The Epidemiology of Combined Pulmonary Fibrosis and Emphysema among Mid-Atlantic Veterans

Rationale: Combined pulmonary fibrosis and emphysema (CPFE) is a unique phenotype with important prognosis and management implications in patients with idiopathic pulmonary fibrosis (CPFE-IPF) and other forms of fibrotic interstitial lung disease (CPFE-fILD). However, the epidemiology of CPFE is not well characterized, creating a barrier to clinical research needed to advance our understanding and management. Objectives: To investigate the incidence, prevalence, and long-term outcomes of CPFE among a regional cohort of veterans. Methods: We retrospectively reviewed records for veterans in the Veterans Affairs Mid-Atlantic Health Care Network (includes North Carolina and Virginia) with International Classification of Disease, Ninth Revision, codes for pulmonary fibrosis between January 1, 2008, and December 31, 2015. We stratified pulmonary fibrosis into IPF and fILD using diagnostic codes and chart review. We reviewed computed tomography reports and classified cases as having CPFE according to documented emphysema; a thoracic radiologist overread a subset of scans for validation. We calculated annual incidence and prevalence of CPFE and compared characteristics between veterans with CPFE and veterans with fibrosis without emphysema using chi-square tests, Mann-Whitney U tests, and paired t tests. We used Kaplan-Meier and Cox models to determine overall survival from diagnosis. Results: We identified 2,414 veterans with fILD. Among 1,880 veterans with IPF, 734 (39.0%) had CPFE-IPF; among 534 veterans with fILD, 194 (36.3%) had CPFE-fILD. Agreement between computed tomography reports and thoracic radiologist review was high (kappa = 0.78). Annual CPFE prevalence ranged from 71 to 100 per 100,000 veterans, and incidence ranged from 16 to 39 per 100,000 veterans. CPFE was associated with male sex, lower body mass index, greater tobacco history, higher forced vital capacity, reduced forced expiratory volume in 1 second/forced vital capacity ratio, reduced diffusing capacity of the lung for carbon monoxide, and increased oxygen use. CPFE was associated with increased mortality in unadjusted models. However, after adjustment for age, sex, and body mass index, CPFE was not associated with survival for CPFE-IPF versus IPF without emphysema (hazard ratio, 1.13; 95% confidence interval, 0.96-1.33) as well as CPFE-fILD versus fILD without emphysema (hazard ratio, 1.16, 95% confidence interval, 0.82-1.63). Conclusions: CPFE has a high incidence and prevalence among veterans with IPF and fILD and has a distinct phenotype with diagnostic and therapeutic implications. Further studies investigating diagnosis, treatment considerations, and long-term impacts in CPFE are merited.