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Acute Lung Injury (ALI) &
Acute Respiratory Distress Syndrome (ARDS)

Acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS), are syndromes of acute respiratory failure that result from acute pulmonary edema and inflammation. The development of ALI/ARDS is associated with several clinical disorders including direct pulmonary injury from pneumonia and aspiration as well as indirect pulmonary injury from trauma, sepsis, and other disorders such as acute pancreatitis and drug overdose.

Although mortality from ALI/ARDS has decreased in the last decade, it remains high. Despite two major advances in treatment, low VT ventilation for ALI/ARDS and activated protein C for severe sepsis (the leading cause of ALI/ARDS), additional research is needed to develop specific treatments and improve understanding of the pathogenesis of these syndromes.

The NHLBI convened a working group to develop specific recommendations for future ALI/ARDS research. Improved understanding of disease heterogeneity through use of evolving biologic, genomic, and genetic approaches should provide major new insights into pathogenesis of ALI. Cellular and molecular methods combined with animal and clinical studies should lead to further progress in the detection and treatment of this complex disease.

Acute lung injury (ALI) and the acute respiratory distress syndrome(ARDS) are syndromes with a spectrum of increasing severity of lung injury defined by physiologic and radiographic criteria in which widespread damage to cells and structures of the alveolar capillary membrane occurs within hours to days of a predisposing insult. In this report we will consider ALI and ARDS together, although we also specially refer to ARDS because it has been studied as a defined entity with exclusion of patients with less severe degrees of lung injury. The time course of ALI/ARDS distinguishes these syndromes of alveolar damage from most other lung diseases, whose natural histories occur over a much longer duration, usually years. ALI/ARDS is a major cause of acute respiratory failure with high morbidity and mortality in critically ill patients.

Recent epidemiologic data indicate that the incidence of ARDS defined by consensus physiologic criteria may account for 36,000 deaths per year in a country the size of the U.S.

There is reason to believe that this number will increase significantly in the future because of increasing frequency of some predisposing conditions that precipitate ALI/ARDS, such as sepsis.

Although there is evidence that mortality in patients with ALI/ARDS may have declined over the last 10 to 15 years, it remains high (30-40%), and it is an important cause of pulmonary and non pulmonary morbidity in patients who leave the hospital . Until recently, there were no specific measures that altered mortality in ALI/ARDS, and management was exclusively expectant and supportive, reflecting major deficiencies in our understanding of the cellular and molecular nature, pathogenesis, and natural history of acute alveolar injury. Recently, however, a prospective multicenter clinical trial demonstrated that a lung-protective ventilatory strategy could substantially reduce mortality. The results of this clinical trial suggest that there are additional opportunities to improve outcomes in ALI/ARDS if we can increase our fund of knowledge at the basic, translational, and clinical levels.

ALI/ARDS is a cause of acute respiratory failure that develops in patients of all ages from a variety of clinical disorders, including sepsis (pulmonary and non pulmonary), pneumonia (bacterial, viral, and fungal), aspiration of gastric and oropharyngeal contents, major trauma, and several other clinical disorders including severe acute pancreatitis, drug over dose,and blood products. Most patients require assisted ventilation with positive pressure. The primary physiologic abnormalities are severe arterial hypoxemia as well as a marked increase in minute ventilation secondary to a sharp increase in pulmonary dead space fraction. Patients with ALI/ARDS develop protein-rich pulmonary edema resulting from exudation of fluid into the interstitial and airspace compartments of the lung secondary to increased permeability of the barrier. Additional pathologic changes indicate that the mechanisms involved in lung edema are complex and that edema is only one of the pathophysiologic events in ALI/ARDS. One physiologic consequence is a significant decrease in lung compliance that results in an increased work of breathing, one of the reasons why assisted ventilation is required to support most lung-failure patients.