Salbutamol Metered-dose Inhaler Research Articles

The environmental impact of inhalers for asthma: A green challenge and a golden opportunity.

The propellants in metered-dose inhalers (MDIs) are powerful greenhouse gases, which account for approximately 13% of the NHS's carbon footprint related to the delivery of care. Most MDI use is in salbutamol relievers in patients with poorly controlled disease. The UK lags behind Europe in this regard, with greater reliance on salbutamol MDI and correspondingly greater greenhouse gas emissions, roughly treble that of our European neighbours. There has been a broad switch towards MDIs in asthma treatment in the UK over the last 20 years to reduce financial costs, such that the treatment for two-thirds of asthma patients in the UK is dominated by salbutamol MDI. Strategies that replace overuse of reliever MDIs with regimes emphasising inhaled corticosteroids have the potential to improve asthma control alongside significant reductions in greenhouse gas emissions. Real-world evidence shows that once-daily long-acting combination dry-powder inhalers (DPIs) can improve compliance and asthma control, and reduce the carbon footprint of care. Similarly, maintenance and reliever therapy (MART), which uses combination reliever and inhaled steroids in one device (usually a DPI), can simplify therapy, improve asthma control and reduce greenhouse gas emissions. Both treatment strategies are popular with patients, most of whom would be willing to change treatment to reduce their carbon footprint. By focussing on patients who are currently using high amounts of salbutamol MDI and prioritising inhaled steroids via DPIs, there are golden opportunities to make asthma care in the UK more effective, safer and greener.

Comparison of clinical efficacy of nebulised salbutamol and salbutamol metered dose inhaler in children with mild or moderate exacerbation of bronchial asthma

Background: Bronchial asthma is the commonest chronic disease in industrialized nations. Aerosol therapy has revolutionized the treatment of bronchial asthma in children as in adults. Even though nebulisation is a simple technique, it is expensive and there is a need for power source. The aim of the study was to compare the clinical efficacy of nebulised salbutamol and salbutamol metered dose inhaler (MDI) in children with mild or moderate exacerbation of Bronchial asthma.Methods: This study was a hospital based randomized control study carried out between March 2009 to December 2009 on children attending OP or casualty of Government Medical College, Alappuzha with mild or moderate exacerbation of bronchial asthma.Results: 60 subjects were selected for the study out of which 30 were assigned to salbutamol MDI group and the other 30 to salbutamol nebulisation group. After the administration of drug, all the studied variables showed significant improvement in both groups (p value <0.001). Percentage predicted PEFR increased by about 27% in nebulisation group and 26% in MDI group; however this difference was not statistically significant (P value = 0.99).Conclusions: In this study we concluded that the efficacy of salbutamol in mild or moderate acute exacerbation of asthma was similar when the drug is delivered either by nebuliser or MDI with spacer.

An In Vitro Aerosolization Efficiency Comparison of Generic and Branded Salbutamol Metered Dose Inhalers

Background: Due to the high rate of pulmonary diseases, respiratory drug delivery systems have been attracted excessive attention for the past decades. Because of limitations and growing drug bill, physicians are encouraged to prescribe generically whenever possible. The purpose of this study was to evaluate whether there was any significant difference in aerosolization performance between a reference brand Salbutamol (A) Metered Dose Inhalers (MDIs) and two generic products (B and C). Methods: The aerosolization performance of MDIs was evaluated by calculating aerosolization indexes including fine particle fraction (FPF), fine particle dose (FPD), geometric standard deviation (GSD) and mass median aerodynamic diameters (MMAD) by using the next generation impactor. Results: Although aerosolization indexes of MDI A were superior than the Iranian brands, but the differences were not statistically significant. Conclusion: These results verified that generic MDIs deliver similar quantities of Salbutamol to the reference brand and aerosolization performance parameters of generic Salbutamol MDIs did not differ significantly from the reference brand.

