Acute lung injury/acute respiratory distress syndrome - a therapeutic challenge

syndrome a therapeutic challenge Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the leading cause of death in critical care, with mortality rates of 40 to 60%. In the US alone, there are 200,000 new cases annually [1]. ALI/ ARDS also constitute a considerable long-term illness and disability burden, with signifi cant neuromuscular, pulmonary and psychological morbidity seen in 50 to 70% of survivors, and just 49% returning to employment one year post-discharge [2]. Despite being a focus of ongoing intensive research eff orts over four decades, there are no pharmacologic therapies for ALI/ARDS [3]. Largescale clinical trials of multiple therapeutic strategies, including nitric oxide [4,5], anti-oxidants [6-9], surfactants [10], corticosteroids [11] and immunomodulating agents such as IL-10 [12] and granulocyte-macrophage colony-stimulating factor [13] have all failed. Consequently, advances in the management of ALI/ARDS have relied on improvements in supportive measures, such as ‘protective’ mechanical ventilation strategies [3], restrictive intravenous fl uid management approaches [14], and prone positioning of severely hypoxaemic patients [15,16]. While these and other improvements in supportive care have decreased mortality [17], the failure of pharmacologic therapies suggests the need to consider novel approaches for ALI/ARDS. ALI/ARDS is a highly complex disease process. Earlier concepts of distinct disease phases, from an early ‘proinfl ammatory’ to a later ‘fi brotic’ phase, now appear to be an over-simplifi cation. Th ese ‘phases’ largely co-exist, with evidence of pro-infl ammatory responses leading to host damage, an impaired immune response to pathogens, and repair and fi brosis all present in the complex milieu that is clinical ALI/ARDS. Given this, it is perhaps not surprising that strategies targeted at one aspect of the disease process have been unsuccessful. Th is suggests the need to consider more complex therapeutic approaches aimed at reducing early injury while maintaining host immune competence, and facilitating (or at least not inhibiting) lung regeneration Abstract