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Immunoglobulin E plays an important role in allergic diseases. In patients with allergic asthma, exposure to allergens releases a wide range of proinflamatory mediators, which are responsible for acute and chronic symptoms of the disease. IgE has become an attractive target in allergic asthma. In 2006, in Europe omalizumab became available. Objectives Our knowledge of who will derive the highest benefit from omalizumab therapy is still limited. The aim of this study was to evaluate the efficacy of omalizumab during one year of therapy carried out under real-life conditions in Polish patients with severe allergic asthma. We also attempted to identify predictors for very good responses to treatment. Methods We enrolled 15 patients due to inclusion criteria of the program for severe allergic asthma funded by the National Health Insurance. All the patients were assessed for asthma control, quality of life, daily dose of oral and inhaled corticosteroids, asthma exacerbation rate, and lung function. The effectiveness of the treatment was analyzed after 16 weeks and one year following the inclusion each patient to the therapy. The patients were divided into two groups according to their response to the treatment: very good and good, based on the GETE scale. Results Omalizumab decreased the severity of symptoms, improved asthma control and quality of life in patients. It helped to reduce episodes of asthma exacerbation and the use of systemic corticosteroids. At present, the overall assessment by physicians is still the best and most reliable method of identifying responders to the omalizumab therapy.

Objective/Background The diagnostics of latent tuberculosis infection in Poland using the tuberculin skin test is challenging due to the obligatory Bacillus Calmette–Guerin vaccinations. Interferon-gamma release assays are still very rarely used for diagnostics. We compared the tuberculin skin test and the QuantiFERON-TB Gold In-Tube test to evaluate the degree of latent tuberculosis infection in at-risk groups for tuberculosis (homeless, close contacts, periodic contacts, nursing-home attendees) and in healthy individuals. Methods QuantiFERON-TB Gold In-Tube tests were carried out on 785 individuals from the homeless ( n = 150), close contacts ( n = 171), periodic contacts ( n = 163), nursing-home attendees ( n = 152), and healthy individuals ( n = 149). The tuberculin skin test was performed on 129, 156, 147, 148, and 121 participants, respectively. We evaluated the (a) correlation between serum concentrations of interferon gamma and the tuberculin-skin-test induration diameter; (b) between the number of QuantiFERON-TB Gold In-Tube-positive results and the tuberculin-skin-test diameter in the studied groups; and (c) agreement between both tests and the kappa coefficient using the tuberculin-skin-test diameters of 5, 10, and 15 mm. Results Larger tuberculin-skin-test induration diameters were associated with elevated serum concentrations of interferon gamma. We found a positive correlation between the number of positive QuantiFERON-TB Gold In-Tube screening results and the tuberculin-skin-test induration diameter. The agreement between QuantiFERON-TB Gold In-Tube and tuberculin-skin-test screening results improved with increasing tuberculin-skin-test induration diameter. Conclusion Based on measures of tuberculin-skin-test induration diameter alone, it is difficult to diagnose latent tuberculosis infection with certainty. The agreement of the QuantiFERON-TB Gold In-Tube test increases with the tuberculin-skin-test diameter. Tuberculin-skin-test diameters larger than 15 mm are more likely to be associated with active infection.

Implementation of omalizumab in the treatment of patients with severe allergic asthma opened the possibility of obtaining optimal control of the disease and improving the quality of life. We present a case of a patient with severe allergic asthma qualified to biological treatment with omalizumab. Before qualification, the patient suffered from numerous severe exacerbations and uncontrolled asthma symptoms, despite treatment with high doses of inhaled medications and systemic corticosteroids. After 2 years of biological therapy, we achieved a significant, but incomplete improvement in asthma control, a marked improvement in the quality of life, and a decrease in the number of exacerbations. We observed persistent elevation of eosinophilia in peripheral blood and bronchoalveolar lavage, despite treatment with anti-IgE and systemic corticosteroids, indicating eosinophil phenotype of severe asthma. Moreover, in the course of therapy, the patient reported joint symptoms of unknown origin, which after further testing were eventually attributed to post-steroid complications and osteoarthritis. In appropriately qualified patients, treatment with omalizumab gives hope for significant improvement in asthma control. The development of new biological agents will allow individualizing asthma treatment depending on asthma phenotype and endotype.

Introduction: Airway remodeling is an important factor in persistent obstruction in severe asthma. High resolution computed tomography (HRCT) is an effective method of detecting changes in airway structure. Our aim was to use HRCT to assess changes in airway remodeling in patients with severe allergic asthma who are treated with omalizumab. Material and methods: In 12 patients with severe allergic asthma, HRCT was performed before and after treatment with omalizumab. In selected bronchial airways, parameters were calculated: bronchial wall area (BA), also corrected for body surface area (BSA); percentage of wall area (WA%); and the ratio of luminal area to total bronchial area (Ai/Ao). Clinical response to treatment was assessed using an asthma control questionnaire (ACQ), asthma quality of life questionnaire (AQLQ), and number of exacerbations per year. Assessment included spirometry and blood eosinophilia. Results: Treatment resulted in significant improvement in ACQ (p = 0.035) and AQLQ (p = 0.001). We observed significant reduction in exacerbations per year (p = 0.002) and reduction of daily systemic steroid dose (p = 0.032). FEV₁ and peripheral blood eospinophilia did not change (p = 0.846 and p = 0.221). Airway dimensions (Ai/Ao) of particular bronchi were consistent with the mean of the parameters calculated for all bronchi measured. Although we observed a significant decrease in WA (p = 0.002) and WA/BSA (p = 0.002), WA% and Ai/Ao did not improve (p = 0.39 and p = 0.49). We found no correlations between changes in airways and changes in spirometry or clinical parameters. Conclusion: Despite clinical effectiveness of omalizumab, its effect on airway remodeling may be limited.

