Pathologic Findings and Prognosis in a Large Prospective Cohort of Chronic Hypersensitivity Pneumonitis

BACKGROUND: The ability of specific histopathologic features to predict mortality or lung transplantation in patients with chronic hypersensitivity pneumonitis (HP) is unknown. METHODS: Patients with chronic HP diagnosed by surgical lung biopsy were identified from an ongoing longitudinal cohort. The surgical lung biopsy slides were evaluated prospectively by an experienced thoracic pathologist using a standardized checklist to differentiate the major pathologic patterns and score the presence of specific histopathologic features. Cox proportional hazard analysis was used to identify independent predictors of transplant-free survival, and Kaplan-Meier analysis was used to visualize outcomes. RESULTS: One hundred nineteen patients were identified. Patients with a fibrotic nonspecific interstitial pneumonia (f-NSIP) pattern, bronchiolocentric fibrosis (BF) pattern, or usual interstitial pneumonia (UIP) pattern had significantly worse transplant-free survival than did those with a cellular NSIP (c-NSIP) pattern or peribronchiolar inflammation with poorly formed granulomas (PI-PFG) pattern. No survival difference among patients with an f-NSIP pattern, a BF pattern, or a UIP pattern was found. Fibroblastic foci were identified in a subset of biopsy samples from all pathologic patterns. Peribronchiolar fibrosis was noted in all UIP cases. Independent predictors of time to death or transplantation included the presence of fibroblast foci or dense collagen fibrosis. CONCLUSIONS: Histopathologic patterns of c-NSIP and PI-PFG had a better transplant-free survival than did patterns of UIP, f-NSIP, and BF. The presence of fibroblast foci or dense collagen fibrosis correlated with progression to death or lung transplantation. Identification of fibroblast foci on biopsy samples, regardless of the underlying histopathologic pattern, may be a clinically useful predictor of survival in patients with HP.