Schiff (AB/PAS)-positive metaplasia. In addition, cells accumulated numerous big electron-lucent granules negative for Clara cell main secretory protein (CC16), and consequently, CC16 was significantly reduced in bronchoalveolar lavage. A concomitant reduction in SP-D and CYP2E1 content was observed. The phenotypic changes induced by allergy were pharmacologically reversed by both treatments; MK was more efficient than BUD in doing so. MK decreased AB/PAS reactivity to control levels whereas they remained persistently elevated after BUD. Moreover, most non-ciliated cells recovered their normal morphology after MK, whereas for BUD normal cells coexisted with 'transitional' cells that contained remnant mucous granules and stained strongly for CC16 and SP-D. Glucocorticoids were also less able to reduce inflammatory infiltration and maintained higher percentage of neutrophils, which may have contributed to prolonged mucin expression. These results show that chronic allergy-induced mucous metaplasia of Clara cells affects their defensive mechanisms. However, anti-inflammatory treatments were able to re-establish the normal phenotype of Clara cell, with MK being more efficient at restoring a normal profile than BUD. This study highlights the role of epithelial cells in lung injuries and their contribution to anti-inflammatory therapies.

Topics: Acetates; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchi; Budesonide; Chronic Disease; Cyclopropanes; Cytochrome P-450 CYP2E1; Disease Models, Animal; Epithelium; Female; Mice; Mice, Inbred BALB C; Ovalbumin; Phenotype; Pulmonary Surfactant-Associated Protein D; Quinolines; Sulfides; Uteroglobin

Compare the effects of montelukast or dexamethasone in distal lung parenchyma and airway walls of guinea pigs (GP) with chronic allergic inflammation.. GP have inhaled ovalbumin (OVA group-2x/week/4weeks). After the 4th inhalation, GP were treated with montelukast or dexamethasone. After 72 hours of the 7th inhalation, GP were anesthetised, and lungs were removed and submitted to histopathological evaluation.. Montelukast and dexamethasone treatments reduced the number of eosinophils in airway wall and distal lung parenchyma compared to OVA group (P < 0.05). On distal parenchyma, both treatments were effective in reducing RANTES, NF- κ B, and fibronectin positive cells compared to OVA group (P < 0.001). Montelukast was more effective in reducing eotaxin positive cells on distal parenchyma compared to dexamethasone treatment (P < 0.001), while there was a more expressive reduction of IGF-I positive cells in OVA-D group (P < 0.001). On airway walls, montelukast and dexamethasone were effective in reducing IGF-I, RANTES, and fibronectin positive cells compared to OVA group (P < 0.05). Dexamethasone was more effective in reducing the number of eotaxin and NF- κ B positive cells than Montelukast (P < 0.05).. In this animal model, both treatments were effective in modulating allergic inflammation and remodeling distal lung parenchyma and airway wall, contributing to a better control of the inflammatory response.

Topics: Acetates; Administration, Inhalation; Animals; Chronic Disease; Cyclopropanes; Dexamethasone; Disease Models, Animal; Guinea Pigs; Hypersensitivity; Inflammation; Leukotriene Antagonists; Lung; Ovalbumin; Quinolines; Sulfides

We evaluated the effects of anti-iNOS (1400W - W) associated with leukotriene antagonist (montelukast - M) or corticosteroid (dexamethasone - D) on distal lung of guinea pigs (GP) with chronic pulmonary inflammation.. GP were inhaled with ovalbumin (OVA-2×/week/4 weeks), treated with M (OVAM), D (OVAD) and/or W (OVAW, OVADW, OVAMW) and distal lungs were evaluated by morphometry.. Isolated treatments were not sufficient to reduce all parameters. In OVADW, all parameters were reduced with greater reduction in elastic fibers, TIMP-1, IL-4, IL-5, IFN-gamma and PGF2-alpha compared with OVAD (p<0.05). OVAMW potentiated the reduction of actin, elastic fibers, TIMP-1, IL-4, IL-5, TGF-beta, IFN-gamma, iNOS, and PGF2-alpha to a greater extent than OVAM (p<0.05). A reduction of TIMP-1, IL-4, IL-5, TGF-beta, IFN-gamma and iNOS was observed in OVADW compared with OVAMW (p<0.05).. Although anti-iNOS paired with montelukast or dexamethasone yields better results than isolated treatments, the most effective pairing for controlling inflammation, oxidative stress and remodeling in this asthma model was found to be corticosteroids and anti-iNOS.

