Aerosol therapy, while a very old method of drug delivery, has become the mainstay of therapy for patients with respiratory disease. Inhalers have been used for more than 80 years, but it was not until the mid 50s that both the hand-held jet nebulizer and the metered-dose inhaler (MDI) were approved for clinical use. The last device added to the list was the dry-powder inhaler (DPI) in 1971.1 While performance of almost every available device is far from providing consistent drug delivery, available evidence has demonstrated that inhalation is the route of choice for the treatment of respiratory diseases.
Over the last few years, newly designed inhaler devices have dramatically improved lung deposition. Their technology and mode of operation may vary considerably, however. The proliferation of inhaler devices has provided the clinician with a wide selection to optimize aerosol therapy; nevertheless, it has also made it more challenging and at times confusing for both clinicians and patients. New guidelines call for evaluation of adherence not only to medical advice but also to inhalation technique when the patient’s disease is poorly controlled.2 In this article we attempt to review general features of the inhaler devices, their advantages, and their limitations, and provide some guidance in making the right selection of inhalers for patients with respiratory disease.
Pressurized-Metered Dose Inhalers (pMDIs). The mechanism by which drug is delivered to the airway when using a pMDI is the manual actuation of the device. Pressure over the canister causes a substance known as propellant to create the force necessary to generate the aerosol cloud. This propellant makes up approximately 99% of the delivered dose of the pMDI. As governed by the 1987 Montreal Protocol on Substances that Deplete the Ozone Layer, all pMDIs that contain CFCs as propellant are being discontinued under the auspices of the UN Environment Programme. The target year is 2010. The newer HFA-pMDIs are environmentally friendly, they can be used in almost every clinical and environmental situation, their dosing is convenient, and they can deliver ultrafine particles (unlike traditional pMDIs). Their efficiency highly depends on the technique utilized by the patient, and, while poor inhalation technique can be minimized by the use of valved holding chambers, they are cumbersome and seldom used.
Breath-Actuated pMDI (BAI). The breath-actuated pMDI is a device that is primed by raising a lever. Once the patient inhales, a vane lifts and a spring forces the canister downward so medication can be released. The BAI should be considered as the best alternative to the conventional pMDI in any patient whose inhaler technique is not known to be satisfactory.3 A study by Price and coworkers found that the use of a BAI in patients with asthma was associated with a 25% reduction in the use of short-acting beta agonist, 64% less oral cortico-steroid, and up to 44% less antibiotic use than in patients using traditional pMDIs.4
Dry Powder Inhalers (DPIs). In a DPI, dispersion of the powder into aerosol particles, typically carried by lactose or glucose, is generated as turbulent flow goes through a dose of finely milled powder. The turbulent energy is proportional to the speed of the inhalation traveling through the DPI. There is a minimum threshold energy required at which the de-aggregation is sufficient to provide a dose with the potential to produce particles with the required size. It has been generally accepted that the minimum threshold is equivalent to an inspiratory flow of 30 LPM. The higher the resistance of the DPI, the lower the flow required to generate an adequate dose and vice versa.5
ADVANTAGES AND LIMITATIONS
Several recent meta-analyses6,7 comparing the clinical effectiveness and cost-effectiveness of inhaler devices in asthma and COPD, including the evidence-based guideline published by the American College of Chest Physicians and the American College of Asthma, Allergy, and Immunology,8 clearly demonstrate that there is no evidence to support clinically important differences between inhalers (Table). There is also insufficient data to verify the ability of in vitro assessments to predict inhaler performance in vivo. The review of technique after teaching the correct technique suggests that there is no difference in patients’ ability to use DPIs or pMDIs.
All important breakthroughs in biotechnology and nanotechnology used in new delivery devices have come at a steep price. As an example, cost of most DPIs is substantially higher than that of pMDIs.
INHALER TECHNIQUE: DOES IT MATTER?
Even if the best inhaler has been selected on the basis of cost, ease of use, and clinical efficacy, a critical factor is the patient’s ability to use a device. There is growing evidence that poor inhaler technique is associated with poor asthma control.9-11 Even factors such as mental-state scores and hand strength have been identified as important predictors of incorrect use of pMDIs.12 In patients with COPD, underuse is followed in frequency by overuse and improper use of the medication-delivering device.13 Misuse of the inhaler has been reported to be as high as 90%.12,14-16 (Figure 1)
|Figure 1. Summary of the most common errors in patient’s use of MDIs and DPIs.|
DO WE KNOW ENOUGH ABOUT THE INHALERS AND HOW TO USE THEM?
Although health care professionals, particularly medical doctors and respiratory therapists, involved in the management of patients with respiratory disease are expected to be versed in the use of all available inhalers, the reality is quite different.17 A survey conducted by Hanania et al18 revealed that RTs’ percent mean knowledge score (67%) was significantly higher than those achieved by either the registered nurses (39%) or the MDs (48%). Similarly, percent mean demonstration scores for each device were significantly higher for RTs than either RN or MD groups (Figure 2). More RTs (77%) had received formal instruction on the use of devices in school than had either RNs (30%) or MDs (43%). However, more instruction was not necessarily correlated with a match between knowledge and demonstration.
|Figure 2. Percent mean knowledge score and demonstration of MDI and DPI by RTs, RNs, and MDs. MDI was evaluated with and without chamber (Aerochamber, Trudell Medical, Canada). The DPI evaluated was the Turbuhaler (Astra Pharmacy Inc, Canada).|
SELECTING AN INHALER DEVICE
The process of selecting the inhaler device cannot be taken lightly. Some of the questions that need to be answered prior to selecting the most appropriate device for patients are:
- In what devices is the desired drug available?
