Biological therapies in the acute respiratory distress syndrome.
BACKGROUND
The acute respiratory distress syndrome (ARDS) is characterised by life-threatening respiratory failure requiring mechanical ventilation, and multiple organ failure. It has a mortality of up to 30 - 45% and causes a long-term reduction in quality of life for survivors, with only approximately 50% of survivors able to return to work 12 months after hospital discharge.


METHODS
In this review we discuss the complex pathophysiology of ARDS, describe the mechanistic pathways implicated in the development of ARDS and how these are currently being targeted with novel biological therapies. These include therapies targeted against inflammatory cytokines, mechanisms mediating increased alveolar permeability and disordered coagulation, as well as the potential of growth factors, gene therapy and mesenchymal stem cells.


CONCLUSIONS
Although understanding of the pathophysiology of ARDS has improved, to date there are no effective pharmacological interventions that target a specific mechanism, with the only potentially effective therapies to date aiming to limit ventilator-associated lung injury. However, we believe that through this improved mechanistic insight and better clinical trial design, there is cautious optimism for the future of biological therapies in ARDS, and expect current and future biological compounds to provide treatment options to clinicians managing this devastating condition.
Queen's University Belfast, Centre for Infection and Immunity , Belfast , UK d.f.mcauley@qub.ac.uk.
Andrew James
AJ
Boyle
James Joseph
JJ
McNamee
Daniel Francis
DF
McAuley
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000068258:Bevacizumab; D001691:Biological Therapy / Q000009:adverse effects; D016207:Cytokines / Q000037:antagonists & inhibitors*; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000628:therapy*; D019851:Thrombophilia / Q000209:etiology / Q000628:therapy*; D055397:Ventilator-Induced Lung Injury / Q000517:prevention & control*
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D000068258:Bevacizumab; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
acute hypoxaemic respiratory failure; acute lung injury; acute respiratory distress syndrome; biological therapies