The Presence of Emphysema in Patients with Idiopathic Pulmonary Fibrosis and Lung Cancer: Impact on Tumor Features, Acute Exacerbation, and Survival

<b>Background:</b> Idiopathic pulmonary fibrosis (IPF) and emphysema often coexist in patients with lung cancer (LC), forming a syndrome with combined pulmonary fibrosis and emphysema (CPFE). The three share the pathogenic mechanisms of smoking, chronic inflammation, and oxidative stress. The clinical management of CPFE patients is challenging, but its impact on tumor characteristics, acute exacerbation (AE), and prognosis is still controversial. The purpose of this study was to clarify the effect of CPFE on tumor biological behavior, AE risk, and survival outcome in patients with IPF-LC so as to optimize individualized treatment strategies. <b>Methods:</b> This was a retrospective and single-center study. Newly diagnosed LC patients with IPF, COPD, and normal lungs were recruited in the west China hospital. Patients with IPF were further categorized into CPFE-LC and isolated IPF-LC groups based on the presence of emphysema. Clinical and tumor features, lung function parameters, and prognosis were obtained and compared. <b>Results:</b> Patients with IPF and LC were more common in older men and heavy smokers. IPF-associated tumors had a higher proportion of carrying EGFR wild-type, occurring in the lower lobe of the lung and developing adenocarcinoma and squamous cell carcinoma. Among IPF-LC patients, 68.2% (103/151) met CPFE criteria. Pulmonary function tests demonstrated preserved VC% but significantly reduced FEV1/FVC in CPFE versus non-emphysema IPF (76.3% vs. 80.7%, <i>p</i> = 0.004), alongside elevated CPI and impaired DLCO. CPI ≥ 40 (HR = 2.087, 95%CI: 1.715-6.089, <i>p</i> = 0.012), combined with COPD (HR = 2.281, 95%CI: 1.139-4.569, <i>p</i> = 0.040), isolated IPF (HR = 5.703, 95%CI: 2.516-12.925, <i>p</i> < 0.001), and CPFE (HR = 6.275, 95%CI: 3.379-11.652, <i>p</i> < 0.001), were independent prognostic risk factors in LC patients. The incidence of treatment-induced AEs (49.5% vs. 29.2%, <i>p</i> = 0.038) and AE-related mortality (28.0% vs. 11.8%, <i>p</i> = 0.045) were significantly higher in the CPFE group than in the isolated IPF group. Logistic regression analysis showed that CPFE (OR: 3.494, 95%CI: 2.014-6.063, <i>p</i> = 0.001) was independently associated with the risk of AE-related mortality in patients with LC and IPF. <b>Conclusions:</b> Compared to LC patients with solely IPF, the presence of emphysema had no significant impact on overall survival, but CPFE increased the risk of treatment-triggered AE and was associated with AE-related mortality. In patients with LC, CPFE with AEs had a worse prognosis than IPF with AEs.