Pulmonary sequelae and lung repair in survivors of the adult respiratory distress syndrome.

The high in-hospital mortality of ARDS has not diminished over the past 10 years, despite improvements in supportive intensive care. Much of the mortality arises from infections, particularly sepsis and pneumonia, and from organ failure, especially kidney failure. The rapid advances in understanding the interlocking pathophysiologic mechanisms of ARDS have not yet been translated into therapeutic trials of new methods for diminishing the injury or for stimulating normal repair. In part, this is because it is difficult to predict which high-risk patients will develop ARDS and then intervene early in the injury process. Patients in whom the risk for ARDS is extremely high have a very high mortality even without ARDS, thereby making efficacy of an early or prophylactic therapy quite difficult to prove. In spite of severe pathologic abnormalities, including fibrosis, early in the course of ARDS, most survivors return to almost normal pulmonary function. The few cases that have been studied with serial biopsies demonstrate resolution of fibrosis. This amazing recovery poses many fascinating questions about how the lung repairs itself. Given the heterogeneous causes of ARDS and the large number of structural, cellular, and biochemical abnormalities described, one can postulate that any one of numerous factors is important in normal repair. Most promising of these are the degree of basement membrane damage, the control of type II cell proliferation and differentiation, the control of collagen synthesis, the anatomic localization of fibrosis, and the control of collagenase action. These interactions of epithelial and mesenchymal tissues probably recreate the process of lung development in the injured adult lung. At a clinical level, the role of oxygen toxicity remains a significant issue. Oxygen acting as an oxidant may be partially responsible for the small airways disease seen in approximately one quarter to one third of survivors. The mortality data stress the need for better ways of preventing and diagnosing lung infections. Better definition of the clinical factors that put survivors at risk for persistent loss of lung function is also needed, and could define a subgroup in which trials of agents designed to improve repair would be most worthwhile. More information about the long-term pathologic course, though difficult to obtain, would also be very important. Perhaps some registry of ARDS survivors would permit closer follow-up and make available more late autopsy pathology when these people die of other causes. The rapid time course of ARDS provides an ideal testing ground for agents designed to either decrease lung injury or stimulate repair.(ABSTRACT TRUNCATED AT 400 WORDS)