The aim of the present study was to determine which bronchoalveolar lavage fluid (BALF) and serological parameters reflect the severity of newly diagnosed pulmonary sarcoidosis.Seventy-four previously untreated sarcoid patients were categorised into three groups: 10 patients with Löfgren9s syndrome, 51 patients with stable disease and 13 patients with progressing disease requiring systemic steroid treatment.Total BALF cell count, percentage of alveolar lymphocytes and lymphocyte CD4/ CD8 ratio were not associated with severity of disease. Interestingly, a significant increase in percentages of BALF neutrophils (5.2¡1.1%) and eosinophils (1.7¡0.6%) was observed in sarcoid patients with progressing disease. Elevated percentages of these two cell types were the only BALF parameters associated with a more frequent necessity for systemic steroid therapy. This association between an elevated percentage of BALF neutrophils and the necessity for steroid treatment was observed in advanced as well as early sarcoidosis (radiological types I and II). Serum levels of soluble interleukin-2 receptor and neopterin were significantly elevated in progressing disease compared to stable disease or Löfgren9s syndrome.The present results demonstrate that increased percentages of neutrophils (w3.0%) and eosinophils (w1%) in bronchoalveolar lavage fluid from newly diagnosed pulmonary sarcoidosis is associated with a significantly higher risk of necessity for steroid therapy and may be helpful markers of progressive disease. Furthermore, of the serological parameters investigated, only serum levels of soluble interleukin-2 receptor and neopterin were associated with disease severity. Eur Respir J 2003; 21: 407-413.

BackgroundBronchoalveolar lavage (BAL) is standard diagnostic procedure. Procedural recommendations have been made by pneumological societies including normal values for interpretation of BAL cytology. These normal values derive from small studies in healthy volunteers and have never been analysed for their sensitivity and specificity.ObjectivesThis study aims to analyse sensitivity and specificity of these normal values by assessing lavage cell composition in healthy and diseased individuals.MethodsMore than 6000 BAL were retrospectively analysed for their cellular distribution including BALs of 250 healthy individuals. All BALs were obtained under similar conditions.ResultsBronchoalveolar lavage cytology of healthy individuals mirrors data from previous studies with smoking being the most important manipulator of BAL cytology. Analyses of proposed normal values demonstrate specificity between 80% and 95%, whereas sensitivity ranges between 35% and 65%. Using different mathematical models, a value summing up the differences to ATS‐proposed normal values of the cytological pattern was found to best discriminate between healthy and diseased individuals with a sensitivity of nearly 60% with a predefined specificity of 95%.ConclusionIn summary, our analysis confirmed prior results for healthy volunteers and enlarged these findings by analysing sensitivity and specificity of lavage results in an independent validation cohort of diseased individuals. Thereby, the study may influence the acceptance of BAL in the diagnostic workup of individuals with pulmonary diseases. Additionally, the study proposes a novel value that facilitates lavage interpretation and may therefore be useful in further studies.

Lipids affect the membrane properties determining essential biological processes. Earlier studies have suggested a role of switch-activated protein 70 (SWAP-70) in lipid raft formation of dendritic cells. We used lipidomics combined with genetic and biochemical assays to analyze the role of SWAP-70 in lipid dynamics. TLR activation using LPS as a ligand represented a pathogenic immunogenic stimulus, physical disruption of cell-cell contacts a tolerogenic stimulus. Physical disruption, but not LPS, caused an increase of phosphatidylcholine ether and cholesteryl esters in CD11c immune cells. An increase of ceramide (Cer) was a hallmark for LPS activation. SWAP-70 was required for regulating the increase and localization of Cers in the cell membrane. SWAP-70 controls Cer accumulation through the regulation of pH-dependent acid-sphingomyelinase activity and of RhoA-dependent transport of endosomal contents to the plasma membrane. Poor accumulation of Cers in cells caused decreased apoptosis. This shows that two different pathways of activation, immunogenic and tolerogenic, induce different changes in the lipid composition of cultured CD11c cells, and highlights the important role of SWAP-70 in Cer dynamics in dendritic cells.

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