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1.
A randomized, open labeled, comparative study to assess the efficacy and safety of controller medications as add on to inhaled corticosteroid and long-acting β2 agonist in the treatment of moderate-to-severe persistent asthma.
Patel, YA, Patel, P, Bavadia, H, Dave, J, Tripathi, CB
Journal of postgraduate medicine. 2010;(4):270-4
Abstract
BACKGROUND The goal of asthma therapy is to achieve clinical control and near normal lung functions. Many patients with persistent asthma fail to achieve this goal with a single controller medication add on to a inhaled corticosteroid. We have checked whether another controller medication add on to inhaled corticosteroid and long-acting β2 agonist helps in achieving the asthma goal or not. OBJECTIVES To identify the effect of controller medication add on to inhaled corticosteroid and the long-acting β2 agonist on the clinical symptom, lung function, and compliance in patients with asthma. MATERIALS AND METHODS We conducted a randomized, open-labeled, comparative trial in 50 participants with moderate-to-severe persistent asthma. The study duration was of 10 weeks. During the first two weeks of the run-in period all the participants received a dry powder inhaler drug delivery of budesonide (400 mcg/day) and formoterol (12 mcg/day) combination. At the end of the run-in period the participants were randomly allocated into three groups: group A (n = 16) received oral montelukast (10 mg/day); group B (n = 17) received oral doxophylline (400 mg/day), and group C (n = 17) received inhaled budesonide (400 mcg) as add on to the above-mentioned drugs of the run-in period. The primary outcome was improvement in forced expiratory volume at 1 second (FEV1 ). RESULTS All the participants of the three groups had significant improvement in FEV1 (P < 0.001) and asthma symptoms at the end of 10 weeks. The mean increase in FEV1 (% of predicted) from the baseline, in groups A, B, and C was: 24.6; 21.33, and 19.86%, respectively. CONCLUSIONS All add on controller medications helped, with a significant improvement of lung functions and asthma symptoms.
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2.
Montelukast as add-on therapy with inhaled corticosteroids alone or inhaled corticosteroids and long-acting beta-2-agonists in the management of patients diagnosed with asthma and concurrent allergic rhinitis (the RADAR trial).
Keith, PK, Koch, C, Djandji, M, Bouchard, J, Psaradellis, E, Sampalis, JS, Schellenberg, RR, McIvor, RA
Canadian respiratory journal. 2009;(Suppl A):17A-31A
Abstract
OBJECTIVE To evaluate the effectiveness of montelukast as add-on therapy for patients diagnosed with asthma and concurrent allergic rhinitis who remain uncontrolled while receiving inhaled corticosteroid (ICS) monotherapy or ICS/long-acting beta-2-agonist (LABA) therapy in a community practice setting. DESIGN An eight-week, multicentre, open-label, observational study. Patients were 15 years of age or older and, while treated with an ICS or ICS/LABA, had allergic rhinitis and uncontrolled asthma symptoms by at least two criteria as per the Canadian Asthma Consensus Guidelines. The primary outcome measure was the percentage of patients with controlled asthma symptoms after eight weeks of treatment with montelukast 10 mg once daily added to ICS or ICS/LABA therapy. RESULTS In total, 1004 patients participated in the survey phase of the study. Of these patients, 319 continued in the treatment phase and 301 (94.4%) completed the eight-week assessment. At baseline, all patients had uncontrolled asthma symptoms based on the Canadian Asthma Consensus Guidelines; at the eight-week assessment, 229 patients (76.1%) achieved asthma control. According to the Asthma Control Questionnaire (as determined by scores of 0.75 or less), 164 patients (54.7%) achieved well-controlled asthma at week 8. The mean (+/- SD) Asthma Control Questionnaire score decreased from 2.03+/-0.80 to 0.92+/-0.80 (P<0.001) for all patients, representing a clinically significant improvement. A statistically and clinically significant reduction in the overall Mini Rhinitis Quality of Life Questionnaire score was achieved with a decrease from 2.57+/-1.20 to 1.12+/-1.00 (-1.45+/-1.35; P<0.001). Patient and physician satisfaction rates with montelukast add-on therapy were also significantly increased when compared with baseline treatment. CONCLUSION Montelukast add-on therapy is effective for managing asthma and allergic rhinitis symptoms in patients who were previously uncontrolled with ICS or ICS/LABA treatment.
