S://www.aarc.org/wp Content/uploads/2015/04/aerosol_guide_rt Aerosol Guide Rt

User Manual: Pdf s://www.aarc.org/wp-content/uploads/2015/04/aerosol_guide_rt How to get your COPD initiative funded

Open the PDF directly: View PDF .
Page Count: 61

A Guide To

Aerosol Delivery Devices

for Respiratory Therapists

4th Edition

Douglas S. Gardenhire, EdD, RRT-NPS, FAARC

Dave Burnett, PhD, RRT, AE-C

Shawna Strickland, PhD, RRT-NPS, RRT-ACCS, AE-C, FAARC

Timothy R. Myers, MBA, RRT-NPS, FAARC

Platinum Sponsor

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

A Guide to Aerosol

Delivery Devices for

Respiratory Therapists,

4th Edition

Produced by the

American Association

for Respiratory Care

Douglas S. Gardenhire, EdD, RRT-NPS, FAARC

Dave Burnett, PhD, RRT, AE-C

Shawna Strickland, PhD, RRT-NPS, RRT-ACCS, AE-C, FAARC

Timothy R. Myers, MBA, RRT-NPS, FAARC

With a Foreword by

Timothy R. Myers, MBA, RRT-NPS, FAARC

Chief Business Ofcer

American Association for Respiratory Care

DISCLOSURE

Douglas S. Gardenhire, EdD, RRT-NPS, FAARC has served as a consultant for the following

companies: Westmed, Inc. and Boehringer Ingelheim.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Foreward

Aerosol therapy is considered to be one of the corner-

stones of respiratory therapy that exemplies the nuances

of both the art and science of 21st century medicine. As

respiratory therapists are the only health care providers

who receive extensive formal education and who are tested

for competency in aerosol therapy, the ability to manage

patients with both acute and chronic respiratory disease as

the experts in aerosol therapy allows the concept of “art”

and “science” to take on a practical reality.

Respiratory therapists continue to be the experts when it

comes to the art and science of aerosol therapy. With the

rapidly changing eld of aerosol medications and delivery

systems, it is imperative that we not only share this expertise

with patients but also other members of the health care

delivery team across the continuum of care. With a renewed

focus on wellness and prevention within the U.S. health care

system and a determined focus to minimize cost and waste,

the choice of appropriate respiratory medications and deliv-

ery devices makes selection of both the drug and optimum

delivery device even more critical.

How does a therapeutic intervention around for centuries

still combine the art with science in the context of aerosol

therapy? The “science” component includes many different

aspects such as pharmacology, cardiopulmonary anatomy

and physiology, physics, and a thorough understanding of

the different aerosol delivery technologies on the market

today. In order to claim expertise in the science of aerosol

therapy and optimize it for patients, the respiratory therapist

must have concrete knowledge and understanding of the

numerous drug formulations, their mode of action, and an

understanding of the respiratory conditions where the drug

and delivery is recommended and supported by the scientic

evidence.

While the “art” of aerosol delivery is much more abstract

than the science, it is as equally important to the appropri-

ate delivery of respiratory medications for optimal outcomes.

For aerosol therapy, the interaction between technology

and human behavior is where “art” comes into play. There

is ample scientic evidence of sub-optimal or ineffective

use of aerosols when self-administered in large part due to

lack of knowledge about proper technique by patients. All

too often, patients do not receive optimum (or sometimes

any) benet from their prescribed metered-dose inhalers,

dry-powder inhalers, and nebulizers simply because they are

not adequately trained or evaluated on their proper use.

The combination of the right medication and the most

optimal delivery device with the patient’s cognitive and

physical abilities is the critical juncture where science inter-

sects with art. For aerosol therapy to be effective, the appro-

priate delivery system for the medication must be matched

to the patient’s ability to use it correctly. The art of aerosol

therapy does indeed arise from the science. When these two

different, but synergistic components of medicine do not

properly align, patient adherence decreases. Medication is

wasted. Minimal patient benet is derived.

Because aerosol therapy is integral to our scope of prac-

tice and because we are considered the experts in this area,

we have a professional obligation to our patients to continue

our learning and competencies in the delivery of aerosolized

medicines. Respiratory therapists must take advantage of

this opportunity to reinforce their value by updating their

knowledge of aerosol delivery systems and combining that

knowledge with effective assessment of patients requiring

this therapy. Recommending an appropriate delivery system

tailored specically to the patient’s abilities is part of that

assessment.

This guide will provide you the opportunity to advance

your knowledge and expertise in aerosol delivery. Mastery

of both the art and science of aerosol delivery can have a

profound impact on appropriately matching medications and

delivery devices to optimize your patients’ clinical outcomes.

You will also contribute to more cost-effective use of health

care system resources.

The fourth edition of this Aerosol Guide delivers detailed

and comprehensive information that, when combined with

your dedication and commitment to be the professional

experts in this important area, will empower you to provide

guidance to your physician, nurse, and pharmacist colleagues

— but, most importantly, to your patients.

Timothy R. Myers, MBA, RRT-NPS, FAARC

Chief Business Ofcer

American Association for Respiratory Care

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Continuing Respiratory

Care Education (CRCE)

As part of your membership benets in the American

Association for Respiratory Care® (AARC), the Association:

• provides you with continuing education opportunities;

• keeps track of all the CRCE® hours you earn from CRCE-

approved programs; and

• allows you to print online a transcript of your CRCE

records.

These services are available to you 24 hours a day, seven

days a week, on the AARC web site (www.AARC.org).

The contents of this book are approved for six CRCE con-

tact hours; and as an AARC member, there is no charge to

you. To earn those CRCE contact hours, please go to the

AARC web site at:

http://c.aarc.org/go/adu

Further instructions will be given on that web site, including:

• how to register to take an examination to assess your

mastery of course objectives;

• how to update your e-mail address so that registration

conrmation can be sent to you.

Learning Objectives

As you read this book, you will be able to:

1. Identify the terminology used in aerosol medicine.

2. State approximate amount of aerosol deposited in

the lower respiratory tract for nebulizers, pressurized

metered-dose inhalers (pMDIs), and dry-powder

inhalers (DPIs).

3. List advantages and disadvantages of inhalation

compared to other routes of drug administration.

4. Identify hazards of aerosol therapy that can impact the

patient receiving therapy as well as care providers and

bystanders.

5. List advantages and disadvantages of nebulizers for

aerosol delivery.

6. Compare the principle of operation of a jet nebulizer,

mesh nebulizer, and ultrasonic nebulizer.

7. Describe types of pneumatic jet nebulizer designs and

methods that are used to decrease aerosol loss from a

jet nebulizer during exhalation.

8. Learn steps for correct use of jet, ultrasonic, and mesh

nebulizers.

9. Describe the basic components of a metered-dose

inhaler.

10. List advantages and disadvantages of metered-dose

inhalers.

11. Compare and contrast performance of pMDIs with HFA

and CFC propellants.

12. Discuss factors affecting the pMDI performance and

drug delivery.

13. Explain the importance of priming and tracking the

number of doses for a metered-dose inhaler.

14. Compare and contrast the design of holding chambers

and spacers.

15. Identify factors that affect dose delivery from a holding

chamber/spacer.

16. List advantages and disadvantages of dry-powder

inhalers.

17. Describe the principle of operation of various

commercially available dry-powder inhalers.

18. Identify factors affecting the DPI performance and drug

delivery.

19. Explain how you know that each DPI is empty.

20. List the correct steps for use of a nebulizer, metered-

dose inhaler, metered-dose inhaler with holding

chamber/spacer, and dry-powder inhaler.

21. Describe causes and solutions of problems seen with

nebulizers, pMDIs, and DPIs.

22. Discuss criteria to assist clinicians in selecting an

aerosol delivery device.

23. Identify special considerations for neonatal and pediat-

ric drug delivery.

24. Explain how to establish an infection control manage-

ment system in aerosol drug delivery.

25. Describe the proper technique of cleaning aerosol

delivery devices.

26. Discuss the importance of occupational health and

safety for respiratory therapists.

27. List common problems and errors with each type of

inhaler.

28. Describe how to instruct and evaluate patients in the

use of inhaler devices.

iii

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Table of Contents

Foreword ..............................................................................i

Acronyms .............................................................................iv

The Science of Aerosol Drug Delivery ......................................................1

Terminology

Mechanisms of Aerosol Deposition and Particle Sizes

Types of Aerosol Generators

Where Does an Inhaled Aerosol Drug Go?

Equivalence of Aerosol Device Types

Advantages and Disadvantages of Inhaled Aerosol Drugs

Hazards of Aerosol Therapy

Currently Available Aerosol Drug Formulations

Small-Volume Nebulizers ................................................................9

Advantages and Disadvantages of SVNs

Types of SVNs

Factors Affecting Jet Nebulizer Performance and Drug Delivery

Nebulizers for Specic Applications

Continuous Aerosol Therapy

Drug-Delivery Technique

Inhalers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Pressurized Metered-Dose Inhalers .......................................................21

Advantages and Disadvantages of pMDIs

Types of pMDIs

Currently Available pMDI Formulations

Factors Affecting pMDI Performance and Drug Delivery

Drug-Delivery Technique

Metered-Dose Inhaler Accessory Devices ..................................................29

Advantages and Disadvantages of pMDI Inhaler Accessory Devices

Spacers

Valved Holding Chambers

Drug-Delivery Technique

Dry-Powder Inhalers ...................................................................32

Advantages and Disadvantages of DPIs

Types of DPIs

Currently Available DPI Formulations

Factors Affecting the DPI Performance and Drug Delivery

Drug-Delivery Technique

Criteria to Select an Aerosol Generator ...................................................40

Patient-Related Factors

Drug-Related Factors

Device-Related Factors

Environmental and Clinical Factors

Neonatal and Pediatric Aerosol Drug Delivery ..............................................42

Age and Physical Ability

Age and Cognitive Ability

Aerosol Drug Delivery in Distressed or Crying Infants

Patient-Device Interface

Parent and Patient Education

Infection Control......................................................................44

IC Management System in Aerosol Drug Delivery

Preventing Infection and Malfunction of Aerosol Generators at Hospitals or Clinics

Occupational Health and Safety of Respiratory Therapists

Educating Patients in Correct Use of Aerosol Devices........................................48

Patient Adherence

Common Patient Errors with pMDIs

Common Patient Errors with Holding Chambers/Spacers

Common Patient Errors with DPIs

Common Patient Errors with SVNs

Instructing and Evaluating Patients in the Use of Inhaler Devices

References ...........................................................................52

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Acronyms

CDC Centers for Disease Control and Prevention

CDER Center for Drug Evaluation and Research

CDRH Center for Devices and Radiological Health

CF cystic brosis

DPI dry-powder inhaler

FDA U.S. Food and Drug Administration

FPF ne-particle fraction

GSD Geometric Standard Deviation

HFA hydrouoroalkane

IC infection control

MMAD mass median aerodynamic diameter

MMD mass median diameter

pMDI pressurized metered-dose inhaler

SPAG small particle aerosol generator

SVN small-volume nebulizer

VHC valved holding chamber

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

The Science of

Aerosol Drug Delivery

Aerosols exist everywhere there is gas to breathe. From

pollen and spores, to smoke and pollution, to man-made

chemicals, the aerosol category includes any ne liquid or

solid particles. A “medical aerosol” is any suspension of liq-

uid (nebulizer or pMDI) or solid drug particles (pMDI or DPI)

in a carrier gas.1 Our respiratory systems evolved to have

ltration and elimination systems that must be overcome

or bypassed in the process of providing local delivery of

medications to the lung. Methods for generating aerosols,

formulating drugs, and administering medications effec-

tively to the desired site of action constitute the science of

aerosol drug delivery. As is the case in any scientic disci-

pline, one must rst understand the terms and denitions

used to describe the principles of aerosol medicine in order

to subsequently master its methods.

Terminology

Denitions of key terms used in aerosol drug delivery are

listed in alphabetical order below.

aerosol: a suspension of liquid and solid particles produced

by an aerosol generator such as the small-volume

nebulizer (SVN), the pressurized metered-dose inhaler

(pMDI), or the dry-powder inhaler (DPI)

aerosol deposition: process of aerosol particles depositing

on absorbing surfaces

aerosol generator: a device used for producing aerosol

particles

aerosol output: mass of medication exiting an aerosol gen-

erator

aerosol therapy: delivery of solid or liquid aerosol particles

to the respiratory tract for therapeutic purposes

dead volume (or residual volume): the amount of medica-

tion that remains in the nebulizer after a treatment is

complete

diffusion: the mechanism of aerosol deposition for small

particles less than 3 µm (Diffusion is also called

Brownian motion.)

dry-powder inhaler: an aerosol device that delivers the

drug in a powdered form, typically with a breath-actu-

ated dosing system

emitted dose: the mass of medication leaving an aerosol

generator as aerosol

ne-particle fraction (FPF): percentage of the aerosol

between 1–5 µm that deposits in the lung

heterodisperse: aerosol particles of different sizes

hydrouoroalkane (HFA): a nontoxic liqueed gas propel-

lant developed to be more environmentally friendly

than CFCs and used to administer the drug from a

pMDI

inhaled dose: the proportion of nominal or emitted dose

that is inhaled

inhaled mass: the amount of medication inhaled

inhaler: device used to generate an aerosolized drug for a

single inhalation

inertial impaction: the mechanism of aerosol deposition

for particles larger than 5 µm

gravitational sedimentation (gravitational settling): the

settling rate of an aerosol particle due to gravity, parti-

cle size, and time

geometric standard deviation (GSD): one standard devi-

ation above and below the median particle sizes in

an aerosol distribution that indicates the variability in

aerosol particle size

mass median aerodynamic diameter (MMAD): average

aerosol particle size as measured by a cascade impac-

tor

monodisperse: aerosol particles of same or similar sizes

nebulizer: an aerosol generator producing aerosol particles

from liquid-based formulations

nominal dose: the total drug dose placed in the nebulizer

plume: a bolus of aerosol leaving the pMDI or other aero-

sol devices

pressurized metered-dose inhaler (pMDI): a drug device

combination that dispenses multiple doses by means

of a metered value; used interchangeably with pMDI

respirable mass: the product of the ne particle fraction

multiplied by the inhaled mass

residual volume (or dead volume): the amount of med-

ication that remains in the nebulizer at the end of a

treatment

spacer: a valveless extension device that adds distance

between the pMDI outlet and the patient’s mouth

valved holding chamber: a spacer with a one-way valve

used to contain aerosol particles until inspiration occurs

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Mechanisms of Aerosol Deposition and

Particle Sizes

The major mechanisms of aerosol deposition include

inertial impaction, gravitational sedimentation (settling),

and diffusion. Inertial impaction occurs with larger (>3 µm),

fast-moving particles. Gravitational settling is a function of

particle mass and time, with the rate of settling proportion-

al to particle size and mass. Diffusion occurs with particles

smaller than 1 µm. These mechanisms come into play as

aerosol particles are inhaled orally or through the nose.

Larger particles (> 10 µm) are ltered in the nose and/or

the oropharynx, largely by inertial impaction; particles of

5–10 µm generally reach the proximal generations of the

lower respiratory tract, and particles of 1–5 µm reach to

the lung periphery.

Particle size plays an important role in lung deposition,

along with particle velocity and settling time. As particle

size increases above 3 µm, aerosol deposition shifts from

the periphery of the lung to the conducting airways.

Oropharyngeal deposition increases as particle size increas-

es above 6 µm. Exhaled loss is high with very small particles

of 1 µm or less. Consequently, particle sizes of 1–5 µm are

best for reaching the lung periphery, whereas 5–10 µm

particles deposit mostly in the conducting airways, and

10–100 µm particles deposit mostly in the nose.

Aerosol devices in clinical use produce heterodisperse

(also termed polydisperse) particle sizes, meaning that

there is a mix of sizes in the aerosol. Monodisperse

aerosols, which consist of a single particle size, are rare

in nature and medicine. A measure that quanties a

polydisperse aerosol is the mass median diameter (MMD).

This measure determines the particle size (in µm) above

and below which 50% of the mass of the particles is con-

tained. This is the particle size that evenly divides the mass,

or amount of the drug in the particle size distribution. This

is usually given as the mass median aerodynamic diameter,

or MMAD, due to the way sizes are measured. The higher

the MMAD, the more particle sizes are of larger diameters.

As seen in Figure 1, larger particles between 10–15 µm

deposit mostly in the upper airways, particles within the

5–10 µm range reach the large bronchi, and particles of

1–5 µm penetrate to the lower airways and lung periph-

ery.2

Types of Aerosol Generators

Three common types of aerosol generators are used for

inhaled drug delivery: the small-volume nebulizer (SVN), the

pressurized metered-dose inhaler (pMDI), and the dry-pow-

der inhaler (DPI). Each device type is described below.

• Small-Volume Nebulizer: The SVN is an aerosol gener-

ator that converts liquid drug solutions or suspensions

into aerosol and is powered by compressed air, oxy-

gen, a compressor, or an electrically powered device.

• Pressurized Metered-Dose Inhaler: The pMDI is a

small, portable self-contained drug device combina-

tion that dispenses multiple doses by a metered value.

Because of high medication loss in the oropharynx and

hand-held coordination difculty with pMDIs, holding

chambers and spacers are often used as ancillary devic-

es with the pMDI.

• Dry-Powder Inhaler: The DPI is an aerosol device that

delivers drug in a powdered form, typically with a

breath-actuated dosing system.

Where Does an Inhaled Aerosol Drug Go?

Lung deposition may range from 1–50% with clinical

aerosol delivery systems.3–7 Deposition is dependent on a

variety of factors such as the device, the patient, the drug,

and the disease. For example, out of 200 micrograms (µg)

of albuterol in two actuations or puffs from a pMDI, only

about 20–40 µg reach the lungs with correct technique.

The remaining drug is lost in the oropharynx, in the device,

or in the exhaled breath. Figure 2 indicates the percentag-

es of drug deposition for different aerosol systems, show-

ing that oropharyngeal loss, device loss, and exhalation/

ambient loss differ among aerosol device types, as do lung

doses.

Figure 1. A simplied view of the effect of aerosol particle

size on the site of preferential deposition in the airways

(From Reference 2, with permission)

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

It is important to realize that different types of aerosol

devices deposit a different fraction of the total dose of a

given drug (also termed “nominal” dose) in the lungs. In

addition, different types of aerosol devices such as nebuliz-

ers and pMDIs do not have the same nominal dose. Using

albuterol as an example, the typical pMDI nominal dose is

two actuations, or about 200 µg, while the typical nebuliz-

er nominal dose is 2.5 mg, or 12 times more drug. Table 1

lists both the pMDI and nebulizer nominal doses for several

drugs, showing this difference.

Equivalence of Aerosol Device Types

Historically, nebulizers were thought to be more effec-

tive than pMDIs, especially for short-acting bronchodilators

in acute exacerbations of airow obstruction. Contrarily,

evidence has shown equivalent clinical results whether

a pMDI, a nebulizer, or a DPI is used, provided that the

patient can use the device correctly.8 For bronchodila-

tors, the same clinical response is often achieved with

the labeled dose from the pMDI or nebulizer, despite the

higher nominal dose for the nebulizer. Because any of

these aerosol generators, if used properly, can be effective

with their label dose, dosage should be device specic and

based on the label claim.

Newer aerosol devices and drug formulations are increas-

ing the efciency of lung deposition when compared

to the traditional devices commonly used. For example,

lung deposition for HFA-beclomethasone dipropionate

(QVAR™, Teva Pharmaceuticals, North Wales, PA) is in

the range of 40–50% of the nominal dose using a pMDI

formulation with hydrouoroalkane propellant, which

replaces the older chlorouorocarbon (CFC) propellants.9

New devices such as the Respimat® inhaler (Boehringer

Ingelheim Pharmaceuticals, Ridgeeld, CT) have shown lung

depositions of 40%.10 Although lung dose efciency varies

between devices, inhalers with relatively low lung depo-

sition fraction have been clinically proven to achieve the

desired therapeutic effect in the target audience.

Figure 2. Drug deposition with common aerosol inhaler devices. Shown by color are the

varying percentages of drug lung deposition and drug loss in the oropharynx, device, and

exhaled breath.

pMDI = pressurized metered-dose inhaler; VHC = valved holding chamber;

SVN = small-volume nebulizer; DPI = dry-powder inhaler

(Modied, with permission, from Reference 1 and Reference 7)

Table 1. Differences in nominal (total) dose between a pMDI and an SVN

for different drug formulations (Modied, with permission, from Reference 1)

Drug pMDI Nominal Dose SVN Nominal Dose

Albuterol 0.2 mg (200 µg) 2.5 mg

Ipratropium 0.04 mg (40 µg) 0.5 mg

Levalbuterol 0.045 mg – 0.09 mg 0.31 mg – 1.25 mg

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Advantages and Disadvantages of

Inhaled Aerosol Drugs

There are a number of advantages and disad-

vantages that go along with the inhalation of

drugs to treat pulmonary disease (Table 2). The

primary advantage of inhaled aerosol therapy

is treating the lung directly with smaller doses,

resulting in fewer side effects than with oral

delivery.11 As seen in Figure 3, inhalation of terbu-

taline, a short-acting beta-2 agonist, from a pMDI

resulted in better airow than with a much larger

oral dose or even with a subcutaneous injection

of drug.

Hazards of Aerosol Therapy

Hazards associated with aerosol drug therapy may occur

as a result of inhaled medication, an aerosol generator

being used, the aerosol administration technique, and the

environment. Hazards of aerosol therapy can impact the

patient receiving therapy, as well as care providers and

bystanders.

Hazards for Patients

Adverse Reaction: Most hazards associated with aerosol

therapy are attributed to adverse reactions to the drug

being used. Therefore, inhaled medications should be

administered with caution. Types of adverse reactions

Figure 3. Changes in FEV1 for three different routes of

administration with terbutaline. Greater clinical effect was seen

with drug delivered as inhaled aerosol from a pMDI, compared

to similar or larger doses delivered orally or by subcutaneous

injection. (From Reference 6, with permission)

Table 2. Advantages and disadvantages of the inhaled aerosolized drugs

(Modied, with permission, from Reference 1)

Advantages

Aerosol doses are generally smaller than systemic

doses.

Onset of effect with inhaled drugs is faster than

with oral dosing.

Drug is delivered directly to the lungs, with

minimal systemic exposure.

