Outcomes of lung transplantation in patients with telomere-related forms of progressive fibrosing interstitial lung disease pulmonary fibrosis: A systematic review

Background Lung transplantation (LTX) is the last life-extending option for patients with progressive fibrosing interstitial lung diseases (fILD). Between 12% and 71% of patients with fILD are patients with underlying telomere-dysfunction (trILD) related to pathogenic telomere-related gene (TRG) variants and/or short telomere length. TrILD patients tend to have earlier disease onset, faster progression, and worse prognosis causing them to be referred for LTX more often. Regarding LTX outcomes in trILD, there are contradictory reports on patient and graft survival, as well as numerous other outcomes. There is no consensus on whether trILD is associated with poorer outcomes after LTX and what considerations regarding candidacy are appropriate.Methods We aimed to systematically review LTX outcomes of patients with trILD in comparison to those with non-trILD.Results A systematic literature search yielded 13 studies that met the inclusion criteria including 933 LTX, 281 in trILD, and 652 in non-trILD. Despite large heterogeneity in the methodological study quality and reported outcomes among the studies, patient and graft survival after LTX in trILD did not evidently seem inferior to LTX in non-trILD. However, there may be increased risk of specific complications, such as cytopenias, airway complications, and cytomegalovirus-reactivation.Conclusions In summary, due to large heterogeneity in methodological study quality and reported outcomes, no firm conclusions can be drawn. Patient and graft survival do not seem unequivocally inferior in patients with trILD deemed eligible for LTX. On top of limited available high-quality data, specific patient selection and post-transplant management strategies may affect the currently acquired results. As such, differences may exist regarding transplant-related outcomes, which could require special attention and consideration. Further high-quality comparative studies on LTX outcomes in trILD are needed to draw final conclusions and provide recommendations regarding patient selection and post-transplantation management.