The earliest nebulizers were invented in the mid-1800s in France and have been developing ever since, becoming more portable, accurate, and sophisticated delivery devices of respiratory medications. Today, physicians have the choice of different types of nebulizer technology, from simple metered dose inhalers (MDIs) to vibrating mesh devices. To keep respiratory care professionals informed about the latest trends in nebulizer technology, RT interviewed representatives from three nebulizer manufacturers:
- Beth Keifer is vice president of sales and marketing at B&B Medical Technologies, Carlsbad, Calif, a developer of specialty airway management and nebulizer technology for infant, pediatric, and adult patients.
- John Power is CEO of Galway, Ireland-based Aerogen, a specialty medical device company that develops and manufactures a broad range of nebulizers and other aerosol drug delivery devices.
- Larry Weinstein is the senior vice president of operations at PARI, which develops a variety of nebulizers, including jet nebulizers, vibrating pulse devices, and metered dose inhalers.
Beth Keifer: In addition to strong economic pressures, changes in nebulizer technology are driven by clinical needs along with development of new pharmacological agents requiring special techniques and performance characteristics. In looking at methods for optimal delivery of newer medications, some of the innovative experimental delivery devices appear to promote improved deposition of medication dependent on access to the airway, invasive or noninvasive. The new experimental methods will have to be assessed for safety, efficacy, and overall cost-effectiveness of the drug and delivery device. That is, does it save personnel cost, supply expense, or capital outlays for the institution and does it promote the patient’s faster transition out of the health care facility?
John Power: The most significant factor driving the evolution of nebulizers today is the potential to deliver traditional and novel systemic drugs via the pulmonary route. We know of several biopharmaceutics companies working on exciting programs ranging from pulmonary delivery of erythropoietin, human growth hormone, antibiotics, and prostacyclin therapy to name but a few. These new applications will require highly efficient drug delivery with minimum waste of drug. Accuracy and repeatable doses are also crucial driving factors in the evolution of nebulizers.
Larry Weinstein: In our view, the number-one driver regarding the evolution of nebulizers is to ensure effective therapy for those taking inhaled medications. Most important, effective therapy comes from matching the correct drug with the correct delivery device. As inhaled medications are being used to treat “more challenging disease states” with more expensive or potentially harmful medications, new devices must deliver medication with better control of particle size to get to the targeted areas and provide less drug waste. Of course, no therapy will be effective unless it is used, indicating that patient compliance must be encouraged with fast treatment times and simple, user-friendly devices.
Power: Pediatric patients are very impatient patients. Off the ventilator, they do not tolerate wearing masks and are put off by noisy and cumbersome technology. Treatments for infants and children need to be short in duration and high in delivered dose. Several devices have been introduced into the market without any research to substantiate effect. Several authors have looked at the impact of mask design with jet nebulizers to minimize ocular deposition. This appears to be less of an issue with pMDIs and vibrating mesh devices. More recently, vibrating mesh nebulizers have been studied to deliver aerosols via nasal cannulas. Providing a dense aerosol that is not dispersed by large volumes of gas seems to be key to providing high inhaled doses to infants and small children. This is an advantage of both ultrasonic nebulizers and vibrating mesh technology, which do not require gas flow to produce aerosol. Traditional jet nebulizers do not work well with infant ventilators, whether traditional or high-frequency oscillatory ventilation. Newer vibrating mesh technology offers opportunity to provide a lightweight, low-volume aerosol generator capable of delivering a greater proportion of the drugs during a wide range of ventilation.
Keifer: The use of heliox [for pediatric patients] has been advocated since the early 1930s. With our latest nebulizers, heliox increases the number of particles within the respirable range from 64% to 78% and is added to the auxiliary port, providing for best nebulization and mixing of the heliox gas. Heliox promotes increases in minute ventilation and carbon dioxide reduction, while acting as an excellent carrier gas to deliver medication through restricted airways and past obstructed lung segments, allowing for better deposition.
Weinstein: The introduction of the first mainstream portable compressor system in 2003 was the first step in providing a good nebulizer alternative for families on the go. That system was powerful, small, and battery operated to provide fast, reliable treatments with a nebulizer. Since then, systems from many manufacturers have been introduced going for smaller size and more convenience.
In addition, a lot more attention has been placed on the interface between the nebulizer and the patient. Several user-friendly “character” masks exist to help encourage compliance, or reduce fear of treatment. Manufacturers have also started looking more closely at mask and system designs to better enhance drug delivery to the pediatric patient, while potentially reducing drug deposition in other areas, such as on the face and eyes.
Weinstein: I do believe that the various manufacturers have identified the same opportunities and are pursuing them in different ways. For example, there are several efforts to improve on compliance, treatment time, respirable dose, and medication waste.
