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Editorials |

Extra-Fine Corticosteroid Aerosols From Hydrofluoroalkane-134a Metered-Dose Inhalers : Potential Advantages and Disadvantages

Donald P. Tashkin, MD, FCCP
Author and Funding Information

Affiliations: Los Angeles, CA 
 ,  Professor and Chief, Division of Pulmonary and Critical Care Medicine.

Correspondence to: Donald P. Tashkin, MD, FCCP, Division of Pulmonary and Critical Care Medicine, UCLA School of Medicine, 10833 LeConte Ave, Los Angeles, CA 90095-1690; e-mail: dtashkin@med1.medsch.ucla.edu



Chest. 1999;115(2):316-318. doi:10.1378/chest.115.2.316
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To comply with the mandatory phase-out of chlorofluorocarbons (CFCs) that destroy ozone in the stratosphere and allow excessive ultraviolet radiation to reach the earth’s atmosphere,1 CFC-based metered-dose therapeutic aerosols are in the process of being reformulated with more environmentally friendly alternative propellants, such as hydrofluoroalkanes (HFAs). This process has created formidable technical challenges as well as new opportunities for potentially improved aerosol delivery. Beclomethasone dipropionate (BDP), the oldest inhaled corticosteroid molecule with high topical-to-systemic activity, has been used in asthma therapy for over two decades. Reformulation of BDP with HFA-134a results in a solution preparation that delivers an aerosol with a much smaller mean particle size (mass median aerodynamic diameter [MMAD] 1.1 μm) than that of aerosols generated by conventional CFC-based metered-dose inhalers of BDP (MMAD, 3.5 to 4 μm).2 Mathematical models that relate particle size to the site of deposition in the respiratory tract predict that extra-fine particles with an MMAD of approximately 1 μm would deposit to a greater extent in the lung periphery than less fine particles with an MMAD of 4 to 5 μm, which would tend to deposit more centrally, as well as in the oropharynx.3 Since this theoretical model does not take into account a number of other factors that influence aerosol particle deposition in vivo, such as variations in inhalation technique (inspiratory flow, breath-holding time) and airway morphology (narrowing or occlusion caused by disease),4in vivo studies are required to ascertain actual sites of aerosol deposition in both healthy subjects and patients with airways disease. Using an optimized method of metered-dose inhaler use and lung imaging techniques incorporating procedures validated to ensure consistency of drug radiolabeling in the different ranges of particle size, Leach2 demonstrated that a large proportion of HFA-BDP (51 to 56%) was delivered uniformly throughout the lungs (ie, presumably to peripheral, as well as large- and medium-sized airways) of both normal volunteers and patients with mild asthma with relatively little oropharyngeal deposition (28 to 30%), in contrast to CFC-BDP that deposited mainly in the oropharynx (94%) and large central airways with little peripheral penetration.


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    Print ISSN: 0012-3692
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