The Future of Nebulization

[Guest guest]

Liquid Nebulization: Emerging Technologies Conference Summary

Dean R Hess PhD RRT FAARC

Most physicians and respiratory therapists are knowledgeable of the use

of aerosolized drugs, but many are less familiar with the performance

characteristics of the nebulizer. In fact, the general opinion is that

the performance of the nebulizer is relatively unimportant. However,

there is accumulating evidence that the nebulizer itself does make a

difference. The decision to replace a good performing nebulizer with a

poor performing nebulizer may decrease the delivered dose in half or

more. Although this is less important for routine bronchodilator therapy,

it may make a big difference with newer aerosolized drugs. Increasingly,

the Food and Drug Administration is approving drugs to be used with a

specific nebulizer brand and new nebulizer designs are becoming available

for use with these drugs. There are several reasons why I think this

conference was important. First, new aerosol drug formulations are

becoming available and these will require better performing nebulizers.

Second, we as clinicians need to be knowledgeable of the newer

generations of nebulizers so that we can make informed purchase

decisions. Third, and perhaps most important, we must gain an increased

appreciation for aerosol therapy as a science. The proceedings of this

conference do much to synthesize the current state-of-the art related to

new nebulizer systems. This provides, in a complete and cogent manner,

the scientific basis for which clinicians can improve their knowledge of

the new generation of nebulizers. Key words: nebulization, aerosol, jet

nebulizer, ultrasonic nebulizer. [Respir Care 2002:47(12):1471-1476]

Introduction

The nebulizer is one of the devices most commonly used by respiratory

therapists (RTs). Drugs used in nebulizers have undergone intensive

scientific scrutiny, including studies of indications, hazards,

complications, and treatment schedules. Many physicians and RTs are

fluent in the mode of action and recommended dose of nebulizer drugs, but

most are relatively ignorant of nebulizer performance characteristics.

Terms such as mass median aerodynamic diameter, dead volume, and inhaled

mass are just not part of the lexicon of most clinicians. Nebulizer

selection is usually based on price, and the nebulizer brand may be

selected by the purchasing department rather than the respiratory care

department. Unfortunately, the general sentiment is that it does not

matter. Contrary to the evidence, the general thinking is that the drug

can be placed in any nebulizer, enough flow is added to generate an

aerosol, and the patient simply breathes the aerosol for 10 minutes. The

evidence is now clear that the nebulizer does make a difference. I

published a paper more than 5 years ago that illustrated that there are

considerable differences in output among commercially available

nebulizers. The decision to replace a good performing nebulizer with a

poor performing nebulizer may decrease the delivered dose by more than

half. Perhaps this does not matter for routine bronchodilator therapy,

but it can make a difference with drugs that are now becoming available.

In the case of tobramycin, for example, it could mean the difference

between effective therapy and ineffective therapy resulting in

pseudomonas infection, or the difference between effective therapy and

aminoglycoside toxicity. Increasingly, the Food and Drug Administration

is approving drugs for use with specific nebulizer brands, and new

nebulizer designs are becoming available for use with these drugs. The

entire text of this article is available in the December 2002 issue of

RESPIRATORY CARE.

The Future of Nebulization

W Barry MD

Introduction

Compliance and Adherence

Size

Appearance

Fashion

Noise

Power Source

Administration Time

End of Treatment/Dose-Remaining Indicators

Interaction with Patient/Patient and Physician Feedback

Multiple Doses

Effectiveness

The Future

Using Complex or Expensive Drugs to Treat Lung Disease

Persistent Pulmonary Hypertension of the Newborn

Delivery of Drugs for Gene Therapy

Gene Therapy in the Treatment of PPHN

Oligonucleotides and Inhalation

Summary

Currently available nebulizers are inefficient, bulky, noisy, and take

longer to use than other inhalation devices. Use of nebulizers is

increasingly confined to patients who cannot use other devices or who

require therapies not available in another form. In the future,

nebulizers will be smaller and more efficient. " Smart " nebulizers that

can monitor patient use and provide feedback to the patient and the

caregiver will be developed. Critical study will be needed to determine

whether these innovations improve patient compliance with therapy.