- What device is the patient likely to be able to use properly, given age and clinical setting?
- For which device and drug combination is reimbursement available?
- Which device is least expensive?
- Can you use the same device for all inhaled drugs that the patient is taking?
- Which device is the most convenient for the patient or family?
- How durable is the device?
- Does the patient or practitioner have a specific device preference?
The ideal device should be one that is small, discrete, compact, easy to hold or grip, and easy to use (even during an attack), has a refillable unit, is disposable, and has a dose counter.
All inhaler devices have advantages and limitations. The selection of the best inhaler, as with any other aerosol delivery device, should be based on the evaluation of device/drug availability; patient age and the ability to use the selected device correctly; device use with multiple medications; convenience in different clinical settings; drug administration time; cost and reimbursement; and physician and patient preference.
Although the fundamental principle of prescribing frequently lies on the use of the most clinical and cost-effective medication and device, choices may become influenced by factors that are not necessarily evidence-based or clinically relevant. Current evidence has demonstrated that when used correctly there is little difference in clinical efficacy between different inhalers. The ability of the patient to use the prescribed device plays a critical role in therapeutic outcomes. Since errors during the inhalation technique are critical to gain disease control, identification of adequate use and misuse of the delivery device should come first when evaluating and treating patients with respiratory diseases. No single inhaler is good enough until both the health care provider and the patient can demonstrate adequate level of competency in the use of the device. The selection of the right device should also come before choosing a new drug.
Ruben Restrepo, MD, RRT, FAARC, is professor; Donna D. Gardner, MSHP, RRT, is assitant professor, program director, Department of Respiratory Care, School of Health Professions, UT Health Science Center, San Antonio
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- Dekhuijzen PNR, Magnan A, Kneussl M, on behalf of the ADMIT Working Group. The ADMIT series—Issues in Inhalation Therapy. 1) The goals of asthma treatment: can they be achieved? Prim Care Resp J. 2007;16:341-8.
- Newman SP, Weisz AW, Talaee N, Clarke SW. Improvement of drug delivery with a breath actuated pressurised aerosol for patients with poor inhaler technique. Thorax. 1991;46:712-6.
- Price D, Thomas M, Mitchell G, Niziol C, Featherstone R. Improvement of asthma control with a breath-actuated pressurised metered dose inhaler (BAI): a prescribing claims study of 5556 patients using a traditional pressurized metered dose inhaler (MDI) or a breath-actuated device. Respir Med. 2003;97:12-9.
- Chrystyn H. Is inhalation rate important for dry powder inhalers? Using the In-Check Dial to identify these rates. Respir Med. 2003;97:181-87.
- Dolovich MB, Ahrens RC, Hess DR. Device selection and outcomes of aerosol therapy: Evidence-based guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology. Chest. 2005;127:335-71.
- Ram FS. Clinical efficacy of inhaler devices containing beta(2)-agonist bronchodilators in the treatment of asthma: cochrane systematic review and meta-analysis of more than 100 randomized, controlled trials. Am J Respir Med. 2003;2:349-65.
- Brocklebank D, Ram F, Wright J, et al. Comparison of the effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature. Health Technol Assess. 2001;5:1-149.
- Giraud V, Roche N. Misuse of corticosteroid metered-dose inhaler is associated with decreased asthma stability. Eur Respir J. 2002;19:246–51.
- Newman SP, Weisz AWB, Talaee N, Clarke SW. Improvement of drug delivery with a breath actuated pressurised aerosol for patients with poor inhaler technique. Thorax. 1991;46:712–6.
- Lindgren S, Bake B, Larsson S. Clinical consequences of inadequate inhalation technique in asthma therapy. Eur J Respir Dis. 1987;70:93–8.
- Rau JL. Practical problems with aerosol therapy in COPD. Respir Care. 2005;51:158-72.
- Restrepo RD, Alvarez MT, Wittnebel LD, et al. Medication adherence issues in patients treated for COPD. Int J Chron Obstruct Pulmon Dis. 2008;3:371-84.
- Giraud V, Roche N. Misuse of corticosteroid metered-dose inhaler is associated with decreased asthma stability. Eur Respir J. 2002;19:246-51.
- Luk H, Chan P, Lam F, et al. Teaching chronic obstructive airway disease patients using a metered-dose inhaler. Chin Med J (Engl). 2006;119:1669-72.
- Van Beerendonk I, Mesters I, Mudde AN, Tan TD. Assessment of the inhalation technique in outpatients with asthma or chronic obstructive pulmonary disease using a metered-dose inhaler or dry powder device. J Asthma. 1998;35:273–9.
- Melani AS. Inhalatory therapy training: a priority challenge for the physician. Acta Biomed. 2007;78:233-45.
- Hanania NA, Wittman R, Kesten S, Chapman KR. Medical personnel’s knowledge of and ability to use inhaling devices. Metered-dose inhalers, spacing chambers, and breath-actuated dry powder inhalers. Chest. 1994;105:111-6.