Acute lung injury (ALI) and
acute respiratory distress syndrome (ARDS) are acute life-threatening forms of
hypoxemic respiratory failure. ALI/ARDS patients require
intensive care with prolonged
mechanical ventilation. Despite advances in our understanding of the pathophysiology of ALI/ARDS, mortality rates remain > 30% and survivors suffer significant decrements in their quality of life. The evolving understanding of ALI/ARDS and the complex interactions involved in ALI/ARDS open the door for many potential targets for treatment. The condition is characterised by an acute inflammatory state that leads to increased capillary permeability and accumulation of proteinaceous pulmonary oedema. The changes that occur as a result of this
inflammation clinically manifest themselves as
hypoxemia, infiltrates on chest radiograph and reduced lung compliance. Many years have been dedicated to analysing the complexities involved in ALI/ARDS in order to improve current and future possibilities for treatment, with the aim of improving patient outcomes. Although some
therapies have demonstrated benefits of improved oxygenation, such as
surfactant and
nitric oxide, these benefits have not translated into reductions in the duration of
mechanical ventilation or mortality. Inflammatory mediator-targeted
therapies were promising early on; however, larger trials have found
therapies such as
cytokine modulation,
platelet-activating factor inhibition and
neutrophil elastase inhibitors to be ineffective in the treatment of ALI/ARDS. Preclinical studies with beta2-agonists and
granulocyte macrophage colony-stimulating factor have shown promise for restoring alveolar capillary barrier integrity or reducing pulmonary oedema, and further studies are being conducted to test for true clinical benefit. Despite previous therapeutic failures, newer
surfactant formulations have shown promise, particularly in patients with direct forms of
lung injury, and are currently in Phase III trials.
Anticoagulant therapy with activated
protein C has been shown to improve survival in
sepsis, the most common risk factor for the development of ALI/ARDS, and is now being studied in ALI/ARDS. Until new data emerge, the focus must remain on supportive care, including optimised
mechanical ventilation,
nutritional support, manipulation of fluid balance and prevention of intervening medical complications.