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Sarcoidosis is granulomatous disease, which complex etiology is yet to be fully discovered. In the majority of cases its course is self-limiting. However it can have different clinical manifestations and can be debilitating condition with great impact on health-related quality of life (HRQL). The aim of our study was to assess if there are any differences in HRQL dependent to gender. We examined a group of 33 males and 42 females (with no differences in mean age, disease activity, TLCO, FEV 1 , FVC, FEV 1 /FVC) with a use of Sarcoidosis Health Questionnaire. We revealed lower total and daily functioning score in female group. Further analyses stratified by sex and activity of the disease presented many significant differences between the groups, revealing important issues for the discussion about gender specific differences in the HRQL of patients with sarcoidosis. In spite of clinical presentation may be similar, expectations and main concerns of sarcoidosis patient can vary between females and males. Therefore, it appears that in terms of education and symptomatic treatment accents should be put differently depending on the gender of the patient. Our results may also point to a need for more gender-oriented patient-physician communication which could enable better understanding, potentially improve adherence to therapy and decrease the risk of possible complications.

Sarcoidosis is an inflammatory disease of unknown etiology. Most commonly it results in the formation of non-caseating granulomas in intrathoracic lymph nodes and lung parenchyma, but the clinical course and picture may be complicated by extrapulmonary involvement and many non-respiratory signs and symptoms which are directly related to the disease. In addition, sarcoidosis patients may suffer from a plethora of symptoms of uncertain or unknown origin. Fatigue is one of these symptoms, and according to some authors it is reported by the majority of patients with active sarcoidosis, but also by a smaller proportion of patients with inactive sarcoidosis, or even with complete clinical and radiological remission. Therefore the term fatigue syndrome is frequently used to name this clinical problem. The definition of fatigue syndrome in sarcoidosis is imprecise and the syndrome is usually recognized by use of validated questionnaires. In this review the uptodate knowledge in this field was presented and different challenges connected with this syndrome were described.

Introduction: Discriminating between active and inactive sarcoidosis may be problematic in everyday clinical practice. There are numerous biochemical markers used in the diagnosis and monitoring of sarcoidosis. Somatostatin receptor (SR) scintigraphy with the use of 99mTc-octreotide may be used to estimate disease activity., Objectives: The aim of the paper was to assess the value of traditional biomarkers (serum angiotensin-converting enzyme [SACE], C-reactive protein, markers of calcium metabolism, bronchoalveolar lavage fluid [BALF] lymphocytes) and a novel biomarker, 8-isoprostane (8-IP) in exhaled breath condensate (EBC), in the assessment of sarcoidosis activity in relation to somatostatin receptor scintigraphy., Patients and Methods: The study included 32 patients with sarcoidosis. Scintigraphy was performed using somatostatin analogue, 99mTc-HYNIC-TOC; planar and SPECT/CT images were recorded. The study group was divided into a subgroup with positive radiotracer uptake (n = 20) and without a visible uptake (n = 12). 8-IP levels were measured in EBC by an immunoenzymatic assay. RESULTS We observed a significantly higher EBC 8-IP levels in the subgroup with positive uptake compared with those with negative uptake (19.1 ± 19.8 vs. 5.4 ± 3.5 pg/ml, P = 0.02). The levels of SACE and the percentage of BALF lymphocytes were also nonsignificantly elevated. In the group of patients with positive scintigraphy results, a positive correlation was observed between the uptake ratio and SACE (r = 0.44, P = 0.041)., Conclusions: The results indicate low value of biochemical markers in the assessment of disease activity. SR scintigraphy may have practical usefulness in the monitoring of sarcoidosis.

Background: Increased activity of metalloproteinases may play a role in the initiation and propagation of inflammation in sarcoidosis, and may also be one of the factors responsible for the development of lung fibrosis. The aim of this study was to verify whether polymorphisms of MMP2 C-735T, MMP7 A-181G, MMP9 T-1702A and tissue inhibitor of metalloproteinase (TIMP)2 G-418C predispose to sarcoidosis., Material/methods: The study included 139 patients with sarcoidosis and 100 healthy subjects. MMPs and TIMP2 mRNA were measured in peripheral blood lysate using real-time RT-PCR. DNA for genetic polymorphism was extracted from peripheral blood by GTC method. Protein concentrations in peripheral blood lysates were measured by ELISA, and MMP2 and 9 activities in BAL fluid were estimated by gel zymography., Results: TT genotype in MMP9 T-1702A was more frequent in sarcoidosis (p<0.0001, OR = 13.71, 95% CI 7.02-26.80) and resulted in higher expression of MMP9 mRNA (p<0.0001). No differences were found between TT and AT/AA patients in terms of radiological stage, lung function test parameters, activity markers and the presence/absence of Löfgren syndrome. There were no differences in the distribution of MMP2, MMP7 and TIMP2 polymorphisms. Messenger RNAs, as well as protein concentrations of MMP2, 7, 9, and TIMP2 were elevated in patients with sarcoidosis (p<0.0001 for each)., Conclusions: The TT homozygotes of MMP9 T-1702A genotype may be predisposed to sarcoidosis. Elevated MMP2, 7, 9, and TIMP2 mRNAs suggest their inducibility.

