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    Chitotriosidase: a sensitive biomarker of sarcoidosis

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    Chitotriosidase is a member of family of glycosylhydrolases, enzymes involved in the degradation of chitin and chitin-like substrate, identified in a wide variety of organisms. Increased concentrations of chitotriosidase have been reported in several lysosomal storage diseases and more recently also in sarcoidosis. In this study chitotriosidase concentrations were evaluated in a population of 233 sarcoidosis patients and 70 controls in order to verify enzyme specificity and sensibility and to evaluate chitotriosidase prognostic meaning. Chitotriosidase has been found significantly increased in serum of patients with sarcoidosis than in controls (p< 0.0001). ROC curve analysis revealed: cut-off value of 39.50 nmol/h/ml, sensitivity 89,70% and specifity 90%. The analysis of chitotriosidase in different phenotypic subgroups of patients revealed very high serum enzyme levels in symptomatic patients requiring systemic steroid therapy at onset and after disease relapses. In conclusion as a new potential biomarker of sarcoidosis severity, chitotriosidase resulted sensitive, reproducible and easily detectable in serum

    Detection of specific antibodies in immune complexes of Farmer's lung patients

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    The authors examined 23 precipitin-positive symptomatic patients with Farmer's Lung(FL) and compared them to different groups of exposed asymptomatic precipitin-positive(EAPP) and precipitin- negative(EAPN) farmers. The sera were tested using several techniques (i.e., immunodiffusion and ELISA for specific antibodies; polyethylene glycol [PEG] for circulating immune complexes [CIC]) in an attempt to find an in vitro test correlated with the disease which could also provide an insight into the pathogenic mechanisms of Farmer's Lung. Circulating immune complexes formed by IgG were significantly higher in Farmer's Lung patients than in EAPP subjects. In polyethlyene glycol precipitates from Farmer's Lung patients, specific antibodies found by ELISA correlated well with serum positivity, but they were not found in EAPP subjects. The possibility that the circulating immune complexes found were Ig aggregates was ruled out, as was the possibility that the antibodies found in the polyethylene glycol precipitate were also due to an unspecific link. The authors suggest that the circulating immune complexes of Farmer's Lung patients contain specific specific antibodies and that since their composition is different in EAPP subjects, these circulating immune complexes may play a role in the pathogenesis of the disease

    Tryptase concentrations in bronchoalveolar lavage from patients with chronic eosinophilic pneumonia

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    In order to characterize BAL (bronchoalveolar lavage) in CEP (chronic eosinophilic pneumonia) and to investigate the possible role of mast cells and tryptase in the pathogenesis of this interstitial disease, cells and tryptase levels were determined in BAL of patients with CEP and in a group of healthy controls. The results show that a statistically significant increase in tryptase concentration was found in patients with CEP compared with the healthy controls. This is the first report that shows an increase in tryptase levels in CEP and could reflect higher mast cell activation as well as larger mast cell populations in the lungs of these patients. These results strongly support the involvement of mast cells and eosinophils in the immunopathogenesis of CEP

    Impaired interferon gamma production by peripheral blood mononuclear cells and effects of calcitriol in pulmonary sarcoidosis

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    Pulmonary sarcoidosis (S) is a granulomatous disease of unknown etiology characterized by spontaneous release of cytokines and 1,25-dihydroxyvitamin D3 (calcitriol) at the sites of granulomatous reaction. Stimulated by our previous findings that high levels of interferon-gamma (IFN-gamma) occur in this disease and that calcitriol reduces IFN-gamma production by peripheral blood mononuclear cells (PBMC) from normal subjects, we designed the present study to evaluate IFN-gamma production and the effect of calcitriol on the release of this cytokine by PBMC in S patients. The cells were stimulated with staphylococcal enterotoxin A (SEA) and A23187 calcium ionophore. Our results show that SEA- and A23187-stimulated PBMC from patients with S released significantly less IFN-gamma than those from control subjects. Calcitriol at 10(-6) M and 10(-9) M concentrations reduced IFN-gamma production by SEA-stimulated PBMC but this inhibitory effect was lower in S patients than controls. With A23187 we observed different behaviour at the various doses: at low doses calcitriol was as effective as in controls, but at 10(-6) M it was significantly less inhibitory in S than in healthy subjects

    Clinical, laboratory and radiological findings in pulmonary fibrosis with and without connective tissue disease

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    Uncertainty exists over whether to consider "lone" idiopathic pulmonary fibrosis (LIPF) and pulmonary fibrosis associated with connective tissue disorders (PFCTD) as significantly different entities. We retrospectively analysed data collected at the time of first diagnosis in 17 patients with LIPF and in 14 patients with PFCTD and compared survival in the two groups. At first evaluation, the time from onset of respiratory symptoms, spirometric volumes and the diffusing capacity for carbon monoxide were not significantly different between the two groups. However, arterial oxygen tension was significantly lower in LIPF than in PFCTD (63 +/- 3 vs 88 +/- 3 mmHg, p < 0.001). The radiological profusion scores relative to the upper and middle lung fields were significantly higher in LIPF than in PFCTD (upper regions: 6.9 +/- 0.6 vs 3.4 +/- 0.6, p < 0.005 - middle regions: 7.1 +/- 0.5 vs 4.8 +/- 0.7, p < 0.025), whereas the scores relative to the lower fields were similar (7.4 +/- 0.4 in LIPF and 8.4 +/- 0.6 in PFCTD). Survival since onset of respiratory symptoms was significantly better in the PFCTD than in LIPF patients, with a hazard ratio of 4.16 (95% CI 1.12-15.58, p=0.034). Thus, in our series of patients, those with LIPF had a more severe disease than those with PFCTD as shown by the higher frequency of hypoxaemia, the more diffuse pulmonary involvement demonstrated by the chest X-ray and the decreased survival
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