Lung transplantation for pulmonary alveolar proteinosis: a retrospective international multicentre analysis

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disease. Only a small number of case reports describing lung transplantation (LTx) as a treatment option for PAP have been published. Due to this limited evidence, current guidelines on LTx for PAP remain vague. To address this gap, we collected cases of LTx for PAP worldwide. METHODS: 214 centres were approached to contribute any cases of LTx performed for PAP. Re-transplantations and multi-organ transplantations were excluded. Patients were divided into two groups based on the presence of PAP recurrence after LTx. Time-to-event analyses were performed using Kaplan–Meier curves and Cox proportional-hazards modelling was performed with PAP recurrence as a time-dependent covariate. RESULTS: At a response rate of 64%, 31 centres contributed 63 patients. Most had primary PAP (n=20; 39.2%). Six patients with secondary PAP were identified (11.8%), while seven (13.7%) had congenital and 18 (35.3%) unclassified PAP. Aetiology was not specified in 12. Patients underwent transplantation at a median (interquartile range) 11 (3–17) years after initial diagnosis. Nine (15%) patients developed PAP recurrence after LTx. No significant difference was found regarding patient characteristics between the patients with versus without recurrence. Freedom from recurrence was 96.2% (1 year), 83.5% (5 years) and 70.1% (10 years) post-LTx. PAP recurrence as time-dependent covariate was not significantly associated with graft loss (hazard ratio 1.88, 95% CI 0.51–6.91; p=0.342) in a Cox proportional-hazards model. CONCLUSION: LTx provides excellent peri-operative and long-term outcomes for patients with end-stage PAP and should be recommended in treatment guidelines. Although recurrence of PAP occurs in ∼15% of cases, overall survival appeared unaffected in our limited dataset.