Review: Pressurized metered-dose inhalers are as effective as other handheld inhalers for β2-agonist bronchodilator use in asthmaPDF
ACP J Club. 2002 May-June;136:111. doi:10.7326/ACPJC-2002-136-3-111
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• Companion Abstract and Commentary: Review: Pressurized metered-dose inhalers are as effective as other handheld inhalers for corticosteroid use in asthma
Ram FS, Wright J, Brocklebank D, White JE, on behalf of the National Health Technology Assessment Inhaler Review Group. Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering β2 agonist bronchodilators in asthma. BMJ. 2001. Oct 20;323:901-5. [PubMed ID: 11668134]
In patients with stable asthma, is the standard chlorofluorocarbon-containing pressurized metered-dose inhaler (PMDI) as effective as other handheld inhaler devices, including chlorofluorocarbon-free PMDIs, for delivering β2-agonist bronchodilators?
Studies published from 1966 to December 2000 were identified by searching the Cochrane Airways Group trials database (derived from MEDLINE, EMBASE/Excerpta Medica, CINAHL; hand searches of 20 relevant journals and proceedings of 3 respiratory societies; and review of the bibliographies of included trials). MEDLINE, EMBASE/Excerpta Medica, CINAHL, and 17 online respiratory Web sites were also independently searched, and pharmaceutical companies that manufacture inhaled asthma drugs were contacted for unpublished studies.
Studies in any language were selected if they were laboratory-, hospital-, or community-based randomized controlled trials of children or adults that compared delivery of β2-agonist bronchodilators by standard PMDI (with or without a spacer) with any other handheld inhaler. Trials comparing different doses of inhaled drug and those that used challenge testing were also included.
2 reviewers independently extracted data on study design, patient characteristics, details of the intervention, study duration, outcomes, and quality. Outcomes included lung function (FEV1), quality-of-life measurements, symptom scores, drugs for additional relief, steroid requirements, nocturnal awakening, acute exacerbations, days off work or school, treatment failures, patient compliance, patient preferences, adverse effects, bronchial hyperreactivity, and systemic bioavailability.
89 articles describing 84 studies met the selection criteria. 71 trials involved adults, and 13 involved children. In most trials, patients had mild-to-moderate asthma (baseline FEV1 > 50% of predicted). Meta-analyses were done using a fixed-effects model. In both adults and children, standard PMDIs did not differ from any of the other 10 handheld inhaler devices (Turbohaler, Diskhaler, hydrofluoroalkane PMDI, Rotahaler, Spiros, Easyhaler, multidose-powder inhaler, Clickhaler, Gentlehaler, and Autohaler) for FEV1, forced vital capacity, peak expiratory flow rate, area under the curve for FEV1, blood pressure, symptoms, bronchial hyperreactivity, systemic bioavailability, inhaled steroid requirement, serum potassium level, or use of additional relief brochodilators. However, regular use of the hydrofluoralkane PMDI containing salbutamol was associated with reduced requirement for short courses of oral corticosteroids (relative risk 0.67, 95% CI 0.49 to 0.91).
In patients with stable asthma, the standard chlorofluorocarbon-containing pressurized metered-dose inhaler (PMDI) is as effective as other handheld inhalers, including chlorofluorocarbon-free PMDIs, for delivering β2-agonist bronchodilators.
Source of funding: NHS Research and Development Health Technology Assessment Programme.
For correspondence: Dr. J. Wright, Bradford Hospitals NHS Trust, Bradford, England, UK. E-mail firstname.lastname@example.org.
PMDIs have been used since the early 1900s to deliver aerosolized β2-agonists and corticosteroids to the lung. In recent years, environmental concern over chlorofluorocarbon propellants has fueled interest in the development of alternative delivery systems. The reviews by Brocklebank and colleagues and Ram and colleagues found no difference between PMDIs and other handheld delivery systems in patients with stable mild-to-moderate asthma. They concluded that the standard PMDI remains the most cost-effective delivery device.
Both device and patient-specific issues influence the success or failure of a particular delivery system. Patient factors influencing drug delivery and therapeutic success include not only coordination but also breath-holding ability and inspiratory flow rate, both influenced by disease severity. Findings in patients with mild-to-moderate asthma may not be applicable to patients with more severe airway obstruction.
Proper education in the use of the various handheld delivery systems is crucial because substantial rates (between 12% and 90%) of incorrect metered-dose inhaler use have been reported (1). In the investigational setting—the “best-case scenario”—patients receive detailed instructions that are reinforced throughout the study. “Real-world” patients receive varying degrees of instruction, and adherence to correct technique, if not reinforced, often wanes in the long term. Psychosocial factors (cultural beliefs, education, and language skills) may also influence the ability to comprehend and follow instructions.
The available delivery systems each have advantages and disadvantages. PMDIs are portable and convenient, but effectiveness is technique dependent. Furthermore, excessive oropharyngeal deposition may lead to local side effects with inhaled corticosteroids. Spacer devices can improve PMDI efficiency and decrease toxicity by decreasing particle size and increasing the lung-throat deposition ratio, but they are cumbersome to use and vary in the efficiency of drug delivery. Their main advantage is in reducing problems with lack of coordination between actuation and inhalation.
The amount of aerosol delivered to the lungs is determined by aerosol particle size, velocity, and inspiratory flow rate. In the hydrofluoroalkane PMDIs, the drug is reformulated as a solution. This approach increases the fine-particle fraction, which results in increased drug delivery to the lung and decreased oropharyngeal deposition. Hydrofluoroalkane PMDIs are portable, convenient, and contain no chlorofluorocarbon propellants.
DPI systems are a portable, propellant-free, breath-actuated alternative to PMDIs that help overcome breath-to-hand coordination difficulties. Many have dose counters that allow patients and physicians to monitor treatment. However, in outpatient settings, delivery that requires loading may be inconvenient and may result in decreased adherence to therapy. The efficiency of drug delivery with DPIs also varies according to a patient’s inspiratory flow rate.
With all handheld delivery systems, drug delivery and efficacy are affected by such patient factors as coordination, inspiratory flow rate, and technique. As clinicians, our primary goal is to enhance compliance with therapy for optimal drug delivery while keeping overall costs low. To maximize treatment success, the choice of a delivery system must take into account patient preference, ability, lifestyle, and disease severity. Cost-effectiveness will be maximized with a delivery device that is tailored to a patient’s needs and abilities because reduced adherence may result from lack of perceived efficacy.
These 2 reviews provide evidence that in an ideal setting, PMDIs can be as effective as newer technologies developed to overcome pitfalls in patient technique and compliance.
Amy R. Blanchard, MD
Medical College of Georgia
Augusta, Georgia, USA
Joseph A. Golish, MD
The Cleveland Clinic Foundation
Cleveland, Ohio, USA
1. McFadden ER Jr. Improper patient techniques with metered dose inhalers: clinical consequences and solutions to misuse. J Allergy Clin Immunol. 1995;96:278-83. [PubMed ID: 7636071]