Acute lung injury: clinical perspective

perspective Acute lung injury (ALI) and its more severe manifestation, acute respiratory distress syndrome (ARDS), are characterised by acute inflammation that affects the function of the gas exchange surface of the lung. The disorder affects all age groups, and has an incidence of approximately 200,000 cases per year in the United States and a mortality of around 35% (Rubenfeld et al., 2005). ARDS was first described by Ashbaugh and colleagues (Ashbaugh et al., 1967) in 1967 in a series of 12 patients. A working definition of ALI and ARDS was established in 1994 by the American European Consensus Conference (AECC) (Bernard et al., 1994). ARDS presents clinically with breathlessness and hypoxaemia in the presence of diffuse pulmonary oedema on the chest radiograph. Hydrostatic lung oedema due to elevation of left atrial pressure should either be clinically improbable or excluded by direct measurement or echocardiography for a diagnosis of ARDS to be confirmed. The severity of hypoxaemia distinguishes ALI from ARDS: when hypoxaemia is severe [partial arterial pressure of oxygen (PaO2)/fractional concentration of oxygen in inspired air (FIO2)<200 mmHg or 26.7 kPa], the disorder is termed ARDS, whereas less severe abnormalities of gas exchange (PaO2/FIO2<300 mmHg or 40 kPa) are termed ALI. In practice, ALI is an umbrella term used by the majority of epidemiological and interventional studies in this field and will be used in this article to encompass both clinical syndromes. ALI can result from both direct pulmonary injury, such as pneumonia, or indirect bloodborne insults – for example, following severe sepsis, a multiple-organ dysfunction syndrome (Ware, 2006). Risk of progression to ALI varies according to the type, number and severity of predisposing conditions, as well as the genetics and other characteristics of the patient (Marshall et al., 2002). The application of mechanical ventilation, which is required in up to 80% of patients, can further damage susceptible lung in a process termed ventilator-associated lung injury (VALI). The clinical impact of VALI was highlighted in The Acute Respiratory Distress Syndrome Network study, in which mortality was reduced from 39.8% to 31% with a low tidal volume ‘protective ventilator strategy’ (P0.007) (A.R.D.S. Network, 2000). To date, the only strategy proven to be effective at reducing mortality in ALI is low tidal volume ventilation targeting a reduction in VALI. Although a recent Phase II study of neuromuscular blockade in early ALI demonstrated a reduction in 28-day mortality from 33.3% to 23.7% compared with placebo (P0.05) (Papazian et al., 2010), this approach requires validation in further clinical trials. Most ALI patients either die or are weaned from supportive treatment within 1-2 weeks, although up to 10% of patients require prolonged (30 days or more) mechanical ventilation. Lung function in most survivors returns to normal over 6-12 months. However, neuromuscular and psychological morbidity can significantly impair longerterm health-related quality of life (Hopkins et al., 1999; Herridge et al., 2003; Wilcox and Herridge, 2010). Despite technological advances, for example in lung imaging, and significant investment in both basic science and large