Effect of formoterol on clinical parameters and lung functions in patients with bronchial asthma: a randomised controlled trial.
(33/2342)
AIMS: To determine the role of formoterol in the treatment of children with bronchial asthma who are symptomatic despite regular use of inhaled corticosteroids. METHODS: A randomised, double blind, parallel group, placebo controlled study to investigate the effects of inhaled formoterol (12 microg twice a day) in 32 children with moderate to severe bronchial asthma. The study consisted of two week run in periods and six week treatment periods, during both of which the patients continued their regular anti-inflammatory drugs. The efficacy parameters were symptom scores, bronchodilator use, daily peak expiratory flow rates (PEFR), methacholine hyper-reactivity, forced expiratory volume in one second (FEV1), lung volumes, and airway conductance. RESULTS: Formoterol treatment for six weeks decreased symptom scores, PEFR variability, and the number of rescue salbutamol doses, and increased morning and evening PEFR significantly. No adverse reactions were seen. CONCLUSION: These findings suggest that inhaled formoterol is effective in controlling chronic asthma symptoms in children who are symptomatic despite regular use of inhaled corticosteroids. (+info)
Pharmacokinetics of theophylline metabolites in 8 Chinese patients.
(34/2342)
AIM: To study theophylline metabolites pharmacokinetics in patients after a therapeutic dose. METHODS: Eight adult patients with mild bronchial asthma and normal liver function were infused aminophylline intravenously (6.6 mumol.kg-1). The plasma concentrations of theophylline and its 4 metabolites: 1,3-dimethyluric acid (DMUA), 3-methylxanthine (3-MX), 1-methyluric acid (MUA), and the intermediate 1-methylxanthine (1-MX) were monitored by HPLC throughout 24 h. RESULTS: The plasma concentration of DMUA was the highest one among the 4 metabolites. 3-MX showed the slowest elimination rate. The plasma concentration of 1-MX throughout a 24-h period showed that there was a picking up of 1-MX (from 0.04 mumol.L-1 to 1.05 mumol.L-1) in the next morning. CONCLUSION: The formation of DMUA was the main metabolites. During night there was an accumulation of 1-MX. (+info)
Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease.
(35/2342)
BACKGROUND: Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, placebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in patients with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 microg of budesonide or placebo, inhaled from a dry-powder inhaler, for three years. RESULTS: Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the three-year period was 140 ml in the budesonide group and 180 ml in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 ml per year in the budesonide group, as compared with a decline of 81 ml per year in the placebo group (P<0.001). From nine months to the end of treatment, the FEV1 declined at similar rates in the two groups (P=0.39). Ten percent of the subjects in the budesonide group and 4 percent of those in the placebo group had skin bruising (P<0.001). Newly diagnosed hypertension, bone fractures, postcapsular cataracts, myopathy, and diabetes occurred in less than 5 percent of the subjects, and the diagnoses were equally distributed between the groups. CONCLUSIONS: In patients with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline. (+info)
Comparison of formoterol, salbutamol and salmeterol in methacholine-induced severe bronchoconstriction.
(36/2342)
The onset of the bronchodilating effect of formoterol (12 microg by Turbuhaler) was compared with that of salbutamol (50 microg by Turbuhaler), salmeterol (50 microg by Diskhaler) and placebo in methacholine-induced severe bronchoconstriction. Seventeen subjects with mild-to-moderate asthma completed this randomized, double blind, cross-over, double-dummy study. On four study days, baseline forced expiratory volume in one second (FEV1) was recorded and the subjects were challenged with methacholine until FEV1 fell by at least 30%. Immediately thereafter, the study drugs were inhaled and lung function was assessed for 60 min. The geometric mean time for FEV1 to return to 85% of baseline was 7.2 min with formoterol, 6.5 min with salbutamol, 14.1 min with salmeterol and 34.7 min with placebo (p=0.0001, overall ANOVA). The difference between formoterol and salmeterol was statistically significant (p=0.01); there was no difference between formoterol and salbutamol (p=0.69). In conclusion, formoterol reversed methacholine-induced severe bronchoconstriction as rapidly as salbutamol and more rapidly than salmeterol. Classifying beta2-agonists as "fast"- and "slow"- acting may be supplemental to "short"- and "long"-acting. (+info)
An in vitro analysis of the output of salbutamol from different nebulizers.
(37/2342)
The objective of this study was to determine the particle size and mass output of salbutamol from different nebulizers used under simulated breathing conditions. Seven nebulizer/compressor combinations were assessed. Each nebulizer was charged with 5 mg salbutamol solution and connected to a breathing simulator operating at tidal volumes of 150 mL and 600 mL. Nebulizers were operated for 15 min. Salbutamol collected on the filters was measured by liquid chromatography. Aerosol particle size was determined separately by laser diffraction. The Pari LC Star nebulizer delivered the most salbutamol at both tidal volumes. The maximal output of the Medicaid Ventstream and Sidestream nebulizers was two-thirds that of the LC Star, and they delivered less salbutamol than the LC Star or LC Plus nebulizers. The Intersurgical Cirrus nebulizer delivered the least salbutamol at both tidal volumes, although there was only a small difference between the Cirrus and Ventstream or Sidestream nebulizers at 150 mL tidal volume. The LC Plus nebulizer produced larger particles, mass median diameter 5.3 microm, compared with 3.6-4.0 microm for the other nebulizers. In conclusion, there were large differences in the delivery of salbutamol between the nebulizers studied, even between nebulizers of apparently the same class, and this should be borne in mind by regulatory authorities, clinicians and researchers. (+info)
Modulation of multidrug resistance protein expression in porcine brain capillary endothelial cells in vitro.