Introduction: Diagnosis of sarcoidosis is usually made on the basis of clinical outcome and imaging techniques but its configuration requires detection of noncaseating granulomas in biopsy specimen. The role of bronchoscopic sampling techniques in diagnosis of sarcoidosis is still discussed. Aims and Objectives: To determine the potential benefit of EBUS-TBNA and EBB (endobronchial biopsy) combination, application of cell blocks and puncturing more than one station of lymph nodes in diagnosis of sarcoidosis. Methods: Fifty two patients mean age 46.4±12.9 with suspicion of sarcoidosis (stage I, II) were included in this prospective study. Patients underwent diagnostic conventional bronchoscopy with EBB followed by EBUS-TBNA. One (group 7) or two (group 7, and 4R/4L or 10R/10L or 11R/11L) lymph nodes stations were punctured. Smear and cell blocks were performed and examined. Results: EBB was positive in 16 patients (30.8%). EBUS-TBNA was diagnostic in 86.5%. Combination of EBUS-TBNA and EBB increased diagnostic yield of sarcoidosis (86.5% vs 98.1%; p=0.02). Sensitivity of EBUS-TBNA with EBB was 100%, specificity 98.1%, PPV 100% and NPV 100%. Granulomas from one lymph nodes group were obtained in 78.8%, in group of two stations punctured cytology was positive in 86.5% (p=0.2). Application of cell blocks did not increase diagnostic yield of EBUS-TBNA in sarcoidosis. Conclusions: Combining of EBUS-TBNA of at least two lymph nodes stations and EBB increase diagnostic yield of sarcoidosis. Cell block specimens have not further impact on the diagnostic yield of the procedure.

Background: Eosinophilic airway inflammation has been demonstrated in 20%–40% of induced sputum samples from patients with stable COPD. Lipid mediators, like eicosanoids are associated with airway inflammation especially with the eosinophilic pattern. Objectives: To investigate the inflammatory cell patterns and eicosanoids in induced sputum in stable COPD. Methods: Induced sputum was collected in COPD and healthy control subjects. Sputum differential cell count and sputum supernatant concentrations of: 5-HETE, 12-HETE, 15-HETE, 5-oxo-ETE, 12-oxo-ETE, 15-oxo-ETE, LTD4, LTE4, LTB4, PGE2, 8-izo-PGE2, PGD2, PGA2, tetranor-PGE-M, tetranor-PGD-M, PGF2a, 8-izo-PGF2a, TBX2, 11-dehydro-TXB2 were measured. Results: In COPD subjects increased eosinophilia in induced sputum (>2%) was found in 42% of subjects (including 34% eosinophilic and 8% mixed eosinophilic and neutrophilic patterns). There was a statistically significant correlation between sputum eosinophilia and induced sputum concentrations of LTE4, LTD4, PGE2, 8-izo-PGE2, 15-HETE,15-oxo-ETE, PGD2, TBX2 and 11-dehydro-TBX2. Induced sputum concentrations of LTE4, LTD4, PGD2, PGE2, 8-izo-PGE2 were significantly higher in COPD subjects compared to healthy controls, whereas concentrations of tetranor-PGE-M and tetranor-PGD-M were lower. Frequent exacerbator COPD subjects had lower sputum but not blood eosinophilia. Conclusions: Stable COPD is often associated with eosinophil influx in the lower airways and elevated concentrations of eicosanoids. Increased sputum eosinophilia is not associated with frequent exacerbations of COPD.

Background Sarcoidosis is characterized by exaggerated immune response to unknown agent and can affect different organs. One of the main players in the pathology of the disease are regulatory T cells (Tregs), however, up to date the mechanisms of the possible molecular alterations of this particular cell subset are not known. Methods In the current study we looked for the global transcriptomic changes of miRNAs, using predefined array, and mRNAs (RNA seq analysis) of Tregs of patients with the most predominant form of the disease - acute pulmonary sarcoidosis (PS). For this purpose sorted CD4+/CD25+/CD127- Tregs from peripheral blood (PB) and CD4+/CD25 + Tregs from bronchoalveolar lavage (BAL) were used. Results MiRNA analysis revealed that Tregs isolated from PB and BAL display significantly different miRNA profile, suggesting an important role of the pulmonary microenvironment in creating these changes. Among disease-related miRNAs of PB Tregs we identified miR-155 and miR-223. Moreover, looking at the global transcriptome of PB Tregs, we recognized alterations in TLR-2 signaling pathway and in the downstream of NF-κB apoptosis and proliferation signals. However, induction of TLR-2 expression was found not only in Tregs, but also in the heterogeneous population of peripheral blood mononuclear cells (PBMC) as well as two PBMC subpopulations (CD4+/CD25-and CD4-/CD25-) of patients with PS. This indicates that activation of TLR signaling pathway in sarcoidosis does not occur only in Tregs. Conclusion Our findings offer a deeper insight into the molecular mechanisms of Tregs reduced suppression and increased apoptosis in patients with PS. Based on the current results, future studies should focus on possible therapeutic effect of TLR-2 signaling inhibition.

Aspirin desensitization is considered to be an effective and well-tolerated therapy for patients with Non-steroidal anti-inflammatory(NSAIDs)-Exacerbated Respiratory Disease (NERD). The aim of the present study was to investigate the influence of aspirin desensitization on inflammatory cell count in induced sputum and nasal lavage in fifteen NERD individuals subjected to one-year aspirin therapy. The decrease in induced sputum count of eosinophils and macrophages was observed. Clinical efficacy of aspirin therapy in improving nasal symptoms and quality of life in NERD patients was also confirmed.

