Idiopathic pulmonary fibrosis - Relationship between histopathologic features and mortality

It is hypothesized that the extent and severity of fibrosis and cellularity found on lung biopsy determine the prognosis and response to therapy in id iopathic pulmonary fibrosis (IPF). The objective of this study was to deter mine which histopathologic features predict survival in IPF. We prospective ly studied 87 patients with usual interstitial pneumonia (UIP) confirmed by surgical lung biopsy. Four pathologists independently graded the extent an d severity of specific histopathologic features. We used Cox proportional-h azards models to assess the effect of histopathologic patterns on patients' survival, The effects of age, sex, and smoking were also included in the a nalysis. Sixty-three patients died during the 17-yr study period. Survival was longer in subjects with lesser degrees of granulation/connective tissue deposition (fibroblastic foci). The degree of alveolar space cellularity, alveolar wall fibrosis, and cellularity did not affect survival. A history of cigarette smoking, the level of dyspnea, and the degree of lung stiffnes s at presentation were also shown to be independent factors predicting surv ival. The extent of fibroblastic foci present on lung biopsy predicts survi val in IPF. These findings support the hypothesis that the critical pathway to end-stage fibrosis is not "alveolitis" but rather the ongoing epithelia l damage and repair process associated with persistent fibroblastic prolife ration. Controlling these processes, rather than stopping inflammation, app ears most important in preventing progressive disease and the fatal outcome common in IPF.