MDIs, nebulizers, and dry powder inhalers have evolved in recent years. Each has advantages and drawbacks depending on a multitude of factors.

Treating disease with inhaled medications has a long tradition, dating back to at least 2000 BC, in India.1 The administration of medications by inhalation provides an optimal delivery route for the treatment of both pulmonary and nonpulmonary conditions. It generally requires smaller doses, offers a rapid onset of drug action, and reduces systemic effects compared with other routes of administration.

Although bronchodilators are currently the most common inhaled medication, many new classes of drugs (eg, antibiotics, antioxidants, and anti-inflammatory agents) lend themselves to administration via inhalation. In addition, “medications aimed at systemic illnesses (eg, insulin, human growth factor, and calcitonin) may also be administered as aerosols, and are being shown to have reliable systemic delivery through alveolar-capillary transport.”2

Nebulizers, metered dose inhalers (MDIs), and dry powder inhalers (DPIs) have each found a niche in the quest for optimal treatment and convenient use. While nebulizers have evolved relatively independently of the drug formulations they deliver, MDIs and DPIs have been developed for the specific pharmaceutical being delivered.

The efficacy of inhaled medications may be affected by patient age, severity of disease, inhalation technique, and specific pharmacological properties of the drug. Oropharyngeal deposition is a consistent confounding factor that continues to challenge each delivery modality. Cost, convenience, and ease of use also can affect patient compliance.

Selection of the optimal delivery device depends on the drug to be administered, the age of the patient, and the condition to be treated. Successful use of any inhaled medication modality continues to be at least somewhat dependent upon patient ability to use the device correctly. The role of the respiratory therapist in patient education is an essential element in that success.

Each delivery method has undergone significant improvements and evolution, further impacted by specific Environmental Protection Agency (EPA), Food and Drug Administration (FDA), and Joint Commission on Accreditation of Healthcare Organizations (JCAHO) requirements or recommendations. Based on growing knowledge of pulmonary cell biology and pathophysiology due to modern methods of molecular biology research, the future characterization of pulmonary drug transport pathways can lead to new strategies in aerosol drug therapy.3

Nebulizers
Handheld nebulizers have long provided a fast, efficient method of delivering medications directly to the airways of the lungs. Conventional nebulizers are highly inefficient because much of the aerosol is wasted during exhalation. However, breath-assisted nebulizers incorporating simple one-way valves can limit the loss of aerosol during exhalation. Although they are considerably more expensive than their disposable counterparts, nondisposable nebulizers can deliver a higher output in the therapeutic range, translating to measurably superior particle deposition, and better outcomes confirmed by both objective and subjective reports. These may become the standard for home care use, and they offer an attractive (though not inexpensive) alternative in the institutional setting.

Several manufacturers have developed portable, compressor-driven nebulizers to meet patient-driven need for portability. Air compressors have a reputation for outstanding long-term reliability, but designing a portable compressor that is both lightweight and powerful has always been a challenge.

Handheld ultrasonic nebulizers can produce a high output of particles in the therapeutic range of 1 to 5 microns.4 Although they can be powered by a variety of electrical sources, including alkaline batteries, and can be very compact and lightweight, their relatively sophisticated design makes it hard for them to surpass compressor-driven nebulizers for long-term reliability. They have continued to evolve, becoming smaller, lighter, and somewhat less expensive. Not all medications are compatible with ultrasonic nebulizers. Budesonide and dornase alfa are not approved for use in ultrasonic nebulizers.

JCAHO and the FDA have both issued “strong recommendations” to discontinue use of multi-dose bottled medications traditionally used in nebulizers and replace them with sterile, premixed, premeasured unit dose medications (UDMs). There are three good reasons. First, the chemical benzal-

konium chloride, or BAC, an antibacterial agent added to some bottled medications as a preservative, can cause airway constriction, potentially blunting the effectiveness of the drugs. Second, bottled, multi-dose medications can act as vector, spreading infections; according to one pharmaceutical representative, there have been reports of deaths from nosocomial sepsis attributed to the use of multi-dose bottles. Third, unit dose medications eliminate possible dosing errors inherent when mixing each individual dose. It is possible to inadvertently administer a nebulizer loaded only with diluents, or containing a double dose of the medication when using bottled multi-dose medications.

