Pathophysiology of ARDS

The marked injury to the epithelium is associated with severe abnormalities in surfactant function that were suspected when ARDS was originally described (9-11). Surfactant dysfunction is a consequence of severe injury to type II pneu-mocytes and inactivation of surfactant by plasma proteins leaking into the alveolar spaces from the vascular compartment. In addition, surfactant-associated proteins are reduced in the airspaces and appear in the systemic circulation, possibly by leakage out of the airspaces into the plasma (12,13). 

The inflammatory changes in the lungs begin within the first few hours following onset of the clinical risk for ARDS and evolve during the course of sustained ARDS. Studies using bronchoalveolar lavage (BAL) have shown that cytokines and PMN are present in the BAL fluid of patients at risk who were studied soon after arrival at the hospital (14). The IL-8 concentration increased before PMN were detectable in BAL fluid. The PMN concentration in the BAL fluid increases dramatically at the onset of clinically defined ARDS and remains markedly elevated for the first 3 days. Thereafter, the PMN concentration tends 

Recent studies of the effects of mechanical ventilation in patients with ARDS suggest that mechanical ventilation itself triggers or amplifies the injury. In a randomized trial, patients ventilated with a protective ventilatory strategy using low inflation volumes and pressures had declining PMN and cytokine con- 

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