Aerosol pentamidine-induced bronchoconstriction. Predictive factors and preventive therapy.

OBJECTIVE: To describe the frequency of aerosol pentamidine-induced bronchoconstriction, its relationship to non-specific airway responsiveness, and its response to preventive therapy using salbutamol, ipratropium bromide, or sodium cromoglycate. METHODS: Consecutive HIV-infected individuals starting prophylactic AP were eligible if they had not been previously treated with this agent. Simple spirometry was performed before and 10 min after a single 60-mg dose given through an ultrasonic nebulizer. Methacholine challenge was performed in all subjects 24 h to four days after the initial AP dose. Subjects with a change in FEV1 (delta FEV1) greater than or equal to 10 percent decrease after the initial AP dose were restudied on three separate occasions (greater than 24 hours apart) after premedication with two puffs of salbutamol (200 micrograms), ipratropium bromide (40 micrograms), or sodium cromoglycate (2 mg), in random order. RESULTS: Fifty-three subjects were studied. The median delta FEV1 after a single dose of AP was -7.0 percent (range: -47 percent, 1.8 percent). The delta FEV1 following AP was only partially predicted by the degree of nonspecific bronchial responsiveness as measured by a standard methacholine challenge. Age, current smoking, history of asthma, baseline FEV1, or a prior episode of PCP failed to predict the delta FEV1 following AP. Eighteen subjects (34 percent) had a delta FEV1 greater than or equal to 10 percent decrease (median: -17.0 percent). In these subjects, after premedication with salbutamol, ipratropium bromide, and sodium cromoglycate, the median delta FEV1 was 1.0, 0.8, and -9.6 percent, respectively. CONCLUSION: Aerosol pentamidine produced a decrease in FEV1 greater than or equal to 10 percent in 34 percent of subjects. This was not accurately predicted by the methacholine response. The bronchoconstriction induced by AP was effectively prevented by either salbutamol or ipratropium, whereas cromoglycate was only partially effective.     

Dose duration of nebulized nedocromil sodium in exercise-induced asthma.

The dose-duration effect of nebulized nedocromil sodium was studied in ten patients with exercise-induced asthma (7 males mean (SEM) age 30.1 (3.5) yrs and predicted forced expiratory volume in one second (FEV1) 102%). All of these patients showed > 40% protection of their exercise asthma with 4 mg of nedocromil sodium delivered via metered dose inhaler. Three concentrations of nedocromil sodium (0.5, 2.5 and 10 mg.ml-1) and placebo were administered in double-blind, randomized manner. One ml of each solution was nebulized via a Wright nebulizer. Effects were assessed from the mean maximal percentage fall in FEV1 after 6-8 min treadmill exercise at 15, 135 and 255 min following each treatment and expressed as percentage protection. The mean baseline FEV1 values before and after treatments were comparable on four days of testing. Nedocromil sodium inhibited exercise-induced fall in FEV1 at all concentrations (p < 0.001) and the inhibitory effect was still present at 255 min. No differences were observed between active treatments.     

Reversibility tests in chronic obstructive airways disease: their predictive value with reference to benefit from domiciliary nebuliser therapy

The role of short-term tests of reversibility in selecting patients with COAD for long-term nebuliser therapy is uncertain. In a double-blind placebo-controlled crossover study we have examined the correlation between short-term reversibility and response to a home nebuliser. We studied 20 patients with severe COAD (mean age 66, mean FEV1 0.81 l) and little reversibility (less than 20% increase in FEV1 post-inhaled salbutamol 200 micrograms and less than 25% increase in peak expiratory flow rate, PEFR, on oral steroids). PEFR, spirometry, lung volumes and airways conductance were recorded before and 1 h after a mixture of nebulised ipratropium 0.5 mg and fenoterol 1.25 mg. Patients then recorded twice-daily PEFR at home while they received nebulised ipratropium plus fenoterol, or saline placebo, four times a day for three week blocks using a double-blind cross over protocol. Mean PEFR on home nebuliser rose from 164 l m-1 (placebo) to 196 l m-1 (ipratropium plus fenoterol), paired t-test P = 0.0001. Correlation coefficients between short-term response for PEFR, spirometry and lung volumes, and improvement in home PEFR on nebulised ipratropium plus fenoterol, were all poor (R = -0.37-0.35, P = 0.83-0.11). We conclude that in severe COAD, reversibility tests of PEFR, spirometry and lung volumes do not correlate with response to a home nebuliser. Home measurements of PEFR are probably the best objective method of assessing response to a home nebuliser in such patients.     

