Search

Diagnosis of sarcoidosis is mainly based on radiological examinations. The most important one is chest X-ray, which in typical cases reveals bilateral enlarged hilar lymph nodes, in a proportion of patients also concomitant parenchymal changes, rarely isolated parenchymal infiltrations or signs of lung fibrosis. The next step is chest computed tomography (CT), most often of high resolution, although strict indications for CT have been defined. Monitoring of sarcoidosis is based on the assessment of serial chest X-ray examinations. Indications for CT in a patient with completed diagnosis are limited. Positron emission tomography (PET) is a valuable tool for the evaluation of especially difficult diagnostic cases, for the assessment of disease activity, identification of yet unidentified extrapulmonary locations or selection of an optimal place for biopsy. In the present paper you will find how to use these radiological techniques for the diagnosis and monitoring of sarcoidosis., (© 2018 MEDPRESS.)

Introduction: The nature of post-sarcoidosis fatigue syndrome (PSFS) is unknown and tools for the assessment of health quality (HQ) in these patients have not been fully assessed. The aim was to validate the Polish version of sarcoidosis health questionnaire (SHQ) and verify the association of HQ with fatigue and depressive symptoms among Polish patients with PSFS., Material and Methods: 71 patients with sarcoidosis (34 women, the mean age 47) were divided to: PSFS (n = 21), active sarcoidosis (S-A, n = 27) and sarcoidosis with complete remission (S-R, n = 23) groups. Fatigue Assessment Scale (FAS) was used to define significant fatigue (≥ 22 points). Polish version of SHQ was prepared by the authors and validated. Beck Depression Index (BDI) and Patient Health Questionnaire 9 (PHQ-9) were used to evaluate self-reported depressive symptoms., Results: Polish version of SHQ was proved reliable and valid. HQ was worse and depressive symptoms were more frequent in PSFS and S-A when compared with S-R group. SHQ total score correlated negatively with depressive symptoms (r = -0.787 for BDI and r = -0,755 for PHQ-9, p < 0.01). A negative correlation between SHQ and FAS score was found (r = -0.784, p < 0.01). FAS score correlated with depressive symptoms (r = 0.726 for BDI and r = 0.755 for PHQ-9, p < 0.01)., Conclusion: Polish version of SHQ is a valuable tool for the assessment of HQ in sarcoidosis. HQ is impaired in PSFS comparing to patients with complete remission, but is comparable to active sarcoidosis. Depressive symptoms impact HQ and may influence perception of fatigue. Both fatigue and depression have a negative impact on HQ in sarcoidosis.

Elevated COX-2 activity is associated with the development of chronic lung diseases leading to bronchial obstruction, including sarcoidosis. The aim of the study was to examine expression pattern of COX-2 messenger RNA (mRNA). Expression was performed by q-PCR method in bronchoalveolar lavage (BAL) cells and peripheral blood (PB) lymphocytes in sarcoidosis patients (n = 61) and control group (n = 30). Analysis of COX-2 mRNA expression level in BAL fluid and PB revealed downregulation in sarcoidosis and control groups. In PB lymphocytes, the statistically significant difference between patients and controls was observed (P = 0.003, Mann-Whitney U test), with higher expression in patients. There were no statistically significant differences between patients without and with parenchymal involvement (stages I vs. II-IV), between patients with acute vs. insidious onset of disease and between patients with abnormal vs. normal spirometry (P > 0.05, Mann-Whitney U test). Results suggest that expression of COX-2 mRNA in patients with pulmonary sarcoidosis is not related to clinical classifications.

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.

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.

Sarcoidosis is an orphan inflammatory disorder that can virtually affect any organ or system in the body, although the lungs and lymph nodes are most frequently involved. Sarcoidosis is believed to derive from an interaction between environmental and genetic agents. Many studies emphasize a strong association between certain human leukocyte antigen (HLA) alleles and sarcoidosis susceptibility. Several new insights have allowed the further evaluation of other candidate genes with a potential function in the immunopathogenesis of sarcoidosis. This review summarizes recent advances in the identification of novel molecular markers that may play a role in different stages of disease, such as the acute phase of inflammation, granuloma formation and fibrosis. Furthermore, this article elucidates the role of both TGF-b/Smad and (HIF)-1a-VEGF-ING-4 signaling pathways in the development of sarcoidosis. The potential epigenetic regulation of the processes occurring in sarcoidosis by miRNA is also discussed.

Introduction:  Sustained inflammation in sarcoidosis may lead to lung fibrosis. The activity of numerous chemokines responsible for proliferation and activity of T lymphocytes may play a crucial role in this process and may have predictive value. These include cytokines induced by interferon γ, such as CXCL9, 10, and 11-ligands of chemokine receptor CXCR3., Objectives:  The aim of the study was to estimate the role of CXCR3 ligands in the pathogenesis of sarcoidosis and the predictive value of their concentrations in bronchoalveolar lavage (BAL) fluid. , Patients and Methods:  CXCL9, 10, and 11 concentrations in BAL fluid were measured by an enzyme‑linked immunosorbent assay in patients with sarcoidosis (n = 59) and controls (n = 34). A total of 46 patients were followed up for 24 months to compare the results between the subgroups with complete remission and with chronic disease., Results:  Protein-standardized CXCL11 concentrations in BAL fluid from patients with stage II sarcoidosis were higher than in those with stage I (median [interquarile range], 0.95 [0.26-2.39] vs. 0.32 [0.13-0.74] pg/μg protein, P = 0.02). CXCL10 levels in BAL fluid from patients without Löfgren syndrome were higher compared with those the syndrome (0.69 [0.51-1.05] vs. 0.40 [0.27-0.70] pg/μg protein, P = 0.05). None of these markers predicted the chronic course of the disease. CXCL10 levels in BAL fluid correlated with serum angiotensin‑converting enzyme, and CXCL11 levels with parenchymal lesions on high‑resolution computed tomography. Only nonstandardized CXC11 concentrations in BAL fluid were higher in sarcoidosis., Conclusions:  Our results support the hypothesis that cytokines CXCL9, 10, and 11 may be involved in the pathogenesis of chronic sarcoidosis. However, the lack of notable differences between the sarcoidosis and control groups, as well as the lack of associations with the chronic course suggest that they should not be considered as potential prognostic markers.

