Respironics’ InsElite

The whole point of nebulizers is they are the simple, easy way to get respiratory drugs in. It’s their great advantage compared to other devices, which might be smaller or more complex,” says Tim H. Gordon, director of marketing for Respironics Respiratory Drug Delivery in Parsippany, NJ. Pulmonary ailments are, by far, the most common diagnoses of patients prescribed nebulizers. The lungs are often the quickest way to deliver treatments for conditions such as asthma, COPD (chronic obstructive pulmonary disease), cystic fibrosis, pneumonia, and pulmonary hypertension.

There are drugs in development, however, that use the lungs as a delivery path to somewhere else in the body. Inhaled insulin is a well-known example, although it is delivered using a dry powder inhaler. “There are drugs in development that will be delivered through the lung … for systemic delivery for treatment of conditions such as migraines, pain management, cancer treatment, and hormone replacement, to name a few,” says Lisa A. Cambridge, BS, RRT, director of clinical development at PARI Respiratory Equipment Inc in Midlothian, Va.

Nebulizers are one of three methods available for the delivery of inhalation treatments; the other two are metered dose inhalers (MDI) and dry powder inhalers (DPI), both handheld devices. Their small size makes them more convenient, but they are also more complex, requiring hand and breath coordination that is sometimes beyond the capabilities of the patient (particularly pediatric and geriatric patients). This will often impact the physician’s decision to prescribe a nebulizer over other options.

The patient also influences the physician’s selection of a specific nebulizer, although it may not be the biggest factor, as physicians must consider the drug delivered and the setting for delivery. In some instances, a drug has been approved for use only with a specific nebulizer, making the decision easy. For example, Ventavis, a prostacyclin therapy from Actelion Pharmaceuticals US Inc, San Francisco, is approved for use only with the I-neb AAD System from Respironics. Novartis’ TOBI (tobramycin), which treats lung infections in cystic fibrosis patients, is approved for use by the FDA only with PARI’s LC Plus Reusable Nebulizer. PARI also offers the eFlow to pharmaceutical companies seeking a customizable drug delivery platform.

These drug-specific nebulizers use advanced technologies to create more efficient delivery than that of conventional devices. Yet even conventional devices are often tested with a drug. The medication package insert includes information about which devices were used in the clinical trials. The information can be important since different types of nebulizers can exhibit different characteristics, including how much drug is actually delivered. They all, however, share some common features. “They all convert liquid solutions or suspensions into aerosols of the size that can be inhaled into the lower respiratory tract,” says Cambridge.

The Nebulizer Family

How they create that aerosol is where they differ. The three current nebulizer technologies include jet, ultrasonic, and vibrating mesh or vibrating membrane.

Monaghan’s Aeroeclipse

The jet nebulizer, also known as the small-volume nebulizer (SVN), is the oldest type of nebulizer and, therefore, the most common. Jim Fink, PhD, RRT, FAARC, Respiratory Science, Nektar Therapeutics, San Carlos, Calif, categorizes jet nebulizers into three types: pneumatic, valve or vented, and breath-actuated.

“[Pneumatic nebulizers] use a pressurized gas stream to suck fluid out of the reservoir and shear it into small particles,” explains Fink. He estimates that simple jet nebulizers have drug delivery efficiency to the lung at 6% to 10%, but adds that most doses take this fact into account. Many of the drugs that use these nebulizers treat common lung conditions, such as asthma and COPD. Pneumatic nebulizers tend to be inexpensive—Fink notes they can cost as little as $0.69 per device—but they require a compressor and tend to be noisy.

Vented nebulizers also make aerosol from pneumatic sources but feature a venting system. “When you breathe in, you inhale a richer mix of aerosol, and when you exhale, you do so through an expiratory valve in the mouthpiece so you continue to collect some aerosol in the nebulizer,” says Fink. As a result, their drug delivery efficiency is greater, at about 10% to 15%, and nebulization time is approximately 50% faster than that of conventional nebulizers. The use of a one-way valve on the mouthpiece reduces the risk of contamination since patients do not exhale into the reservoir.

