Pirfenidone exerts beneficial effects in patients with IPF undergoing single lung transplantation

Abstract

Pirfenidone demonstrated pleiotropic antiinflammatory effects in various experimental and clinical settings. The aim of this study was to assess the impact of previous treatment with pirfenidone on short-term outcomes after single lung transplantation (SLTx). Therefore, patients with idiopathic pulmonary fibrosis (IPF) who were undergoing SLTx were screened retrospectively for previous use of pirfenidone and compared to respective controls. Baseline parameters and short-term outcomes were recorded and analyzed. In total, 17 patients with pirfenidone were compared with 26 patients without antifibrotic treatment. Baseline characteristics and severity of disease did not differ between groups. Use of pirfenidone did not increase blood loss, wound-healing, or anastomotic complications. Severity of primary graft dysfunction at 72 hours was less (0.3 ± 0.6 vs 1.4 ± 1.3, P = .002), and length of mechanical ventilation (37.5 ± 34.8 vs 118.5 ± 151.0 hours, P = .016) and intensive care unit (ICU) stay (6.6 ± 7.1 vs 15.6 ± 20.3, P = .089) were shorter in patients with pirfenidone treatment. An independent beneficial effect of pirfenidone was confirmed by regression analysis while controlling for confounding variables (P = .016). Finally, incidence of acute cellular rejections within the first 30 days after SLTx was lower in patients with previous pirfenidone treatment (0.0% vs 19.2%; P = .040). Our data suggest a beneficial role of previous use of pirfenidone in patients with IPF who were undergoing SLTx. K E Y W O R D Sclinical research/practice, critical care/intensive care management, lung (allograft) function/ dysfunction, lung (native) function/dysfunction, lung disease, lung transplantation/ pulmonology, organ transplantation in general

Antifibrotic drugs in lung transplantation and chronic lung allograft dysfunction: a review

“…This is partly due to the implementation of the Lung Allocation Score, prioritising patients most in need of transplantation and most likely to benefit. Dependent on age, comorbidities, local experience and donor availability, both single LTx and bilateral LTx are performed in patients with IPF [3,31].…”

“…Furthermore, VEIT et al [31] demonstrated a possible beneficial effect in IPF patients treated with pirfenidone undergoing single LTx, with shorter length of mechanical ventilation and intensive care stay, less severe primary graft dysfunction at 72 h, and lower incidence of acute cellular rejection within the first 30 days. ZHANG et al [48] also reported that IPF patients treated with pirfenidone had less histopathological evidence of acute lung injury (less diffuse alveolar damage and organising pneumonia) at time of LTx, and a trend towards less lymphocytic interstitial infiltration in lungs of patients treated with nintedanib.…”

“…Pirfenidone has both antifibrotic and anti-inflammatory effects and may, subsequently, have lung allograft protective properties. These effects are believed to be mediated through inhibition of expression of pro-fibrotic and pro-inflammatory cytokines, and enhanced expression of anti-inflammatory cytokines [31,58]. Several reports demonstrated graft-protective effects and reduced development of fibrosis in tracheal, lung and cardiac animal transplant models [58][59][60][61][62][63].…”

“…Several reports demonstrated graft-protective effects and reduced development of fibrosis in tracheal, lung and cardiac animal transplant models [58][59][60][61][62][63]. In addition to its antifibrotic effects, animal models demonstrated the ability of pirfenidone to limit alloimmune inflammatory responses by impairing T-cell activation and proliferation, and by inhibiting effects upon dendritic cell activation, maturation and function [31,58,63,64]. Moreover, it exhibits antioxidant properties by scavenging reactive oxygen species and preventing lipid peroxidation [65,66].…”

Rationale of Using Common Antifibrotic Therapy in Post COVID Fibrosis

“…27 In the ASCEND trial Of Pirfenidone , A decline in FVC occured slowly in both chronic fibrotic lung disease and Idiopathic Pulmonary Fibrosis. 28,29 Acute exacerbation of IPF has the clinical, imaging, and histological characteristics of diffuse alveolar damage mimicking ARDS. 30 The applicability of these data to COVID-19 depends on the rapidity of action of antifibrotic drugs and their introduction before severe acute lung injury leading to diffuse alveolar damage( ARDS), threatens for Mechanical Ventilation has supervened…”