The C/C/G, G/G/G, and G/C/C haplotype clades of IL-6 were strongly associated with increased mortality and more organ dysfunction in a cohort of critically ill patients who had SIRS. Haplotype-based analysis succeeded in identifying this association, whereas individual single nucleotide polymorphism-based analysis failed.

Introduction β2 agonists have several properties that could be beneficial in acute lung injury (ALI). We therefore chose to study the effect of inhaled β2 agonist use (salbutamol) on duration and severity of ALI.

SARS is a highly contagious, infectious process that can advance to significant hypoxemic respiratory failure requiring ICU monitoring and support. Early recognition is critical for effective management and containment of this disease.

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Severe sepsis and septic shock is a common problem encountered in the critical care unit with an estimated incidence in the US of 750,000 cases/year and a mortality rate of 30-50%. Sepsis involves a complex interaction between bacterial factors and the host immune system producing a systemic inflammatory state that may progress to multiple organ failure and death. Endotoxin (a lipopolysaccharide) released from Gram-negative bacteria has been implicated as a potent, prototypical stimulus of the immune response to bacterial infection. Current antiendotoxin strategies utilise various approaches ranging from the prevention of binding to endotoxin receptors with antibodies (monoclonal or polyclonal) against endotoxin or endotoxin receptor/carrier molecules (antiCD14 or antilipopolysaccharide-binding protein antibodies), enhancing clearance or neutralisation (haemoperfusion, lipoproteins, lipopolysaccharide-neutralising proteins) or impairing cellular signalling (lipid A analogues, tyrosine kinase inhibitors). In the future, innovative therapies involving Toll-like receptors and their downstream signalling elements will be developed. This review discusses current knowledge regarding endotoxin signalling, antiendotoxin therapies currently under development, and future areas for research.

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234 ALI = acute lung injury; AQP = aquaporin; ARDS = acute respiratory distress syndrome; FiO 2 = fractional inspired concentration of oxygen; IL = interleukin; PaO 2 = partial pressure of oxygen; TNF-α = tumor necrosis factor alpha. Critical Care August 2004 Vol 8 No 4 Groshaus et al. IntroductionAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are important because of the continued high mortality and costs of care of these conditions. Beta adrenergic agonists are inexpensive and are actually often used in the treatment of patients who have ALI or ARDS for reasons not related to attempts to improve resolution of lung injury. For example, inhaled beta-2 adrenergic agonists are used to decrease airway resistance when it is increased in ALI and ARDS. Intravenously infused beta adrenergic agonists are used when the circulation requires inotropic support because of shock or ventricular dysfunction, both of which are common in ALI and ARDS. It is unknown whether beta adrenergic agonists used for these other reasons also improve the resolution of ALI.We have chosen to focus on the evidence that beta-2 adrenergic agonists act through three mechanisms (increased clearance of salt and water from alveoli, anti-inflammatory effects, and bronchodilation) to improve the pathophysiology, and possibly the rate and success of resolution, of pulmonary edema and ALI. This leads to the hypothesis that beta-2 adrenergic agonists may be beneficial therapy for patients with ALI or with ARDS. DefinitionsDifferent definitions and scoring systems have been developed since the "adult respiratory distress syndrome" was first described by Ashbaugh and colleagues in 12 patients in 1967 [1]. The most current consensus conference definition of ALI is acute onset of acute respiratory failure characterized by PaO 2 /FiO 2 ≤300 mmHg, bilateral infiltrates, and pulmonary capillary wedge pressure AbstractAcute lung injury (ALI) and the acute respiratory distress syndrome are complex syndromes because both inflammatory and coagulation cascades cause lung injury. Transport of salt and water, repair and remodeling of the lung, apoptosis, and necrosis are additional important mechanisms of injury. Alveolar edema is cleared by active transport of salt and water from the alveoli into the lung interstitium by complex cellular mechanisms. Beta-2 agonists act on the cellular mechanisms of pulmonary edema clearance as well as other pathways relevant to repair in ALI. Numerous studies suggest that the beneficial effects of beta-2 agonists in ALI include at least enhanced fluid clearance from the alveolar space, anti-inflammatory actions, and bronchodilation. The purposes of the present review are to consider the effects of beta agonists on three mechanisms of improvement of lung injury: edema clearance, anti-inflammatory effects, and bronchodilation. This update reviews specifically the evidence on the effects of beta-2 agonists in human ALI and in models of ALI. The available evidence suggests that beta-2 agonists may be efficacious t...

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