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3.
Pretreatment with albuterol versus montelukast for exercise-induced bronchospasm in children.
Raissy, HH, Harkins, M, Kelly, F, Kelly, HW
Pharmacotherapy. 2008;(3):287-94
Abstract
STUDY OBJECTIVES To compare pretreatment with albuterol versus montelukast added to the current asthma regimen for protection against exercise-induced bronchospasm in children with mild-to-moderate asthma, and to determine whether cysteinyl leukotriene (Cys-LT) concentrations measured in the exhaled breath condensate correlated with response to montelukast. DESIGN Prospective, randomized, double-blind, double-dummy, crossover study. SETTING Asthma clinic at a university-affiliated medical center. PATIENTS Eleven children aged 7-17 years with physician-diagnosed mild-to-moderate asthma for at least 6 months and with self-reported exercise-induced bronchospasm (defined as > or = 15% decrease in forced expiratory volume in 1 sec [FEV(1)] at screening and baseline visit). INTERVENTION Patients were randomly assigned to receive 3-7 days of oral montelukast 5-10 mg/day or 2 puffs of an albuterol metered-dose inhaler just before an exercise challenge and then were crossed over to the alternate therapy for the last visit. MEASUREMENTS AND MAIN RESULTS Serial spirometry was performed before and at 0, 5, 10, 15, 30, 45, and 60 minutes after the exercise challenge at each visit. Measurement of exhaled breath condensate was performed at the screening visit and study visits 1 and 2. The primary outcome was the maximum change in FEV(1) after exercise. Secondary outcomes were the area under the curve for FEV(1) (expressed as percentage decrease from baseline) during the first 60 minutes (AUC(0-60)) after exercise and the proportion of patients in whom exercise-induced bronchospasm was prevented (defined as < 15% decrease in FEV(1) after exercise challenge). The mean +/- SD maximum decrease in FEV(1) was 27.5 +/- 7.9% at baseline. Patients receiving montelukast had an 18.3 +/- 13.7% decrease in FEV(1) compared with 0.7 +/- 1.6% in patients receiving albuterol (p=0.002, paired t test). Exercise-induced bronchospasm was prevented in 100% of the patients receiving albuterol compared with 55% receiving montelukast (p<0.05, McNemar's test). The AUC(0-60) was significantly smaller with albuterol compared with montelukast (p<0.001, Wilcoxon signed rank test). No correlations were found between Cys-LT concentration and the severity of exercise-induced bronchospasm or the response to montelukast. CONCLUSION Pretreatment with albuterol is more effective than montelukast for prevention of exercise-induced bronchospasm in children with asthma.
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4.
[Comparison of different vehicles for nebulized salbutamol in treatment of bronchial asthma exacerbations: a Meta-analysis].
Lu, XY, Zhou, JY
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences. 2006;(3):336-41
Abstract
OBJECTIVE To assess the efficacy of two vehicles for nebulized salbutamol in treatment of asthma exacerbations with Meta-analysis. METHODS All relevant randomized controlled clinical trials (RCT) with isotonic magnesium sulphate and saline as vehicles for inhaled salbutamol in treatment of asthma exacerbations were searched. A Meta-analysis was performed to evaluate the results of the two therapies. RESULT Five relevant RCTs from literature were collected and total 219 cases were included for analysis. The meta-analysis indicated that the significant improvements were obtained from isotonic magnesium sulphate as a vehicle for nebulized salbutamol, in comparison with saline [pooled standardized mean difference (SMD)=0.55(95% CI 0.28 - 0.83), P <0.001]. By further subgroup analysis, this change was properly significant in the subgroup of severe patients with their baseline FEV1% <30% [FEV1 weighted mean difference (WMD)=0.72 L(95% CI 0.30 L - 1.14 L), P <0.01]. The pooled results of vital signs between two vehicles did not demonstrate statistical significance. Overall, the risk of admission to hospital was not statistically reduced in patients using magnesium sulphate, who presented to the emergency department with an asthma exacerbation [pooled RR=0.64(95% CI 0.38 - 1.08), P >0.05]. CONCLUSION Compared with saline,the use of isotonic magnesium sulfate as an adjuvant to nebulize salbutamol is a beneficial therapy with improving spirometric airway function in the severe asthma exacerbation.
