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

Yoshiaki Zaizen; Yuri Tachibana; Yukio Kashima; Andrey Bychkov; Kazuhiro Tabata; Kyoko Otani; Yoshiaki Kinoshita; Yasuhiko Yamano; Kensuke Kataoka; Kazuya Ichikado; Masaki Okamoto; Tomoo Kishaba; Remi Mito; Koichi Nishimura; Mari Yamasue; Kazuki Nabeshima; Kentaro Watanabe; Yasuhiro Kondoh; Junya Fukuoka

doi:10.3390/jcm10050895

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

J Clin Med. 2021 Feb 24;10(5):895. doi: 10.3390/jcm10050895.

Authors

Yoshiaki Zaizen^{1

2}, Yuri Tachibana¹, Yukio Kashima³, Andrey Bychkov^{1

4}, Kazuhiro Tabata⁵, Kyoko Otani⁶, Yoshiaki Kinoshita⁷, Yasuhiko Yamano⁸, Kensuke Kataoka⁸, Kazuya Ichikado⁹, Masaki Okamoto², Tomoo Kishaba¹⁰, Remi Mito¹¹, Koichi Nishimura¹², Mari Yamasue¹³, Kazuki Nabeshima¹⁴, Kentaro Watanabe¹⁵, Yasuhiro Kondoh⁸, Junya Fukuoka^{1

4}

Affiliations

¹ Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
² Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-830-0011, Japan.
³ Department of Pathology, Hyogo Prefectural Awaji Medical Center, 1-1-137 Shioya, Sumoto, Hyogo 656-0021, Japan.
⁴ Department of Pathology, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba 296-8602, Japan.
⁵ Division of Pathology, Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
⁶ Department of Pathology, Yodogawa Christian Hospital, 1-7-50 Kunijima, Higashiyodogawa-ku, Osaka 533-0024, Japan.
⁷ Department of Respiratory Medicine, Fukuoka University Chikushi Hospital, 1-1-1 Zokumyouin, Chikushino, Fukuoka 818-8502, Japan.
⁸ Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake, Seto, Aichi 489-8642, Japan.
⁹ Department of Respiratory Medicine, Saiseikai Kumamoto Hospital, 5-3-1 Chikami, Minami-ku, Kumamoto 861-4193, Japan.
¹⁰ Department of Respiratory Medicine, Okinawa Chubu Hospital, 281 Miyazato, Uruma, Okinawa 904-2293, Japan.
¹¹ Department of Respiratory Medicine, Kumamoto University Hospital, 1-1-1 Honjou, Chuou-ku, Kumamoto 860-8556, Japan.
¹² Department of Respiratory Medicine, National Center for Geriatrics and Gerontology, 7-430 Morioka-chou, Oobu, Aichi 474-8511, Japan.
¹³ Department of Respiratory Medicine, Oita University Hospital, 1-1 Idaigaoka, Hasamamachi Yufu, Oita 879-5593, Japan.
¹⁴ Department of Pathology, Fukuoka University School of Medicine and Hospital, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
¹⁵ Department of Respiratory Medicine, Nishi Fukuoka Hospital, 3-18-8 Ikinomatsubara, Nishi-ku, Fukuoka 819-8555, Japan.

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.