Eur Respir J ****; **: **** ****

DOI: **.****/***31936.00166410

Copyright ERS 2011

ERS/ISAM TASK FORCE REPORT

What the pulmonary specialist should know

about the new inhalation therapies

B.L. Laube, H.M. Janssens, F.H.C. de Jongh, S.G. Devadason, R. Dhand, P. Diot,

M.L. Everard, I. Horvath, P. Navalesi, T. Voshaar and H. Chrystyn

ABSTRACT: A collaboration of multidisciplinary experts on the delivery of pharmaceutical AFFILIATIONS

For a list of the authors affiliations

aerosols was facilitated by the European Respiratory Society (ERS) and the International Society

see the Acknowledgements section.

for Aerosols in Medicine (ISAM), in order to draw up a consensus statement with clear, up-to-date

recommendations that enable the pulmonary physician to choose the type of aerosol delivery CORRESPONDENCE

device that is most suitable for their patient. The focus of the consensus statement is the patient- B.L. Laube

Johns Hopkins University School of

use aspect of the aerosol delivery devices that are currently available.

Medicine

The subject was divided into different topics, which were in turn assigned to at least two 200 North Wolfe Street

experts. The authors searched the literature according to their own strategies, with no central Suite 3015

literature review being performed. To achieve consensus, draft reports and recommendations Baltimore

MD 21287

were reviewed and voted on by the entire panel.

USA

Specific recommendations for use of the devices can be found throughout the statement. E-mail: abqb00@r.postjobfree.com

Healthcare providers should ensure that their patients can and will use these devices correctly.

This requires that the clinician: is aware of the devices that are currently available to deliver the Received:

Oct 25 2010

prescribed drugs; knows the various techniques that are appropriate for each device; is able to

Accepted after revision:

evaluate the patient s inhalation technique to be sure they are using the devices properly; and Jan 05 2011

ensures that the inhalation method is appropriate for each patient. First published online:

Feb 10 2011

KEYWORDS: Inhalation technique, inhalation therapy, inhalation treatment, pulmonary delivery

CONTENTS

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1309

Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1309

Pulmonary aerosol delivery: overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1309

Limitations of aerosol therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1310

Particle- and patient-related factors that influence aerosol deposition . . . . . . . . . . . . . . . . . . . . 1310

Lung disease and deposition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1311

Drug receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1311

Nasal versus oral inhalation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1311

Patient behaviour and deposition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1311

Choice of delivery device . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1312

Regulation of delivery devices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1312

Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1312

Aerosol device options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1312

Pressurised metered-dose inhalers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1312

Breath-actuated pressurised metered-dose inhalers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1318

Spacers and valved holding chambers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1320

Dry powder inhalers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1321

Nebulisers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1323

European Respiratory Journal

Soft mist inhalers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1324

Print ISSN 0903-1936

Choice of drug device combinations to use at home . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1324 Online ISSN 1399-3003

1308 VOLUME 37 NUMBER 6 EUROPEAN RESPIRATORY JOURNAL

B.L. LAUBE ET AL ERS/ISAM TASK FORCE: INHALATION THERAPIES

Patients with pulmonary arterial hypertension . . . . . . . 1324 Choice of drug device combinations to use in special

HIV-infected (AIDS) or immunocompromised patients . 1324 populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1325

Patients with cystic fibrosis . . . . . . . . . . . . . . . . . . . . 1324 Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1325

Choice of drug device combinations to use in the The elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1326

emergency room and in hospital . . . . . . . . . . . . . . . 1325

Intubated and mechanically ventilated patients . . . . . . 1326

Pressurised metered-dose inhalers with spacers versus

Patients on noninvasive mechanical ventilation . . . . . . 1327

nebulisers to administer short-acting bronchodilators in the

The future . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1327

emergency room . . . . . . . . . . . . . . . . . . . . . . . . . 1325

Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1327

Nebulisers and patients with severe asthma and chronic

Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1327

obstructive pulmonary disease in the emergency room. . 1325

Nebulisers and non-cystic fibrosis diseases in hospital. . 1325 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1328