Systemic side effects are less frequent and severe

with inhalation when compared to systemic

delivery.

Inhaled drug therapy is less painful than injection

and is relatively comfortable.

Disadvantages

Lung deposition is a relatively low fraction of the

total dose.

A number of variables (correct breathing pattern,

use of device) can affect lung deposition and dose

reproducibility.

The difculty of coordinating hand action and

inhalation with the pMDIs reduces effectiveness.

The lack of knowledge of correct or optimal use of

aerosol devices by patients and clinicians decreases

effectiveness.

The number and variability of device types confuses

patients and clinicians.

The lack of standardized technical information on

inhalers for clinicians reduces effectiveness.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

include headache, insomnia, and nervousness with adren-

ergic agents, local topical effects with anticholinergics, and

systemic/local effects of corticosteroids.12,13 If any of these

adverse reactions are seen during aerosol drug therapy, the

treatment should be ended and the physician should be

notied.

Bronchospasm: Administering a cold and high-density

aerosol may induce bronchospasm in patients with asthma

or other respiratory diseases.13-15 If bronchospasm occurs

during aerosol therapy, the therapy should be immediately

discontinued for 15-20 minutes. If it persists, the physician

should be notied.

Drug Concentration: In both jet and ultrasonic nebulizers,

drug concentration may increase signicantly during aero-

sol therapy.16-18 An increase in drug concentration may be

due to evaporation, heating, or the inability to efciently

nebulize suspensions.13,16,18,19 As a result of changes in drug

concentration, the amount of the drug remaining in the

nebulizer at the end of aerosol therapy is increased and

the patient is exposed to higher concentrations of inhaled

medications. This is a great problem with continuous-feed

nebulization.

Infection: It has been well documented that aerosol gener-

ators can become contaminated with bacteria and increase

the risk of infection in patients with respiratory diseases.20-25

The risk of transmission of an infection is dependent upon

duration of exposure of drugs with pathogens and the pro-

cedures taken by respiratory therapists to avoid pathogen

exposure. Proper practices of medication handling, device

cleaning, and sterilization can greatly reduce this risk.

Eye Irritation: Inhaled medications delivered with a face

mask may inadvertently deposit in the eyes and result in eye

irritation. Improving the interface between the face mask

and patient may eliminate this problem and increase the

amount of drug delivered to the distal airways. Therefore,

caution should be exercised when using a face mask during

aerosol drug administration.

Hazards for Care Providers and Bystanders

Exposure to Secondhand Aerosol Drugs: Care providers

and bystanders have the risk of exposure to inhaled medica-

tions during routine monitoring and care of patients. While

workplace exposure to aerosol may be detectable in the

plasma,26 it may also increase the risk of asthma-like symp-

toms and cause occupational asthma.27-29 The development

and implementation of an occupational health and safety

policy in respiratory therapy departments can minimize

exposure to secondhand aerosol drugs.

Infection: Care providers, bystanders, and even other

patients have the risk of inhaling pathogens during aerosol

therapy. The risk of infection can be minimized with the

development and implementation of an infection control

management system including use of masks, lters, and

ventilation systems.30-32

Currently Available Aerosol Drug

Formulations

Some aerosol drugs are available in more than one for-

mulation. Others (often newer drugs) are available only in a

single formulation. Table 3 provides currently available aero-

sol drug formulations, their brand names, their FDA-approved

aerosol delivery devices, and their costs.

Table 3. Currently available aerosol drug formulations with corresponding inhaler devices and costs

for use in the United States.

HFA = hydrouoroalkane; pMDI = pressurized metered-dose inhaler; SVN = small-volume nebulizer; DPI = dry-powder inhaler

Cost information from www. goodrx.com. Prices used were from WalMart in 2017.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Short-Acting Bronchodilator

Long-Acting Bronchodilator

Drug Brand Device Strength Doses Cost Cost/Dose

Albuterol AccuNeb® SVN 0.63 25 $50.20 $2.01

Sulfate 1.25 25 $50.20 $2.01

Albuterol Sulfate SVN 2.5 25 $15.30 $0.61

ProAir® HFA pMDI 200 $58.99 $0.30

ProAir RespiClick® DPI 200 $55.73 $0.28

Proventil® HFA pMDI 200 $73.74 $0.37

Ventolin® HFA pMDI 200 $56.42 $0.28

Levalbuterol Xopenex® SVN 0.31/3ml 24 $39.16 $1.63

Inhalation 0.63/3ml 24 $39.16 $1.63

Solution 1.25/3ml 24 $39.16 $1.63

1.25/0.5ml 24 $23.08 $0.96

Xopenex HFA™ pMDI 200 $61.61 $0.31

Ipratropium Ipratropium SVN vial 25 $4.57 $0.18

Bromide Bromide

Atrovent HFA® pMDI 200 $331.32 $1.66

Ipratropium Ipratropium SVN 120 $59.57 $0.25

Bromide and Bromide and

Albuterol Sulfate Albuterol Sulfate

DuoNeb® SVN 120 $284.54 $2.37

Combivent® pMDI 120 $336.97 $2.81

Respimat®

Drug Brand Device Strength Doses Cost Cost/Dose

Aclidinium Tudorza Pressair® DPI 400 mcg 60 $318.10 $5.30

Bromide

Arformoterol Brovana® SVN 15 mcg/2ml 30 $457.06 $15.24

60 $907.12 $15.12

Formoterol Perforomist® SVN 20 mcg/2ml 60 $873.92 $9.57

Indacaterol Arcapta® DPI 75 mcg 30 $227.70 $7.59

Salmeterol Serevent® DPI 50 mcg 60 $340.31 $5.67

Tiotropium Spiriva® DPI 18 mcg 30 $359.25 $11.98

Spiriva Respimat® pMDI 1.5 mcg 30 $359.25 $11.98

Spiriva Respimat® pMDI 2.5 mcg 30 $359.25 $11.98

Olodaterol Stiverdi pMDI 2.5 mcg 60 $180.74 $3.01

Respimat®

Umeclidinium Incruse® Ellipta® DPI 62.5 mcg 30 $314.17 $10.47

Glycopyrrolate Seebri Neohaler DPI 15.6 mcg 60 $313.67 $5.23

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Table 3. (continued)

Corticosteroids

Drug Brand Device Strength Doses Cost Cost/Dose

Beclomethasone QVAR™ 40 pMDI 40 mcg 120 $162.14 $1.35

QVAR™ 80 pMDI 80 mcg 120 $211.57 $1.76

Budesonide Pulmicort SVN 0.25 mg 30 $277.14 $9.24

Respules 0.5 mg 30 $324.93 $10.83

1.0 mg 30 $642.92 $21.43

Generic SVN 0.25 mg 30 $63.48 $2.12

0.5 mg 30 $73.47 $2.45

1.0 mg 30 $145.49 $4.85

Pulmicort® DPI 90 mcg 120 $164.14 $1.37

Flexhaler® 180 mcg 120 $214.12 $1.79

Ciclesonide Alvesco® pMDI 80 mcg 60 $243.51 $4.06

160 mcg 60 $243.51 $4.06

Flunisolide Aerospan® pMDI 80 mcg 120 $214.56 $1.79

Fluticasone Flovent Diskus® DPI 50 mcg 60 $165.03 $2.75

propionate 100 mcg 60 $173.96 $2.90

250 mcg 60 $226.57 $3.78

Flovent HFA® pMDI 44 mcg 120 $173.96 $1.45

110 mcg 120 $226.57 $1.89

220 mcg 120 $348.05 $2.90

ArmonAir® DPI 55 mcg 60 Newly approved

RespiClick® 113 mcg 60 No pricing available

232 mcg 60

Fluticasone Arnuity® Ellipta® DPI 100 mcg 30 $164.41 $4.48

furoate 200 mcg 30 $214.43 $7.15

Mometasone Asmanex® HFA pMDI 100 mcg 120 $191.68 $1.60

furoate 200 mcg 120 $224.06 $1.87

Asmanex® DPI 110 mcg 30 $190.00 $6.33

220 mcg 30 $205.00 $6.83

Mucoactive Drugs

Drug Brand Device Strength Doses Cost Cost/Dose

Dornase Alpha Pulmozyme® SVN 2.5mg/2.5ml 30 $3173.13 $105.77

N-Acetylcysteine SVN 4ml/10% 1 $2.46 $2.46

10ml/10% 1 $4.16 $1.64

30ml/10% 1 $9.81 $1.31

4ml/20% 1 $3.21 $3.21

10ml/20% 1 $6.02 $2.41

30ml/20% 1 $12.00 $1.60

Hyperosmolar HyperSal® SVN 3.5% 60 $52.99 $0.88

Saline 7% 60 $91.94 $1.03

PulmoSal™ (ph 7.4) SVN 7% 60 $51.94 $0.87

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Table 3. (continued)

Other Drugs

Drug Brand Device Strength Doses Cost Cost/Dose

Zanamivir Relenza® DPI 5 mg 20 $65.49 $3.28

Tobramycin TOBI® SVN 300mg/5ml 56 $7,578.95 $135.33

generic 300mg/5ml 56 $1590.21 $28.40

Bethkis SVN 300mg/4ml 56 $5862.93 $209.40

Tobi Podhaler DPI 28 mg 224 $9152.54 $40.85

Aztreonam Cayston® SVN 75 mg 84 $8254.28 $98.27

Cromolyn Sodium SVN 20mg/2ml 60 $211.63 $3.53

Ribavirin Virazole® SPAG 6g 1 $25766.30 $25766.30

Mannitol Aridol® DP Bronchial Challenge Test Kit, No pricing available

Combination Drugs

Drug Brand Device Strength Doses Cost Cost/Dose

Fluticasone and Advair HFA® pMDI 45/21 mcg 120 $285.26 $2.38

Salmeterol 115/21 mcg 120 $352.74 $2.94

230/21 mcg 120 $461.72 $3.85

Advair Diskus® DPI 100/50 mcg 60 $285.26 $4.75

250/50 mcg 60 $352.74 $5.88

500/50 mcg 60 $461.72 $7.70

AirDuo RespiClick® DPI 55/14 mcg 60 Newly approved

113/14 mcg 60 No pricing available

232/14 mcg 60

Budesonide and Symbicort® pMDI 80/4.5 mcg 120 $270.22 $2.25

Formoterol 160/4.5 mcg 120 $307.87 $2.57

Mometasone/ Dulera® pMDI 100/4 mcg 120 $290.54 $2.42

Formoterol 200 120 $290.54 $2.42

Fluticasone furate/ Breo® Ellipta® DPI 100/25 mcg 60 $314.80 $5.25

Vilanterol 200/25 mcg 60 $314.80 $5.25

Tiotropium/ Stiolto® Respimat® pMDI 2.5/2.5 mcg 60 $333.16 $5.55

Olodaterol

Umeclidinium/ Anoro® Ellipta® DPI 62.5/25 mcg 60 $333.16 $5.55

Vilanterol

Indacaterol/ Utibron Neohaler® DPI 27.5/15.6 mcg 60 $313.67 $5.23

Glycopyrrolate

Formoterol/ Bevespi pMDI 9/4.8 mcg 120 $333.16 $2.78

Gylcopyrrolate Aerosphere®

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Small-Volume

Nebulizers

Small-volume nebulizers (SVNs) are popular aerosol gen-

erators in acute care settings with clinicians and patients

as they convert drug solutions or suspensions into aerosols

that deposit into the patient’s lower respiratory tract while

requiring minimal patient cooperation.

Advantages and Disadvantages of SVNs

Nebulizers have long been the cornerstone of medical

aerosol therapy in the acute and critical care setting. Also,

they are frequently the device selected for patients such as

infants, small children, and the elderly who are unable to

operate, coordinate, or cooperate with the use of various

inhalers that require active participation and hand-eye-

breath coordination. This functionality offsets the issues of

portability, weight, noise, cost, and time of administration

associated with nebulizers. Table 4 lists the advantages and

disadvantages of small-volume nebulizers.

Nebulizers are regulated as medical devices by the U.S.

Food and Drug Administration (FDA) Center for Devices and

Radiological Health (CDRH). They are tested in accordance

with applicable standards for medical device electrical safe-

ty, electromagnetic compatibility, environmental tempera-

ture and humidity, shock and vibration, as well as for their

biocompatibility of materials.

Nebulizers are designed to be used with a broad range

of liquid formulations. Drugs for use with nebulizers are

approved by the FDA and the Center for Drug Evaluation

and Research (CDER). Historically, drug solutions for inha-

lation were approved based on studies using standard jet

nebulizers (the rst type of SVN) ranging in efciency from

6–12%. The use of more efcient nebulizers created the risk

of delivering inhaled dose above the upper threshold of the

therapeutic window, increasing the risk of side effects and

toxicity. Consequently, the FDA requires that the drug label

of new liquid formulations identify the nebulizers used in

the clinical studies (Table 5). Because drug delivery varies

with different nebulizer types, it is important to use the

nebulizer cited on the drug “label” when possible. At the

Table 4. Advantages and disadvantages of SVNS (Modied, with permission, from Reference 1)

Advantages

Ability to aerosolize many drug solutions

Ability to aerosolize drug mixtures (>1 drug), if

drugs are compatible

Minimal patient cooperation or coordination is

needed.

Useful in very young, very old, debilitated, or

distressed patients

Drug concentrations and dose can be modied.

Variability in performance characteristics among

different types, brands, and models

Normal breathing pattern can be used, and an

inspiratory pause (breath-hold) is not required for

efcacy.

Disadvantages

Treatment times may range from 5–25 minutes.

Equipment required may be large and

cumbersome.

Need for power source (electricity, battery, or

compressed gas)

Potential for drug delivery into the eyes with face

mask delivery

Potential for drug delivery exposure to clinicians

and caregivers

Assembly and cleaning are required.

Contamination is possible with improper handling

of drug and inadequate cleaning.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

very least, clinicians should be aware of the relative perfor-

mance of the “label” nebulizer.

Pneumatic jet nebulizers most commonly used in the

hospital or clinic are low-cost, mass-produced, single-pa-

tient-use disposable devices. Newer, more efcient nebuliz-

ers that operate at a higher efciency and require shorter

treatment durations tend to be more expensive (Table 6).

Nebulizer systems may include a nebulizer hand set, com-

pressor or power pack, tubing, and accessories. In general,

the compressor or electronics are durable and long-lasting,

whereas handsets and accessories require more frequent

replacement. Replacement costs are shown in Table 7.

Table 5. Drug formulations and approved nebulizers for that formulation

(Modied, with permission, from Reference 1)

Drug Formulation

Bronchodilator

Acetylcysteine

Arformoterol

Formoterol

Budesonide (Pulmicort Respules®)

Tobramycin (TOBI®)

Dornase alfa (Pulmozyme®)

Pentamadine (NebuPent)

Ribavirin (Virazole®)

Iloprost (Ventavis®)

Aztreonam (Cayston®)

Treprostinil (Tyvaso®)

Approved Nebulizer

Nebulizer type not specied

Should not be used with ultrasonic nebulizer

Pari LC®, Sidestream Plus

Hudson T Up-draft II, Marquest Acorn® II, Pari LC®,

Durable Sidestream®, Pari Baby™

Marquest Respirgard II

Small Particle Aerosol Generator

I-neb Adaptive Aerosol (AAD) System

Altera™ Nebulizer System

Tyvaso® Inhalation System

Table 6. Relative costs of different nebulizer systems

(Modied, with permission, from Reference 1)

Nebulizer Type Approximate Cost Range

Pneumatic compressor nebulizer $30–$200

Ultrasonic nebulizer $70–$250

Vibrating mesh/horn nebulizer $200–$1,200

Microprocessor-controlled breath-actuated nebulizer $750–$2,000

Table 7. Replacement costs of nebulizer components

(Modied, with permission, from Reference 1)

Nebulizer Components (Interval) Approximate Cost Range

Disposable jet nebulizer (1–7 days in acute care, longer use at home) $1–3

Jet nebulizer with bag reservoir (1–3 days) $4–15

Jet nebulizer with lter (1–3 days) $10–12

Breath-enhanced nebulizer $4–20

Breath-actuated jet nebulizer $4–6

Ultrasonic nebulizer medication chamber (daily or weekly) $1–5

USN handset replacement (3–12 months) $100–250

Vibrating mesh replacement (3–12 months) $40–150

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Types of SVNs

Jet Nebulizers

Jet nebulizers are

operated by com-

pressed air or oxygen

in order to aerosolize

liquid medications.

They are commonly

used because they are

the least expensive

kind of nebulizer. A

jet nebulizer delivers

compressed gas through a jet, causing a region of negative

pressure. The solution to be aerosolized is entrained into

the gas stream and is sheared into a liquid lm. This lm is

unstable and breaks into droplets due to surface tension

forces. A bafe located in the aerosol stream impacts these

droplets producing smaller particles. The operating perfor-

mance of jet nebulizers is affected by both the technical

and patient-related factors described in Table 8.

Factors Affecting Jet Nebulizer

Performance and Drug Delivery

There are many factors for respiratory therapists to keep

in mind during aerosol therapy. Nebulizer design holds a

key determining factor in the size of particles and output

performance produced, which results in the ultimate ef-

ciency of medication according to the factors discussed

below. Various types of nebulizers are available on the

market, and several studies have indicated that perfor-

mance varies between manufacturers and also between

nebulizers from the same manufacturer.1,33,34

• Gas Flow and Pressure: Jet nebulizers are designed

to operate by means of varied levels of compressed

gas ow and pressure. Each model of jet nebulizer is

designed to work best at a specic ow, ranging from

2–8 L/min, which should be listed on the device label.

Operating any jet nebulizer at a lower ow or pressure

will increase particle size. For example, a jet nebulizer

designed to operate at 6–8 L/min at 50 psi will pro-

duce larger particles if driven by a compressor pro-

ducing 13 psi. Consequently, jet nebulizers should be

matched with a compressor or gas source that match-

es their intended design. Gas ow is also inversely relat-

ed to nebulization time. Using a higher gas ow rate in

aerosol therapy will decrease the amount of treatment

time needed to deliver the set amount of drug.

• Fill and Dead Volumes: Altering the ll volume is

another factor that impacts the efciency of jet neb-

ulizers. Studies report increased efciency with this

due to nebulizers with a xed dead volume, and thus

an increase in ll volume reduces the proportion of

dead volume within the nebulizer. Although efciency

increases with a greater ll volume, there is also an

increase in nebulization time.34

Likewise, these nebu-

lizers do not function well with small ll volumes like

2 mL or less because this is close to dead volume (also

termed residual volume). Jet nebulizers do not aerosol-

ize below dead volume; therefore, it is recommended

to use a ll volume of 4–5 mL unless the nebulizer is

specically designed for a smaller ll volume.1,34 This

precaution dilutes the medication, allowing for a great-

er proportion to be nebulized, though it increases the

treatment time. Dead volume, the amount of medi-

cation remaining in the jet nebulizer at the end of a

treatment, can range from 0.5 to 2.0 mL. The greater

the dead volume, the less drug is nebulized.

• Gas Density: By a similar offsetting, the density of gas

used to run a jet nebulizer can impact aerosol deposi-

tion by affecting aerosol output and particle size. For

example, delivering aerosol with helium-oxygen (heliox)

gas mixtures can increase lung deposition by as much

as 50%. Using heliox at the same ow rate as with air

or oxygen reduces particle size and aerosol output, ulti-

mately increasing treatment times. Consequently, the

ow with heliox should be increased by 1.5–2 times to

bring particle size and output back to levels achieved

with air or oxygen.

• Humidity and Temperature: Humidity and tempera-

ture can also affect particle size and residual volume.

Table 8. Factors affecting penetration and deposition of therapeutic

aerosols delivered by jet nebulizers (Modied, with permission, from Reference 1)

Technical Factors

Design and model of nebulizer

Flow used to power nebulizer

Fill volume of nebulizer

Solution characteristics

Composition of driving gas

Designs to enhance nebulizer output

Continuous vs. breath-actuated

Patient Factors

Breathing pattern

Nose vs. mouth breathing

Composition of inspired gas

Airway obstruction

Positive pressure delivery

Articial airway and mechanical ventilation

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Specically, water evaporation

during aerosol therapy can

reduce the temperature of an

aerosol, which results in an

increase in solution viscosity and

a decrease in the nebulizer out-

put of drug.

• Breathing Pattern: Breathing

pattern inuences aerosol depo-

sition in the lower respiratory

tract. The patient should be

instructed to do tidal breath-

ing with periodic deep breaths

during aerosol therapy.

• Device Interface: Medical

aerosols can be administered using

either a mouthpiece or a face mask. Ideally, a mouth-

piece should be used. The nose tends to lter more

aerosol than the mouth, so use of a mouthpiece should

be encouraged, when appropriate. Mouthpieces can-

not be used for infants and small children. In addition,

the use of a mouthpiece may be uncomfortable for

longer aerosol therapy. Use of a mask increases the

amount of aerosol deposited on the face, in the eyes,

and into the nose. Whether a mouthpiece or a face

mask is used, it is important to instruct the patient

to inhale through the mouth during aerosol therapy.

Proper mask t and design can optimize the inhaled

dose and reduce deposition to the eyes. The respira-

tory therapist must keep all of these factors in mind

when practicing or equipping patients.

Types of Pneumatic Jet Nebulizer Designs

Nebulizer design changes over the past decade have

created different nebulizer categories.35,36 There are four

different designs of the pneumatic jet nebulizer: jet nebu-

lizer with reservoir tube, jet nebulizer with collection bag

or elastomeric reservoir ball, breath-enhanced jet nebuliz-

er, and breath-actuated jet nebulizer. All four of these are

depicted in Figure 4 and described below.

A. Jet Nebulizer with a Reservoir Tube: This is the least

expensive and most widely used nebulizer. It provides

continuous aerosol during inhalation, exhalation, and

breath-hold, causing the release of aerosol to ambient air

during exhalation and anytime when the patient is not

breathing (Figure 4-A).36-37 Consequently, only 8-15% of

the emitted aerosol is inhaled. In order to decrease drug

loss and increase inhaled mass, a t-piece and large bore

tubing are attached to the expiratory side of the nebuliz-

er. These types of nebulizers have been considered to be

inefcient due to their providing a low percentage of the

dose to the patient.38 Figure 5 illustrates the functioning of

a jet nebulizer. Examples of a jet nebulizer with a reservoir

tube model include the Sidestream Nebulizers™ (Philips,

Murrysville, PA) and the Micro Mist® (Teleex Medical,

Research Triangle Park, NC).