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 chi2 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 chi2 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.

Introduction: Hepatocyte growth factor (HGF) is a strong mitogen stimulating lung epithelial cell growth. Elevated levels of HGF have been reported in various biological materials of patients with acute respiratory distress syndrome and in patients recovering from pneumonia or pneumonectomy. Sarcoidosis may be complicated by lung fibrosis. Consequently, HGF could be considered a new biomarker identifying patients with a higher risk of lung fibrosis. The aim of the study was to verify whether: 1. HGF is measurable in bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC); 2. HGF in BALF or EBC is impaired in sarcoidosis; and 3. HGF correlates with chosen activity and prognostic markers., Material and Methods: Sixty-four EBC and 30 BALF of sarcoid patients, and 15 and 9 of healthy controls, respectively, were collected for the measurement of HGF using an ELISA test., Results: HGF was detectable in 62% of EBC samples (56% sarcoidosis and 87% of controls) and in all the BALF samples. EBC and BALF concentrations were not different in comparison to the controls. Moreover, no correlation was found between EBC/BALF concentrations and radiological stage, lung function tests, duration of disease, number of relapses, BALF lymphocytes, serum ACE, or serum and urine calcium concentrations., Conclusions: HGF is detectable in BAL and EBC. However, it does not distinguish sarcoidosis patients from healthy subjects. The above, as well as the lack of correlations with various parameters of disease activity and severity rule out EBC/ /BALF HGF as a biomarker for sarcoidosis monitoring.

Introduction: Increased generation of superoxide anion (O(2)(-).) by bronchoalveolar lavage (BAL) cells has been reported in various inflammatory disorders. However, the clinical relevance of this phenomenon is unclear., Objectives: The aim of the study was to investigate whether production of O(2)(-). is enhanced in smoking-related chronic bronchitis and sarcoidosis, and to assess a relationship between O(2)(-). generation and lung function impairment and changes in BAL cellular pattern., Patients and Methods: Forty-two patients with sarcoidosis, 24 smokers with chronic bronchitis, and 17 controls were examined. A number/percentage of BAL cells was calculated. Spontaneous and phorbol myristate acetate (PMA)-stimulated O(2)(-). production was measured in BAL cells. Spirometry was performed., Results: Patients with smoking-related chronic bronchitis produced more O(2)(-). spontaneously (6.42 -/+1.24 vs. 15.39 -/+2.47 nmol/106 cells, P = 0.003) and after stimulation (3.73 -/+1.32 vs. 14.76 -/+2.79 nmol/106 cells; P = 0.001). PMA-stimulated excess production correlated with the percentage of neutrophils (r = 0.66, P = 0.0005). In sarcoidosis, only spontaneous production of O(2)(-). was higher (vs. 18.07 -/+2.49 nmol/106 cells, P = 0.004) and correlated with the percentage of BAL lymphocytes. There was no correlation between O(2)(-). production and lung function parameters., Conclusions: Patients with smoking-related chronic bronchitis produce more O(2)(-)., and this phenomenon is related to BAL neutrophils. In sarcoidosis, spontaneous release of O(2)(-). from BAL cells is related to the extent of lymphocytic alveolitis. Higher O(2)(-). generation did not impair lung function.

Background: Measurement of inflammatory mediators in exhaled breath condensate (EBC) is an easy and noninvasive diagnostic method, which has gained popularity in the past few years. However, the source of these mediators is not precisely defined. It has been only presumed that inflammatory cells present in the airway lumen are the main source. Therefore, the aim of this study was to verify the relationship between EBC and BAL fluid (BALF) eicosanoids, and the percentage, number, and activity of cells in BALF., Methods: In 28 sarcoidosis patients and 17 healthy subjects, 8-isoprostane, cysteinyl leukotrienes (CysLTs), and leukotriene B4 (LTB4) were measured in EBC by enzyme immunoassay. Eicosanoids were also examined in BALF in the study group. Cell count, percentage, and superoxide production by BALF cells were estimated., Results: The mean (+/- SEM) CysLT and 8-isoprostane concentrations were higher in the sarcoidosis group (6.5 +/- 0 vs 27.82 +/- 6.65 pg/mL, respectively; and 2.67 +/- 0.16 vs 13.95 +/- 2.59 pg/mL, respectively). There were positive correlations between EBC and BALF 8-isoprostane concentration (r = 0.68, p < 0.0001) and LTB4 concentration (r = 0.43; p = 0.026). EBC LTB4 levels correlated with the number of lymphocytes per milliliter of BALF. The percentage and number of eosinophils in BALF correlated with EBC 8-isoprostane and BALF CysLT concentrations. No positive correlation was found between concentrations of EBC eicosanoids and percentages BALF lymphocytes, BALF macrophages, or superoxide production., Conclusions: The levels of 8-isoprostane and CysLT are elevated in EBC in sarcoidosis patients; however, a lack of correlation with BALF lymphocyte percentage does not encourage us to recommend the measurement of eicosanoids as activity markers. The positive correlation of EBC 8-isoprostane and BALF CysLT concentrations with the percentage of eosinophils in BALF, and the higher percentage of eosinophils in BALF from patients with grade 3 sarcoidosis, may suggest the possible prognostic value.