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

Respiratory Research

Ken J Snibson⁵  Francis HY Green⁴  John H Dennis³  Cora A Pieron³  Grishma Shrestha¹  Joanne Van der Velden²  Emmanuel Koumoundouros⁵  Richard Leigh¹  Parichita Choudhury¹  Tamer Y El Mays¹ 

[1] Airway Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada;Lung Health Research Centre, University of Melbourne, Melbourne, VIC, Australia;SolAero Ltd, Calgary, AB, Canada;Department of Pathology & Laboratory Medicine, HRIC 4AC62 3280 Hospital Drive N.W, Calgary T2N 4Z6, AB, Canada;Centre for Animal Biotechnology, University of Melbourne, Melbourne, VIC, Australia

关键词: Perflubron;    Carbon dioxide;    Allergic airway disease;    Sheep model;    Novel treatments;    Asthma;   

Others  :  1137268
DOI  :  10.1186/s12931-014-0098-x

 received in 2014-04-01, accepted in 2014-08-13,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 El Mays et al.; licensee BioMed Central Ltd.

【 图 表 】

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