Figure 4. Different types of pneumatic jet nebulizer designs and their aerosol

output indicated by the shaded area: A. pneumatic jet nebulizer with reservoir

tube; B. jet nebulizer with collection bag; C. breath-enhanced jet nebulizer; D.

breath-actuated jet nebulizer. (From Reference 1, with permission)

Figure 5. Schematic illustration of the function of a jet

nebulizer (From Reference 1, with permission)

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

B. Jet Nebulizer with Collection Bag or Elastomeric

Reservoir Ball: These types of nebulizers generate

aerosol by continuously lling a reservoir (Figure 4-B).

The patient inhales aerosol from the reservoir through

a one-way inspiratory valve and exhales to the atmo-

sphere through an exhalation port between the one-

way inspiratory valve and the mouthpiece.35,37 Figure

6 illustrates the principle of operation and patterns

of gas ow during inhalation and exhalation with

the Circulaire® II (Westmed, Tucson, AZ) which is one

model of the nebulizer with a collection bag or elasto-

meric reservoir ball.

C. Breath-Enhanced Jet Nebulizer: Breath-enhanced

nebulizers use two one-way valves to prevent the

loss of aerosol to environment (Figure 4-C). When

the patient inhales, the inspiratory valve opens and

gas vents through the nebulizer. Exhaled gas passes

through an expiratory valve in the mouthpiece. Figure

7 illustrates the operation principle of the breath-en-

hanced nebulizer. PARI LC® Sprint (PARI, Midlothian,

VA), NebuTech HDN® (Salter Labs, Arvin, CA), and

SideStream Plus® (Philips, Murrysville, PA) are the

breath-enhanced nebulizers available on the market.

D. Breath-Actuated Jet Nebulizer: Breath-actuated

nebulizers are designed to increase aerosol drug

delivery to patients by generating aerosol only during

active inspiration. Consequently, loss of medication

during expiration phase is greatly reduced, as shown

in Figure 4-D.37 Whereas breath actuation can increase

the inhaled dose by more than three-fold, this ef-

ciency is achieved only by an increase in dosing time.

Breath-actuation mechanisms can be classied as man-

ual, mechanical, and electronic:

1. Manual Breath-Actuated: The rst generation of

breath-actuated nebulizers uses a thumb control to

regulate aerosol production during inspiration and

expiration. Blocking the patient-controlled thumb port

directs gas to the nebulizer only during inspiration;

releasing the thumb at the port pauses the nebuliza-

tion (Figure 8). The thumb control breath-actuated

nebulizer wastes less of the medication being aerosol-

ized, but it signicantly increases the treatment time

and requires good hand-breath coordination.

2. Mechanical Breath-Actuated: The AeroEclipse® II BAN

Figure 6. Schematic illustration of the function

of a jet nebulizer with collecting bag

(From Reference 37, with permission)

Figure 7. Schematic illustration of the

function of a breath-enhanced jet nebulizer

(From Reference 37, with permission)

Figure 8. Schematic illustration of the function of

a manual breath-actuated jet nebulizer

(From Reference 7, with permission)

aerosol

storage bag

one-way valve exhale

inhale

power gas

open vent

air intake

exhale

inhale

power gas

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

(Monaghan Medical Corporation, Plattsburgh, NY) is an

example of mechanical breath-actuated nebulizers. As

shown in Figure 9, the mechanical breath-actuated neb-

ulizer has a breath-actuated valve that triggers aerosol

generation only during active inspiration and eliminates

the need for a storage bag or reservoir. Patients must

be able to generate a sufcient inspiratory ow to

trigger the nebulizer. Therefore, the sensitivity of this

mechanism makes it suitable only for some children and

adults.

3. Microprocessor Breath-Actuated: The nal type of

breath-actuated jet nebulizer is more complex but

more appropriate to a wider range of users. In this

type, compressor-driven jet nebulizers are actuated by

an electronic circuit, commonly triggered by a pres-

sure transducer sensing inspiratory effort. For several

decades these devices have been used in pulmonary

function and research labs to administer precise boluses

of aerosol for methacholine challenge. A newer gener-

ation of “smart” microprocessor-controlled breath-ac-

tuated nebulizers uses computer programs and sensing

technology to control the pattern of aerosol generation

and even to calculate and track the delivered dose. The

I-neb AAD® system (Philips) is one model of the micro-

processor, breath-actuated that uses vibrating mesh

nebulization.

Ultrasonic Nebulizers

Ultrasonic nebulizers convert electrical energy to

high-frequency vibrations using a transducer. These

vibrations are transferred to the surface of the solution,

creating a standing wave that generates aerosol (Figure

10). Ultrasonic nebulizers were initially introduced as

large-volume nebulizers most commonly used to deliver

hypertonic saline for sputum inductions. Small-volume

ultrasonic nebulizers are now commercially available for

delivery of inhaled bronchodilators but should not be

used with suspensions such as budesonide. Ultrasonic

nebulizers tend to heat medication. This raises concerns

about disrupting proteins, but that does not affect com-

monly inhaled medications. The MicroAir® Ultrasonic

Model (Omron Healthcare, Bannockburn, IL) and MABIS®

NebPak™ and MiniBreeze™ Ultrasonic Nebulizers (Mabis

Healthcare, Waukegan, IL) are different models of the

ultrasonic nebulizer.

Mesh Nebulizers

Mesh nebulizers use electricity to vibrate a piezo (at

approximately ~128 KHz) element that moves liquid

formulations through a ne mesh to generate aerosol.

The diameter of the mesh or aperture determines the

size of the particle generated. Mesh nebulizers are very

efcient and result in minimal residual volume (0.1–0.5

mL). As seen in Figure 11, mesh nebulizers utilize two

basic mechanisms of action: active vibrating mesh and

passive mesh.

Figure 9. Schematic illustration of the function of

a mechanical breath-actuated nebulizer

(From Reference 37, with permission)

Figure 10. Components and operation principle of an ultrasonic

nebulizer (From Reference 1, with permission)

air intake

(spring-loaded valve)

exhale

inhale

power gas

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Active Vibrating Mesh: Active vibrat-

ing mesh nebulizers have an aperture

plate with 1,000–4,000 funnel-shaped

holes vibrated by a piezo-ceramic ele-

ment that surrounds the aperture plate.

The Aeroneb® Ultra and Solo (Aerogen,

Galway, Ireland), Akita® Jet (Inamed,

Germany) and eRapid® (PARI, Midlothian,

VA) are models of the active vibrating

mesh nebulizers (Figure 11, left).

Passive Mesh: These types of nebulizers

utilize an ultrasonic horn to push uid

through a mesh (Figure 11, right). I-neb®

AAD System® (Philips) and MicroAir™ U22

(Omron Healthcare) are models of the

passive mesh nebulizer. A third-gener-

ation adaptive aerosol delivery (AAD)

system such as the I-neb® has a small,

battery-powered, lightweight, and silent

drug delivery device designed to deliver

a precise, reproducible dose of drug. The

aerosol is created by a passive mesh, and

aerosol is injected into the breath at the

beginning of inhalation (Figure 12). The

dosage of the drug is controlled through

specic metering chambers. The meter-

ing chambers can deliver a pre-set vol-

ume ranging from 0.25 to 1.7 mL with

a residual volume of about 0.1 mL. The

I-neb® model incorporates an AAD algo-

rithm that pulses medication delivery

into 50–80% of each inspiration, based

on a rolling average of the last three

breaths. Throughout the treatment, the

I-neb® provides continuous feedback to

the patient through a liquid crystal dis-

play; and upon successful delivery of the

treatment, the patient receives audible

and tactile feedback.

Nebulizers for Specic

Applications

Nebulizer for Ribavirin Administration

The small-particle aerosol

generator (SPAG) is a large-volume

nebulizer designed solely to deliver

Figure 11. Basic congurations of mesh nebulizers

Figure 12. Adaptive aerosol delivery as provided by the Philips I-neb®. As illustrated,

aerosol is injected into the breath at the beginning of inhalation.

(With permission of Philips)

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

aerosolized ribavirin (Virazole®, Valeant

Pharmaceuticals, Aliso Viejo, CA) for

prolonged periods of nebulization. It

consists of a nebulizer and a drying

chamber that reduces the MMAD to

about 1.3 µm. Because of teratogenic

characteristics of ribavirin, a scavenging

system is strongly recommended for use

during its administration.

Nebulizer for Aerosolized Pentamidine

Administration

When administering aerosolized pent-

amidine, an SVN tted with inspiratory

and expiratory one-way valves and with

expiratory lter is used. These valves

prevent exposure of secondhand pent-

amidine aerosol and contamination of

the ambient environment with exhaled

aerosol. In 2014, the National Institute

for Occupational Safety and Health

(NIOSH) removed pentamidine from

its hazardous drug list indicating it no longer requires

these devices or aerosol treatments to be delivered in a

negative pressure room.

Continuous Aerosol Therapy

Continuous aerosol drug administration is a safe

treatment modality and is used to treat patients suffer-

ing acute asthma exacerbations. Researchers reported

that it may be as effective as intermittent aerosol ther-

apy or may, in fact, be superior to intermittent nebuli-

zation in patients with severe pulmonary dysfunction.39

Figure 13 illustrates a basic setup for continuous aero-

sol therapy that includes an infusion pump, a one-way

valved oxygen mask, and a reservoir bag. Commercial

nebulizers used in continuous nebulization common-

ly have luer lock ports designed for use with infusion

pumps. The nebulization is most commonly adminis-

tered using standard aerosol masks.

Drug-Delivery Technique

Because different types of nebulizers are available on

the market, the respiratory therapist should carefully

review operation instructions prior to giving aerosol

therapy and certainly prior to instructing patients in

at-home aerosol delivery. Proper technique is provided

in Technique Box 1.

Figure 13. Setup for continuous aerosol therapy (From Reference 1, with permission)

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Technique Box 1. Steps for Correct Use of Nebulizers

Technique for Jet Nebulizers: When a jet nebulizer is used, the patient should:

1. Assemble tubing, nebulizer cup, and mouthpiece (or mask).

2. Place medicine into the nebulizer cup.

3. Sit in an upright position.

4. Connect the nebulizer to a power source.

5. Breathe normally with occasional deep breaths until sputter occurs or until the end of nebulization.

6. Keep the nebulizer vertical during treatment.

7. Rinse the nebulizer with sterile or distilled water and allow to air dry.

Technique for Mesh and Ultrasonic Nebulizers: When a mesh or ultrasonic nebulizer is used,

the patient should:

1. Correctly assemble the nebulizer per manufacturer’s specications.

2. If applicable, follow manufacturer’s instructions in performing a functionality test prior to the rst use

of a new nebulizer as well as after each disinfection to verify proper operation.

3. Pour the solution into the medication reservoir. Do not exceed the volume recommended by the

manufacturer.

4. Sit in an upright position.

5. Turn on the power.

6. Hold the nebulizer in the position recommended by the manufacturer.

7. Follow the instructions for breathing technique that is recommended by the manufacturer for these

uniquely designed mesh and ultrasonic nebulizers.

8. If the treatment must be interrupted, turn off the unit to avoid waste.

9. At the completion of the treatment, disassemble and clean as recommended by the manufacturer.

10. When using a mesh nebulizer, do not touch the mesh during cleaning. This will damage the unit.

11. Once or twice a week, disinfect the nebulizer following the manufacturer’s instructions.

General Steps To Avoid Reduced or No Dosing for All Nebulizers: When using nebulizers, the following

steps should be used in order to avoid reduced or no dosing during aerosol treatment. The patient should:

1. Read and follow the instructions.

2. Make sure that the nebulizer is properly assembled and all connections are secured tightly.

3. Make sure that the nebulizer is cleaned and dried between uses.

4. Make sure that the nebulizer operated in its proper orientation.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Technique Box 1. Steps for Correct Use of Nebulizers (continued)

*Cleaning: Please refer to the Infection Control section on pages

44–47 for the cleaning instructions of small-volume nebulizers.

When Does the Treatment Need To Be Ended?

Troubleshooting

Problem with Jet Nebulizers: Absent or Low Aerosol

Causes Solutions

Loose or unattached connections Check the connections and make sure that they are

properly attached.

Inappropriate owmeter setting Check the owmeter setting and adjust the ow

if it is not appropriate.

Obstruction in the orice of the Check the orice of the jet nebulizer and

jet nebulizer clear obstructions when needed.

Problems with Mesh and Ultrasonic Nebulizers: The Unit Does Not Operate

Causes Solutions

Incorrect battery installation (seen in both Check the battery installation and reinstall if needed.

mesh and ultrasonic nebulizers)

External power source connection (seen Check the connections with the AC adapter

in both mesh and ultrasonic nebulizers) and the electrical output.

Overheated unit (seen in ultrasonic Turn off the unit, wait until it cools down, and restart

nebulizers) the unit.

Incorrect connection of the control module Check the connections with the control module cable

cable (seen in mesh nebulizers) and attach them properly, if needed.

Malfunctioning electronics (seen in both mesh Replace the unit.

nebulizers and ultrasonic nebulizers)

Nebulizers are commonly used for intermittent

short-duration treatments and typically have a set vol-

ume of drug formulation placed in the medication res-

ervoirs. The drug remaining in a nebulizer after therapy

ranges from 0.1 to 2 mL.18 Whereas some respiratory

therapists and patients tap the nebulizer in order to

reduce dead volume and increase nebulizer output,40

others continue aerosol therapy past the point of sput-

tering in an effort to decrease dead volume.18 Some

nebulizers will sputter for extended periods of time

after the majority of the inhaled dose has been adminis-

tered. Evidence suggests that after the onset of sputter,

very little additional drug is inhaled.18,41 Because the

time it takes to administer the drug is a critical factor

for patient adherence to therapy, some clinicians have

adopted recommendations to stop nebulizer therapy

at, or one minute after, the onset of sputter. Newer

nebulizers may use microprocessors to monitor how

much dose has been administered and automatically

turn off the nebulizer at the end of each dose.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Inhalers

The pressurized metered-dose inhaler and dry-powder

inhaler are medical aerosol delivery devices that combine

a device with a specic formulation and dose of drug. Each

actuation of the inhaler is associated with a single inspira-

tion of the patient. These are typically single-patient-use

devices dispensed from the pharmacy with a specic quan-

tity of medication and disposed of when the medication

has been depleted.

Inhalers are approved by the FDA Center for Drug

Evaluation Research (CDER) as drug and device combina-

tions. They typically are required to go through the com-

plete drug development process from pre-clinical to pivotal

trials in hundreds to thousands of patients. Inhaler-based

drugs must have reproducible doses (+/- 20) from rst to

last dose and have a shelf life with drug of at least 12–24

months. Once an inhaler enters the Phase III trials, the

design and materials are set and cannot be changed with-

out additional expensive clinical trials.

There is a large variety of inhaler designs, and many

drugs are available only in a single inhaler form (Figure

14). Patients are commonly prescribed several types of

inhalers with different instructions for operation. Confusion

between device operation can result in suboptimal therapy.

For example, pMDIs typically require slow inspiratory ow

(<30 L/min) with a breath-hold, while a DPI may require

signicantly high ows (30–90 L/min) based on their resis-

tive properties to disperse a full dose. Patients may confuse

which inspiratory ow to use with which device and may

get much less drug from both devices. Therefore, educa-

tion and repetitive return demonstration is the key to prop-

er inhaler use.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Figure 14. Common Inhalers Available in the United States

Spiriva®

Handihaler®

(tiotropium

bromide)

Inhalation Powder

Boehringer Ingelheim

Pharmaceuticals, Inc.

Atrovent® HFA

(ipratropium

bromide HFA)

Inhalation

Aerosol

Boehringer Ingelheim

Pharmaceuticals, Inc.

Anticholinergics/b2-Agonist Combination

Combivent®

Respimat®

(ipratropium

bromide and

albuterol sulfate)

Inhalation Spray

Boehringer Ingelheim Pharmaceuticals, Inc.

Stiolto®

Respimat®

(tiotropium

bromide

and olodaterol)

Inhalation Spray

Boehringer Ingelheim Pharmaceuticals, Inc.

Utibron™

Neohaler®

(indacaterol

and

glycopyrrolate)

Inhalation Powder

Sunovion Pharmaceuticals Inc.

Anoro®

Ellipta®

(umeclidinium

and vilanterol)

Inhalation

Powder

GlaxoSmithKline

Bevespi

Aerosphere™

(glycopyrrolate

and formoterol

fumarate)

Inhalation Aerosol

AstraZeneca Pharmaceuticals

Alvesco®

(ciclesonide)

Inhalation

Aerosol

Nycomed

Flovent® Diskus®

(uticasone

propionate)

Inhalation

Powder

GlaxoSmithKline

ArmonAir™ RespiClick®

(uticasone propionate)

Inhalation Powder

Teva Specialty Pharmaceuticals

Flovent® HFA

(uticasone

propionate)

Inhalation

Aerosol

GlaxoSmithKline

Arnuity®

Ellipta®

(uticasone

furoate)

Inhalation

Powder

GlaxoSmithKline

Pulmicort®

Flexhaler®

(budesonide)

Inhalation Powder

AstraZeneca LP

Asmanex

Twisthaler®

(mometasone)

Inhalation

Powder

Schering Corporation

QVAR®

(beclomethasone

dipropionate)

Inhalation

Aerosol

Teva Specialty Pharmaceuticals

Aerospan®

(unisolide)

Inhalation

Aerosol

Mylan Pharmaceuticals

Corticosteroids

Anticholinergics

ProAir® HFA

(albuterol sulfate)

Inhalation Aerosol

Teva Specialty

Pharmaceuticals

ProAir® RespiClick®

(albuterol sulfate)

Inhalation Powder

Teva Specialty

Pharmaceuticals

Arcapta™

Neohaler™

(indacaterol)

Inhalation Powder

Novartis Pharmaceuticals

Striverdi®

Respimat®

(olodaterol)

Inhalation Spray

Boehringer Ingelheim

Pharmacueticals, Inc.

Ventolin® HFA

(albuterol sulfate HFA)

Inhalation Aerosol

GlaxoSmithKline

Serevent® HFA

(salmeterol xinafoate)

Inhalation Aerosol

GlaxoSmithKline

Xopenex® HFA

(levalbuterol tartare)

Inhalation Aerosol

Sunovion Pharmaceuticals Inc.

Serevent® Diskus®

(salmeterol xinafoate)

Inhalation Powder

GlaxoSmithKline

b2-Agonists

Proventil® HFA

(albuterol sulfate)

Inhalation Aerosol

3M Pharmaceuticals Inc.

Advair® Diskus®

(uticasone

propionate and

salmeterol)

Inhalation Powder

GlaxoSmithKline

Advair® HFA

(uticasone propionate

and salmeterol

xinafoate)

Inhalation Aerosol

GlaxoSmithKline

Breo® Ellipta®

(uticasone furoate

and vilanterol)

Inhalation Powder

GlaxoSmithKline

Symbicort®

(budesonide and

formoterol fumarate

dihydrate)

Inhalation Aerosol

AstraZeneca

AirDuo

RespiClick®

(uticasone

propionate

and salmeterol)

Inhalation Powder

Teva Specialty Pharmaceuticals

b2-Agonist/Corticosteroid Combination Other

Dulera®

(mometasone

furoate/

formoterol

fumarate

dihydrate)

Inhalation Aerosol

Merck

Tudorza™

Pressair™

(aclidinium

bromide)

Inhalation Powder

Forest Pharmaceuticals, Inc.

Incruse®

Ellipta®

(umeclidinium)

Inhalation

Powder

GlaxoSmithKline

Seebri™

Neohaler®

(glycopyrrolate)

Inhalation

Powder

Sunovion Pharmaceuticals Inc.

TOBI® Podhaler®

(tobramycin)

Inhalation

Powder

Novartis Pharmaceuticals

Relenza®

(zanamivir)

Inhalation Powder

GlaxoSmithKline

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Pressurized

Metered-Dose Inhalers

Since its development by Dr. George Maison in 1955,

the pMDI has been the most common aerosol generator

prescribed for patients with asthma and COPD. This is

because it is compact, portable, easy to use, and provides

multi-dose convenience in a single device.

Advantages and Disadvantages of pMDIs

The pMDI was designed and developed as a drug and

device combination that delivers precise doses of specic

drug formulations. Unlike nebulizers, drug preparation

and handling is not required with pMDIs, and the internal

components of pMDIs are difcult to contaminate. Table

9 gives the advantages and disadvantages associated with

the use of pMDIs.

Types of pMDIs

There are two major types of pMDIs: conventional pMDIs

and soft-mist inhalers. Regardless of manufacturer or active

ingredient, the basic components of the pMDI include the

canister, propellants, drug formulary, metering valve, and

actuator. The characteristics of each pMDI component are

described in Table 10.

Conventional pMDI

As seen in Figure 15, the pMDI consists of a canister, the

medication, the propellant/excipient, a metering valve, the

mouthpiece, and actuator.42 The medication represents

only 1–2% of the mixture emitted from the pMDI and is

either suspended or dissolved in the propellant/excipient

mixture. The propellant of the pMDI makes up 80% of the

mixture. These agents prevent aggregation of the drug

particles and lubricate the metering valve. They also ensure

that the drug is well suspended in the canister. The meter-

ing valve acts to prepare a pre-measured dose of medica-

tion along with the propellant. The volume of the metering

valve changes from 25–100 µL and provides 50 µg to 5 mg

of drug per actuation, depending on the drug formulation.

The conventional pMDI has a press-and-breathe design.

Depressing the canister into the actuator releases the

drug-propellant mixture, which then expands and vaporizes

to convert the liquid medication into an aerosol. The initial

vaporization of the propellant cools the aerosol suspension.

The canister aligns the hole in the metering valve with the

metering chamber when it is pressed down. Then, the high

propellant vapor pressure forces a pre-measured dose of

Table 9. Advantages and disadvantages of pMDIs (Modied, with permission, from Reference 1)

Advantages

Portable, light, and compact

Multiple dose convenience

Short treatment time

Reproducible emitted doses

No drug preparation required

Difcult to contaminate

Disadvantages

Hand-breath coordination required

Patient activation, proper inhalation pattern, and

breath-hold required

Fixed drug concentrations and doses

Reaction to propellants in some patients

Foreign body aspiration from debris-lled

mouthpiece

High oropharyngeal deposition

Difcult to determine the dose remaining in the

canister without dose counter

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

medication out of this hole and through the actuator noz-

zle. Last, releasing the metering valve rells the chambers

with another dose of the drug-propellant mixture. The pro-

pellants used with pMDIs are HFAs. HFAs are pharmacolog-

ically inert and do not contain surfactant or use alcohol for

this purpose.