Drug delivery in asthma: A comparison of spacers with a jet nebuliser

Background: Although spacer devices are frequently used for aerosol therapy in asthma, the commonly used spacers have undergone little controlled evaluation, and their relation to nebuliser therapy is unclear. Aims: The aims of this study were to compare three delivery methods (Breath-A-Tech spacer, Volumatic spacer and jet nebuliser) for the administration of salbutamol to reverse acute histamine induced airway narrowing in asthma (Study 1); and to assess asthma control during two weeks use of inhaled therapy via Volumatic or Breath-A-Tech spacer (Study 2). Methods: A randomised double-blind cross-over comparison was conducted. In Study 1, 27 adults with stable asthma who were currently using pressurised metered dose inhaler therapy attended for three study days. On each study day subjects inhaled doubling doses of histamine and were randomised to receive: (a) salbutamol 200 μg via Breath-A-Tech spacer and placebo 200 μg via Volumatic spacer; (b) placebo two puffs via Breath-A-Tech spacer and salbutamol 200 μg via Volumatic spacer; or (c) salbutamol 1 mg in 2 mL saline via jet nebuliser. FEV and FEF 25–75% were measured at two minute intervals for 20 minutes. In Study 2, subjects were randomised to use regular asthma medication by Volumatic or Breath-A-Tech spacers and recorded symptoms and peak expiratory flow (PEF) in a daily diary. Results: Lung function improved from a baseline FEV, of 51% predicted to 72% after salbutamol inhalation from each of the delivery systems. The spacers and nebulisers produced the same maximum improvement in FEVi, however, lung function improved more rapidly when salbutamol was delivered by spacer. There was no difference in asthma control comparing inhaler use via Breath-A-Tech with Volumatic spacer over two weeks use. Subject preference favoured the Breath-A-Tech spacer (72%vs 4%). Conclusions: The Volumatic and Breath-A-Tech spacer devices are effective delivery systems in asthma and may offer a more rapid response than jet nebulisation at a lower cost.     

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.     

Comparison of the effects of nebulised and inhaled salbutamol on breathlessness in severe COPD

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often report greater relief of breathlessness with nebulised bronchodilators than with the same medicine administered from a metered dose inhaler (MDI). This suggests that the nebulised medicines may have an effect on breathlessness over and above changes in lung function resulting from bronchodilatation. METHODS: Twenty-four subjects with COPD and breathlessness at rest participated in this randomised, crossover trial. The mean age was 72 years and the mean FEV(1) was 26% of predicted. Subjects were studied on four separate days. On two days they were treated with nebulised salbutamol and on the other 2 days with salbutamol from an MDI and spacer. With each method of delivery, local anaesthetic cream was applied to the face on one day and to the back of the hand on the other. RESULTS: Five minutes after administration of salbutamol the subjects were significantly less breathless with nebulised salbutamol but by 45 min both treatments resulted in equivalent relief. There was no difference between the treatments in the change in FEV(1) or VC and application of local anaesthetic to the face did not influence the response. CONCLUSION: There was a small early benefit with nebulised salbutamol but this was not sustained and was not affected by topical anaesthesia. The benefit of nebulisation does not appear to be large enough to warrant the routine, widespread use of nebulised bronchodilators for the treatment of stable COPD.     

Inhibition of fog-induced bronchoconstriction by nedocromil sodium and sodium cromoglycate in intrinsic asthma: a double-blind, placebo-controlled study

The efficacy of pretreatment with two doses of nedocromil sodium (4 and 8 mg) and sodium cromoglycate 12 mg were compared with placebo in inhibiting the bronchoconstriction induced by inhalation of ultrasonically nebulized distilled water ('fog') in 10 subjects with intrinsic asthma. Each fog challenge consisted of three inhalations of 30, 60 and 120 s duration, respectively, given at 4-min intervals, and the bronchoconstrictor response was assessed as the postchallenge percentage fall in FEV1 from baseline. Statistically significant drug effects (p less than 0.05) were observed after 120 s of fog challenge: both nedocromil sodium 4 and 8 mg and sodium cromoglycate were significantly more effective than placebo in inhibiting fog-induced bronchoconstriction; in addition, nedocromil sodium 4 mg proved statistically significantly more effective than sodium cromoglycate.     

Effect of different inhaled bronchodilators on recovery from methacholine-induced bronchoconstriction in asthmatic children.