Smaller, more powerful, faster systems with good drug delivery performance are the approach taken by traditional jet nebulizer manufacturers. In addition, breath-enhanced or breath-actuated approaches are also being used to further improve drug delivery and reduce waste. Newer technologies, such as vibrating membrane nebulizers, have demonstrated significantly faster treatments, virtually no residual medication, and, in some cases, the ability to tightly control the particle size. Additional work with breath-actuated and breathing-controlled systems [offers] other future possibilities. Another trend is for pharma companies to partner with device manufacturers to customize delivery systems for use. Optimization of a delivery system for specific drugs provides less risk from the drug [by ensuring] correct, consistent dosing; and therefore more appropriate clinical results, while possibly reducing treatment times and lessening adverse results.
Power: The key factors to development are convenience, consistency, and effectiveness. Portability is important, especially in therapies that require dosing throughout the day. High output, high efficiency equates to shorter treatment. Consistency means that there is a better chance to develop drug/device combinations for specific drugs, rigorously studied and approved for inhalation.
Weinstein: User friendliness comes in many ways. Quieter, smaller size, lightweight, and portable devices (plug in, battery operated, or car adapter) are becoming more popular. Many manufacturers have made these advances while also maintaining or improving drug delivery performance and treatment times. Many systems are now available with user-friendly features such as handles, carrying cases, fewer parts, child-friendly character masks, stickers, and educational materials.
Power: Feedback from critical care providers is crucial for product development and design processes. Although manufacturers are the experts in medical devices, they are not the experts in patient therapy. Manufacturers must rely on critical care providers to help ensure that products meet their clinical needs and expectations.
Keifer: Manufacturers are taking into account the use of newer materials that will maintain the features of the products without sacrificing the benefits of performance and quality. Some manufacturers are also evaluating green materials that will allow for recycling of the disposable products with a smaller carbon footprint.
Power: It is important not to fall into the trap of being “penny-wise and dollar-foolish.” While it is always important to look at product acquisition costs, it is of far greater importance to the caregiver to evaluate total cost of care facilitated by the product. If conventional technologies fail to deliver significant respirable dose or require high levels of interaction, eg, vent setting changes during administration, where are these costs accounted for? When multiple treatments are ordered because the patient does not respond to therapy, the incremental costs of clinician time, medication cost, and extended patient suffering may greatly outweigh the cost difference in nebulizer technology.
Weinstein: It’s difficult to speak about other manufacturers. It is clear that several manufacturers have systems made in the Far East (China) to help lower costs. There is also at least one manufacturing company that supplies different compressor systems to multiple US “manufacturers” to provide some economies of scale. New innovations have also helped reduce the number of parts in the nebulizer, while improving performance and adding new user-friendly features.
Power: Reimbursement for home respiratory care has been steadily cut over the past number of years, which puts nebulizer providers and manufacturers under significant pressure to meet their patients’ needs and make a profit. The Deficit Reduction Act, which was passed by the US Senate in 2005, aims to reduce the expense of home medical equipment to the federal government. The changes that result from this legislation include competitive acquisition. Providers will submit bids for selected home medical equipment products and the Centers for Medicare and Medicaid Services will use these bids to determine the Medicare payments for those products. Medicare payments will be the median of these bids and will heavily influence reimbursement available from private insurers. This may mean that patients who want the best and most efficient technology for their nebulizer treatments would have to make some form of co-payment. (In July, the House and Senate overrode President Bush’s veto of HR 6331, which delays competitive bidding for 18 to 24 months—Ed.)
Weinstein: I am not a reimbursement expert, but it is clear that in the home care market, reimbursements for services, devices, and medications are being squeezed, convincing some providers to look for the “low cost” products instead of clinically proven nebulizers.
Keifer: Multiple factors will influence future nebulizer technology. These will include transitioning patients from emergent delivery of medication to a more proactive approach to treatment, which should show cost benefits, although this remains to be seen. As nebulizer technology develops, we expect to see smaller nebulizers that address the delivery mechanism of specific drugs for a faster, more targeted response and the use of adjunct gas therapy to supplement the drug’s features by aiding in the transport of the drug into the small airways. In the literature, a helium-oxygen mixture has been shown to improve the delivery of aerosols.
Power: Approximately one third of the patients in an acute care setting today are there as a result of a respiratory condition. When setting up my company, I had a vision that we could raise the performance of our nebulizer technology to such levels of performance that would see it on par with intravenous delivery as an accepted means of targeted drug delivery treatment for these patients. While we are not there yet, I believe the advances we made over the following years have resulted in a much greater appreciation of the ultimate potential of such products and it is only a matter of time before this vision is realized.
Weinstein: Treatments will continue to get faster and more efficient. New nebulizers and new medications will tend to be more closely connected to help ensure appropriate treatment. Therapies for non-respiratory-related diseases will become more prevalent, as will more targeted deliveries of aerosol to specific locations. Aids for breath control, breath actuation, positive pressure, or localized delivery should also be expected to progress.
Tor Valenza is the staff writer for RT. For further information, contact [email protected]