Objective: This study was designed to examine the mutual relationship between 8-isoprostane in exhaled breath condensate (EBC) and superoxide anion generation by bronchoalveolar lavage fluid (BALF) cells in patients with sarcoidosis., Design: About 29 patients with sarcoidosis, 34 healthy never smokers (control group for EBC) and 15 healthy never smokers (control group for BAL) were examined. EBC was collected directly before bronchoscopy. 8-Isoprostane was measured by ELISA, and superoxide anion by colorimetry., Results: Exhaled breath condensate 8-isoprostane is increased in sarcoidosis (median, 25-75 percentile): 2.50; 2.50-3.90 versus 6.20; 2.50-16.95 pg/ml, p ≤ 0.05). Spontaneous superoxide anion release from BALF cells was significantly elevated only in patients with a high percentage of lymphocytes in BALF (6.42 ± 1.24 vs. 23.52 ± 4.30 nmol/10(6) cells, p ≤ 0.01). There were no correlations between 8-isoprostane and spontaneous or stimulated superoxide anion release., Conclusions: We confirmed higher concentrations of EBC 8-isoprostane in sarcoidosis and higher spontaneous release of superoxide anion from BALF cells in patients with sarcoidosis. The increase of EBC 8-isoprostane is not directly related to superoxide anion released from BALF cells.

Introduction: The imbalance between metalloproteinases (MMPs) and their tissue inhibitors TIMPs) may be involved in the pathogenesis of lung sarcoidosis, a granulomatous inflammatory disease which may lead to lung fibrosis., Objectives: The aim of the study was to verify whether the expression of MMP-9, MMP-2, TIMP-1, and TIMP-2 in peripheral lung biopsies of patients with sarcoidosis correlate with lung function tests, radiological pattern, and bronchoalveolar lavage (BAL) cells. We compared the expression of MMPs and TIMPs between patients with sarcoid-positive vs. - negative biopsy and fibrosing vs. non-fibrosing high-resolution computed tomography (HRCT)pattern., Patients and Methods: We examined patients with histologically proven stage II and III sarcoidosis (n = 17). Immunohistochemistry with antibodies against the studied molecules was performed in the lung and bronchial tissue specimens obtained from transbronchial lung biopsies. The radiological pattern was evaluated based on HRCT. The total cell number and percentage of cells were calculated in the BAL samples., Results: MMPs and TIMPs were present in the cells of sarcoid granuloma, and were more prevalent in the parenchyma than in the bronchi. We found no correlation between MMP-9, MMP-2, TIMP-1, TIMP-2 and HRCT pattern or BAL cells. There were inverse associations between MMP-9 and FEV1 (% predicted), and also between MMP-2 and maximal expiratory flow 25-75% (L and % predicted) in patients with sarcoidosis diagnosed by transbronchial lung biopsy. There were no differences in the measured parameters between patients with and without fibrotic changes and between those with negative vs. positive lung biopsy results., Conclusions: Our study provides an indirect evidence for a potential involvement of MMPs/TIMPs in the sarcoid inflammation of the distal airways.

Sarcoidosis is a systemic granulomatous disease with a variety of presentations. One of the known symptoms are altered vitamin D metabolism and hypercalcemia. In our study, we aimed to assess associations between disease activity, inflammatory parameters, and vitamin D and calcium status. The secondary aim was to find any dependencies between calcium and vitamin D metabolism and fatigue and quality of life in patients with sarcoidosis. We enrolled 58 patients with sarcoidosis (47 classified as active disease, 11 classified as non-active) and compared them with 25 healthy volunteers. Calcium concentration was significantly higher in the study group than in healthy controls. It correlated with some inflammatory markers but not with vitamin D status. Not calcium nor vitamin D, but phosphate concentration correlated with life quality was assessed with the use of the Sarcoidosis Health Questionnaire. An association between phosphate concentration and fatigue was also noted, but it did not reach statistical significance. Calcium concentration was higher in patients with sarcoidosis, but it was not an indicator of the disease activity, while phosphate concentration was significantly lower in patients with active sarcoidosis. [ABSTRACT FROM AUTHOR]

Background: miRNAs control important cellular functions including angiogenesis/angiostasis or fibrosis and reveal altered expression during pathological processes in the lung. Methods: The aim of the study was to investigate the expression of selected miRNAs (miR-let7f, miR-15b, miR-16, miR-20a, miR-27b, miR-128a, miR-130a, miR-192 miR-221, miR-222) in patients with pulmonary sarcoidosis (n = 94) and controls (n = 50). The expression was assessed by q-PCR in BALF cells and peripheral blood lymphocytes (PB lymphocytes). For statistical analysis, the Kruskal-Wallis test, Mann-Whitney U- test, Neuman-Keuls' multiple comparison test, and Spearman's rank correlation were used. Results: In BALF cells, significantly higher expression of miR-192 and miR-221 and lower expression of miR-15b were found in patients than controls. MiR-27b, miR-192 and miR-221 expression was significantly higher in patients without parenchymal involvement (stages I) than those at stages II-IV. Patients with acute disease demonstrated significantly higher miR-27b, miR-192 and miR-221 expression than those with insidious onset. For PB lymphocytes, patients demonstrated significantly greater miR-15b, miR-27b, miR-192, miR-221 and miR-222 expression, but lower miR-let7f and miR-130a expression, than controls. Stage I patients demonstrated significantly higher miR-16 and miR-15b expression than those in stages II-IV, and patients with the acute form demonstrated higher miR-130a and miR-15b expression. In BALF cells, miR-16 and miR-20a expression was significantly higher in patients with lung volume restriction, and miR-let7f was higher in the PB lymphocytes in patients with obturation. Several correlations were observed between the pattern of miRNA expression, lung function parameters and selected laboratory markers. Conclusion: The obtained results suggest that the studied miRNAs play a role in the pathogenesis of sarcoidosis, and that some of them might have negative prognostic value. [ABSTRACT FROM AUTHOR]