Two hundred fourteen children with mild to moderate asthma were studied to determine bronchodilator effects 5 min after administration of five different metered dose inhaler (MDI) aerosol formulations available in our country, and results were compared to placebo. Methacholine bronchial challenge was performed by the tidal breathing method, using increasing concentrations until a fall in forced expired volume in 1 s (FEV(1)) >/=20% was achieved (PC20). Immediately after FEV(1) had fallen 20% or more, children were randomly allocated into 1 of 6 groups to receive: salbutamol 200 microg (S), fenoterol 200 microg (F), salbutamol 200 microg + beclomethasone 100 microg (S + B), fenoterol 200 microg + ipratropium bromide 80 microg (F + IB), salmeterol 50 microg (SM), and placebo (P). The bronchodilator effect was determined by measuring FEV(1) 5 min after inhalation of medications. Nonparametric tests were used for statistical analysis. The six groups were similar in anthropometric and in respiratory characteristics. All five inhaled aerosols containing beta-agonists caused a significant bronchodilator effect as compared to placebo. However, the effect was significantly greater in the groups treated with F or F + IB (P < 0.05) compared to other formulations. We conclude that the five types of aerosols used in this study are able to reverse methacholine-induced bronchoconstriction 5 min after inhalation of a bronchodilator.     

Effect on spirometry of distilled water and cromoglycate solutions nebulised by a small portable ultrasonic nebuliser

The airway response to inhaled ultrasonically nebulised distilled water and three disodium cromoglycate solutions (DSCG in distilled water, normal saline and buffered saline) produced by a small portable nebuliser was determined by spirometry in 12 stable adult asthmatics in a double-blind trial. The mean percentage falls in forced expiratory volume in 1s (FEV1) were 13.4% following distilled water, 5.6% following DSCG in distilled water, 4.8% following DSCG in normal saline, 6.9% after DSCG in buffered saline. The fall in FEV1 was significantly greater (p less than 0.01) after distilled water than after all DSCG solutions with no significant difference between the DSCG solutions. Coughing was also greater during inhalation of nebulised distilled water than during inhalation of nebulised DSCG solutions (p less than 0.01).     

Relative lung bioavailability of generic sodium cromoglycate inhalers used with and without a spacer device

The relative lung bioavailability of sodium cromoglycate following inhalation has been evaluated using urinary drug excretion in nine healthly volunteers. Each inhaled four 5 mg sodium cromoglycate doses from a generic metered dose inhaler (MDI) and when it was attached to large volume spacer (MDI + VOL). A breath-actuated MDI was also evaluated either used on its own (EB) or attached to a small volume spacer tube (EBO). The mean (SD) urinary excretion of sodium cromoglycate in the first 30 min post-inhalation was 34.1 (20.2), 211.7 (123.5), 29.3 (19.5) and 52.8 (36.0) microg following MDI, MDI+VOL, EB and EBO, respectively. The cumulative mean (SD) urinary excretion of sodium cromoglycate over the 24 h post-inhalation was 364.7 (266.2), 1227.1 (459.0), 280.2 (155.4) and 429.5 (176.7) microg. A metered dose inhaler attached to a large volume spacer delivers more sodium cromoglycate to the lungs than any other inhalation method. Copyright Academic Press.     

Bronchodilator response to inhaled beta-2 agonist and anticholinergic drugs in patients with bronchiectasis

OBJECTIVE: An increase in incidence of reversible airflow obstruction and bronchial hyperresponsiveness occurs in patients with bronchiectasis. We conducted a study to assess the efficacy of bronchodilators in the treatment of bronchiectasis. METHODOLOGY: Twenty-four patients with confirmed bronchiectasis were studied. Each patient inhaled fenoterol 400 microg administered by metered dose inhaler via a spacer after a baseline lung function and a lung function test was repeated 30 min later. This was followed by a second dose of fenoterol 5 mg via nebulizer and another lung function test 30 min later. A repeat study was done at least 24 h later with ipratropium bromide 40 microg by metered dose inhaler and 500 microg by a nebulizer. RESULTS: The results showed a significant improvement from baselines (mean percentage change +/- SD) of peak expiratory flow rate (PEF) by 8.5 +/- 8.72% and 15.3 +/- 11.63%, forced expiratory volume in 1 s (FEV1) by 8.77 +/- 9.69% and 10.2 +/- 12.2% and forced vital capacity (FVC) by 10.25 +/- 11.61% and 10.09 +/- 10.88% after low- and high-dose fenoterol, respectively. The improvements after low- and high-dose ipratropium bromide for PEE FEV1 and FVC were 9.89 +/- 9.35% and 14.39 +/- 12.82%, 9.38 +/- 10.41% and 13.52 +/- 17.09%, and 8.03 +/- 10.85% and 9.63 +/- 13.85%, respectively. Eleven patients (45.8%) responded to one or both bronchodilators significantly (> 15% improvement in FEV1). Five patients (20%) responded to both, three (12%) to fenoterol alone and another three (12%) to ipratropium bromide alone. CONCLUSION: There is significant bronchodilator response in a subset of patients with bronchiectasis and patients with bronchiectasis should therefore undergo bronchodilator testing. Skin prick testing against a panel of nine allergens done on each individual yielded a positive result in 13 patients (54.2%).     