Soft-Mist pMDI

The Respimat® (Boehringer Ingelheim Pharmaceuticals,

Ridgeeld, CT) is a propellant-free soft-mist inhaler. The

Respimat® utilizes mechanical energy in the form of a ten-

sioned spring to generate the soft aerosol plume. The ener-

gy from turning the transparent base to the right one-half

turn draws a predetermined metered volume of solution

from the medication cartridge through a capillary tube into

a micro-pump. When the dose release button is depressed,

the energy from the spring forces the solution to the

mouthpiece, creating a soft aerosol plume that lasts approx-

imately 1.5 seconds. Similar to pMDIs, the Respimat® will

need to be primed before use and at times when the device

has had no use. If not used for more than 3 days, actuate

the inhaler once. After more than 21 days of no use, it is

Figure 15. Standard components of pMDI (Modied with

permission from Reference 42)

Table 10. Basic components of the pMDI (From Reference 1 with permission)

Component Particulars

Canister Inert, able to withstand high internal pressures and utilize a coating to prevent

drug adherence

Propellants Liqueed compressed gases in which the drug is dissolved or suspended

Drug Formulary Particulate suspensions or solutions in the presence of surfactants

or alcohol that allocate the drug dose and the specic particle size

Metering Valve Most critical component that is crimped onto the container and is responsible for

metering a reproducible volume or dose

Elastomeric valves for sealing and preventing drug loss or leakage

Actuator Frequently referred to as the “boot,” partially responsible for particle size based

on the length and diameter of the nozzle for the various pMDIs (Each boot is

unique to a specic pMDI/drug.)

Dose Counter This component provides a visual tracking of the number of doses remaining in

the pMDI

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

recommended to actuate the device until aerosol is seen,

then actuate 3 more times. Since the device is propellant

free, there is no need to shake it. The Respimat® has a dose

indicator and will lock once all medication is used. Figure

16 shows the standard components of the Respimat®.

Currently Available pMDI Formulations

A number of aerosol formulations are available for use in

pMDIs today (Figure 14). Pressurized metered-dose inhalers

are presently used to administer beta-2 agonists, anticho-

linergics, anticholinergic/beta-2 agonist combinations, cor-

ticosteroids, and anti-asthmatic drugs.

Factors Affecting pMDI Performance and

Drug Delivery

Most pMDIs are designed to deliver a drug dose of 100

µm per actuation. Just like other aerosol generators, drug

delivery with the pMDIs is approximately 10–20% of the

nominal dose per actuation. The particle size of aerosols

produced by the pMDI is in the ne particle fraction range

in which the aerodynamic diameter of aerosols is less than

5 µm. Several factors inuence the pMDI performance and

aerosol drug delivery. Understanding the effects of these

factors will improve the efcacy of pMDIs when used for

patients with pulmonary diseases. Therefore, both respira-

tory therapists and patients must actively control the fol-

lowing effects:

• Shaking the Canister: Not shaking a pMDI canister that

has been standing overnight decreases total and respi-

rable dose by 25% and 35%, respectively, because the

drugs in pMDI formulations are usually separated from

the propellants when standing.43 Therefore, pMDIs must

be shaken before the rst actuation after standing in

order to rell the metering valve with adequately mixed

suspension from the canister.12

• Storage Temperature: Outdoor use of pMDIs in very

cold weather may signicantly decrease aerosol drug

delivery. Dose delivery was constant with HFA pMDIs

over the range of -20º to 20ºC.

• Nozzle Size and Cleanliness: The amount of med-

ication delivered to the patient is dependent upon

nozzle size, cleanliness, and lack of moisture. Actuator

nozzle is pMDI specic, and the coordination of the

nozzle with the medication will inuence both inhaled

dose and particle size. In general, there is an inverse

relationship between the inner diameter of the nozzle

extension and the amount of drug delivered to the

patient.44 A nozzle extension with an inner diameter < 1

mm increases drug delivery.44 White and crusty residue

due to crystallization of medication may inuence drug

delivery. Therefore, the nozzle should be cleaned peri-

odically based on the manufacturer’s recommendations.

• Timing of Actuation Intervals: The rapid actuation of

more than two puffs with the pMDI may reduce drug

delivery because of turbulence and the coalescence

of particles.43 A pause between puffs may improve

bronchodilation, especially during asthma exacerba-

tions with episodes of wheezing and poor control of

symptoms.45 In other cases, such as in the day-to-day

management of pre-adolescents with a beta agonist

(terbutaline) and a corticosteroid (budesonide), pauses

between puffs have not been found to be benecial.46

Although early research was mixed regarding the impor-

tance of a pause between the two actuations, recent

literature suggests a pause of one minute between

actuations for effective aerosol therapy.1,7,13

• Priming: Priming is releasing one or more sprays into

the air. Initial and frequent priming of pMDIs is required

in order to provide an adequate dose. The drug may be

Figure 16. Soft-mist inhaler

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

separated from the propellant and other ingredients in

the canister and metering valve when the pMDI is new

or has not been used for awhile. Because shaking the

pMDI will mix the suspension in the canister but not

the metering chamber, priming of the pMDI is required.

Table 11 provides the recommended guidelines for

priming the various pMDIs available on the market.

• Characteristics of the Patient: Characteristics of the

patient using the pMDI will result in a variability of aero-

sol deposition. For example, aerosol deposition will be

lower in infants and children due to differences in their

anatomy and their physical and cognitive abilities.

• Breathing Techniques: There are two primary tech-

niques for using a pMDI without a spacer: the open-

mouth technique and the closed-mouth technique.

The manufacturers of pMDIs universally recommend

the closed-mouth technique for using a pMDI. In this

method, the mouthpiece of the boot is placed between

the sealed lips of the patient during drug administra-

tion. On the other hand, some researchers and clini-

cians have advocated an open-mouth technique in

an attempt to reduce oropharyngeal deposition and

increase lung dose.47,48

Table 11. Priming requirements for commercially available pMDIs (Modied, with permission, from Reference 1)

Short-Acting Bronchodilators

Inhaled Corticosteroids

Combination Drugs

Generic Name Brand Name Time to Prime No. of Sprays

Albuterol Sulfate HFA Proventil® HFA New and when not used for 2 weeks 4

Ventolin® HFA New and when not used for 14 days 4

Levalbuterol HCl Xopenex® HFA New and when not used for 3 days 4

Ipratropium Bromide HFA Atrovent® HFA New and when not used for 3 days 2

Ipratropium Bromide/ Combivent® HFA New and when not used for 24 hours 3

Albuterol Sulfate Combination

Generic Name Brand Name Time to Prime No. of Sprays

Beclomethasone QVAR™ New and when not used for 10 days 2

Propionate HFA

Ciclesonide Alvesco® New and when not used for 10 days 3

Fluticasone Propionate Flovent® HFA New 4

Not used more than 7 days or if dropped 1

Generic Name Brand Name Time to Prime No. of Sprays

Budesonide combined Symbicort® HFA New and not used more than 7 days or 2

with Formoterol if dropped

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

When using the open-mouth technique, the inhaler is

placed two nger widths away from the lips of an open

mouth and aimed at the center of the opening of the

mouth. Studies suggest that the open-mouth technique

reduces unwanted oropharyngeal deposition by allow-

ing aerosol plume more distance to slow down before

reaching the back of the mouth and up to two-fold more

drug deposition to the lung than with use of the closed-

mouth technique.47,49 In contrast, other researchers

suggest that the open-mouth technique does not offer

any advantage over the closed-mouth technique,50,51 but

that it does create additional hazards such as the aerosol

plume being misdirected from the mouth and into the

eye or elsewhere.52 Therefore, the best technique should

be determined based on the patient’s physical abilities,

coordination, and preference. If the patient is well coordi-

nated and can master the open-mouth technique better,

it can be used by following the directions below. Also,

the patient’s aerosol administration technique should be

observed continuously and corrected when appropriate.

Proper technique is provided in Technique Box 2.

Drug-Delivery Technique

Because different types of pMDIs are available on the

market, the respiratory therapist should carefully review

operation instructions prior to giving aerosol therapy

and certainly prior to instructing patients in at-home use.

Proper technique is provided in Technique Box 2.

How To Know the pMDI Is Empty: Since their intro-

duction in the 1950s, pMDIs have not been packaged

with dose counters that allow patients

to determine when a pMDI should be

discarded.53-55 After the pMDI delivers

the number of puffs stated on their

label, it may look, taste, and feel like it

is still working, but the dose delivered

may be very low. This “tailing off effect”

may last long after the pMDI is “empty

of drug.”13,56 Also, the pMDI without a

dose counter could lead to waste if the

inhaler is discarded prematurely. Indirect

methods such as oating the canister in

water are misleading and can reduce the

ability of the pMDI to work properly.55,57,58

Therefore, they should not be used to

determine the amount of medication remaining in the

canister.

The only reliable method to determine the number of

doses remaining in a pMDI is counting the doses given

either manually or with a dose counter. Manual methods

include reading the label to determine the total number

of doses available in the pMDI and using a log to indicate

every individual actuation given (including both priming

and therapy doses). This tally is subtracted from the num-

ber of actuations on the label until all have been used.

At that time, the pMDI should be properly discarded.

Unfortunately, manually counting doses may be imprac-

tical and undependable, especially in patients who use

reliever medications on the go.

Therefore, the U.S. Department of Health and Human

Services FDA requires new pMDIs to have integrated

dose counters and recommends that all pMDIs have

dose counting devices that indicate when the pMDI

is approaching its last dose.59 The dose counter is a

counting device attached to the top of the pMDI can-

ister or to the boot of the device. When the pMDI is

actuated, it counts down the number of actuations

from the total remaining in the canister. The Ventolin®

HFA (GlaxoSmithKline, Research Triangle Park, NC) and

Flovent® HFA (GlaxoSmithKline) have built-in dose count-

ers (Figure 17).

Also, mechanical or electronic dose counters have been

available from third parties for use by attachment to a

range of pMDIs. Although research has conrmed accept-

able performance and patient satisfaction by pMDIs with

(continued on page 28)

Figure 17. Counter on Ventolin® HFA and Flovent® HFA pMDIs

Technique Box 2. Steps for Correct Use of pMDIs

Technique for pMDIs

Open-Mouth Technique: The patient should be instructed to:

1. Remove the mouthpiece cover and shake the pMDI thoroughly.

2. Prime the pMDI into the air if it is new or has not been used for several days.

3. Sit up straight or stand up.

4. Breathe all the way out.

5. Place the pMDI two nger widths away from their lips.

6. With mouth open and tongue at (tip of tongue touching inside of their lower front teeth), tilt outlet

of the pMDI so that it is pointed toward the upper back of the mouth.

7. Actuate the pMDI as she/he begins to breathe in slowly.

8. Breathe slowly and deeply through the mouth and hold their breath for 10 seconds. If she/he cannot

hold their breath for 10 seconds, then for as long as possible.

9. Wait one minute if another puff of medicine is needed.

10. Repeat Steps 2–10 until the dosage prescribed by the physician is reached.

11. If taking a corticosteroid, she/he should rinse their mouth after the last puff of medicine, spit out the

water, and not swallow it.

12. Replace the mouthpiece cover on the pMDI after each use.

Closed-Mouth Technique: The patient should be instructed to:

1. Remove the mouthpiece cover and shake the inhaler thoroughly.

2. Prime the pMDI into the air if it is new or has not been used for several days.

3. Sit up straight or stand up.

4. Breathe all the way out.

5. Place the pMDI between their teeth; make sure that their tongue is at under the mouthpiece and

does not block the pMDI.

6. Seal their lips.

7. Actuate the pMDI as they begin to breathe in slowly.

8. Hold their breath for 10 seconds. If they cannot hold their breath for 10 seconds, then for as long as

possible.

9. Wait one minute if another puff of medicine is needed.

10. Repeat Steps 2–10 until the dosage prescribed by the patient’s physician is reached.

11. If taking a corticosteroid, she/he should rinse the mouth after the last puff of medicine, spit out the

water and not swallow it.

12. Replace the mouthpiece cover on the pMDI after each use.

Breath-Actuated pMDI (Autohaler™) Technique: When using the Autohaler™, the patient

should be instructed to:

1. Remove the mouthpiece cover and check for foreign objects.

2. Keep the Autohaler™ in a vertical position while the arrow points up, and do not block the air vents.

3. Prime the Autohaler™ into the air if it is new or has not been used recently.

4. Push the lever up.

5. Push the white test re slide on the bottom of the mouthpiece for priming the Autohaler™.

6. Push the lever down in order to release the second priming spray.

7. Return the lever to its down position and raise the lever so that it snaps into place.

8. Sit up straight or stand up.

9. Shake the Autohaler™ three or four times.

10. Breathe out normally, away from the Autohaler™.

11. Place the pMDI between their teeth. Make sure that their tongue is at under the mouthpiece and

does not block the pMDI.

12. Seal their lips around the mouthpiece.

13. Inhale deeply through the mouthpiece with steady moderate force,

14. Pay attention to the click sound and the feel of a soft puff when the Autohaler™ triggers the release of

medicine.

15. Continue to inhale until the lungs are full.

16. Remove the mouthpiece from the mouth.

17. Hold breath for 10 seconds or as long as possible.

18. Repeat steps above until the dosage prescribed by the patient’s physician is reached.

19. Replace the mouthpiece cover and make sure the lever is down.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Technique Box 2. Steps for Correct Use of pMDIs (continued)

Technique for pMDIs

Soft Mist pMDI (Respimat™) Technique: When using the Respimat™, the patient

should be instructed to:

Preparation:

1. With the cap closed, press the safety catch while pulling off the clear base. Be careful not to touch the

piercing element located inside the bottom of the clear base.

2. Push the narrow end of the cartridge into the inhaler. The base of the cartridge will not sit ush with

the inhaler. About 1/8 of an inch will remain visible when the cartridge is correctly inserted.

3. The cartridge can be pushed against a rm surface to ensure it is correctly inserted.

4. Do not remove the cartridge once it has been inserted into the inhaler.

5. Write the discard by date on the label of the inhaler. The discard by date is 3 months from the date the

cartridge is inserted.

6. Put the clear base back into place. Do not remove the clear base again. The inhaler should not be

taken apart after they have inserted the cartridge and put the clear base back.

Priming:

7. Hold the inhaler upright with the cap closed to avoid accidental release of dose.

8. Turn the clear base in the direction of the white arrows on the label until it clicks (half a turn).

9. Flip the cap until it snaps fully open.

10. Point the inhaler toward the ground. Press the dose-release button. Close the cap.

11. Repeat steps 7–10 until a spray is visible.

12. Once the spray is visible, repeat steps 7–10 three more times to make sure the inhaler is ready for use.

Patient-Use Instructions:

1. Hold the inhaler upright with the cap closed to avoid accidental release of dose.

2. Turn the clear base in the direction of the white arrows on the label until it clicks (half turn).

3. Flip the cap until it snaps fully open.

4. Breathe out slowly and fully, and then close lips around the end of the mouthpiece without covering

the air vents.

5. Point inhaler toward the back of mouth.

6. While taking in a slow, deep breath through the mouth, press the dose-release button and continue to

breathe in slowly for as long as possible.

7. Hold breath for 10 seconds or for as long as comfortable.

8. Close the cap until next prescribed dose.

General Steps To Avoid Reduced or No Dosing for pMDIs: The patient should:

1. Remove the cap of the pMDI from the boot.

2. Prime as directed (Table 11 on page 24).

3. Clean and dry the boot of the pMDI based on the manufacturer’s guidelines.

4. Track remaining doses.

Troubleshooting

Problem with Jet Nebulizers: Absent or Low Aerosol

Causes Solutions

Incorrect pMDI assembly Check the assembly and reassemble when needed.

Incorrect pMDI and spacer assembly Check the assembly of the pMDI/spacer and reassemble if

needed.

Empty the pMDI Check the dose counter or daily log sheet to ensure there is

enough medicine in the canister. Otherwise, replace the

pMDI.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Figure 18. Currently available pMDI dose counters on the market

(continued from page 25)

dose counters,60-62 care must

be taken to assure that a

third-party dose counter works

with the specic pMDI being

used.18,63 Some of the built-

in counters may not t the

spacer, and improper t to the

canister may interfere with

proper actuation, resulting

in no or partial drug being

emitted and in a miscount

of remaining doses.63 Using

a third-party dose-counting

device increases the cost of

aerosol therapy, which may

limit their wide acceptance.

Figure 18 shows currently

available pMDI dose counters

in the United States.

With any third-party counter, read the product label and accompanying package

information for each pMDI before use and follow the manufacturer’s recommend-

ed doses. When attempting to keep track of the number of doses remaining in the

pMDI, Table 12 outlines monitoring recommendations with and without integrated

dose counters.

Cleaning: Please refer to the Infection Control section on page 44 for the cleaning

instructions for inhalers.

Table 12. Monitoring remaining pMDI doses

Without Dose Counter: The user should:

1. Determine the number of puffs that the pMDI has when it is full.

2. Calculate how long the pMDI will last by dividing the total number of puffs in the pMDI by the total puffs used. Also

remember that the medication will run out sooner if the pMDI is used more often than planned.

3. Identify the date that the medication will run out and mark it on the canister or on the calendar.

4. Keep track of how many puffs of medicine administered on a daily log sheet and subtract them to determine the

amount of medication left in the pMDI.

5. Keep the daily log sheet in a convenient place such as bathroom mirror.

6. Replace the pMDI when all of the puffs have been administered.

With Dose Counter: The user should:

1. Determine how many puffs of medicine that the pMDI has when it is full.

2. Track the pMDI actuations used and determine the amount of medication left in the pMDI by checking the counter

display.

3. Learn to read the counter display. Each dose counter has a specic way of displaying doses remaining in the canis-

ter. For example, turning red indicates that the number of actuations is less than 20 puffs and it is time to rell the

pMDI. Reading the manufacturer’s guidelines to interpret the counter display is recommended before its use.

4. When the last dose is dispensed, properly dispose of the pMDI.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Metered-Dose Inhaler

Accessory Devices

Metered-dose inhaler accessory devices were designed

to overcome the difculties experienced when using a

pMDI and are available in different forms and sizes.

Advantages and Disadvantages of pMDI

Inhaler Accessory Devices

The use of these devices improves the effectiveness of

aerosol therapy and reduces oropharyngeal deposition by

adding volume and space between the metering valve and

the patient’s mouth. They overcome problems with hand-

breath coordination. Table 13 lists both advantages and

disadvantages seen with valved holding chambers (VHCs)

and spacers used in conjunction with pMDIs.

While the term spacer is used in clinical practice to refer

to all types of extension add-on devices, these devices are

categorized into spacers or holding chambers (or valved

holding chambers) based on their design. A spacer is a sim-

ple tube or extension device which adds space and volume

between the pMDI and mouth with no one-way valves to

contain the aerosol plume after pMDI actuation. A holding

chamber (valved holding chamber) is an extension spacer

device with one-way valve(s) to contain the aerosol until

inhaled and direct exhalation away from the aerosol in the

chamber, reducing aerosol losses with poor hand-breath

coordination. In addition to the major design difference

that denes spacers versus (valved) holding chambers,

there are other design differences among brands of hold-

ing chambers and spacers. Volume may vary, although in

the United States most holding chambers/spacers are less

than 200 mL. Direction of spray may vary between forward

(toward the mouth) and reverse (away from the mouth).

The AeroChamber® (Monaghan Medical Corporation),

OptiChamber Diamond® and the OptiChamber® Advantage

(Philips) are examples of forward sprays. The ACE® Aerosol

Cloud Enhancer (Smiths Medical, Dublin, OH) is an example

of reverse spray. Some holding chambers/spacers accept

the manufacturer’s mouthpiece-actuator (the boot), while

others have a nozzle receptacle for accepting only the can-

ister. As an example, the ACE® has a canister nozzle recep-

tacle, while the AeroChamber®, OptiChamber Advantage®

and OptiChamber Diamond® have malleable openings to

accept the pMDI mouthpiece. While boots are designed

specic to each pMDI, the canister nozzles vary and may

not t any one specic nozzle receptacle, reducing drug

efcacy. Figure 19 shows examples of spacers and holding

chambers.

Table 13. Advantages and disadvantages of holding chambers or spacers (“add-on”

devices) used with pMDIs (Modied, with permission, from Reference 64)

Advantages

Reduced oropharyngeal drug impaction and loss

Increased inhaled drug by two to four times than

the pMDI alone

Allows use of the pMDI during acute airow

obstruction with dyspnea

No drug preparation required

Simplies coordination of pMDI actuation and

inhalation

Helps reduce local and systemic side effects.64

Disadvantages

Large and cumbersome compared to the pMDI

alone

More expensive and bulky than a pMDI alone

Some assembly may be needed

Patient errors in ring multiple puffs into chamber

prior to inhaling or there is a delay between

actuation and inhalation

Possible contamination with inadequate cleaning

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Figure 19. Examples of VHCs and spacers

Spacers

The use of a spacer with

pMDIs should produce at

least an equivalent inhaled

dose and clinical effect to

that of a correctly used

pMDI alone. A spacer pro-

vides additional volume that

slows the aerosol velocity

from a pMDI, allowing a

reduction in particle size.

Aerosol retention and dis-

charged dose depends on

the size and shape of the

spacer, and electrostatic

charge on the inner walls

of plastic spacers. Spacers

decrease oral deposition,

but they only provide limit-

ed protection against poor

hand-breath coordination.

When using a spacer, it is

important for the patient

to coordinate their inhalation to occur slightly before

actuating the inhaler. Some spacers require removal of

the inhaler canister from the manufacturer’s actuator

and incorporation into a special orice on the spacer. It is

important to understand that dose delivery can be affected

in some spacer designs if the device does not t the pMDI

properly or if the design uses a special orice or actuator

incorporated into the spacer itself. Occasionally, clinicians

or patients construct homemade holding chambers from

plastic containers (e.g., soda bottle) or other devices (e.g.,

toilet paper roll). These may function as a spacer and pro-

vide protection against reduced dose with pMDI actuation

before inhalation, but they do not protect against actua-

tion during exhalation. Also, their performance is variable,

so they should not be considered as suitable replacements

for a commercially available spacer.

