The role of domiciliary nebulizers in managing patients with severe COPD

The difficulty of assessing nebulizer responses in chronic obstructive pulmonary disease (COPD) has been demonstrated before. This study aims to re-examine both the role of domiciliary nebulizers in COPD and also bronchodilator (BD) assessment in individuals. In a double-blind, randomized, cross-over trial, 19 stable patients with severe COPD were given the following medication 6-hourly for 2-week periods: (1) nebulized salbutamol 2.5 mg with ipratropium 0.5 mg and placebo inhalers (MDI) with spacer; (2) placebo nebules and inhaled salbutamol 400 microg with ipratropium 80 microg via MDI with spacer; (3) inhaled salbutamol 400 microg with ipratropium 80 microg via MDI with spacer (but no placebo nebulized drugs). Both nebulized and MDI drugs produced highly significant improvements in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), specific airways conductance, 6-min walking distance (6MWD) and residual volume. There were no significant differences between BD responses obtained after active nebulized and active MDI BDs. From the diary cards, 2 weeks of active nebulized BDs produced a slightly higher median peak expiratory flow (PEF) than active MDI BDs (236 and 219 l m(-1), respectively, P=0.01) and slightly less extra inhaler use (0.8 and 1.1 puffs, respectively, P<0.05) but no significant difference in dyspnoea or quality of life (QOL) scores. There were significant correlations between domiciliary PEF and acute BD-induced changes in FVC and 6MWD, and also between domiciliary dyspnoea scores and acute changes in both total lung capacity and 6MWD. In conclusion, nebulized medication conferred little clinical advantage over the regular use of inhalers with spacers in this group of patients with severe COPD. However, acute changes in total lung capacity, FVC and 6MWD may be useful predictors of the longer-term effects of nebulized BDs in individual patients.     

Beclomethasone dipropionate and salbutamol by metered dose inhaler in infants and small children with recurrent wheezing

The efficacy of beclomethasone dipropionate (BDP) to control respiratory symptoms was evaluated in 31 children under age 2 years with recurrent wheezing. The study was conducted in a double-blind, parallel, and placebo-controlled fashion. The two study groups received either salbutamol plus BDP 200 microg bid by metered dose inhaler (MDI) with a spacer, or salbutamol MDI plus a placebo. Inhaled corticosteroid (IC) and placebo were administered for 8 weeks. Patients were seen every 2 weeks as outpatients, and their progress was evaluated by clinical examination and a daily symptom score card.At the end of the study, patients in both groups had significantly decreased symptoms. No significant difference was found between BDP and placebo groups regarding clinical score, number of salbutamol doses, sleep disturbances, number of symptom-free days, feelings of insecurity of mothers regarding the infants' life due to wheezing, and mothers' perceptions of progress in their infants' respiratory symptoms.We conclude that salbutamol plus 200 microg bid of BDP inhaled from an MDI with a spacer for 8 weeks is no better than salbutamol alone for decreasing recurrent wheezing in small children under age 24 months.     

Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD patients: influence of flow pattern.

In mechanically ventilated patients the flow pattern during bronchodilator delivery by metered-dose inhaler (MDI) could be a factor that might influence the effectiveness of this therapy. In order to test this the effect of two different inspiratory flow patterns on the bronchodilation induced by beta2-agonists administered via MDI and spacer in a group of mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) was examined. Eighteen mechanically ventilated patients with COPD, were prospectively randomized to receive two (n=8, protocol A) or six (n=10 protocol B) puffs salbutamol (100 microg x puff(-1)) either under pressure control (decelerating flow pattern) or under volume control (square wave flow pattern). With both modes, tidal volume and inspiratory time were identical. Salbutamol was administered via an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud-enhancer spacer. After a 6-h washout, patients were crossed over to receive the same dose of salbutamol (200 or 600 microg, respectively in protocols A and B) by the alternative mode of administration. Static and dynamic airway pressures, minimum (Rint) and maximum (Rrs) inspiratory resistance and the difference between Rrs and Rint (deltaR) were measured before and at 15, 30 and 60 min after salbutamol. Independent of the dose, salbutamol caused a significant decrease in dynamic and static airway pressures, Rint and Rrs. These changes were not influenced by the inspiratory flow pattern and were evident at 15, 30 and 60 min after salbutamol. It is concluded that salbutamol delivered via metered dose inhaler and spacer device, induces significant bronchodilation in mechanically ventilated patients with chronic obstructive pulmonary disease, the magnitude of which is not affected by the inspiratory flow/time profile.     

