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Considerations for Optimal Inhaler Device Selection in Chronic Obstructive Pulmonary Disease

January 31, 2018|Cleveland Clinic Journal of Medicine
Rajiv Dhand, MD;Tricia Cavanaugh, MD;Neil Skolnik, MD
Author and Disclosure Information

Rajiv Dhand, MD
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Tennessee Medical Center, Knoxville, Tennessee

Tricia Cavanaugh, MD
Abington Hospital–Jefferson Health, Abington, Pennsylvania

Neil Skolnik, MD
Abington Family Medicine, Jenkintown, Pennsylvania

Dr. Dhand has participated on advisory boards for AstraZeneca, Bayer Healthcare, Cipla Limited, and GlaxoSmithKline, and has received honoraria from AstraZeneca, Cipla Limited, and Sunovion Pharmaceuticals Inc.

Dr. Cavanaugh has no financial interests to declare.

Dr. Skolnik has participated on advisory boards for AstraZeneca; Boehringer Ingelheim GmbH; Eli Lilly and Company; Intarcia Therapeutics, Inc.; Janssen Pharmaceuticals, Inc.; sanofi-aventis U.S. LLC; and Teva Pharmaceutical Industries, Ltd.; as a speaker for AstraZeneca and Boehringer Ingelheim GmbH; and has received research support from AstraZeneca and sanofi-aventis U.S. LLC.

Funding for this article was provided by AstraZeneca LP (Wilmington, DE, USA). Medical writing support was provided by Hannah Burke, BSc, of Core (London, UK) and editorial support was provided by Maryam Vahdat, PGDip, of Core (London, UK), which were funded  by AstraZeneca LP (Wilmington, DE, USA), in accordance with Good Publication Practice guidelines (Battisti WP et al. Ann Intern Med. 2015;163:461–464. doi: 10.7326/M15-0288).

This article is being co-published in The Journal of Family Practice and Cleveland Clinic Journal of Medicine.

Key characteristics of different device types
Inhalation is the standard route of administration for drugs used to treat chronic obstructive pulmonary disease (COPD) and asthma.1 Inhalation is a quick drug delivery method that offers both efficacy and safety.2,3 Inhaled administration allows targeted delivery of the active drug to the site of action, enabling lower doses and resulting in fewer systemic adverse events than oral therapy.3 There are 4 main types of devices used to deliver inhaled medication: pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), soft mist inhalers (SMIs), and nebulizers. Each type of inhaler device is associated with advantages and limitations that determine their suitability for any given patient with COPD4,5 (Table 1).3,6,7 Understanding those advantages and limitations helps clinicians in choosing the proper device for the individual patient’s clinical needs and preferences. However, with the wide range of permutations of drug combinations now possible, inhaler selection remains challenging.4 For all inhaler devices, adequate training for patients on how to use their device is required to achieve optimal therapeutic benefits.1

Device considerations

Examples of different inhaler device and spacer types.
Figure 1. Examples of different inhaler device and spacer types.
Examples of the different inhaler devices available for COPD treatments are provided in Figure 1, and their key characteristics are summarized in Table 2.3,7 Traditional pMDIs require actuation of the device at the beginning of a slow, deep inhalation to optimize drug delivery. This technique requires hand–breath coordination, which can be difficult for some patients, particularly those who are elderly or severely short of breath; spacers can be used in combination with pMDIs to help to overcome some technique issues (Figure 1).3,8 Breath-actuated (BA) pMDIs may also be used in some countries (though are not currently licensed in the United States); these devices release the dose on inhalation, removing the need for hand–breath coordination.3

Table 2. Characteristics of inhaler devices
DPIs are also breath-actuated, with the patient providing the force necessary to deliver the drug on inhalation; drug delivery with DPIs is therefore dependent on patients achieving a high enough peak inspiratory flow (PIF) rate to disperse the drug, in contrast to BA pMDIs, which are activated at a lower PIF rate.3,8 Generating the inspiratory flow required for effective function of DPIs can be problematic for some patients with COPD.9 Suboptimal PIF rates have been associated with age (≥60 years), female gender, shorter height, and lower values for forced vital capacity and inspiratory capacity as percentage predicted in stable patients with severe COPD10; in addition, patients with COPD can have a temporarily reduced PIF rate after hospitalization for an acute exacerbation.11,12 There is a range of DPIs available in three main categories: single-dose, multi-dose, and power-assisted devices.7 It is important to protect DPI devices from the effects of humidity, which can increase particle adhesion and therefore reduce efficacy.13

The SMI delivers the aerosol as a fine mist with slow velocity lasting >1 second, which is considerably slower than spray delivery with pMDIs.14 The aim of this design is to make it easier for patients to coordinate actuation with inhalation, but it is important to note that some coordination is still required for SMI devices to function correctly.14 In addition, the SMI is not dependent on a patient’s ability to generate sufficient PIF for effective drug delivery. A limitation of the SMI is the need to assemble the device, as patients with poor manual dexterity may encounter difficulty when attempting to load the drug cartridge.15

Nebulizers deliver aerosolized drug in a fine mist. Newer-generation portable vibrating mesh nebulizers can deliver a dose over a period of ~2 minutes, compared with 10 minutes for conventional pneumatic devices.16 Patients find them effective and easy to use, and the newer generation devices overcome problems with portability and length of treatment, which may be an issue during the daytime for ambulatory patients, along with the requirement for cleaning after each dose.4,8 However, drug delivery may be somewhat compromised with nebulizers compared with other inhalation devices, as medication can be dispersed into the atmosphere and lost, rather than inhaled.7 An additional point to consider is medication availability; some medications, particularly fixed-dose combination maintenance therapies, are currently unavailable in a nebulized format.16

The most important device-related factors influencing the site of deposition within the lungs are aerosol velocity and particle size of the inhaled drug.3,7,17 To maximize clinical effectiveness, adequate distribution throughout the lung is required to reach target sites of action for β2-agonists, anticholinergics, and corticosteroids.17 Particle size differs between inhaler device types, but all available devices generate drug particles sufficient for deposition throughout the lower airways and lung periphery, ie, within the range of 1–5 microns.3,18-21 Extra fine particles of <1 micron (or “submicron particles”) can be deposited deeper in the pulmonary acinus, but a higher fraction of such particles may be exhaled compared with particles 1–5 microns in size.3,20,22 In contrast, particles >5 microns deposit in the oropharynx and may be swallowed, potentially leading to systemic adverse effects.3,20,22

When more than one drug is required, it may be preferable to deliver them via a single device where possible to facilitate patient compliance with correct technique, and decrease confusion about how to use different inhalers.23 The inhaler device ideally serves as a platform on which many treatments are available; the greater the number of devices employed by the patient, the greater the likelihood of making an error with the usage of each device.24

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