Safety of Anti-Fibrotic Therapy for Interstitial Lung Disease Prior to Lung Transplantation

Abstract

Purpose The use of anti-fibrotic drugs before lung transplantation (LTx) may interfere with wound-healing and increase peri-operative bleeding. The aim of this study was to assess the safety of pre-transplant administration of anti-fibrotic agents as a bridge to LTx for interstitial lung disease (ILD). Methods This is a single-center retrospective cohort study. A total of 91 patients with ILD underwent LTx between June 2008 and December 2019. Among them, 36 patients received anti-fibrotic therapy (pirfenidone: n=27; nintedanib: n=5; both: n=4) before LTx (treatment group), and 55 patients did not receive it (control group). Early post-transplant outcome was compared between the two groups. The anti-fibrotic treatment was discontinued the day before surgery in brain-dead donor lung transplantation, whereas it was discontinued in advance in living-donor lobar lung transplantation (17±12 days before LTx). Results Blood loss during surgery did not significantly differ between the two groups (median: 740 ml in the treatment group vs. 1185 ml in the control group, P=0.38). Re-thoracotomy for hemothorax was required in 3 patients (8.3%) in the treatment group and 2 patients (3.6%) in the control group (P=0.38). Chest wound healed normally in all patients. Anastomotic airway complication occurred in 4 patients (11.1%) in the treatment group and 5 patients (9.1%) in the control group (P=0.74). Among the 4 patients who developed airway complication in the treatment group, two patients with bronchial stenosis required bronchoscopic intervention, including balloon dilation, endobronchial stent placement, and laser ablative therapy. Other two patients with anastomotic dehiscence could be conservatively managed. No patient died within the first 30 days after LTx, and in-hospital mortality was similar in both groups (2.8% in the treatment vs. 1.8% in the control group, P=1.00). Conclusion Pre-transplant anti-fibrotic therapy did not negatively affect the early post-transplant outcomes without any significant increase in the risk of post-operative would-healing and bleeding problems and anastomotic airway complications.