Effects of salbutamol delivery from a metered dose inhaler versus jet nebulizer on dynamic lung mechanics in very preterm infants with chronic lung disease

Treatment of chronic lung disease of prematurity requires effective aerosol delivery of different therapeutic agents. Aerosols can be generated by a metered dose inhaler (MDI) or a jet nebulizer. An MDI combined with a spacer device is easier to use and avoids undesirable effects noted in conjunction with jet nebulization. We compared the clinical effectiveness of 200 μg (2 puffs) salbutamol delivered from an MDI in conjunction with a valved spacer device (Aerochamber®), and 600 μg given via jet nebulizer (PariBaby®) on 2 consecutive days, the order being randomized. Thirteen spontaneously breathing very preterm infants [mean (SD) gestational age 27.2 (1.8) weeks; birth weight 0.90 (0.34) kg] were studied at a corrected age of 37 (2.3) weeks. Mean (SD) study weight was 1.83 (0.38) kg. Dynamic lung compliance and resistance were determined from measurements of flows, volumes, and transpulmonary pressures, using a pneumotachometer and a small esophageal microtransducer catheter before and 20 min after salbutamol application. Baseline values before salbutamol administration were similar on both occasions: the mean (SD) compliance was 7.7 (3.0) mL · kPa⁻¹ · kg⁻¹ pre-MDI plus-spacer and 8.4 (3.1) pre-jet nebulizer; the resistance was 10.4 (4.0) kPa · L⁻¹ · s pre-MDI plus-spacer and 9.7 (3.4) pre-jet nebulizer. Following salbutamol, compliance did not change significantly with either MDI plus spacer or jet nebulizer. Resistance fell significantly with MDI plus spacer (mean −2.2; 99.9% CI −0.35, −4.35) and jet nebulizer (−2.4; 99% CI −0.39, −4.42). We conclude that even in small preterm infants 200 μg salbutamol via MDI plus spacer improves dynamic resistance as effectively as 600 μg via jet nebulizer and may therefore be a preferable mode of aerosol administration. Pediatr. Pulmonol. 1997; 23:442–448. © 1997 Wiley-Liss, Inc.     

Randomized trial of salbutamol via metered-dose inhaler with spacer versus nebulizer for acute wheezing in children less than 2 years of age

The aim of this study was to compare the efficacy of salbutamol delivered via a metered-dose inhaler with a spacer and facial mask (MDI-S) vs. a nebulizer (NEB) for the treatment of acute exacerbations of wheezing in children. In a single-blind, prospective, randomized clinical trial, 123 outpatients (1-24 months of age), presenting with "moderate to severe" wheezing, were seen in the emergency department. Children were randomly assigned to one of two salbutamol treatment groups. In the first hour, the MDI-S group received 2 puffs (100 microg/puff) every 10 min for 5 doses, and the NEB group received 0.25 mg/kg every 13 min for 3 doses. If the clinical score was >5 at the end of the first hour, the patients received another hour of the same treatment and also betamethasone (0.5 mg/kg intramuscular). On enrollment and after the first and the second hour of treatment each child had a validated clinical score assigned by a blinded investigator. There were no differences at the time of admission to the emergency department between groups in clinical score or demographic data. Success (clinical score 0.05). We conclude that in this study population, children less than 2 years of age with moderate-severe exacerbations of wheezing responded faster to salbutamol delivered by MDI with a spacer and facial mask than to salbutamol delivered by nebulizer.     