P165 The reliability and performance of electronic monitors of inhaler use in a real world asthma clinical trial

Introduction Electronic monitoring is one method to measure the use of inhaled therapy in asthma patients in clinical trials, though the reliability of these devices has been variable. Implementation of trial quality control processes and reporting on the performance of electronic monitors during patient use may help to better understand their utility and limitations. The Smartinhaler Tracker is an electronic monitor for metered dose inhalers (MDIs) that records the date, time and number of actuations to the nearest second. Objectives In a recently completed 24-week real-world randomised controlled trial of 303 asthma patients at risk of severe exacerbations, Smartinhaler Tracker electronic monitors were used to measure actual use of budesonide/formoterol and salbutamol MDI therapy with two treatment regimens. Our aim is to report on the performance of these monitors, based on the implementation of extensive pre-trial and within-trial validation protocols for their use. Methods Pre-study use checks involved two actuations of the MDI, with a further two actuations performed at least two hours later. Within-study monitor checks, performed prior to dispensing at follow-up clinic visits, included a computerised check of monitor clock function, actuation accuracy and battery life. Within-study data checks, performed after use of MDIs by participants during the trial, involved computerised checks of monitor clock function prior to data upload. Results 2678/2728 (98.2%) monitors passed pre-study use checks; 46/50 monitors failed pre-study checks either because they did not record actuations that were performed, or erroneously recorded extra actuations. 76/2642 (2.9%) monitors dispensed to participants failed within-study monitor checks; 33/76 monitors failed because the battery was not fully charged. 51/2642 (1.9%) monitors failed data upload checks, mostly as a result of fluid immersion during participant use. 93/2642 (3.5%) monitors were lost or thrown away by participants. Complete data was available from 2498/2642 (94.5%) of dispensed monitors and 2498/2549 (98.0%) of returned monitors. Conclusions The Smartinhaler Tracker is a reliable monitor for measuring MDI use in a real-world asthma clinical trial. Implementation of extensive monitor and data-checking protocols reduces data loss. The use of validated and reliable electronic monitors is the optimal method to assess patterns of inhaled medication use.

P164 Use of beta-agonists prior to hospital attendance for severe exacerbations of asthma: insights from a randomised controlled trial using electronic monitoring of inhaler use

IntroductionObservational studies have reported that the overuse of inhaled beta-agonists during severe asthma is a common feature associated with a fatal outcome. However, patterns of actual use of beta-agonists prior...

Evaluating a clinical practice intervention to promote delivery of salbutamol by metered-dose inhalers with holding chambers in a pediatric emergency department

The primary objective of this study was to quantify the impact of a clinical practice intervention to promote the delivery of salbutamol by metered-dose inhaler (MDI) in a pediatric emergency department (PED). A secondary objective was to retrospectively document the components of the intervention. PED inventory data for salbutamol inhalation solution (nebules), MDIs, and holding chambers were obtained from the pharmacy department. Patient data were obtained from the hospital's decision support unit. Interrupted time series analysis was used to evaluate trends in salbutamol inventory data, patient triage acuity, and hospital admissions from January 1, 2003, to May 31, 2010. Interviews and administrative documents were used to identify components of the intervention, which began in 2006. There was a 1,215% increase in the proportion of salbutamol delivered as MDIs compared to total inhaled salbutamol (MDI plus nebulization solution) following the intervention (95% CI 1,032% to 1,396%, p < 0.001). Increases in salbutamol MDI use were associated with the implementation of an institution-specific asthma care map. A relative decrease of 32% in the hospital admission rate (absolute -7.25%: 95% CI -8.31 to -6.19, p < 0.001) was associated with the change in salbutamol MDI use and the use of the asthma care map. A multifaceted intervention, designed and implemented by local PED clinical leaders, resulted in a pronounced change in salbutamol inhalation practice, with an associated decrease in admission rates. This intervention demonstrated many of the criteria for successful health system change. Findings from this research may be contextualized to inform change elsewhere.

Medication Records in the Emergency Department: Agreement Between Paper-Based Charts and Automated Dispensing Device