Nebulizers will also be refined for delivering complex molecules for both

pulmonary and systemic disease. One example is in the use of gene

therapy, in which issues such as the best gene vector are unresolved.

Nebulizing these complex molecules without damaging them may be

difficult, and nebulizers of the future will have to be more efficient to

avoid wasting expensive drugs. For the delivery of widely used, less

expensive medications, such as some bronchodilators, these innovations

will not be cost-effective, so cheaper, less efficient nebulizers will

continue to be used. Key words: nebulization, nebulizer, aerosol,

vaporizer, critical care, surfactant, gene therapy, persistent pulmonary

hypertension of the newborn, PPHN. [Respir Care 2002:47(12):1459-1469]

Introduction

Looking into the future is an attractive pastime for a number of reasons:

you can champion causes that are dear to your heart; other people cannot

contradict you, at least not in the present; and, as long as you predict

far enough into the future, you are unlikely to be around to hear the

opprobrium of your successors that the predictions were wrong. However,

prediction is also a difficult pastime, with many potential outcomes and

areas to be covered. In this review I will concentrate on a small number

of clinical situations to illustrate some areas in which nebulizer

therapy may be developed. Our path to the future is influenced by our

starting point in the past and by how we have traveled to get to our

present. Inhalational therapy has a long history, with vapors and smokes

being used in the treatment of respiratory disease and other ailments

more than 4,000 years ago. In the modern era, Sir Crichton

described the use of the vapors of boiling tar in the treatment of

tuberculosis, a practice continued in Berlin in the first half of the

nineteenth century. In 1859 a portable device was marketed in France that

generated an aerosol of liquid tar for medicinal use. Many types of

nebulizer have since been developed, but the commonest type in use today

remains similar in principle to the on nebulizer, a jet nebulizer

constructed of ebonite with a plate baffle to filter out large drug

particles. Until recently, improvements in nebulizer therapy have been

made by modifications of that type of device. Other reviews in this and

the previous issue of RESPIRATORY CARE have documented the

characteristics of the main nebulizer types and described various

approaches to improve the efficiency of the jet nebulizer, as well as new

approaches to nebulization that are being developed. This review will use

examples from clinical practice to speculate on how nebulizers may be

used in the future, to address 3 issues:

Patient compliance with inhaled medication therapy

Using complex or expensive drugs to treat lung disease

Delivering complex molecules for gene therapy The entire text of this

article is available in the December 2002 issue of RESPIRATORY CARE.

Smart Nebulizers

Gerald C Smaldone MD PhD

Introduction

Principles

Oropharyngeal Deposition

Deposition in the Deep Lung

Variability in Particle Deposition

Smart Nebulizers

Breath Actuation

Control of Dose During Tidal Breathing (Adaptive Aerosol Delivery)

" Slow and Deep " Aerosol Delivery Systems

Summary

Physicians are familiar with conventional nebulizers, which deliver

aerosols in a relatively uncontrolled manner. As aerosol medications

evolve beyond bronchodilators, the need for control of dose variability,

the possibility of overdose, and the need for efficient delivery have

provoked the industry to redesign aerosol delivery systems. The need to

target aerosol delivery to specific lung regions has focused efforts to

coordinate aerosol delivery with defined breathing maneuvers. This review

summarizes the major factors affecting aerosol deposition, discusses how

those factors are guiding new designs for aerosol delivery systems, and

describes some examples of the improved precision and efficiency of those

systems. Key words: nebulization, nebulizer, aerosol, lung deposition.

[Respir Care 2002:47(12):1434-1441]

Introduction

As aerosol delivery systems, nebulizers typically deliver aerosols

continuously while the patient breathes tidally. Advances in aerosol

device development involve both changes to aerosol-generating technology

and a direct interaction between the device and the patient. To

understand this interaction it is useful to review the basic factors that

affect the clinical delivery and deposition of aerosols. This review

focuses on physiologic factors that affect deposition and how those

factors have been incorporated into " smarter " aerosol delivery systems.

