Idiopathic pulmonary fibrosis - Clinical relevance of pathologic classification

1. Four pathologically distinct interstitial pneumonias comprise the clinical syndrome of IPF. The past inclusion of these different entities under a single designation may explain the perplexing variation in presentation, response to steroid therapy, and clinical course that has been noted in patients with IPF. 2. The fact that all the idiopathic interstitial pneumonias are characterized histologically by varying amounts of inflammation and fibrosis explains why they have previously been lumped together under a single designation. Recognition of qualitative differences in the nature of the fibrosis as well as appreciation of the temporal characteristics of the changes, allows their distinction from one another. 3. The term "idiopathic pulmonary fibrosis" should be reserved for cases of UIP, the most common idiopathic interstitial pneumonia. This disease has an insidious onset, is chronically progressive, usually does not respond to therapy, and is fatal in most cases. 4. DIP is a rare form of idiopathic interstitial pneumonia that has an insidious onset and a good prognosis. It maybe related to cigarette smoking. Consideration should be given to replacing the anatomically inaccurate and controversial term "desquamative interstitial pneumonia" with RBILD, which is anatomically more appropriate and conveys pathogenetic implications. 5. AIP is an acute, fulminant form of idiopathic interstitial pneumonia that corresponds to the cases described by Hamman and Rich in 1944 (21). The course is rapid, evolving over several months, and the mortality rates are high. The pathologic changes are a manifestation of severe, extensive acute lung injury. 6. NSIP is a temporally uniform interstitial pneumonia that does not fit histologically with any other idiopathic interstitial pneumonia. Interstitial inflammation is often prominent, and the prognosis is generally good with a beneficial response to steroids in most patients. 7. There has been a longstanding misconception that UIP evolves from an early "cellular" lesion into a later fibrotic state. The earliest change in UIP is the fibroblast focus, a manifestion of acute lung injury. Interstitial inflammation and intraalveolar macrophage accumulation, if they occur at all, are secondary events. 8. There has been considerable emphasis on the grading of cellularity and fibrosis in IPF, because of potential prognostic implications. The evidence suggests that the division of IPF into the four forms of idiopathic interstitial pneumonia is more important prognostically than any one grading system. However, within each category of disease, the extent of fibrosis appears to have significance. The relative roles of the different types of fibrosis (collagen versus fibroblast foci) in determining prognosis have not yet been examined. 9. Acceptance of this pathologic classification of the idiopathic interstitial pneumonias has important implications for future clinical and basic-science investigations of IPF, as well as for understanding patient prognosis and treatment.