Baseline lung epithelial permeability was altered in smokers and asthmatics compared to the controls. Furosemide was effective only in asthmatics in reverting the permeability almost back to the normal range. Inhaled furosemide was effective even in moderate and severe asthmatics. Furosemide has multiple mechanisms of action. It possibly acts at bronchial level in view of the pathology in asthmatics lying in the airways.

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Background: In non-traumatic respiratory failure, pre-hospital application of CPAP reduces the need for intubation. Primary blast lung injury (PBLI) accompanied by haemorrhagic shock is common after mass casualty incidents. We hypothesised that pre-hospital CPAP is also beneficial after PBLI accompanied by haemorrhagic shock. Methods: We performed a computer-based simulation of the cardiopulmonary response to PBLI followed by haemorrhage, calibrated from published controlled porcine experiments exploring blast injury and haemorrhagic shock. The effect of different CPAP levels was simulated in three in silico patients who had sustained mild, moderate, or severe PBLI (10%, 25%, 50% contusion of the total lung) plus haemorrhagic shock. The primary outcome was arterial partial pressure of oxygen (PaO 2 ) at the end of each simulation. Results: In mild blast lung injury, 5 cm H 2 O ambient-air CPAP increased PaO 2 from 10.6 to 12.6 kPa. Higher CPAP did not further improve PaO 2 . In moderate blast lung injury, 10 cm H 2 O CPAP produced a larger increase in PaO 2 (from 8.5 to 11.1 kPa), but 15 cm H 2 O CPAP produced no further benefit. In severe blast lung injury, 5 cm H 2 O CPAP inceased PaO 2 from 4.06 to 8.39 kPa. Further increasing CPAP to 10e15 cm H 2 O reduced PaO 2 (7.99 and 7.90 kPa, respectively) as a result of haemodynamic impairment resulting from increased intrathoracic pressures. Conclusions: Our modelling study suggests that ambient air 5 cm H 2 O CPAP may benefit casualties suffering from blast lung injury, even with severe haemorrhagic shock. However, higher CPAP levels beyond 10 cm H 2 O after severe lung injury reduced oxygen delivery as a result of haemodynamic impairment.

Computer simulation offers a fresh approach to traditional medical research that is particularly well suited to investigating issues related to mechanical ventilation. Patients receiving mechanical ventilation are routinely monitored in great detail, providing extensive high-quality data-streams for model design and configuration. Models based on such data can incorporate very complex system dynamics that can be validated against patient responses for use as investigational surrogates. Crucially, simulation offers the potential to “look inside” the patient, allowing unimpeded access to all variables of interest. In contrast to trials on both animal models and human patients, in silico models are completely configurable and reproducible; for example, different ventilator settings can be applied to an identical virtual patient, or the same settings applied to different patients, to understand their mode of action and quantitatively compare their effectiveness. Here, we review progress on the mathematical modeling and computer simulation of human anatomy, physiology, and pathophysiology in the context of mechanical ventilation, with an emphasis on the clinical applications of this approach in various disease states. We present new results highlighting the link between model complexity and predictive capability, using data on the responses of individual patients with acute respiratory distress syndrome to changes in multiple ventilator settings. The current limitations and potential of in silico modeling are discussed from a clinical perspective, and future challenges and research directions highlighted.