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2626087 
Journal Article 
Abstract 
Opening constricted airways using perfluorocarbon aerosol and carbon dioxide in a sheep model of asthma 
El Mays, T; Choudhury, P; Leigh, R; Koumoundouros, E; Snibson, KJ; Green, F 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A1349 
English 
WOS:000208771000350 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Introduction/Rationale: The low toxicity of perfluorocarbons (PFCs), their high affinity for respiratory gases and compatibility with lung surfactant, have made them useful candidates for treating respiratory diseases such as adult respiratory distress syndrome. With partial liquid ventilation (PLV) large quantities of PFC are administered to the lungs. We report promising results for treating acute allergic asthma using small volumes of PFC aerosol driven by a carbon dioxide-rich gas mixture. The carbon dioxide, which is highly soluble in PFC, was used to relax airway smooth muscle.

Methods: Sheep previously sensitized to house dust mite (HDM) were challenged with HDM aerosols to induce early phase asthmatic responses. At the peak of these responses (characterised by an increase in airway resistance) the sheep were treated for two minutes with an aerosol of perfluoro-octylbromide (PFOB) driven by a gas mixture containing 12% CO2 Airway resistance was monitored for 20 minutes. In other sheep, a segmental bronchus was pre-contracted with methacholine (MCh) and treated with PFOB/12% CO2 aerosol generated through a bronchoscope catheter. Throughout this procedure, airway opening was recorded using a digital video-camera attached to a bronchoscope.

Results: Treatment with PFOB/12% CO2 for 2 minutes following HDM challenge resulted in a decrease in airway resistance (see figure) with a significant percent drop of airway resistance (mean ± SE) immediately (53.8 ± 7.7 vs no change) (p = 0.002), at 1 to 10 minutes (52.4 ± 8.1 vs 1.9 ± 4.7) (p = 0.014) and 10 to 20 minutes (56.9 ± 8.8 vs 24.4 ± 4.2) (p = 0.018) after treatment compared with no treatment respectively. Video bronchoscopy showed an immediate (within 10 seconds) re-opening of MCh-constricted airways following treatment with PFOB/12% CO2.

Conclusions: The ability of this formulation to re-open airways obstructed by smooth muscle spasm is a unique property of this treatment. We predict that the low surface tension and reduced adhesivity of PFCs will also facilitate the penetration of mucous plugs. This will allow delivery of the relaxant carbon dioxide gas to the distally obstructed airways. It thus complements, rather than replaces, existing treatments for asthma. It also has potential applications to other chronic obstructive lung diseases such as chronic bronchitis and bronchiectasis. Data from six sheep showing percent change in airway resistance relative to baseline. In all animals the increase in airway resistance following HDM challenge was rapidly reversed by administration of an aerosol of PFOB/12% CO2. The drop in airway resistance was maintained for 20 minutes in the treated animals. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010