Combined pulmonary fibrosis and emphysema and lung transplantation: current evidence and future directions

Background: Combined pulmonary fibrosis and emphysema (CPFE) patients generally have a poorer prognosis compared to those with either pulmonary fibrosis or chronic obstructive pulmonary disease (COPD)/emphysema alone, as demonstrated by several studies. Our study aimed to identify undiagnosed CPFE cases within a lung transplantation cohort initially diagnosed with interstitial lung fibrosis or COPD/emphysema. It was hypothesized that the patient cohort might contain overlooked CPFE cases, and CPFE patients would exhibit a higher incidence of pre-transplant pulmonary hypertension and post-transplant chronic lung allograft dysfunction (CLAD). Methods: This is a single-center, retrospective cohort study conducted at the University Hospital of Zurich, Switzerland. Expert review of pre-transplant computed tomography (CT) scans by a thoracic radiologist aimed to identify undiagnosed CPFE cases. Diagnostic criteria followed established guidelines, requiring both emphysema and pulmonary fibrosis on CT imaging. A total of 133 consecutive adult bilateral lung transplantations were performed for patients with interstitial lung disease, emphysema, or both (January 1, 2013, to December 31, 2021). A total of 113 patients could be analyzed, 20 patients were excluded because of missing data. The study analyzed pulmonary function tests, pre-transplant pulmonary hypertension screening, and CLAD staging in CPFE and non-CPFE patients. Primary outcome was the incidence of CPFE among lung transplantation candidates initially diagnosed with interstitial lung fibrosis or COPD/emphysema. Secondary outcomes were comparison of pulmonary function, diffusing capacity, invasively measured pulmonary hypertension, and CLAD stages between CPFE and non-CPFE patients. Results: Based on pre-transplant CT scans, out of 113 patients, 12 (10.6%) were reclassified as previously undiagnosed CPFE, 49 (43.4%) as non-CPFE fibrosis, and 50 (44.2%) as non-CPFE emphysema. A solitary patient (0.9%) was classified as having both fibrosis and emphysema but did not meet the criteria of CPFE. One additional patient (n=1, 0.9%) exhibited a tree-in-bud pattern. Prior to the radiological review, none of the patients had been classified as CPFE and had instead received a radiological diagnosis of COPD, emphysema, sarcoidosis, interstitial pulmonary fibrosis (IPF) or hypersensitivity pneumonitis (HP). Conclusions: The study confirmed undiagnosed CPFE cases in 12 (10.6%) in the lung transplantation cohort, suggesting potential underdiagnosis or misclassification. Objective analysis revealed similarities in lung function, diffusing capacity, pulmonary hypertension and CLAD between CPFE and non-CPFE groups. Further exploration is warranted to understand CPFE's diagnostic nuances and clinical implications in lung transplantation.