• Yingwei Zhang, Kirk D Jones, Natalia Achtar-Zadeh, Gary Green, Jasleen Kukreja, Biyun Xu, and Paul J Wolters.
• Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
• Histopathology. 2019 Jan 1; 74 (2): 341-349.

AimsThe 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).Methods And ResultsWe 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.ConclusionPirfenidone and nintedanib do not modulate expression of senescence markers, levels of p-SMAD3 or the amount of fibrosis in IPF lungs. Treated patients have less histopathological evidence of acute lung injury at the time of lung transplantation.© 2018 John Wiley & Sons Ltd.

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