Bronchodilating effects of salbutamol from a novel inhaler Airmax

This randomized, placebo-controlled, evaluator-blind, five-way crossover study compared the equivalence in terms of FEV1 response to single ascending cumulative doses of salbutamol (100-400 micrograms) from Airmax, a new multidose dry powder inhaler, in comparison with placebo, the same dose from a standard pressurized metered dose inhaler (Ventolin) or at double the dose from the dry powder inhalers Diskhaler and Accuhaler. Sixty-one adult asthmatic subjects with FEV150-80% predicted and > or = 15% increase in FEV1 to salbutamol took part. Equivalence was declared if the 95% CI for the ratio of the FEV1 responses to the two treatments was within the range 90-111%. Following the cumulative four doses, FEV1 (1) changes pre-dose to the highest dose were: 2.53-3.31, 2.47-3.30, 2.51-3.35, 2.52-3.31 and 2.57-2.55 for Airmax salbutamol, salbutamol Ventolin, salbutamol Diskhaler, salbutamol Accuhaler and placebo, respectively. The 95% CIs for the ratio of Airmax salbutamol to each of the active devices were within +/- 5% demonstrating a 1:1 dose equivalence between Airmax salbutamol and Ventolin and a 1:2 dose equivalence between each of the other two salbutamol dry powder devices. Adverse events profiles were similar for all treatments. In conclusion, the novel multidose inhaler Airmax salbutamol is as efficacious and safe as the pressurized metered dose inhaler without the need for co-ordinating actuation and inhalation and with the added benefit of a dose counter.     

The efficacy of a new salbutamol metered-dose powder inhaler in comparison with two other inhaler devices

An open cross-over and randomized study was carried out in order to compare the efficacy and safety of inhaled salbutamol delivered from a new 50 microg dose(-1) metered-dose dry powder inhaler Taifun, and a commercially available 50 microg dose(-1) dry powder inhaler Turbuhaler, and a conventional 100 microg dose(-1) pressurized metered-dose inhaler with a spacer (pMDI+S). Twenty-one patients, aged 21-70 years, with stable asthma and with demonstrated reversibility upon inhalation of salbutamol were included in the study. On three separate study days, the patients received a total dose of 400 microg of salbutamol from the dry powder inhalers and a dose of 800 microg from the pMDI+S in a cumulative fashion: 1,1, 2 and 4 doses at 30 min intervals. The percent change in forced expiratory volume in 1 sec (FEV1), was used as the primary efficacy variable. Salbutamol inhaled via the Taifun produced greater bronchodilation than the other devices. The difference in percent change in FEV1 between the Taifun and the other devices was statistically significant at the two first dose levels, but diminished towards the higher doses when the plateau of the dose-response curve was reached. The estimated relative dose potency of the Taifun was approximately 1.9- and 2.8-fold compared to the Turbuhaler and the pMDI+S, respectively. The Taifun caused a slight, but clinically insignificant, decrease in serum potassium concentration. There were no significant changes in the other safety parameters (blood pressure, heart rate and electrocardiogram recordings) with any of the used devices. In conclusion, this study indicates that salbutamol inhaled via the Taifun is more potentthan salbutamol inhaled from the other devices tested. In practise, a smaller total dose of salbutamol from theTaifun is needed to produce a similar bronchodilatory response. All treatments were equally well tolerated.     

Comparative efficacy and safety of albuterol sulfate Spiros inhaler and albuterol metered-dose inhaler in asthma