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5.
Antagonistic growth regulation of cell lines derived from human lung adenocarcinomas of Clara cell and aveolar type II cell lineage: Implications for chemoprevention.
Adissu, HA, Schuller, HM
International journal of oncology. 2004;(6):1467-72
Abstract
Lung cancer continues to be the leading cause of cancer death in industrialized countries and there is an urgent need for the development of preventive treatments that inhibit the progression of initiated cells into overt lung cancer in smokers who quit. Murine pulmonary adenocarcinoma models are widely used to test prospective cancer preventive agents. These tumors are of alveolar type II cell lineage, express growth-regulating signal transduction pathways that are stimulated by epidermal growth factor and protein kinase C while being inhibited by agents that increase intracellular cyclic AMP (cAMP). By contrast, pulmonary adenocarcinomas induced in hamsters are derived from bronchial and bronchiolar Clara cells, are under beta-adrenergic receptor control and their development is promoted by agents that increase intracellular cAMP. Adenocarcinomas of either cell lineage develop in humans, raising the possibility that agents with strong chemopreventive activity in murine lung cancer models due to stimulation of cAMP may selectively promote human pulmonary adenocarcinomas derived from Clara cells. We therefore compared the effects of the beta-adrenergic agonist isoproterenol and the activator of cAMP forskolin under controlled in vitro conditions on the human pulmonary adenocarcinoma cell line NCI-H322 which expresses a Clara cell phenotype versus the human pulmonary adenocarcinoma cell line A549 which expresses features of alveolar type II cells. Our data show that isoproterenol significantly stimulated cAMP, ERK1/2 activity and DNA synthesis in NCI-H322 cells and that this response involved transactivation of the EGF receptor. By contrast, we found that isoproterenol had no effect on A549 cells whereas forskolin significantly inhibited DNA synthesis and ERK1/2 activity. Our findings are consistent with the interpretation that human pulmonary adenocarcinomas of Clara cell lineage are highly sensitive to the cancer promoting effects of beta-adrenergic agonists and other agents that stimulate cAMP whereas human cancers of the same histological family but derived from alveolar type II cells are resistant to beta-adrenergic agonists and respond with a reduction in cell growth to stimulation of cAMP. Our findings suggest that some widely advertised cancer preventive agents such as green tea, retinoids and beta-carotenes are unsafe to be used by smokers or by ex-smokers due to their tumor promoting effects via stimulation of cAMP on initiated cells of Clara cell lineage.
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Effects of dopexamine in comparison with fenoterol on carbohydrate, fat and protein metabolism in healthy volunteers.
