Seminars in respiratory and critical care medicine
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Acute lung injury (ALI) is a complex syndrome involving the interplay of both environmental (such as the addition of mechanical ventilation) and genetic factors. Clinical models have identified risk factors for development and poor outcome but these strategies remain imprecise. ⋯ Although valuable information has been reported to date, intense analyses are needed in this developing discipline to assure significant clinical utility. The detailing of specific associated polymorphisms will continue to provide new insights in the understanding of disease pathogenesis, and promise to reveal novel molecular targets and personalized treatments to prevent the disease.
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Semin Respir Crit Care Med · Aug 2006
Review Historical ArticleTreatment of acute lung injury: historical perspective and potential future therapies.
The acute respiratory distress syndrome (ARDS) was first described by Ashbaugh and colleagues in 1967. However, despite considerable efforts, early progress in treatment was slowed by lack of consistent definitions and appropriately powered clinical trials. In 1994, the American-European Consensus Conference on ARDS established criteria defining ARDS as well as acute lung injury (ALI). ⋯ Mechanical ventilation, using positive end-expiratory pressure and reduced tidal volumes and inspiratory pressures, along with improved supportive care has increased survival rates. However, to date, pharmacological therapies have failed to improve survival in multicenter clinical trials. This article focuses on clinical treatments for ALI that have been tested in phase II and III clinical trials as well as a discussion of potential future therapies.
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Semin Respir Crit Care Med · Aug 2006
ReviewRadiological imaging in acute lung injury and acute respiratory distress syndrome.
Computed tomography (CT) has been utilized to study acute respiratory distress syndrome (ARDS) since the middle 1980s, when it revealed the inhomogeneous pattern of the lung lesion. Its advantages rely on the strict correlation between CT density and the lung physical density, allowing a quantification of lung compartments with different degrees of aeration. By CT scans, ARDS lung appeared to be "small" rather than "stiff," leading to the "baby lung" concept. ⋯ The amount of recruitable lung varies among ARDS patients. This knowledge is necessary for a rational positive end-expiratory pressure (PEEP) setting because the amount of tissue maintained aerated by PEEP is closely associated with the amount of recruitable lung. CT scans may also help to diagnose ARDS because CT provides a good estimate of the high-permeability lung edema, the characteristic lesion of this syndrome.
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Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) describe syndromes of diffuse parenchymal lung injury resulting from a variety of inflammatory triggers. The pathophysiological consequences include stiff, low-compliance lungs with impaired gas exchange. Importantly, there is often marked heterogeneity of disease. ⋯ To this end, the goals of mechanical ventilatory support of ALI and ARDS have shifted over the last decade to providing smaller (and thus less injurious) tidal volumes and accepting consequently lower arterial values for PaO(2) and the development of respiratory acidosis. This has resulted in significant improvements in outcomes. Future developments will need to further refine this lung protective concept.
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Semin Respir Crit Care Med · Aug 2006
ReviewThe role of the coagulation cascade in the continuum of sepsis and acute lung injury and acute respiratory distress syndrome.
Sepsis is a common and life-threatening condition with a high mortality rate. Severe sepsis includes multiorgan dysfunction syndrome. The organ most often affected is the lung, with development of acute lung injury (ALI), which, in its most severe form, is referred to as acute respiratory distress syndrome (ARDS). ⋯ With this clinical success, administration of drotecogin alfa (recombinant activated protein C), the importance of coagulation in the pathogenesis of human sepsis is becoming clearer. This review summarizes the current understanding of the role of coagulation and fibrinolytic abnormalities in sepsis and the development of ALI and ARDS. Both in vitro and in vivo studies of the role of the coagulation cascade in sepsis and lung injury will be discussed, including initiation of coagulation through modulation of tissue factor and tissue factor pathway inhibitor, propagation of coagulation via protein C and thrombomodulin, inhibition of thrombin generation and resolution through thrombolysis by plasminogen activator, and plasminogen activator inhibitor-1.