Combined Pulmonary Fibrosis and Emphysema: When Scylla and Charybdis Ally

Abstract

Combined pulmonary fibrosis and emphysema (CPFE) is a recently recognized syndrome that, as its name indicates, involves the existence of both interstitial lung fibrosis and emphysema in one individual, and is often accompanied by pulmonary hypertension. This debilitating, progressive condition is most often encountered in males with an extensive smoking history, and is presented by dyspnea, preserved lung volumes, and contrastingly impaired gas exchange capacity. The diagnosis of the disease is based on computed tomography imaging, demonstrating the coexistence of emphysema and interstitial fibrosis in the lungs, which might be of various types and extents, in different areas of the lung and several relative positions to each other. CPFE bears high mortality and to date, specific and efficient treatment options do not exist. In this review, we will summarize current knowledge about the clinical attributes and manifestations of CPFE. Moreover, we will focus on pathophysiological and pathohistological lung phenomena and suspected etiological factors of this disease. Finally, since there is a paucity of preclinical research performed for this particular lung pathology, we will review existing animal studies and provide suggestions for the development of additional in vivo models of CPFE syndrome.

Keywords: CPFE; animal models; emphysema; lung fibrosis.

Figure 1

Histopathological findings in combined pulmonary fibrosis and emphysema (CPFE) lungs. The donor and CPFE lungs were stained with HE (first two rows) and trichrome (last two rows) staining. In comparison to the donor’s lungs, CPFE pathology is characterized by emphysema, occasionally accompanied by localized fibrous thickening of alveolar septa known as smoking-related interstitial fibrosis (SRIF), interstitial fibrosis with numerous fibrotic foci, fibrotic regions and honeycombing. Scale bars = 100 µm.

Figure 2

Pulmonary vascular remodeling in the pathology of combined pulmonary fibrosis and emphysema (CPFE). The lungs of donors and patients with chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and CPFE were stained with HE. Remodeled pulmonary vessels in these diseases were shown in comparison to each other and in contrast to the “healthy” donor vessels. Scale bars = 50 µm.