STUDY OBJECTIVE: To compare the long-term efficacy and safety of albuterol administration using a Spiros Inhalation System (Dura Pharmaceuticals; San Diego, CA) dry powder inhaler (DPI) and albuterol (Ventolin; Glaxo Wellcome; Research Triangle Park, NC) administration using a metered-dose inhaler (MDI) in patients with asthma. MATERIALS AND METHODS: This was a phase III, 12-week, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 283 adolescent and adult patients with mild to moderate asthma. The patients were randomized into one of three treatment groups: the Spiros group, who were given 108 microg/actuation of albuterol sulfate equivalent to 90 microg of albuterol base; the MDI group, who were given 90 microg/actuation of albuterol; and the placebo group. RESULTS: Over the length of the study, the Spiros and MDI groups were comparable in all FEV1 parameters. Both active treatment groups were superior to the placebo group for each FEV1 parameter at all visits. With the exception of differences at treatment week 0 for the maximum percent change in the FEV1, the duration of effect, and the area under the curve at baseline, there were no statistically significant differences between the Spiros and MDI groups for any FEV1 parameters. Using a repeated-measures analysis, the FEV1 parameters at week 0 for the Spiros group were not statistically significantly different from the parameters at weeks 4, 8, and 12. The same analysis effect at week 0 for the MDI group was greater for maximum percent change in the FEV1 from baseline (weeks 4, 8, and 12) and duration of effect. Adverse events and changes in clinical laboratory values, vital signs, ECG results, and physical examinations were reported with similar incidence in each of the three treatment groups. CONCLUSION: Both active treatments were superior to the placebo treatment. The Spiros DPI was well tolerated and was as effective as the albuterol MDI in treating patients with moderate asthma.     

Comparison of domiciliary nebulized salbutamol and salbutamol from a metered-dose inhaler in stable chronic airflow limitation

Nineteen patients (12 men) mean age, 63.4 years (range, 32 to 78), with stable chronic airflow limitation, mean FEV, 0.55 L (range, 0.3 to 1.05 L), completed an eight-week, double-blind, double cross-over study comparing nebulized salbutamol and salbutamol from a metered-dose inhaler (MDI). Salbutamol from both delivery systems produced bronchodilation. The doses of salbutamol inhaled via the nebulizer and MDI producing maximal bronchodilation were established by cumulative dose-response curves. The contents of the nebulizer and MDI were inhaled four times a day, one system containing salbutamol and the other a placebo. Cross-over of salbutamol from one system to the other occurred every two weeks. There was no significant difference between the two delivery methods in daily peak expiratory flow rate (PEFR), severity of symptoms, or extra bronchodilator usage. Two weekly laboratory assessments of spirometry, PEFR, and exercise tolerance also showed no significant differences. Careful assessment is recommended before the provision of domiciliary nebulizers.     

Improved delivery of fenoterol plus ipratropium bromide using Respimat compared with a conventional metered dose inhaler.

Asthma can be effectively treated by the use of bronchodilator therapies administered by inhalation. The objective of this study was to describe the dose-response relationship of combined doses of fenoterol hydrobromide (F) and ipratropium bromide (I) (F/I) delivered via Respimat, a soft mist inhaler, and to establish the Respimat dose which is as efficacious and as safe as the standard marketed dose of F/I (100/40 microg) which is delivered via a conventional metered dose inhaler (MDI). In a double-blind (within device) cross-over study with a balanced incomplete block design, 62 patients with stable bronchial asthma (mean forced expiratory volume in one second (FEV1) 63% predicted) were randomized at five study centres to receive five out of eight possible treatments: placebo, F/I 12.5/5, 25/10, 50/20, 100/40 or 200/80 microg delivered via Respimat; F/I 50/20 or 100/40 microg delivered via MDI. Pulmonary function results were based on the per-protocol dataset, comprising 47 patients. All F/I doses produced greater increases in FEV1 than placebo. A log-linear dose-response was obtained for the average increase in FEV1 up to 6 h (AUC0-6 h) and peak FEV1 across the dose range administered by Respimat. Statistically, therapeutic equivalence was not demonstrated between any F/I dose administered by Respimat compared with the MDI. However 12.5/5 and 25/10 microg F/I administered via Respimat were closest (slightly superior) to the F/I dose of 100/40 microg delivered via MDI. Pharmacokinetic data from 34 patients indicated a two-fold greater systemic availability of both drugs following inhalation by Respimat compared to MDI. In general, the active treatments were well tolerated and safe with regard to vital signs, electrocardiography, laboratory parameters and adverse events. In conclusion, combined administration of fenoterol hydrobromide and ipratropium bromide via Respimat, is as effective and as safe as higher doses given via a metered dose inhaler.     

Bronchodilation and bronchoprotection in asthmatic preschool children from formoterol administered by mechanically actuated dry-powder inhaler and spacer.

