Considerations for Optimal Inhaler Device Selection in Chronic Obstructive Pulmonary Disease

Rajiv Dhand; Tricia Cavanaugh; Neil Skolnik

doi:10.3949/ccjm.85.s1.04

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FIGURE 1
Examples of different inhaler device and spacer types
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FIGURE 2
Preferences of patients and physicians regarding different aspects of inhaler device design³⁸

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TABLE 1

Key characteristics of different device types^3,6,7

Characteristics	pMDIs	DPIs	SMIs	Nebulizers
Ease of use	Requires coordination between actuation and inhalation (which can be eased when used in conjunction with a spacer, or by using a breath-actuated pMDI)	Varies; they are generally breath-actuated and do not require coordination between actuation and inhalation	Requires assembly and coordination between actuation and inhalation	No specific breathing techniques have to be taught for using nebulizers
Suitable for maintenance or reliever medication	Reliever and maintenance	Reliever and maintenance	Reliever and maintenance	Reliever and maintenance
Treatment time	Short	Short	Short	Longer than pMDIs / DPIs (duration depends on nebulizer device type)
Portability	High	High	High	Depends on type
Multi-dose device	Yes	Some DPIs	Yes	No
Dose counter	Yes	Yes	Yes	No

Abbreviations: DPIs, dry powder inhalers; pMDIs, pressurized metered-dose inhalers; SMIs, soft mist inhalers.

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TABLE 2

Characteristics of inhaler devices^3,7

Device type	Mechanism of action
HFA pMDI	Pressurized suspension of micronized drug particles distributed in propellant; others are ethanolic solutions Precise amount (20–100 μL) dispensed with each press of canister Shaking not required as with CFC pMDIs Pressing canister releases drug
Breath-actuated pMDI	Pressurized canister with flow-triggered system driven by a spring Inhalation drives spring to trigger inhalation Requires higher PIF than HFA pMDIs, but lower than DPIs
DPI	Dry powder inside capsule (manual loading) or inside device Micronized drug particles (1–5 μm) blended with inactive excipient (40 μm) or used alone Inhalation deaggregates medication particles and disperses them within airways Minimum PIF rate required for deaggregation (varies by DPI device) Passive (breath-actuated)
SMI	Propellant-free Drug stored inside cartridge (loaded on first use) Spring releases dose into micropump; dose released when button is pressed "Uniblock" passes dose through minute channels releasing jet streams of drug solution
Breath-enhanced jet nebulizer	Air stream moves through jet causing drug solution to be aerosolized; powered by compressor Additional room air taken into nebulizer during inhalation drives aerosolization Nebulizer drug solution cools during nebulization Vents the expired air outside device Tabletop and portable models available
Breath-actuated jet nebulizer	Air stream moves through tube causing drug solution to be aerosolized; powered by compressor Patient inhalation drives aerosolization (does not occur unless patient inhales) Tabletop and portable models available
Ultrasonic nebulizer	Piezoelectric crystals vibrate causing aerosolization Nebulized drug solution gets heated during nebulization Portable
Vibrating mesh nebulizer	Piezoelectric crystals vibrate a mesh plate causing aerosolization Very fine droplets No significant change in temperature of the solution during nebulization Lower residual drug remaining in chamber compared with jet nebulizers Portable

Abbreviations: CFC, chlorofluorocarbon; DPI, dry powder inhaler; HFA, hydrofluoroalkane; PIF, peak inspiratory flow; pMDI, pressurized metered-dose inhaler; SMI, soft mist inhaler.

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TABLE 3

Critical errors and their reported frequencies for pressurized metered-dose inhalers and dry powder inhalers²⁶

pMDIs		DPIs
Critical error	Frequency (% of users)	Critical error	Frequency (% of users)
Critical error	Frequency (% of users)	Critical error	HandiHaler /Aerolizer	Diskus	Turbuhaler
Failure to remove mouthpiece cap	0.15	Failure of priming
Actuation against teeth, lips, or tongue	0.7	Failure to open the device	0	0.65	0
Activation after end of inhalation	5	Failure to insert the capsule	9	NA	NA
Stopped inhalation immediately after firing	10	Failure to pierce the capsule	3	NA	NA
Inhalation through nose during and after actuation	2	Failure of loading
		Incorrect dose loading	NA	7.3	14
		Keep inhaler inclined ≤45° from the vertical axis during loading	NA	NA	23
		Inhaling by nose	2	1	0
		Not sealing lips around mouthpiece during inhalation	5	5	4
		Slow and not forceful inhalation	24	28	22

Abbreviations: DPI, dry powder inhaler; NA, not applicable; pMDI, pressurized metered-dose inhaler.
Reprinted from Respiratory Medicine, 105(6). Melani AS, Bonavia M, Cilenti V, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control, 930–938, Copyright 2011, with permission from Elsevier.

