Dr Lam Sin Man, Grace
Department of Medicine, Pamela Youde Nethersole Eastern Hospital
Inhalation is the preferred means of drug delivery for many pulmonary diseases because it allows a high drug concentration to be achieved selectively in the airways while minimizing systemic side effects. On the other hand, inhaler drugs are generally less convenient to administer than their oral counterparts, and require proper techniques to ensure drug delivery and efficacy. There are a number of inhaler devices, each with its own advantages and disadvantages that we have to consider to suite the individual needs of our patients.
Nebulizers appeared as early as in the 19th century. The early jet nebulizers are driven by compressed air, while newer ultrasonic nebulizers utilize high-frequency acoustical energy for aerosolization of a solution. These devices are able to deliver large doses of medications and require no patient coordination. However, they are generally less portable and are more expansive.
The widely-used pressurized metered-dose inhaler (MDI) was developed in 19551. It is highly portable and unlike the nebulizers, no drug preparation is necessary. Its major disadvantage is the need for coordination of MDI actuation and patient inhalation. Previous studies have demonstrated that up to 70% of patients fail to use this device properly2. Inappropriate use leads to increase pharyngeal deposition, and in the case of inhaled corticosteroid will result in oral candidiasis, hoarseness, and increased absorption into the systemic circulation when swallowed. Combining the use of a MDI with a holding chamber or spacer will reduce the demand on patient coordination3. Spacers were first developed in the late 1970s. They hold aerosol delivered by the MDI for a short period of time, thus removing the need for tight coordination between actuation and inhalation. In addition, fast particles bombard and deposit on the walls of the spacer instead of the pharynx, thereby reducing local side effects. The increased distance travelled allows evaporation of the propellant molecule from the drug molecule. This increases the proportion of respirable particles that penetrate further into the lungs.
Another disadvantage of MDI lies with its propellant, which provides the chemical energy for dispersion and delivery of the medication. Previously, chlorofluorocarbon (CFC) was the only propellant used. However, CFC has been shown to deplete the ozone layer, without which unabsorbed ultraviolet B irradiation will increase the risk of skin cancer, cataract, immune suppression, and global warming. The Montreal protocol signed in 1987 was an international concerted effort to phase out ozone-depleting substances, including CFC. In response, pharmaceutical companies identified hydrofluoroalkane (HFA) to be used as a propellant that is not ozone-depleting. The essential-use status of CFC-inhalers will be withdrawn by the end of this year in the United States4.
Dry powder inhaler (DPI) was the next to appear in market in 19715. These devices are breath-actuated, meaning that drug is only provided when demanded by patient inhalation. As a result, less coordination is required. However, it requires a relatively rapid inhalation rate for drug aerosolization, which may be difficult to achieve in patients in acute distress.
Table 1 summarizes the advantages and disadvantages of the various inhalation devices.
Evidence-based guideline based on a systematic review of randomized controlled trials on the selection of inhalation device was published earlier6. Current evidence suggests that the delivery of β2–agonists in the emergency department and inpatient hospital settings by nebulizer or MDI with spacer are equally effective in improving pulmonary function. Because of a larger dose administered by nebulizers, its use in the emergency setting was associated with greater increases in heart rate. Recommendations on DPI and MDI without spacer cannot be made in the acute setting because of limited data. In the outpatient setting, DPI produces comparable results to MDI (with spacer in the case of inhaled corticosteroid) and both are considered appropriate devices.
In conclusion, a number of inhalation devices are available for the treatment of pulmonary diseases, each with its own advantages and disadvantages. None has proven to be superior to the others in any of the clinical situations tested. Whichever device is chosen, the key to successful treatment lies at a proper inhaler technique. Inhalers should not be prescribed without checking that the patient can use the device properly.
1. Freedman T. Medihaler therapy for bronchial asthma: a new type of aerosol therapy. Postgrad Med J 1956; 20: 667-673
2. De Blaquiere P, Christensen DB, Carter WB, et al. Use and misuse of metered-dose inhalers by patients with chronic lung disease: a controlled, randomized trial of two instruction methods. Am Rev Respir Dise 1989; 140: 910-916
3. Rees J. Methods of delivering drugs. BMJ 2005; 331: 504-506
4. Hendeles L, Colice GL, Meyer RJ. Withdrawal of albuterol inhalers containing chlorofluorocarbon propellants. N Engl J Med 2007; 356: 1344-51
5. Bell JH, Hartley PS, Cox JSG. Dry powder aerosols: I. A new powder inhalation device. J Pharm Sci 1971; 60: 1559-1564
6. Dolovich MB, Ahrens RC, Hess DR, et al. Device selection and outcomes of aerosol therapy: Evidence-based guidelines. Chest 2005; 127: 335-371