We evaluated the bronchodilatory and the bronchoprotective effect of the long-acting beta(2)-agonist formoterol administered as dry powder from a mechanically actuated dry-powder inhaler (DPI) using spacer in 12 asthmatic children 2 to 5 yr of age. Lung function was measured as the specific airway resistance (sRaw) in a whole body plethysmograph. Hyperventilation of cold, dry air was used as bronchial challenge, and the responsiveness was estimated as change in sRaw. The bronchoprotective effect of formoterol Turbohaler 9 microg was compared with salbutamol 200 microg and placebo at 15 min, 4 and 8 h postdose in a randomized, double-blind, placebo-controlled, crossover study. All treatments were administered from DPI (Turbohaler) actuated mechanically into a spacer. Formoterol and salbutamol caused similar and significant bronchodilation at the first measurement 3 min postdose. Formoterol offered a sustained and stable bronchodilation for at least 8 h. Salbutamol provided significant bronchodilation for less than 4 h. Formoterol caused significant bronchoprotection of 80% for at least 8 h compared with placebo, and from 4 h onward compared with salbutamol. Bronchoprotection from salbutamol lasted less than 4 h. In conclusion, formoterol administered as dry powder in a single dose provided rapid and sustained bronchodilation and clinically significant bronchoprotection for at least 8 h in 2- to 5-yr-old asthmatic children. Furthermore, this study suggests that mechanical actuation of DPI using a spacer is effective for aerosol treatment of young asthmatic children.     

Delivery of fenoterol via Respimat, a novel 'soft mist' inhaler. a randomised, double-blind (within device), placebo-controlled, cross-over, dose-ranging study in asthmatic patients

BACKGROUND: The phase-out of chlorofluorocarbons (CFCs) for metered dose inhalers (MDIs) has prompted the development of alternative propellants and the design of propellant-free devices for inhalation therapy. OBJECTIVE: This study was carried out to determine the dose of fenoterol inhaled from Respimat (RMT), a new propellant-free soft mist inhaler, which is equivalent in terms of efficacy and safety to 1 puff of either 100 or 200 microg fenoterol inhaled from a conventional CFC-MDI (Berotec). METHODS: Sixty-two asthmatic patients (35 male, 27 female) with a mean baseline FEV(1) of 1.7 liters, corresponding to 55% of the predicted normal value, were randomized at two study centers to 4 of a total of 8 possible treatments: placebo; 12.5, 25, 50, 100, or 200 microg fenoterol via RMT, and 100 or 200 microg fenoterol delivered via the MDI. RESULTS: Fifty-nine patients completed the study as planned. Results of the therapeutic equivalence test for the primary endpoint, average FEV(1) (AUC(0-6))/6 and for the secondary endpoint, peak FEV(1), showed that the 12.5- and 25-microg fenoterol doses administered via RMT were equivalent to the 100 microg fenoterol dose from the MDI. The 50-, 100- and 200-microg fenoterol doses delivered by RMT did not meet the criterion for therapeutic equivalence with the 100-microg dose from the MDI, and if tested for a difference would have been significantly different in favor of RMT. All 5 RMT fenoterol doses were therapeutically equivalent to the MDI 200-microg fenoterol dose. Headache, reported by 4 patients on test days and 2 patients between test days in those randomized to RMT, was the most common adverse event, but the active treatments were generally well tolerated with no dose-dependent increases in incidence or severity of adverse events observed. CONCLUSIONS: The results from the study suggest that safe and efficacious bronchodilation can be obtained from single-dose fenoterol administered via RMT. Use of lower absolute doses to obtain a clinically significant improvement in pulmonary function may be possible because of the increased lung deposition achievable with the novel soft mist inhaler.     

