Diffuse alveolar damage (DAD) is a term that describes a tissue response to a wide variety of acute lung injuries. The lung has limited ways to respond to injury; therefore, the pathologic findings present in this entity are similar regardless of the causal agent. The clinical expression of this tissue reaction is acute respiratory distress syndrome (ARDS), also known in the literature as acute lung injury, traumatic wet lung, Da Nang lung, noncardiogenic pulmonary edema, congestive atelectasis, and adult hyaline membrane disease. Causes of DAD include infections, trauma including neurotrauma, burns, shock, inhalation of fumes and toxins, drug reactions, chemotherapy and radiation, aspiration, oxygen and ventilation, and other insults. Many patients with ARDS/DAD have a combination of several possible causes superimposed on one another, such as trauma followed by oxygen therapy and infection. Approximately 50% of cases resolve. In some cases, there is progression to a fibrotic phase with end-stage fibrosis. From clinical and experimental observations it is known that DAD progresses through several histologic and clinical stages. Most authors recognize an early exudative, a proliferative, and a late resolving phase.

During early stages, grossly the lungs are heavy due to congestion and edema. The histologic findings depend on the stage of the disease. The early exudative phase shows edema and necrosis of alveolar epithelium. After 72 hours, fibrin and hyaline membranes appear. During the proliferative phase, there is fibroblastic and myofibroblastic interstitial proliferation, as well as type II cell hyperplasia. Finally, the fibrotic phase is characterized by areas of interstitial fibrosis with occasional cystic spaces and occasionally changes that resemble the bronchopulmonary dysplasia seen in infants. Acute interstitial pneumonia has histopathologic features similar to organizing DAD and is a pathologic correlate of the idiopathic clinical Hamman-Rich syndrome (see Chapter 91).