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.     

Effect of sodium cromoglycate and nifedipine on adenosine-induced bronchoconstriction

Inhaled adenosine causes bronchoconstriction in asthmatic patients. In 7 symptom-free asthmatics a study was performed to investigate the effect of sodium cromoglycate and nifedipine on adenosine-induced bronchoconstriction. All patients were challenged with increasing doses (from 0.03 to 2 mg) of nebulized adenosine to assess airway reactivity. The same procedure was repeated on different days at the same time each morning after administration of placebo and drugs in a randomized double-blind study. Airway response was measured as the forced expiratory volume in 1 s (FEV1). The PD20 value and the fall of FEV1 at the provocative dose were calculated. The PD20 data were modified in log values and the statistical analysis was performed by two-way analysis of variance. Mean decrease of FEV1 after adenosine challenge was 26.02 and 28.87% with placebo sodium cromoglycate and placebo nifedipine, respectively. Sodium cromoglycate and nifedipine gave a mean decrease of FEV1 of 6.44% (p less than 0.05) and 22.22%, respectively. PD20 values (geometric mean) after adenosine inhalation were 0.72 and 0.74 mg for placebo sodium cromoglycate and placebo nifedipine and 0.86 mg for nifedipine. Sodium cromoglycate gave a significant protection against adenosine in all subjects and in no case did the maximum dose used (2 mg) result in a fall in FEV1 value greater than 20%. Adenosine antagonism could be considered as a possible factor contributing to the pharmacologic efficacy of sodium cromoglycate in asthmatic patients. No protective effect was noticed with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bronchial responsiveness after human heart-lung transplantation

We evaluated bronchial responsiveness to inhaled albuterol (salbutamol), ipratropium bromide, methacholine, and propranolol in eight heart-lung transplant (HLT) recipients 2.3 +/- 1.5 months (mean +/- SD) (range, 1 to 4.5 months) after HLT. All patients had a restrictive ventilatory defect but none had airflow limitation (FEV1/FVC = 0.93 +/- 0.05) (range, 0.86 to 0.97). Specific airway conductance (sGaw) improved significantly with both albuterol (p less than 0.01) and ipratropium bromide (p less than 0.01) but FEV1 did not. Only one HLT patient had bronchoconstriction with propranolol, whereas all but one were hyperresponsive to methacholine. Prior inhalation of ipratropium bromide blocked the response to methacholine (p less than 0.005). Serial methacholine provocation tests performed in seven long-term survivors of HLT 24.6 +/- 16.0 months (range, 12 to 51 months) after HLT revealed no time-dependent evolution of bronchial hyperresponsiveness to methacholine. Limited maximal airway narrowing to methacholine was seen in five HLT recipients who showed a 29 +/- 4 percent (range, 23 to 35 percent) fall in FEV1 compared with two patients who did not achieve a plateau with a 47 percent and 63 percent fall in FEV1, respectively. These results further our understanding of bronchial responsiveness in the denervated transplanted lung. The findings of stable hyperresponsiveness to methacholine over a prolonged time interval, limited maximal airway narrowing to methacholine, and blockade of methacholine hyperresponsiveness by ipratropium bromide support the concept of denervation hypersensitivity of muscarinic receptors.     

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.     

Does high dose ipratropium bromide added to salbutamol improve pulmonary function for patients with chronic obstructive airways disease in the emergency department?*

Background: To determine the effect of high dose ipratropium bromide, both alone or in combination with standard dose salbutamol, on pulmonary function in patients presenting to the Emergency Department (ED) with acute exacerbation of chronic obstructive airways disease (COAD). Method: The trial was a prospective, randomised, double blind trial of adult patients with COAD. All patients received nebulised salbutamol 5 mg and 500 μg ipratropium and hydrocortisone 250 mg IV at time=0, then were randomised to receive further nebulisers at time=15 minutes and time=30 minutes of salbutamol 5 mg combined with ipratropium 500 μg or salbutamol 5 mg alone or ipratropium 500 μg alone. Pulmonary function tests were conducted at time=0 and time=90 minutes. The primary endpoints were absolute and percent change in FEV₁. Results: The group randomised to receive 5 mg salbutamol and 500 μg ipratropium (n=18) showed a mean percentage change of FEV₁ of 6.4% with a mean absolute change of 0.06 L (SD 0.18 L). Those who received 5 mg salbutamol (n=16) had a mean percentage change of 18.6% with a mean absolute change of 0.13 L (SD of 0.21 L). Those who received 500 μg ipratropium (n=16) had a mean percentage change of 4.8% with a mean absolute change of 0.023 L (SD of 0.07 L). There was no significant difference between the groups in FEV₁ (p=0.56 for percentage change; p=0.36 for absolute change). Conclusion: The addition of 500 μg ipratropium to 5 mg salbutamol in subsequent nebulisers adds no benefit to pulmonary function after the initial nebuliser of both bronchodilators in the treatment of COAD in the ED.     