Bronchodilator delivered by metered dose inhaler and spacer improves respiratory system compliance more than nebulizer-delivered bronchodilator in ventilated premature infants

We compared the change in passive respiratory system compliance (Crs) and resistance (Rrs) after albuterol aerosol treatment administered by either low-flow nebulizer (NEB) or a metered dose inhaler (MDI) and spacer into a ventilator circuit. We hypothesized that albuterol delivered to ventilated infants older than 7 days of life by an MDI and a spacer would improve Crs more than albuterol delivered by a low-flow nebulizer. The treatments were administered 6 hr apart to premature infants with Crs < or = 0.8 mL/cm H2O per kg, requiring ventilation after 7 days of age. Patients served as their own controls and treatment order was randomized. Eighteen studies were performed in eight infants before and 1 and 3 hr after treatment. Differences between methods were compared by analyses of variance. Mean (range) birth weight and study age were 888 (619-1,283) g and 12 (7-29) days, respectively. Mean respiratory system compliance increased by 34% with MDI and by 11% with NEB at 1 hr after treatment (P < 0.02). By 3 hr after treatment, Crs returned to baseline with both methods of aerosol delivery. There was no significant difference in Rrs between the two methods at 1 and 3 hr after treatment. We conclude that albuterol delivered by MDI improves Crs more than low-flow NEB in ventilated premature infants.     

What is the optimal treatment strategy for chronic obstructive pulmonary disease exacerbations?

The present study aims to determine whether treating chronic obstructive pulmonary disease (COPD) exacerbations with intravenous steroids and aerosol bronchodilators (group I) is superior to oral steroids and multiple dose inhaler (MDI) bronchodilators with a spacer (group II). Group I received 40 mg methylprednisolone x day(-1) intravenously with a decrease to 20 mg after 10 days and a further decrease of 4 mg x 4 days(-1). Aerosol therapy consisted of 10 mg salbutamol and 1 mg ipratropiumbromide x day(-1). Group II received 32 mg methylprednisolone orally for 1 week followed by 24 mg x day(-1) for 4 days and a subsequent decrease of 4 mg x week(-1). Duovent MDI with a spacer was given at a dose of 1.6 mg fenoterol and 640 microg ipratropiumbromide x day(-1). In group I (n=19) forced expiratory volume in one second (FEV1) rose from 0.82+/-0.46 to 0.91+/-0.47 L and average dyspnoea decreased from 6.0+/-1.9 to 4.1+/-2.6 within 10 days. The Chronic Respiratory Disease Index Questionnaire (CRQ) score increased from 78+/-24 to 90+/-24 points after 4 weeks. In group II (n=18) FEV1 increased from 0.70+/-0.27 to 0.90+/-0.29 L, dyspnoea regressed from 6.2+/-2.4 to 2.7+/-2.6 and CRQ from 67+/-17 to 86+/-20. Both groups showed similar results in dropout rate, length of hospital stay and patient satisfaction. In conclusion, the two treatment strategies appear equally effective in treating chronic obstructive pulmonary disease exacerbations, although oral steroids and metered dose inhaler bronchodilators appear associated with a higher risk of hospital re-admission.     

Rapid onset of bronchodilation in COPD: a placebo-controlled study comparing formoterol (Foradil Aerolizer) with salbutamol (Ventodisk)

Formoterol fumarate is a beta2-agonist bronchodilator that combines a fast onset of action with a long duration of action. Its fast onset of action is well documented in asthma but has not been directly compared with that of salbutamol in patients with chronic obstructive pulmonary disease (COPD). This randomized, double-blind, placebo-controlled study was conducted to assess the bronchodilatory effects over the first 3 h after inhalation of single doses of formoterol 24 microg delivered via the Aerolizer dry powder inhaler device (double-blind), or salbutamol 400 microg delivered by a Diskhaler dry powder inhaler (single-blind) in patients with COPD. A total of 24 patients with COPD were randomized [mean age 61.6 +/- 7.8 years, mean forced expiratory volume in 1 sec (FEV1) 1.38 +/- 0.32 l and 45.8 +/- 9.6% of predicted]. Inhalation of formoterol or salbutamol resulted in similar increases in FEV from 0 to 3 h post-dose. Both drugs produced similar bronchodilation by 5 min, which became almost maximal by 30 min. The primary efficacy variable, the area under the curve (AUC) of the FEV increase above predose baseline from 0 to 30 min (AUC(0-30 min)), demonstrated significant effects for formoterol (mean 5.89 +/- 4.67 l min(-1)), and salbutamol (mean 6.06 +/- 4.34 l min(-1)), which were not statistically different from each other but statistically significantly higher (P<0.0001) than that observed with placebo (-0.32 +/- 2.59 l min(-1)). In addition, both formoterol and salbutamol produced similar and rapid increases in forced vital capacity (FVC). In summary, this study confirms the rapid onset of action of formoterol and indicates that the onset of action of formoterol and salbutamol are similar in patients with COPD.     