Introduction Bronchofiberoscopy (BF) is a key tool used in the management of patients with respiratory diseases. Describing factors that contribute to patient anxiety surrounding BF has the potential to influence patient management and willingness to undergo the procedure again in the future if needed. Objectives This study sought to understand what factors influence anxiety and satisfaction experienced by patients undergoing BF under conscious sedation. Methods This study had a prospective observational character and evaluated 463 consecutive patients undergoing BF. Participants were divided into two groups, those undergoing BF for the first time and those who had undergone the procedure at least once in the past. Data were collected from three questionnaires prepared by the research team. Results Patients who had undergone multiple bronchoscopies were more satisfied with their physician's explanation of the procedure (P

Introduction Endoscopic biopsy techniques are useful in the diagnosis of sarcoidosis. There is a need for randomized trials to establish where these procedures fit in the diagnosis of sarcoidosis. Objectives The aim of the study was to compare the diagnostic yield of conventional transbronchial needle aspiration (TBNA) with endobronchial ultrasound-guided TBNA (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in stages I and II of pulmonary sarcoidosis. Patients and methods Patients suspected of sarcoidosis were randomized to undergo TBNA or EBUS-TBNA or EUS-FNA. Patients with negative TBNA and EBUS-TBNA results underwent EUS-FNA and those with negative EUS-FNA results—EBUS-TBNA. If both tests were negative, patients in stage I were scheduled for mediastinoscopy (MS) and those in stage II—for transbronchial lung biopsy (TBLB). Results In 100 patients, 34 TBNA, 30 EBUS-TBNA, and 36 EUS-FNA procedures were performed at baseline. TBNA was positive in 20 patients (58.8%); EBUS-TBNA, in 23 (76.7%); and EUS-FNA, in 31 patients (86.1%). In patients with negative biopsy results, the second procedure was performed. The results of EUS-FNA were positive in 9 patients and of EBUS-TBNA—in none. Of 17 patients with negative results of both procedures, MS was performed in 6 patients and was positive in 2. In the remaining 11 patients, sarcoidosis was confirmed by TBLB. Sensitivity and accuracy of TBNA compared with EBUS-TBNA and EUS-FNA were 62.5% and 64.7%, 79.3% and 80%, and 88.6% and 88.9%, respectively. Sensitivity and accuracy of EBUS-TBNA were higher (P = 0.139) and of EUS-FNA were significantly higher compared with TBNA (P = 0.012). Conclusions In stages I and II of pulmonary sarcoidosis, endoscopic ultrasound is a reasonable approach but EUS-FNA seems to be the method of choice.

The paper presents the system for the integration of heterogeneous data sources in the domain of Obstructive Sleep Apnea. The main goal of the system is to facilitate patient diagnose and treatment process by integration of the results of performed medical examinations and analyzes. Data source contains: clinical interviews, physical examinations, lab tests, and the data collected from the devices used to monitor patient's sleep parameters (PSG, CPAP). This article describes the concept of the system, its main functionalities, IT architecture and technology and some details of its implementation. Also the data sources and the methods of data acquisition from medical devices integrated with the system are characterized. In addition, basic methods of analyzing data gathered in the system are presented, which in the future can be developed towards automatic mechanisms supporting the process of diagnosis and treatment of patients in this domain.

Background: ACT proved to be a reliable tool in assessment of asthma control. Psychopathological factors can influence asthma control and the result of ACT. Aim: Analysis of psychopathological and personality factors on ACT outcomes. Methods: Asthma control was assessed using ACT among 104 stable asthmatics. Quality of life was assessed by Asthma Quality of Life Questionnaire (AQLQ). Patients were evaluated for psychopathologies using 28-item General Health Questionnaire (GHQ28). Personality traits were assessed with Eysenck’s Personality Inventory (EPI). Acceptance of asthma was measured by Acceptance of Illness Scale (AIS). Results: Patients with uncontrolled asthma (ACT score Conclusions: Uncontrolled asthma patients have more frequent psychopathologies estimated by GHQ28 and lower acceptance of their disease. However, they do not differ from controlled asthmatics in terms of personality traits.

Background: Good asthma control is considered as the main goal of asthma treatment. ACT is one of the simpliest and most widespread tools developed to assess asthma control. Aim: To analyze clinical factors influencing asthma control assessed by ACT. Methods: Asthma control was assessed using ACT among 104 stable asthmatics. Detailed clinical data was obtained by designed questionnaire. Spirometry was also evaluated. Results: Patients with uncontrolled asthma (ACT score Conclusions: Uncontrolled asthma according to ACT, is associated with more severe disease and increased incidence of asthma exacerbations during the last 12 months. Despite ACT assesses control of asthma in the last 4 weeks, it seems to be a useful screening tool in detection of patients who are prone to more frequent asthma exacerbations. Asthmatics with higher BMI, GERD or depression require profound evaluation as they are at risk of uncontrolled asthma.

Wstęp: Remodeling dróg oddechowych jest istotną składową utrwalonej obturacji w ciężkiej astmie. Tomografia komputerowa wysokiej rozdzielczości (TKWR) to skuteczna metoda wykrywania zmian w strukturze dróg oddechowych. Celem pracy jest wykorzystanie TKWR do oceny zmian w remodelingu dróg oddechowych u pacjentów z ciężką astmą alergiczną leczonych biologicznie omalizumabem. Materiał i metody: U 12 pacjentów z ciężką astmą alergiczną, wykonano TKWR klatki piersiowej przed i po leczeniu omalizumabem. W wybranych oskrzelach obliczono następujące parametry: pole powierzchni ściany oskrzela (BA, bronchial wall area), również skorygowane o powierzchnię ciała (BSA, body surface area); procent powierzchni ściany oskrzela (WA%, wall area); i stosunek powierzchni światła do całkowitej powierzchni oskrzela (Ai / Ao). Odpowiedź kliniczną na leczenie oceniano za pomocą kwestionariusza kontroli astmy (ACQ, asthma control questionnaire), kwestionariusza jakości życia w astmie (AQLQ, asthma quality of life questionnaire) i liczby zaostrzeń w ciągu roku. Ocena obejmowała również spirometrię i eozynofilię krwi obwodowej. Wyniki: Leczenie spowodowało istotną poprawę ACQ (p = 0.035) i AQLQ (p = 0.001). Zaobserwowano istotną redukcję zaostrzeń w ciągu roku (p = 0.002) i zmniejszenie dziennej dawki steroidu sytemowego (p = 0.032). Natężona objętość wydechowa pierwszosekundowa (FEV1, forced expiratory volume in 1 second) i eozynofilia krwi obwodowej nie uległy zmianie (p = 0.846 i p = 0.221). Wymiary dróg oddechowych (Ai/Ao) poszczególnych oskrzeli były zgodne ze średnią parametrów obliczonych dla wszystkich zmierzonych oskrzeli. Chociaż zaobserwowano znaczny spadek WA (p = 0.002) i WA/BSA (p = 0.002), WA% i Ai/ /Ao nie uległy poprawie (p = 0.39 i p = 0.49). Nie stwierdzono korelacji między zmianami w drogach oddechowych a zmianami w spirometrii lub parametrach klinicznych. Wniosek: Pomimo skuteczności klinicznej omalizumabu, jego wpływ na remodeling dróg oddechowych może być ograniczony.