Which apparatus for inhaled pentamidine? A comparison of pulmonary deposition via eight nebulisers

Aerosolised pentamidine 300 mg in 5 or 6 ml solution was administered via 8 different nebuliser systems to 12 patients with acquired immunodeficiency syndrome. Using 99mTc human serum albumin as an indirect marker for pentamidine, pulmonary, extrapulmonary (gastric and oropharyngeal) and alveolar deposition of pentamidine were measured using a gamma camera. Side effects (visual analogue scales) and changes in lung function associated with each treatment were also quantified. Deposition was completed more rapidly with the ultrasonic than the jet nebulisers. Mean total pulmonary depositions (mg +/- SEM) were Respirgard II, 6.1 +/- 0.5; Centimist, 7.3 +/- 1.0, System 22 Mizer, 14.3 +/- 2.1; System 22 Mizer with particle separator; 4.5 +/- 0.4; System 22 Mizer with Optimist 2, 6.3 +/- 0.9; Fisoneb, 6.0 +/- 1.2; Pentasonic (Portasonic); 4.6 +/- 0.9; Samsonic, 2.9 +/- 0.4. Differences between the nebulisers for peripheral lung and alveolar deposition reflected this pattern. Side effects scores were largest with System 22 Mizer, Pentasonic (Portasonic), and Fisoneb, and these produced the greatest oropharyngeal and gastric deposition. The largest reductions in lung function were associated with System 22 Mizer. A 300 mg dose of pentamidine nebulised via Respirgard II is known to be effective prophylaxis for Pneumocystis carinii pneumonia when given once monthly. Our results show that equivalent pulmonary deposition can be produced by other nebulisers. System 22 Mizer gives over twice the deposition associated with Respirgard II, and used with a pentamidine dose of 150 mg is likely to produce an adequate lung dose for prophylaxis. This nebuliser, however, is associated with more marked side effects.     

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.     

Formoterol (OXIS) Turbuhaler as a rescue therapy compared with salbutamol pMDI plus spacer in patients with acute severe asthma

Formoterol has a similar onset of effect to salbutamol but a prolonged duration of action. However, the relative efficacy of the two drugs in acute severe asthma is not known. This double-blind, double-dummy study compared the safety and efficacy of the maximum recommended daily dose of formoterol and a predicted equivalent dose of salbutamol in 88 patients presenting to the emergency department with acute severe asthma. Patients were randomized to formoterol 54 microg via Turbuhaler or salbutamol 2400 microg via pressurized metered dose inhaler (pMDI) plus spacer in three equal doses over 1 h. Following the full dose, mean FEV1 at 75 min increased by 37% for formoterol and 28% for salbutamol (P = 0.18). The maximum increase in FEV1 over 4 h was significantly greater with formoterol compared with salbutamol (51% vs. 36%, respectively P < 0.05) and formoterol was as effective as salbutamol at improving symptoms and wellbeing. Both treatments were well tolerated. Formoterol caused a greater decrease in serum potassium (difference -0.2 mmol/l). In severe acute asthma, bronchodilator therapy with high-dose (54 microg) formoterol Turbuhaler provided equally rapid improvements in lung function of greater magnitude over 4 h than high-dose (2400 microg) salbutamol pMDI plus spacer.     

Comparison of Ipratropium Bromide and Salbutamol by Aerosolized Solution

Abstract: lpratropium bromide (0,125 mg, 0.25 mg and 0.5 mg) and salbutamol (5 mg) by aerosolized solution produced equivalent peak broncho-dilatation between one and two hours after administration to ten patients with chronic partially reversible airways obstruction. The duration of action of the two higher doses of ipratropium bromide (0.25 mg —6 hours; 0.5 mg — 5 hours) was significantly greater than salbutamol (4 hours). FVC increases with both drugs and saline were greater than FEV, increases which may indicate dilatation of small peripheral airways or removal of bronchial mucus from these sites after coughing. A dose of 0.25 mg ipratropium bromide as an aerosolised solution is recommended for clinical use .