Risk of anastomotic dehiscence in patients with pulmonary fibrosis transplanted while receiving anti-fibrotics: Experience of the Australian Lung Transplant Collaborative

J Heart Lung Transplant. 2019 May;38(5):553-559. doi: 10.1016/j.healun.2019.02.005. Epub 2019 Feb 12.

Abstract

Background: The new anti-fibrotics pirfenidone and nintedanib are now in widespread use for idiopathic pulmonary fibrosis (IPF), but they may have an adverse impact on pathways involved in wound-healing. This study aimed to establish the safety of anti-fibrotic therapy in the peri-transplant period, particularly with regard to healing of the bronchial anastomosis.

Methods: In this work we assessed a retrospective cohort of patients who had undergone lung transplantation with a diagnosis of pulmonary fibrosis between January 2012 and December 2017. Pre-transplant use of pirfenidone and nintedanib was identified. Anastomotic dehiscence of any extent was determined at bronchoscopy. Known risk factors for anastomotic dehiscence were evaluated in both anti-fibrotic and control groups.

Results: Two hundred twenty-six patients (160 males; mean age 59.7 ± 7.8 years) underwent transplantation in Australia for pulmonary fibrosis during the study period. Forty (17.7%) were receiving anti-fibrotics at the time of transplantation (29 with pirfenidone and 11 with nintedanib). There were 7 anastomotic dehiscence events, with overall incidence rates of 7.5% and 2.2% in the anti-fibrotic and control groups, respectively (p = 0.08). All episodes of dehiscence in the anti-fibrotic group and 2 of 4 in the comparator group occurred <6 weeks post-transplant. Survival at 30days was 100% and 96% (p = 0.21) and at 1 year was 93% and 88% (p = 0.01) in the anti-fibrotic and comparator groups, respectively. Two patients with dehiscence died. The other 5 anastomotic defects resolved, with 1 requiring stent insertion.

Conclusions: The incidence of bronchial dehiscence after transplantation for IPF is low and is not significantly higher in patients receiving anti-fibrotic therapy at the time of transplantation.

Keywords: anastomotic dehiscence; anti-fibrotic; lung transplant; nintedanib; pirfenidone; pulmonary fibrosis.

Publication types

  • Multicenter Study

MeSH terms

  • Anastomotic Leak / epidemiology
  • Anastomotic Leak / etiology*
  • Australia / epidemiology
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy
  • Idiopathic Pulmonary Fibrosis / surgery*
  • Indoles / therapeutic use*
  • Lung Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Prednisone / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use
  • Retrospective Studies
  • Risk Management
  • Wound Healing*

Substances

  • Glucocorticoids
  • Indoles
  • Protein Kinase Inhibitors
  • nintedanib
  • Prednisone