Topics: Acetates; Amidines; Animals; Anti-Inflammatory Agents; Benzylamines; Chronic Disease; Cyclopropanes; Cytokines; Dexamethasone; Disease Models, Animal; Enzyme Inhibitors; Eosinophils; Guinea Pigs; Lung; Male; Ovalbumin; Pneumonia; Quinolines; Statistics, Nonparametric; Sulfides

The literature on chronic idiopathic urticaria (CIU) lacks large-scale population-based studies.. To characterize an insured population with CIU, including their demographic characteristics and comorbidities.. We conducted a cross-sectional analysis using insurance claims. We included patients with 1 outpatient claim with an International Classification of Diseases, 9(th)Edition, Clinical Modification (ICD-9-CM) code for idiopathic, other specified, or unspecified urticaria (ICD-9-CM 708.1, 708.8, or 708.9) and either (1) another of these claims 6 or more weeks later; (2) a claim for angioedema (ICD-9-CM 995.1) 6 or more weeks from the urticaria diagnosis; or (3) overlapping claims for 2 prescription medications commonly used for CIU.. We identified 6,019 patients who had claims consistent with CIU. The mean age was 36 years. Fifty-six percent of patients had primary care physicians as their usual source of care, 14% had allergists, and 5% had dermatologists. Allergic rhinitis was diagnosed in 48%, asthma in 21%, other allergy in 19%, and atopic dermatitis in 8%. Sixty-seven percent of patients used prescription antihistamines, 54% used oral corticosteroids (OCSs), 24% used montelukast, and 9% used oral doxepin. Antihistamine users received a mean of 152 days of prescription antihistamines, OCS users 30 days of OCSs, montelukast users 190 days of montelukast, and oral doxepin users 94 days of doxepin.. Primary care physicians managed most patients with CIU. Antihistamines were the most common treatment for CIU, although OCSs were frequently prescribed. Thirty days of OCS supply among users may represent multiple steroid bursts each year. Given the known risks of OCSs, identifying other CIU treatments with more favorable safety profiles may be beneficial.

Topics: Acetates; Administration, Oral; Adolescent; Adrenal Cortex Hormones; Adult; Angioedema; Chronic Disease; Cross-Sectional Studies; Cyclopropanes; Doxepin; Drug Prescriptions; Fees, Pharmaceutical; Female; Health Care Costs; Histamine Antagonists; Humans; Insurance Claim Review; Male; Middle Aged; Practice Patterns, Physicians'; Quinolines; Sulfides; Urticaria; Young Adult

Chronic idiopathic urticaria is a common skin disorder characterized by recurrent appearance of wheals and/or angioedema for more than 6 weeks without an identifiable cause. Consensus guidelines suggest use of leukotriene receptor antagonists (montelukast or zafirlukast) in patients whose urticaria is resistant to antihistamines. Our objectives were (1) document the efficacy of montelukast in our patients, and (2) evaluate whether any clinical features or available laboratory investigations were associated with a response to montelukast. Patients who received montelukast between the years 2008-2011 (4-year period) were retrospectively identified from clinic letters. Clinical features and laboratory investigations were collected and analyzed. The primary end point was adequate control of disease without the need for systemic steroid therapy. 25 patients (10 males and 15 females; median age, 33 years; age range, 13-66 years) with an average duration of urticaria at 3.8 years received montelukast 10mg daily. 12 patients (48%) were better on montelukast with combined anti-H1 and anti-H2 therapy, with no statistical significance between median age and duration of urticaria between males and females. In 11 patients, montelukast had no effect and in 2 patients the urticaria worsened after montelukast was started. 15 patients had peripheral blood basopenia of which 5 patients responded to montelukast. Two patients had positive antinuclear antibody, 3 thyroid peroxidase antibodies and 4 with positive basophil histamine release. All 20 patients who had complement C3 and C4 levels done were within normal limits. Four of 6 patients (67%) with positive specific IgE responded to montelukast and combined anti-H1/H2 therapy. Almost half of our patients with chronic urticaria responded to montelukast and combined anti-H1 and anti-H2 therapy. We were unable to identify any clinical features or laboratory markers that were associated with a response to montelukast. Further studies are required to understand the failure of response of leukotriene inhibition in urticaria.

