The Science Guiding Selection of an Aerosol Delivery...

The Science Guiding Selection of an Aerosol Delivery Device

Timothy R Myers MBA RRT-NPS FAARC

IntroductionTypes of Aerosol Delivery DevicesSmall-Volume Nebulizers

Pneumatically Powered NebulizersUltrasonic NebulizerMesh NebulizerOther Nuances and Characteristics of SVNs

Pressurized Metered Dose Inhalers and AccessoriesConventional pMDIBreath-Actuated and Breath-Controlled pMDISoft-Mist pMDIAccessory Devices

Dry Powder InhalerSingle-Dose DPIMultiple Unit-Dose DPIMultiple-Dose DPI

Selecting an Aerosol Delivery DeviceConclusions

Aerosol therapy continues to be considered as one of the cornerstones of the profession of respi-ratory care, even after 60 years. Aerosol therapy serves as a critical intervention for both exacer-bations and chronic maintenance for a variety of respiratory care conditions. Aerosol therapyuniquely blends both the art and science of medicine together to produce the practical and neces-sary clinical outcomes for patients with respiratory diseases. This review was presented as part ofthe New Horizons Symposium on how to guide the scientific selection of an appropriate aerosoldevice. Key words: aerosol therapy; respiratory care; inhaler; nebulizer. [Respir Care 2013;58(11):1963–1973. © 2013 Daedalus Enterprises]

Introduction

Medications are part of the management regimen andcare in hundreds of medical conditions. The use of inhaled

aerosols allows selective treatment of the lungs by achiev-ing a high drug concentration in the airway while reducingsystemic adverse effects.1 Safe and effective medication

Mr Myers is an Associate Executive Director of the American Associa-tion for Respiratory Care (AARC).

Mr Myers presented a version of this paper at the 28th New Horizons inRespiratory Care Symposium, “The Scientific Basis for Respiratory Care,”at the AARC Congress 2012, held November 10–13, 2012, in NewOrleans, Louisiana.

The author has disclosed no conflicts of interest.

Correspondence: Timothy R Myers MBA RRT-NPS FAARC, AmericanAssociation for Respiratory Care, 9425 N MacArthur Boulevard,Suite 100, Irving TX 75063. E-mail: [email protected].

DOI: 10.4187/respcare.02812

RESPIRATORY CARE • NOVEMBER 2013 VOL 58 NO 11 1963

delivery is a major focal area in hospitals and medicine ingeneral today. This increased focus and scrutiny from amedical regulatory standpoint have led to numerous qual-ity initiatives surrounding the 5 “rights” (Table 1) of med-ication delivery. While these 5 “rights” also apply to aero-solized medications, the delivery of inhaled medications oraerosol therapy is also intricately tied to the delivery de-vices themselves, which is not always the case with oralor injected medications. Table 2 lists the advantages anddisadvantages of inhaled medications.

Aerosols are part of everyday life and play a criticalrole in the management and treatment of patients withchronic respiratory conditions. Understanding the scienceof the therapy and its associated technology are vital tosuccessful intervention, treatment, and education for thecare and management of chronic respiratory disease.

Methods for generating aerosols, formulating drugs,and administering medications effectively to the desiredsite of action constitute the science of aerosol drug deliv-ery,2 an intricate science in that it is also an art. The art ofthe therapy involves matching the right aerosol deliverydevice with the patient’s physical and cognitive abilities topromote optimized care.

Effective inhalation of aerosolized medications from ascientific perspective relies on both the mechanism of aero-sol deposition and its relationship to aerosol particle size.The size of aerosol particles plays an important function in

lung deposition, in addition to the velocity of the particle,and settling time during the inspiratory cycle of breathing.

The primary mechanism of aerosol deposition withinthe respiratory system involves 3 distinct factors of depo-sition: inertial impaction, gravitational sedimentation (set-tling), and diffusion. When aerosolized particles tend to belarger (� 5 �m) and faster-moving, inertial impactionoccurs most commonly in the upper airways or is filteredout in the naso-oropharynx by the narrow passages andhigh airways resistance. Particles that fall within the 1–5 �msize typically deposit based on a function of particle massand inspiratory time, with the rate of settling proportionalto particle size and mass, which is referred to as gravita-tional settling. The smallest aerosol particles (� 1 �m)tend to be deposited based on diffusion. Particle size isespecially important when dealing with the pediatric pop-ulation.