A joint Task Force of multidisciplinary experts on the delivery always be taught and assessed by competent healthcare

professionals.

of pharmaceutical aerosols was approved by the European

Respiratory Society (ERS) and the International Society for

In this consensus statement, we focus on the patient-use aspect

Aerosols in Medicine (ISAM), in order to draw up clear, up-to-

of the aerosol delivery devices that are currently available, so

date recommendations that enable the pulmonary physician to

that prescribers understand the inhalation methods needed for

choose the type of aerosol delivery device that is most suitable

these devices and can make an informed choice as to the type

for their patients at home and in hospital.

of device that is most suitable for their patient s use at home

and in hospital. Devices under development were not included

Many drugs are currently delivered directly to the lungs as

because they were not available to the physician at the time of

an aerosol. These include short-acting b2-adrenergic agonists

review.

and long-acting b2-adrenergic agonists (LABA), anticholiner-

gics, inhaled corticosteroids (ICSs), nonsteroidal anti-inflam-

matories, antibiotics and mucolytics. Other drugs are under METHODS

development for aerosol delivery. These include insulin to The Task Force was composed of 11 invited participants who

treat diabetes, gene therapy vectors to treat cystic fibrosis (CF), were identified on the basis of their expertise in the area of

vaccines for measles and papilloma virus, chemotherapy agents pulmonary aerosol delivery. The subject was divided into

for lung cancer, new formulations for antibiotics, anti-proteases different topics, which were in turn assigned to at least two

to treat CF and a1-antitrypsin deficiency, morphine to relieve experts. Topic-writers searched the literature according to their

pain, and ergotamine to relieve headaches. own strategies and determined their own databases. No attempt

was made to grade evidence or recommendations. The literature

Devices that are available to deliver these drugs include

search ended in December 2009.

pressurised metered-dose inhalers (pMDIs), used either alone

or attached to spacers or valved holding chambers (VHCs), breath- Draft reports written by the experts on each topic were dis-

actuated (BA)-pMDIs, dry powder inhalers (DPIs), nebulisers tributed to the entire expert panel and comments were solicited

and soft mist inhalers. in advance of meetings that were held at the 2009 ISAM

Congress and the 2009 ERS Congress, as well as a small group

Treatment guidelines for the management of asthma [1] and

meeting at the 2009 ERS School Course on Medical Aerosols.

chronic obstructive pulmonary disease (COPD) [2] are well

During these meetings, the recommendations and evidence

established. Both recommend inhaled therapy as the primary

supporting the recommendations were reviewed and discussed

route to administer medication. A comprehensive comparison

by the entire panel. Approval of the recommendations required

of the dose equivalence of inhaled steroids has been presented [3].

consensus, which was defined as a majority approval. Dif-

Treatment guidelines for CF also include inhalation of aerosolised

ferences of opinion were accommodated by revising the recom-

medications [4, 5]. mendations until consensus was reached. Despite differences

between guidelines and the availability of drugs and devices,

Meta-analysis reports indicate that when patients use the

the Task Force tried its utmost to develop a consensus statement

inhalation technique recommended by the manufacturer, all

that is valid all over the world.

inhalers are effective and can achieve the same therapeutic

effect, although different doses may be required [6, 7]. How-

ever, many patients do not use the correct technique when PULMONARY AEROSOL DELIVERY: OVERVIEW

using their inhalers [8], either because they have never been Unlike oral or intravenous therapies, aerosolised therapy

taught or because they have modified the technique following delivers drugs directly to the internal lumen of the airways

instruction. As is the case with most therapeutic areas, poor and onto the therapeutic sites. For this reason, the systemic

adherence with the optimal treatment regimen is common [9]. dose of most aerosolised drugs is reduced compared to oral

For this reason, treatment guidelines state that a patient s and i.v. treatments. Direct delivery to the lungs also permits

inhaler technique and their level of adherence should be a more rapid bronchodilation in response to b2-adrenergic

c

determined before a change is made to a patient s pre- agonists and anticholinergics, and with some LABAs the

duration of the effect is enhanced compared to oral treatments.