Topics: Acetates; Adolescent; Adult; Aged; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Female; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Immunoglobulin E; Leukotriene Antagonists; Male; Middle Aged; Practice Guidelines as Topic; Quinolines; Retrospective Studies; Sulfides; Treatment Outcome; Urticaria; Young Adult

Histamine is the main mediator of urticaria and H1-receptor antagonists represent the treatment of choice in all patients with chronic urticaria. Leukotriene receptor antagonists as montelukast have also been used in patients with chronic urticaria unresponsive to H1-antihistamines alone. We report a patient with chronic urticaria whose disease was paradoxically exacerbated by H1-antihistamines and montelukast, and controlled by immunosuppressive drugs as ciclosporin and azathioprine. Urticaria exacerbations were caused by different molecules including either piperidine (fexofenadine, desloratadine, ebastine, rupatadine) or piperazine (hydroxyzine, cetirizine) derivatives as well as by montelukast suggesting that an IgE-mediated mechanism was not involved. A possible explanation of the observed urticaria exacerbation is that H1-antihistamines and montelukast may shift the H1 histamine receptor and the leukotriene receptor to the active conformation instead of the inactive state. The beneficial effects of ciclosporin and azathioprine confirm that immunosuppressive drugs have an important role in the treatment of refractory chronic urticaria and back the hypothesis that an autoimmune/autoreactive mechanism often underlies the disease.

Topics: Acetates; Adult; Azathioprine; Chronic Disease; Cyclopropanes; Cyclosporine; Histamine H1 Antagonists; Humans; Male; Quinolines; Sulfides; Urticaria

Topics: Acetates; Anti-Asthmatic Agents; Chronic Disease; Cyclopropanes; Female; Humans; Immunologic Tests; Middle Aged; Quinolines; Sulfides; Urticaria

Chronic graft versus host disease (GvHD) is a major complication after allogeneic stem cell transplantation (SCT), which is usually progression from acute GvHD. Chronic GvHD is the main cause of severe morbidity and mortality in long-term survivors after SCT. The cysteinyl leukotrienes (cysLTs) and eosinophils play an important role in the pathogenesis of GvHD, which is the rationale for the combined use of montelukast (Mk) in the treatment of this illness.. Mk was administrated to 19 eligible patients with refractory chronic GvHD, in addition to their standard immunosuppressive regimens. Mk was given orally (10 mg once daily) for a mean period of 10 months (range, 2-21 months). Organ-specific response was determined by the new scoring criteria established by the National Institutes of Health consensus project.. Based on organ involvements endpoints, overall response to the combined therapy with Mk was observed in 15 of 19 (79%) patients. Significant improvement of skin liver and gastrointestinal was observed in 53%, 62%, and 46%, respectively. Generally, Mk was notably beneficial in milder stages of GvHD, which lead to earlier withdrawal of other immunosuppressive agents. Side effects of Mk administration were not documented, nor were cases of relapse of the basic disease.. Our preliminary prospective investigation supports the potential efficacy of Mk as a safe and toxicity-sparing supplement to standard therapy for patients with chronic GvHD. Future clinical studies are necessary to establish the optimal dose of Mk and its role in the symptomatic and prophylactic treatment of acute and chronic GvHD.

Topics: Acetates; Administration, Oral; Adolescent; Adult; Chronic Disease; Cyclopropanes; Female; Graft vs Host Disease; Humans; Leukotriene Antagonists; Male; Middle Aged; Pilot Projects; Quinolines; Retrospective Studies; Sulfides; Treatment Outcome

Topics: Acetates; Administration, Oral; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Cyclopropanes; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Quinolines; Sulfides; Treatment Outcome; Urticaria