The breath-actuated pneumatic nebulizer is the newest type. Currently, only one device has been approved for use with general purpose nebulizer medications: the AeroEclipse II Breath Actuated Nebulizer (BAN) by Monaghan Medical Corp of Plattsburgh, NY. (The I-neb is also a breath-actuated device but is approved only for specific medications.) Breath-actuated devices produce aerosol when the patient inhales and do not when the patient exhales. Because the drug is not constantly being aerosolized, delivery is more efficient and less of the drug is wasted. Fink estimates drug delivery efficiency at 30% to 35%, but it can require longer to administer the drug. Julie Cusano, product manager with Monaghan, notes the respirable dose of the AeroEclipse II has been measured at 78%.

The AeroEclipse II is approved for 7 days of use, making it a disposable device, but not all nebulizers are disposable. Reusable devices are typically recommended for replacement every 6 months to ensure optimum drug delivery. Disposables generally last for a much shorter time; some suggest 2 days are typical. “If used beyond that time, the plastic can break down, and the efficiency can decrease,” says Cambridge.

Ultrasonic nebulizers tend to be more efficient than pneumatic and vented nebulizers, but not quite as efficient as breath-actuated devices, according to Fink. Ultrasonic nebulizers create aerosol using sound waves generated by a vibrating piezo crystal. The device does not require a compressor. It cannot be used with all drugs, however, particularly suspensions such as Pulmicort Respules, a pediatric asthma medication. With these types of medications, too much of the drug remains suspended in the nebulizer and is not aerosolized. In addition, ultrasonic nebulizers can heat medication by more than 20° Celsius in 15 to 20 minutes, cautions Fink, which can degrade the drug. An example is the cystic fibrosis drug Pulmozyme.

Vibrating mesh nebulizers are the newest technology and are able to generate high overall output respirable fractions. The technology reduces the amount of drug that is wasted by vibrating a mesh or plate with multiple apertures (precisely placed, according to Cambridge), which aerosolizes virtually all of the drug solution.Vibrating mesh may be active where the mesh is vibrated directly and acts as an electronic micropump (Airon and PARI) or passive (Omron and Respironics) where an ultrasonic horn pushes medication through a mesh. Aerogen’s Aeroneb, Omron’s NEU-22, PARI’s eFlow, and Respironics’ I-neb are examples of this type of nebulizer. These devices tend to have higher output rates than do standard nebs with particle size dictated by the size of the apertures. With drug delivery efficiency rates greater than 50% (and often closer to 60%), treatment time is much shorter. eFlow can complete delivery of medication within 2 to 3 minutes. Cambridge compares this to the 7 to 15 minutes conventional nebulizers need to deliver the same dose.

The Drugs

Because of the differences in drug delivery efficiency, the drug prescribed will influence the selection of a nebulizer. “Physicians should consult the medication package insert—the FDA–approvable document is also in the Physicians’ Desk Reference. It will list the nebulizers that were used in the clinical trial and tell how efficient the nebulizer is in actual patients, not just bench testing,” says Cambridge.

Some drugs require a specific nebulizer, most often one of the newer technologies with greater efficiency. Because they waste less drug, they are ideal for medications that are expensive. “Smart” nebulizers, such as I-neb, can save even more drug. The device has a sensing system that averages the patient’s inspiration every three breaths and adjusts the timing and dose accordingly. The Adaptive Aerosol Delivery (AAD) algorithm emits the drug into 50% to 80% of each inspiration. “I-neb is constantly adjusting, not only for each patient but also for each breath. So if the patient is breathing stronger at the beginning of the treatment and weaker toward the end, the nebulizer adjusts the drug delivery,” says Respironics’ Gordon.

“Smart nebulizers are ideal for drugs with a narrow therapeutic window,” says Fink. The frequency of the dose can also impact the nebulizer selection. If needed just a few times a day, home therapy may be possible, but if more frequent dosing is necessary, a portable system may be needed. Similarly, night therapy may also influence the decision. “If a child needs an asthma treatment at 3 am, a noisy nebulizer will wake the rest of the family,” says Fink.

The Patient

Patient satisfaction with the device can impact compliance. Patients are more likely to comply with treatment prescriptions when the treatment is shorter, quieter, and/or portable. “It’s important to select the right device for the patient that will ensure they will comply and a positive outcome will be achieved,” says Cambridge. For instance, the family with the 3 am wake-up call may decide to skip the nightly dose.

