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Background: The coronavirus disease 19 (COVID-19) recently became one of the leading causes of death worldwide, similar to cardiovascular disease (CVD). Coexisting CVD may influence the prognosis of patients with COVID-19. Aims: We analyzed the impact of CVD and the use of cardiovascular drugs on the in-hospital course and mortality of patients with COVID-19. Methods: We retrospectively studied data for consecutive patients admitted to our hospital, with COVID-19 between March 6th and October 15th, 2020. Results: 1729 patients (median interquartile range age 63 [50–75] years; women 48.8%) were included. Overall, in-hospital mortality was 12.9%. The most prevalent CVD was arterial hypertension (56.1%), followed by hyperlipidemia (27.4%), diabetes mellitus (DM) (25.7%), coronary artery disease (16.8%), heart failure (HF) (10.3%), atrial fibrillation (13.5%), and stroke (8%). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) were used in 25.0% of patients, β-blockers in 40.7%, statins in 15.6%, and antiplatelet therapy in 19.9%. Age over 65 years (odds ratio [OR], 6.4; 95% CI, 4.3–9.6), male sex (OR, 1.4; 95% CI, 1.1–2.0), pre-existing DM (OR, 1.5; 95% CI, 1.1–2.1), and HF (OR, 2.3; 95% CI, 1.5–3.5) were independent predictors of in-hospital death, whereas treatment with ACEIs/ARBs (OR, 0.4; 95% CI, 0.3–0.6), β-blockers (OR, 0.6; 95% CI, 0.4–0.9), statins (OR, 0.5; 95% CI, 0.3–0.8), or antiplatelet therapy (OR, 0.6; 95% CI: 0.4–0.9) was associated with lower risk of death. Conclusions: Among cardiovascular risk factors and diseases, HF and DM appeared to increase in-hospital COVID-19 mortality, whereas the use of cardiovascular drugs was associated with lower mortality.

The course of consecutive COVID‑19 waves was influenced by medical and organizational factors.We aimed to assess the outcomes of patients hospitalized for COVID‑19 during the first 3 waves of the pandemic.We performed a retrospective analysis of medical records of all COVID‑19 patients admitted to the University Hospital in Kraków, Poland, a designated COVID‑19 hospital in Małopolska province, between March 1, 2020 and May 31, 2021. The waves were defined as 1, 2, and 3, and covered the periods of March 2020 to July 2020, August 2020 to January 2021, and February 2021 to May 2021, respectively. Patients' characteristics and outcomes for waves 1 through 3 were compared.Data analyses included 5191 patients with COVID‑19. We found differences in age (mean [SD], 60.2 [17.3] years vs 62.4 [16.8] years vs 61.9 [16.1] years, respectively, for waves 1, 2, and 3; P = 0.003), sex distribution (proportion of women, 51.4% vs 44.2% vs 43.6%; P = 0.003), as well as concentrations of inflammatory markers and oxygen saturation (the lowest and the highest for wave 1, respectively; P0.001). Hospital death rates in subsequent waves were 10.4%, 19.8%, and 20.3% (P0.001). Despite similarities in patients' characteristics, the length of hospital and intensive care unit stay was shorter for wave 3 than for wave 2. The risk factors for in‑hospital death were: advanced age, male sex, cardiovascular or chronic kidney disease, higher C‑reactive protein level, and hospitalization during the second or third wave.We identified differences in patients' clinical characteristics and outcomes between consecutive pandemic waves, which probably reflect changes in terms of COVID‑19 isolation policy, hospitalization and treatment indications, and treatment strategies.

Introduction: The coronavirus disease 2019 (COVID-19) is one of the greatest clinical challenges of the last decades. Clinical factors associated with severity of the disease remain unclear. The aim of the study was to characterize Polish patients hospitalized due to COVID-19 and to evaluate potential prognostic factors of severe course of the disease. Material and methods: An observational study was conducted from March to July 2020 in the Pulmonology and Allergology Department of the University Hospital in Kraków, Poland. Consecutive patients with confirmed SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection were enrolled, and data about past medical history, signs and symptoms, laboratory results, imaging studies results, in-hospital management and outcomes was prospectively gathered. Results: The study sample comprised 100 patients at the mean age of 59.2 (SD 16.1) years among whom 63 (63.0%) were male. Among them 10 (10.0%) died, 47 (47%) presented respiratory failure, 15 (15.0%) were transferred to the intensive care unit, 17 (17.0%) developed acute kidney injury, 7 (7.0%) had sepsis and 10 (10.0%) were diagnosed with pulmonary embolism. Multivariable analysis revealed age (OR 1.1; 95% CI 1.01–1.15), body mass index (BMI; OR 1.24; 95% CI 1.01–1.53), modified early warning score (MEWS; OR 3.95; 95% CI 1.48–12), the highest d-dimer value (OR 1.73; 95% CI 1.03–2.9) and lactate dehydrogenase (LDH; OR 1.16; 95% CI 1.03–1.3) to be associated with severe course of COVID-19. Conclusion: This observational study showed that almost half of hospitalized patients with COVID-19 developed respiratory failure in the course of the disease. Increasing age, BMI, MEWS, d-dimer value and LDH concentration were associated with the severity of COVID-19.