Use of leukotriene receptor antagonists improves disease control in children and adults with asthma. However, the relationship between cysteinyl leukotriene levels and indices of daily asthma control has not been studied directly.. We sought to assess the relationship between daily variability in urinary leukotriene E(4) (LTE(4)) levels and daily lung function in children primarily taking inhaled corticosteroids (ICSs) and long-acting beta-agonists (LABAs).. Fifty children primarily with moderate-to-severe asthma were followed with measurements of urinary LTE(4), monitoring of FEV(1), and albuterol use.. Increasing urinary LTE(4) levels were associated with significant (P = .006) decreases in percent predicted FEV(1) (ppFEV(1)) averaging 4.7% per interquartile range increase in LTE(4) and accompanied by increased albuterol use (P = .03). Children with lower FEV(1)/forced vital capacity ratios demonstrated larger LTE(4)-related FEV(1) decreases (6.4%) compared to those with higher ratios (4.2%, P = .009). This association was blunted in children taking montelukast (1.4% ppFEV(1) decrease) compared with that in children not taking this medication (5.4% ppFEV(1) decrease, P = .05). Children with lower lung function ratios demonstrated greater blunting of the LTE(4) effect with montelukast (0.9% ppFEV(1) decrease) compared to those with higher ratios (3.6% ppFEV(1), P = .0002).. Daily variability in LTE(4) levels is associated with clinically significant decreases in pulmonary function. In children who demonstrate a response associated with an increase in urinary LTE(4) levels, leukotriene receptor antagonists protect against daily FEV(1) decreases. This protection might be greatest in those with persistent airway obstruction despite use of ICS and LABA therapy.. Therapies designed to block cysteinyl leukotriene production or function might benefit children receiving ICS and LABA therapy who continue to experience persistent disease.

Topics: Acetates; Adolescent; Airway Obstruction; Albuterol; Asthma; Child; Chronic Disease; Cyclopropanes; Disease Susceptibility; Female; Forced Expiratory Volume; Humans; Leukotriene E4; Male; Quinolines; Severity of Illness Index; Sulfides

Leukotriene receptor antagonists have been demonstrated in several studies to possess bronchodilating and anti-inflammatory properties in asthma. However, there are few experimental studies performed to compare the effects of anti-leukotrienes and glucocorticoids, most used anti-inflammatory agents in asthma. In the present study, we evaluated the effects of treatment with dexamethasone or montelukast on eosinophil and mononuclear cell recruitment in an experimental model of allergen-induced chronic airway inflammation in guinea-pigs (GP).. GP were submitted to increasing concentrations of aerosols of ovalbumin (OVA) twice a week for 4 weeks. After 2 weeks, animals were treated daily with dexamethasone, montelukast or saline solution. After this period, GP were anaesthetized, tracheostomized, mechanically ventilated and challenged with OVA aerosol.. Maximal changes of respiratory system resistance and elastance induced by OVA challenge were attenuated by dexamethasone (P<0.001), but not by montelukast treatment. Neither dexamethasone nor montelukast significantly influenced bronchial oedema formation. Dexamethasone but not montelukast induced a decrease in mononuclear cells in airways (P<0.001). Eosinophil infiltration in the bronchial wall was reduced by both dexamethasone and montelukast (P<0.005). Only dexamethasone treatment reduced the levels of exhaled nitric oxide (P<0.025).. Although leukotriene receptor antagonist treatment reduces eosinophil accumulation induced by multiple antigen challenges, glucocorticoid treatment attenuates both eosinophil and mononuclear cell infiltration.

Topics: Acetates; Animals; Asthma; Chronic Disease; Cyclopropanes; Dexamethasone; Eosinophils; Glucocorticoids; Guinea Pigs; Leukocyte Count; Leukotriene Antagonists; Lung; Male; Quinolines; Sulfides

Topics: Acetates; Aminocaproic Acid; Child; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Humans; Male; Quinolines; Ranitidine; Sulfides; Urticaria

