Abstract
BackgroundThe 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.MethodsSheep 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.ResultsTreatment 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.ConclusionsS-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0098-x) contains supplementary material, which is available to authorized users.
Highlights
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
In this study we show that inhaled nebulized perflubron + CO2 (S-1226) rapidly opens constricted airways in an ovine model of allergic asthma using house dust mite as allergen [38,39]
The mean rate of perflubron delivered was 598 mg/minute, of which some 203 mg/minute consisted of aerosol with the remaining 395 mg/minute was estimated to be in vapor form – the majority was delivered in vapor form
Summary
Experimental sheep Female merino-cross farm-reared sheep aged 6 months were used in the experiments described here. The nebulizer was connected to a dosimeter system consisting of a solenoid valve and a source of compressed (20 psi driving pressure) gas mixture (12% CO2, 21% O2 and 67% N2) for S-1226 or compressed medical air (21% O2 and 79% N2) for perflubron and salbutamol. Treatments with CO2 alone and medical air were performed following the same protocol but with an empty nebulizer. HDM challenge followed by treatment Sheep (previously HDM sensitized) were challenged with HDM aerosols to induce early phase asthmatic responses. The airway was treated with nebulized S-1226 delivered through a Trudell Pty Ltd bronchoscope catheter and the effects video recorded in real time. Data analysis In each experiment several intervals were analysed: Baseline, HDM-induced early phase response, and three post-treatment periods (immediately, 1–10 minute and 10 to 20 minutes after treatment cessation).
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