PURPOSE: In North America, asthma results in over 1.6 million emergency room visits. In the US approximately 11,305 individuals die each year from asthma, with 38% dying in hospital, and the rest dying before they are able to access medical care. The purpose of this study was to evaluate a novel inhaled perfluorocarbon/carbon dioxide (CO2) formulation for the treatment of severe asthma.
METHODS: Sheep 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 either not treated or treated for two minutes with one of the following treatments; an aerosol of perfluorooctylbromide (PFOB)/12% CO2, an aerosol of PFOB alone or 12% CO2 alone. Airway resistance was monitored for 20 minutes. In other sheep, a segmental bronchus was pre-contracted with methacholine (MCh) and treated with an aerosol of PFOB/12% CO2. Airway opening was monitored by real time video-recording.
RESULTS: Treatment with PFOB/12% CO2 for 2 minutes following HDM challenge resulted in a rapid and more prolonged drop in airway resistance compared with no treatment and treatment with PFOB alone or 12% CO2 alone. The video bronchoscopy showed an immediate re-opening of MCh-constricted airways following treatment with PFOB/12% CO2.
CONCLUSIONS: PFOB/12% CO2 is a potent and rapid formulation for re-opening constricted airways. Its mechanism of action seems to involve both biophysical and physiological pathways. The two components act synergistically.
CLINICAL IMPLICATIONS: We propose that, in addition to this formulation’s ability to re-open airways obstructed by smooth muscle spasm, the low surface tension and reduced viscosity of perfluorocarbons facilitates 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.
DISCLOSURE: Tamer El Mays: Shareholder: SolAeroMed Inc.
Richard Leigh: Shareholder: SolAeroMed Inc.
John Dennis: Shareholder: SolAeroMed Inc.
Francis Green: Shareholder: SolAeroMed Inc.
The following authors have nothing to disclose: Parichita Choudhury, Emmanuel Koumoundouros, Ken Snibson
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