Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

Objective: To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/µl) (GPA HE) to develop a differentiating strategy. Methods: A retrospective analysis of the POLVAS registry. Results: The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/µl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Conclusion: Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

The Role of Interaction between Mitochondria and the Extracellular Matrix in the Development of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a condition which affects mainly older adults, that suggests mitochondrial dysfunction and oxidative stress, which follow cells senescence, and might contribute to the disease onset. We have assumed pathogenesis associated with crosstalk between the extracellular matrix (ECM) and mitochondria, mainly based on mitochondrial equilibrium impairment consisting of (1) tyrosine kinases and serine-threonine kinase (TKs and ST-Ks) activation via cytokines, (2) mitochondrial electron transport chain dysfunction and in consequence electrons leak with lower ATP synthesis, (3) the activation of latent TGF-ß via αVß6 integrin, (4) tensions transduction via α2ß1 integrin, (5) inefficient mitophagy, and (6) stress inhibited biogenesis. Mitochondria dysfunction influences ECM composition and vice versa. Damaged mitochondria release mitochondrial reactive oxygen species (mtROS) and the mitochondrial DNA (mtDNA) to the microenvironment. Therefore, airway epithelial cells (AECs) undergo transition and secrete cytokines. Described factors initiate an inflammatory process with immunological enhancement. In consequence, local fibroblasts exposed to harmful conditions transform into myofibroblasts, produce ECM, and induce progression of fibrosis. In our review, we summarize numerous aspects of mitochondrial pathobiology, which seem to be involved in the pathogenesis of lung fibrosis. In addition, an increasing body of evidence suggests considering crosstalk between the ECM and mitochondria in this context. Moreover, mitochondria and ECM seem to be important players in the antifibrotic treatment of IPF.

Gender differences in health-related quality of life measured by the Sarcoidosis Health Questionnaire.

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, FEV1, FVC, FEV1/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.

The prognostic value of fixed time and self-paced walking tests in patients diagnosed with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic fibrosing interstitial pneumonia that has an unknown etiology. The natural history of the disease is characterized by a progressive decline in pulmonary function and overall health and well-being. The median survival time is between 2-3 years; however, the disease course is variable and unpredictable. The twelve-minute walking test (12MWT) and six-minute walking test (6MWT) are two fixed time tests that are commonly used in clinical practice. Our short and clinically oriented narrative review attempted to summarize current evidence supporting the use of fixed time, self-paced walking tests in predicting the outcome of patients diagnosed with IPF. A number of studies have justified that the 6MWT is a simple, cost-effective, well documented, fixed time, and self-paced walking test which is a valid and reliable measure of disease status and can also be used as a prognostic tool in patients with IPF. However, there is a need for dedicated and validated reference equations for this population of patients. It is also necessary to fill the knowledge gap about the role of the 12MWT. We hypothesize that it would be useful in evaluating patients that are in the early stages of the disease.

The role of bronchoscopy in diagnosis of chronic cough in adults: a retrospective single-center study.

INTRODUCTION: Cough is one of the most frequent symptoms reported to pulmonologists. The role of bronchoscopy in the diagnostic work-up of chronic cough is not clearly defined. The aim of this study was to evaluate the utility of fiberoptic bronchoscopy (FOB) and additional testing of samples collected during FOB in the differential diagnosis of chronic cough in adults. MATERIAL AND METHODS: This was a single-center retrospective study. Out of 7115 conventional white light FOB examinations, we finally selected 198 with cough as the only indication. RESULTS: In 40.9% of bronchoscopic examinations, no visible cause of cough was found. Visual signs of chronic bronchitis (CB) were detected in 57.6% of reports. Only in 3 cases (1.5%) bronchoscopy revealed a potential cause of chronic cough other than CB. Mycobacterium tuberculosis or other mycobacteria were spotted in none of the samples. In 91.1% of bronchoalveolar lavage (BAL) cytologic examinations, at least one cell count abnormality was detected, but only in case of increased percentage of eosinophils, it might be considered clinically relevant. In 53% of bacteriological culture results, at least one potentially pathogenic bacterium was isolated. CONCLUSIONS: The present study results strengthen the evidence that FOB combined with additional testing of airway specimens obtained during FOB is not a powerful tool in the differential diagnosis of chronic cough, and FOB as a diagnostic tool may be overused. The appropriate timing and decision regarding referral for FOB and additional testing of achieved material requires careful clinical consideration.

