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Sarcoidosis is an inflammatory, granulomatous disease of unknown etiology that most commonly afflicts the lungs. Despite aggressive immunosuppressive therapies, many sarcoidosis patients still chronically present significant symptoms. Infliximab, a therapeutic tumor necrosis factor alpha (TNF-α) monoclonal antibody (MAb), produced a small but significant improvement in forced vital capacity (FVC) in sarcoidosis patients in a double-blind, placebo-controlled, phase II clinical trial. In the current study, serum samples from this clinical trial were assessed to evaluate the underlying hypothesis that treatment with infliximab would reduce systemic inflammation associated with sarcoidosis, correlating with the extent of clinical response. A 92-analyte multiplex panel was used to assess the expression of serum proteins in 134 sarcoidosis patients compared with sera from 50 healthy controls. A strong systemic inflammatory profile was associated with sarcoidosis, with 29 analytes significantly elevated in sarcoidosis (false-discovery rate, <0.05 and >50% higher than controls). The associated analytes included chemokines, neutrophil-associated proteins, acute-phase proteins, and metabolism-associated proteins. This profile was evident despite patients receiving corticosteroids and immunosuppressive therapies. Following infliximab treatment, sarcoidosis patients expressing the highest levels of TNF-α, who had more severe disease, had the greatest improvement in FVC and reduction in serum levels of the inflammatory proteins MIP-1β and TNF-RII. This study supports the need for further exploration of anti-TNF therapy for chronic sarcoidosis patients, particularly for those expressing the highest serum levels of TNF-α.

We conducted a retrospective study to evaluate an immunochromatographic membrane test (ICT), applied to bronchoalveolar lavage (BAL) fluid samples obtained in patients with suspected pneumonia, for the detection of Streptococcus pneumoniae antigen. The NOW Streptococcus pneumoniae test was assessed on 96 BAL fluid samples. Sensitivity was tested in 20 samples obtained from patients diagnosed as having pneumococcal pneumonia (growth of S. pneumoniae in blood cultures and/or in BAL fluid samples of > or =10(4) CFU/ml). Specificity was tested in BAL fluid samples of nonpneumococcal etiology (n = 41) and in samples with no respiratory pathogen and a total bacterial count of <10(4) CFU/ml (n = 35). Using the ICT, pneumococcal antigen was detected in 29 (30.2%) BAL fluid samples, with a sensitivity of 95.0% (95% confidence interval [CI], 90.6% to 99.4%) and a specificity of 86.8% (95% CI, 80.1% to 93.8%). The ICT was easy to perform and revealed unequivocal and reproducible results. No interference was observed with high cell counts, red blood cells, or elevated protein levels. Four out of 10 false-positive readings occurred in samples with S. pneumoniae counts below the 10(4) CFU/ml threshold limit of pneumonia. In BAL fluid samples obtained after pneumococcal bacteremia, positive test results were found for up to 35 days after bacteremia. The ICT test applied to BAL fluid specimens is reproducible and accurate in the diagnosis of pneumococcal antigen. Further studies are required to establish the impact of the ICT on patient care.

For enumeration of intracellular organisms (ICO) in bronchoalveolar lavage fluid samples, the May-Grünwald-Giemsa (MGG) stain displayed higher interobserver agreement than the acridine orange and Gram stains. The MGG stain offered a reliable enumeration of ICO when 200 cells were counted by one observer.