Research exploring the agreement between traditional medication records and electronic records generated by an automated dispensing device has been limited. To evaluate the extent of agreement between medication administration records written in paper-based emergency department charts and records generated by an automated dispensing device with regard to the presence or absence of a single, prespecified medication. Medication administration records in paper-based emergency department charts and medication dispensation records generated by an automated dispensing device were evaluated for concordance. The primary outcome measure was agreement between the 2 sources with regard to the presence or absence of a record for salbutamol by metered-dose inhaler (MDI) for randomly selected patients who presented to a pediatric emergency department with wheeze-related illness from January 1, 2008, to December 31, 2009. In total, 1172 patient visits met the inclusion criteria. Of these, records for 1013 visits showed agreement between the paper-based emergency department chart and the dispensation record of the automated dispensing device (kappa = 0.71, 95% confidence interval 0.67-0.75). This value did not meet the target kappa of 0.80. Stratification by time of day, day of week, month, season, or year of presentation at triage or by triage level or disposition (whether or not the patient was admitted to the hospital ward) did not significantly affect the level of agreement between the 2 sources. Agreement between records of salbutamol MDI administration in paper-based charts and dispensation records from an automated dispensing device was substantial, but discrepancies were present. There are significant quality management, legal, clinical, and research reasons to strive for concordance between multiple records with respect to medication use in the emergency department. Data generated by automated dispensing devices have potential value for research, but their strengths and limitations need to be understood.

Oral thermal injury associated with puncture of a salbutamol metered‐dose inhaler in a dog

To describe the clinical features, diagnostic work-up, treatment, and outcome of a dog with oral thermal injury secondary to chewing on a salbutamol metered-dose inhaler (MDI). A Boxer dog was presented after chewing on a salbutamol MDI. The dog was anxious, tachycardic and had moderate hypokalemia. The dog was treated with potassium supplementation and discharged after 24-hour hospitalization. Five hours after the discharge, the dog represented for dysphagia, anorexia, cervical pain, and a left-sided head tilt. Oral examination revealed edematous and erythematous swelling of the soft palate causing airway compromise; histopathology demonstrated vascular necrosis and infarction. The dog was treated with supportive care including the placement of a tracheostomy tube. The dog recovered fully and was discharged 8 days after initial presentation. Salbutamol toxicity has been documented previously in dogs but oral thermal injury associated with a salbutamol MDI has not been reported in dogs. Although a rare complication, dogs who have been exposed to MDIs should have a thorough oral exam and be monitored closely for signs of respiratory compromise.

SALBUTAMOL INHALER MISUSE: A PERSISTING PROBLEM?

We have become concerned that misuse of salbutamol metered dose inhalers (MDIs) may be more widespread than previously thought. Dependency upon salbutamol inhalers has been previously described 1. The precise substance of dependence was difficult to establish at this time as it was unclear whether salbutamol, or the associated propellant, was the responsible trigger for the misuse of the medicine. It has been argued that since salbutamol does not distribute well in animal brains 2, and addictive effects have also been produced by other drugs delivered by aerosol, that the propellant was the most likely responsible agent of abuse 3. After the adoption and steady implementation of the Montreal protocol by the UK and other countries in 1989 4, most MDIs now use HFA 134a (a hydrofluorocarbon less damaging to ozone) as a propellant. Our clinical experience with a group of homeless people in the UK has drawn us to consider that salbutamol MDI misuse may continue despite this change. Collectively, alongside other volunteers, we provide healthcare services to a leading UK homeless charity at Christmas time over an eight day period, offering voluntary clinical services to homeless people in need. Following our 2006 service, anecdotally we noted that homeless individuals who had substance misuse problems appeared to be frequently requesting salbutamol MDIs, although clinicians did not always feel they were necessary. Requests were often made without any clear complaint and were typically accompanied by requests for drugs with commonly recognised abuse potential, such as benzodiazepines and opiates. Furthermore, one of the authors found a discarded blue MDI with a charred mouthpiece in one of the clinical areas. The appearance of the apparently modified MDI was reminiscent of other homemade apparatus used for inhaling volatile substances. The charity provides clinical services across eight separate centres in London. One centre is co-ordinated to particularly serve the needs of individuals with alcohol and drug problems. Following our 2007 episode we noted that salbutamol MDIs were prescribed much more frequently at the alcohol and drug centre (13 prescriptions) than at each of the other centres (a mean of five prescriptions per centre). Although we acknowledge that there are many potential confounders of this recent observation, including varying clinical need and clinical practices, we believe that it could in part be related to salbutamol MDI misuse. The potential articles of interest may include the plastic MDI casing (to manufacture apparatus to inhale volatile chemicals), the propellants or alternative aspects of the medicine. We are of the opinion that clinicians should be vigilant when prescribing MDIs to individuals known or suspected to misuse volatile substances, and consider further research on salbutamol MDI misuse is required. Stewart Glaspole has acted as a consultant to a number of pharmaceutical companies. His association with these companies is in no way connected to the content of this paper.