Valved Holding Chambers

A valved holding chamber (VHC) has a low-resistance

one-way valve that allows aerosol particles to be contained

within the chamber for a short time until an inspiratory

effort opens the valve. Although the presence of a one-way

valve prevents aerosol particles from exiting the chamber

until inhalation begins, optimal aerosol dosing still depends

on inhaling as close to or simultaneously with pMDI actua-

tion into the chamber. Time delays can signicantly reduce

the available dose for inhalation from a VHC. The one-way

valve should have a low resistance so that it opens easily

with minimal inspiratory effort. Valves placed between the

chamber and the patient also act as an impaction point,

further reducing oropharyngeal deposition. It’s important

to assure the valve works properly, as dysfunctional valves

can cause ineffective delivery of medication.65 Ideally,

there should be a signal to provide feedback if inspiratory

ow is too high. Children with low tidal volumes (less than

device dead space) may need to take several breaths from

a VHC through a face mask for a single pMDI actuation. In

this case, the VHC should incorporate one-way valves for

both inhalation and exhalation to decrease rebreathing

and avoid blowing aerosol from the chamber. A VHC with

mouthpiece costs as little as $15–$20, and a static-free

device with mask can cost as much as $50–$60.

Drug-Delivery Technique

While spacers and VHCs provide many benets for opti-

mal drug delivery with pMDIs, there are also potential

problems with their use (Table 13). Improper technique

may decrease drug delivery or, in some cases, cause the

dose to be lost. Possible causes of decreased drug delivery

include multiple actuations into the device, electrostatic

charge, inhaling before actuating the pMDI, delay between

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

actuation and inhaling the dose, or improper insertion of

actuator into spacer and/or VHC.66 It has been shown that

improper insertion of the actuator can contribute to a

spray of medication that does not follow the optimal axis

of the chamber and a good proportion of medicine ends

up deposited on the inside of the chamber.67 Also, it has

been suggested that spacer size and shape may provide

better deposition of specic particle sizes.66 More research

is needed on length, shape, and volume of spacers. In

children, lack of a proper mask t, a spacer volume that is

greater than tidal volume (mechanical dead space), and

crying are problematic. Proper technique is provided in

Technique Box 3.

Cleaning: Please refer to the Infection Control section on

page 44 for cleaning instructions for the pMDI chamber

and collapsible bag device.

Technique Box 3. Steps for Correct Use of pMDI with Spacer/VHC

Technique for pMDIs with Spacer/VHC: The patient should be instructed to:

1. Remove the mouthpiece cover and shake the inhaler thoroughly.

2. Prime the pMDI into the air if it is new or has not been used for several days.

3. Assemble the apparatus and check for foreign objects.

4. Keep the canister in a vertical position.

5. Sit up straight or stand up.

6. Breathe all the way out.

7. Follow the instructions below based on the type of device interface used:

With the mouthpiece:

a. Place the mouthpiece of the spacer between their teeth and seal their lips. Make sure that their

tongue is at under the mouthpiece and does not block the pMDI.

b. Actuate the pMDI as they begin to breathe in slowly. Also make sure to inhale slowly if the device

produces a “whistle” indicating that inspiration is too rapid.

c. Move the mouthpiece away from the mouth and hold their breath for 10 seconds. If they cannot

hold their breath for 10 seconds, then hold for as long as possible.

With the mask:

d. Place the mask completely over the nose and mouth and make sure it ts rmly against the face.

e. Hold the mask in place and actuate the pMDI as they begin to breathe in slowly. Also make sure to

inhale slowly if the device produces a “whistle” indicating that inspiration is too rapid.

f. Hold the mask in place while the child takes six normal breaths (including inhalation and exhalation),

then remove the mask from the child’s face.

8. Wait 15–30 seconds if another puff of medicine is needed.

9. Repeat steps above until the dosage prescribed by the patient’s physician is reached.

10. If taking a corticosteroid, rinse the mouth after the last puff of medicine, spit out the water, and do not

swallow it.

11. Replace the mouthpiece cover on the pMDI after each use.

General Steps To Avoid Reduced or No Dosing for pMDIs with Spacer/VHC: The patient should:

1. Assure proper t of the pMDI to the spacer or VHC.

2. Remove cap from the pMDI boot.

3. Clean and reassemble the pMDI spacers and VHCs based on the manufacturers’ instructions.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Dry-Powder Inhalers

Dry-powder inhalers (DPIs) are portable, inspiratory-

ow-driven inhalers that administer dry-powder formula-

tions to the lungs. DPIs do not contain propellant and are

breath-actuated. The patient’s inspiratory effort, both their

inspiratory ow rate and the volume inhaled, creates the

energy to disaggregate the small drug particles from larger

carrier particles and disperse the particles as aerosol emit-

ted from the device. DPIs coordinate release of the drug

with the act of inhalation. They have been developed to

overcome the difculties of using metered-dose inhalers

and are often prescribed with the intention of providing

the patient with an overall more user-friendly and predict-

able therapy.

Advantages and Disadvantages of DPIs

Dry-powder inhalers have both advantages and disad-

vantages as seen in Table 14. Because they do not require

hand-held coordination, the patient’s inspiratory ow

should be adequate enough to draw the drug from the

device. It is important that the patient understands how

the DPI works and how it should be used. For example,

the patient should know that they should not exhale into

the device. This will prevent the introduction of ambient

humidity into the mouthpiece and the resulting negative

effect to the medication. Such precautions and others,

explored in greater detail below, should be considered by

clinicians when prescribing a DPI for individual patients and

when performing follow-up evaluations of patient success

with a DPI.

Types of DPIs

Currently, DPIs can be classied into three categories

based on the design of their dose containers, i.e., sin-

gle-dose DPIs, multiple unit-dose DPIs, and multiple-dose

DPIs (Figure 20). While the single-dose DPIs have individually

wrapped capsules that contain a single-dose of medication,

multiple unit-dose DPIs disperse individual doses that are

premetered into blisters of medication by the manufacturer.

The third type, the multiple-dose DPI, either measures the

dose from a powder reservoir or uses blister strips prepared

by the manufacturers to deliver repeated doses. Regardless

of the type of DPI, they all have the same essential compo-

nents incorporated within the inhaler. They all have a drug

holder, an air inlet, an agglomeration compartment, and a

mouthpiece. The design of these components allows DPIs to

induce sufcient turbulence and particle-to-particle collision

Table 14. Advantages and disadvantages of DPIs (Modied, with permission, from Reference 1)

Advantages

Small and portable

Built-in dose counter

Propellant free

Breath-actuated

Short preparation and administration time

Disadvantages

Dependence on patient’s inspiratory ow

Patient less aware of delivered dose

Relatively high oropharyngeal impaction

Vulnerable to ambient humidity or exhaled

humidity into mouthpiece

Limited range of drugs

Different DPIs with different drugs

Easy for patient to confuse directions for use with

other devices

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Figure 20. Currently available dry-powder aerosol formulations in the United States

categorized by design features (see text description of design features)

that detaches particles from

their carrier surface and deag-

glomerates larger particles into

smaller particles.

Single-Dose DPIs

Single-dose DPIs operate

by evacuating powder med-

ication from a punctured

capsule. The HandiHaler®

(Boehringer Ingleheim), The

TOBI Podhaler® (Novartis),

and the Neohaler (Sunovion)

are examples of single-dose

DPIs (Figure 20). While the

HandiHaler® is used for the

delivery of tiotropium bro-

mide, the TOBI Podhaler is uti-

lized for the administration of

tobramycin. The Neohaler® is

used for the delivery of glyco-

pyrrolate as well as Utibron®,

the combination of indacaterol

and glycopyrrolate. Although

the HandiHaler®, Podhaler,

and Neohaler® have different congurations, their principle

of operation is similar. When using a single-dose DPI, the

user places each capsule into the drug holder. Then, the

user must prime the device by piercing the single-dose

capsule and allowing entrainment of air into the device

for dispersion with inhalation. The primary disadvantage of

single-dose DPIs is the time needed to load a dose for each

use. Also, patients should be instructed not to swallow the

capsules.

Multiple Unit-Dose DPIs

The Diskhaler® (GlaxoSmithKline) is an example of the

multiple unit-dose DPI. It is used for the administration of

zanamivir through a rotating wheel that contains a case

with four or eight blisters of medication. Each blister is

mechanically punctured when the cover is lifted, allowing

the medication to be inhaled though the mouth. When

using the Diskhaler®, the inspiratory ow rate should be

greater than 60 L/min to achieve an adequate drug deposi-

tion into the lungs.

Multiple-Dose DPIs

Multiple-dose DPIs measure doses from a powder res-

ervoir or disperse individual doses through pre-metered

blister strips. The most common types of multi-dose DPIs

include the RespiClick®, the Flexhaler® and the Pressair®

(AstraZeneca, Wilmington, DE), and the Diskus® and Ellipta®

(GlaxoSmithKline). The Twisthaler® is a multi-dose DPI used

to deliver mometasone furoate. The Flexhaler® delivers

budesonide, and the Diskus® administers salmeterol, utica-

sone, or a combination of salmeterol and uticasone.

In the Twisthaler® and the Flexhaler®, the DPI nozzle

is comprised of two parts: a lower swirl chamber and an

upper chimney in the mouthpiece. Their uted chimney

designs produce a stronger vortex with an increased num-

ber of particle collisions with the chimney for deagglomer-

ation. When using a new Flexhaler®, it should be primed by

holding it upright and then twisting and clicking the brown

grip at the bottom twice. The Twisthaler® does not require

priming before use.

The Diskus® is a multi-dose DPI that contains 60 doses of

dry-powder medication individually wrapped in blisters. The

wrapping in blisters protects the drug from humidity and

other environmental factors. Sliding the dose-release lever

punctures the wrapped blister on a foil strip and prepares

the dose for inhalation. When the Diskus® cover is closed,

the dose release lever is automatically returned to its start-

ing position. As with the Twisthaler®, no priming is neces-

sary with the Diskus®.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

The Ellipta® is similar to the Diskus® and is used in the

delivery of various long-acting beta agonists and combina-

tion medications such as Brea® and Anoro® as well as other

drugs such as Incruse®, an ultra-long-acting anticholinergic,

and Arnuity®, a corticosteroid. Similar to the Diskus®, this

multi-dose DPI utilizes two coiled blister strips containing

individually wrapped doses of dry-powder medication.

Opening the mouthpiece cover peels the foil to expose

the medication dosage. After inhaling the medication, the

mouthpiece cover is returned to its closed position. It is

important to note that, if the mouthpiece cover is opened

and the dose is prepared, closing the mouthpiece cover

without inhalation of the medication will result in a lost

dose.

The Pressair® is multi-dose dry power inhaler that admin-

isters aclidinium bromide in 30 or 60 doses. The device

utilizes a button that once depressed loads the medication.

This can be conrmed visually by checking the control

window that changes from red to green once a new dose

is ready. Once the patient inhales a click can be heard,

noting the dose was inhaled. The individual may conrm by

looking at the control window that changes from green to

red to indicate a dose has been taken. Patients will need to

have a minimum peak inspiratory ow of 35 L/min to effec-

tively use this device.

Currently Available DPI Formulations

As seen in Figure 20, the device design largely deter-

mines whether a DPI model is single dose (loading a single

dose prior to each use), multiple unit-dose (loading four or

eight blisters of medication), or multiple-dose (containing

an entire month’s prescription).

Factors Affecting DPI Performance and

Drug Delivery

Respiratory therapists and patients must actively control

the following effects:

• Intrinsic Resistance and Inspiratory Flow: Each type

of DPI has a different intrinsic resistance to airow that

determines how much inspiratory ow needs to be

created in the device to release the correct amount of

drug. For example, the HandiHaler® has a higher resis-

tance than the Diskus® and therefore requires a greater

inspiratory effort. When the patient inhales through

the DPI, she/he creates an airow with a pressure drop

between the intake and exit of the mouthpiece. Thus,

the patient can lift the powder from the drug reser-

voir, blister, or capsule depending on the model being

used. The patient’s inspiratory effort is also important

in its deaggregating of the powder into ner particles.

Whereas higher inspiratory ows improve drug deag-

gregation, ne-particle production, and lung delivery,

excessive inspiratory ow can increase impaction on

the oral cavity and thus decrease total lung deposition.

• The Patient’s Inspiratory Flow Ability: DPIs depend

on the patient’s ability to create adequate inspiratory

ows. Very young children and patients with acute

airow obstruction due to asthma or COPD may not be

able to generate an adequate inspiratory ow when

using the DPI. Because very low inspiratory ows result

in reduced drug delivery, especially ne-particle deliv-

ery, potential DPI patients should be evaluated for the

ability to generate a minimal inspiratory ow.

• Exposure to Humidity and Moisture: Because all DPIs are

affected by humidity and moisture, which can cause pow-

der clumping and reduce deaggregation and ne-particle

development during inhalation, they must be kept dry.

Capsules and drug blisters generally offer more protection

from ambient humidity than a reservoir chamber contain-

ing multiple doses for dispensing. Therefore, designs with

a reservoir chamber such as the Twisthaler® and Pressair ®

should be protected from humidity and moisture as much

as possible. Whereas it is easy to keep the Twisthaler® and

Pressair ® out of the bathroom, avoiding use in ambient

humidity is difcult if it is carried to the beach, kept in a

house with no air conditioning, or left in a car. An alter-

native DPI design or availability of the drug in a different

aerosol system, such as a pMDI, might be considered for

such situations. All DPIs are also affected by exhaled air

introduced into the mouthpiece, especially after the device

is cocked and loaded and when the powder is exposed.

Therefore, patients must be instructed to exhale away

from the DPI prior to inhalation.

Drug-Delivery Technique

Because different types of DPIs are available on the mar-

ket, respiratory therapists should carefully review operation

instructions prior to giving aerosol therapy and certainly

prior to instructing patients in at-home use. Proper tech-

nique is provided in Technique Box 4.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Technique Box 4. Steps for Correct Use of Each Model of DPIs

Technique for Single-Dose DPIs

HandiHaler®: The patient should be instructed to:

1. Peel back the aluminum foil and remove a capsule immediately before using the HandiHaler®.

2. Open the dust cap by pulling it upward.

3. Open the mouthpiece.

4. Place the capsule in the center chamber; it does not matter which end is placed in the chamber.

5. Close the mouthpiece rmly until they hear a click; leave the dust cap open.

6. Hold the HandiHaler® with the mouthpiece up.

7. Press the piercing button once and release; this makes holes in the capsule and allows the medication to

be released during inhalation.

8. Exhale away from the HandiHaler®.

9. Place the mouthpiece into the mouth and close lips tightly around the mouthpiece.

10. Keep head in an upright position.

11. Breathe in at a rate sufcient to hear the capsule vibrate, until the lungs are full.

12. Remove the mouthpiece from the mouth and hold breath for 10 seconds or as long as comfortable.

13. Exhale away from the HandiHaler®.

14. Repeat the inhalation from the HandiHaler®.

15. Open the mouthpiece, remove the used capsule, and dispose of it. Do not store capsules in the

HandiHaler®.

16. Close the mouthpiece and dust cap for storage of the HandiHaler®.

17. Store the device in a cool, dry place.

Neohaler®: The patient should be instructed to:

1. Remove the mouthpiece cover.

2. Hold the base of the inhaler and tilt the mouthpiece to open the Neohaler®.

3. Remove the capsule from the blister pack immediately before use.

4. Place the capsule into the chamber in the base of the Neohaler®.

5. Close the inhaler; a click will sound to indicate the inhaler is closed.

6. Simultaneously press both buttons on the side of the Neohaler® to pierce the capsule and then release.

7. Keep the head in a neutral, upright position.

8. Do not exhale into the device.

9. Hold the device horizontal, with the buttons on the left and right.

10. Place the mouthpiece into the mouth and close lips tightly around the mouthpiece.

11. Breathe in a full breath rapidly and deeply; the capsule should be heard vibrating in the device.

12. Remove the mouthpiece from the mouth and perform a 10-second breath hold (or as long as comfort-

able).

13. Do not exhale into the device.

14. Open the chamber and examine the capsule; if there is powder remaining, repeat the inhalation process.

15. After use, remove and discard the capsule. Do not store the capsule in the Neohaler®.

16. Close the mouthpiece and replace the cover.

17. Store in a cool, dry place.

Podhaler: The patient should be instructed to:

1. Hold base of Podhaler and unscrew lid in a counter-clockwise direction, setting aside lid once complete.

2. Stand Podhaler upright in the base of the case.

3. Hold body of Podhaler and unscrew mouthpiece in a counter-clockwise direction, setting aside mouth-

piece on a clean, dry surface.

4. Take blister card and tear the pre-cut lines along the length and width.

5. Peel foil that covers one Podhaler capsule on blister card.

6. Remove capsule one at a time and place in capsule chamber at the top of Podhaler.

7. Place mouthpiece back on Podhaler and screw mouthpiece in a clockwise direction until tight.

8. Hold Podhaler pointing mouthpiece down.

9. Placing the thumb on the blue button, pressing the blue button all the way down once.

10. Exhale as completely as possible away from the inhaler.

11. Place the mouthpiece into the mouth and close lips tightly around mouthpiece.

12. Breathe in a full breath deeply and slowly and perform a 10-second breath hold (or as long as

comfortable).

13. Exhale away from the device.

14. To ensure the entire dose has been inhaled, repeat steps 10 through 12.

15. Unscrew the mouthpiece and remove capsule from chamber and throw away.

16. Repeat steps 4 to 15 three more times until all four doses (4 capsules) have been used.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Technique Box 4. Steps for Correct Use of Each Model of DPIs (continued)

Technique for the Multiple Unit-Dose DPI

Diskhaler®: The patient should be instructed to:

1. Remove the cover and check that the device and mouthpiece are clean.

2. Extend tray and push ridges to remove tray.

3. Load medication disk on the rotating wheel.

4. Pull the cartridge all the way out and then push it all the way in until the medication disk is seen in the

dose indicator. This will be the rst dose that will be given.

5. Keep the device at and lift the back of the lid until it is lifted all the way up to pierce the medication

blister.

6. Click back into place.

7. Move the Diskhaler® away from the mouth and breathe out as much as possible.

8. Place the mouthpiece between the teeth and lips and make sure the air hole on the mouthpiece is not

covered.

9. Inhale as quickly and deeply as possible.

10. Move the Diskhaler® away from the mouth and perform a 10-second breath hold or as long as

comfortable.

11. Breathe out slowly.

12. If another dose is needed, pull the cartridge out all the way and then push it back in all the way in order

to move the next blister into place. Then repeat Steps 4 through 12.

13. Place the mouthpiece cover back on after the treatment. Make sure the blisters remain sealed until

inspiration in order to protect them from humidity and loss.

Technique for Multiple-Dose DPIs

Diskus®: The patient should be instructed to:

1. Open the device.

2. Slide the lever from left to right.

3. Breathe out normally; do not exhale into the device.

4. Place the mouthpiece into the mouth and close lips tightly around the mouthpiece.

5. Keep device horizontal while inhaling dose with a rapid and steady ow.

6. Remove the mouthpiece from the mouth and perform a 10-second breath hold or as long as comfort-

able.

7. Be sure not to exhale into the device.

8. Store the device in a cool dry place.

9. Observe the counter for the number of doses remaining and replace when appropriate.

Twisthaler®: The patient should be instructed to:

1. Hold the inhaler straight up with the pink portion (the base) on the bottom.

2. Remove the cap while it is in the upright position to ensure the right dose is dispensed.

3. Hold the pink base and twist the cap in a counter-clockwise direction to remove it.

4. As the cap is lifted off, the dose counter on the base will count down by one. This action loads the dose.

5. Make sure the indented arrow located on the white portion (directly above the pink base) is pointing to

the dose counter.

6. Breathe out normally; do not exhale into the device.

7. Place the mouthpiece into the mouth and close the lips tightly around the mouthpiece.

8. Inhale the dose with a rapid and steady ow while holding the Twisthaler® horizontal.

9. Remove the mouthpiece from the mouth and perform a ve to 10-second breath hold or as long as

comfortable.

10. Do not exhale into the device.

11. Immediately replace the cap, turn in a clockwise direction, and gently press down until a click is heard.

12. Firmly close the Twisthaler® to assure that the next dose is properly loaded.

13. Be sure that the arrow is in line with the dose-counter window.

14. Store device in cool, dry place.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Technique Box 4. Steps for Correct Use of Each Model of DPIs (continued)

Technique for Multiple-Dose DPIs (continued)

Flexhaler®: The patient should be instructed to:

1. Twist the cover and lift it off.

2. Hold the Flexhaler® in the upright position (mouthpiece up) while loading a dose.

3. Do not hold the mouthpiece when the inhaler is loaded.

4. Twist the brown grip fully in one direction as far as it goes. It does not matter which way is turned

rst.

5. Twist it full back in the other direction as far as it goes.

6. Make sure to hear a click during each of the twisting movements.

7. Do not exhale into the device.

8. Place the mouthpiece into the mouth, close the lips tightly around the mouthpiece, and inhale deeply

and forcefully through the inhaler.

9. Remove the inhaler from the mouth and exhale.

10. Do not exhale into the device.

11. If more than one dose is required, repeat the steps above.

12. Put the cover back on the inhaler and twist it shut.

13. Rinse the mouth with water after each dose to reduce the risk of developing thrush. Do not swallow

the rinse water.

Tudorza Pressair: The patient should be instructed to:

1. Wash and dry hands thoroughly.

2. Remove the protective cap by gently squeezing the marked arrows on each side of the cap and pulling

outward.

3. Hold the inhaler with the mouthpiece facing toward the patient and the green button on top. DO NOT

place in the mouth yet.

4. Press the green button all the way down and release it. DO NOT hold the button down.

5. Check the control window on the device (above the mouthpiece) to ensure the color has changed

from red to green, indicating the dose and device are ready for use.

6. Exhale away from the device before placing the mouthpiece into the mouth.

7. Place the mouthpiece into the mouth and breathe in quickly and deeply.

8. A click is heard when the dose is delivered, but continue the deep breath until at full capacity.

9. Remove the device from the mouth and breathe out.

10. Check the control window on the device (above the mouthpiece) to ensure the color has changed

from green to red. IF NOT, repeat Step 7.