Formoterol Turbuhaler as reliever medication in patients with acute asthma.

The aim of this study was to compare the efficacy and safety of formoterol versus salbutamol as reliever medication in patients presenting at an emergency dept with acute asthma. A randomised, double-blind, double-dummy, parallel group study was performed in four Australian emergency treatment centres. The study included a total of 78 adult patients (mean baseline forced expiratory volume in one second (FEV1) 1.83 L; 59% predicted) with acute asthma. Based on the expected dose equivalence of formoterol Turbuhaler 4.5 microg (delivered dose) and salbutamol pressurised metered-dose inhaler 200 microg (metered dose), patients received a total of formoterol Turbuhaler 36 microg (delivered) or salbutamol pressurised metered-dose inhaler with spacer 1,600 microg (metered), divided into two equal doses at 0 and 30 min. FEV1, peak expiratory flow and systemic beta2-agonist effects were monitored for 4 h. The primary variable was FEV1% pred at 45 min. At 45 min, mean increases in FEV1 expressed in % pred were 6.6% and 9.3%, respectively, with a small adjusted mean difference in favour of salbutamol (3.0%, 95% confidence interval -2.0-8.0). Transient increases in systemic beta2-agonist effects occurred predominantly with salbutamol, although no significant treatment differences were observed. Eight patients discontinued due to adverse events. In this study of patients presenting at emergency depts with acute asthma, formoterol Turbuhaler 36 microg was well tolerated and, as rescue therapy, had an efficacy that was not different from that of salbutamol pressurised metered-dose inhaler with spacer 1,600 microg in the number of patients studied.     

Salbutamol dry powder inhaler: efficacy, tolerability, and acceptability study

Dry powder inhaler (DPI) devices are frequently used in children over 5 years of age in order to avoid coordination difficulties often seen with the use of pressurized metered dose inhalers (pMDI). This study assessed the efficacy, tolerability, and acceptability of salbutamol delivered via two delivery systems, in a population of pediatric patients. The primary aim of the study was to investigate the bronchodilator efficacy of a single dose (100 microg) of salbutamol administered via a dry powder inhaler (Clickhaler) compared to a similar dose administered by a pressurized metered dose inhaler via a large-valved holding chamber (VHC) to children with asthma. The study comprised two phases: the first comparator phase, followed by an open 4-week treatment period. Sixty-one children with a mean (SD) age of 11.3 years (2.9) (range, 6-17) and mild or moderate asthma completed the study. The primary efficacy endpoint, forced expiratory volume in 1 sec (FEV1), indicated that there was no clinically or statistically significant difference between the bronchodilator effects of salbutamol delivered via either device, with a maximum posttreatment percentage change in FEV1 (SD) of 12.4% (10.0) and 14.15 (9.3) for Clickhaler and pMDI plus VHC, respectively. Most patients rated the Clickhaler as easy to use (97%) and liked the device (84%). Both treatments were well--tolerated. These results support the suitability of salbutamol Clickhaler as an acceptable, well-tolerated, and effective alternative to a pMDI plus VHC in mild to moderate asthmatic children over age 6 years.     

A comparison of bronchodilator therapy delivered by nebulization and metered-dose inhaler in mechanically ventilated patients.