A pilot study comparing the antispasmodic effects of inhaled salmeterol, salbutamol and ipratropium bromide using different aerosol devices on muscarinic bronchoconstriction in healthy cats

This study compared the duration and magnitude of the antispasmodic effects of salmeterol (SLM), salbutamol (SAL), ipratropium bromide (IB) and the combination of SAL and IB (SAL/IB) against carbachol-induced bronchoconstriction in healthy cats, and investigated the gain in efficacy using a two or fourfold increase in drug dosages. The drug regimens used were: (1) SLM 25 μg, SAL 100 μg, IB 20 μg and SAL/IB 100 μg/20 μg for bronchodilators delivered by a metered-dose inhaler (MDI); (2) SAL 3.75 mg and IB 62.5 μg for nebulised (NEB) medications. To monitor the bronchodilator effect, airway responsiveness was assessed at different time points using barometric whole-body plethysmography and calculation of the concentration of inhaled carbachol inducing a 300% increase of baseline Penh (enhanced pause), an estimator of airflow limitation. Maximum C-Penh300 was recorded 15 min after NEB SAL, IB MDI, NEB IB and 1 h after SAL MDI and 4 h after SLM MDI, respectively. C-Penh300 was significantly different from control values (without treatment) up to 24 h for SLM MDI, 8 h for IB MDI and 4 h for other drugs. In terms of efficacy, SAL/IB MDI showed a synergistic antispasmodic effect at 15 min, 4 h and 8 h after administration. A fourfold increase of the initial dose of IB MDI and NEB IB significantly increased C-Penh300. Despite a fourfold dose increase, SLM displayed the weakest degree of bronchoprotection compared to other bronchodilators. The study provides evidence that inhaled bronchodilators are efficient at preventing muscarinic-induced bronchospasm in healthy cats and that SAL and IB appear to be short-acting bronchodilators in contrast to SLM.

A Study of Patient Responses to a Perceived Change in Salbutamol Metered Dose Inhalers

Experience in the clinic reveals that some patients have attributed negative changes in their respiratory health status to generic substitution of inhaled medications, even though — from a pharmacological perspective — therapeutic equivalence would be expected. The objective of this study was to evaluate patient-reported changes in efficacy or toxicity following a perceived switch of an inhaled drug product. Forty-eight patients with air flow limitation had their usual brand of salbutamol metered-dose inhaler (MDI) replaced for one week with a new MDI. Patients were not informed that the replacement MDI was exactly the same brand as their usual MDI, and the product identity was disguised by a label. Forced expiratory volume in one second, respiratory symptoms and MDI use were compared between the week when the patients knew they were using their usual brand of MDI and the week they were using the perceived new MDI. Patient MDI preference was assessed at the end of the study. Even though there was no change in the brand of salbutamol MDI, 46 per cent of patients thought that the new MDI was better at managing their symptoms, 27 per cent thought that the new MDI was worse and 27 per cent perceived no difference (p&lt;0.05 for rejecting the null hypothesis that all responses would be for no difference). Seventy per cent of patients stated that they had a preference for one MDI over the other, even though there had been no change in inhaler. Factors other than product differences are likely to be responsible for patient claims of changes in respiratory health status subsequent to generics substitution with inhaled medications when equivalent products are used. If such changes are reported following the introduction of a new generic product, the changes may be incorrectly attributed to the new product, confounding the ability to assess the quality of the new product in post-marketing evaluation.

Metered dose inhalers: A need for dose counters

This study investigated the ability of patients to assess when a metered dose inhaler (MDI) is empty. A total of 17 patients assessed, by shaking, the number of doses remaining in a salbutamol MDI that had been partially emptied. Another 100 patients were asked to collect all salbutamol MDIs they considered to be empty and would have thrown away. These MDI canisters were weighed and the number of doses that had been used was estimated. Using the 'shaking method', patients overestimated the amount remaining by around 40 doses. The mean number of doses delivered from an MDI labelled to contain 200 doses before it was discarded was 224 (range, 155-289). These findings confirm that patients are unable to determine when an MDI should be discarded, resulting in insufficient drug delivery at the end of the life of an MDI for the majority of patients, and wastage of the drug for others.