Ageing, sex, obesity, smoking and COVID-19 - truths, myths and speculations.

In early December 2019, in the city of Wuhan in Hubei Province, China, the first infections by a novel coronavirus were reported. Since then, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been spreading to other cities and countries becoming the global emerging epidemiological issue and quickly reaching the status of a pandemic. Multiple risk factors of disease severity and mortality have been identified so far. These include old age, male sex, smoking, and obesity. This concise narrative review highlights the important role of these factors in the pathobiology and clinical landscape of Coronavirus Disease 2019 (COVID-19). We especially focused on their significant role in disease severity and mortality. However, in spite of intensive research, most of the presented pieces of evidence are weak and need further verification.

Sarcoidosis and calcium homeostasis disturbances-Do we know where we stand?

The majority of cases involving hypercalcemia in the setting of sarcoidosis are explained by the overproduction of calcitriol by activated macrophages. Vitamin D takes part in the regulation of granuloma formation. However, using vitamin D metabolites to assess the activity of the disease is still problematic, and its usefulness is disputable. In some cases, though, a calcium metabolism disorder could be a valuable tool (i.e. as a marker of extrathoracic sarcoidosis). Although sarcoidosis does not cause a decrease in bone mineral density, increased incidence of vertebral deformities is noted. Despite increasing knowledge about calcium homeostasis disorders in patients with sarcoidosis, there is still a need for clear guidelines regarding calcium and vitamin D supplementation in these patients.

Overexpression of chitotriosidase and YKL-40 in peripheral blood and sputum of healthy smokers and patients with chronic obstructive pulmonary disease.

Background: Despite the absence of endogenous chitin in humans, chitinases are present in the serum of healthy subjects and their levels are increased in a variety of chronic inflammatory conditions. It has been shown that chitotriosidase and structurally related chitinase-like protein-YKL-40 contribute to the pathogenesis of COPD. However, details regarding the relation of their systemic and local airways levels remain unknown. Objectives: To examine peripheral blood and sputum chitotriosidase and YKL-40 expression in smokers and patients with COPD. Methods: Forty patients with COPD, 20 healthy smokers and 10 healthy never-smokers were studied. Serum and induced sputum chitotriosidase protein and activity levels, YKL-40 concentrations, and their gene expression in sputum cells and peripheral blood mononuclear cells (PBMC) were evaluated. Results: Both chitotriosidase protein levels and activity were higher in sputum obtained from COPD subjects compared to healthy never-smokers (P<0.05 and P<0.01, respectively). A similar pattern was observed for PBMC chitotriosidase mRNA expression (P<0.001). YKL-40 serum concentrations were elevated in healthy smokers and COPD subjects compared to healthy never-smokers (P<0.001 and P<0.01, respectively). In sputum, YKL-40 levels were increased in COPD compared to healthy never-smokers (P<0.01). PBMC YKL-40 mRNA expression was increased in COPD and healthy smokers compared to healthy never-smokers (P<0.0001). No associations were found between chitotriosidase or YKL-40 peripheral blood levels and sputum levels. Conclusions: Our results demonstrate that chitotriosidase and YKL-40 are overexpressed in peripheral blood and airways in both healthy smokers and COPD subjects which may indicate smoking-related activation of macrophages, neutrophils, and epithelial cells.

Epithelial alarmin levels in exhaled breath condensate in patients with idiopathic pulmonary fibrosis: A pilot study.

INTRODUCTION: Interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP) are epithelial alarmins involved in innate immune responses and have been shown to play an important role in chronic lung diseases. No data are available regarding their levels in exhaled breath condensate (EBC) in idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To examine IL-25, IL-33 and TSLP levels in the EBC obtained from patients with IPF and compare them to those in healthy controls, patients with asthma and chronic obstructive pulmonary disease (COPD). METHODS: Twenty-three patients with asthma, 25 patients with COPD, 15 patients with IPF and 16 healthy controls were studied. Concentrations of alarmins in the EBC were evaluated by means of ELISA. RESULTS: IL-25 EBC levels were numerically lowest in IPF (25.33 ± 8.84 pg/ml). However, they did not differ significantly from healthy subjects (43.18 ± 5.53 pg/ml), but were significantly lower compared to asthma (72.07 ± 6.03 pg/ml; P < .001). IL-33 EBC levels were significantly increased in IPF (3.41 ± 0.55 pg/ml) compared to healthy controls (1.20 ± 0.60 pg/ml; P < .01) but did not differ from asthma (3.68 pg/ml) and COPD levels (2.47 ± 0.34 pg/ml). There were significant correlations between IL-33 EBC levels and lung diffusion capacity of carbon monoxide (DLco ) absolute (r = .63; P < .05) and % of predicted values (r = .67; P < .01) as well as with time since diagnosis (r = -.59; P < .05) in IPF subjects. TSLP was undetectable in examined samples. CONCLUSION: IL-25 and IL-33 are detectable in the EBC obtained from IPF subjects. Increased levels of IL-33 compared to healthy controls indicate its possible role in the pathobiology of IPF.