scription. They also indicate that inhaler technique should

1309

EUROPEAN RESPIRATORY JOURNAL VOLUME 37 NUMBER 6

ERS/ISAM TASK FORCE: INHALATION THERAPIES B.L. LAUBE ET AL

Limitations of aerosol therapy in the lungs [13]. Aerodynamic diameter is generally thought

to be the most important particle-related factor that affects

Not all inhalation devices are appropriate for all patients. This is

aerosol deposition. Figure 1 shows the relationship between

because of differences in the way the devices perform and the

aerodynamic diameter and lung deposition [14]. Upon enter-

need to master specific inhalation techniques, which require

ing the oral cavity, particles will deposit by impaction,

varying levels of cognitive ability depending on the device.

sedimentation and Brownian motion depending on their size.

Reviews of randomised controlled trials comparing different

Particles .5 mm are most likely to deposit by impaction in the

inhalers have concluded that they are all equivalent [6, 7].

oropharynx and be swallowed [13]. This is partially the result

However, patients in randomised controlled trials receive more

of the inertia associated with the particle s mass, which

inhaler-technique training and counselling on the importance of

reduces its ability to follow the airstream when it changes

adherence than patients who are seen as part of routine clinical

direction toward the lower airways. It is important to minimise

practice. For this reason, the Global Initiative for Asthma

corticosteroid deposition in the oropharynx because it can give

(GINA) and the British Thoracic Society (BTS) guidelines

rise to local side-effects, such as hoarseness and oral

recommend that inhaler technique and the degree of adherence

candidiasis with ICS [15].

with dose regimens should be assessed before changing a

patient s inhalation therapy [1 3].

Figure 1 also shows that particles that are,5 mm have the

Based on a real-life setting, it has been reported that 76% of greatest potential for deposition in the lungs. The proportion of

patients using a pMDI and 49 54% of those using a BA-pMDI particles within an aerosol that are,5 mm is often referred to

make at least one error when using their inhaler [10]. In as the fine-particle fraction (FPF), or the fine-particle dose

addition, between 4 and 94% of patients using a DPI do not use (FPD) if expressed in absolute mass of drug in particles,5 mm

it correctly and 25% have never received inhaler-technique (table 1). Aerosols with high FPFs have a high probability of

training [11]. Failure to exhale to functional residual capacity penetrating beyond the upper airways and depositing in the

before inhaling through their DPI device and failure to use a lungs. Thus, it is not surprising that current devices generate

forceful, deep inhalation were two of the most common pro- aerosols with a significant proportion of their particles in the

blems with DPIs [11]. With pMDIs, the most common problems 1 5 mm range. The optimal particle size range for aerosols

were lack of actuation inhalation coordination and stopping delivered to children is not known. It is likely that it is smaller

inhalation due to the cold freon effect [12]. Despite these errors, than the optimal size range for adults, due to narrower airway

50, 66 and 70 80% of general practitioners report that their diameters and higher intraluminal flows.

patients inhale the right dose when they use a pMDI, BA-pMDI

Figure 1 shows that particles of 4 5 mm deposit primarily in

and a DPI, respectively [10].

the bronchial/conducting airways, whereas smaller particles

When patients inhale a short-acting bronchodilator, they inhale remain in the airstream and are carried into the peripheral

another dose if they do not obtain a sufficient response from airways and the alveolar region. In the periphery of the lung,

the first dose. As a result of this, they can overcome poor airflow rate is reduced and particles deposit predominantly by

technique and potentially poor disease control by increasing sedimentation, with gravity causing them to rain out and

their dose. Patients do not get this feedback from other inhaled deposit. Most particles of 0.1 1 mm diffuse by Brownian

therapies. For those drugs, it is important that patients use motion and deposit when they collide with the airway wall.

their device in an optimal manner and this often requires a The longer the residence time in the smaller, peripheral airways,

specific and relatively complex inhalation manoeuvre that is the greater the deposition from sedimentation and Brownian

tailored to the patient s needs and preferences [8]. motion processes [16]. It is recommended that patients hold their

breath after inhalation of an aerosolised medication because the

breath-hold increases the residence time and this enhances

Particle- and patient-related factors that influence aerosol

deposition in the peripheral airways. Inhaled particles that do

deposition

not deposit are exhaled [13].

