Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)

Acute lung injury (ALI) and its most severe manifestation of Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome of inflammation of the lung triggered by both direct (e.g. pneumonia) and indirect (e.g. sepsis) inciting events that result in the loss of the capillary-alveolar integrity. As a consequence, patients suffer from high-permeability, non-hydrostatic pulmonary edema. Compensatory mechanisms regulating lung fluid flux are overcome and interstitial and alveolar edema develops leading to reduced lung compliance and alveolar collapse. These physiologic derangements cause ventilation and perfusion (V_A/Q) mismatch and consequently intrapulmonary shunting leads to hypoxemia that is the hallmark of ALI/ARDS. The incidence of ALI/ARDS places it among the most burdensome health care challenges in pediatrics. A complex interaction of cellular components, cytokine and chemokine mediators, and adhesion molecules of the immune system orchestrate the pathophysiology of ALI/ARDS. The mainstay of therapy is institution of positive pressure mechanical ventilation that requires careful attention to minimizing distending pressures responsible for ventilator-induced exacerbation of injury as well as optimal recruitment strategies to avoid repetitive opening and closing of lung units. Avoidance of fluid overload following adequate fluid resuscitation appears to be of benefit, while additional therapies such as prone positioning, corticosteroids, inhaled nitric oxide and high frequency oscillatory ventilation may improve arterial oxygenation, though none have been systematically proven to improve overall clinical outcomes in limited pediatric studies. Novel approaches to identifying new therapeutic targets for attenuating the pathophysiology of ALI/ARDS are discussed.