Effect of pirfenidone on wound healing in lung transplant patients

Amber Mortensen,Rajat Walia,Lauren Cherrier

doi:10.1186/s40248-018-0129-4

Abstract

BackgroundThe drug pirfenidone has been shown to slow the progression and decrease mortality of idiopathic pulmonary fibrosis (IPF). Its exact mechanism is unknown, but it likely inhibits pro-fibrotic cytokine transforming growth factor beta, a known contributor to wound healing. We evaluated whether patients taking pirfenidone until lung transplantation had increased risk of impaired wound healing post-transplant. This information could determine whether pirfenidone should be discontinued prior to listing to allow for a wash-out period.MethodsWe retrospectively reviewed patients who underwent lung transplantation for pulmonary fibrosis at Norton Thoracic Institute in Phoenix, Arizona, from January 2014 to December 2015.ResultsWe describe 18 patients who took pirfenidone up to a month before transplant. Aside from one patient who experienced sternal dehiscence due to a surgical issue, all remaining patients did well with no evidence of airway dehiscence. Each of these 17 patients had been on pirfenidone for at least 30 days; nine patients had been on pirfenidone for over 90 days. Baseline characteristics including age, sex, body mass index, renal function, liver function, glucose level, pre-transplant corticosteroid use, and post-transplant immunosuppressant therapy were similar.ConclusionsIn our experience, pirfenidone may be safely continued until lung transplantation. Only one patient in our series experienced impaired wound healing related to a surgical issue, even when pirfenidone was continued until lung transplantation. We found no evidence of impaired wound healing or airway complications after lung transplantation in patients who were treated with pirfenidone before lung transplantation.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a progressive disease involving the replacement of normal lung parenchyma with fibrotic tissue
The exact mechanism of action of pirfenidone is unknown [5], but its anti-fibrotic effect is thought to result from inhibition of transforming growth factor beta (TGF-β), a pro-fibrotic cytokine [6]
The incidence of sternal complications with the traditional clamshell incision, which includes sternal dehiscence, has been reported as 34 to 36% [14]. These complications are real threats to the success of a lung transplantation procedure, and so in this study we considered whether the use of pirfenidone pre-transplant would increase the risk of impaired wound healing after lung transplantation

Summary

Introduction

Idiopathic pulmonary fibrosis (IPF) is a progressive disease involving the replacement of normal lung parenchyma with fibrotic tissue. Pirfenidone decreases inflammation and has antioxidant effects [6] In fibrotic diseases such as IPF, TGF-β is excessively produced, accumulating and replacing healthy tissue and leading to overproduction of fibroblasts [7]. The drug pirfenidone has been shown to slow the progression and decrease mortality of idiopathic pulmonary fibrosis (IPF). We evaluated whether patients taking pirfenidone until lung transplantation had increased risk of impaired wound healing post-transplant. This information could determine whether pirfenidone should be discontinued prior to listing to allow for a wash-out period

Methods

Results

Discussion

Conclusion