Pathogenesis of combined pulmonary fibrosis and emphysema. Common pathogenetic pathways

摘要

Emphysema is defined on pathology grounds as an abnormal permanentenlargement of air spaces distal to the terminal bronchioles, accompaniedby the destruction of alveolar walls and without obvious fibrosis1. IdiopathicPulmonary Fibrosis (IPF) has a distinct appearance on HRCT defined as theUIP and possible UIP pattern2. Although initially considered as two separatedisorders (as it is clearly depicted in the definition of emphysema),emphysema and fibrosis have been found to co-exist. The widespread useof HRCT given its high accuracy for the diagnosis of emphysema and IPFhelped in recognizing the co-existence of these two diseases. The associationof IPF and emphysema was initially described by Wiggins et al in 19903.The term Combined Pulmonary Fibrosis and Emphysema (CPFE) was firstproposed by Cottin et al4, who retrospectively described a homogenousgroup of 61 patients with both emphysema of the upper zones and diffuseparenchymal lung disease with fibrosis of the lower zones of the lungs onchest computed tomography. The patients were all smokers, male (butone), presenting with dyspnea on exertion, relatively preserved lung volumesand a disproportionate reduction in DLco. Although in the pivotalstudy by Cottin, patients with connective tissue disease were excluded, theCPFE syndrome has been described in the latter group5. Interestingly, ina retrospective study by Tzouvelekis et al6, a significant increased numberof CPFE patients exhibited elevated serum ANA with or without positivep-ANCA titers compared to patients with IPF without emphysema. Furthermore,patients with CPFE and positive autoimmune markers (mainlyANA) exhibited improved survival compared to patients with a negativeautoimmune profile. This improvement in survival was also correlated withthe presence of a massive infiltration of clusters of CD20+ B cells forminglymphoid follicles6.