The move to replace multi-dose medications with UDMs has been endorsed by the Institute for Safe Medication Practices and the American Society of Health-System Pharmacists.

Metered Dose Inhalers
The development of the metered dose inhaler was a response to a suggestion by the 13-year-old asthmatic daughter of Dr George Maison, and it received FDA approval in 1956.5 MDIs require a propellant to deliver each puff, and the traditional propellant has been chlorofluorocarbons (CFCs). To lower the risk of health and environmental problems caused by ozone depletion and to help restore the ozone layer, most countries have agreed to stop using CFCs. The agreement, made in 1987, is known as the Montreal Protocol.

The United States EPA subsequently mandated the discontinuation of CFC propellants in MDIs due to their effect on the earth’s ozone layer. Development of non-CFC propellants has been reasonably successful, but the safety and effectiveness of every new non-CFC inhaler must be reviewed by the FDA before it is approved.

In 2002 the FDA published its final rule on “Use of Ozone-Depleting Substances: Essential Use Determinations,” which established the criteria under which CFC metered dose inhalers would be deemed nonessential and removed from the US market. Exceptions were made for MDIs for which a non-CFC alternative was not available. However, the final rule also specified that the FDA would evaluate the essentiality of any remaining CFC MDIs available after January 1, 2005. In many cases, pharmaceuticals that worked well with CFC propellants were not compatible with their non-CFC counterparts. Some MDIs using hydrofluoroalkane propellant already have been proven safe and effective and have successfully been placed into use. Complete elimination of all CFC propellants (there is currently one exception still in use) is imminent.

Proper technique is essential for MDI effectiveness, and several studies have shown an alarming lack of ability of medical staff to correctly instruct patients in optimal technique. In one study, for example, “only 5% used an MDI perfectly. This improved to 13% after a lecture and demonstration, and 73% after an intensive one-on-one session.”6 Using MDIs with a holding chamber reduces the need for patient coordination while increasing delivery of medication to the airways and diminishing oropharyngeal deposition by 10 to 15 times.

Dry Powder Inhalers
The first dry powder inhalers, introduced in 1971, were slow to gain acceptance. Due to the phaseout of CFC propellant inhalers and improvements in DPI engineering, their acceptance and use have increased exponentially. Salmeterol prescriptions via DPI, for example, increased by 250% in 3 years, compared to the MDI formulation.7

The ability of clinicians to properly instruct patients in proper technique has been challenging with DPIs, just as it has been with MDIs. A 1997 study showed that when tested for MDI and DPI knowledge, RTs scored 67%, MDs scored 48%, and RNs scored 39%. When demonstrating use, RTs scored only 60% on a DPI device and MDs scored 21%.8 The pharmaceutical industry has responded with improvements in DPI design, making the use of current products much easier for clinicians to demonstrate and for patients to use. Still essential to effective medication delivery with DPIs is the patient’s ability to generate sufficient inspiratory flow, and DPIs are not recommended for patients with acute bronchospasm or children under 6 years of age.4 However, the latest designs are able to deliver therapeutic doses with much lower inspiratory flows than previous designs required.9

Conclusion
For at least the past 30 years, marketplace competition to provide inhaled medications that are more effective and easier and more convenient to use, while minimizing side effects, has continuously evolved. More recent awareness of environmental and infection control concerns has spawned recommendations and regulations to address the issues. The industry has embraced the challenges, and the net result has been more and better tools for providing optimal patient care. On the horizons are inhaled medications that will need to be administered only once a day, offering the utmost in convenience, and further enhancing patient compliance.

John A. Wolfe, RRT, is a contributing writer to RT and a member of the editorial advisory board.

References
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