Delivery technology for aerosolized medications, re-gardless of device, produces a mixture of aerosol particlesizes (polydisperse particles). The scientific unit of mea-sure (in �m) that quantifies a polydisperse aerosol is re-ferred to as the mass median diameter. When the sciencetalks about deposition, it is typically reported as the massmedian aerodynamic diameter, or MMAD. The MMAD isthe numerical value where particle size evenly divides themass, or amount of the drug above and below which 50%of the mass of the particles is contained.

Optimal particle size for most inhaled respiratory med-ications to achieve deposition in the periphery of the lungfalls into the particle size range of 1–5 �m. As particle sizeincreases above 5 �m, aerosol deposition shifts from theperiphery of the lung to the conducting airways. Oropha-ryngeal deposition increases as particle size increases above10 �m. Exhaled loss is high with very small particles of1 �m or less.

In addition to particle size, the inspiratory flow rate ofthe patient also plays a synergistic role in the location ofthe medication deposition. Higher inspiratory flow in theupper airways promotes impaction of particles from thenares to the larynx, particularly for particles of MMAD of3–5 �m.3

When dealing with an infant or a child, these principlesalso apply, but are also influenced by other variables aswell. Studies of a variety of respiratory tract disordershave shown that the major patient related factors that de-termine and/or limit lower respiratory tract aerosol depo-sition are lower respiratory tract anatomy and physiopa-thology, rather than specific diseases.4

Types of Aerosol Delivery Devices

Aerosol delivery devices predominantly reside in one of3 classifications: small-volume nebulizer (SVN), pressur-ized metered-dose inhaler (pMDI), and dry powder inhaler

Table 1. Five “Rights” of Medications

The right patientThe right medicationThe right timeThe right routeThe right dose

Table 2. Advantages and Disadvantages of Inhaled Medications

AdvantagesGenerally smaller than systemic dosesFaster onset of action than oral dosingDirect deliveryLess frequent and severe systemic effectsLess painful and relatively easy, compared to injections

DisadvantagesLung deposition is lowMany variables affect efficacy and dose reproducibilityHand-eye coordination required with pressurized metered-dose

inhaler (pMDI)Lack of knowledge among patients and cliniciansNumber and variability of device typesLack of standardization

(From Reference 2.)

THE SCIENCE GUIDING SELECTION OF AN AEROSOL DELIVERY DEVICE

1964 RESPIRATORY CARE • NOVEMBER 2013 VOL 58 NO 11

(DPI). Table 3 provides a brief description for each of thedelivery devices. Each specific device has its own nu-ances, which leads to a large potential disadvantage forinhaled medications. Inappropriate technique can lead tosuboptimal dosing of medications and less than acceptabledisease control. In the last few decades (Fig. 1), a prolif-eration of inhalation devices has resulted in a confusingnumber of choices for the healthcare provider, and in con-fusion for both clinicians and patients trying to use thesedevices correctly.5

For several decades, clinicians and patients alike be-lieved that SVNs were more effective than pMDIs, par-ticularly for quick relief mediations during exacerbationsof air-flow obstruction. A systematic review of the evi-dence documented equivalent clinical results, regardless ofthe device used, for quick relief medications, provided thatthe patient utilizes the device correctly, despite the SVNproviding the higher nominal dose.5

As science has continued to refine the technology anddevices for aerosol delivery, newer aerosol devices anddrug formulations are increasing the efficiency of lungdeposition, when compared to the traditional devices com-monly used. New devices, such as the Respimat inhaler(Boehringer Ingelheim Pharmaceuticals, Ingelheim, Ger-many), have shown lung depositions of 40%.6 While thedose of drug delivered to the lung has high variabilitybetween devices, aerosol delivery devices with relativelylow lung deposition fraction have clinically demonstrateddesired therapeutic outcomes in their target audience.