Table 1 provides the definitions of terms commonly used to

describe an aerosol. These terms are derived from in vitro

Important patient-related factors include the morphology of

measurements of particle-related characteristics and include

the oropharynx and larynx and the patient s inspiratory

dose and aerodynamic diameter. In terms of dose, physicians

volume and flow rate. The patient s inspiratory flow rate

should be particularly aware that some countries label the

generally determines the velocity of the airborne particle and

inhaler with the nominal dose (which is the dose that is metered),

this, in turn, also affects the probability of its impaction in the

while others use the emitted dose (which is the dose that comes

oropharynx and larynx [17]. To minimise deposition in the

out of the actuator and is available for inhalation at the mouth).

upper airways and enhance delivery of the drug to the lungs

For example, beclomethasone pMDI (hydrofluoroalkane (HFA)

when using a pMDI with or without a spacer, or a BA-pMDI,

formulation, QVAR1 (see Appendix for all product/drug

patients should inhale slowly. Slowly translates into inhal-

manufacturer details)) is labelled as 100 mg (the nominal dose)

ing fully over 2 3 s in a child and 4 5 s in an adult after a deep

in Europe and as 80 mg (the emitted dose) in the USA. Although

exhalation. This ensures that flows are,30 L?min-1, which is

these two references to dose are not the same, the dose that the

the ideal flow when using a pMDI [18]. With DPIs, the patient

patient receives is the same.

has to inhale as deeply and as hard as they can to overcome

the internal resistance to flow and generate the aerosol for

Drug delivery via the respiratory tract is more complex than

inhalation. DPIs also require turbulent energy to de-aggregate

oral therapy. Successful therapy requires a delivery system

their formulations and produce a FPD during the inhalation

that generates drug particles of an appropriate size, such that

manoeuvre. The greater the energy imparted by the patient s

they penetrate beyond the oropharynx and larynx and deposit

1310 VOLUME 37 NUMBER 6 EUROPEAN RESPIRATORY JOURNAL

B.L. LAUBE ET AL ERS/ISAM TASK FORCE: INHALATION THERAPIES

Definitions of commonly used terms that describe an aerosol

TABLE 1

Term Abbreviation Definition

Labelled dose or nominal dose# The mass of drug that is available within the aerosol generator per actuation. This is the dose that is metered.

Total emitted dose or delivered dose# TED The mass of drug emitted per actuation that is actually available for inhalation at the mouth.

The mass of particles,5 mm in size within the total emitted dose.

Fine-particle dose FPD

Fine-particle fraction FPF The fine particle dose divided by the total emitted dose.

The diameter of a fictitious sphere of unit density (1 g?cm-3) that has the same gravitational

Aerodynamic equivalent diameter dae

(settling) velocity in the same gas as the actual particle.

Mass median aerodynamic diameter dae,mm or MMAD The MMAD divides the aerosol size distribution in half. It is the diameter at which 50% of the

particles of an aerosol by mass are larger and 50% are smaller.

sg or GSD

Geometric standard deviation The GSD measures the dispersion of particle diameter and is defined as the ratio of the median

(s) from the median diameter. In a cumulative distribution plot

diameter to the diameter at 1 SD

of the aerodynamic diameter and mass of particles, the GSD is calculated as the ratio of the

median diameter to the diameter at 15.9% of the probability scale, or the ratio of the diameter at

84.1% on the probability scale to the median diameter. Aerosols with a GSD o1.22 are considered

polydisperse. Most therapeutic aerosols are polydisperse and have GSDs in the range of 2 3.

#

: lung deposition can be presented as a percentage of the nominal or emitted dose. Note that these two parameters are not the same.

inspiratory flow rate, the more effective the particle de- receptors in the smooth muscle located in the conducting

aggregation. airways. By targeting these receptors, bronchodilators open up

(dilate) the larger airways.

