Idiopathic Pulmonary Fibrosis and Lung Transplantation: When it is Feasible

Abstract

Despite the availability of antifibrotic therapies, many patients with idiopathic pulmonary fibrosis (IPF) will progress to advanced disease and require lung transplantation. International guidelines for transplant referral and listing of patients with interstitial lung disease are not specific to those with IPF and were published before the widespread use of antifibrotic therapy. In this review, we discussed difficulties in decision-making when dealing with patients with IPF due to the wide variability in clinical course and life expectancy, as well as the acute deterioration associated with exacerbations. Indeed, the ideal timing for referral and listing for lung transplant remains challenging, and the acute deterioration might be influenced after transplant outcomes. Of note, patients with IPF are frequently affected by multimorbidity, thus a screening program for occurring conditions, such as coronary artery disease and pulmonary hypertension, before lung transplant listing is crucial to candidate selection, risk stratification, and optimal outcomes. Among several comorbidities, it is of extreme importance to highlight that the prevalence of lung cancer is increased amongst patients affected by IPF; therefore, candidates’ surveillance is critical to avoid organ allocation to unsuitable patients. For all these reasons, early referral and close longitudinal follow-up for potential lung transplant candidates are widely encouraged.

Idiopathic pulmonary fibrosis: Current and future treatment

“…[82][83][84] Generally accepted benchmarks for lung transplant referral as well as contraindications to the procedure are based on guidelines proposed by the International Society of Heart and Lung Transplantation (ISHLT). 77,85 Among the key criteria for placement on the transplant list are rapid decline in FVC or DL CO , oxygen desaturation, or decrease in distance covered during 6-min walk test, pulmonary hypertension, or hospitalization due to respiratory decline, pneumothorax, or acute exacerbation. Importantly, telomere shortening and mutations in genes that control telomere function such as Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC) are associated with familial and sporadic cases of IPF and this may be considered in transplant decision-making.…”

“… 82 , 83 , 84 Generally accepted benchmarks for lung transplant referral as well as contraindications to the procedure are based on guidelines proposed by the International Society of Heart and Lung Transplantation (ISHLT). 77 , 85 Among the key criteria for placement on the transplant list are rapid decline in FVC or DL CO , oxygen desaturation, or decrease in distance covered during 6‐min walk test, pulmonary hypertension, or hospitalization due to respiratory decline, pneumothorax, or acute exacerbation.…”

“…Follow‐up generally involves monitoring of FVC, DL CO , and pulmonary hypertension. 85 Chronic lung allograft dysfunction and noncytomegalovirus infections are early causes of mortality. 99 Other possible complications include immunosuppression, drug toxicity, infection, and neoplasia.…”

Management of patients with fibrosing interstitial lung diseases

“… 91 Because the observational IPF Prospective Outcomes (IPF-PRO) Registry found that mortality was independently associated with patient-reported increasing symptom burden and reduced tolerance of physical activity, these manifestations should prompt early referral for lung transplant evaluation. 92 , 93 Although they are beyond the scope of this review, the International Society for Heart and Lung Transplantation has published guidelines for timing lung transplantation in IPF patients based upon various prognostic indicators. 91 …”

Prevention of Drug-Induced Lung Fibrosis via Inhibition of the MRTF/SRF Transcription Pathway

“…While two anti-fibrotics have been clinically approved, they only slow the progression of the disease. The definitive treatment for end-stage lung fibrosis remains lung transplant, which has a median survival as low as 50% at five years post-operation (6). Given the poor prognosis, it is imperative to prevent the development of lung fibrosis before it can progress to end stage disease.…”