Background: Omalizumab(OMA) is the youngest medicine in asthma therapy. It is being evaluated in real-world clinical practice to provide complete understanding of the benefit of this otherwise expensive medicine. Objectives: To evaluate efficacy of OMA during one year of therapy in real-life conditions in Polish patients with severe allergic asthma. Methods: Due to the introduction of Program for Severe Allergic Asthma funded by the National Health Insurance OMA became more commonly available for Polish patients. Strict inclusion criteria should be met to enter the program. The study is one-year open-label observation lead in 15 patients qualified to the program in Pulmonary Department in Krakow. All patients have been assessed for asthma control (Asthma Control Questionnaire-ACQ), quality of life (Asthma Quality of Life Questionnaire-AQLQ), daily dose of oral corticosteroids (OCS) and asthma exacerbation rate. Results: All patients have shown good (47%,n=7,GR) or very good (53%,n=8) response (VGR) to OMA according to Global Evaluation of Treatment Effectiveness (GETE) scale after one-year therapy. OMA significantly reduced asthma exacerbation rate by 80% (by 91% in VGR and by 65% in GR group) and the dose of OCS by 62% (by 76% in VGR and by 46% in GR). ACQ declined by 34% in the group (p=0.005), by 52% in VGR (p=0,01) and by 10% in GR(p=0,2). AQLQ grew in the whole group by 34%(p=0,03) and in VGR by 40%(p=0.01). In GR group the increase by 25% was insignificant. Conclusions: Omalizumab has shown high effectiveness in real-world Polish patients in reduction of asthma exacerbations and the dose of oral corticosteroids, improvement in asthma control and quality of life indicators.

INTRODUCTION: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is a key diagnostic tool to obtain cytological specimens from enlarged mediastinal lymph nodes and is recommended to use in diagnosis of sarcoidosis.However the mean of diagnostic yield is between 70-80%. AIMS AND OBJECTIVES: To determine the potential benefit from puncturing more than one station of mediastinal lymph nodes, and how adding endobronchial biopsy (EBB) increase diagnostic yield. METHODS: Fifty two patients with suspicion of sarcoidosis (stage I,II) were included in this prospective study. Patients underwent diagnostic conventional bronchoscopy with EBB followed by EBUS-TBNA. In 19 patients one station of lymph nodes was biopsied. In 33 cases more than one (two or three) stations (7, and 4R/4L and/or 10R/10L and/or 11R/11L) were punctured. RESULTS: The presence of noncaseating granulomas that corresponded to clinical and radiological picture of sarcoidosis was obtained in 49 patients (94.23%).One patient was confirmed by VTS, one by skin biopsy and one had reactive lymph nodes. The overall diagnostic accuracy for EBUS-TBNA was 86.53%. Endobronchial biopsy was positive in 12 patients (23.07%)and increased verification to 94.23%. Sensitivity of EBUS-TBNA with EBB was 96,1%, specificity 100%, PPV 100% and NPV 33,3%. Granulomas from one lymph nodes group were obtained in 73.68%. In group of two or three stations punctured cytology was positive in 93.93% (p=0.039) CONCLUSIONS: The diagnostic yield of the EBUS/TBNA performed from more than one lymph node stations was significantly higher. Addition EBB to EBUS-TBNA in sarcoidosis verification may also increase the diagnostic yield.

INTRODUCTION Airway remodeling plays an important role in the development of chronic obstructive pulmonary disease (COPD). Imaging methods, such as computed tomography (CT) and endobronchial ultrasound (EBUS), may be useful in the assessment of structural alterations in the lungs. OBJECTIVES The aim of this study was to evaluate a relationship between the severity of emphysema assessed by chest CT, the thickness of bronchial wall layers measured by EBUS, and the markers of remodeling in bronchoalveolar lavage fluid (BALF) in patients with COPD. PATIENTS AND METHODS The study included 33 patients with COPD who underwent pulmonary function tests, emphysema score assessment by chest CT, as well as bronchofiberoscopy with EBUS in order to measure the total bronchial wall thickness and, separately, layers L1, L2, and L3-5. Selected remodeling (matrix metalloproteinase 9 [MMP-9], tissue inhibitor of metalloproteinase 1, transforming growth factor β1 [TGF-β1]) and inflammatory markers (neutrophil elastase, eosinophil cationic protein) were measured in BALF samples using an enzyme-linked immunosorbent assay. RESULTS MMP-9 levels in BALF were significantly higher in patients with very severe bronchial obstruction than in those with moderate and mild bronchial obstruction (P = 0.02), and showed a negative correlation with forced expiratory volume in 1 second (r = -0.538, P = 0.002). The thickness of L1 and L2, which histologically correspond to the mucosa, submucosa, and smooth muscle, demonstrated a positive correlation with TGF-β1 levels in BALF (r = 0.366, P = 0.046 and r = 0.425, P = 0.02) and the thickness of L1 showed a negative association with neutrophil elastase levels (r = -0.508, P = 0.004). There was no significant correlation between the analyzed markers in BALF and the emphysema score. CONCLUSIONS Significant correlations of TGF-β1 and elastase with the thickness of bronchial wall layers, and of MMP-9 with the severity of obstruction, may suggest the involvement of these markers in airway remodeling in patients with COPD.