Geisser, W, Vogt, J, Wachter, U, Hofbauer, H, Georgieff, M, Ensinger, H
Intensive care medicine. 2004;(4):702-8
Abstract
OBJECTIVE In critically ill patients adrenergic agonists are used to treat haemodynamic disorders. Their metabolic actions should be considered in controlling metabolic homeostasis. Dopexamine has assumed effects on carbohydrate, fat and protein metabolism. The aim of this study was to define its metabolic actions and compare these with those of fenoterol by using a stable isotope dilution technique. DESIGN Prospective, randomized experimental study. SETTING Experimental section of a university anaesthesiology department. PARTICIPANTS Twenty-seven healthy male volunteers in three groups with nine participants each. INTERVENTIONS Participants received a 4-h infusion of dopexamine (2.25 microg/kg per min), fenoterol (at least 0.025 microg/kg per min) or saline. MEASUREMENTS AND RESULTS Before and every 80 min during drug infusion, we measured endogenous glucose production and the plasma appearance rates for leucine and urea. In addition, we measured plasma concentrations of glucose, lactate, free fatty acids (FFAs), noradrenaline, adrenaline, insulin, glucagon and potassium. Endogenous glucose production did not differ among the groups. Glucose plasma concentration and glucose clearance remained constant during the dopexamine infusion. Fenoterol increased glucose plasma concentration and decreased glucose clearance. Lactate, FFAs, insulin and noradrenaline plasma concentrations were increased and the rate of leucine appearance was decreased by both drugs. The rate of urea appearance did not differ from the control group. CONCLUSIONS Dopexamine has no or only weak effects on carbohydrate metabolism, its effects on fat and protein metabolism are comparable to those of fenoterol. This metabolic profile may be advantageous in increasing cardiac output in patients with impaired glucose tolerance.
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7.
Comparative effects of desloratadine versus montelukast on asthma symptoms and use of beta 2-agonists in patients with seasonal allergic rhinitis and asthma.
Baena-Cagnani, CE, Berger, WE, DuBuske, LM, Gurné, SE, Stryszak, P, Lorber, R, Danzig, M
International archives of allergy and immunology. 2003;(4):307-13
Abstract
BACKGROUND Asthma and seasonal allergic rhinitis (SAR) are recognized as manifestations of a single airway disease. Desloratadine has demonstrated efficacy in treating SAR symptoms, including nasal obstruction. METHODS Safety and efficacy of desloratadine and montelukast each were assessed in a double-blind, placebo-controlled trial of patients with SAR and symptoms of asthma, who were assigned randomly to once-daily treatment with desloratadine 5 mg, montelukast 10 mg, or placebo for 4 weeks. Change from baseline of AM/PM reflective total asthma symptom severity scores (TASS), FEV(1), individual asthma symptom scores, and beta(2)-agonist usage were assessed. RESULTS Desloratadine and montelukast each were associated with statistically significant reductions from baseline in the mean TASS averaged over the 4-week period (p < or =0.022 vs. placebo). Individual asthma symptom scores also improved significantly for both therapies (p < or = 0.05). Patients treated with desloratadine or montelukast demonstrated improvement from baseline in FEV(1) versus placebo; significant improvement was seen in a subset of patients with baseline FEV(1) <80% of predicted normal (both p < 0.05). Both active therapies significantly reduced beta(2)-agonist use (both p < 0.01). Improvements for both therapies were comparable for all efficacy parameters; they were tolerated well with adverse event profiles similar to placebo. CONCLUSIONS Asthma symptoms and beta(2)-agonist were improved significantly in patients with concomitant SAR and asthma treated with desloratadine 5 mg as well as montelukast 10 mg once daily. Both therapies significantly improved FEV(1) in a subset of patients with FEV(1) <80% of predicted normal at entry. Improvements in asthma symptoms were comparable for both active treatment groups.
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8.
Levalbuterol is as effective as racemic albuterol in lowering serum potassium.
Pancu, D, LaFlamme, M, Evans, E, Reed, J
The Journal of emergency medicine. 2003;(1):13-6
Abstract
Albuterol is an effective treatment for hyperkalemia through beta-adrenergic induction of potassium (K+) uptake. Levalbuterol, the R-enantiomer of racemic albuterol, is used for the treatment of asthma and 0.63 mg of levalbuterol has the same therapeutic efficacy as 2.5 mg of albuterol but with a decreased adverse effects profile. We hypothesized that levalbuterol can reduce serum K+ levels similarly to albuterol when used in equipotent doses. In a randomized, double blind, placebo-controlled prospective study, we compared the K+-lowering effects of nebulized saline and equipotent bronchodilatory doses of albuterol (10 mg) and levalbuterol (2.5 mg) in healthy adult volunteers. Nine subjects entered each of the three study groups. Serum K+ was measured at baseline, at 30 min (immediately after treatment), at 60 min, and at 90 min. All adverse effects were recorded. The three groups had similar baseline K+ values. Immediately after nebulization, only levalbuterol showed a significant decrease in potassium level (p = 0.024). At 30 and 60 min after treatment, both albuterol and levalbuterol groups had significantly lower K+ values compared to placebo. No significant difference occurred between the albuterol and levalbuterol groups. Levalbuterol caused fewer reported adverse effects compared to albuterol.
