HRCT and histopathological evaluation of fibrosis and tissue destruction in IPF associated with pulmonary emphysema

Abstract

Idiopathic pulmonary fibrosis has been associated with emphysema in cigarette smokers as a new clinical entity: combined pulmonary fibrosis and emphysema (CPFE). In order to compare histomorphometrical, roentgenological and immunohistochemical aspects of usual interstitial pneumonia (UIP) with and without associated pulmonary emphysema, 17 patients with biopsy-proven UIP were evaluated. Morphometrical evaluation of lung parenchyma destruction was used to divide patients in two subgroups: emphysema/UIP (n=9) and UIP alone (n=8); four patients with biopsy-proven emphysema without fibrosis were also evaluated. At HRTC scan, emphysematous lesions were prevalent in the upper fields of both emphysema/UIP and emphysema groups and the distribution of fibrotic lesions was similar in emphysema/UIP compared to UIP alone. The semiquantitative histopathological fibrotic score was also similar in emphysema/UIP and UIP alone. In addition, the expression of tumor necrosis factor (TNF)-alpha, matrix metalloproteinase (MMP)-2, MMP-9, MMP-7 and membrane type 1-metalloproteinase (MT1-MMP) by fibroblasts of myofibroblastic foci was similar in emphysema/UIP and UIP alone patients. In contrast, fibroblasts in areas of parenchymal destruction of emphysema/UIP expressed MMP-2, MMP-9, MMP-7 and MT1-MMP at variable but significantly higher levels when compared to emphysema subjects, in the presence of similar levels of TIMP-1, TIMP-2 and TNF-alpha. Fibrotic and emphysematous lesions in emphysema/UIP patients appear to follow the roentgenological and histopathological patterns expected for either UIP or emphysema. Interstitial fibroblast activation is more pronounced in the areas of lung destruction in emphysema/UIP compared to those with emphysema alone, as for exaggerated tissue remodeling.

Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study

“…This observation is intriguing, as it may identify a particular phenotype of patients. We previously showed a higher expression of metalloproteinases in the lungs of CPFE patients compared with those without CE, hypothesising that this could determine a more aggressive activation of fibroblasts, remodelling and tissue destruction and, consequently, a more precipitous course [50]. Whether this phenomenon is reflected by the severely impaired gas exchange commonly observed in CPFE, and whether this is implicated in the occurrence of AE, has to be further elucidated.…”

The impact of emphysema in pulmonary fibrosis

“…centrilobular and/or paraseptal emphysema in 90% of cases [26]), and diffuse infiltrating fibrosing lung disease at the bases (subpleural reticular opacities, honeycomb images and traction bronchiectasis), with more frequent ground-glass opacities than in IPF. However, patients with CPFE show a high HRCT fibrotic score (p50.015) [13,14,37].…”

Combined pulmonary fibrosis and emphysema: an increasingly recognized condition

“…Laboratory animal studies have demonstrated that oxidative stress inducing inflammatory cell activation, elevated matrix metalloproteinase levels causing proteolytic activity, ( 17 , 18 ) and overexpression of other mediators, such as PDGF, ( 19 ) TNF-α, and TGF-β, ( 20 , 21 ) are potential pathways explaining the lesions that lead to emphysema and fibrosis. A study analyzing inflammatory mediators in BAL fluid from patients with IPF showed significantly higher concentrations of chemokine (C-X-C motif) ligand 5 and chemokine (C-X-C motif) ligand 8 in those with concomitant HRCT findings of emphysema.…”

“…Estudos em animais de laboratório demonstraram que o estresse oxidativo que induz a ativação de células inflamatórias, os níveis elevados de metaloproteinases da matriz que causam a atividade proteolítica ( 17 , 18 ) e a superexpressão de outros mediadores, tais como PDGF, ( 19 ) TNF-α e TGF-β, ( 20 , 21 ) são potenciais vias que explicam as lesões que levam a enfisema e fibrose. Um estudo em que se analisaram os mediadores inflamatórios no lavado broncoalveolar de pacientes com FPI mostrou concentrações significativamente maiores das quimiocinas CXCL5 e CXCL8 naqueles que concomitantemente apresentaram enfisema na TCAR.…”