Lung disease and deposition

Corticosteroid receptors are also present throughout the

The degree of lung disease at the time of inhalation

airways [26] and inflammation has been shown to exist in all

significantly influences the pattern of drug deposition within

regions of the lungs in asthma [26] and COPD [27]. For these

the lungs. Several studies have shown that central airway

reasons, uniform distribution of an ICS throughout the air-

deposition is enhanced as mucus plugging, turbulent airflow

ways, following inhalation, may be preferable. Further studies

and airway obstruction increase [19 23]. This means that in the

are needed to confirm this before recommendations can

face of severe lung disease, little or no drug may deposit in the

be made. Furthermore, there is doubt about the effective-

lung periphery. This may not be clinically important for

ness, or role, of ICS in COPD [28], as reflected in the Global

bronchodilators, but could be important for corticosteroids.

Initiative for Chronic Obstructive Lung Disease (GOLD)

guidelines [2].

Drug receptors

Receptors for inhaled bronchodilators are distributed through-

Nasal versus oral inhalation

out the lungs [24, 25], but they have their greatest effect on

The nose is a more effective filter than the mouth. Thus,

inhalation through the mouth is the preferred route for aerosol

100

delivery to the lungs. This is a potential issue when treating

infants and toddlers. For example, when children are treated

Total with nebulisers, or pMDIs with spacers or holding chambers,

80

they frequently breathe through their noses using a facemask.

While absolute efficiency in terms of lung dose is low during

Deposition %

60

nose breathing, compared to mouth breathing [29], the total

Oropharynx

inhaled dose per kg of body weight is relatively higher in

nose-breathing children compared with older patients using

40

mouthpieces. Therefore, the dose to the lungs per kg body

Bronchial/

conducting weight in nose-breathing infants is probably similar to that

airways

achieved by mouth-breathing adults [29].

20 Alveolar

Patient behaviour and deposition

0

0.5 1 2 3 4 5 6 7 8 910 20 For inhaled therapy to be effective, the patient must use a

device effectively and adhere to a regular treatment regimen

Log aerodynamic diameter m

[8]. Adherence to treatment regimens is known to be fre-

quently poor in all therapeutic areas and is probably not signi-

FIGURE 1. The International Commission on Radiological Protection model

c

ficantly worse with inhaled as compared with oral therapy.

showing the relationship between aerodynamic diameter and lung deposition. Data

However, even if a patient is fully adherent with a treatment

from [14].

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EUROPEAN RESPIRATORY JOURNAL VOLUME 37 NUMBER 6

ERS/ISAM TASK FORCE: INHALATION THERAPIES B.L. LAUBE ET AL

regimen, inhaled therapy may be ineffective if poor inhala- Although previous publications have provided general inhalation

technique recommendations for inhalers [7, 35], table 4 pro-

tion technique limits the amount of drug available for lung

deposition. Studies have shown that a very high proportion of vides more detailed instructions on how to use pMDIs, BA-

patients do not have the competence to use their device pMDIs, pMDIs with spacers, DPIs, nebulisers and soft mist

inhalers. The major advantages and disadvantages of pMDIs

effectively, either because they have never been shown or

because they have forgotten what they were taught [8, 30]. with and without spacers, BA-pMDIs, nebulisers and DPIs are

This is a particular problem in the elderly, but it does affect all summarised in table 5 [9].

age groups. Furthermore, many patients soon forget the

Regulation of delivery devices

correct technique that they have been trained to use [31]. In

In Europe, aerosol devices are regulated by the European

addition, many of those who are able to demonstrate a good

technique in the clinic will contrive to use the device inef- Medicines Agency (EMA; www.ema.europa.eu). In the USA,

the regulatory agency is the Food and Drug Administration

fectively in routine use. The most common example of con-

trivance is spacer disuse (e.g. patient s failure to use a spacer (www.fda.gov).

at home).

