Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb 24;10(5):895.
doi: 10.3390/jcm10050895.

Alveolar Epithelial Denudation Is a Major Factor in the Pathogenesis of Pleuroparenchymal Fibroelastosis

Yoshiaki Zaizen  1   2 , Yuri Tachibana  1 , Yukio Kashima  3 , Andrey Bychkov  1   4 , Kazuhiro Tabata  5 , Kyoko Otani  6 , Yoshiaki Kinoshita  7 , Yasuhiko Yamano  8 , Kensuke Kataoka  8 , Kazuya Ichikado  9 , Masaki Okamoto  2 , Tomoo Kishaba  10 , Remi Mito  11 , Koichi Nishimura  12 , Mari Yamasue  13 , Kazuki Nabeshima  14 , Kentaro Watanabe  15 , Yasuhiro Kondoh  8 , Junya Fukuoka  1   4
Affiliations

Alveolar Epithelial Denudation Is a Major Factor in the Pathogenesis of Pleuroparenchymal Fibroelastosis

Yoshiaki Zaizen et al. J Clin Med. .

Abstract

The pathogenesis of pleuroparenchymal fibroelastosis (PPFE), a rare interstitial lung disease, remains unclear. Based on previous reports and our experience, we hypothesized that alveolar epithelial denudation (AED) was involved in the pathogenesis of PPFE. This multicenter retrospective study investigated the percentage of AED and the features of the denudated areas in 26 PPFE cases, 30 idiopathic pulmonary fibrosis (IPF) cases, and 29 controls. PPFE patients had lower forced vital capacities and higher residual volume/total lung capacities in pulmonary function tests compared to IPF and control patients. Histopathologically, subpleural fibroelastosis was observed in PPFE, and AED was observed in 12.01% of cases in the subpleural or interlobular septa regardless of fibroelastosis. The percentage of AED in the PPFE group was significantly higher than that in the IPF group (6.84%; p = 0.03) and the normal group (1.19%; p < 0.001). In the IPF group, the percentage of AED and the presence of PPFE-like lesions in the upper lobes were examined radiologically, but no correlation was found. We showed that AED frequently occurred in PPFE. AED was less frequent in IPF, which, in combination with imaging data, suggests that PPFE may have a different pathogenesis from IPF.

Keywords: classification; epithelial denudation; epithelial detachment; idiopathic pulmonary fibrosis; image analysis; pathogenic mechanism; pathology; pleuroparenchymal fibroelastosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Histopathological images with annotations used in the current study. The red and green arrowheads each indicate the same location. The details of the colors in the annotation lines are as follows: red, subpleural zone; yellow, paraseptal zone; green, alveolar epithelial denudation (AED) in the subpleural zone; blue, AED in the paraseptal zone. (A): Annotated pleuroparenchymal fibroelastosis (PPFE) case in middle power view. (B): Annotated PPFE case in high power view. (C): Annotated idiopathic pulmonary fibrosis (IPF) case in middle power view. (D): Annotated IPF case in high power view.
Figure 2
Figure 2
Histopathological findings in the cases investigated for the current study. (A,B): In the PPFE group, fibroelastosis was significant under the pleura, and there was marked increase in elastic fibers with EVG staining. (C,D): In the IPF group, the development of dense fibrosis and fibroblastic foci was significant in subpleural and interlobular septa, and lung architecture destruction was highlighted with EVG staining.
Figure 3
Figure 3
Epithelial denudation in the PPFE group. (A): Alveolar epithelial denudation (AED) was detected in the border between the subpleural fibroelastosis and normal lung (blue arrowhead). (B): Cytokeratin AE1/AE3 immunohistochemical staining. The denudated epithelium and detached surface were highlighted in this staining (red arrowhead). (C,D): AED was also seen in the subpleural area without fibroelastosis (arrowhead).
Figure 4
Figure 4
Epithelial denudation in the IPF group. (A,B): Dense fibrosis and abrupt changes in the normal lung were seen, with noticeable AED in those areas (arrowhead). (C,D): Fibroblastic foci were well observed, some of which were also accompanied by AED, but most were covered with regenerating epithelium (arrowhead).
Figure 5
Figure 5
Percentage of alveolar epithelial denudation in each group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Amitani R., Niimi A., Kuse F. Idiopathic pulmonary upper lobe fibrosis (IPUF) Kokyu. 1992;11:693–699.
    1. Frankel S.K., Cool C.D., Lynch D.A., Brown K.K. Idiopathic pleuroparenchymal fibroelastosis: Description of a novel clinicopathologic entity. Chest. 2004;126:2007–2013. doi: 10.1378/chest.126.6.2007. - DOI - PubMed
    1. Travis W.D., Costabel U., Hansell D.M., King T.E., Jr., Lynch D.A., Nicholson A.G., Valeyre D. An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am. J. Respir. Crit. Care Med. 2013;188:733–748. doi: 10.1164/rccm.201308-1483ST. - DOI - PMC - PubMed
    1. Reddy T.L., Tominaga M., Hansell D.M., Von der Thusen J., Rassl D., Parfrey H., Nicholson A.G. Pleuroparenchymal fibroelastosis: A spectrum of histopathological and imaging phenotypes. Eur. Respir. J. 2012;40:377–385. doi: 10.1183/09031936.00165111. - DOI - PubMed
    1. Khiroya R., Macaluso C., Montero M.A., Rice A., Nicholson A.G. Pleuroparenchymal Fibroelastosis: A Review of Histopathologic Features and the Relationship Between Histologic Parameters and Survival. Am. J. Surg. Pathol. 2017;41:1683–1689. doi: 10.1097/PAS.0000000000000928. - DOI - PubMed

LinkOut - more resources