Is it possible to predict the outcome of the whole lung lavage (WLL) in pulmonary alveolar proteinosis (PAP)?

Rationale: PAP is a rare disorder characterized by the accumulation of lipoproteinaceous material within alveolar spaces. The clinical course is variable, ranging from an asymptomatic presentation to respiratory failure and death. WLL is the current standard treatment for PAP patients and although it is effective in the majority of cases, disease persistence is not an unusual outcome. Although the introduction of the WLL has changed the natural history of PAP, little is known about the intimate mechanisms of action of WLL. Aims: Our aim is to identify blood biomarkers able to predict the outcome of the WLL: total resolution/persistent improvement (positive outcome) or transient resolution/progressive deterioration (negative outcome). Methods: We collected total RNA from peripheral mononuclear cells of 8 PAP patients who underwent WLL, at the baseline and 24 months from the lavage. After the 24-month follow up, they were dichotomized in positive vs negative outcome and a microarray analysis, with around 20000 genes screened (SurePrint G3 Human Gene, Agilent) was performed. Results: Our preliminary data show 86 genes significantly differentially expressed, between PAP patients with a positive outcome (n=4) vs negative outcome (n=4), which could be predictive of the response to the lavage; whereas WLL seems not to induce difference in gene expression, in the same subject, at least after two years. Conclusion: The identification of an expression signature, able to discriminate between PAP patients with a positive outcome vs negative outcome, will lead us to select biomarkers useful to follow up the clinical response to WLL. Funding: AIFA(FARM7MCPK4), eRARE(EuPAPNet).