Inhaler Devices for Patients with COPD

Figures & data

Table 1.  Examples of inhalers containing one or more COPD medications

SABAs
• Albuterol (Proventil® HFA, Ventolin® HFA, ProAir® HFA)
• Levalbuterol (Xopenex® HFA)
SAACs
• Ipratropium (Atrovent® HFA, nebulizer)
SABA/SAAC combinations
• Ipratropium/Albuterol (Combivent® CFC, DuoNeb® Inhalation Solution nebulizer, Respimat® SMI)
• Ipratropium/Fenoterola (Berodual® Inhalation Solution nebulizer, HFA pMDI, Respimat® SMI)
LABAs
• Formoterol (Foradil® Aerolizer® DPI, Foradil® Certihaler® DPI, Perforomist® Inhalation Solution nebulizer)
• Arfomoterol (Brovana® Inhalation Solution nebulizer)
• Salmeterol (Serevent® Diskus® DPI)
LAAC
• Tiotropium (Spiriva® HandiHaler® DPI, Respimat® SMI)
• LABA/ICS combinations
• Salmeterol/fluticasone (Advair® Diskus® DPI, Advair® HFA)
• Budesonide/Formoterol (Symbicort® Turbuhaler® DPI)


SABA = short-acting β2-agonist, SAAC = short-acting anticholinergic, LABA = long-acting β2-agonist, LAAC = long-acting anticholinergic, ICS = inhaled corticosteroid, CFC = chlorofluorocarbon, HFA = hydrofluoroalkane, pMDI = pressurized metered-dose inhalers, DPI = dry powder inhaler, SMI = Soft Mist inhaler.

Figure 1.  Milestones in inhaler development. In accordance with the Montreal Protocol on Substances That Deplete the Ozone Layer (1987) (26), the U.S. Food and Drug Administration (FDA) announced the worldwide phase out of pressurized metered-dose inhalers (p-MDIs) that contained chlorofluorocarbon (CFC) by 2013 (25). The CFC-Combivent® inhaler still maintains ‘essential use’ status, i.e., patients can use the CFC-based device, but the FDA has scheduled finalization of its discontinuation for 2013 (25). DPI = dry powder inhaler, HFA = hydrofluoroalkanes, SMI = Soft Mist inhaler, MDI = metered-dose inhaler.

Table 2.  Patient-related variables impacting correct device use (41)

• Pulmonary function and GOLD disease stage (mild, moderate, severe, and very severe)
• Smoking status, age, sex, being overweight
• Comorbidities
• Manual dexterity
• Ability to understand and follow instructions
• Eyesight
• Psychosocial issues

GOLD = Global Initiative for Chronic Obstructive Lung Disease (1).

Table 3.  Preferred versus actual inhaler properties relevant to patients (16,21,23,48–54)

Preferred Properties of a User-friendly Inhaler	Nebulizer	pMDI	DPI	SMI
Lung deposition	∼6–20%	∼4–55%	∼10–40%	46–57%
Low oropharyngeal deposition	10–20%	∼30–85%	∼50–80%	15–24%
Simple to use	8–10 steps	6 steps	Range from 6–17 steps; simplicity varies widely among DPIs	5 steps
Easy to maintain	Regular washing and daily disinfection required	Periodic cleaning required; wash/dry actuator	Periodic cleaning required; varies by device	Periodic cleaning required; damp cloth to mouthpiece
Short treatment time	No (5–20 min)	Yes	Yes	Yes
Small size and easy to carry	No	Yes	Generally	Heavier than pMDI or DPI
Multi-dose convenience	No	Yes	Some DPIs are single-dose units	Yes
Resistance to bacterial contamination	No	Yes	Yes	Yes
Impacted by environmental temperature and humidity	No	Yes (CFC more than HFA)	Yes	No
Dose counter	No	On newer HFA designs	Yes –vary in sophistication	Yes
Low ambient aerosol contamination	>60% to atmosphere	Prime to atmosphere and exhaled	Only exhaled	Prime to atmosphere and exhaled
Specific device design available with range of COPD drugs required	Yes	No	No	No
Functional placebo devices available for teaching	Yes	Varies by manufacturer	Varies according to device	Yes
Environmental impact	No propellants	CFCs and HFAs have global warming potential	No propellants	No propellants
Liked by patients and physicians	Limited acceptance (Noise, size, and maintenance issues)	Generally well accepted	Generally well accepted	Generally well accepted

pMDI = pressurized metered-dose inhaler, DPI = dry powder inhaler, SMI = Soft Mist inhaler, CFC = chlorofluorocarbon,

HFA = hydrofluoroalkane.

Table 4.  Suitability of commonly used portable inhalers based on patient inhalation capabilities (90,91)

Devices	Good PIF > 30 L/min	Poor PIF < 30 L/min
pMDI	Yes	pMDI + VHC
DPI	Yes	DPI (limited to low flow design, eg, HandiHaler®)
SMI	Yes	Yes

PIF = peak inspiratory flow rate, pMDI = pressurized metered-dose inhaler, DPI = dry powder inhaler, SMI = Soft Mist inhaler, VHC = valved holding chamber.

Table 5.  Priming requirements for some portable inhalers (105)

Medication	Inhaler	Number of priming sprays	When to reprime^a
SABAs:
levalbuterol	Xopenex® HFA	4	>3 days
albuterol	Proventil® HFA	4	>14 days
	Ventolin® HFA	4	>2 weeks
	ProAir® HFA	3	>2 weeks
SAACs:
ipratropium	Atrovent® HFA	2	>3 days
SABA/SAAC combination:
ipratropium + albuterol	Combivent® CFC^b	3	1 day
LAACs:
tiotropium
	Respimat® SMI^c	1^d	>7 days
LABA/ICS combinations:			>4 weeks with 2 primes for HFA; Reprime if canister is dropped
fluticasone + salmeterol	Advair® HFA	4
budesonide + formoterol	Symbicort® HFA	2	>7 days or when canister has been dropped

^aBrand new inhalers may also have to be primed prior to first use as per manufacturer instructions.

^bU.S. Food and Drug Administration recommendations to discontinue inhaler by December 31, 2013 per The Montreal Protocol on Substances That Deplete the Ozone Layer (25).

^cOnly available in Europe.

dFour actuations prior to first use and full priming after 21 days of no use; fenoterol + ipratropium and albuterol + ipratropium combinations also formulated for this inhaler.

SABA = short-acting β2-agonist, HFA = hydrofluoroalkanes, SAAC = short-acting anticholinergic, CFC = chlorofluorocarbons, LAAC = long-acting anticholinergic, SMI = Soft Mist inhaler, LABA = long-acting β2-agonist, ICS = inhaled corticosteroid.

Table 6.  Considerations for device selection (55)

• Device/drug availability

• Clinical setting and environment

• Patient age and ability to use the device correctly

• Device use with multiple medications

• Cost and reimbursement

• Drug administration time

• Convenience in both acute and outpatient setting

• Physician and patient preference