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01-10-2018 | INTERSTITIAL LUNG DISEASE

Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone

Authors: Nicola Ronan, Deirdre M. Bennett, Kashif A. Khan, Yvonne McCarthy, Darren Dahly, Louise Bourke, Adeline Chelliah, Alberto Cavazza, Kevin O’Regan, Fiachra Moloney, Barry J. Plant, Michael T. Henry

Published in: Lung | Issue 5/2018

Abstract

Background

Pirfenidone is a novel anti-fibrotic agent in idiopathic pulmonary fibrosis with proven clinical benefit. Better human tissue models to demonstrate the immunomodulatory and anti-fibrotic effect of pirfenidone are required.

Objectives

The purpose of the study was to use transbronchial lung cryobiopsy (TBLC), a novel technique which provides substantial tissue samples, and a large panel of biomarkers to temporally assess disease activity and response to pirfenidone therapy.

Methods

Thirteen patients with confirmed idiopathic pulmonary fibrosis (IPF) underwent full physiological and radiological assessment at diagnosis and after 6-month pirfenidone therapy. They underwent assessment for a wide range of potential serum and bronchoalveolar lavage biomarkers of disease activity. Finally, they underwent TBLC before and after treatment. Tissue samples were assessed for numbers of fibroblast foci, for Ki-67, a marker of tissue proliferation and caspase-3, a marker of tissue apoptosis.

Results

All patients completed treatment and investigations without significant incident. There was no significant fall in number of fibroblast foci per unit tissue volume after treatment (pre-treatment: 0.14/mm² vs. post-treatment 0.08/mm², p = 0.1). Likewise, there was no significant change in other markers of tissue proliferation, Ki-67 or Caspase-3 with pirfenidone treatment. We found an increase in three bronchoalveolar lavage angiogenesis cytokines, Placental Growth Factor, Vascular Endothelial Growth Factor-A, and basic Fibroblast Growth Factor, two anti-inflammatory cytokines Interleukin-10 and Interleukin-4 and Surfactant Protein-D.

Conclusions

TBLC offers a unique opportunity to potentially assess the course of disease activity and response to novel anti-fibrotic activity in IPF.

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Title: Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone
Authors: Nicola Ronan
Deirdre M. Bennett
Kashif A. Khan
Yvonne McCarthy
Darren Dahly
Louise Bourke
Adeline Chelliah
Alberto Cavazza
Kevin O’Regan
Fiachra Moloney
Barry J. Plant
Michael T. Henry
Publication date: 01-10-2018
Publisher: Springer US
Published in: Lung / Issue 5/2018
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI: https://doi.org/10.1007/s00408-018-0140-8

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Results

Conclusions

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