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The syndrome now referred to as acute lung injury (ALI) is a condition defined by noncardiogenic pulmonary edema, originally described almost 50 years ago as Da Nang lung and subsequently as acute or adult respiratory distress syndrome (ARDS). The commonly used definition of ALI includes four elements: acute onset of symptoms, bilateral alveolar infiltrates on chest radiography, a PaO2 (partial pressure of oxygen)/FIO2 (fraction of inspired oxygen) ratio below 300 (200 defines the more severe subset of the patients as ARDS), and no evidence of left atrial hypertension. Histologically, the syndrome is identified by the classic finding of diffuse alveolar damage, but few patients undergo lung biopsy during the course of their clinical illness.


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More than 200,000 patients are diagnosed with ALI each year in the United States alone. That number is projected to increase over time as the prevalence of risk factors that lead to ALI increases. The most common risk factors for the development of ALI are sepsis, trauma, pneumonia, aspiration of gastric contents, pancreatitis, and blood transfusion. The incidence of ALI or ARDS, the mortality rate, and the pathogenesis vary with the underlying risk factor. Other conditions that impact the incidence, pathogenesis, and mortality rate of ALI or ARDS include alcohol use, diabetes, acute kidney injury, obesity, age, gender, ethnicity, and genetics. Although the primary manifestation of ALI is hypoxemic respiratory failure, the syndrome is not necessarily limited to the lungs. Many patients develop multiple organ dysfunction syndrome, which further contributes to morbidity and mortality.



The hallmark of ALI is increased alveolar permeability caused by a failure of the alveolar-capillary membrane. The initial insult may be either direct (e.g., aspiration) or indirect (e.g., sepsis, nonpulmonary trauma), with the common end point being the initiation of an inflammatory cascade with the release of inflammatory mediators and activation of both the endothelium and circulating neutrophils. The subsequent damage to the alveolar-capillary membrane results in an influx of proteinaceous material into the alveolar space that impedes oxygen transport and decreases compliance. The ability of the injured alveolar epithelium to reabsorb alveolar fluid is rapidly overwhelmed, leading to further fluid accumulation. The influx of edema fluid and the injury to the alveolar epithelium (specifically type II cells) also impact surfactant function, which increases lung surface tension, allowing for further alveolar collapse and decreased lung compliance. In some patients, the inflammatory response is self-limited, and the alveolar-capillary membrane is able to be repaired. In other patients, the inflammation persists, and fibrotic lung injury ensues.



Despite years of investigation, no pharmacologic intervention has improved the morbidity or mortality rate for patients with ALI. This is likely related to the heterogeneity of the patient population with the syndrome. Although no drugs impact mortality in patients with ALI, there have been significant advances in the management of these patients that have contributed to a decrease in mortality. The cornerstone of therapy for patients with ALI is low tidal volume ventilation with sufficient positive end-expiratory pressure (PEEP). A landmark trial published by the National Institutes of Health ARDS Clinical Trials Network showed that the mortality rate could be decreased from 40% to 31% using a tidal volume of 6 mL/kg predicted body weight and a plateau pressure limit of 30 cm H2O. The mechanism responsible for this improvement is, at least in part, a modulation of the inflammatory cascade. Nosocomial infection is a significant cause of morbidity and mortality in patients with ALI, so attention to daily, routine care is critical to management. Elevation of the head of the bed to more than 40 degrees is associated with a decreased incidence of ventilator pneumonia, a common cause of death in patients with ALI.



When the syndrome was originally described, the mortality rate was approximately 60%. More recently, the mortality rate is closer to 30% to 40%. With an apparent decrease in mortality, there has been a renewed focus on patients who survive ALI. The primary impairment of these patients was originally thought to be loss of pulmonary function, but it is now clear that neuromuscular and neuro sychiatric impairment are actually far greater issues.