Combined pulmonary fibrosis and emphysema (CPFE) in systemic sclerosis

Background/Purpose: Combined pulmonary fibrosis and emphysema (CPFE) is a recently defined syndrome, in which centrilobular and/or paraseptal emphysema in upper lung zones coexist with pulmonary fibrosis in the lower lobes. These patients have a characteristic lung function profile, with unexpected subnormal dynamic and static lung volumes, contrasting with a significant reduction of carbon monoxide transfer capacity (DLco) and exercise hypoxemia. CPFE has recently been described in association with connective tissue disease. The aim of this study was to describe the recently individualized syndrome of CPFE in a population of patients with systemic sclerosis (SSc).

Methods: In this multicenter case-control study, we retrospectively investigated data from patients with SSc who also had CPFE. The demographic characteristics of the patients, the results of pulmonary function testing, high-resolution computed tomography, and treatment, and the outcomes of the patients were analysed retrospectively. For each patient with CPFE and SSc, two patients with SSc and pulmonary fibrosis without emphysema were included as controls.

Results: Thirty one SSc patients with CPFE were identified and paired with 62 controls. In one center (Cochin), the prevalence of CPFE was 3.5% in SSc patients, and 8.2 % in SSc with interstitial lung disease. CPFE patients with SSc were more likely to be male (77% vs 18%, p< 10^-5), smokers (84 vs 37%, p< 10^-5), and to have a limited SSc (62 vs 26%, p< 0.01) than control SSc patients. Pulmonary function testing revealed a marked decrease in DLco at diagnosis (39% vs 50% of predicted, p<0.001) and at the end of follow-up (30% vs 44%, p<0.0001) in CPFE patients compared to controls, despite similar lung volumes (total lung capacity 78 vs 81%, forced vital capacity 78 vs 78%). Autoantibody profiles did not differ significantly between SSc patients with or without CFPE.

During follow up, CPFE patients with SSc developed more frequently pulmonary hypertension (48 vs 12%, p<0.0001), had more frequent unscheduled hospitalisation (48% vs 22%, p<0.01) and had decreased survival (p<0.05 by Log rank test) as compared to those with SSc and pulmonary fibrosis without emphysema.

Conclusion: The CPFE syndrome presents with distinct pulmonary manifestations within the spectrum of lung diseases occurring in patients with SSc, with a higher risk of pulmonary hypertension and a shorter survival as compared to those with pulmonary fibrosis without emphysema.