Phosgene induced acute lung injury

Abstract

Phosgene is an extremely toxic vapour used to devastating effect during World War 1. The ease with which it can be manufactured means that it remains a high threat compound as a terrorist weapon and its extensive use in the chemical and pharmaceutical industry as a Toxic Industrial Chemical (TIC). It predominantly affects the lungs, at the alveolar level, causing an acute lung injury with extensive non-cardiogenic pulmonary oedema. Signs and symptoms manifest after a latent phase, largely dependent upon inhaled dose, to the point where they can occur at 24h post exposure. In amass release, it will be impossible to identify intoxicated individuals until they become symptomatic or hypoxaemic. Additionally, the logistic burden of providing supplemental oxygen and transporting large numbers of patients to hospitals may be too great. If a reliable biomarker of phosgene toxicity could be identified, then this burden is reduced. Furthermore, a commercial off the shelf device that provides Continuous Positive Airway Pressure (CPAP) to affected patients could safely extend transfer times while minimising oxygen toxicity. Defence Scientific and Technology Laboratory Porton Down is the only establishment in the World capable of evaluating the response of large animals to highly toxic inhaled compounds. In this study we used an established pig model to evaluate the effects of a Positive End Expiratory Pressure after exposure to phosgene. The survival and physiological data show that it is extraordinarily effective. Access to some plasma and bronchoalveolar lavage samples made during the experiments was granted and an analysis of lipid content was made using electrospray ionisation tandem mass spectrometry. This has not been done to this level of detail before. This novel work has shown that CPAP is extraordinarily effective at improving survival, physiological markers of critical illness and modulating surfactant composition.

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Identifiers

ORCID for Anthony Postle: orcid.org/0000-0001-7361-0756

ORCID for Mike Grocott: orcid.org/0000-0002-9484-7581

ORCID for Ahilanandan Dushianthan: orcid.org/0000-0002-0165-3359

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