Pari’s eFlow

Quicker treatments may encourage adherence in patients of all types, even more than do quieter devices. “Patients who are having an acute attack want to breathe as fast as possible. Those who have been using nebulizers for an extended time are tired of the long treatments. Patients in the hospital need time for other tests. Those in clinics can get one-on-one time with the clinician, which assures proper use and therefore optimum dose,” says Monaghan’s Cusano.

Quicker treatments also benefit health care professionals. Cusano believes treatment trends are moving away from stacking patients and toward one-on-one treatments with constant clinician attendance. (Stacking, or concurrent therapy, refers to multipatient protocols, where the therapist starts one patient and moves to another while the first patient undergoes therapy and continues for as many patients as time allows; the therapist then returns to the first patient to complete the procedure and again moves down the line of patients.) The change is related to evidence that clinician supervision produces optimum results. In addition, the American Association for Respiratory Care notes medical and billing errors are also concerns. Payors and quality organizations may require individual treatment for reimbursement and approvals.

The difference in treatment delivery times can be significant, particularly for therapists, says Cusano. Conventional nebulizers may need 10 minutes or longer, whereas newer technologies, such as breath-actuated nebulizers, can deliver the treatment in 5 minutes or less. Clinicians can use that time to update the patient’s record, particularly if using a portable, computerized system.

Nektar/Aerogen’s Aeroneb Pro

A therapist in attendance for the entire procedure can also make sure the patient uses the device correctly. Proper use helps to assure a complete dose, therefore the patient’s capabilities also play a role in selection. For instance, “weak breathers” may need a more powerful nebulizer, such as a vented inhaler. “Our Sidestream nebulizers have a passive venturi system that allows outside air to be drawn into the nebulizer to boost the amount a patient inhales. Patients also do not need to breathe as strongly to open a valve,” says Gordon.

Children can pose a particular challenge in treatment delivery. Pediatric patients often cry, which can negatively impact delivery, says Cambridge. Subsequently, some manufacturers attempt to appeal to kids with bright colors and fun design. PARI offers Bubbles The Fish II Pediatric Aerosol Mask, which is intended to help remove the scary aspect of treatment.

But beauty is not everything. Cambridge suggests that physicians also take note of the efficiency of delivery devices and accessories, such as masks, when prescribing. “Just because something is cute doesn’t mean it is efficient,” says Cambridge. Bubbles is cute but is also designed to reduce the amount of aerosol that gets in the eyes and deposits on the patient’s face.

Unfortunately, nebulizer selection may be restricted by economic concerns. “Reimbursement tends toward the lowest common denominator so anything more complex than pneumatic nebulizers is often out-of-pocket,” says Fink. The good news, he adds, is that newer technologies do decrease in price over time. “In the case of the Aeroneb technology used for delivery in critical care, what was a $300 nebulizer 4 years ago is a $40 nebulizer today (Aeroneb Solo),” says Fink.

The Setting

Size matters. Active patients who require therapy throughout the day are likely to want the more expensive nebulizers as they are often smaller and more portable than older types. If the device has to travel to an office or even overseas, the handheld devices are easier to transport. Alternatively, patients who do not travel frequently and take the drug only once or twice a day might find it less inconvenient to work with a larger, less expensive system, according to Fink.

To learn more about the nebulizers pictured and other fine nebulizer products, go to the online Product Focus
 

“The compressor-driven nebulizers tend to be less expensive but are also bulkier and noisier. The ultrasonics and vibrating mesh nebulizers tend to be quieter but more expensive,” says Fink.

Gordon suggests that simpler devices might be more desirable for at-home use. “People need to take the device apart and put it back together again when they clean it so fewer pieces are beneficial,” says Gordon.

He also recommends reusable devices for at-home use. “In many instances, the reusables are better because they last for 6 months and maintain their performance over that time period,” says Gordon. Cambridge concurs, suggesting they may last even longer, for up to 1 year, depending on use. “They can also be easily cleaned—boiled or put in the dishwasher—and are less expensive for long-term use,” says Cambridge. Disposable units are better for short-term use, such as hospital visits.

Patients who have some say in the selection of their nebulizers tend to show more compliance with treatment plans, according to Cambridge. Adherence is often a primary goal in nebulizer selection. It ensures patients get their breath of medicated air.

Renee DiIulio is a contributing writer for RT. For more information, contact [email protected].