Formoterol as dry powder oral inhalation compared with salbutamol metered-dose inhaler in acute exacerbations of chronic obstructive pulmonary disease

Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are managed with increased doses or frequency of the patient's existing bronchodilator therapy. The use of formoterol in the treatment of mild acute exacerbations of COPD has been suggested; however, a comparison of cumulative doses of formoterol with salbutamol, the gold standard bronchodilator agent for this pathologic condition, is still lacking. Objective: The aim of the study was to compare the inhaled beta 2-agonists salbutamol (rapid onset, short duration of action) and formoterol (rapid onset, long duration of action), both used as needed in patients attending outpatient clinics because of mild acute exacerbations of COPD (Anthonisen exacerbation type I or II). Methods: A dose-response curve to formoterol via Turbuhaler ® or salbutamol via pressurized metered-dose inhaler (pMDI) was constructed. On 2 consecutive days, the patients received, in randomized order, both of the following active dose regimens: A = 12 + 12 + 24 μg formoterol via Turbuhaler (48-μg cumulative metered dose); B = 200 + 200 + 400 μg salbutamol via pMDI (800-μg cumulative metered dose). Dose increments were given at 30-minute intervals, with measurements made 25 minutes after each dose. The maximum forced expiratory volume in 1 second (FEV 1) value during the dose-response curve to formoterol or salbutamol was chosen as the primary outcome variable to compare the 2 treatments. Oxygen saturation by pulse oximetry (SpO 2) and pulse rate were also measured at each assessment period. Every adverse event, either reported spontaneously by the patients or observed by the investigators, was recorded. Results: Sixteen patients (2 women, 14 men) aged 51 to 77 years (most older than 65 years) participated in the study. Both formoterol and salbutamol induced a large, significant, dose-dependent increase in FEV 1, inspiratory capacity (IC), and forced vital capacity (FVC). There was no significant difference between FEV 1, IC, and FVC values after 48 μg formoterol and 800 μg salbutamol. There was no significant difference in FEV 1 after 24 and 48 μg formoterol and 800 μg salbutamol; however, the difference in FEV 1 after 24 and 48 μg formoterol was significant. Neither heart rate (mean differences from baseline after 48 μg formoterol, 1.9 beats/min [95% CI, −3.4, 7.2] and 800 μg salbutamol, 3.7 beats/min [95% CI, −1.1, 8.5]) nor SpO 2 (mean percentage differences from baseline after 48 μg formoterol, −0.37% [95% CI, −1.22, 0.47] and 800 μg salbutamol, −0.75% [95% CI, −1.73, 0.23]) changed significantly. However, SpO 2 decreased below 90% in 2 patients after the highest dose of formoterol and in 1 patient after the highest dose of salbutamol. Conclusions: In this small, selected group of patients with mild acute exacerbations of COPD, formoterol via Turbuhaler induced a fast bronchodilation that was dose dependent and not significantly different from that caused by salbutamol. Furthermore, formoterol appeared to be as well tolerated as salbutamol.

Cost effectiveness of asthma treatment with a breath-actuated pressurised metered dose inhaler (BAI) - a prescribing claims study of 1856 patients using a traditional pressurised metered dose inhaler (MDI) or a breath-actuated device

SummaryHigh levels of asthma resource use in the UK indicate that optimal control is not being achieved. This may be at least partly due to improper inhaler technique with metered dose inhalers (MDIs). One solution may be to prescribe inhalers that are easier to use, i.e. breath-actuated inhalers (BAIs). This analysis used a primary care database to assess the extent to which BAI (Easi-Breathe®) patients differ from MDI patients in terms of their asthma related-resource costs. A child using the BAI had annual asthma medication costs that were £16.83 higher than a child using an MDI and an adult using the BAI had medication costs that were £3.02 higher. This was expected due to the higher unit cost of the salbutamol BAI compared to the salbutamol MDI. However, a breakdown of medication costs showed that antibiotic and oral steroid costs were lower in the BAI group. The higher medication costs for BAI users were offset by the lower non-medication costs (£46.57 and £69.09 less for children and adults using the BAI, respectively). The result was a lower cost overall for BAI users compared to MDI users. Asthma is a therapeutic area which imposes a significant burden on both patients and health services. Given its increasing prevalence and morbidity levels, it is important to ensure that all possible steps are taken by clinicians to reduce this burden wherever possible. Such steps may include the prescription of BAIs.Easi-Breathe® is a registered trademark of IVAX Pharmaceuticals UK Ltd.