Small-Volume Nebulizers

SVNs are typically powered from a gas, electrical, orbattery powered source and convert drug solutions or sus-pensions into aerosols that target the patient’s lower re-spiratory tract with minimal patient cooperation. The mech-anism of action and design of SVNs has a large variability,and each has its own specific design that requires back-ground and knowledge to utilize the device to its fullestfunctionality. SVNs are typically designed and classifiedinto one of 3 categories: pneumatic, ultrasonic, or mesh.

Pneumatically Powered Nebulizers

The main mechanism of action for the pneumaticallypowered nebulizer is to entrain the solution or suspensionto be aerosolized through the generated gas stream, caus-ing a shearing into a liquid film. As this liquid film ishighly unstable, it disperses into droplets secondary tosurface tension forces. A baffle in the SVN causes theaerosol stream to yield smaller particles. Aerosol particlescan be further impacted by environmental factors such asthe relative humidity of the carrier gas. Table 4 lists otherfactors that can impact SVN aerosol output. Nebulizerdesign changes over the past decade have created differentnebulizer categories.7,8 Figure 2 pictures the 4 differentclasses of pneumatically powered nebulizer: jet nebulizerwith reservoir tube, jet nebulizer with collection bag orelastomeric reservoir ball, breath-enhanced jet nebulizer,and breath-actuated jet nebulizer.

Jet Nebulizer with a Reservoir Tube. These nebulizersare typically mass produced and are the least expensiveand most widely used type of nebulizers in the markettoday (see Fig. 2A). Jet nebulizers continuously aerosol-ize, during both inhalation and exhalation, and require abreath-hold to promote optimal deposition. Jet nebulizers,due to their design, emit aerosol to the ambient air duringthe expiratory phase and any time when the patient is notbreathing.8,9

Jet Nebulizer With Collection Bag or Elastomeric Res-ervoir Ball. This class of SVN creates aerosol particlesby continuously filling a reservoir (see Fig. 2B). A built-inreservoir with a one-way inspiratory valve allows the pa-tient to inhale medication from the reservoir, and exhalesto the atmosphere through an exhalation port between theone-way inspiratory valve and the mouthpiece.8,9

Breath-Enhanced Jet Nebulizer. Breath-enhanced neb-ulizers utilize 2 one-way valves to prevent the loss ofaerosol to the environment (see Fig. 2C), while using areservoir with the inspiratory valve to front-end load med-ication at the beginning of inspiration. During the expira-tory phase, gas passes through an expiratory valve in themouthpiece to the atmosphere.

Breath-Actuated Jet Nebulizer. Perhaps the most tech-nical and expensive class of SVN nebulizers is the breath-actuated nebulizers. The construct of these devices is de-signed to increase aerosol drug delivery to patients bygenerating aerosol only during inspiration. Consequently,loss of medication during expiration is greatly reduced(see Fig. 2D).9 Breath-actuation triggering mechanisms arecategorized as manual, mechanical, and electronic.

Table 3. Types of Aerosol Delivery Devices

Small-volumenebulizer

Converts liquid drug solution or suspension intoaerosol particles of varying particle sizes

Metered-doseinhaler

Small, portable device that dispenses multiple dosesby metered value; self-contained system

Dry-powderinhaler

Small, portable device that delivers powdered drugwith breath-actuated dosing system based oninspiratory flow

(From Reference 2.)



Fig. 1. Common inhalers available in the United States. (From Reference 2.).



