PT  - JOURNAL ARTICLE
AU  - Jonathan Miles
AU  - James W Pinkerton
AU  - Sara J Bonvini
AU  - Eric Dubuis
AU  - Michael A Wortley
AU  - Silvia Pontis
AU  - Marcello Trevisani
AU  - Gino Villetti
AU  - Riccardo Patacchini
AU  - Philip L Molyneaux
AU  - Toby M Maher
AU  - Mark A Birrell
AU  - Maria G Belvisi
TI  - Modelling IPF-associated chronic cough: role for oxidative stress?
AID  - 10.1183/13993003.congress-2020.604
DP  - 2020 Sep 07
TA  - European Respiratory Journal
PG  - 604
VI  - 56
IP  - suppl 64
4099  - http://erj.ersjournals.com/content/56/suppl_64/604.short
4100  - http://erj.ersjournals.com/content/56/suppl_64/604.full
SO  - Eur Respir J2020 Sep 07; 56
AB  - Introduction: Chronic cough is a key symptom that plagues the lives of IPF patients, indeed, it is often the reason the disease is initially diagnosed. The aim of this project was to develop a pre-clinical model of IPF-associated cough and compare the mediator profiles with clinical samples, to aid in the search for effective treatments.Methods: Male guinea pigs (around 325g) were intratracheally dosed with vehicle (saline) or bleomycin (6 USP/kg) and coughs were quantified through manual observation of in-cage video footage, by watching 4.5 hours a day, for 3 weeks. Lung tissue, bronchoalveolar lavage fluid (BALF) and blood was harvested from a parallel group of animals. These were used to assess the extent of fibrosis and measure mediator production (e.g. a marker of oxidative stress: 8-isoprostane). Human BALF was obtained from IPF patients and healthy controls.Results: Spontaneous coughing was recorded in guinea pigs given bleomycin, which was associated with an increase in lung fibrosis and BALF 8-isoprostane (a marker of oxidative stress). We noted similar increases in BALF 8-isoprostane levels in the clinical samples.Conclusions: We have developed a preclinical model to aid in the search for a treatment for IPF-associated coughing. Furthermore, initial data suggests that an increase in oxidative burden (a known trigger of coughing) could be an attractive target.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 604.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).