Clinical characteristics of asthmatic patients prescribed various beta-agonist metered-dose inhalers at Yamagata University Hospital.

To determine the prescription characteristics of beta-agonist metered-dose inhalers (MDI), we retrospectively investigated all prescriptions containing one of five types of beta-agonist MDIs available at Yamagata University Hospital in 1997, as well as patients' characteristics. The total number of asthmatic patients was 225 (age, 11-79, mean, 47.2) in 1997. Fenoterol MDI was prescribed to patients who visited the hospital at regular periods and had more severe asthma. Isoprenaline MDI also was not prescribed for first-time patients. Patients who were prescribed tulobuterol MDI had mild or moderate asthma and some of them were only occasional or first-time visitors. Salbutamol and procaterol MDIs were also prescribed for first-time patients; however, tulobuterol MDI was the most frequently prescribed for first-time patients. Patients prescribed fenoterol and isoprenaline MDIs had adequate knowledge of proper asthma management, because sufficient information had been provided about the use of MDIs in the past. Patients prescribed tulobuterol MDI should be provided with detailed instructions because they had little knowledge of handling MDIs and self-management of asthma as many of them were first or intermittent visitors. Patients prescribed salbutamol or procaterol MDIs should be evaluated regarding their past medications and some of them should be instructed regarding the use of the MDI. Although these clinical aspects might be applicable only to our hospital, the same or other prescription patterns will be found in other hospitals and/or by other physicians. Adequate instructions to individual patients who are prescribed a particular beta-agonist MDI should be provided by the medical staff, especially to outpatients, to reduce hospitalization and death from asthma.

Mast cell tryptase release and asthmatic responses to allergen increase with regular use of salbutamol

Background: Increased asthmatic responses to allergen, both early and late, have been demonstrated after regular use of β2-agonists in as few as 7 days. Desensitization of β2-adrenergic receptors on airway mast cells may contribute to this effect by allowing greater release of mast cell mediator on allergen-induced degranulation. Tryptase released from lung mast cells can be measured in serum 1 hour after allergen challenge and serves as a marker of mast cell degranulation. Objective: To examine the effect of regular treatment with salbutamol, a β2-agonist, on mast cell mediator release after allergen challenge and its influence on the early asthmatic response (EAR) and the late allergic response, we measured the EAR, serum tryptase levels, the 7-hour FEV1, and sputum tryptase levels and cell profiles. Methods: We conducted a placebo-controlled, double-blind, randomized cross-over comparison of treatments for 10 days with either a salbutamol metered-dose inhaler (100 μg, 2 puffs 4 times daily) or a matched placebo inhaler with at least a 7-day washout between treatments. Atopic subjects (n = 14) with mild-to-moderate asthma performed same-dose allergen inhalation tests after both treatments 12 to 15 hours after the last dose of study inhaler. Baseline and 7-hour FEV1 and the EAR to allergen were measured by using spirometry; venous blood was drawn at 1 hour for analysis of serum tryptase; and sputum was induced and collected at 1 and 7 hours. Results: Salbutamol treatment resulted in a significantly greater EAR (20% ± 1.6% [SEM] vs 15% ± 2.1%; P = .047); increased 1-hour serum tryptase levels (9.09 ± 1.57 vs 7.52 ± 1.12 μg/L; P = .011); increased proportions of eosinophils in the 7-hour sputum sample (39.1% ± 5.1% vs 28.4% ± 4.4%; P < .05); increased proportion of metachromatic cells in the 7-hour sputum sample (4.4% ± 1.1% vs 2.2% ± 0.6%; P = .032); and lower 7-hour FEV1 (2.77 ± 0.18 vs 2.97 ± 0.20 L; P = .014). Baseline FEV1 was not significantly different after salbutamol treatment compared with values after placebo treatment (2.90 ± 0.20 vs 3.00 ± 0.19 L; P = .11). Conclusion: Regular 10-day treatment with salbutamol increases the allergen-induced release of mediator from airway mast cells, and this is reflected in an increased EAR to allergen. Late-phase responses to allergen were also enhanced, as demonstrated by decreased 7-hour FEV1 and increased eosinophilia and percentage of metachromatic cells in the 7-hour sputum sample. Increased allergen-induced mast cell degranulation could, in part, explain the increased asthmatic responses to allergen after β2-agonist treatment and could contribute to the deterioration of asthma control that is associated with regular use of β2-agonist by potentiating allergic inflammation. (J Allergy Clin Immunol 2000;106:57-64.)