Ultrasonic Nebulizer

Ultrasonic nebulizers convert electrical energy to high-frequency vibrations using a transducer. These high fre-quency vibrations are transmitted to the surface of theliquid solution, producing a standing wave that generatesaerosol. Small-volume ultrasonic nebulizers are commer-cially available for delivery of inhalable bronchodilators,but should not be used with suspensions such as budes-onide. Ultrasonic nebulizers tend to heat the medication.This raises concerns about disrupting proteins, but thatdoes not affect commonly inhaled medications.10

Mesh Nebulizer

Mesh nebulizers use electricity to vibrate a piezo (atapproximately �128 kHz) plate or aperture that forcesliquid formulations through a fine mesh to generate aero-sol. The aerosol particle size can be manipulated to avariety of particle sizes, based on the diameter of the meshor aperture. Mesh nebulizers are highly efficient and pro-duce minimal residual or dead volume (0.1–0.5 mL) leftover in the device at the end of a treatment. Mesh nebu-lizers operate on one of 2 basic mechanisms of action:active vibrating mesh, and passive mesh. Active vibratingmesh nebulizers have aperture plates with thousands offunnel-shaped holes vibrated by a piezo-ceramic elementthat surrounds the aperture plate, while passive mesh neb-ulizers employ an ultrasonic horn to drive fluid through amesh screen.

Other Nuances and Characteristics of SVNs

The design of SVNs and the medications that they aero-solize also add one other unique characteristic: the abilityof the pneumatically powered nebulizers to be utilized forcontinuous aerosol delivery or powered by alternative gassources (helium-oxygen combinations).

Continuous aerosol drug administration of a bronchodi-lator is often a consideration in asthma exacerbations. Con-tinuous nebulization therapy is a safe treatment modality,administered with a typical dose range for continuous al-

buterol of 5–15 mg/h.11 Several configurations have beendescribed for continuous nebulization, including frequentrefilling of the nebulizer, use of a nebulizer and infusionpump (Fig. 3), and use of a large-volume nebulizer.

While often an area of clinical controversy, studies havedemonstrated that continuous nebulization may be as ef-fective as intermittent aerosol therapy, or may, in fact, besuperior to intermittent nebulization in patients with se-vere pulmonary dysfunction.12,13 A meta-analysis of re-sults from 6 randomized trials indicated that intermittentadministration and continuous administration have similareffects on both lung function and the overall rate of hos-pitalization,14 whereas a Cochrane review of findings from8 trials suggested that continuous administration resultedin greater improvement in peak expiratory flow and FEV1,and a greater reduction in hospital admissions, particularlyamong patients with severe asthma.12

The second area of aerosol therapy that is unique toSVNs is the use of an alternative gas to power the nebu-lizer: in this case a combined mixture of helium and ox-ygen, or, as it is more commonly referred to, heliox. Inobstructive airways disease the opportunity to decreaseturbulent air flow through obstructive airways with a lessdense gas offers the hypothetical advantage of deliveringaerosol particles and medications distal to the obstruc-tions.15–18 Heliox is a gas mixture of helium (60–80%)and oxygen, which is used to improve air flow in patientswith partial airway obstruction.19

Clinical studies utilizing heliox as the driving gas fordelivery of aerosolized asthma medications in asthmaticshave reported conflicting results,20 which makes evidence-based decisions on its use undeterminable for several pos-sible reasons. As an example, one of the possible reasonsfor variability in results can be traced to the liter flow usedto power the nebulizer. Hess et al21 determined that theflow of heliox with 80% helium and 20% oxygen must beincreased by about 50% to generate optimally sized respi-rable particles.

Nevertheless, new evidence suggests certain benefits inpatients with more severe obstruction. In a review, Frazierand Cheifetz summarized the possible uses of heliox inasthma exacerbation (Table 5).22 However, since that in-formation is based on between-group comparisons andsmall studies, the conclusions are not definitive.23

Often a question of effective nebulization time becomesa clinical question, and when to discontinue treatment.Two frequently seen practices are for clinicians and pa-tients to tap the SVN to reduce dead volume and increaseoutput,24 while the second practice continues nebulizationbeyond device sputtering, to decrease dead volume.1 Infact, research has suggested that after the onset of sputtervery little additional drug is inhaled.1,25 As patient adher-ence to therapy is a critical component to out-patient main-

Table 4. Factors That Impact Aerosol Drug Delivery With Small-Volume Nebulizers

Gas flow and pressureFill volume and dead volumeGas densityHumidity and temperatureBreathing patternDevice interface

(From Reference 2.)



tenance therapy, many clinicians recommend discontinu-ing treatment either at or 1 min after sputter onset.

