Histopathological and molecular analysis of idiopathic pulmonary fibrosis lungs from patients treated with pirfenidone or nintedanib

Histopathology
Yingwei ZhangPaul J Wolters

Abstract

The objective of this study was to quantify the impact of pirfenidone or nintedanib treatment on lung histopathology and molecular mediators of fibrosis in patients with idiopathic pulmonary fibrosis (IPF). We collected lung tissue from IPF patients at the time of lung transplantation. Histopathological changes were quantified using a blinded scoring method. Proteins associated with senescence or active TGF-β were quantified in lung tissues by immunoblot and immunostaining. Histopathological quantification showed similar amounts of dense collagen fibrosis, fibroblast foci and alveolar macrophages in untreated or pirfenidone- or nintedanib-treated IPF patients. There was less diffuse alveolar damage and organising pneumonia in pirfenidone-treated IPF patients. Lungs of nintedanib-treated patients had a trend towards less lymphocytic interstitial infiltration. There was no difference in expression of p-SMAD3, p21 or p16 in the lungs of untreated, pirfenidone- or nintedanib-treated IPF patients. Alveolar epithelial cells, but not fibroblast foci, were immunoreactive to p16. Pirfenidone or nintedanib treatment did not inhibit activation of senescence programming in cultured lung epithelial cells mediated by hydrogen peroxide. Pirfe...Continue Reading

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Citations

Jan 23, 2020·American Journal of Respiratory Cell and Molecular Biology·Saleela M RuwanpuraPhilip G Bardin
Nov 24, 2018·The European Respiratory Journal·Argyris Tzouvelekis, Paul J Wolters
Aug 21, 2019·Journal of Clinical Medicine·Hasancan BilgiliWojciech J Piotrowski
Mar 20, 2019·The European Respiratory Journal·Paul J Wolters, Vincent Cottin
Jul 10, 2020·European Respiratory Review : an Official Journal of the European Respiratory Society·Martina KorfeiSilke Meiners
Oct 22, 2020·Clinical Science·Kaj E C BloklandJanette K Burgess
Jan 14, 2021·Seminars in Arthritis and Rheumatism·B WuM Kapoor
Aug 21, 2021·European Respiratory Review : an Official Journal of the European Respiratory Society·Saskia BosRobin Vos
Oct 30, 2021·Frontiers in Pharmacology·K M RoachP Bradding

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