11. Replace the protective cap on the mouthpiece.

RespiClick®: The patient should be instructed to:

1. Hold the inhaler upright with the red mouthpiece cover facing the patient.

2. Remove the red mouthpiece cover in the upright position until a click is heard. This exposes the

mouthpiece as well as loads the medication. The dose counter on the back of the device will count

down one number each time the medication is delivered.

3. Exhale away from the device.

4. Place the mouthpiece into the mouth and close lips tightly around the mouthpiece.

5. Do not block the air vent above the mouthpiece.

6. Inhale deeply through the RespiClick®.

7. Remove the mouthpiece from the mouth and perform a 10-second breath hold or as long as comfort-

able.

8. Check the dose counter on the back of the device to make sure the dose was delivered.

9. Firmly close the cap over the mouthpiece.

10. Store the device in a cool dry place.

11. Observe the counter for the number of doses remaining and replace when appropriate.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

How To Know the DPI Is Empty

Single-Dose DPI: Single-dose DPIs such as the HandiHaler®

use a single capsule for each dose, and only full capsules

should be used when each dose is given. The capsule

should be inspected to assure that the patient took the full

dose. If there is powder remaining, the capsule should be

returned to the inhaler and inhalation should be repeat-

ed.68 Then, the capsule should be disposed of after treat-

ment. Prescription renewal should be based on the remain-

ing capsules.

Multiple Unit-Dose DPI: The Diskhaler® is a multiple unit-

dose DPI with a rell disk that contains 4- or 8-unit-dose

blisters.69 Because there is not a dose counter on the DPI,

doses must be tracked manually. Therefore, visual inspec-

tion will conrm use of all packets. The disk is disposed of

when all the doses have been used.

Technique Box 4. Steps for Correct Use of Each Model of DPIs (continued)

Technique for Multiple-Dose DPIs (continued)

Ellipta®: The patient should be instructed to:

1. Open the device by sliding the mouthpiece cover down until a click is heard. This exposes the mouth-

piece as well as loads the medication. The center dose counter will count down one number each

time the mouthpiece cover is opened.

2. Hold the Ellipta® in an upright position.

3. Exhale away from the Ellipta®.

4. Place the mouthpiece into the mouth and close lips tightly around the mouthpiece. Do not block the

air vent on the device,

5. Keep the device horizontal while inhaling the dose with a rapid and steady breath.

6. Remove the mouthpiece from the mouth and perform a 10-second breath hold or as long as comfort-

able.

7. Do not exhale into the device.

8. Close the mouthpiece cover.

9. Store the device in a cool dry place.

10. Observe the counter for the number of doses remaining and replace when appropriate.

General Steps To Avoid Reduced or No Dosing for DPIs: The patient should:

1. Read and follow the instructions for proper assembly.

2. Make sure to keep the DPI clean and dry.

3. Keep the DPI in proper orientation during the treatment.

4. Be sure to puncture the capsule or blister pack.

5. Do not exhale into the DPI.

6. Make sure to generate adequate inspiratory ow.

7. Track the doses remaining in the DPI.

Troubleshooting

Problem with DPIs: Malfunctioning DPIs

Causes Solutions

Incorrect DPI assembly Check the assembly and reassemble, when needed.

Failure to discharge medicine Replace the unit.

Empty DPI Check the dose counter to ensure that it is not empty.

Otherwise, replace the DPI.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Multiple-Dose DPIs: Multiple-dose DPIs historically come with

integrated mechanical devices that indicate the number of

doses remaining in the inhaler.68 The devices give a particular

display when the doses are coming to an end so that a new

DPI can be ordered from the pharmacist. The dose counter of

each type of multiple-dose DPI is explained in Table 15.

Cleaning: Please refer to the Infection Control section on

page 44 for the cleaning instructions for DPIs.

Table 15. Monitoring remaining doses of multiple-dose DPI

Dose No. of Type of Meaning of

Container Doses Indicator Dose Indicator

Flexhaler® Reservoir 60 or 120 “0” Although the indicator counts down every time a dose is

loaded, it will not move with each individual dose but

intervals of ve or so doses.

The indicator is marked in intervals of 10 doses, alternating

numbers and dashes. When it is down to “0,” it must

be thrown away.

Twisthaler® Reservoir 30 “01” The dose display showing “01”indicates the last dose of

medicine in the Twisthaler®, and the medicine must be

relled.

Diskus® Blister Strip 60 Red The numbers turning red in the dose display indicates that

numbers there are ve doses left.

When the dose window shows “0,” there is no medicine

left, and the discus should be disposed.

RespiClick® Reservoir 60 or 200 “0” When the dose counter displays “0,” there is no

medicine left and the device should be disposed.

Ellipta® Blister strip 30 “0” When the dose counter displays “0”, this is the

last dose. Discard the device after inhalation.

Pressair® Reservoir 30 or 60 “0” When dose counter displays “0,” there is no

medicine left and the device should be disposed.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Criteria To Select

an Aerosol Generator

The selection of the delivery device is very important for

optimizing the results of aerosol drug therapy. Evidence

indicates that all three types of aerosol generators can be

equally effective if they are used correctly by the patient.8

The criteria to select an aerosol generator can be divid-

ed into four categories: patient-related, drug-related,

device-related, and environmental and clinical factors.

Patient-Related Factors

Age, Physical, and Cognitive Ability of Patients

An aerosol generator should be selected in accord with

the patient’s age, physical, and cognitive ability. Age

changes anatomic and physiologic factors such as airway

size, respiratory rate, and lung volume.13,69-76 The patient’s

cognitive ability to understand how and when to use a

device and drug as well as his/her physical ability and

coordination in using an aerosol generator should guide

the selection of an aerosol generator.8,13,18,69,75,77-79 Aerosol

devices have different requirements for proper use. For

guidance about the device selection in infants and pediat-

rics, see “Neonatal and Pediatric Aerosol Drug Delivery” on

pages 42-43.

As for adults and the elderly who cannot manage hand-

held coordination or proper inhalation technique,77,80-82

pMDIs may not be a good option. Also, the inability to gen-

erate sufcient inspiratory ow (>40–60 L/min) eliminates

the use of aerosol generators such as DPIs.77,83

Preference of Patients

Patient preference is a critical factor in the selection of

an aerosol generator and the effectiveness of aerosol ther-

apy. Patients tend to use devices they prefer more regularly

than devices they dislike.84-87 Therefore, the selection of

an aerosol generator should be tailored according to the

patient’s needs and preferences.

Drug-Related Factors

Availability of Drug

Some drug formulations are available with only one type

of aerosol generator. If a drug can be administered with

the three types of aerosol generators, the clinician should

select an aerosol generator based on the patient’s needs

and preference.8,18,79,87 Otherwise, a drug formulation that

can be used with only a single aerosol generator dictates

which aerosol generator to choose.

Combination of Aerosol Treatments

Many patients are prescribed more than one inhaled

drug. In that case, using the same type of aerosol genera-

tor may increase the patient’s adherence to therapy while

minimizing the patient’s confusion caused by the use of

different aerosol devices.8,18,87-88

Device-Related Factors

Convenience of Aerosol Generator

Selecting the most convenient aerosol generator for the

patient is very important to adherence. Ease of use, treat-

ment time, portability, cleaning, and maintenance required

for each device should guide the selection process. For

example, a rescue medication needs to be small, light, and

portable so the patient can easily have it available when

needed.69,79 Also, nebulizers may be less preferable to deliv-

er inhaled medications as they are more expensive, require

a power source, and need regular maintenance.69,87,89-90

When all other factors are equal, the most convenient

device should be chosen for patients.

Durability of Aerosol Generator

A selected aerosol generator should have good durability

so that it can withstand rigorous treatment and cleaning

procedures every day. Devices that require extensive clean-

ing are not a good choice for patients unwilling to routine-

ly clean and maintain the device.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Cost and Reimbursement of Aerosol Generator

It is very important to select an aerosol generator that is

the least out-of-pocket expense for the patient. Patients do

not use drugs and devices they cannot afford.91-93 As shown

in Table 3, Table 6, and Table 7, costs of aerosol generators

and drug formulations vary widely. The cost to the patient

will depend on the presence and type of medical insurance

they have.79 If the “best” device/drug is not one that the

patient can afford, the least costly aerosol generator and

drug combination should be identied in order to meet

the patient’s needs. Therefore, it is important to work with

the patient to identify strategies to access affordable drug/

device options in order to meet their clinical needs. If all

the other factors are constant, the least costly aerosol gen-

erator and drug combination should be selected.

Environmental and Clinical Factors

When and where the aerosol therapy is required can

impact device selection. For example, therapy that is given

routinely, once or twice a day, before or after bedtime does

not need to be as portable as rescue medications that may

be required at anytime. Also, noisy compressors may not be

good in small homes where a late-night treatment might

awaken other members of the family. In environments

where patients are in close proximity to other people, sec-

ondhand exposure to aerosols may be a factor, and devices

that limit or lter exhaled aerosol should be selected.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Neonatal and Pediatric

Aerosol Drug Delivery

Infants are not simply anatomically scaled-down adults.

Therefore, aerosol drug administration differs fundamen-

tally in infants and children. Cognitive ability (i.e., under-

standing how and when to use a device and drug) and

physical ability (i.e., coordination to use that device) as

well as age-related anatomic and physiologic factors (i.e.,

airway size, respiratory rate, lung volumes) create substan-

tial challenges for effective aerosol delivery at each stage

of development.70-73,94-95 When respiratory therapists gain a

clear understanding of these challenges, they can optimize

aerosol drug delivery and its therapeutic outcomes in less

developed patients. This section explores the challenges

and solutions that may optimize aerosol drug delivery in

infants and pediatrics.

Age and Physical Ability

Selection of an aerosol device is critical to successful

aerosol therapy in infants and children.70,78,95 Children

under the age of three may not reliably use a mouthpiece,

making delivery via mask necessary for both nebulizers and

pMDIs.95-99 Especially at low tidal volumes, VHCs are the

preferred method for pMDI delivery in infants and small

children.97-98 Breathing patterns, inspiratory ow rates,

and tidal volumes change with age. Even healthy children

below four years of age cannot reliably generate sustained

inspiratory ow rates of 60–90 L/min required for optimal

use of many DPIs. Thus, the use of breath-actuated nebu-

lizers or DPIs may not be reliable in children younger than

four years.73,100

Age and Cognitive Ability

The choice of aerosol device should be tailored to the

patient’s age and to cognitive ability to use the device

correctly. Table 16 presents the recommended ages for

introducing different types of aerosol generators to chil-

dren.69-71,100-103 Small-volume nebulizers and pMDIs with

VHCs are recommended for use with infants and children up

to ve years of age.70-71,100 Since children up to three years

of age typically cannot use a mouthpiece, both nebulizers

and pMDIs with holding chambers should be administered

via masks.70,97-98 Independent of age, a face mask should

be used until the child can comfortably use a mouthpiece.

A child below ve years of age may not be able to master

specic breathing techniques.70-71,100 With low tidal volumes

and short inspiratory times, breath-actuated nebulizers

may increase inhaled dose compared to continuous neb-

ulization.104 However, it may take three-fold more time to

administer that dose. Also, time constraints and portability

of compressor nebulizers make them less desirable for pre-

school children.70 It is generally accepted that the cognitive

ability to control breathing and hand/breath coordination

develops by age ve or six.69,70,101 Once children reach age

four and above, they may have a sufcient understanding of

how to use a pMDI or DPI successfully.73,100

Table 16. Age guidelines for use of aerosol delivery device types

Aerosol Generator Age

SVN with mask or hood Infant94

SVN with mask ≤ 3 years

SVN with mouthpiece ≥ 3 years

pMDI with valved holding chamber/spacer and mask < 4 years

pMDI with valved holding chamber/spacer ≥ 4 years

Dry-powder inhaler ≥ 4 years

Metered-dose inhaler ≥ 5 years

Breath-actuated MDI (e.g., Autohaler®) ≥ 5 years

Breath-actuated nebulizer ≥ 5 years

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Aerosol Drug Delivery in Distressed or

Crying Infants

Inhaled drugs should be given to infants when they are

settled and breathing quietly. Crying children receive vir-

tually no aerosol drug to the lungs,94,96,102,105-106 with most

of the inhaled dose depositing in the upper airways or

pharynx, which is then swallowed.71-72,94,106-107 Therefore, it

is essential to develop approaches that minimize distress

before administering aerosol drugs. These approaches

include, but are not limited to, playing games, comforting

babies, and providing other effective forms of distraction.

Also, aerosol drugs can be administered while the infant is

asleep as long as administration does not wake up or agi-

tate the infant. Although sleep breathing patterns indicated

a higher lung dose in an infant-model study,108 an in-vivo

study showed that 69% of the children woke up during

aerosol administration and 75% of them were distressed.109

Patient-Device Interface

Even infants and small children can make known their

preferences for specic devices. This should be a consider-

ation in device selection. Using a device that is preferred by

the child and parent can increase adherence, inhaled dose,

and desired clinical response.

Mouthpiece or Face Mask?

Mouthpieces and face masks are commonly used for

aerosol drug delivery in children above three years of age.

Studies suggest that the mouthpiece provides greater

lung dose than a standard pediatric aerosol mask104,110 and

is effective in the clinical treatment of children.104,111-112

Consequently, the use of mouthpieces should be encour-

aged, but a mask that is consistently used is better than a

mouthpiece that is not.

Importance of a Closely Fitting Face Mask

A good face mask seal is a critical factor in achieving

optimal drug deposition and avoiding getting aerosol into

eyes. Even small leaks of 0.5 cm around the face mask

decrease drug inhaled by children and infants by more

than 50%.113-117 Initially, a small child may refuse to use a

face mask when feeling sick or irritable. However, parental

education, play activities, encouragement to hold the mask

rmly against the child’s face, and close supervision can

reduce poor tolerance of face masks and improve aerosol

drug delivery.

Face Mask or Blow-by?

Blow-by is the administration of aerosolized drug

through the nebulization port of a nebulizer that is direct-

ed toward the patient’s face. Although blow-by is a tech-

nique commonly used for crying babies or uncooperative

children, it has been documented that it is less efcient

compared with a face mask as aerosol drug deposition

decreases signicantly as the distance from the device

to the child’s face is increased. Therefore, evidence sug-

gests blow-by to be ineffective and use should be discour-

aged.97,113,118-119

Parent and Patient Education

As children grow and their aerosol device needs to be

changed, they and their care providers should be taught

the best techniques for the use and maintenance of aerosol

devices. Also, children may demonstrate poor adherence to

aerosol drug delivery because they lack the ability to use

a device correctly or contrive to use it ineffectively.120-121

Therefore, respiratory therapists should explain the effects

of medications prescribed, the importance of aerosol

therapy, and the proper use of aerosol generators to the

patient and the parent. After initial training is provided,

frequent follow-up demonstration is essential to optimize

aerosol drug delivery and adherence to prescribed therapy

in infants and children.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Infection Control

Aerosol generators can become contaminated with

pathogens from the patient, the care provider, and the

environment. The contamination of nebulizers has been

documented in patients with cystic brosis (CF),20-22 asth-

ma,23-24 and immunodeciency.122 A survey of respiratory

therapists and cystic brosis patients found a wide dispar-

ity of nebulizer cleaning methods.123 In another survey, it

was shown that only 60% of cystic brosis caregivers were

aware of infection control guidelines.124 In the absence of

infection control (IC), an aerosol generator will be contam-

inated and may cause bacterial colonization in the respira-

tory tract.20-22,25,125 Therefore, it is essential to establish an

IC management system that will reduce nosocomial infec-

tions, length of stay in the hospital, and costs associated

with hospitalization.24,125-126

IC Management System in Aerosol Drug

Delivery

Patient Education and Awareness

Patient Education: It has been documented that aerosol

generators used at home are frequently contaminated with

bacteria.23-24,127-128 Therefore, the importance of cleaning

and maintaining aerosol equipment should be emphasized

in IC education programs129 with patients and caregivers

through repeated oral and written instructions.

Patient Adherence: Approximately 85% of patients with

CF fail to disinfect their nebulizers at home.130 It has been

determined that, in addition to the constraints of cleaning

and disinfecting instructions provided by the manufactur-

ers, adherence can be inuenced by personal, socio-cul-

tural, and psychological factors.131 Furthermore, a major-

ity of cystic brosis health care workers reported a low

self-efcacy with using infection control guidelines, which

can be linked to poor adherence.124 Changing aerosol gen-

erators every 24 hours, using disposable equipment with

health insurance approval, and partnering with patients to

increase adherence85 can increase patient compliance to IC

and minimize the risk of infection.

Cleaning and Maintenance of Aerosol Generators

Cleaning: The cleaning instructions for the different types

of aerosol generators are given below.

• Pressurized Metered-Dose Inhalers: The plastic container

of pMDIs should be cleaned at least once a week132-133

as shown in Table 17.

• Metered-Dose Inhalers Accessory Devices: When a spac-

er is used with a pMDI, it should be cleaned before rst

use and then periodically cleaned based on the manu-

facturer’s suggestions. Table 18 provides the steps for

cleaning the pMDI accessory devices.

• Dry-Powder Inhaler: It is important to note that DPIs

should not be submerged in water. Also, they should

be kept dry as moisture will decrease drug delivery.

Although there is no clear evidence about the DPI

cleaning practice, each manufacturing company has

Table 17. Cleaning instructions for the pMDI

Cleaning the pMDI

Clean once a week and as needed. Look at the hole where the drug sprays out from the inhaler.

Clean the inhaler if you see powder in or around the hole.

Remove the pMDI canister from the plastic container so it does not get wet.

Rinse the plastic container with warm water and shake out to remove excess water.

Dry overnight.

Replace the canister back inside the mouthpiece and recap the mouthpiece.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

recommendations for periodic cleaning and suggests

wiping the mouthpiece of the DPI with a clean dry

cloth.

• Nebulizers: In the home, nebulizers should be cleaned

after every treatment. A study showed that 73% of

nebulizers were contaminated with microorganisms

and 30% had potentially pathogenic bacteria.134

Moreover, there was a signicant increased risk of

COPD exacerbation in COPD patients that had nebuliz-

ers with pathogens versus those with non-pathogenic

bacteria. However, nebulizer contamination can be

signicantly improved with proper instruction on infec-

tion control.135 The longer a dirty nebulizer sits and is

allowed to dry, the harder it is to thoroughly clean.

Rinsing and washing the nebulizer immediately after

each treatment can go a long way in reducing infec-

tion risk. According to the Cystic Fibrosis Foundation

guidelines,136 parts of aerosol generators should be

washed with soap and hot water after each treatment,

with care taken not to damage any parts of the aerosol

generator. Table 19 provides the cleaning instructions

for the jet nebulizer. Mesh and ultrasonic nebulizers

should be cleaned and disinfected based on the man-

ufacturer’s recommendations. Also, it is important to

remember not to touch the mesh during the cleaning

of mesh nebulizers because this will damage the unit.

Disinfection: Periodic disinfection and nebulizer replace-

ment is highly recommended to minimize contamination.

Each manufacturer suggests a different method of disinfec-

tion for its product. Therefore, the manufacturer’s specic

instructions on disinfecting aerosol generators should be

followed. It is also important to note that all solutions

should be discarded after disinfection. The varied methods

for disinfection include having the patient:

Heat methods:

1. Boil or microwave137 the nebulizer parts for ve minutes.

This disinfection process does not require a nal rinse.

2. Wash in a dishwasher if the dishwasher achieves a tem-

perature of > 158°F or 70°C for 30 min.137

Cold Methods:

1. Soak them in solution of one-part household bleach and

50-parts water for three minutes.

2. Soak the parts in 70% isopropyl alcohol for ve minutes.

3. Soak them in 3% hydrogen peroxide for 30 minutes.

4. Soak them in one-part distilled white vinegar in three-

parts hot water for one hour (not recommended for CF

patients).

The patient should disinfect the nebulizer once or twice

a week by using one of the methods for disinfection listed

above. Evidence suggests that a quaternary ammonium

compound can also be used for disinfecting jet nebulizers

as it has comparable effectiveness with the combined dis-

infection procedure of a detergent pre-wash and 1.25%

acetic acid soak. Also, a quaternary ammonium compound

Table 18. Cleaning instructions for the pMDI chamber

Cleaning the Chamber Device

Clean every two weeks and as needed.

Disassemble the device for cleaning.

Soak the spacer parts in warm water with liquid detergent and gently shake both pieces back and forth.

Shake out to remove excess water.

Air dry spacer parts in the vertical position overnight.

Do not towel dry the spacer as this will reduce dose delivery because of static charge.

Replace the back piece on the spacer when it is completely dry.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

soak need only be 10 minutes, while the acetic acid soak

should not be less than one hour. Another advantage of

using the quaternary solution is that it can be reused for up

to one week, as opposed to the acetic acid solution that

cannot be reused.138

Final Rinse: The patient should use sterile water (not dis-

tilled or bottled) for the nal rinse.136 Sterile water can be

made by boiling tap water for ve minutes.

Drying and Maintenance: Because bacteria grow in wet,

moist places, nebulizers should be thoroughly dried and

stored in a clean dry place between treatments. Drying

can be enhanced by attaching gas ow to the nebulizer

for a short time after it is rinsed. It has been reported that

nebulizer performance may change in time due to incor-

rect cleaning, maintenance, and disinfection procedures.139

Nebulizers must be kept from being contaminated by fol-

lowing the manufacturer’s instructions for care and clean-

ing. This is necessary for all aerosol generators used for

inhaled medication.

Preventing Infection and Malfunction of

Aerosol Generators at Hospitals or Clinics

Aerosol Generators: Bacterial contamination of nebulizers

at the hospital has been associated with nosocomial infec-

tions.140-141 The Centers for Disease Control and Prevention

(CDC) recommends that nebulizers be cleaned, rinsed with

Table 19. Cleaning instructions for the jet nebulizer

Cleaning After Each Use

Wash hands before handling equipment.

Disassemble parts after every treatment.

Remove the tubing from the compressor and set it aside.

The tubing should not be washed or rinsed.

Rinse the nebulizer cup and mouthpiece with either sterile

water or distilled water.

Shake off excess water.

Air dry on an absorbent towel.

Store the nebulizer cup in a zippered plastic bag.

Cleaning Once or Twice a Week

Wash hands before handling equipment.

Disassemble parts after every treatment.

Remove the tubing from the compressor and set it

aside. The tubing should not be washed or rinsed.

