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    Nebulized perflubron and carbon dioxide rapidly dilate constricted airways in an ovine model of allergic asthma

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    Authors
    El Mays, Tamer Y
    Choudhury, Parichita
    Leigh, Richard
    Koumoundouros, Emmanuel
    Van der Velden, Joanne
    Shrestha, Grishma
    Pieron, Cora A
    Dennis, John H
    Green, Francis HY
    Snibson, Ken J
    Issue Date
    2014-09-16
    Keywords
    RESPIRATORY DISORDER
    Local subject classification
    ASTHMA
    ANIMAL RESEARCH
    
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    Citation
    El Mays TY et al. Nebulized perflubron and carbon dioxide rapidly dilate constricted airways in an ovine model of allergic asthma. Respiratory Res. 2014 Sep 16;15(1):98
    URI
    http://dx.doi.org/10.1186/s12931-014-0098-x
    http://hdl.handle.net/10147/331806
    Abstract
    Abstract Background The low toxicity of perfluorocarbons (PFCs), their high affinity for respiratory gases and their compatibility with lung surfactant have made them useful candidates for treating respiratory diseases such as adult respiratory distress syndrome. We report results for treating acute allergic and non-allergic bronchoconstriction in sheep using S-1226 (a gas mixture containing carbon dioxide and small volumes of nebulized perflubron). The carbon dioxide, which is highly soluble in perflubron, was used to relax airway smooth muscle. Methods Sheep previously sensitized to house dust mite (HDM) were challenged with HDM aerosols to induce early asthmatic responses. At the maximal responses (characterised by an increase in lung resistance), the sheep were either not treated or treated with one of the following; nebulized S-1226 (perflubron + 12% CO2), nebulized perflubron + medical air, 12% CO2, salbutamol or medical air. Lung resistance was monitored for up to 20 minutes after cessation of treatment. In additional naïve sheep, a segmental bronchus was pre-contracted with methacholine (MCh) and treated with nebulized S-1226 administered via a bronchoscope catheter. Subsequent bronchodilatation was monitored by real time digital video recording. Results Treatment with S-1226 for 2 minutes following HDM challenge resulted in a more rapid, more profound and more prolonged decline in lung resistance compared with the other treatment interventions. Video bronchoscopy showed an immediate and complete (within 5 seconds) re-opening of MCh-constricted airways following treatment with S-1226. Conclusions S-1226 is a potent and rapid formulation for re-opening constricted airways. Its mechanism(s) of action are unknown. The formulation has potential as a rescue treatment for acute severe asthma.
    Item Type
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    Language
    en
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