Recommendations

Data regarding the impact of education on regimen adherence

Prescribers should:

is at best mixed, and it is very difficult to influence this aspect

1) Know the types of devices that are available to deliver

of patient behaviour. Having a good rapport with the patient

specific drugs and classes of drugs (table 2).

has been shown to improve regimen adherence after a con-

sultation, but this may be as transient as 1 week [31]. Patients

2) Appreciate the advantages and disadvantages of each device

may be more adherent with an inhaler that combines two

(table 5).

drugs (i.e. LABA and ICS) in the same dose, compared with

using two separate inhalers [32]. Although this may simplify 3) Choose devices that the patient can and will use effectively

the regimen, the effect is far from universal. While education (table 3).

per se probably does not have a significant impact on regimen

4) Choose devices that have been approved by the appropriate

adherence, patient feedback in terms of regimen adherence

authorities (table 2).

and automated reminders appear to influence this aspect of

behaviour and are likely to become more frequently employed 5) Train patients about the correct inhalation manoeuvre that is

in clinical practice in the future [33]. appropriate for the device being prescribed (table 4).

Healthcare providers have a particular duty to ensure that 6) Check the patient s inhaler technique regularly.

patients are able to use their inhalers effectively [8]. Physicians

7) Review the patient s adherence to treatment at each visit.

must ensure that a suitable device is prescribed, that the

patient is competent in the use of it and that the patient 8) Not switch to a new device without the patient s involve-

understands that little or no drug may reach the lungs if the ment and without follow-up education on how to use the

device is not used according to the specified instructions. Com- device properly.

petence and contrivance are amenable to educational inter-

vention, though it is important to review these issues with the AEROSOL DEVICE OPTIONS

patient on a regular basis. Once a patient is familiar and Pressurised metered-dose inhalers

stabilised on one type of inhaler, they should not be switched

Transition to HFA products

to new devices without their involvement and without follow-

The pMDI was introduced in the 1950s as the first portable,

up education on how to use the device properly.

multi-dose delivery system for bronchodilators. It is still the

most widely prescribed inhalation device. Until recently, the

Choice of delivery device

drugs delivered by pMDIs were formulated with chlorofluoro-

The choice of device for a particular drug is determined by the

carbon (CFC) propellant and small amounts of excipients

devices that are available for that drug and whether the patient

(such as valve lubricants). CFCs are now being replaced by

can and will use it effectively. Table 2 provides a summary

HFAs due to a ban on CFCs. At present, there are only a few

of the devices that are currently available for delivery of the

pMDIs that still contain CFCs. In most European countries,

most commonly prescribed brand-name drugs, broken down

CFC-pMDIs have been totally replaced by non-CFC inhalers.

according to pMDIs, BA-pMDIs, nebulisers, soft mist inhalers

After 2013, CFC-pMDIs will no longer be available in the USA

and DPIs. A pMDI requires good actuation inhalation coordi-

[36]. Table 2 presents drugs that are delivered by HFA- versus

nation for optimal lung deposition, whereas a DPI requires

CFC-pMDIs.

sufficient inspiratory flow. Table 3 provides information for

choosing the right aerosol delivery device for patients with There are some differences between the CFC and HFA

good versus poor actuation inhalation coordination and suf- products. Two of the major differences are that the plume

ficient inspiratory flow [34]. Patients with poor actuation released from many HFA-pMDIs has a slower velocity and is

inhalation coordination include children and elderly patients. warmer [37]. These changes partially overcome the cold freon

Where possible, patients should use one type of device for all effect that has caused some patients to stop inhaling their CFC-

of their inhaled therapies [1, 3]. However, this is not always pMDIs [12]. Another difference is that many HFA-pMDI

possible. In the USA, there is no salbutamol DPI; patients may formulations contain a small amount of ethanol. This affects

therefore have to use both a pMDI for their b2-adrenergic the taste, as well as further increasing the temperature and

decreasing the velocity of the aerosol. Exceptions to the alcohol

agonist and a DPI for their other prescribed medications.

1312 VOLUME 37 NUMBER 6 EUROPEAN RESPIRATORY JOURNAL

B.L. LAUBE ET AL ERS/ISAM TASK FORCE: INHALATION THERAPIES

Devices currently available for delivery of commonly prescribed brand-name drugs by pressurised metered-dose

TABLE 2

inhalers (pMDI), breath actuated (BA)-pMDIs, nebulisers, soft mist inhalers and dry powder inhalers (DPI)

Comments"

Drug/device (brand name)#

Drug class Dose available

Nominal Emitted

pMDIs+

21 mg

Anticholinergics Ipratropium bromide (Atrovent1)

b2-adrenergic agonists 12 mg

Formoterol (Atimos1 or Foradil1) Atimos1 emits extra-fine particles.