The aim of this pilot study was to evaluate changes in the concentration of prostaglandin E2 (PGE2) in induced sputum supernatant in 3 groups: sub- jects with NSAID-exacerbated respira- tory disease (NERD), aspirin tolerant asthma (ATA) and healthy controls (HC), before and after oral aspirin chal- lenge test. The study was conducted in the years 2014-2015 at the Clinical Department of the Pulmonology Clinic at the University Hospital in Cracow. 43 patients were enrolled in the study (NERD - n = 15, ATA - n = 15 and HC - n = 13). All of them underwent a placebo-controlled oral aspirin challenge. Sputum was induced 24 hours before the challenge and immediately after the test. Induced sputum was processed in order to obtain cystospin slides to depict inflammatory cell patterns and supernatants, in which PGE2 was measured. The concentration of PGE2 was determined using mass spectrometry coupled with gas chromatography (gas chromatography/mass spectrometry - GC/MS). After aspirin challenge, the concentration of PGE2 in induced sputum supernatant decreased in both asthmatics hypersensitive to aspirin (p = 0.01) and those who tolerated aspirin well (p = 0.17). The change in the healthy control group was not statistically significant. These results support the cyclooxygenase theory of PGE2 inhibition by aspirin. However, the mechanism of bronchoconstriction after aspirin administration alone in patients with NSAID-exacerbated respiratory disease remains unclear.

INTRODUCTION In the pathogenesis of diffuse parenchymal lung diseases (DPLDs), growth factors, including transforming growth factor beta1 (TGF-beta1), are responsible for cell proliferation, apoptosis, chemotaxis, and angiogenesis, and also for the production and secretion of some components of the extracellular matrix. OBJECTIVES The aim of the study was to evaluate correlations in DPLDs between TGF-beta1 levels in bronchoalveolar lavage (BAL) fluid and high-resolution computed tomography (HRCT) score. PATIENTS AND METHODS The study was performed in 31 DPLD patients in whom a selection of lung segments with high and low intensity of abnormalities was estimated by HRCT score. All patients underwent BAL with TGF-beta1 measured by an enzyme immunoassay in BAL fluid and video-assisted thoracic surgery lung biopsy from both selected segments. RESULTS All 31 patients were diagnosed, and based on histopathology, they were classified into 2 groups: idiopathic interstitial pneumonia (usual interstitial pneumonia - 12, nonspecific inter stitial pneumonia - 2, cryptogenic organizing pneumonia - 2, and desquamative interstitial pneumonia - 1) and granulomatous disease (sarcoidosis - 7, extrinsic allergic alveolitis - 5, and histiocytosis X - 2). The final analysis was performed in 28 patients who showed nonhomogenous distribution on HRCT. TGF-beta1 levels in BAL fluid were significantly higher in the areas with high intensity of abnormalities assessed by HRCT score (P = 0.018, analysis of variance). These levels were not different between the groups, but a trend towards higher levels in idiopathic inter stitial pneumonia was observed. CONCLUSIONS The results confirm that TGF-beta1 may be a good but not specific marker of fibrosis in DPLDs. A significant positive correlation between TGF-beta1 levels in BAL fluid and the HRCT score was observed.

Background Endobronchial ultrasound (EBUS) is a new technique that enables the assessment of bronchial wall layers. The aim of the study was to verify the utility of EBUS for the assessment of bronchial wall remodeling in patients with asthma. Methods In 35 patients with asthma and 23 control subjects, high-resolution CT (HRCT) scanning and EBUS were used to measure bronchial wall thickness in the 10th segment of the right lung. With a radial 20-MHz probe, EBUS identified the 5-laminar structure of the bronchial wall. Layer 1 (L 1 ) and layer 2 (L 2 ) were analyzed separately, and layers 3 through 5 (L 3–5 ), which corresponded to cartilage, were analyzed jointly. Digitalized EBUS images were used for the quantitative assessment of bronchial wall thickness and the wall area (WA) of the layers. Finally, bronchial biopsy specimens were taken for measuring the thickness of the reticular basement membrane (RBM). The thickness and WA of the bronchial wall layers, which were assessed using EBUS, were correlated with FEV 1 and RBM. Results There was no significant difference in the measurements of total bronchial wall thickness using EBUS and HRCT scanning. The thickness and WA of the bronchial wall and its layers were significantly greater in patients with asthma than in the control subjects. A negative correlation among the thicknesses of L 1 , L 2 , and L 3–5 and FEV 1 , and a positive correlation with RBM were observed only in the patients with asthma. Conclusions EBUS allows precise measurement of the thickness and WA of bronchial wall layers. The correlation of these parameters with asthma severity suggests implementation of EBUS in the assessment of bronchial wall remodeling in patients with asthma.

SummaryIncreased risk of thrombotic events occurs in chronic obstructive pulmonary disease (COPD). Elevated fibrinogen and C-reactive protein (CRP), being common in COPD, are associated with formation of dense fibrin clots resistant to lysis. Statins have been found to display anti-inflammatory and antithrombotic effects. We investigated fibrin clot properties in COPD patients prior to and following statin therapy. Ex vivo plasma fibrin clot permeability, compaction, and fibrinolysis were assessed in 56 patients with stable COPD,aged 64.9 ±9.2 years (mean FEV1, 54.7 ±15.9% predicted), versus 56 controls matched for age, sex and cardiovascular risk factors. Patients were then randomly assigned to receive simvastatin 40 mg/day (n = 28) or to remain without statins for three months (n = 28). Patients with COPD had lower clot permeability (6.1±1.07 versus 9.2 ±0.9 10−9 cm2; p

Background: Altered eicosanoid metabolismis a characteristic finding of aspirin induced asthma (AIA). Oral aspirin challenge is confirmatory diagnostic test for this clinical condition. Induced sputum allows to measure mediators of asthmatic inflammation in bronchial secretions. Objectives: The influence of aspirin on sputum supernatant concentration of eicosanoids during the oral challenge test was studied, using chromatography-mass spectrometry measurements. Methods: Induced sputum was collected before and following oral aspirin challenge. Sputum differential cell count and sputum supernatant concentrations of prostaglandin E 2 (PGE 2 ) was measured. Results: Aspirin precipitated bronchoconstriction was reported in all AIA (n=15) subjects, but in none of HC (n=13) and ATA (n=15). AIA was characterized by the dominance of the eosinophilic airway inflammation, whereas the paucigranulocytic phenotype was most frequent in HC. At baseline, mean induced sputum supernatant level of PGE 2 did not differ between the groups. Following the challenge, PGE 2 decreased in asthmatics patients independent of aspirin hypersensitivity (AIA p=0.002; ATAp=0.02), but not in HC (p=0.07). Cumulative doses of aspirin or the duration of the challenge had no effect on the magnitude of the PGE 2 alterations. Conclusions: During the oral aspirin challenge, PGE 2 decreases significantly in asthmatics as compared to healthy ones. The results support the theory on the inhibition of PGE 2 biosynthesis as a trigger for bronchoconstriction mediated by cysteinyl leukotrienes in AIA.