E-cigarettes or heat-not-burn tobacco products - advantages or disadvantages for the lungs of smokers.

This is a narrative review considering the use of e-cigarettes and heat-not-burn tobacco products. Advantages and disadvantages of both devices, including biological and clinical consequences, were described. The role of these products in limiting tobacco dependence was also discussed. Possible implications for clinical practice were addressed as well.

Mitochondrial functioning abnormalities observed in blood platelets of chronic smoke-exposed guinea pigs - a pilot study.

BACKGROUND: COPD represents a major global health issue, which is often accompanied by cardiovascular diseases. A considerable body of evidence suggests that cardiovascular risk is elevated by the activation of blood platelets, which in turn is exacerbated by inflammation. As reactive oxygen species are believed to be an important factor in platelet metabolism and functioning, the aim of our study was to perform a complex assessment of mitochondrial function in platelets in chronic smoke exposed animals with COPD-like lung lesions. MATERIALS AND METHODS: Eight-week-old, male Dunkin Hartley guinea pigs (the study group) were exposed to the cigarette smoke from commercial unfiltered cigarettes (0.9 mg/cig of nicotine content) or to the air without cigarette smoke (control group), using the Candela Constructions® exposure system. The animals were exposed for 4 hours daily, 5 days a week, with 2×70 mL puff/minute, until signs of dyspnea were observed. The animals were bled, and isolated platelets were used to monitor blood platelet respiration. The mitochondrial respiratory parameters of the platelets were monitored in vitro based on continuous recording of oxygen consumption by high-resolution respirometry. RESULTS: An elevated respiration trend was observed in the LEAK-state (adjusted for number of platelets) in the smoke-exposed animals: 6.75 (5.09) vs 2.53 (1.28) (pmol O2/[s ⋅ 1108 platelets]); bootstrap-boosted P 1α=0.04. The study group also demonstrated lowered respiration in the ET-state (normalized for protein content): 12.31 (4.84) vs 16.48 (1.72) (pmol O2/[s ⋅ mg of protein]); bootstrap-boosted P 1α=0.049. CONCLUSION: Our results suggest increased proton and electron leak and decreased electron transfer system capacity in platelets from chronic smoke-exposed animals. These observations may also indicate that platelets play an important role in the pathobiology of COPD and its comorbidities and may serve as a background for possible therapeutic targeting. However, these preliminary outcomes should be further validated in studies based on larger samples.

Morphometric analysis of mitochondria in lymphocytes of patients with exacerbations of chronic obstructive pulmonary disease - pilot study.

Introduction: Exacerbations of chronic obstructive pulmonary disease (ECOPD) are important events in the course of the disease, negatively influencing health status and disease progression. Therefore, there is a strong need for deeper understanding of the pathology of ECOPD to elaborate new therapeutic approaches and ameliorate prognoses. Contributions of mitochondria to pathobiology of COPD are still under investigation, although growing evidence suggests their important role in this disease. The aim of our study was to assess the morphometric parameters of mitochondria in lymphocytes of patients with ECOPD. Patients and methods: Lymphocytes were isolated from the peripheral blood of patients with COPD. Transmission electron microscopy was used to assess absolute number of mitochondria per cell, mitochondrial content, and morphometric parameters of individual mitochondria. We also counted indexes for elongation and interconnectivity. Results: Eighteen patients (9 with ECOPD and 9 in the stable period of the disease) were analyzed. We observed significantly lower length of mitochondrion (P=0.03) and significant decrease both in elongation (P=0.03) and interconnectivity indexes (P=0.04) in ECOPD patients. Conclusions: The morphometric parameters of mitochondria in lymphocytes derived from patients during the early period of ECOPD requiring hospitalization are altered in comparison to patients in the stable period of the disease. This suggests their contribution to pathobiology of ECOPD. These preliminary outcomes should be further validated in larger size samples.

