, Volume 196, Issue 5, pp 543–552 | Cite as

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

  • 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



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.


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.


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.


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.


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


Pirfenidone Idiopathic pulmonary fibrosis Transbronchial lung cryobiopsy 



This project was part funded by an unrestricted educational grant from Roche Pharmaceuticals, Basel, Switzerland.

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.

Supplementary material

408_2018_140_MOESM1_ESM.docx (19 kb)
Supplementary material 1 (DOCX 18 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Nicola Ronan
    • 1
    • 2
  • Deirdre M. Bennett
    • 3
  • Kashif A. Khan
    • 1
    • 2
  • Yvonne McCarthy
    • 1
  • Darren Dahly
    • 1
  • Louise Bourke
    • 4
  • Adeline Chelliah
    • 4
  • Alberto Cavazza
    • 5
  • Kevin O’Regan
    • 6
  • Fiachra Moloney
    • 6
  • Barry J. Plant
    • 1
    • 2
  • Michael T. Henry
    • 1
    • 2
  1. 1.Health Research Board Clinical Research FacilityUniversity College CorkCorkIreland
  2. 2.Department of Respiratory MedicineCork University HospitalCorkIreland
  3. 3.Medical Education UnitUniversity College CorkCorkIreland
  4. 4.Department of HistopathologyCork University HospitalCorkIreland
  5. 5.Department of Pathology, Arcispedale S Maria NuovaIstituti di Ricovero e Cura a Carattere ScientificoReggio EmiliaItaly
  6. 6.Department of RadiologyCork University HospitalCorkIreland

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