Asthma is a chronic disease, the two main components of which are inflammation and bronchoconstriction. Fluticasone propionate (FP) and salmeterol, a strategy that treats both main components of asthma, has been recently compared with FP plus montelukast in a randomised clinical trial. The present study reports economic evaluation of these two strategies.. To determine the relative cost effectiveness when persistent asthma is treated with FP/salmeterol 100/50 microg twice daily administered via a single Diskus inhaler device versus treatment with FP 100 microg twice daily via a Diskus inhaler plus oral montelukast 10mg once daily.. A cost-effectiveness analysis was performed by applying cost unit data to resource utilisation data collected prospectively during a US randomised, double-blind, 12-week trial of FP/salmeterol (n = 222) versus FP + montelukast (n = 225). Patients were > or =15 years of age and were symptomatic despite inhaled corticosteroid (ICS) therapy.. Efficacy measurements in this analysis included improvement in forced expiratory volume in 1 second (FEV(1)) and symptom-free days. Direct costs included those related to study drugs, emergency room department visits, unscheduled physician visits, treatment of drug-related adverse events (oral candidiasis), and rescue medication (salbutamol [albuterol]). The study assumed a US third-party payer's perspective with costs in 2001 US dollars.. Treatment with FP/salmeterol resulted in a significantly higher proportion (p < 0.001) of patients who achieved a > or =12% increase in FEV(1) than treatment with FP + montelukast (54% [95% CI 47%, 61%] vs 32% [95% CI 26%, 38%]). Lower daily costs and greater efficacy of FP/salmeterol resulted in a cost-effectiveness ratio of US6.77 dollars (95% CI US5.99 dollars, US7.66 dollars) per successfully treated patient in the FP/salmeterol group compared with US14.59 dollars (95% CI US12.12 dollars, US17.77 dollars) for FP + montelukast. In addition, FP/salmeterol achieved similar efficacy in terms of symptom-free days compared with FP + montelukast (31% [95% CI 26%, 35%] vs 27% [95% CI 23%, 32%]), but at a significantly lower daily per-patient cost (US3.64 dollars [95% CI US3.60, US3.68 dollars] vs US4.64 dollars [95% CI US4.56 dollars, US4.73 dollars]). Sensitivity analyses demonstrated the stability of the results over a range of assumptions.. From a US third-party payer's perspective, these findings suggest that treating the two main components of asthma (inflammation and bronchoconstriction) with FP/salmeterol may not only be a more cost-effective strategy but may actually lead to cost savings compared with the addition of montelukast to low-dose FP in patients with persistent asthma. The results were found to be robust over a range of assumptions.

Topics: Acetates; Administration, Inhalation; Administration, Oral; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cost-Benefit Analysis; Cyclopropanes; Drug Therapy, Combination; Female; Fluticasone; Humans; Male; Nebulizers and Vaporizers; Prospective Studies; Quinolines; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Sulfides

Twenty-two children (13 boys and 9 girls) with chronic cough were treated with the leukotriene receptor antagonist montelukast (Singulair tbl. 5 mg) administered once daily for four weeks. In 14 children (68%), the cough ceased during the third week of treatment. Children responding to montelukast were found to have higher blood levels of eosinophil cationic protein (S-ECP) in the pretreatment blood sample than children with no response (responders 14.88+/-2.651 microg/l versus nonresponders 6.62+/-0.948 microg/l; p<0.01). Blood S-ECP levels remained higher also in the post-treatment blood sample in responders (10.55+/-1.631 microg/l) compared to nonresponders (6.13+/-0.937 microg/l; p<0.05). The difference is statistically significant. There were also differences in absolute eosinophil blood count and IgE blood levels between the two groups in the pretreatment blood sample. Using 24-hour pH-metry, two children not responding to therapy were subsequently diagnosed to have gastroesophageal reflux. Judging from the results, one might deduct that patients with chronic cough who have increased levels of serum ECP and absolute eosinophil blood counts are likely to benefit from treatment with montelukast.

Topics: Acetates; Biomarkers; Chronic Disease; Cough; Cyclopropanes; Dose-Response Relationship, Drug; Drug Administration Schedule; Eosinophil Cationic Protein; Eosinophils; Female; Follow-Up Studies; Humans; Immunoglobulin E; Leukotriene Antagonists; Male; Probability; Prospective Studies; Quinolines; Risk Assessment; Severity of Illness Index; Sulfides; Treatment Outcome

Topics: Acetates; Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Asthma; Bronchodilator Agents; Budesonide; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Humans; Leukotriene Antagonists; Middle Aged; Quinolines; Sulfides