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TABLE 4

Inhaled drugs by device type (with current FDA approval for patients with COPD)

		Drugs available
		SAMA	SABA	SAMA/ SABA	LAMA	LABA	LAMA/ LABA	ICS/LABA	ICS/ LAMA/ LABA
HFA MDIs		IPR (Atrovent)^a	ALB (ProAir HFA,^b Ventolin HFA,^c Proventil HFA^d)				GLY/FOR (Bevespi Aero- sphere)^f	FP/SAL (Advair)^cBUD/FOR Inhalation Aerosol (Symbicort)^f
HFA MDIs		IPR (Atrovent)^a	LLB (Xopenex HFA^e)				GLY/FOR (Bevespi Aero- sphere)^f	FP/SAL (Advair)^cBUD/FOR Inhalation Aerosol (Symbicort)^f
DPIs	Aerolizer^g					FOR (Foradil)
	Diskus^c					SAL (Serevent)		FP/SAL (Advair)
	Ellipta^c				UME (Incruse)		UME/VIL (Anoro)	FF/VIL (Breo)	FF/UME/ VIL (Trelegy)
	HandiHaler^a				TIO (Spiriva)
	Neohaler^g				GLY (Seebri)	IND (Arcapta)	GLY/IND (Utibron)
	Pressair^f				ACL (Tudorza)
SMIs	Respimat^a			IPR/ALB (Combi- vent)	TIO (Spiriva)	OLO (Striverdi)	TIO/OLO (Stiolto)
Nebulizers*	Breath- enhanced jet (eg, PARI LC Plus ) ^h	IPR (Atrovent)^a	ALB (Proventil^d, Ventolin^c) LLB (Xopenex^e)	IPR/ALB (DuoNeb)^l		ARF (Brovana)^eFOR (Performo- mist)^l
	Breath-actuatedjet (eg, AeroEclipse II BANⁱ)
	Ultrasonic (eg, UltraNeb^j)
	Vibrating mesh^† (eg, AKITA APIXNEB^k)

Abbreviations: ACL, aclidinium; ALB, albuterol; ARF, arformoterol; BAN, breath actuated nebulizer; BUD, budesonide; COPD, chronic obstructive pulmonary disease; DPI, dry powder inhaler; FDA, US Food and Drug Administration; FF, fluticasone furoate; FOR, formoterol; FP, fluticasone propionate; GLY, glycopyrrolate; HFA, hydrofluoroalkane; ICS, inhaled corticosteroid; IND, indacaterol; IPR, ipratropium bromide; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic receptor antagonist; LLB, levalbuterol; MDI, metered-dose inhaler; OLO, olodaterol; SABA, short-acting β₂-agonist; SAL, salmeterol; SAMA, short-acting muscarinic receptor antagonist; SMI, soft mist inhaler; TIO, tiotropium; UME, umeclidinium; VIL, vilanterol.
The SAMA and SABA treatments above are indicated for rescue therapy in patients with COPD. The LAMA, LABA, LAMA/LABA and ICS/LABA treatments are indicated for the maintenance treatment of COPD. Ipratropium (Atrovent) and ipratropium/albuterol (Combivent and DuoNeb) may be used as both a maintenance and rescue therapy.
↵a Boehringer Ingelheim;
↵b Teva Respiratory;
↵c GlaxoSmithKline;
↵d Schering;
↵e Sunovion;
↵f AstraZeneca;
↵g Novartis;
↵h PARI International;
↵i Monaghan Medical Corporation;
↵j DeVilbiss Healthcare;
↵k Activaero GmbH;
↵l Mylan.
* One example of each nebulizer device type provided.
↵† Not yet approved for therapy in patients with COPD.

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TABLE 5

Factors affecting inhaler device selection and solutions

	Selection and usage considerations	Measures to address these
Patient-related factors	• Understanding of need for inhaler device/medication(break/)• Age(break/)• Coordination(break/)• Manual dexterity(break/)• PIF rates(break/)• Cognitive impairment(break/)• Comorbidities(break/)• Patient preference	• Provide adequate training for all patients(break/)• Older patients may need additional time for training(break/)• Consider using BA devices or spacers if coordination/manual dexterity is poor(break/)• DPIs usually require good inspiratory flow; consider other devices if PIF is very low(break/)• Consider easier-to-use/passive inhalation devices with cognitive impairment (eg, nebulizers)(break/)• Where possible, combine multiple medications in one device, or maintain consistency of device types across medications(break/)• Take patient preference/finances into account
System/health care professional factors	• Knowledge/training of health care professional(break/)• Device availability(break/)• Cost (including out-of-pocket cost to patient)	• Provide adequate training to health care professionals as well as patients(break/)• Ensure device is available to patient(break/)• Evaluate cost vs clinical benefit