Wash nebulizer parts in warm water with liquid dish soap.

Disinfect the nebulizer based on the manufacturer’s rec-

ommendations. The nebulizer parts may be soaked in one

of the following solutions:

1. One-part household bleach and 50-parts water

for three minutes

2. 70% isopropyl alcohol for ve minutes

3. 3% hydrogen peroxide for 30 minutes

4. One-part distilled white vinegar in three-parts hot water

for one hour (not recommended for CF patients).

Rinse parts with sterile or distilled water.

Shake off excess water and place all parts on a clean paper

towel.

Allow them to air dry completely on an absorbent towel.

Reassemble the nebulizer and store in a clean, dry bag

container.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

sterile water, and air-dried between treatments.142 Also,

each hospital or out-patient clinic should have an infection

surveillance program that can determine local IC practices

based on the continuous and systematic collection, analy-

sis, and interpretation of infection data. Nebulizers should

be changed every 24 hours.143-144 If an aerosol generator is

labeled “For Single Patient Use,” it should be used on a sin-

gle patient and then discarded.

MDI – Common Canister Use: Many hospital pharmacies

see a robust number of MDI canisters still containing med-

ication returned, leading to strategies for reducing cost.10

As a result, some hospitals practice common canister pro-

tocol for specic patient populations. A review focusing on

common canister protocol and the risk of infection found

some evidence of cross-contamination.145 However, the

evidence from the studies in this review is weak since none

of the research is in the form of peer-reviewed publications.

A recent study indicated a common canister protocol was

associated with signicant cost savings when compared

to single-patient MDI, and reported similar rates of venti-

lator assisted pneumonia, mortality, and length of stay.146

Hospital decision makers must perform a full risk-benet

evaluation before incorporating a common canister pro-

tocol in their institution, as more work needs to be done

in this area before best-practices can be suggested with a

high degree of condence.

Inhaled Drugs: Multi-dose drug containers have been asso-

ciated with contaminated nebulizers and are a potential

source of spreading nosocomial infections.149-151 Therefore,

unit-dose medications are recommended when possible.142

Also, it is important to avoid contaminating drug solutions.

Infection Transmission: The transmission of infection from

therapist to patient can be reduced by therapists washing

their hands with water and soap or cleaning hands with

hand sanitizers before and after treatment.151-152 The use of

gloves should be considered an adjunct to hand hygiene. A

respiratory therapist must change gloves between patients

and clean hands after gloves are removed due to the fact

that gloves create a warm and moist environment that sup-

ports the growth of microbial contamination and, thereby,

the transmission of infection.30,153 Goggles, face masks, and

face shields should be used alone or in combination to seal

out airborne pathogens that therapists may inhale with

aerosol drug therapy.

Compliance to IC Management System: The IC manage-

ment system can be effective only with the practice of the

dedicated and knowledgeable respiratory therapists who

implement it. Therefore, respiratory therapists should be

trained appropriately in using set protocols established by

the IC management system in aerosol drug delivery.

Infection Surveillance: It is essential for hospitals to estab-

lish simple and sensible infection surveillance measures to

periodically evaluate the IC activities used by respiratory

therapists.

Occupational Health and Safety of

Respiratory Therapists

Respiratory therapists undergo not only the risk of expo-

sure to inhaled medications but are also faced with the risk

of inhaling pathogens during aerosol therapy. The elements

of occupational health and safety for the respiratory thera-

pist are shown below.

Health Assessment and Immunization: Screening respira-

tory therapists for infection and immunization must occur

from the beginning to the end of employment.

Hand Hygiene: It has been documented that hand hygiene

is effective in decreasing the transmission of respiratory

viruses.31,152,154-156 Also, the World Health Organization’s

guidelines suggest that inadequate hand hygiene is the

leading cause of nosocomial infection and spread of multi-

drug resistant organisms.157 Health care workers who self-

reported handwashing during patient care had a lower risk

of having respiratory infections.31,154-156

Protective Equipment: Respiratory therapists must have

access to the appropriate personal protective equipment,

such as masks and eye protectors, when needed.30

Ventilation System: These systems exchange room air

six to 10 times per hour31 and create a negative-pressure

environment in patient rooms that is effective in removing

99.9% of airborne contaminants in 69 minutes.32

Filtered Nebulizers: Placing a lter on the exhalation part

of a nebulizer may protect respiratory therapists from infec-

tion and reduce secondhand aerosol breathing in hospitals

and out-patient clinics.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Educating Patients

in Correct Use of

Aerosol Devices

A number of problems occur with patient use of aerosol

devices. Knowledge of these problems can help the respira-

tory therapist better instruct patients. Understanding there

are problems with use of aerosol devices can also direct

the therapist in evaluating a patient who has poor manage-

ment of airways disease. Either poor patient adherence to

prescribed aerosol therapy or errors in the use of aerosol

devices can reduce the effectiveness of inhaled drug ther-

apy. Both of these problem areas should be evaluated and,

if possible, ruled out in a patient who presents with poor

control of their airway disease before other changes in

their disease management are initiated.

Patient Adherence

A general problem with the use of inhaled medications

is patient adherence with prescribed use, although this

problem is not unique to inhaled drugs. “Adherence”

refers to a patient’s choice to follow prescribed therapy,

whereas “compliance” implies following of orders and pas-

sivity on the patient’s part. Lack of adherence can result in

poor health outcomes and increased healthcare costs.158

Both long- and short-term adherence may be inuenced

by patient and social factors.158-159 There are a number of

ways to monitor patient adherence with prescribed aero-

sol therapy such as provider interview, patient self-report,

dose counting, and electronic monitoring devices attached

to the inhaler. Monitoring devices attached to inhaler

devices are considered the most accurate and objective.

In one study, diary reports from patients showed a median

use of beta agonists of 78%, while data from an electron-

ic pMDI monitor reported only 48%.160 Therapists should

be aware that patients tend to over-report use of inhaled

drugs compared to data obtained from device monitors.

Failure to adhere to prescribed therapy is categorized as

“unintentional” or “intentional.” Table 20 lists both types

of non-adherence with denitions and examples.131 Upon

assessing poor patient adherence, a strategy incorporating

patient-centered care may help the caregiver understand

patient beliefs, views, and concerns about their treatment.

Goal setting and action plans are two motivational tools

Table 20. General types of non-adherence to prescribed aerosol therapy and potential factors that

can predispose to each type (Modied, with permission, from Reference 1 and Reference 131)

Unintentional Factors:

Not Understanding Therapy Correctly

Misunderstanding prescribed drug regimen:

• Poor physician-patient communication

• Poor therapist-patient communication

Language barriers

Intentional Factors:

Understanding Therapy But Not Adhering Correctly

Patient beliefs:

• Do not really require regular medication

• Are not really sick

• Gain attention from parents and kept at home (children)

• Medication too expensive

• Concern about side effects

• Perceived lack of effect from medication

Patient forgetfulness

Patient stress and busy lifestyle

Complex and demanding aerosol regimens

Psychological factors (e.g., depression)

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

that may improve patient adherence and can be discussed

in a supportive bi-directional conversation with the patient

during the patient-centered approach.

Note that one example of unintentional non-adherence

is incorrect aerosol device technique due to misunder-

standing prescribed drug regimen, which can be corrected

through patient training. There is no perfect, fail-safe,

error-proof inhaler on the market today. The pMDI is rec-

ognized as a difcult inhaler for patients to use without

proper training. Even holding chambers and spacers intro-

duced to address these issues present additional problems

(Table 21). DPIs were also introduced, in part, with the

rationale that their use would be simpler than with a

pMDI.161-162 Nebulizers are probably the simplest inhaler

type for a patient to use if we assume that assembly, prop-

er cleaning, and maintenance is not a problem. However,

Table 21. Common problems, disadvantages, and errors with each type of aerosol generator

(Modied, with permission, from References 1 and 132)

Pressurized Metered-Dose Inhalers

Errors in technique

• Failure to coordinate pMDI actuation on inhalation

• Too short a period of breath hold after inhalation

• Too rapid an inspiratory ow rate

• Inadequate priming/shaking/mixing before use

• Abrupt discontinuation of inspiration as aerosol hits throat

• Actuating pMDI at total lung capacity

• Actuating pMDI prior to inhalation

• Firing pMDI multiple times during single inhalation

• Firing pMDI into mouth but inhaling through nose

• Exhaling during actuation

• Putting wrong end of inhaler in mouth

• Holding canister in the wrong position

• Failing to remove cap before use

• Excessive use of pMDI beyond rated capacity (loss of dose count)

• Failure to clean boot

• Wasting remaining doses

Lack of adequate patient training in use of pMDI

Cognitive impairment of users

Lack of adequate hand strength or exibility to activate pMDI

Ideomotor dyspraxia

Valved Holding Chambers/Spacers

Incorrect assembly of add-on device

Failure to remove electrostatic charge in non-electrostatic holding

chambers/spacers can decrease emitted dose in new holding chamber/

spacer

Lengthy delay between pMDI actuation and inhalation from holding

chamber/spacer

Inhaling too rapidly

Firing multiple puffs into holding chamber/spacer before inhaling

Lack of patient instruction in assembly or use

Dry-Powder Inhalers

Errors in technique

• Not holding device correctly while loading dose

• Failure to pierce or open drug package

• Using the inhaler in wrong orientation

• Failure to prime

• Exhaling through the mouthpiece

• Not exhaling to residual volume before inhaling

• Not inhaling forcefully enough

• Inadequate or no breath hold

• Exhaling into mouthpiece after inhaling

Use of multi-dose reservoir designs in high ambient

humidity, which can reduce ne-particle dose

Lack of patient instruction in assembly or use

Nebulizers

Failure to assemble equipment properly

Spillage of dose by tilting some nebulizers

Failure to keep mouthpiece in mouth during nebulization

Failure to mouth breathe

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

there can be problems with all types of inhaler devices.

Table 20 lists the common errors and mistakes that can

occur with each type of device.131,161-162

Common Patient Errors with pMDIs

Although hand-breath coordination with a pMDI has long

been recognized as a problem, there are a number of other

potential mistakes a patient can make when using a pMDI

(Table 21). A large systematic review on errors in inhaler

use revealed that incorrect inhaler technique is frequent

and has not improved over the last 40 years.163 Lack of

coordination, improper inhalation (speed and/or depth),

and no post-inhalation breath hold were the most frequent

MDI technique errors.163 Also, failure to shake a pMDI

before each use can interfere with correct drug release.

Failure to prime a pMDI can also affect correct drug

release. A very practical problem and a real inconvenience

for users is the lack of a built-in dose counter to indicate

when a pMDI is empty. Dose counters are commercially

available, but this involves purchasing an additional item. In

one survey, 72% of patients said they continued to use their

pMDI until there was no sound when it was actuated.94

A pMDI can continue to produce a spray with propellant

and little or no drug if it is actuated after its rated capac-

ity, whether that is 120 or 200 puffs. Therapists should

instruct patients in the importance of tracking the number

of doses remaining in the pMDI (see page 39). It has been

shown that MDI’s without a counter results in signicantly

poorer adherence (underuse and overuse) when compared

to MDI’s with a counter.164 Furthermore, signicantly more

asthma and COPD patients visited the ED when not using

a dose counter when compared to a group using a dose

counter.165

Common Patient Errors with Holding

Chambers/Spacers

Common errors that can occur with holding chambers/

spacers are also listed in Table 21. Incorrect assembly of

the holding chamber/spacer is a potential problem. Many

patients mistakenly believe that pausing before inhaling

from a holding chamber/spacer after the MDI is actuated

has no effect on the delivered dose. This technique can

cause reduced drug availability. The ideal technique is to

place the mouthpiece between the lips and take a slow,

deep inhalation beginning when the pMDI is actuated.

Available dose can also be reduced if multiple puffs are

red into a holding chamber/spacer followed by a single

inhalation. Electrostatic charge is present on the chamber

walls of a new plastic holding chamber/spacer, which can

be removed by pre-washing with an ionic detergent or by

actuating 10–20 puffs from the pMDI through the cham-

ber.33,166 An alternative is to purchase a non-electrostatic

holding chamber/spacer.

Common Patient Errors with DPIs

Problems have also been identied with patient use of

DPIs (Table 21). Error rates, dened as failure to correctly

perform an essential step, have been shown to be similar

for pMDIs and DPIs.167 In contrast, another study revealed

that the DPI had a signicantly lower rate of improper

handling compared to the MDI.167 A large study on asthma

patient errors with a DPI showed that the most common

mistakes included failure to exhale prior to inhalation, insuf-

cient breath hold at end of inhalation, and lack of forceful

inhalation.168 Moreover, factors signicantly associated with

one or more of these major errors included an asthma-re-

lated hospitalization or no inhaler technique review during

the previous year.167 One of the unfortunate aspects of DPIs

is that the models currently available in the United States

all have a somewhat different design. They look different,

and there are differences in the details of cocking and load-

ing the DPIs.161 One of the highest error rates is failing to

hold the device correctly, which is an aspect of loading and

cocking the device for use.

Common Patient Errors with SVNs

The usual problems cited with SVNs are not problems

of patient use but rather general disadvantages with this

type of aerosol device (Table 21). Disadvantages include

bulk and size of equipment, need for external power source

(compressed gas or electricity), and lengthy treatment

times. Also, aerosol generators can function at suboptimal

levels for providing adequate medication delivery.169 Of all

the inhaler devices, however, nebulizers are the simplest

for patients to use. In addition, newer nebulizer technology

is directed at reducing the overall size of devices, elimi-

nating the need for an external power source, providing

shorter treatment times, and eliminating drug loss during

exhalation.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

Instructing and Evaluating Patients in the

Use of Inhaler Devices

There is an increasing variety of aerosol devices and oper-

ation, even within the same category of device type (e.g.,

DPIs). Confusion and errors of use can result. The following

general steps are recommended for clinicians to ensure

correct patient use:

1. Review device instructions carefully and practice with a

placebo device prior to teaching others.

2. Demonstrate assembly and correct use of device to

patients using a checklist.

3. Provide the patient with written instructions on how

to use the device, and include a written plan for use of

the medication (frequency based on symptoms).

a. Written instructions should be accompanied by pic-

tures for patients with low literacy.

4. Have the patient practice use of the device while being

observed by the clinician.

5. Review patient use of the device at each return visit.

6. Review the patient’s understanding of the inhaled med-

ications at each return visit (when to use, purpose of

drug, prescribed frequency).

7. Have a high index of suspicion for incorrect use or

non-adherence if poor management of airway disease

occurs.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

References

1. Hess DR, Myers TR, Rau JL. A guide to aerosol delivery devices for respi-

ratory therapists. American Association for Respiratory Care, Dallas,

Texas 2005.

2. Gardenhire, D.S. Rau’s Respiratory Care Pharmacology. St. Louis:

Elsevier, 2016.

3. Newman S, Hollingworth A, AR C. Effect of different modes of inha-

lation on drug delivery from a dry powder inhaler. Int J Pharm 1994;

102:127-132.

4. Newman SP, Pavia D, Moren F, et al. Deposition of pressurised aerosols

in the human respiratory tract. Thorax 1981; 36(1):52-55.

5. Newman SP, Woodman G, Clarke SW, Sackner MA. Effect of InspirEase on

the deposition of metered-dose aerosols in the human respiratory tract.

Chest 1986; 89(4):551-556.

6. Lewis RA, Fleming JS. Fractional deposition from a jet nebulizer: how

it differs from a metered-dose inhaler. Br J Dis Chest 1985; 79(4):361-

367.

7. Fink JB. Humidity and aerosol therapy. In: Mosby’s respiratory care

equipment. St. Louis MO: Mosby-Elsevier Inc; 2010:91-140.

8. Dolovich MB, Ahrens RC, Hess DR, et al. Device selection and out-

comes of aerosol therapy: evidence-based guidelines: American

College of Chest Physicians/ American College of Asthma, Allergy, and

Immunology. Chest 2005; 127(1):335-371.

9. Leach CL, Davidson PJ, Hasselquist BE, Boudreau RJ. Inuence of

particle size and patient dosing technique on lung deposition of HFA-

beclomethasone from a metered dose inhaler. J Aerosol Med 2005;

18(4):379-385.

10. Geller DE. New liquid aerosol generation devices: systems that force

pressurized liquids through nozzles. Respir Care 2002; 47(12):1392-

1404.

11. Dulfano MJ, Glass P. The bronchodilator effects of terbutaline: route of

administration and patterns of response. Ann Allergy 1976; 37(5):357-

366.

12. Gardenhire DS. Airway pharmacology. In: Egan’s fundamentals of respi-

ratory care. St Louis MO: Mosby Elsevier; 2009:667-692.

13. Fink JB. Aerosol drug therapy. In: Egan’s fundamentals of respiratory care.

St Louis MO: Mosby Elsevier; 2009:801-842.

14. Babu KS, Marshall BG. Drug-induced airway diseases. Clin Chest Med

2004; 25(1):113-122.

15. Leuppi JD, Schnyder P, Hartmann K, et al. Drug-induced bronchospasm:

analysis of 187 spontaneously reported cases. Respiration 2001;

68(4):345-351.

16. Steckel H, Eskandar F. Factors affecting aerosol performance during

nebulization with jet and ultrasonic nebulizers. Eur J Pharm Sci 2003;

19(5):443-455.

17. O’Callaghan C, Barry PW. The science of nebulised drug delivery.

Thorax 1997; 52(Suppl 2):S31-S44.

18. Hess DR. Aerosol delivery devices in the treatment of asthma. Respir

Care 2008; 53(6):699-723.

19. Ip AY, Niven RW. Prediction and experimental determination of solute

output from a Collison nebulizer. J Pharm Sci 1994; 83(7):1047-1051.

20. Pitchford K, Corey M, Highsmith A, et al. Pseudomonas species contam-

ination of cystic brosis patients’ home inhalation equipment. J Pediatr

1987; 111(2):212-216.

21. Rosenfeld M, Emerson J, Astley S, et al. Home nebulizer use among

patients with cystic brosis. J Pediatr 1998; 132(1):125-131.

22. Vassal S, Taamma R, Marty N, et al. Microbiologic contamination study

of nebulizers after aerosol therapy in patients with cystic brosis. Am J

Infect Control 2000; 28(5):347-351.

23. Barnes KL, Clifford R, Holgate ST, et al. Bacterial contamination of

home nebuliser. Br Med J (Clin Res Ed) 1987; 295(6602):812.

24. Wexler MR, Rhame FS, Blumenthal MN, et al. Transmission of gram-neg-

ative bacilli to asthmatic children via home nebulizers. Ann Allergy

1991; 66(3):267-271.

25. Jakobsson BM, Onnered AB, Hjelte L, Nystrom B. Low bacterial contam-

ination of nebulizers in home treatment of cystic brosis patients. J

Hosp Infect 1997; 36(3):201-207.

26. Carnathan B, Martin B, Colice G. Second hand (S)-albuterol: RT expo-

sure risk following racemic albuterol (Abstract). Respir Care 2001;

46(10):1084.

27. Dimich-Ward H, Wymer ML, Chan-Yeung M. Respiratory health survey

of respiratory therapists. Chest 2004; 126(4):1048-1053.

28. Christiani DC, Kern DG. Asthma risk and occupation as a respiratory

therapist. Am Rev Respir Dis 1993; 148(3):671-674.

29. Kern DG, Frumkin H. Asthma in respiratory therapists. Ann Intern Med

1989; 110(10):767-773.

30. Rhinehart E, Friedman MM. Personal protective equipment and staff

supplies. In: Infection control in home care (An ofcial APIC publica-

tion). Gaithersburg MD: Aspen Publishers, Inc.; 2006:61-69.

31. Gamage B, Moore D, Copes R, et al. Protecting health care workers

from SARS and other respiratory pathogens: a review of the infection

control literature. Am J Infect Control 2005; 33(2):114-121.

32. Segal-Maurer S, Kalkut G. Environmental control of tuberculosis: con-

tinuing controversy. Clin Infect Dis 1994; 19(2):299-308.

33. Dennis JH. Standardization issues: in vitro assessment of nebulizer per-

formance. Respir Care 2002; 47(12):1445-1458.

34. Hess D, Fisher D, Williams P, et al. Medication nebulizer performance.

Effects of diluent volume, nebulizer ow, and nebulizer brand. Chest

1996; 110(2):498-505.

35. Dennis JH. A review of issues relating to nebulizer standards. J Aerosol

Med 1998; 11(Suppl 1):S73-S79.

36. Welch MJ. Nebulization therapy for asthma: a practical guide for the

busy pediatrician. Clin Pediatr (Phila) 2008; 47(8):744-756.

37. Rau JL, Ari A, Restrepo RD. Performance comparison of nebulizer

designs: constant-output, breath-enhanced, and dosimetric. Respir

Care 2004; 49(2):174-179.

38. Alvine GF, Rodgers P, Fitzsimmons KM, Ahrens RC. Disposable jet nebu-

lizers. How reliable are they? Chest 1992; 101(2):316-319.

39. Camargo CA Jr, Spooner CH, Rowe BH. Continuous versus intermittent

beta-agonists in the treatment of acute asthma. Cochrane Database

Syst Rev 2003; (4):CD001115.

40. Everard ML, Evans M, Milner AD. Is tapping jet nebulisers worthwhile?

Arch Dis Child 1994; 70(6):538-539.

41. Malone RA, Hollie MC, Glynn-Barnhart A, Nelson HS. Optimal duration

of nebulized albuterol therapy. Chest 1993; 104(4):1114-1118.

42. Newman SP. Principles of metered-dose inhaler design. Respir Care

2005; 50(9):1177-1190.

43. Everard ML, Devadason SG, Summers QA, Le Souef PN. Factors affecting

total and “respirable” dose delivered by a salbutamol metered dose

inhaler. Thorax 1995; 50(7):746-749.

44. Niven RW, Kacmarek RM, Brain JD, Peterfreund RA. Small bore nozzle

extensions to improve the delivery efciency of drugs from metered

dose inhalers: laboratory evaluation. Am Rev Respir Dis 1993; 147(6 Pt

1):1590-1594.

45. Pedersen S. The importance of a pause between the inhalation of two

puffs of terbutaline from a pressurized aerosol with a tube spacer. J

Allergy Clin Immunol 1986; 77(3):505-509.