The entire text of this article is available in the December 2002 issue

of RESPIRATORY CARE.

> Nebulizers That Use a Vibrating Mesh or Plate with Multiple Apertures to

Generate Aerosol

> Rajiv Dhand MD

> Introduction

> Design Features of Aerosol Generators That Use a Vibrating Mesh

> or Plate with Multiple Apertures to Generate Aerosol

> Aerogen's Aerosol Generator

> Omron's Vibrating Mesh Technology

> ODEM's TouchSpray Technology

> Characteristics of Devices

> Aerogen Devices

> Omron Devices

> ODEM TouchSpray Inhaler Devices

> PARI eFlow

> Comparison of Vibrating Mesh/Plate Devices and Conventional Jet

> and Ultrasonic Nebulizers

> In Vitro Comparisons of Efficiency in Aerosolizing Solutions

> In Vitro Comparisons of Efficiency in Aerosolizing Suspensions

> Scintigraphic Evaluation of Pulmonary Deposition of Aerosol

> Clinical Evaluation of Devices

> Aerosolization of Insulin

> Aerosolization of Deoxyribonucleic Acid

> Limitations/Drawbacks of Vibrating Plate/Mesh Devices

> Summary

>

> Several electronic nebulizer devices that use a vibrating mesh or plate

> with multiple apertures to generate a fine-particle, low-velocity aerosol

> have been marketed or will shortly become available for clinical use.

> These devices have a high efficiency of delivering aerosol to the lung,

> such that the nominal dose of drugs to be administered could be

> substantially reduced. Moreover, the volume of drug solution left in

> these new devices when the nebulization has ceased is negligible, so

> there is potential to improve the cost-effectiveness of administering

> expensive medications. Because these devices nebulize at a faster rate

> than conventional jet or ultrasonic nebulizers, the duration of each

> treatment could be shortened. These devices efficiently nebulize

> solutions and suspensions; they have been successfully used for

> aerosolizing insulin, other proteins and peptides, and fragments of DNA.

> They could be employed for a wide variety of clinical applications,

> including the delivery of aerosols for systemic therapy and gene

> transfer. These devices have overcome many of the limitations associated

> with conventional jet and ultrasonic nebulizers, and they offer the

> versatility to modify the aerosol characteristics according to the

> clinical application for which they are employed. With these devices

> clinicians will be able to precisely control drug delivery to the

> respiratory tract. Key words: nebulization, nebulizer, aerosol, vibrating

> mesh, vibrating plate. [Respir Care 2002:47(12):1406-1416]

>

> Introduction

>

> Nebulizers convert liquids into aerosol particles for deposition in the

> lower respiratory tract. A pneumatic (jet) nebulizer uses the energy

> provided by compressed gas flow to generate an aerosol, whereas an

> ultrasonic nebulizer uses electricity to vibrate a piezoelectric crystal

> at high frequency. Standing waves are generated when the high-frequency

> vibrations are focused onto the surface of the medication solution.

> Liquid droplets break off from the wave crest to form an aerosol. For

> several decades nebulizers have been employed to deliver medications via

> inhalation. Indications for aerosol therapy, however, are rapidly

> expanding. In the not-so-distant future, aerosols could be used to

> deliver drugs to the respiratory tract for systemic effects and to

> deliver genes to the respiratory tract. There is a need for better

> technology to improve the efficiency, precision, and consistency of

> aerosol deposition in the lung, to use new formulations, and to allow

> efficient aerosolization of suspensions and drugs with high lipid

> solubility. In addition, there needs to be a concerted effort to protect

> respiratory therapists and other health care workers from occupational

> exposure to aerosolized drugs. This review discusses several new devices

> that have in common the ability to aerosolize a drug solution by using a

> vibrating mesh or plate with multiple apertures. These devices offer

> important advances in our ability to deliver aerosolized drugs to the

> respiratory tract. The entire text of this article is available in the

> December 2002 issue of RESPIRATORY CARE.