BACKGROUND: The optimal method of delivering bronchodilators in mechanically ventilated patients is unclear. The purpose of this study was to compare the pulmonary bioavailability of albuterol delivered by the nebulizer, the metered-dose inhaler (MDI) and spacer, and the right-angle MDI adaptor in ventilated patients using urinary analysis of drug levels. METHODS: Mechanically ventilated patients who had not received a bronchodilator in the previous 48 h and who had normal renal function were randomized to receive the following: (1) five puffs (450 microg) of albuterol delivered by the MDI with a small volume spacer; (2) five puffs of albuterol delivered by the MDI port on a right-angle adaptor; or (3) 2.5 mg albuterol delivered by a nebulizer. Urine was collected 6 h after the administration of the drug, and the amounts of albuterol and its sulfate conjugate were determined in the urine by a chromatographic assay. RESULTS: Thirty patients were studied, 10 in each group: their mean age and serum creatinine level were 62 years and 1.3 mg/dL, respectively. With the MDI and spacer, (mean +/- SD) 169+/-129 microg albuterol (38%) was recovered in the urine; with the nebulizer, 409+/-515 microg albuterol (16%) was recovered in the urine; and with the MDI port on the right-angle adaptor, 41+/-61 microg albuterol (9%) was recovered in the urine (p = 0.02 between groups). The level of albuterol in the urine was below the level of detection in four patients in whom the drug was delivered using the right-angle MDI adaptor. CONCLUSION: The three delivery systems varied markedly in their efficiency of drug delivery to the lung. As previous studies have confirmed, this study has demonstrated that using an MDI and spacer is an efficient method for delivering inhaled bronchodilators to the lung. The pulmonary bioavailability was poor with the right-angle MDI port. This port should not be used to deliver bronchodilators in mechanically ventilated patients.     

Bronchodilating effect of oxitropium bromide in heart disease patients with exacerbations of COPD: double-blind, randomized, controlled study

Anti-cholinergic agents are considered the bronchodilator therapy of first-choice in the treatment of patients with stable chronic obstructive pulmonary disease (COPD) associated with heart disease since they may be as effective or more effective than inhaled beta2-agonists and, moreover, they do not interact with cardiac beta-adrenoceptors. The aim of our study was to evaluate the bronchodilator activity of oxitropium bromide in outpatients suffering from exacerbations of COPD associated with heart diseases (ischaemic heart disease and/or arrhythmias). We recruited 50 consecutive outpatients (33 males and 17 females, mean age 68.6 years, 15 current smokers and 35 ex-smokers). Each patient performed body plethismography in basal condition and 30 min after inhalation of 200 microg metered dose inhaler (MDI) oxitropium bromide administered by a device (Fluspacer). FEV1, FVC, MMEF25-75, sRaw and tRaw were evaluated. Thirty minutes after 200 microg oxitropium bromide administration, we observed a significant improvement in FEV1 11.6% +/- 1 (mean +/- SEM) (P<0.01); FVC, MMEF25-75 sRaw variation was respectively: 9.2% +/- 0.6, 31.4 +/- 2.9, -19.9 +/- 1.1. Placebo did not significantly change pulmonary function. Our data suggest that oxitropium bromide bronchodilator activity is effective in exacerbations of COPD.     

Comparison of outpatient nebulized vs metered dose inhaler terbutaline in chronic airflow obstruction

Eighteen patients (nine asthmatic patients and nine with poorly reversible airflow obstruction) with stable, severe chronic airflow obstruction, completed a four-week randomized, doubled-blind, placebo-control, crossover trial comparing the acute and chronic effects of terbutaline administered by metered-dose inhaler (MDI) and nebulizer (NEB). Equipotent doses of terbutaline were selected from the comparison of separate cumulative dose-response curves for MDI and NEB. The MDI and NEB given acutely produced similar bronchodilatation and improvement in exercise performance. Spirometric indices, 6 min walking distance, symptom scores and extra beta-agonist use were no different between MDI and NEB treatment fortnights in the outpatient study. We conclude that the degree of bronchodilatation achieved in these patients is a reflection of the dose of bronchodilator administered and not the mode of administration. There is no justification for the preferred outpatient use of nebulized bronchodilators in patients with stable chronic airflow obstruction who can use adequate doses of bronchodilators via a metered-dose inhaler.