Combined Pulmonary Fibrosis and Emphysema (CPFE): A "New" Smoking-Related Interstitial Lung Disease (ILD)

Background: Combined Pulmonary Fibrosis and Emphysema (CPFE) is a distinct syndrome characterized by upper-lobe emphysema and lower-lobe fibrosis, predominantly in older male smokers. Despite often preserved spirometric volumes, patients exhibit severely reduced diffusing capacity and high susceptibility to complications, including pulmonary hypertension (PH), acute exacerbations, and lung cancer, contributing to poor prognosis. Purpose: This review aims to synthesize current evidence on CPFE, focusing on clinical phenotype, functional impairment, differential diagnosis, complications, and emerging management strategies, highlighting distinctions from idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Methods: A narrative review of observational cohorts, retrospective series, and clinical studies examining CPFE patients was performed. Data on demographics, smoking history, symptomatology, pulmonary function, radiology, comorbidities, complications, and treatment approaches were extracted and integrated. Results: CPFE affects mainly males aged 65-70, with >90% reporting > 40 pack-years smoking history. Dyspnea is the cardinal symptom (>95%), often disproportionate to preserved FVC and TLC, accompanied by chronic cough in 30-70%. Exercise-induced desaturation is frequent, correlating with PH, observed in 47-90% of patients. Pulmonary function tests reveal preserved volumes, normal or near-normal FEV1/FVC, and severely reduced DLCO (35-45%), distinguishing CPFE from COPD and IPF. HRCT confirms the combined emphysematous and fibrotic pattern, critical for differential diagnosis. Acute exacerbations occur in 20-28% of cases, lung cancer in 22-46% (mostly squamous cell), and long-term oxygen therapy is required in >70%. Five-year survival is 35-55%, lower than emphysema alone and comparable or worse than IPF. Management focuses on smoking cessation, antifibrotics, oxygen therapy, and complication-specific treatments, and selected patients may undergo lung transplantation. Conclusions: CPFE is a clinically and functionally unique entity with a high burden of pulmonary and systemic complications. Accurate recognition using HRCT and DLCO, along with early intervention and tailored management, is essential to improve patient outcomes and guide prognostic stratification.