Efficacy of Inhaled Steroids (Beclomethasone Dipropionate) for Treatment of Mild to Moderately Severe Asthma in the Emergency Department: A Randomized Clinical Trial

Study objective: To examine the efficacy of an inhaled steroid, when added to a standard regimen of β-agonist therapy, in the treatment of patients with mild to moderately severe asthma in the emergency department. Methods: A convenience sample of adult patients with asthma (FEV 1 %predicted 40% to 69%) presenting to the ED was randomly assigned in a double-blind fashion into 2 treatment groups. The first group received 2.5 mg nebulized salbutamol plus 1 mg (4 puffs) of beclomethasone dipropionate (BDP) at baseline, 30 minutes, and at 1, 2, and 4 hours, delivered by a metered-dose inhaler (MDI) attached to a spacer device (Vent-AH-aler, Glaxo). The second group was given the same salbutamol regimen plus MDI placebo through the Vent-AH-aler. The primary endpoint was improvement in FEV 1 %predicted at 6 hours. Results: Of 54 patients enrolled, 28 were assigned to the BDP group and 26 to the placebo group. Spirometry improved significantly in both groups over the 6 hours compared with baseline (ANOVA, P <.001). At 6 hours, the mean absolute improvement in FEV 1 %predicted for BDP was 18% versus 17% for placebo (95% confidence interval for the absolute difference of 1% [–8% to 10%]). The proportion of patients in the BDP group who were hospitalized was 7% compared with 19% for patients in the placebo group (95% confidence interval for the difference of 12% [–6%, 30%]). Conclusion: In this group of patients with mild to moderately severe asthma, 5 mg BDP delivered by MDI during the initial 4 hours of an emergency visit was of no added benefit over standard therapy, as measured by improvement in FEV 1 %predicted at 6 hours. However, a trend toward a difference in admission favoring BDP was observed. [Afilalo M, Guttman A, Colacone A, Dankoff J, Tselios C, Stern E, Wolkove N, Kreisman H: Efficacy of inhaled steroids (beclomethasone dipropionate) for treatment of mild to moderately severe asthma in the emergency department: A randomized clinical trial. Ann Emerg Med March 1999;33:304-309.]

In Vitro Comparison of Beclomethasone and Salbutamol Metered-Dose Inhaler Aerosols Inhaled During Pediatric Tidal Breathing From Four Valved Holding Chambers

To determine the amount of salbutamol or beclomethasone delivered from metered-dose inhalers (MDIs) in particle sizes appropriate for inhalational treatment with four common holding chambers (AeroChamber, OptiChamber, Space Chamber, E-Z Spacer) when used under simulated pediatric tidal breathing conditions. Five devices of each type were tested with salbutamol (100 microg, Glaxo-Wellcome) and beclomethasone (50 microg, Glaxo-Wellcome) MDIs. Each device was connected to face replicas representative of 7-month-old (infant), 2-year-old (toddler), and 4-year-old (child) children and aerosol inhaled into a cascade impactor (Anderson) using a valve system and simulated tidal breathing patterns representative of children of these ages. Amounts of drug inhaled in fine particles varied significantly between devices and ages (p < 0.01), eg, for beclomethasone, from 4 microg (infant, Space Chamber) to 8 microg (toddler, OptiChamber), and for salbutamol, from 18 to 36 microg. The AeroChamber and OptiChamber behaved quite similarly, delivering more drug in the fine particles than the other two devices, and having insignificant variations in these amounts with age (p > 0.05). Amounts of drug inhaled in fine particles during pediatric tidal breathing from valved holding chambers are dependent on the holding chamber model, the drug used, and the breathing pattern, although dependence on the breathing pattern is relatively small for some of the devices tested.