The final area of clinical concern revolves around thepatient-device interface, which occurs mainly in the pedi-atric and in-patient settings. Mouthpieces and face masksare the 2 interfaces with SVNs, and studies suggest that amouthpiece interface promotes greater lung deposition thana face mask26,27 and is effective in the clinical treatment of

children.26,28,29 However, using a preferred device can pro-mote adherence, inhaled dose, and desired clinical response.The importance of a closely fitting face mask is a critical

Fig. 2. Types of pneumatic jet nebulizer. The aerosol output is indicated by the shaded areas. 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 2.)

Fig. 3. Setup for continuous aerosol therapy. (From Reference 2.)

Table 5. Summary of the Clinical Application of Heliox in AsthmaExacerbation

Heliox may benefit initial treatment of pediatric asthma, serving as abridge until corticosteroids have clinical effect.

Heliox benefits initial treatment of moderate-to-severe asthmaexacerbation in the emergency department.

Heliox is most beneficial in the initial treatment period; clinicalimprovement with heliox, as compared to oxygen-enriched air,becomes less evident over time.

Heliox appears to improve gas exchange in patients with asthma torequire intubation, potentially decreasing the ventilator supportrequired.

Heliox allows lower ventilator settings and lower FIO2, decreasing the

risk of ventilator-induced lung injury.With the increasing use of noninvasive ventilation, heliox might be an

adjunct.

(From Reference 2.)



factor in achieving optimal drug deposition and avoidingnebulizing aerosol into the patient’s eyes. Even small leaksof 0.5 cm around the face mask decrease drug inhaled bychildren and infants by more than 50%.30-34

Delivery of aerosolized medications in a blow-by fash-ion is commonly used for crying babies or uncooperativechildren, where the nebulization port of a nebulizer isdirected toward the patient’s face. Studies have documentedblow-by medication administration is less efficient, com-pared with a face mask, as aerosol drug deposition de-creases significantly with distance, and this use should bediscouraged.30,34-36

In summary, while the domain of SVNs can be highlyvariable, based on the nuances and characteristics describedpreviously, the entire category has some common advan-tages and disadvantages, which are listed in Table 6.

Pressurized Metered Dose Inhalers and Accessories

The pMDI has not changed much in the last 50 years. Itis a marvel of engineering science, containing a valve thatallows a metering of the drug, an actuator boot to triggerthe medication and direct it toward the mouth, and medi-cation formulation, which contains a propellant, excipi-ents, and the medication (Fig. 4).37

The pMDI is a medical aerosol delivery system thatcombines a device with a specific formulation and dose ofdrug.2 Actuation of the pMDI delivers a metered dose ofmedication that must be coordinated with a single inspi-ration of the patient. Each pMDI canister is required tocreate reproducible doses (� 20) from first to last dose,with a drug shelf life of 12–24 months.

Pressurized MDIs provide a mobile, manually actuatedportable device that patients can utilize anywhere at any

time, and can be used either alone or with an accessorydevice such as a spacer or valved holding chamber (VHC).There are 3 major types of pMDI: conventional, breath-actuated, and soft-mist. Table 7 lists the advantages anddisadvantages of pMDIs in general terms.

Conventional pMDI

The conventional pMDI has a press-and-breathe design.Actuation of the canister into the device boot aligns thehole in the metering valve with the metering chamber andreleases the drug-propellant mixture, which then expandsand vaporizes to convert the liquid medication into anaerosol. Release of the canister allows the metering valve

Table 6. Advantages and Disadvantages of Small-VolumeNebulizers

AdvantagesMany drug solutionsCan deliver combinationsMinimal patient cooperation requiredCan deliver to all patient agesConcentration and dose can be modifiedNormal breathing pattern

DisadvantagesTreatment time variation (5–25 min)Poor portabilityNeed for power sourceRisk of drug exposure to eyesPerformance variabilityAssembly and cleaning issues

(From Reference 2.)

Fig. 4. Standard components of a pressurized metered-dose in-haler. (From Reference 2.)

