Differences in FVC decline by extent of emphysema in patients with combined pulmonary fibrosis and emphysema (CPFE) syndrome

Background: Concurrent emphysema may be associated with spurious preservation of FVC in CPFE. Serial FVC measurement used to monitor progression of idiopathic pulmonary fibrosis (IPF) might therefore fail to capture disease progression in CPFE. Objective: To evaluate the relationship between extent of emphysema and disease progression in patients with CPFE. Methods: Patients (n = 309) enrolled previously in a placebo-controlled clinical trial of interferon γ-1b to treat IPF were stratified at baseline based on emphysema extent using HRCT. At week 48, the relationship between emphysema extent and ΔFVC was evaluated. A bootstrap analysis was also performed at 5% intervals of emphysema extent to support these findings. Results: FVC did not decline in patients with an emphysema extent ≥15% while it did in patients with no emphysema (ΔFVC=0.17 vs -4.61; P =0.045). In contrast, patients with an emphysema extent P =0.344; 5-15%, ΔFVC=-4.10 vs -4.61; P =0.733). Bootstrap analysis supported the identified 15% threshold (Figure). Other functional measures (DLco, 6MWT distance, SOBQ and CPI score) were not impacted by emphysema extent. Conclusions: For patients with ≥15% extent of emphysema, the course of FVC decline may be confounded. These findings may inform clinical trial design and care of patients with CPFE.