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

Abstract

This review aims to provide an overview of pre-transplant antifibrotic therapy on peri-transplant outcomes and to address the possible role of antifibrotics in lung transplant recipients with chronic lung allograft dysfunction.Lung transplantation is an established treatment modality for patients with various end-stage lung diseases, of which idiopathic pulmonary fibrosis and other progressive fibrosing interstitial lung diseases are growing indications. Theoretically, widespread use of antifibrotics prior to lung transplantation may increase the risk of bronchial anastomotic complications and impaired wound healing.Long-term graft and patient survival are still hampered by development of chronic lung allograft dysfunction, on which antifibrotics may have a beneficial impact.Antifibrotics until the moment of lung transplantation proved to be safe, without increasing peri-transplant complications. Currently, best practice is to continue antifibrotics until time of transplantation. In a large multicentre randomised trial, pirfenidone did not appear to have a beneficial effect on lung function decline in established bronchiolitis obliterans syndrome. The results of antifibrotic therapy in restrictive allograft syndrome are eagerly awaited, but nonrandomised data from small case reports/series are promising.

Antifibrotics and lung transplantation: A Spanish multicentre case‐controlled study

“…Regarding post‐transplant complications, no significant differences were found in either group, except for the fact that, despite being equally frequent, chest wall dehiscences appeared earlier in patients with IPF who had reached the transplantation stage while taking antifibrotic drugs. Although the half‐life of both drugs is short (2.4 h for pirfenidone and 9.5 h for nintedanib), 24 one of the main concerns in patients on these drugs who undergo lung transplantation is the possibility of poorer healing and significant perioperative morbidity. However, we found no differences in the dehiscence of the bronchial sutures—another serious complication.…”

Diagnostic performance of electronic nose technology in chronic lung allograft dysfunction

“…More results are expected later in 2022. 37 Finally, if all treatment options fail re-transplantation can be a last resort to treat advanced CLAD. Nevertheless, a minority of patients qualifies for re-transplantation and outcomes are inferior to primary transplantation.…”

Lung transplantation for interstitial lung disease: evolution over three decades

“…However, IPF patients are particularly negatively affected when such age-specific restrictions are applied. 28 …”

“…This is especially important in the antifibrotic era, where attenuation of disease progression could delay the need for lung transplantation beyond the age of eligibility. 28 The International Society for Heart and Lung Transplantation does not endorse a strict upper age limit, and candidacy in elderly patients remains a centre-specific decision. 29 …”