Impact of emphysema on mortality in idiopathic pulmonary fibrosis: A systematic review and meta-analysis

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrosing interstitial lung disease. The effects of emphysema on mortality in IPF remains unclear. Methods: MEDLINE, Embase and Cochrane Library databases were searched. Studies were included if they compared mortality in IPF patients with and without emphysema. In included studies, the diagnosis with IPF or IPF combined emphysema was according to the ATS and ERS statements. From eligible studies, we extracted HR and 95% CI, if HRs were not reported, they were extracted based on Kaplan-Meier curves. Results: A total of 2605 patients across 15 cohort studies were included in the systematic review and meta-analysis. Emphysema was associated with increased risk of all-cause mortality with a pooled HR 1.37 (95% CI, 1.04-1.80) and I2 = 64%. However, the level of evidence was 'very low' according to GRADE criteria. Subgroup analysis according to IPF with emphysema patients revealed that DLCO%pre<40 (HR 1.75 (95% CI, 1.02-3.01) and I2 = 74%), FVC%pre<80 (HR 1.81 (95% CI, 1.24-2.64) and I2 = 61%), location on North America and Europe (HR 2.00 (95% CI, 1.09-3.67) and I2 = 76%), and Smoking Pack-years<40 (HR 1.38 (95% CI, 1.02-1.87) and I2 = 15%) were risk factors for all-cause mortality. Sensitivity analysis revealed that one study had a disproportional effect on the pooled rate. Conclusions: Our findings suggested emphysema increased the risk of all-cause mortality in patients with IPF. This conclusion should be re-evaluated by a large-scale randomized controlled trial.