Discard Atimos1 12 weeks after

dispensing.

100 mg

Salbutamol Airomir1, Proventil1 and ProAir1

contain a small amount of alcohol. In

some countries, Ventolin1 has a dose

counter. In some countries, some

generic versions are formulated with

CFC products.

25 mg

Salmeterol (Serevent1)

45 mg

Levalbuterol (r-salbutamol) (Xopenex1) Contains a small amount of alcohol.

50 and 100 mg

Corticosteroids Beclomethasone (QVAR1) QVAR1 aerosol inhaler and Alvesco1

inhaler emit extra-fine particles.

40, 80 and 160 mg

Ciclesonide (Alvesco1) Due to greater lung deposition, the

prescribed dose of QVAR1 is half that

of the traditional beclomethasone

dose. Licensed with the

Aerochamber1, in some countries.

50, 100, 200 and 250 mg

Beclomethasone (Clenil1) Formulated with HFA propellants but

has particle size characteristics that

are similar to CFC-beclomethasone.

Licensed with the Aerochamber1, or

the Volumatic1, in some countries.

50, 100 and 250 mg

Beclomethasone (Beclazone1) Formulated with CFC propellant, but

will be discontinued in the near future.

50 mg

Budesonide (Pulmicort1) Currently formulated with CFC propellants.

50, 125 and 250 mg

Fluticasone (Flixotide1, Flovent1)

80 mg

Flunisolide HFA (Aerospan1)

100/6 mg

Combinations Beclomethasone/formoterol (Foster1). In Beclomethasone and formoterol in

some countries, this product is known as this combination product are

Fostair1, Fostex1 or Innovair1. formulated as extra-fine particles.

80/4.5 mg,

Budesonide/formoterol (Symbicort1) Should be discarded 12 weeks after

160/4.5 mg dispensing. Has a dose counter.

50/25, 125/25 and 250/25 mg

Fluticasone/salmeterol (Seretide1) Has a dose counter. Licensed with

the Volumatic1, or Aerochamber1,

in some countries.

18/100 mg

Ipratropium bromide/salbutamol Formulated with CFC propellant, but

(Combivent1) will be discontinued in the near future.

Cromones Nedocromil sodium (Tilade1) 2 mg Has been discontinued in many

countries.

Sodium cromoglycate (Intal1) 1 mg and5 mg Formulated with CFC propellant,

but will be discontinued in the

near future.

BA-pMDIs+

b2-adrenergic agonists 100 mg

Salbutamol Easi-Breathe1 Inhaler and Airomir1

Autohaler.

200 mg

Pirbuterol Maxair1 Autohaler; discontinued

after December 31, 2010.

50 and 100 mg

Corticosteroids Beclomethasone (QVAR1) QVAR1 Autohaler1 and QVAR1

Easi-Breathe1 Inhaler. Beclomethasone

c

formulated as extra-fine particles.

1313

EUROPEAN RESPIRATORY JOURNAL VOLUME 37 NUMBER 6

ERS/ISAM TASK FORCE: INHALATION THERAPIES B.L. LAUBE ET AL

TABLE 2 Continued

Comments"

Drug/device (brand name)#

Drug class Dose available

Nominal Emitted

Nebulisers

b2-adrenergic agonists 20 mg/2 mL

Formoterol fumarate inhalation

solution (Perforomist1)

Salbutamol inhalation solution 0.083% Vials do not require dilution.

Vials with 1, 2 and 5 mg?mL-1 Add saline until 4-mL total for jet nebuliser.

15 mg

Arformoterol tartrate (r-formoterol)

inhalation solution

Levalbuterol (r-salbutamol) inhalation 0.31 mg/3 mL, 0.63 mg/3 mL Store in foil pouch. Once pouch is

solution and 1.25 mg/3 mL opened, use vials within 2 weeks.

Metaproterenol sulfate (Alupent1) 0.5, 0.6 and 5%

Nonsteroidal Cromolyn

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