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9.
[Clinical and biochemical aspects of flixotide administration in patients with moderate bronchial asthma].
Medvedeva, IV, Lapik, SV, Gur'eva, SA, Savina, IA
Terapevticheskii arkhiv. 2002;(3):21-5
Abstract
AIM: To compare clinical, device and biochemical aspects of monotherapy with flixotide vs combination of flixotide with serevent in patients with moderate bronchial asthma (MBA). MATERIAL AND METHODS 18 patients with MBA received flixotide and 18 MBA patients flixotide plus serevent for two weeks of lead-in and eight weeks of basic treatment. A special study was made of neutrophils which were examined for activity of LPO-antioxidants and phospholipid spectrum of membranes. RESULTS There were similar changes in function of the system LPO-antioxidants and lipid structure in neutrophilic membranes of moderate BA patients of both the groups. CONCLUSION Clinicobiochemical efficacy of mean doses of a new topic inhalation glucocorticoid flixotide alone or in combination with prolonged beta 2-adrenostimulator serevent is demonstrated. There were positive trends in metabolic processes in neurophilic membrane. Use of flixotide in combination with serevent is clinically preferable.
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10.
Low-dose levalbuterol in children with asthma: safety and efficacy in comparison with placebo and racemic albuterol.
Milgrom, H, Skoner, DP, Bensch, G, Kim, KT, Claus, R, Baumgartner, RA, ,
The Journal of allergy and clinical immunology. 2001;(6):938-45
Abstract
BACKGROUND Racemic albuterol (RAC) is an equal mixture of (R)-albuterol and (S)-albuterol. Only the (R)-isomer, levalbuterol (LEV), is therapeutically active. Lower doses of LEV, devoid of (S)-albuterol, have demonstrated efficacy comparable to that of higher doses of the (R)-isomer administered as a component of RAC. OBJECTIVE The purpose of this study was to determine whether LEV results in improved safety and efficacy in children. METHODS Asthmatic children aged 4 to 11 years (n = 338; FEV(1), 40% to 85% of predicted) participated in this multicenter, randomized, double-blinded study and received 21 days of 3-times-a-day treatment with nebulized LEV (0.31 or 0.63 mg), RAC (1.25 or 2.5 mg), or placebo. The primary endpoint was FEV(1) (peak percent change). Adverse events, clinical laboratory test results, vital signs, and electrocardiograms were evaluated for safety. RESULTS All active treatments significantly improved the primary endpoint in comparison with placebo (P < .001). Significant differences in FEV(1) were noted immediately after nebulization (median change, 2.0%, 19.0%, 18.1%, 12.4%, and 15.6% for placebo, LEV 0.31 and 0.63, RAC 1.25 and 2.5 mg, respectively; P < .05 vs placebo; P < .05 for LEV 0.31 and 0.63 vs RAC 1.25 mg). LEV 0.31 mg was the only treatment not different from placebo for changes in ventricular heart rate, QT(c) interval, and glucose (P > .05). All active treatments decreased serum potassium (range, -0.3 to -0.6; P < .002 vs placebo), and RAC 2.5 mg caused the greatest change (P < .005 vs other actives). In a patient subset with severe asthma, a dose-response relationship was observed for levalbuterol, indicating that higher doses were more effective. CONCLUSION LEV was clinically comparable to 4- to 8-fold higher doses of RAC, and it demonstrated a more favorable safety profile. LEV 0.31 mg should be used as the starting dose in 4-11 year old children with mild to moderate persistent asthma. Patients with severe disease might benefit from higher doses.