The Expression Levels of IL-4/IL-13/STAT6 Signaling Pathway Genes and SOCS3 Could Help to Differentiate the Histopathological Subtypes of Non-Small Cell Lung Carcinoma.

BACKGROUND: The interleukin (IL)-4/IL-13/signal transducer and activator of transcription (STAT) 6 signaling pathway and the SOCS3 gene, one of its main regulators, constitute an important link between the inflammation process in the epithelial cells and inflammatory-related tumorigenesis. The present study is the first to evaluate IL-4, IL-13, STAT6, and SOCS3 mRNA expression in non-small cell lung carcinoma (NSCLC) histopathological subtypes. METHODS: Gene expression levels were assessed using TaqMan® probes by quantitative reverse transcription PCR (qRT-PCR) in lung tumor samples and unchanged lung tissue samples. RESULTS: Increased expression of IL-4, IL-13, and STAT6 was observed in all histopathological NSCLC subtypes (squamous cell carcinoma [SCC], adenocarcinoma [AC], and large cell carcinoma [LCC]). Significantly higher expression of IL-13 and STAT6 (p = 0.019 and p = 0.008, respectively) was found in SCC than in LCC. No statistically significant differences were found for IL-4. Significantly higher SOCS3 expression was found in LCC than in AC (p = 0.027). A negative correlation (rho = -0.519) was observed for the STAT6 and SOCS3 genes in SCC (p = 0.005). No associations were found between gene expression and tumor staging (post-operative Tumor Node Metastasis [pTNM], American Joint Committee on Cancer [AJCC]), patients' age, sex, or history of smoking. CONCLUSIONS: As the number of LCC cases in our study was quite low, the statistically significant results obtained should be confirmed in a larger group of patients, particularly as the relationships identified between increased IL-4, IL-13, and STAT6 mRNA expression and decreased SOCS3 expression suggest that these genes may serve as potential diagnostic markers for differentiating between NSCLC histopathological subtypes.

Is bronchoscopy always justified in diagnosis of haemoptysis?

INTRODUCTION: Fiber-optic bronchoscopy (FOB) is commonly performed in the first line in diagnostic process of haemoptysis. However, lots of evidences suggest that in haemoptysis FOB do not always provide additional, useful information to radiological diagnostics. Therefore, this study aimed to evaluate the validity of performing FOB as a method of choice in first line diagnostics of haemoptysis. MATERIAL AND METHODS: Data comprised consecutively collected results from patients referred for FOB assessment for clinical purposes were retrospectively analysed. We included all examinations, which were performed due to haemoptysis as the only indication, excluding any other lung-related conditions. RESULTS: 114 patients were finally included to the study. The median age was 59 (IQR: 46-64.75). Active bleeding was visualized during examination of 13 (11.4%) patients. Patients with active bleeding did not differ significantly according to age: 59 (54-69) vs 59 (45-64) years; W = 532.5, p-value = 0.27, and gender: c2 = 1.68, p-value = 0.2. On the other hand, in 29 (25.44%) patients, FOB revealed no visible abnormalities. This subgroup of patients was significantly younger - 46 (34-62) years vs 60 (53-67) years; W = 782, p-value = 0.003. CONCLUSION: Low number of visualized active bleeding sites suggest overuse of bronchoscopy in diagnosis of haemoptysis. Indications for this examination should be reconsidered especially in young patients with non-massive haemoptysis.

Skin condition and its relationship to systemic inflammation in chronic obstructive pulmonary disease.

