Secondary pulmonary alveolar proteinosis after lung transplantation: a single-centre series

The occurrence of secondary PAP in our single cohort of lung-transplant recipients within a 4-year period suggests a possible under-recognition of this complication in this population. This situation could result from the difficulty in diagnosing PAP using post-transplantation BALF, which often contains microorganisms, inflammatory cells and mucus, or from the absence of routine systematic PAS staining of BALF after lung transplantation. In this setting, the positivity of PAS staining can also allow exclusion of other causes of intra-alveolar material accumulation, such as oedema or fibrin, and causes of vacuolated macrophages as seen with amiodarone toxicity. In our series, histological diagnosis of PAP was additionally supported (when performed) by positive staining with an anti-surfactant antibody (figure 1h). Exclusion of silicoproteinosis was systematically performed by polarized light examination with no birefringent silica particles. In all patients, PAP developed early after lung transplantation (before month 3, post-transplantation) with a fatal outcome being associated with this onset. Diagnosis was delayed in the four case studies and was established only after specific re-examination of the transbronchial biopsies/BALF. In the autoimmune and genetic forms of PAP [6, 9], the alveolar macrophage dysfunction is known to be driven by impaired GM-CSF signalling. A similar impaired GM-CSF pathway was found in one patient by using a recently described test based on the ability of GM-CSF to rapidly increase cell-surface CD11b levels on neutrophils in flow cytometry [6, 9]. A coincidental primary form of PAP was ruled out by the lack of anti-(GM-CSF) antibodies (n=3). The striking lack of involvement of the native lung in recipients of single-lung transplantation may indicate an alveolar macrophage injury linked to a pathogenic process located specifically in the graft; however, this remains to be determined. In addition, the promoting role of immunosuppressive therapy has previously been evoked in cases of symptomatic PAP reported to develop in lung- or kidney-transplant recipients [2-4, 10], including almost all well-described cases related to mammalian target of rapamycin inhibitor (mTOR inh) use [4, 10]. In the lung-transplantation setting, it is important to be able to distinguish between PAP and an acute rejection episode, especially as inter- and intra-lobular septal thickening are included in the features of acute rejection [11, 12]. In our patients, the initial misdiagnosis of PAP was associated with a suspected or proven acute rejection episode, which was treated with increased immunosuppression that possibly worsened the alveolar macrophage dysfunction. Finally, our cases often showed subsequent pulmonary infection, which is consistent with the less-efficient alveolar macrophage reported in PAP for anti-infection defence [13, 14]. Due to these diagnostic challenges, physicians should be aware of this rare, life-threatening, post-transplantation complication in an attempt to provide specific treatment. © Copyright ERS 2017.