46. Pedersen S, Steffensen G. Simplication of inhalation therapy in asth-

matic children. A comparison of two regimes. Allergy 1986; 41(4):296-

301.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

47. Dolovich M, Rufn RE, Roberts R, Newhouse MT. Optimal delivery of

aerosols from metered dose inhalers. Chest 1981; 80(6 Suppl):911-915.

48. Lawford P, McKenzie. Pressurized bronchodilator aerosol technique:

inuence of breath-holding time and relationship of inhaler to the

mouth. Br J Dis Chest 1982; 76(3):229-233.

49. Thomas P, Williams T, Reilly PA, Bradley D. Modifying delivery technique

of fenoterol from a metered dose inhaler. Ann Allergy 1984; 52(4):279-

281.

50. Unzeitig JC, Richards W, Church JA. Administration of metered-dose

inhalers: comparison of open- and closed-mouth techniques in child-

hood asthmatics. Ann Allergy 1983; 51(6):571-573.

51. Chhabra SK. A comparison of “closed” and “open” mouth techniques

of inhalation of a salbutamol metered-dose inhaler. J Asthma 1994;

31(2):123-125.

52. Newman S, Clark A. Inhalation techniques with aerosol bronchodilators.

Does it matter? Pract Cardiol 1983; 9:157-164.

53. Holt S, Holt A, Weatherall M, et al. Metered dose inhalers: a need for

dose counters. Respirology 2005; 10(1):105-106.

54. Ogren R, Baldwin J, Simon R. How patients determine when to replace

their metered dose inhalers. Ann Allergy Asthma Immunol 1995; 75(6

Pt 1):485-489.

55. Rubin BK, Durotoye L. How do patients determine that their metered-

dose inhaler is empty? Chest 2004; 126(4):1134-1137.

56. Schultz RK. Drug delivery characteristics of metered-dose inhalers. J

Allergy Clin Immunol 1995; 96(2):284-287.

57. Cain WT, Oppenheimer JJ. The misconception of using oating patterns

as an accurate means of measuring the contents of metered-dose

inhaler devices. Ann Allergy Asthma Immunol 2001; 87(5):417-419.

58. Brock TP, Wessell AM, Williams DM, Donohue JF. Accuracy of oat test-

ing for metered-dose inhaler canisters. J Am Pharm Assoc (Wash) 2002;

42(4):582-586.

59. U.S. Department of Health and Human Services, U.S. Food and Drug

Administration. Guidance for industry: integration of dose-counting

mechanisms into MDI drug products. Rockville MD, 2003.

60. Sheth K, Wasserman RL, Lincourt WR, et al. Fluticasone propionate/

salmeterol hydrouoroalkane via metered-dose inhaler with integrated

dose counter: Performance and patient satisfaction. Int J Clin Pract

2006; 60(10):1218-1224.

61. Simmons MS, Nides MA, Kleerup EC, et al. Validation of the Doser, a

new device for monitoring metered-dose inhaler use. J Allergy Clin

Immunol 1998; 102(3):409-413.

62. Julius SM, Sherman JM, Hendeles L. Accuracy of three electronic moni-

tors for metered-dose inhalers. Chest 2002; 121(3):871-876.

63. Williams DM, Wessell A, Brock TP. The Doser external counting device.

Chest 1999; 116(5):1499.

64. Momeni S, Nokhodchi A, Ghanbarzadeh S, et al. The effect of spacer

morphology on the aerosolization performance of metered-dose inhal-

ers. Adv Pharm Bull 2016; 6(2):257-260.

65. Mitchell JP, Nagel MW. Valved holding chambers (VHCs) for use with

pressurised metered-dose inhalers (pMDIs): a review of causes of

inconsistent medication delivery. Prim Care Respir J 2007; 16(4):207-

214.

66. Yazdani A, Normandie M, Youse M, et al. Transport and deposition

of pharmaceutical parti cles in three commercial spacer-MDI combina-

tions. Comput Biol Med 2014; 54:145-155.

67. Ogrodnik N, Azzi V, Sprigge E, et al. Nonuniform deposition of pressur-

ized metered- dose aerosol in spacer devices. J Aerosol Med Pulm Drug

Deliv 2016; 29(6):490-500.

68. American College of Chest Physicians. Patient instructions for inhaled

devices in English and Spanish. Northbrook IL, 2006.

69. Rau JL. The inhalation of drugs: advantages and problems. Respir Care

2005; 50(3):367-382.

70. Fink JB, Rubin BK. Aerosol and medication administration. In: Czerviske

MP, Barnhart SL, editors. Perinatal and pediatric respiratory care. St

Louis MO: Elsevier Science; 2003.

71. Everard ML. Aerosol delivery to children. Pediatr Ann 2006; 35(9):630-

636.

72. Everard ML. Inhalation therapy for infants. Adv Drug Deliv Rev 2003;

55(7):869-878.

73. Ahrens RC. The role of the MDI and DPI in pediatric patients: “Children

are not just miniature adults”. Respir Care 2005; 50(10):1323-1328.

74. Pongracic JA. Asthma delivery devices: age-appropriate use. Pediatr Ann

2003; 32(1):50-54.

75. Boe J, Dennis JH, O’Driscoll BR, et al. European Respiratory Society

Guidelines on the use of nebulizers. Eur Respir J 2001; 18(1):228-242.

76. Rubin BK, Fink JB. Optimizing aerosol delivery by pressurized metered-

dose inhalers. Respir Care 2005; 50(9):1191-1200.

77. Rau JL. Practical problems with aerosol therapy in COPD. Respir Care

2006; 51(2):158-172.

78. Rubin BK. Nebulizer therapy for children: the device-patient interface.

Respir Care 2002; 47(11):1314-1319.

79. Geller DE. Comparing clinical features of the nebulizer, metered-dose

inhaler, and dry powder inhaler. Respir Care 2005; 50(10):1313-1321.

80. Gray SL, Williams DM, Pulliam CC, et al. Characteristics predicting incor-

rect metered-dose inhaler technique in older subjects. Arch Intern Med

1996; 156(9):984-988.

81. Allen SC, Ragab S. Ability to learn inhaler technique in relation to

cognitive scores and tests of praxis in old age. Postgrad Med J 2002;

78(915):37-39.

82. McFadden ER Jr. Improper patient techniques with metered-dose

inhalers: clinical consequences and solutions to misuse. J Allergy Clin

Immunol 1995; 96(2):278-283.

83. Atkins PJ. Dry powder inhalers: an overview. Respir Care 2005;

50(10):1304-1312.

84. Fink JB, Rubin BK. Problems with inhaler use: a call for improved clini-

cian and patient education. Respir Care 2005; 50(10):1360-1375.

85. Lewis RM, Fink JB. Promoting adherence to inhaled therapy: building

partnerships through patient education. Respir Care Clin N Am 2001;

7(2):277-301, vi.

86. Fink JB. Inhalers in asthma management: is demonstration the key to

compliance? Respir Care 2005; 50(5):598-600.

87. Berlinski A. Assessing new technologies in aerosol medicine. Respir Care

2015;60(6):833-849.

88. van der Palen J, Klein JJ, van Herwaarden CL, et al. Multiple inhalers

confuse asthma patients. Eur Respir J 1999; 14(5):1034-1037.

89. Castro-Rodriguez JA, Rodrigo GJ. Beta-agonists through metered-dose

inhaler with valved holding chamber versus nebulizer for acute exac-

erbation of wheezing or asthma in children under 5 years of age: a

systematic review with meta-analysis. J Pediatr 2004; 145(2):172-177.

90. Meadows-Oliver M, Banasiak NC. Asthma medication delivery devices. J

Pediatr Health Care 2005; 19(2):121-123.

91. Chan PW, DeBruyne JA. Parental concern towards the use of inhaled thera-

py in children with chronic asthma. Pediatr Int 2000; 42(5):547-551.

92. Apter AJ, Reisine ST, Afeck G, et al. Adherence with twice-daily dosing

of inhaled steroids. Socioeconomic and health-belief differences. Am J

Respir Crit Care Med 1998; 157(6 Pt 1):1810-1817.

93. Rubin BK. What does it mean when a patient says, “my asthma medica-

tion is not working?” Chest 2004; 126(3):972-981.

94. DiBlasi RM. Clinical controversies in aerosol therapy for infants and chil-

dren. Respir Care 2015;60(6):894-916.

95. Everard ML. Inhaler devices in infants and children: challenges and solu-

tions. J Aerosol Med 2004; 17(2):186-195.

96. Tal A, Golan H, Grauer N, et al. Deposition pattern of radiolabeled

salbutamol inhaled from a metered-dose inhaler by means of a spacer

with mask in young children with airway obstruction. J Pediatr 1996;

128(4):479-484.

97. Everard ML, Clark AR, Milner AD. Drug delivery from holding chambers

with attached facemask. Arch Dis Child 1992; 67(5):580-585.

98. Nikander K, Berg E, Smaldone GC. Jet nebulizers versus pressurized

metered dose inhalers with valved holding chambers: effects of the

facemask on aerosol delivery. J Aerosol Med 2007; 20(Suppl 1):S46-S55.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

99. Bower L, Barnhart S, Betit P, et al. American Association for Respiratory

Care. AARC Clinical Practice Guideline: selection of an aerosol deliv-

ery device for neonatal and pediatric patients. Respir Care 1995;

4(12):1325-1335.

100. National Asthma Education and Prevention Program. Expert Panel

Report III: guidelines for the diagnosis and management of asthma.

Bethesda MD: National Institutes of Health; 2007.

101. Everard ML. Guidelines for devices and choices. J Aerosol Med 2001;

14(Suppl 1):S59-S64.

102. Ritson S JD, Everard ML. Aerosol delivery systems acceptable to young chil-

dren improve drug delivery. Thorax 1998; 53:A55.

103. Fink JB. Aerosol delivery to ventilated infants and pediatric patients.

Respir Care 2004; 49(6):653-665.

104. Nikander K, Agertoft L, Pedersen S. Breath-synchronized nebulization dimin-

ishes the impact of patient-device interfaces (face mask or mouthpiece) on

the inhaled mass of nebulized budesonide. J Asthma 2000; 37(5):451-459.

105. Iles R, Lister P, Edmunds AT. Crying signicantly reduces absorption of

aerosolised drug in infants. Arch Dis Child 1999; 81(2):163-165.

106. Everard ML. Trying to deliver aerosols to upset children is a thankless task.

Arch Dis Child 2000; 82(5):428.

107. Murakami G, Igarashi T, Adachi Y, et al. Measurement of bronchial

hyperreactivity in infants and preschool children using a new method.

Ann Allergy 1990; 64(4):383-387.

108. Janssens HM, van der Wiel EC, Verbraak AF, et al. Aerosol therapy and

the ghting toddler: is administration during sleep an alternative? J

Aerosol Med 2003; 16(4):395-400.

109. Esposito-Festen J, Ijsselstijn H, Hop W, et al. Aerosol therapy by pressured

metered-dose inhaler-spacer in sleeping young children: to do or not to

do? Chest 2006; 130(2):487-492.

110. Restrepo RD, Dickson SK, Rau JL, Gardenhire DS. An investigation of

nebulized bronchodilator delivery using a pediatric lung model of spon-

taneous breathing. Respiratory Care 2006; 51(1):56-61.

111. Kishida M, Suzuki I, Kabayama H, et al. Mouthpiece versus facemask for

delivery of nebulized salbutamol in exacerbated childhood asthma. J

Asthma 2002; 39(4):337-339.

112. Lowenthal D, Kattan M. Facemasks versus mouthpieces for aerosol treat-

ment of asthmatic children. Pediatr Pulmonol 1992; 14(3):192-196.

113. Smaldone GC, Berg E, Nikander K. Variation in pediatric aerosol deliv-

ery: importance of facemask. J Aerosol Med 2005; 18(3):354-363.

114. Amirav I, Newhouse MT. Aerosol therapy with valved holding chambers

in young children: importance of the facemask seal. Pediatrics 2001;

108(2):389-394.

115. Janssens HM, Tiddens HA. Facemasks and aerosol delivery by metered-

dose inhaler valved holding chamber in young children: a tight seal

makes the difference. J Aerosol Med 2007; 20(Suppl 1):S59-S65.

116. Everard ML, Clark AR, Milner AD. Drug delivery from jet nebulisers. Arch Dis

Child 1992; 67(5):586-591.

117. Esposito-Festen JE, Ates B, van Vliet FJ, et al. Effect of a facemask leak

on aerosol delivery from a pMDI-spacer system. J Aerosol Med 2004;

17(1):1-6.

118. Kesser B, Geller D, Amirav I, Fink J. Baby don’t cry: in vitro comparisons

of “baby’s breath” aerosol delivery hood vs. face mask or blow-by using

the “Saint” infant upper airway model and “Aeroneb Go” vs. T-piece

nebulizer (Abstract). Respir Care 2003; 48(11):1079.

119. Rubin BK. Bye-bye, Blow-by. Respir Care 2007; 52(8):981.

120. Everard ML. Aerosol therapy: regimen and device compliance in daily

practice. Paediatr Respir Rev 2006; 7(Suppl 1):S80-S82.

121. Everard ML. Regimen and device compliance: key factors in determin-

ing therapeutic outcomes. J Aerosol Med 2006; 19(1):67-73.

122. Craven DE, Lichtenberg DA, Goularte TA, et al. Contaminated medi-

cation nebulizers in mechanical ventilator circuits. Source of bacterial

aerosols. Am J Med 1984; 77(5):834-838.

123. Lester MK, Flume PA, Gray SL, et al. Nebulizer use and maintenance by

cystic brosis patients: a survey study. Respir Care 2004; 49(12):1504-

1508.

124. Garber E, Desai M, Zhou J, et al. Barriers to adherence to cystic brosis

infection con trol guidelines. Pediatr Pulmonol 2008; 43(9):900-907.

125. Hutchinson GR, Parker S, Pryor JA, et al. Home-use nebulizers: a poten-

tial primary source of Burkholderia cepacia and other colistin-resistant,

gram-negative bacteria in patients with cystic brosis. J Clin Microbiol

1996; 34(3):584-587.

126. Saiman L, Siegel J. Infection control recommendations for patients with

cystic brosis: microbiology, important pathogens, and infection con-

trol practices to prevent patient-to-patient transmission. Infect Control

Hosp Epidemiol 2003; 24(5 Suppl):S6-S52.

127. Cohen HA, Kahan E, Cohen Z, et al. Microbial colonization of nebulizers

used by asthmatic children. Pediatr Int 2006; 48(5):454-458.

128. Blau H, Mussaf H, Mei Zahav M, et al. Microbial contamination of neb-

ulizers in the home treatment of cystic brosis. Child Care Health Dev

2007; 33(4):491-495.

129. Saiman L, Siegel J. Infection control in cystic brosis. Clin Microbiol Rev

2004; 17(1):57-71.

130. Lester MK, Flume PA, Gray SL, et al. Nebulizer use and maintenance by

cystic brosis patients: A survey study. Respir Care 2004; 49(12):1504-

1508.

131. Rau JL. Determinants of patient adherence to an aerosol regimen.

Respir Care 2005; 50(10):1346-1359.

132. Chew NY, Reddel HK, Bosnic-Anticevich SZ, Chan HK. Effect of mouth-

piece washing on aerosol performance of CFC-free Ventolin. J Asthma

2004; 41(7):721-727.

133. American College of Chest Physicians. Priming and cleaning your MDI

and spacer, 2006.

134. Jarvis S, Ind PW, Thomas C, et al. Microbial contamination of domicil-

iary nebulisers and clinical implications in chronic obstructive pulmo-

nary disease. BMJ Open Respir Res 2014; 1(1):e000018.

135. Della Zuana A, Garcia Dde O, Juliani RC, et al. Effect that an educa-

tional program for cystic brosis patients and caregivers has on the

contamination of home nebulizers. J Bras Pneumol 2014; 40(2):119-

127.

136. The Cystic Fibrosis Foundation. Stopping the spread of germs, 2009.

137. Saiman L, Siegel JD, LiPuma JJ, et al. Infection prevention and con-

trol guideline for cystic brosis: 2013 update. Infect Control Hosp

Epidemiol 2014; 35 Suppl 1:S1-S67.

138. Chatburn RL, Kallstrom TJ, Bajaksouzian S. A comparison of acetic acid

with a quaternary ammonium compound for disinfection of hand-held

nebulizers. Respir Care 1988; 33(3):179-187.

139. Le Brun PP, de Boer AH, Heijerman HG, Frijlink HW. A review of the

technical aspects of drug nebulization. Pharm World Sci 2000;

22(3):75-81.

140. Grieble HG, Colton FR, Bird TJ, et al. Fine-particle humidiers. Source of

Pseudomonas aeruginosa infections in a respiratory-disease unit. N Engl

J Med 1970; 282(10):531-535.

141. Mertz JJ, Scharer L, McClement JH. A hospital outbreak of Klebsiella

pneumonia from inhalation therapy with contaminated aerosol solu-

tions. Am Rev Respir Dis 1967; 95(3):454-460.

142. Tablan OC, Anderson LJ, Besser R, et al. Guidelines for preventing health

care-associated pneumonia, 2003: recommendations of CDC and the

Healthcare Infection Control Practices Advisory Committee. MMWR

Recomm Rep 2004; 53(RR-3):1-36.

143. O’Malley CA, VandenBranden SL, Zheng XT, et al. A day in the life of a

nebulizer: surveillance for bacterial growth in nebulizer equipment of

children with cystic brosis in the hospital setting. Respir Care 2007;

52(3):258-262.

144. American Association for Respiratory Care. AARC Clinical Practice

Guideline: selection of an aerosol delivery device. Respir Care 1992;

37(8):891-897 (retired August 2006).

145. Larson T, Gudavalli R, Prater D, et al. Critical analysis of common can-

ister programs: a review of cross-functional considerations and health

system econom ics. Curr Med Res Opin; 2015; 31(4):853-860.

146. Gowan M, Bushwitz J, Watts P, et al. Use of a shared canister protocol

for the delivery of metered-dose inhalers in mechanically ventilated

subjects. Respir Care 2016; 61(10):1285-1292.

147. Estivariz CF, Bhatti LI, Pati R, et al. An outbreak of Burkholderia cepacia

associated with contamination of albuterol and nasal spray. Chest 2006;

130(5):1346-1353.

A Guide to Aerosol Delivery Devices for Respiratory Therapists, 4th Edition

148. Hamill RJ, Houston ED, Georghiou P, et al. An outbreak of Burkholderia

(formerly Pseudomonas) cepacia respiratory tract colonization and

infection associated with nebulized albuterol therapy. Ann Intern Med

1995; 122(10):762-766.

149. Rau JL, Restrepo RD. Nebulized bronchodilator formulations: unit-dose

or multi-dose? Respir Care 2003; 48(10):926-939.

150. U.S. Food and Drug Administration, Center for Drug Evaluation and

Research. Public health advisory: contamination of multi-dose bottles of

Albuterol Sulfate Solution for Inhalation (0.5%), 2002.

151. Center for Disease Control and Prevention. Clean hands save lives, 2008.

152. Center for Disease Control and Prevention. Guideline for hand hygiene

in healthcare settings, 2008.

153. Larson EL. APIC guideline for handwashing and hand antisepsis in

health care settings. Am J Infect Control 1995; 23(4):251-269.

154. Paes BA. Current strategies in the prevention of respiratory synctial

virus disease. Pediatr Respir Rev 2003; 4(1):21-27.

155. Purssell E. Preventing nosocomial infection in paediatric wards. J Clin

Nurs 1996; 5(5):313-318.

156. Hall CB. Nosocomial respiratory syncytial virus infections: the “Cold

War” has not ended. Clin Infect Dis 2000; 31(2):590-596.

157. World Health Organization (WHO). WHO Guidelines on Hand Hygiene

in Health Care: First Global Patient Safety Challenge Clean Care Is

Safer Care. World Health Organization: Geneva; 2009.

158. Braido F, Baiardini I, Blasi F, et al. Adherence to asthma treatments:

‘we know, we intend, we advocate’. Curr Opin Allergy Clin Immunol

2015; 15(1):49-55.

159. Bourbeau J, Bartlett SJ. Patient adherence in COPD. Thorax 2008;

63(9):831-838.

160. Milgrom H, Bender B, Ackerson L, et al. Noncompliance and treatment

failure in children with asthma. J Allergy Clin Immunol 1996; 98(6 Pt

1):1051-1057.

161. Melani AS, Zanchetta D, Barbato N, et al. Inhalation technique and

variables associated with misuse of conventional metered-dose inhal-

ers and newer dry powder inhalers in experienced adults. Ann Allergy

Asthma Immunol 2004; 93(5):439-446.

162. McFadden ER Jr. Improper patient techniques with metered-dose

inhalers: clinical consequences and solutions to misuse. J Allergy Clin

Immunol 1995; 96(2):278-283.

163. Sanchis, J., I. Gich, and S. Pedersen, Systematic Review of Errors in

Inhaler Use: Has Patient Technique Improved Over Time? Chest, 2016.

150(2): p. 394-406.

164. Koehorst-ter Huurne K, Moviq K, van der Valk P, et al. The inuence of

type of inhalation device on adherence of COPD patients to inhaled

medication. Expert Opin Drug Deliv 2016; 13(4):469-475.

165. Price DB, Rigazio A, Buatti Small M, et al. Historical cohort study

examining comparative effectiveness of albuterol inhalers with and

without integrated dose counter for patients with asthma or chronic

obstructive pulmonary disease. J Asthma Allergy 2016; 9:145-154.

166. Wildhaber JH, Devadason SG, Eber E, et al. Effect of electrostatic

charge, ow, delay and multiple actuations on the in vitro delivery

of salbutamol from different small volume spacers for infants. Thorax

1996; 51(10):985-988.

167. Khassawneh BY, Al-Ali MK, Alzoubi KH, et al. Handling of inhaler devic-

es in actual pulmo nary practice: metered-dose inhaler versus dry pow-

der inhalers. Respir Care 2008; 53(3):324-328.

168. Westerik JA, Carter V, Chrystyn H, et al. Characteristics of patients

making serious inhaler errors with a dry powder inhaler and associa-

tion with asthma-related events in a primary care setting. J Asthma

2016; 53(3):321-329.

169. Rau JL. Practical problems with aerosol therapy in COPD. Respir Care

2006; 51(2):158-172.

S://www.aarc.org/wp Content/uploads/2015/04/aerosol_guide_rt Aerosol Guide Rt

Navigation menu

Versions of this User Manual:

Views

Navigation