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

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 30 days 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.