Sarcoidosis is a multisystem granulomatous disorder predominantly involving the lungs. The disequilibrium between effector and regulatory lymphocytes (Treg cells) in sarcoidosis has been suggested. MicroRNAs (miRNAs) are small non-coding molecules necessary for proper T cell functioning. Certain miRNAs can lead to polarization of the inflammatory response via IL-2 and IFN-g signaling pathways, implicated in sarcoidosis. In the current study, increase in the plasma levels of IFN-g induced protein 10, MIG, IL-12, IL-2R and VEGF was found in patients with pulmonary sarcoidosis (PS). These results point at persistence of the Th1 immune response with putative defective Treg functions. Therefore, the global miRNA expression of Treg (CD4+/CD25+) subpopulation, from peripheral blood (PB) and bronchoalveolar lavage (BAL) of PS patients, was assessed. As a control Treg cells from PB of healthy individuals (HI) were used. In the array 743 miRNAs were tested, but only 139 miRNA were found to be expressed in Tregs. Among them 15 were significantly different from the Treg cells of HI. Most of those miRNAs were up-regulated in BAL Treg cells and only two of them were down-regulated (miR-130b and miR-150). According to DIANA miR-Path the miRNAs differentially expressed (DE) in PS Treg cells target genes from MAPK signaling pathway. Interestingly the same DE-miRNAs also target genes in FOXO signaling pathway. Several DE-miRNAs (miR-223, -155 and -132) were predicted to target FOXO directly, suggesting impairment in PS Treg cell function and differentiation. Acknowledgments: Supported by OPUS grant No. 2012/07/B/NZ5/02506 (NCN) and KNOW grants.

Introduction While spirometry plays a key role in diagnosing chronic obstructive pulmonary disease (COPD), imaging methods including endobronchial ultrasound (EBUS) and chest computed tomography (CT) appear to be useful for investigating structural changes in the lungs. Objectives The aim of this study was to evaluate remodeling in COPD patients using EBUS and chest CT. Patients and methods The study included 33 patients with COPD, 15 patients with severe asthma, and 15 control subjects. All subjects underwent pulmonary function tests and bronchoscopy with EBUS to measure the total thickness of the bronchial wall and its layers. Additionally, in COPD patients, a chest CT was performed to measure total bronchial wall thickness. Results The total bronchial wall thickness measured by EBUS in patients with COPD (1.192 ±0.079 mm) was significantly smaller than that in asthmatic patients (1.433 ±0.230 mm, P = 0.001) and significantly greater than in control subjects (1.099 ±0.095 mm, P = 0.04), and was positively correlated with residual volume (RV) / total lung capacity (r = 0.5, P = 0.02), RV (r = 0.6, P = 0.007), and RV (%) (r = 0.5, P = 0.05). The thickness of the bronchial wall layers in patients with COPD were as follows: L1 = 0.135 ±0.018 mm, L2 = 0.151 ±0.026 mm, and L3-5 = 0.906 ±0.065 mm. There was no correlation between the thickness of the bronchial wall layers and forced expiratory volume in 1 second. Conclusions The results of this study show that EBUS is a useful method for evaluating bronchial wall layers not only in asthma but also in COPD, and suggest that the pattern of remodeling differs in each of these diseases.

Despite modern medicine's greatest efforts, many patients suffering from chronic obstructive pulmonary disease (COPD) and asthma remain refractory to the best treatments available. Bronchoscopy is increasingly being used to explore new approaches for treating these diseases, and several new techniques have recently shown encouraging results. The purpose of this review will be to shed some light on these methods.We searched Pubmed and Embase for English language articles from 1995 to September 2014, as well as ongoing trials on ClinicalTrials.gov. The following prespecified terms were used to search for clinical trials and case reports from the past 20 years: "endoscopic treatment of COPD", "endobronchial valve", and "bronchial thermoplasty".In search for new COPD treatments, several trials have assessed the efficacy of one-way valves and other conceptually similar techniques including biological sealants and thermal vapor ablation. These methods all operate within a similar paradigm where the intention is to maximize ventilation of the remaining healthy parts of the lung, and to minimize the use and the space occupied by the diseased lung tissue. Similarly, a new non-pharmacologic therapeutic approach in asthma, bronchial thermoplasty (BT), was recently approved for use in the United States for adults with severe disease. The goal is to reduce the mass of hypertrophied smooth muscle in the bronchi to decrease bronchoconstriction.Both BT and the bronchoscopic treatments for COPD have shown promising results in recent studies, suggesting the onset of a new direction in obstructive lung disease treatment.

Sarcoidosis is a granulomatous disease of unknown etiology. The disease has an important inflammatory and immune component; however, its immunopathogenesis is not completely understood. Recently, the role of microRNAs (miRNAs), the small non-coding RNAs, has attracted attention as both being involved in pathogenesis and serving as disease markers. Accordingly, changes in the expression of some miRNAs have been also associated with different autoimmune pathologies. However, not much is known about the role of miRNAs in sarcoidosis. Therefore, the aim of this study was to compare the level of expression of selected miRNAs in healthy individuals and patients with sarcoidosis. We detected significantly increased level of miR-34a in peripheral blood mononuclear cells isolated from sarcoidosis patients. Moreover, significantly up-regulated levels of interferon (IFN)-γ, IFN-γ inducible protein (IP-10) and vascular endothelial growth factor were detected in sera of patients when compared to healthy subjects. Our results add to a known inflammatory component in sarcoidosis. Changes in the levels of miR-34a may suggest its involvement in the pathology of this disease.

