EuPAPNet

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by accumulation of lipoproteinaceous, eosinophilic, PAP-positive material within the alveolar spaces . PAP is an extremely rare disorder, occurring worldwide with an estimated prevalence of 0.1 per 100,000 individuals. Being PAP a neglected respiratory disorder, this project was aimed at creating, for the first time, a network for PAP among four centers from three countries (Italy, Germany and the Netherlands) with special interest in this disease. Three centers have skill in management of adult cases and one in pediatric cases of PAP. Major aims of the project were to establish a database to include retrospectively and prospectively cases of PAP. Based on cohorts already available in the centers, we expected to enrol one of the largest series of PAP patients ever reported. We expected to understand more about the epidemiology of the different forms of PAP in Europe. We also collected biomaterials form PAP patients (genomic DNA, blood and BAL cell mRNA, serum) to perform genome-wide and transcriptomic analysis, as well as candidate gene and targeted biochemical investigations, to create a library of biomarkers, putatively predicting the natural history of the disease, and the clinical course following whole lung lavage (WLL), which is the current standard of care of PAP. Molecular and biochemical data obtained provided information on the pathogenesis of the disorder, such as genes/ gene products acting as modifiers of the clinical course. Finally, the outcome of the disorder has been evaluated in function of the different WLL techniques, to establish the optimal methodology. The transnational collaboration planned in the present project was a unique opportunity to translate basic information into the clinical assessment and management of PAP.

Many of the biological measurements reported in the aims of the project are still in progress; we expect to publish these data within the next 12 months. However, at the end of the timeframe allowed for the project, we can list the following results achieved :
1) Establishment of a novel European Network for PAP and Surfactant disorders;
2) Establishment of a common database, first step to the development of a Registry for Surfactact disoders
3) Establishment of a biobank;
4) Completion of a worldwide Survey for whole lung lavage (WLL), the current standard of care for PA, first step to the development of a consensus document aimed at standardising the WLL
5) Publication of 4 peer review papers and 2 abstracts presented to international meetings