Topics: Acetates; Adrenergic beta-Agonists; Albuterol; Asthma; Bronchodilator Agents; Chronic Disease; Cyclopropanes; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Leukotriene Antagonists; Quinolines; Salmeterol Xinafoate; Sulfides

Topics: Acetates; Adrenergic beta-Agonists; Albuterol; Androstadienes; Asthma; Bronchodilator Agents; Chronic Disease; Cyclopropanes; Delayed-Action Preparations; Drug Therapy, Combination; Ethanolamines; Fluticasone; Formoterol Fumarate; Humans; Leukotriene Antagonists; Quinolines; Salmeterol Xinafoate; Sulfides

Airway inflammation and remodeling in chronic asthma are characterized by airway eosinophilia, hyperplasia of goblet cells and smooth muscle, and subepithelial fibrosis. We examined the role of leukotrienes in a mouse model of allergen-induced chronic lung inflammation and fibrosis. BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on Days 0 and 14, received intranasal OVA periodically Days 14-75. The OVA-treated mice developed an extensive eosinophil and mononuclear cell inflammatory response, goblet cell hyperplasia, and mucus occlusion of the airways. A striking feature of this inflammatory response was the widespread deposition of collagen beneath the airway epithelial cell layer and also in the lung interstitium in the sites of leukocytic infiltration that was not observed in the saline-treated controls. The cysteinyl leukotriene(1) (CysLT(1)) receptor antagonist montelukast significantly reduced the airway eosinophil infiltration, mucus plugging, smooth muscle hyperplasia, and subepithelial fibrosis in the OVA-sensitized/challenged mice. The presence of Charcot-Leyden-like crystals in airway macrophages and the increased interleukin (IL)-4 and IL-13 mRNA expression in lung tissue and protein in BAL fluid seen in OVA-treated mice were also inhibited by CysLT(1) receptor blockade. These data suggest an important role for cysteinyl leukotrienes in the pathogenesis of chronic allergic airway inflammation with fibrosis.

Topics: Acetates; Acute Disease; Allergens; Analysis of Variance; Animals; Asthma; Bronchoalveolar Lavage Fluid; Chronic Disease; Cyclopropanes; Disease Models, Animal; Drug Evaluation, Preclinical; Eosinophils; Fibrosis; Glycoproteins; Goblet Cells; Hyperplasia; Inflammation; Leukotriene Antagonists; Leukotrienes; Lysophospholipase; Macrophages, Alveolar; Mice; Ovalbumin; Quinolines; Respiratory Mechanics; Sulfides

Peak expiratory flow (PEF) is an important measure of airway functin in asthma. PEF variability (PEFvar) assessment is described in asthma treatment guidelines as another means of evaluating patient status and response to therapy.. The goal of this study was to determine the clinical effect of oral montelukast, a leukotriene receptor antagonist, on PEFvar in asthmatic patients and to assess the relationship of PEFvar with other clinical measures.. This was a retrospective analysis of data from a multicenter, randomized, double-blind, placebo-controlled, parallel-group study, details of which have been published previously. Eligible patients had chronic stable asthma, had a forced expiratory volume in 1 second (FEV1) that was 50% to 85% of the predicted value, used inhaled beta-agonists, had at least 15% improvement in absolute FEV1 after inhaled beta-agonist administration, and showed a minimal predefined level of daytime asthma symptoms. Treatment consisted of a 2-week, single-blind, placebo run-in period followed by a 12-week, double-blind treatment period (montelukast 10 mg or matching placebo once daily at bedtime).. Six hundred eighty-one patients (age range, 15-79 years) were randomized to treatment at 50 centers. Baseline PEFvar was 11.44% +/- 6.55% and 10.62% +/- 6.48% in the montelukast and placebo groups, respectively. PEFvar decreased 20.1% and 7.5% from baseline in the montelukast and placebo groups, respectively. The between-group difference was significant (P < 0.001). PEFvar had low correlation with other clinical measures.. Over 12 weeks of treatment, montelukast significantly reduced PEFvar compared with placebo, indicating improved asthma control. The relative reduction in PEFvar was similar in patients with different degrees of variability at baseline. PEFvar did not correlate highly with other outcome variables and may measure different aspects of the disease.