Table 7. Advantages and Disadvantages of Pressurized Metered-Dose Inhalers

AdvantagesPortable, light, and compactMultiple-dose convenienceShort treatment timeReproducible dosingNo drug preparationLower risk of contamination

DisadvantagesHand-breath coordination requiredActive patient required: activation, inhalation pattern, breath-holdFixed concentration/dosePropellant reactionAerosol particle impaction in upper airwaysMost lack dose counting

(From Reference 2.)



to refill the chamber with another dose of the drug-pro-pellant mixture. An important component of the pMDI,often overlooked, is the need to prime the metering cham-ber before use. Although improvements in valve designhave reduced the need for priming, it remains prudent toprime the pMDI if it has not been used recently.38,39

Breath-Actuated and Breath-Controlled pMDI

The breath-activated nebulizer is a technology that sensesthe patient’s inspiratory flow and delivers aerosol onlywhen flow triggers the opening of a valve and decreasesmedication wastage.40 Its mechanism is triggered by inha-lation through a breath-actuated nozzle, which provides anautomatic response to the patient’s inspiratory effort. It isimportant to assess the patient to ensure that they are ableto generate a high enough inspiratory flow to activate thetriggering mechanism. Breath-actuated pMDIs are not rec-ommended for the younger pediatric patient.

Breath-controlled nebulizers use computer technologyto determine a patient’s inspiratory flow and volume, anduse those to deliver the medication at the beginning ofinhalation, allowing the inspired air at the end of inhala-tion to drive the aerosol deep into the airway.41 The theorybehind these devices is that less medication is deposited inthe oropharyngeal cavity and upper airways, increasingdrug availability and deposition in the lung periphery. Thesedevices require a slow inspiratory maneuver, contrasted tobreath-actuated or DPIs that require higher inspiratory flow.

Soft-Mist pMDI

The Respimat (Boehringer Ingelheim Pharmaceuticals,Ingelheim, Germany) is a newly released, propellant-free,soft-mist inhaler that employs mechanical energy from atensioned spring to generate the soft aerosol plume. Whenthe dose release button is depressed, the energy from thespring forces solution to the mouthpiece, creating a softaerosol plume that lasts approximately 1.5 seconds.2 Thesoft mist pMDI, similar to a conventional pMDI, requirespriming before use and at times when the device has had

no use. Since the device is propellant-free, there is no needto shake it.

Most pMDIs are manufactured to deliver a targeted drugdose per actuation, of which approximately 10–20% of thenominal dose per actuation reaches the lung periphery as afine particle fraction range in which the MMAD is � 5 �m.Several factors influence the pMDI performance and aero-sol drug delivery, and are listed in Table 8.

Accessory Devices

Spacer devices typically are reservoir-type devices thatfacilitate delivery of aerosol in patients who are unable tocoordinate device actuation and inspiration, by allowingthe patient to direct the aerosol into his or her mouththrough the reservoir. The mechanism of a spacer device isto provide additional volume to decrease pMDI aerosolvelocity, allowing a reduction in particle size. Aerosol

Table 8. Factors Affecting Pressurized Metered-Dose InhalerPerformance and Drug Delivery

Not shaking the pressurized metered-dose inhaler (pMDI) prior to useStorage temperatureNozzle size and cleanlinessTiming of actuation intervalsNot priming the pMDI per the manufacturer’s recommendationPatient characteristics (eg, age)Breathing technique

(From Reference 2.)

Table 9. Advantages and Disadvantages of Pressurized Metered-Dose Inhaler Accessory Devices

AdvantagesReduce oropharyngeal deposition and dose lossIncrease deposition 2–4 times, compared to pressurized metered-

dose inhaler (pMDI) aloneAllows pMDI use in patients with acute illness/dyspneaNo drug preparationSimplifies drug delivery/coordination issues

DisadvantagesAccessory device decreases portability, compared to pMDI aloneAdditional costDevice assembly necessaryPossible dosing errors with use/compatibilityPotential source of contamination/infection

(From Reference 2.)

