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Professor Declan Bates

The project: Reducing and replacing animal models of blast and chemical lung injury using computational simulation

Primary blast lung injury (PBLI) and chemical lung injury are increasingly common features of military conflict and terrorist attacks on civilian populations. PBLI occurred in 7% of UK casualties in the most recent conflict in Afghanistan despite the rudimentary nature of the opposition forces, and it is likely that PBLI will be more widely encountered in future, more industrialised, conflicts. The disease is more prevalent in civilian casualties resulting from terrorist attacks on transport infrastructure with over 150 PBLI casualties caused by the train bombings suffered in Madrid in 2004 and half of the serious casualties seen in the London underground and bus bombings affected. Military and civilian casualties exposed to PBLI are increasingly likely to survive to reach a hospital, as improvements in personal protective equipment and prehospital care have reduced immediate fatalities due to penetrating injury. The toxic industrial chemicals (TIC’s) Phosgene (COCl2) and Chlorine (Cl2) are both ubiquitous within the plastics, agricultural and other chemical industries. Whilst a well-recognised risk to heath following industrial and transportation accidents, their ease of production combined with their lethality has resulted in their use as chemical weapons, most notably against civilian populations in the Middle East over recent years. Both agents cause a severe chemical lung injury that leads to acute respiratory distress syndrome (ARDS) and frequently death.

The unpredictable and sporadic nature of human lung injury from both blast or TIC exposure makes clinical study in human casualties practically impossible, and research on improving treatment strategies is therefore almost wholly reliant on the use of animal models. This project will develop a new approach, based on the use of validated high-fidelity computer simulations, with the dual aims of radically reducing the current dependence of researchers in this field on animal models, and developing novel and improved treatment strategies.

[1] Animal models of acute lung injury, Matute-Bello & Matthay, American Thoracic Society, 2011.

[2] Development of animal models for acute respiratory distress syndrome, Bastarache & Blackwell, Disease Models and Mechanisms, 2009.

[3] Acute respiratory distress syndrome induction by pulmonary ischemia-reperfusion injury in large animal models, Fard et al, Journal of Surgical Research, 2014.

[4] Large-animal models of acute respiratory distress syndrome, Ballard-Croft et al, Annals of Thoracic Surgery, 2012.

[5] Moderately high-frequency ventilation with a conventional ventilator allows reduction of tidal volume without increasing mean airway pressure, Cordioli et al, Intensive Care Medicine Experimental, 2014.

[6] Computational simulation indicates that moderately high-frequency ventilation can allow safe reduction of tidal volumes and airway pressures in ARDS patients, W. Wang et al, Intensive Care Medicine Experimental, 2015.

[7] Evaluation of lung recruitment manoeuvres in Acute Respiratory Distress Syndrome using computer simulation, Das et al, Critical Care, 2015.

[8] High PEEP in ARDS: evaluating the trade-off between improved oxygenation and decreased oxygen delivery”, Chikhani et al, British Journal of Anaesthesia, 2016.

[9] The primary blast lung injury simulator: A new computerised model, Haque et al, Journal of the Royal Army Medical Corps, 2018.