In Vitro Performance Characteristics of Valved Holding Chamber and Spacer Devices With a Fluticasone Metered-Dose Inhaler

Michael J. Asmus, PharmD; Judy Liang, PharmD; Intira Coowanitwong, PhD; Günther Hochhaus, PhD


Pharmacotherapy. 2004;24(2) 

In This Article

Abstract and Introduction


Study Objective: To compare the in vitro aerosol deposition characteristics of several commercially available valved holding chamber (VHC) and spacer devices used with a fluticasone metered-dose inhaler (MDI).
Design: In vitro aerosol deposition study.
Setting: University-affiliated research center.
Devices: Seven VHC devices: BreatheRite, E-Z Spacer, EasiVent, AeroChamber, InspirEase, OptiChamber, and Space Chamber. Six spacer devices: OptiHaler, Aerosol Cloud Enhancer (ACE), Gentle-Haler, MediSpacer, Ellipse, and a 6-inch tube (1-inch inside diameter).
Intervention: The respirable dose (aerosol particles 1-5 µm) of fluticasone was determined by sampling 10 220-µg actuations from five runs with each spacer or VHC plus MDI combination, by using a well-established in vitro cascade impactor method.
Measurements and Main Results: Fluticasone aerosol was washed from the impactor with methanol and quantified by means of high-performance liquid chromatography. Differences among outcomes were determined with analysis-of-variance testing. Among spacers, Ellipse had the highest respirable dose (104 µg, p<0.01). Respirable doses for the 6-inch tube (74.3 µg), Gentle-Haler (81.7 µg), and MediSpacer (82.6 µg) were no different from that of the MDI (p>0.05), whereas respirable doses of OptiHaler (44.6 µg) and ACE (47.2 µg) were less than those of all other spacers (p<0.001). Among VHC devices, respirable doses from EasiVent (35.6 µg), AeroChamber (47.0 µg), InspirEase (52.7 µg), OptiChamber (53.1 µg), and Space Chamber (58.3 µg) were not different (p>0.05), whereas BreatheRite (13.1 µg) and E-Z Spacer (27.3 µg) respirable doses were less than those of the other VHC devices (p<0.05).
Conclusion: Spacers and VHC devices available in the United States do not demonstrate equivalent in vitro performance with the fluticasone MDI. The difference between highest and lowest respirable doses in each device category would likely lead to clinically relevant differences in the quantity of fluticasone delivered to a patient.


Today in the United States, more than a dozen different valved holding chamber (VHC) and spacer devices are commercially available to aid the delivery of inhaled drugs from a metered-dose inhaler (MDI). The primary purpose of the MDI spacer device is to allow the MDI propellant time and distance to evaporate after actuation.[1] Evaporation of propellant promotes formation of small aerosol particles (1-5 µm) likely to be carried by the inspired breath into small human airways. Furthermore, MDI spacers collect large aerosol particles (> 10 µm) that would otherwise deposit into the oropharynx.[1] The National Institutes of Health's National Asthma Education and Prevention Program recommends a spacer for all patients with asthma who are prescribed an inhaled corticosteroid, to reduce the risk of topical corticosteroid-induced adverse effects such as thrush and dysphonia.[2] A VHC device does everything a spacer does and, because of a valve inside the device, also functions to hold the MDI puff briefly before inhalation in order to minimize the detrimental effects of poor timing between MDI actuation and patient inhalation.[1] Technically, a spacer (not a VHC) requires patient-coordinated actuation and inhalation for maximum efficiency.

With so many different VHC and spacer devices ranging in price to the consumer from $10-40 each, it is no surprise that confusion exists among clinicians as to which device is the preferred choice. In many states, depending on the payer, even if a clinician indicates a specific device on the prescription, unless he or she indicates that the device choice was "medically necessary" (or similar conventional language), the payer will specify substitution of another device based solely on acquisition cost, not efficacy with the specific drug prescribed. Also, because many published reports of in vitro and in vivo device performance are of devices available only in Europe (e.g., made from metal or a larger volume), American clinicians often are unaware of how devices available in the United States compare. To further complicate the picture, the availability of these devices is quite dynamic. Device manufacturers frequently tout "new and improved" versions of their device, with little objective evidence to support those claims. Clearly, American clinicians are in need of objective information that can help guide their selection of drug-specific MDI device combinations that promote efficient delivery to the patient.

In vitro aerosol deposition data indicate that the choice of VHC or spacer device has little impact on the aerosol characteristics of bronchodilators delivered by an MDI.[3,4,5,6,7,8] Furthermore, clinical studies in asthmatic subjects have been unable to discern measurable differences in bronchodilator effect among various VHC and spacer devices when used with an albuterol MDI.[9,10] Therefore, many clinicians and third-party payers have concluded that all VHC and spacer devices available in the United States are equivalent. This assumption may not be true for inhaled corticosteroids, however, since several aerosol deposition experiments have indicated drug-delivery characteristics are distinctive for each combination of corticosteroid and VHC or MDI spacer.[3,4,6,7,11,12,13,14,15,16] These in vitro studies have indicated that interchanging one VHC or spacer with another can result in 3-fold fluctuations in the dose of aerosol that eventually reaches the lungs.

Because the fluticasone propionate MDI (Flovent; GlaxoSmithKline, Research Triangle Park, NC) is the most frequently prescribed inhaled glucocorticoid in the United States,[17] we thought that the most clinically relevant assessment of performance of the various VHC and spacer devices should be carried out with this drug. Our objective was to compare the in vitro aerosol deposition characteristics of this fluticasone propionate MDI when used with several VHC and MDI spacer devices available in the United States.


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