Background Non-steroidal anti-inflammatory drugs exacerbated respiratory disease (N-ERD) asthma is characterized by chronic rhinosinusitis and intolerance to aspirin and other cyclooxygenase-1 inhibitors. Clinical data point to a heterogeneity within N-ERD phenotype. Objectives To investigate immune mediator profiles in lower airways of patients with N-ERD. Methods Levels of cytokines (luminex) and eicosanoids (mass spectrometry) were measured in bronchoalveolar lavage fluid (BALF) from patients with N-ERD (n=22), NSAIDs-tolerant asthma (NTA, n=21) and control subjects (n=11). mRNA expression was quantified in BALF cells using TaqMan low-density arrays. Results Lower airway eosinophilia was more frequent in N-ERD (54.5%) than in NTA (9.5%, P=0.009). Type-2 (T2) immune signature of BALF cells was more pronounced in eosinophilic subphenotype of N-ERD. Similarly, BALF concentrations of Periostin and CCL26 were significantly increased in eosinophilic N-ERD and correlated with T2-signature in BALF cells. Multiparameter analysis of BALF mediators of all asthma patients revealed the presence of two immune endotypes: ‘T2-like’ with elevated Periostin in BALF, and ‘non-T2/pro-inflammatory’ with higher levels of MMPs and inflammatory cytokines. N-ERD patients were classified mostly as T2 endotype (68%). Changes in eicosanoid profile, e.g. increased LTE4, were limited to N-ERD patients with airway eosinophilia. Blood eosinophilia appeared to be useful predictor of airway T2-signature (AUC=0.83), however, surrogate biomarkers had moderate performance in distinguishing eosinophilic N-ERD (blood eosinophils: AUC=0.72, Periostin: AUC=0.75). Conclusions Lower airway immune profiles show considerable heterogeneity of N-ERD, with skewing toward T2-response and eosinophilic inflammation. Increased production of LTE4 was restricted to a subgroup of patients with lower airway eosinophilia. Clinical implications N-ERD patients are heterogeneous in terms of lower airway inflammation and eicosanoid profiles. Better understanding of inflammatory diversity of N-ERD might help in selection of personalized therapies.

Background: The aim of the research presented here was to find a set of parameters enabling discrimination between three types of fibroblasts, i.e., healthy ones and those derived from two disorders mimicking each other: idiopathic pulmonary fibrosis (IPF), and nonspecific interstitial pneumonia (NSIP). Methods: The morphology and growth of cells were traced using fluorescence microscopy and analyzed quantitatively using cell proliferation and substrate cytotoxicity indices. The viability of cells was recorded using MTS assays, and their stiffness was examined using atomic force microscopy (AFM) working in force spectroscopy (FS) mode. To enhance any possible difference in the examined parameters, experiments were performed with cells cultured on substrates of different elasticities. Moreover, the chemical composition of cells was determined using time-of-flight secondary ion mass spectrometry (ToF-SIMS), combined with sophisticated analytical tools, i.e., Multivariate Curve Resolution (MCR) and Principal Component Analysis (PCA). Results: The obtained results demonstrate that discrimination between cell lines derived from healthy and diseased patients is possible based on the analysis of the growth of cells, as well as their physical and chemical properties. In turn, the comparative analysis of the cellular response to altered stiffness of the substrates enables the identification of each cell line, including distinguishing between IPF- and NSIP-derived fibroblasts.