BACKGROUND: The systemic (extrapulmonary) effects and comorbidities of chronic obstructive pulmonary disease (COPD) contribute substantially to its burden. The supposed link between COPD and its systemic effects on distal organs could be due to the low-grade systemic inflammation. The aim of this study was to investigate whether the systemic inflammation may influence the skin condition in COPD patients. MATERIALS AND METHODS: Forty patients with confirmed diagnosis of COPD and a control group consisting of 30 healthy smokers and 20 healthy never-smokers were studied. Transepidermal water loss, stratum corneum hydration, skin sebum content, melanin index, erythema index, and skin temperature were measured with worldwide-acknowledged biophysical measuring methods at the volar forearm of all participants using a multifunctional skin physiology monitor. Biomarkers of systemic inflammation, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α), were measured in serum using commercially available enzyme-linked immunosorbent assays. RESULTS: There were significant differences between COPD patients and healthy never-smokers in skin temperature, melanin index, sebum content, and hydration level (P<0.05), but not for transepidermal water loss and erythema index. No significant difference was noted between COPD patients and smokers in any of the biophysical properties of the skin measured. The mean levels of hsCRP and IL-6 in serum were significantly higher in COPD patients and healthy smokers in comparison with healthy never-smokers. There were significant correlations between skin temperature and serum hsCRP (R=0.40; P=0.02) as well as skin temperature and serum IL-6 (R=0.49; P=0.005) in smokers. Stratum corneum hydration correlated significantly with serum TNF-α (R=0.37; P=0.01) in COPD patients. CONCLUSION: Differences noted in several skin biophysical properties and biomarkers of systemic inflammation between COPD patients, smokers, and healthy never-smokers may suggest a possible link between smoking-driven, low-grade systemic inflammation, and the overall skin condition.

Expression level and methylation status of three tumor suppressor genes, DLEC1, ITGA9 and MLH1, in non-small cell lung cancer.

Despite therapeutic advances, lung cancer remains one of the most common causes of cancer-related death in the world. There is a need to develop biomarkers of diagnostic and/or prognostic value and to translate findings in basic science research to clinical application. Tumor suppressor genes (TSGs) represent potential useful markers for disease detection, progression and treatment target. We tried to elucidate the role of three 3p21.3 TSGs: DLEC1, ITGA9 and MLH1, in non-small cell lung cancer (NSCLC). We assessed their expression pattern by qPCR in 59 NSCLC tissues and in the matched macroscopically unchanged lung tissues. Additionally, we analyzed gene promoter methylation status by methylation-specific PCR in NSCLC samples. We did not find significant correlations between gene expression and methylation. In case of DLEC1 and ITGA9, expression levels were decreased in 71-78 % of tumor samples and significantly different between tumor and normal tissues (P = 0.0001). It could point to their diagnostic value. ITGA9 could also be regarded as a diagnostic marker differentiating NSCLC subtypes, as its expression level was significantly lower in squamous cell carcinoma (P = 0.001). The simultaneous down-regulation of DLEC1 and ITGA9 was observed in 52.5 % of NSCLCs. MSPs revealed high frequencies of gene promoter methylation in NSCLCs: 84 % for DLEC1 and MLH1 and 57 % for ITGA9. Methylation indexes reflected moderate gene methylation levels: 34 % for ITGA9, 27 % for MLH1 and 26 % for DLEC1. However, frequent simultaneous methylation of the studied genes in more than 50 % of NSCLCs suggests the possibility of consider them as a panel of epigenetic markers.

Antipsychotic Drugs Differentially Affect mRNA Expression of Genes Encoding the Neuregulin 1-Downstream ErbB4-PI3K Pathway.

BACKGROUND/AIMS: The PIK3CD gene encodes the delta catalytic subunit of phosphoinositide 3-kinase (PI3K), an element of the neuregulin 1-downstream ErbB4-PI3K signaling pathway, which was recently identified as a molecular target for the treatment of schizophrenia. The aim of the study was to examine the effect of haloperidol (HALO), clozapine (CLO), olanzapine (OLA), quetiapine (QUE) and amisulpride (AMI) on the mRNA and protein expression of genes encoding the elements of ErbB4-PI3K pathway, in a human central nervous system cell line. METHODS: The U-87MG human glioblastoma cell line was used as an experimental model. Quantitative polymerase chain reaction was used to examine the expression of mRNA and enzyme-linked immunosorbent assay for protein expression. RESULTS: At concentrations reached in clinical settings in the brain, CLO, as well as OLA and QUE to a lesser extent, but not AMI and probably not HALO, decreased the mRNA expression of PIK3CD. Protein expression of the gene did not confirm the mRNA expression profile. CONCLUSIONS: The tested antipsychotic drugs (APDs) in the U-87MG glioblastoma cell line differentially regulates the mRNA expression of PIK3CD; however, the protein expression does not confirm these findings. The results of the study may help deepen the understanding of the mechanism of action of APDs.

Altered miRNA expression in pulmonary sarcoidosis.

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.