Clinical Outcomes and Acute Exacerbation Incidence in Combined Pulmonary Fibrosis and Emphysema.
BACKGROUND AND OBJECTIVE Combined pulmonary fibrosis and emphysema (CPFE) is characterized by coexisting upper-zone emphysema and lower-zone fibrosis, but standardized diagnostic criteria and clinical outcomes remain poorly defined. This study aimed to evaluate survival, acute exacerbation incidence, and disease progression in CPFE patients using international classification criteria with visual assessment of emphysema extent. METHODS This multicentre prospective cohort study at 29 Japanese hospitals enrolled 1016 patients with idiopathic interstitial pneumonias (IIPs) or chronic obstructive pulmonary disease (COPD) between 2013 and 2016. CPFE was defined as ≥ 5% emphysema determined by visual assessment of CT scans for IIP patients, according to international classification criteria. Patients were followed for 5 years. RESULTS Among 528 IIP patients, 92 (17.4%) had CPFE. CPFE patients showed a significantly worse 5-year survival compared with non-CPFE IIP patients (51.4% vs. 63.1%, p = 0.026) and COPD patients (51.4% vs. 84.0%, p < 0.001). After adjustment for covariates including IIP subtype, CPFE remained independently associated with increased mortality among IIP patients (HR of 1.85 [95% CI, 1.27-2.69], p < 0.001). CPFE patients also had a significantly higher acute exacerbation rate than did non-CPFE IIP patients (p < 0.001). The prognostic impact of CPFE was most pronounced in patients with idiopathic pulmonary fibrosis (IPF), with CPFE/IPF patients showing the worst outcomes. CONCLUSION Visual assessment with a ≥ 5% emphysema threshold effectively identified CPFE patients with a distinct clinical phenotype characterized by poor survival and an increased acute exacerbation incidence. These findings validate international classification criteria and emphasize the need for enhanced surveillance and tailored management strategies for this high-risk population.