This study presents the use of endobronchial ultrasound (EBUS) for imaging and dimensional measurements of a trachea. An assessment of shape reproduction accuracy was based on a comparative method using one- and two-later models. It was found that dimensions determined from EBUS scans of digital models are overstated by 1.2–2.9 mm on average. Developed 2-D and 3-D models of tracheal structures facilitate the evaluation of dimensions and thickness distribution for tissue layers.

Aspirin causes bronchoconstriction in aspirin-intolerant asthma (AIA) patients by triggering cysteinyl-leukotriene (cys-LT) production, probably by removing PGE2-dependent inhibition. To investigate why aspirin does not cause bronchoconstriction in all individuals, we immunostained enzymes of the leukotriene and prostanoid pathways in bronchial biopsies from AIA patients, aspirin-tolerant asthma (ATA) patients, and normal (N) subjects. Counts of cells expressing the terminal enzyme for cys-LT synthesis, LTC4 synthase, were fivefold higher in AIA biopsies (11.5+/-2.2 cells/mm2, n = 10) than in ATA biopsies (2.2+/-0.7, n = 10; P = 0. 0006) and 18-fold higher than in N biopsies (0.6+/-0.4, n = 9; P = 0. 0002). Immunostaining for 5-lipoxygenase, its activating protein (FLAP), LTA4 hydrolase, cyclooxygenase (COX)-1, and COX-2 did not differ. Enhanced baseline cys-LT levels in bronchoalveolar lavage (BAL) fluid of AIA patients correlated uniquely with bronchial counts of LTC4 synthase+ cells (rho = 0.83, P = 0.01). Lysine-aspirin challenge released additional cys-LTs into BAL fluid in AIA patients (200+/-120 pg/ml, n = 8) but not in ATA patients (0. 7+/-5.1, n = 5; P = 0.007). Bronchial responsiveness to lysine-aspirin correlated exclusively with LTC4 synthase+ cell counts (rho = -0.63, P = 0.049, n = 10). Aspirin may remove PGE2-dependent suppression in all subjects, but only in AIA patients does increased bronchial expression of LTC4 synthase allow marked overproduction of cys-LTs leading to bronchoconstriction.

We have shown that inhalation of lysine aspirin enhances leukotriene production in the lungs of patients with aspirin-induced asthma (AIA). To assess the specificity of this reaction, we compared two well-matched groups of patients: eleven with AIA versus 14 asthmatics tolerant to aspirin (ATA). All subjects underwent bronchoalveolar lavage (BAL) with saline followed immediately by instillation of 10 mg of lysine aspirin, into a right middle lobe segmental bronchus, which was lavaged 15 min later. At baseline the two groups did not differ with respect to BAL fluid concentrations of cyclooxygenase products, peptido-leukotrienes, histamine, tryptase, interleukin-5 (IL-5), eosinophil cationic protein (ECP), or eosinophil number. Fifteen minutes after aspirin instillation, there was a statistically significant rise in peptido-leukotrienes, IL-5, and eosinophil number in AIA, but not in ATA, but not in ATA patients. In the former, but not in the latter group, mean histamine concentrations rose in response to aspirin, approaching the level of statistical significance. Tryptase and ECP levels showed no significant change. Aspirin significantly depressed PGE2 and thromboxane B2 (TXB2) in both groups, however PGD2, PGF2 alpha, and 9 alpha, 11 beta-PGF2 decreased only in ATA patients. A characteristic disturbance in eicosanoid balance, produced by aspirin in patients intolerant to this drug, might explain precipitation of asthma attacks.

Introduction: The aim of the study was to evaluate the concentration of 9a11b prostaglandin F2, a stable metabolite of prostaglandin D2 (PGD2) and leukotriene E4 (LTE4), in patients with stable and exacerbated chronic obstructive pulmonary disease (COPD). Material and methods: The study included 29 COPD patients aged 73 ± 8.34 years, with mean FEV1 = 48.64 ± 15.75% of predicted normal value, and 29 healthy controls aged 57.48 ± 10.86 years, with mean FEV1 = 97.17 ± 13.81% of predicted normal value. Urine and blood samples were taken from COPD patients during exacerbation and in the stable phase of the disease; LTE4 was measured in urine using commercial enzyme immunoassay (EIA), and 9a11b prostaglandin F2 (9a11bPGF2), a stable metabolite of PGD2, was measured in blood and urine using GC/MS. Results: Urine concentrations of LTE4 in urine (677.15 vs. 436.4 pg/mg of creatinine; p = 0.035) and serum levels of 9a11bPGF2 (5.35 vs. 3.07 pg/mL; p = 0.007) were significantly higher in patients with exacerbated COPD than in the control group. There was no difference in LTE4 levels in urine and 9a11bPGF2 in serum between exacerbated and stable COPD. The urinary 9a11bPGF2 concentration did not differ between the studied groups. We found a positive correlation between smoking history and urine LTE4 level (r = 0.395; p = 0.002) as well as blood 9a11bPGF2 concentration (r = 0.603; p = 0.001) in COPD patients. Conclusions: Urine levels of 9a11bPGF2 and LTE4 did not differ between the stable COPD group and the control group. There were no differences between urine LTE4 levels and blood and urine 9a11bPGF2 levels between exacerbated and stable COPD. Finally, LTE4 concentration in urine and 9a11bPGF2 in blood were significantly higher in exacerbated COPD patients than in the control group.

Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for thromboembolic events. We investigated thrombin generation profiles in COPD patients and their dependence on plasma factor/inhibitor composition.Factors (f) (fII, fV, fVII, fVIII, fIX, fX), antithrombin, protein C (PC) and free tissue factor pathway inhibitor (fTFPI) from 60 COPD patients (aged 64.2 ± 10.1 years; a mean forced expiratory volume in 1 second [FEV(1)], 55.6 ± 15.8% of predicted values) were compared with those for 43 controls matched for age, sex, weight and smoking. Patients receiving anticoagulation were excluded. Using each individual's plasma coagulation protein composition, tissue factor-initiated thrombin generation was assessed computationally.COPD patients had higher fII (115 ± 16 vs 102 ± 10%, p0.0001), fV (114 ± 19 vs 102 ± 12%, p = 0.0002), fVII (111 ± 15 vs 102 ± 17%, p = 0.002), fVIII (170 ± 34 vs 115 ± 27%, p0.0001), and fIX (119 ± 21 vs 107 ± 17%, p = 0.003), and lower fTFPI (17.7 ± 3.2 vs 18.9 ± 3.2 ng/ml, p = 0.047) compared with controls, while fX, antithrombin, and PC were similar in both groups. Computational thrombin generation profiles showed that compared with controls, COPD patients had higher maximum thrombin levels (+28.3%, p0.0001), rates of thrombin generation (+46.1%, p0.0001) and total thrombin formation (+14.4%, p0.001), together with shorter initiation phase of thrombin generation (p0.0001) and the time to maximum thrombin levels (p0.0001). Thrombin generation profiles in COPD patients can be normalized via correction of fII, fVIII , fIX and TFPI. The severity of COPD and inflammatory markers were not associated with thrombin generation profiles.Prothrombotic phenotype in COPD patients is largely driven by increased prothrombin, fVIII, fIX, and lower fTFPI.

The inflammatory process in asthma and COPD are involved in remodelling of airways. It has been suggested that the clinically observed distinctions between these two diseases are reflected by differences in structural changing of the airways. In asthma the epithelium appears to be more fragile than that of chronic obstructive pulmonary disease (COPD), the epithelial reticular basement membrane (RBM) is significantly thicker, and there is marked enlargement of the mass of bronchial smooth muscle. In COPD it has been observed epithelial mucous metaplasia, airway wall fibrosis, and the inflammation is associated with loss of surrounding alveolar attachments. The remodelling of bronchial wall in asthma can be assessed using the histological examination of bronchial biopsies, high-resolution computed tomography (HRCT) and endobronchial ultrasound (EBUS). The assessment of air trapping in HRCT is an important tool in the evaluation of irreversible airway changes in asthmatics. Diffuse air trapping markedly correlates with bronchial thickness and probably reflects remodelling in the entire bronchial tree. EBUS also allows precise distinguishing and measurement of the thickness and wall area of bronchial wall layers. The results of recently published studies suggest the possibility of employing EBUS to remodelling assessment. Until now there are unknown any effective pharmacology methods to treat of remodelling in asthma. Bronchial thermoplasty (BT) is a novel intervention for asthma that delivers controlled thermal energy to the airway wall during bronchoscopy resulting in a prolonged reduction of airway smooth muscle mass and may allow to treat the remodelling in asthma.

In the pathogenesis of diffuse parenchymal lung diseases (DPLDs), growth factors, including transforming growth factor beta1 (TGF-beta1), are responsible for cell proliferation, apoptosis, chemotaxis, and angiogenesis, and also for the production and secretion of some components of the extracellular matrix.The aim of the study was to evaluate correlations in DPLDs between TGF-beta1 levels in bronchoalveolar lavage (BAL) fluid and high-resolution computed tomography (HRCT) score.The study was performed in 31 DPLD patients in whom a selection of lung segments with high and low intensity of abnormalities was estimated by HRCT score. All patients underwent BAL with TGF-beta1 measured by an enzyme immunoassay in BAL fluid and video-assisted thoracic surgery lung biopsy from both selected segments.All 31 patients were diagnosed, and based on histopathology, they were classified into 2 groups: idiopathic interstitial pneumonia (usual interstitial pneumonia - 12, nonspecific inter stitial pneumonia - 2, cryptogenic organizing pneumonia - 2, and desquamative interstitial pneumonia - 1) and granulomatous disease (sarcoidosis - 7, extrinsic allergic alveolitis - 5, and histiocytosis X - 2). The final analysis was performed in 28 patients who showed nonhomogenous distribution on HRCT. TGF-beta1 levels in BAL fluid were significantly higher in the areas with high intensity of abnormalities assessed by HRCT score (P = 0.018, analysis of variance). These levels were not different between the groups, but a trend towards higher levels in idiopathic inter stitial pneumonia was observed.The results confirm that TGF-beta1 may be a good but not specific marker of fibrosis in DPLDs. A significant positive correlation between TGF-beta1 levels in BAL fluid and the HRCT score was observed.

Hypersensitivity reactions to drugs account for 25% of all side effects related to drugs, affecting more than 7% of the population. One in four such reactions is caused by acetylic acid and other non-steroidal anti-inflammatory drugs.Between 1998 and 2000 epidemiological research was carried out in various centers, with the aim of estimating the frequency of allergy-based diseases in Poland. The objective of the study was to evaluate the frequency of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs), based on an epidemiological questionnaire, in the Polish adult population.Bronchial asthma was diagnosed in 582 patients (5.4%). Of that group, 75 patients (12.9%) additionally reported symptoms of hypersensitivity to NSAIDs. Aspirin-induced asthma was diagnosed in 11 patients (14.7%) with clinical manifestations of hypersensitivity responses. Frequency of aspirin-induced asthma with clinical symptoms amounted to 1.9% of asthmatics. In the assessment of severity of the disease, aspirin intolerance was the only statistically significant factor (p = 0.0003; odds ratio 28.6 with assumed 95% confidence interval).In the population of adults in Poland, the frequency of aspirin-induced asthma amounted to 0.1%. Hypersensitivity to NSAIDs was observed in 12.9% of asthmatics. In asthmatics with symptoms of hypersensitivity to non-steroidal anti-inflammatory drugs, which takes the course of clinically demonstrable aspirin-induced asthma, the risk of severe asthma is 30-fold higher.

In modern pulmonology there are new sufficient and noninvasive diagnostic method for staging of lung cancer. Bronchoscopy as a diagnostic and therapeutic tool was introduced to medicine at the end of XIX and early XX century. Recently a new image technique such as endobronchial ultrasonography has been developed. This method has an effect on the qualitative changes in bronchoscopic investigation.