Advanced Drug Delivery Reviews

Volume 55, Issue 7, 18 July 2003, Pages 879-923

The influence of inhaler selection on efficacy of

asthma therapies ☆
P.W. Barry , C. O’Callaghan

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https://doi.org/10.1016/S0169-409X(03)00083-8
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Abstract

Many different devices are available to aid inhalational drug delivery. Although each device is claimed to
have advantages over its rivals, the evidence to support greater efficacy of a particular device is scanty. Most
comparative studies are underpowered or flawed in their design. They may use inappropriate end-points, or
involve healthy subjects, whose response may be very different from the patient with acute severe asthma.
The dosage of drug used in a trial may be at the shallow part of the dose–response curve, masking
differences in devices. Only in a few cases have clinical trials detected a significant difference between
devices, and trials have rarely taken patient preference into account. The most efficacious device in practice
is likely to be the one that the patient will use regularly and in accordance with a health care workers’
recommendations.

Introduction

Efficacy may be defined as success in producing an intended result and, in the context of this article,
efficacy implies success in treating asthma. However, this success is very difficult and costly to measure, and
studies often rely on other outcomes, such as short-term changes in lung function or subjective
improvement in symptom control, to estimate the efficacy of a particular treatment regime. Changes in such
surrogate end-points may have little relevance to ‘treating asthma’, and the use of many different measures
in different studies makes it difficult to compare their findings.

Another difficulty in comparing devices arises when a particular device is only available with a particular
drug. Comparisons between such a device and its competitors are therefore comparisons between
device/drug combinations, rather than just the device itself.
Some devices may be more efficacious not because they are more efficient in delivering medication, but
because they are more acceptable to the patient. Patient adherence with prescribed therapy is a complex
and under-researched area, and the factors that improve adherence are poorly understood.

Furthermore, efficacy in one context or situation may not be continued in another. For instance some
devices may be less efficacious with certain drugs or formulations, such as ultrasonic nebulisers with drug
suspensions, whilst some devices may be less efficacious with certain patient types, such as dry powder
inhalers and young children, or unmodified metered dose inhalers and patients with arthritis.

In this review, we will discuss some of the difficulties in measuring efficacy of inhaler devices; briefly
mention differences between their in vitro characteristics; discuss the relationship between in vitro
characteristics of devices, lung deposition of drug from them and their clinical efficacy; and summarise
published data comparing the clinical efficacy of different devices.

Section snippets

What is efficacy?

Efficacy may be defined as the capacity or power of the subject to produce a desired effect. In the treatment
of asthma, these desired effects may include the relief of symptoms, the prevention of ongoing disease
processes such as lung inflammation, or improvement in a particular measurement of lung function or
response to a bronchoprovocative test. Some aspects of efficacy may be easily measured in an ‘in vitro’
experiment. It is however, not so easy to define or measure efficacy at the…

Efficacy in producing drug—differences between in vitro characteristics of devices

The amount of inhaled drug that deposits in the lungs is dependent upon many factors. One of the most
important is the aerodynamic size of the drug-containing particles emitted from the inhaler. Aerodynamic
particle size is defined as the size of a spherical, unit density particle that settles with the same velocity as
the particle in question. Clearly, a very dense particle will have a different aerodynamic behaviour (an
increased aerodynamic size) to an equivalently sized, but less dense…

The relationship between in vitro characteristics, lung deposition and clinical efficacy
between different devices

In vitro testing is useful for quality control purposes, and for product development, but do measures of in
vitro efficacy show any correlation with lung deposition, measured by scintigraphy or by pharmacokinetic
methods, or with clinical effect?…

Differences in clinical efficacy

A number of studies have compared the clinical effectiveness of different inhalers, and these have been
summarised in recent systematic reviews [15], [98], [99]. The following discussion is drawn from these
reviews, from narratives [20] and from other clinical studies.…
Device selection at different ages

Efficacy of a device will be affected by the age and abilities of the patient who is asked to use it. For
instance, young children and the elderly may have difficulty coordinating pMDI actuation and inhalation
[159], [280]; devices requiring a high inspiratory flow rate, such as the Turbohaler, may also be used less
efficiently by younger children [281], [282]. Recent articles have given guidance regarding the choice of
inhaler [283], [284], [285] and this is summarised in Table 5. These…

Compliance issues

The most effective inhaler for any given patient is the one that the patient will use on a regular basis and in
an effective manner. Patient compliance with inhaled medication is poor, and patients often report
compliance rates in excess of those objectively measured.

In one study [286], adherence with inhaled beta-agonists and corticosteroids in asthmatic children was
tracked using an electronic monitor (Metered Dose Inhaler Chronolog). Patients seldom took all of their
medications as…

Conclusions

There are many different devices available for inhalational therapy in the treatment of asthma. Comparative
studies between them are often poorly designed, and may be unable to detect a difference between two
devices. In vitro studies, while useful to determine the relative efficacy of devices in producing drug that
may be deposited in the lungs, do not always reflect the clinical situation and should be used to guide
clinical trials. Even if a device is found to be more efficacious in a well…

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References (334)

K. Bauer et al.
Effect of solution and suspension type aerosol of formoterol on tremor response and airways in
patients with asthma
J. Allergy Clin. Immunol. (1995)

B.J.O. Wong et al.

Bioequivalence of metered dose inhaler
medications
J. Allergy Clin. Immunol. (1993)

R.K. Schultz
Drug delivery characteristics of metered dose
inhalers
J. Allergy Clin. Immunol. (1995)
E.F. Fiese et al.
Test method for evaluation of loss of prime in metered-dose
aerosols
J. Pharm. Sci. (1988)

F. Moren
Drug deposition of pressurised inhalation aerosols. II. Influence of vapour pressure and
metering volume
Int. J. Pharm. (1978)

S.P. Newman et al.

Bronchodilator delivery from Gentlehaler, a new low-velocity pressurized aerosol inhaler
Chest (1993)

K.A. Gunawardena et al.

The Spacehaler for delivery of salbutamol: a comparison with the standard metered-dose
inhaler plus Volumatic spacer device
Respir. Med. (1997)

A. Cripps et al.
Pharmaceutical transition to non-CFC pressurised metered dose inhalers
Respir. Med. (2000)

A.R. Clark et al.

The use of reservoir devices for the simultaneous delivery of two metered-dose
aerosols
J. Allergy Clin. Immunol. (1990)

F. Moren
Drug deposition of pressurised inhalation aerosols. 1. Influence of actuator tube
design
Int. J. Pharm. (1978)

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☆ A statement from the authors on conflicts of interest: ‘Professor O’Callaghan and Dr Barry have received or are currently
receiving support for their research in the form of salaries for technical and research staff, costs of research consumables,
donation of equipment and reimbursement for presenting data at scientific conferences from most major pharmaceutical
companies producing asthma medications and devices, including 3M Pharmaceuticals, AstraZeneca, GlaxoSmithKline and
Rhone Poulenc Rorer. They have acted in an advisory capacity to a number of pharmaceutical and drug delivery device
manufacturers. Dr Barry’s PhD studies were funded by the Astra Foundation. They have also received, or are currently
negotiating, grants from device manufacturers, including Medicaid, Pari GmbH, and Clement Clarke International. Professor
O’Callaghan is producing multimedia educational information on respiratory disease and asthma with sponsorship from 3M
and GlaxoSmithKline.’

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