(38/2342)
Multidrug resistance-associated protein (MRP) is a transport system that is involved in the elimination of xenobiotics and biologically active endogenous substrates. Recently, the presence of MRP has been demonstrated in cultured brain capillary endothelial cells (BCECs). The time-dependent, functional expression of MRP in porcine BCECs was investigated to assess the value of this cell culture model for drug transport at the blood-brain barrier. Western blot analysis was used to investigate MRP expression in freshly isolated porcine BCECs and compared to MRP expression at days 8 and 10 in culture. Subcellular localization of MRP was investigated by immunocytochemistry with an MRP-specific monoclonal antibody, MRPr1. Functional activity of MRP was assessed by efflux studies with the fluorescent MRP substrate glutathione-methylfluorescein (GS-MF). No significant MRP expression was detected in freshly isolated endothelial cells. However, MRP expression is up-regulated in cell culture in a time-dependent manner. Immunostaining revealed predominantly perinuclear and, to a lesser degree, plasma membrane localization of MRP. At 10 degrees C GS-MF efflux was significantly decreased, indicating the involvement of an energy-dependent transport system. Efflux of GS-MF was apparently inhibited by MK571, a specific inhibitor for MRP. Porcine BCECs demonstrate up-regulation of functional MRP expression during culture, as observed in human tissue, and therefore might serve as a useful in vitro system for studying MRP-mediated blood-brain barrier transport. (+info)
Maximal response plateau to methacholine as a reliable index for reducing inhaled budesonide in moderate asthma.
(39/2342)
Although some studies suggest that asthma deteriorates after reducing inhaled steroids, results of long-term studies indicate that this might not be true for all patients. The aim of this study was to determine the utility of the detection of a plateau on the concentration-response curves to inhaled methacholine as a marker for safely reducing the dose of inhaled budesonide in asthmatic patients who are well-controlled with a moderately high dose of this inhaled steroid. A total of 46 patients with moderate asthma, well-controlled for at least 6 months by treatment with 800 microg budesonide daily, were included in the study. Subjects were treated for a 2-week run-in period with their usual dose of budesonide. At the end of the run-in, all subjects were challenged with methacholine (0.095-200 mg x mL(-1)). Plateau responses, median effective concentration values, slopes and provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) values were measured. For the subsequent 12 weeks, patients were treated in an open design with budesonide at a reduced dose (200 microg once daily), and were asked to record their peak expiratory flow (PEF) in the morning and in the evening. In addition, asthma symptoms and use of rescue terbutaline were recorded in diaries. Plateaus were present in 24 patients, whereas 22 subjects showed concentration-response curves without evidence of a plateau. Ten patients in the nonplateau group deteriorated after reducing inhaled budesonide, compared to one patient in the plateau group (p = 0.002). In the nonplateau group, FEV1 decreased from a baseline value of 3.28+/-0.19 L to 2.94+/-0.20 L at week 12 (p<0.0001). Likewise, morning PEF decreased from 419+/-19 L x min(-1) at baseline to 394+/-19 L x min(-1) at week 12 (p = 0.02). By contrast, these variables remained unchanged in the plateau group. In conclusion, in asthmatic patients, well-controlled with a moderately high dose of budesonide, the detection of a plateau on the concentration-response curve to inhaled methacholine may be used as a marker for safely reducing the corticosteroid dose. (+info)
Inhomogeneity in response to air pollution in European children (PEACE project).
(40/2342)
OBJECTIVES: The PEACE study is a multicentre panel study of the acute effects of particles with a 50% cut off aerodynamic diameter of 10 microns (PM10), black smoke (BS), sulphur dioxide (SO2), and nitrogen dioxide (NO2) on respiratory health of children with chronic respiratory symptoms. In the complete panels no consistent association between air pollution and respiratory health was found. The study evaluated whether potentially more sensitive subgroups in the panels did show effects of air pollution. METHODS: To evaluate heterogeneity in response to air pollution, effect estimates of air pollution on peak expiratory flow (PEF) and respiratory symptoms were calculated in subgroups based on presence of chronic respiratory symptoms, use of respiratory medication, atopy, sex, and baseline lung function. RESULTS: The association between PEF and air pollution was positive in asthmatic children who used respiratory medication whereas the associations tended to be negative in children who did not use respiratory medication selected only on cough. No consistent association was found among asthmatic children who did not use medication. The association between daily prevalence of symptoms and concentrations of air pollution was not different between these subgroups. CONCLUSION: None of the predefined potentially more sensitive subgroups showed a consistent association between air pollution, PEF, and respiratory symptoms. (+info)