Abstract
BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is associated with high mortality, poor prognosis, and a substantial societal burden. This study aimed to identify and summarize prognostic factors in patients with CPFE through a systematic review and meta-analysis, with the goal of informing clinical management and treatment strategies. METHODS: A systematic search was conducted in PubMed, Web of Science, the Cochrane Library, and Embase from database inception to August 15, 2025, to identify studies investigating prognostic factors in patients with CPFE. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Hazard ratio (HR) with 95% confidence interval (CI) was used to determine prognostic factors for CPFE. RESULTS: This study included 14 studies involving 1,874 patients. A meta-analysis of 10 studies, comprising 1,471 patients, demonstrated that age (HR =1.03; 95% CI: 1.02, 1.05; P<0.001), smoking history (HR =1.63; 95% CI: 1.04, 2.55; P=0.03), lung cancer (HR =5.00; 95% CI: 3.01, 8.31; P<0.001), diffusing capacity of the lung for carbon monoxide (DLCO) (HR =0.96; 95% CI: 0.94, 0.98; P<0.001), percent predicted DLCO (DLCO%pred) (HR =0.97; 95% CI: 0.95, 1.00; P=0.04), an annual increase in composite physiologic index (CPI) (≥5 points) (HR =8.43; 95% CI: 1.46, 48.72; P=0.02), and usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) (HR =1.89; 95% CI: 1.10, 3.25; P=0.02) were prognostic factors for mortality in patients with CPFE. Lung cancer (HR =3.47; 95% CI: 1.74, 6.90; P<0.001) was identified as a prognostic factor for acute exacerbation (AE) in CPFE patients. CONCLUSIONS: Age, smoking history, DLCO, DLCO%pred, lung cancer, an annual increase in CPI(≥5points), and UIP pattern on HRCT may be prognostic factors for mortality in patients with CPFE. Lung cancer may be a prognostic factor for AE in CPFE patients. However, due to the limited number and quality of the included studies, these conclusions need to be validated by further research.