Topics: Acetates; Adolescent; Adult; Aged; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Middle Aged; Multicenter Studies as Topic; Peak Expiratory Flow Rate; Quinolines; Randomized Controlled Trials as Topic; Respiratory Function Tests; Retrospective Studies; Sulfides

Topics: Acetates; Adult; Aged; Chronic Disease; Cyclopropanes; Female; Follow-Up Studies; Humans; Indoles; Leukotriene Antagonists; Leukotrienes; Male; Middle Aged; Phenylcarbamates; Quinolines; Remission Induction; Severity of Illness Index; Sulfides; Sulfonamides; Tosyl Compounds; Treatment Outcome; Urticaria

Topics: Acetates; Albuterol; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Chronic Disease; Cyclopropanes; Humans; Peak Expiratory Flow Rate; Quinolines; Salmeterol Xinafoate; Sulfides

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; Sulfides

Although there is evidence from randomised controlled trials that leukotriene receptor antagonists are efficacious in chronic rhinosinusitis there are still little data on their use in everyday real life clinical practice. We report on a pragmatic case series of 32 patients referred from primary care with uncontrolled chronic rhinosinusitis (allergic or non-allergic) who have been treated with montelukast in our joint medical/surgical rhinology clinic. Patients' symptoms were scored according to "facial pain", "headache", "nasal blockage", "nasal discharge", "sense of smell" and "daily activity", and measurements of peak inspiratory nasal flow were made, before and after the introduction of montelukast 10 mg/day. There were significant (p < 0.05) improvements in subjective scoring for headache, nasal discharge & blockage, sense of smell and daily activity but not for facial pain, when montelukast was added along with other alterations in chronic rhinosinusitis medication (all receiving intra-nasal corticosteroids). Subgroup analysis of 10 patients, were the addition of montelukast was the only change to medical therapy, showed significant (p < 0.05) improvements in headache, nasal discharge and blockage and their daily activity. There was no significant improvements in nasal peak inspiratory flow or spirometry. In conclusion, montelukast may be a useful therapeutic option in addition to standard therapy (i.e. intra-nasal corticosteroids or anti-histamines) when treating patients with chronic rhinosinusitis in a real life clinical setting.

Topics: Acetates; Chronic Disease; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; Rhinitis; Sinusitis; Spirometry; Sulfides

Montelukast (Singulair), an antiasthma drug belonging to the leukotriene antagonist family, has two indications: as adjunctive treatment for mild-to-moderate chronic asthma when regular inhaled steroid therapy and short-acting inhaled beta2 stimulants "on demand" are inadequate; and in prevention of effort-induced asthma. The clinical file on montelukast contains no methodologically acceptable comparisons with reference treatments. Several placebo-controlled trials have shown the efficacy of montelukast, with improvement in clinical scores and respiratory function tests in those with chronic asthma and prevention of effort-induced asthma. For chronic asthma, montelukast has not been compared with oral or inhaled long-acting beta2 stimulants or with sustained-release theophylline in patients inadequately controlled by steroid therapy. For effort-induced asthma, only two trials have compared montelukast with salmeterol. On the basis of preliminary results, the authors of both studies concluded that montelukast was superior. Clinical trials showed no clear difference in the frequency of side effects in patients taking montelukast and patients taking placebo. Montelukast, however, might be associated with Churg-Strauss syndrome in rare cases. Montelukast is expensive.

Topics: Acetates; Administration, Inhalation; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Drug Costs; Humans; Quinolines; Steroids; Sulfides

Topics: Acetates; Adult; Chronic Disease; Cyclopropanes; Drug Therapy, Combination; Female; Humans; Leukotriene Antagonists; Prednisone; Quinolines; Sulfides; Urticaria

Topics: Acetates; Administration, Inhalation; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Beclomethasone; Chronic Disease; Cyclopropanes; Double-Blind Method; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Middle Aged; Quinolines; Randomized Controlled Trials as Topic; Reproducibility of Results; Sulfides; Treatment Outcome

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Chronic Disease; Cyclopropanes; Humans; Indoles; Leukotriene Antagonists; Phenylcarbamates; Quinolines; Sulfides; Sulfonamides; Tosyl Compounds