Table 10. Advantages and Disadvantages of Dry Powder Inhalers

AdvantagesSmall and portableBuilt-in dose countingPropellant-freeBreath-actuatedShort preparation and delivery time

DisadvantagesInspiratory flow dependentPatient dose awarenessHigh oropharyngeal depositionHumidity problemsLimited range of drugsDevice instructions specific to brand

(From Reference 2.)



retention and discharged dose depend on the size and shapeof the spacer, and on the electrostatic charge on the innerwalls of plastic spacers.2 While actuation-breath coordina-tion is less important with an accessory device, it is stillimportant for the patient to coordinate their inhalation withactuating the inhaler. Table 9 lists the advantages anddisadvantages of pMDI accessory devices.

A VHC is a spacer device that incorporates a one-wayvalve that holds medication within the device until thepatient inhales and directs exhalation away from the aero-sol in the chamber, reducing aerosol losses resulting frompoor hand-breath coordination. For patients unable to usea VHC with a mouthpiece, a low-resistance face mask canbe placed on the patient to allow the medication to flowfrom the chamber into the mask. As with face mask neb-ulizer therapy, it is important that the mask seals comfort-ably and completely on the face. Optimal aerosol dosingstill depends on inhaling as close to or simultaneously withpMDI actuation into the chamber.

Volume may vary, although in the United States mostholding chambers/spacers are � 200 mL. Direction ofspray may vary between forward (toward the mouth) andreverse (away from the mouth). Children with low tidalvolumes (less than device dead space) may need to takeseveral breaths from a VHC through a face mask for asingle pMDI actuation.2

An area of clinical concern with pMDI accessory de-vices is electrostatic charge acquired by the aerosol whengenerated, or present on the accessory device surface, as ithas been demonstrated to decrease aerosol delivery fromVHCs.42,43 A solution to electrostatic charge was to man-

ufacturer VHCs made from conducting materials such asstainless steel or aluminum.44,45 Electrostatic free VHCstend to be more expensive than their counterparts, andthere are some practical solutions. Priming a new spacer’swalls with 20 doses will coat the inner surface and mini-mize static charge,45 but is probably not cost-effective, asit utilizes up to 10% of a pMDI’s doses. A more practicaland real world solution is to wash a nonconducting VHCwith dishwashing detergent to reduce surface electrostaticcharge, and detergent-washing is now incorporated in mostmanufacturer instructions.43 If this method is utilized, theVHC should not be towel-dried; the VHC should be al-lowed to air-dry.42

Dry Powder Inhaler

DPIs have become the trendy device over the past de-cade, and consist of powdered drug formulations that areeither in a pure drug form or mixed with an inactive ex-cipient such as lactose.46 DPIs are inspiratory flow-driven,do not contain propellant, and are breath-actuated by thepatient’s inspiratory effort.

Based on the specific device (usually between 30 and60 L/min, depending on the device), the patient’s inspira-tory flow creates energy to deaggregate small drug parti-cles and disperses the particles as aerosol emitted from thedevice. DPIs do not require coordinated efforts of the pa-tient with the act of inhalation.

There are some unique characteristics of DPIs that makethem not applicable to all patient populations. All DPIs,due to the formulary of the drug as a powder, are humiditysensitive. The higher-resistance DPIs may be difficult for

Fig. 5. Dry powder inhalers (DPIs) currently available in the United States, categorized by design features. (From Reference 2.)



young children to use, particularly when they are ill.47 Ifpatients exhale into the device, they risk blowing out themedication, and the humidification from exhaled breathcan decrease the efficiency of the inhaler, as the particlesstick to the orifice.48 Table 10 lists the advantages anddisadvantages of DPIs.