Background: The chronic course of pulmonary sarcoidosis can lead to lung dysfunction due to fibrosis, in which the signalling pathways TGF-β/Smad and VEGF-A may play a key role. Methods: We evaluated immunoexpression of TGF-β1, Smad2, 3, and 7, and VEGF-A in serum and bronchoalveolar lavage (BAL) fluid of patients (n = 57) classified according to the presence of lung parenchymal involvement (radiological stage I vs. II-III), acute vs. insidious onset, lung function test (LFT) results, calcium metabolism parameters, percentage of BAL lymphocytes (BAL-L%), BAL CD4+/CD8+ ratio, age, and gender. Immunoexpression analysis of proteins was performed by ELISA. Results: The immunoexpression of all studied proteins were higher in serum than in BAL fluid of patients (p >0.05). The serum levels of TGF-β1 (p = 0.03), Smad2 (p = 0.01), and VEGF-A (p = 0.0002) were significantly higher in sarcoidosis patients compared to healthy controls. There were no differences within the sarcoidosis group between patients with vs. without parenchymal involvement, acute vs. insidious onset, or patients with normal vs. abnormal spirometry results. In patients with abnormal spirometry results a negative correlation was found between forced vital capacity (FVC) % predicted value and TGF-β1 immunoexpression in BAL fluid, and positive correlations were observed between the intensity of lung parenchymal changes estimated by high-resolution computed tomography (HRCT scores) and Smad 2 level in serum. Conclusions: TGF-β/Smad signalling pathway and VEGF-A participate in the pathogenesis of sarcoidosis. BAL TGF- β1, and Smad 2 in serum seem to be promising biomarkers with negative prognostic value, but further studies are required to confirmed our observations. [ABSTRACT FROM AUTHOR]

Background: 8-Isoprostane (8-IP) is a marker of lipid peroxidation. Elevated concentrations have been reported in BAL fluid and exhaled breath condensate (EBC) in sarcoidosis (S). To validate the prognostic value of this marker we tested whether: 1. high initial EBC 8-IP predispose to more severe disease; 2. low initial concentrations increase a chance of early remission; 3. remissions are connected with the decrease of EBC 8-IP. Methods: 40 patients (S) have been examined initially (V1) and after 8.5 ± 0.5 months (V2). EBC 8-IP concentrations were measured by ELISA. Chest X-ray, lung function test, serum ACE and Ca2+ concentrations, 24 hrs Ca2+loss, abdominal ultrasonography, symptoms evaluation were performed. Results: We confirmed higher concentrations of 8-IP in EBC of patients with sarcoidosis (p = 0.001). Relative risk (RR) of persistence of disease at V2 when initial 8-IP was above 20 pg/mL was 1.04, and the frequency distributions estimated by χ² test were not significantly different. A chance (RR) of early complete remission when V1 8-IP was below DL, was 3.33 (p = 0.04 by χ² test). A significant decrease of 8-IP at V2 was observed only in patients who received treatment (p = 0.03), but not in those with spontaneous remission. Conclusions: We come to the conclusion, that low initial 8-IP may be a positive prognostic factor. A decrease of 8-IP in treated patients reflects a non-specific effect of treatment and is not related to mere regression of disease. [ABSTRACT FROM AUTHOR]

The article presents information on a study which investigates the association between exhaled breath condensate (EBC) and BAL fluid (BALF) eicosanoids. The study involved 28 sarcoidosis patients and 17 healthy subjects. It used enzyme immunoassay to measure cysteinyl leukotrienes (CysLTs), and leukotriene B4 (LTB4) in EBC.

Sarcoidosis is a chronic multisystemic disease of unknown etiology. It is characterized by formation of non-caseating granulomas in involved organs. The disease most often affects lungs and hilar lymph nodes. Head and neck organs involvement is rare. In this paper we present three cases of sarcoidosis. In all of them enlargement of parotid glands and cervical lymph nodes were primary symptoms of the disease. All patients underwent surgical biopsy of affected organs and then radiological and functional examination of respiratory system. In one case intrathoracic sarcoidosis was revealed. In the other cases no systemic manifestations were detected. No progression of the disease was revealed in the follow-up examination in any of the patients. [ABSTRACT FROM AUTHOR]