Combined Pulmonary Fibrosis and Emphysema (CPFE) Clinical Features and Management

René Hage,^1,2 Fiorenza Gautschi,^1,2 Carolin Steinack,^1,2 Macé M Schuurmans<sup>1,2

1</sup>University Hospital Zurich, Division of Pulmonology, Zurich, Switzerland; ²University of Zurich, Faculty of Medicine, Zurich, Switzerland

Correspondence: René Hage
University Hospital Zurich, Division of Pulmonology, Raemistrasse 100, Zurich 8091, Switzerland
Tel +41 44 2559111
Email rene.hage@usz.ch

Background: Combined pulmonary fibrosis and emphysema (CPFE) is an underrecognized syndrome characterized by chronic, progressive disease with a dismal prognosis. Frequent co-morbidities with a higher incidence than in idiopathic pulmonary fibrosis or emphysema alone are pulmonary hypertension (WHO group 3) in 47– 90% of the patients and lung cancer in 46.8% of the patients.
Objective: Review current evidence and knowledge concerning diagnosis, risk factors, disease evolution and treatment options of CPFE.
Methods: We searched studies reporting CPFE in original papers, observational studies, case reports, and meta-analyses published between 1990 and August 2020, in the PubMed, Embase, Cochrane Library, Wiley Online Library databases and Google Scholar using the search terms [CPFE], [pulmonary fibrosis] OR [IPF] AND [emphysema]. Bibliographies of retrieved articles were searched as well. Further inclusion criteria were publications in English, French, German and Italian, with reference to humans. In vitro data and animal data were not considered unless they were mentioned in studies reporting predominantly human data.
Results: Between May 1, 1990, and September 1, 2020, we found 16 studies on CPFE from the online sources and bibliographies. A total of 890 patients are described in the literature. Although male/female ratio was not reported in all studies, the large majority of patients were male (at least 78%), most of them were current or former heavy smokers.
Conclusion: CPFE is a syndrome presenting with dyspnea on exertion followed by disruptive cough and recurrent exacerbations. The disease may progress rapidly, be aggravated by pulmonary hypertension WHO group 3 and is associated with an increased risk of lung cancer. Smoking and male sex are important risk factors. There is a need for more research on CPFE especially relating to etiology, influence of genetics, treatment and prevention options. Antifibrotic therapy might be an interesting treatment option for these patients.

Keywords: COPD, pulmonary hypertension, autoimmune hypothesis