Currently, DPIs can be organized into 3 categories cen-tered on the dispenser design: single-dose, multiple unit-dose, and multiple-dose (Fig. 5). Regardless of the type ofDPI, they all have the same essential components incor-porated with the inhaler: a drug holder, an air inlet, anagglomeration compartment, and a mouthpiece.2

Single-Dose DPI

Single-dose DPIs have individually wrapped capsulesthat contain a single-dose of medication and function bydispersing powder medication from a punctured capsule.When using a single-dose DPI, a new drug capsule mustbe loaded prior to each dose, and the old, used capsulediscarded. A potential disadvantage of single-dose DPI isthe time and manual dexterity needed to load a dose foreach use. Moreover, the capsules should be used only inthe intended device and should not be administered in anyother device.1

Multiple Unit-Dose DPI

Multiple unit-dose DPIs disperse individual doses thatare pre-metered into blisters of medication by the manu-facturer. Each blister is mechanically punctured when thecover is lifted, allowing the medication to be inhaled throughthe mouth without damaging other blister capsules withinthe device. This design eliminates the potential disadvan-tages of the single-dose DPI with each capsule, but thepatient still needs to periodically load a blister pack intothe device.

Multiple-Dose DPI

Multiple-dose DPI either measures the dose from a pow-der reservoir or uses blister strips prepared by the manu-facturer to deliver repeated doses.2 All doses for the pre-scription (device-drug combination) are self-contained andrequire no medication loading or manipulation by the pa-tient prior to or after use.

Selecting an Aerosol Delivery Device

At the end of the day, we are back to where we began:selecting the most appropriate delivery device is very im-portant for optimizing the results of aerosol drug therapy.Evidence indicates that all 3 types of aerosol generatorscan be equally effective if they are used correctly by thepatient.5 The criteria to select an aerosol generator can bedivided into 4 categories: patient-related, drug-related, de-vice-related, and environmental and clinical factors.

In a Journal Conference review by Hess in RESPIRATORY

CARE in 2008,1 a systematic approach to a series of ques-tions was presented in a step-wise, practical manner, ques-tions that ultimately should be asked by every clinicianwho is responsible for prescribing or educating patients onrespiratory medications and their associated delivery de-vices. Those patient/device related questions are high-lighted in Table 11.

Conclusions

The science, characteristics, and nuances of each devicehas been described here, and it is critical that these con-siderations and factors, along with the specifications of thedevice, be considered and evaluated with each individualpatient. Patient/caregiver evaluation and education are par-amount to establish correct device/patient matching, properadministration techniques, and the ultimate efficacy of thedrug provided to the patient.

REFERENCES

1. Hess DR. Aerosol delivery devices in the treatment of asthma. Re-spir Care 2008;53(6):699-723.

Table 11. Questions to Consider in Matching Patient to AerosolDelivery Device

In what devices is the desired drug available? Some formulations areavailable only for a single device, which dictates the device usedwith that formulation.

What device is the patient likely to be able to use properly, given thepatient’s age and the clinical setting? Devices that require manualdexterity will be more difficult for elderly patients. Devices thatrequire considerable patient/device coordination may be difficult forthe very young or elderly.

For which device and drug combination is reimbursement available?This is an important consideration if the cost is not covered by athird-party payer and the patient cannot afford the out-of-pocketexpense.

Which device is least costly? This is an important consideration in thehospital.

Can all the types of inhaled drugs for asthma and COPD that areprescribed for the patient be delivered with the same type ofdevice? Using the same type of device for all the patient’s inhaleddrugs may facilitate patient teaching and decrease the chance ofconfusion with multiple devices that require different inhalationtechniques, although one study reported that concurrent use ofpressurized metered-dose inhaler (pMDI) and dry powder inhaler(DPI) by children with persistent asthma did not adversely affecttechnique.

Which devices are the most convenient for the patient, family (out-patient use), or medical staff (acute care setting), given the timerequired for drug administration and device cleaning, and theportability of the device?

How durable is the device?Does the patient or clinician have any specific device preferences?

(From Reference 2.)



2. Gardenhire DS, Hess DR, Myers TR, Rau JL. A guide to aerosoldelivery devices for respiratory therapists, 3rd edition. AmericanAssociation for Respiratory Care; Irving, Texas; 2013.

3. Howarth PH. Why particle size should affect clinical response toinhaled therapy. J Aerosol Med 2001;14(Suppl 1):S27-S34.

4. Amirav I, Newhouse MT. Deposition of small particles in the lung.Paediatr Respir Rev 2012;13(2):73-78.

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