CME questions to asthma

Background: Increased asthmatic responses to allergen, both early and late, have been demonstrated after regular use of β2-agonists in as few as 7 days. Desensitization of β2-adrenergic receptors on airway mast cells may contribute to this effect by allowing greater release of mast cell mediator on allergen-induced degranulation. Tryptase released from lung mast cells can be measured in serum 1 hour after allergen challenge and serves as a marker of mast cell degranulation. Objective: To examine the effect of regular treatment with salbutamol, a β2-agonist, on mast cell mediator release after allergen challenge and its influence on the early asthmatic response (EAR) and the late allergic response, we measured the EAR, serum tryptase levels, the 7-hour FEV1, and sputum tryptase levels and cell profiles. Methods: We conducted a placebo-controlled, double-blind, randomized cross-over comparison of treatments for 10 days with either a salbutamol metered-dose inhaler (100 μg, 2 puffs 4 times daily) or a matched placebo inhaler with at least a 7-day washout between treatments. Atopic subjects (n = 14) with mild-to-moderate asthma performed same-dose allergen inhalation tests after both treatments 12 to 15 hours after the last dose of study inhaler. Baseline and 7-hour FEV1 and the EAR to allergen were measured by using spirometry; venous blood was drawn at 1 hour for analysis of serum tryptase; and sputum was induced and collected at 1 and 7 hours. Results: Salbutamol treatment resulted in a significantly greater EAR (20% ± 1.6% [SEM] vs 15% ± 2.1%; P = .047); increased 1-hour serum tryptase levels (9.09 ± 1.57 vs 7.52 ± 1.12 μg/L; P = .011); increased proportions of eosinophils in the 7-hour sputum sample (39.1% ± 5.1% vs 28.4% ± 4.4%; P < .05); increased proportion of metachromatic cells in the 7-hour sputum sample (4.4% ± 1.1% vs 2.2% ± 0.6%; P = .032); and lower 7-hour FEV1 (2.77 ± 0.18 vs 2.97 ± 0.20 L; P = .014). Baseline FEV1 was not significantly different after salbutamol treatment compared with values after placebo treatment (2.90 ± 0.20 vs 3.00 ± 0.19 L; P = .11). Conclusion: Regular 10-day treatment with salbutamol increases the allergen-induced release of mediator from airway mast cells, and this is reflected in an increased EAR to allergen. Late-phase responses to allergen were also enhanced, as demonstrated by decreased 7-hour FEV1 and increased eosinophilia and percentage of metachromatic cells in the 7-hour sputum sample. Increased allergen-induced mast cell degranulation could, in part, explain the increased asthmatic responses to allergen after β2-agonist treatment and could contribute to the deterioration of asthma control that is associated with regular use of β2-agonist by potentiating allergic inflammation. (J Allergy Clin Immunol 2000;106:57-64.)

Nebulized Wet Aerosol Treatment in Emergency Department—Is It Essential?: Comparison With Large Spacer Device for Metered-Dose Inhaler

To determine the efficacy of a metered-dose inhaler (MDI) with a large spacer device as compared to nebulized wet aerosols in the treatment of an unselected population with severe airflow limitation. Randomized, double blind, placebo-controlled trial. University Hospital Department of Emergency Medicine (DEM). Fifty patients, referred to the DEM between October 1, 1994 and March 31, 1995 with a severe, acute obstructive pulmonary event. Thirteen patients were diagnosed as having COPD; 37 patients were diagnosed as having asthma. Patients received either placebo MDI through a 750-mL cone-shaped spacer (Glaxo) [2 puffs] and nebulized salbutamol aerosol 0.5 mL in 1.5 mL saline solution (group 1, n=25) or salbutamol MDI and 0.5 mL saline solution in 1.5 mL saline solution administered in the same manner as above (group 2, n=25). The above treatment was repeated three times every 15 min, unless side effects appeared. Upon enrollment into the study, the FEV1 in group 1 was 0.78+/-0.7 L (mean+/-SD), 32% of predicted, and in group 2, 0.74+/-0.51 L, 29% of predicted (p=0.83). The FEV1 values after the first, second, and third interventions were as follows: in group 1, 1.18+/-0.99 L, 1.40+/-0.8, and 1.47+/-0.79, respectively, and in group 2, 1.17+/-0.99 L, 1.46+/-1.01, and 1.54+/-0.79 (p=0.83, 0.36, and 0.48, respectively). We observed no difference in spirometric measurements between the two groups at any time. Even in the setting of the unselected group of patient referrals to the DEM for episodes of severe airflow limitation, the clinical and the objective bronchodilator responses to the administration of salbutamol are independent of the method of delivery: MDI with a large spacer vs aerosol nebulization.