The Asthma Control Test (ACT) consists of five items, one of which is self-assessment of asthma control. The goal of this study was to compare the responses to the first four ACT items with the response to the fifth item and determine whether this response affects the final ACT score.Adult asthmatics (Asthma was uncontrolled in 42.5% of patients. Based upon scores of the first four ACT items, three clusters of patients were identified. Cluster 1 comprised very well-controlled asthmatics [mean (sd) ACT total score 24.7 (0.7)]. Cluster 2 included both controlled and uncontrolled asthmatics [ACT total score 20.1 (2.5)]. Cluster 3 comprised poorly controlled asthmatics [ACT total score 12.1 (2.9)]. Misjudgment of asthma control in the fifth ACT item had no impact on the ACT total score in clusters 1 and 3. In cluster 2, the response to this item caused misclassification in 10.2% of patients.In patients with either very well or very poorly controlled asthma, the response to the fifth ACT item did not alter the assignment into the appropriate asthma control group. Only in a small group of patients with a total ACT score of approximately 20 points did the asthma group classification result in either controlled or uncontrolled.

Background and Objectives: Poor sleep quality in patients with obstructive sleep apnea (OSA) may be associated with different clinical and polysomnographic features. The aim of this study was to identify features associated with poor sleep quality in OSA patients. Materials and Methods: This was a cross-sectional study enrolling patients with OSA confirmed by polysomnography (PSG). In addition to gathering clinical data, patients were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Clinical Global Impression Scale. Univariate and multivariable analyses were performed to identify factors associated with an increased risk of poor sleep quality in this population. Results: Among 505 enrolled patients (mean age of 57.1 years, 69.7% male) poor quality of sleep (PSQI score ≥ 5) was confirmed in 68.9% of them. Multivariable analysis revealed the following factors associated with poor sleep quality: chronic heart failure (OR 3.111; 95% CI, 1.083–8.941, p = 0.035), male sex (OR 0.396; 95% CI, 0.199–0.787, p = 0.008), total ESS score (OR 1.193; 95% CI, 1.124–1.266, p < 0.001), minimal saturation during sleep (OR 1.034; 95% CI, 1.002–1.066, p = 0.036), and N3 percentage of total sleep time (OR 1.110; 95% CI, 1.027–1.200, p = 0.009). Conclusions: Our study suggests that both the female sex and coexistence of heart failure are independent risk factors for poor sleep quality. Moreover, we hypothesize that nocturnal hypoxia may lead to a misperception of sleep quality and may explain the counterintuitive association between a higher proportion of deep sleep and poor sleep quality.

To evaluate association between bariatric surgery and changes in obstructive sleep apnea (OSA) severity and sleep architecture was as well as to asses continuous positive airway pressure (CPAP) effectiveness and compliance. We enrolled patients undergoing bariatric surgery. Polysomnography was performed in each patient preoperatively and 12 months after the procedure in a subgroup of patients diagnosed with OSA. STOP-BANG, Epworth Sleepiness Scale (ESS) and Berlin questionnaire scores were obtained pre- and postoperatively. CPAP compliance data was recorded during follow-up hospitalization. Among 44 patients with median age of 49.5 years, predominantly women (68.2%) pre- and postoperative polysomnography was performed. We observed significant improvement in STOP-BANG (6.0 vs. 3.0, p

Background The asthma-related airway wall remodeling is associated i.a. with a damage of bronchial epithelium and subepithelial fibrosis. Functional interactions between human bronchial epithelial cells and human bronchial fibroblasts are known as the epithelial-mesenchymal trophic unit (EMTU) and are necessary for a proper functioning of lung tissue. However, a high concentration of the transforming growth factor-β1 (TGF-β1) in the asthmatic bronchi drives the structural disintegrity of epithelium with the epithelial-to-mesenchymal transition (EMT) of the bronchial epithelial cells, and of subepithelial fibrosis with the fibroblast-to-myofibroblast transition (FMT) of the bronchial fibroblasts. Since previous reports indicate different intrinsic properties of the human bronchial epithelial cells and human bronchial fibroblasts which affect their EMT/FMT potential beetween cells derived from asthmatic and non-asthmatic patients, cultured separatelly in vitro, we were interested to see whether corresponding effects could be obtained in a co-culture of the bronchial epithelial cells and bronchial fibroblasts. In this study, we investigate the effects of the TGF-β1 on the EMT markers of the bronchial epithelial cells cultured in the air-liquid-interface and effectiveness of FMT in the bronchial fibroblast populations in the EMTU models. Results Our results show that the asthmatic co-cultures are more sensitive to the TGF-β1 than the non-asthmatic ones, which is associated with a higher potential of the asthmatic bronchial cells for a profibrotic response, analogously to be observed in '2D' cultures. They also indicate a noticeable impact of human bronchial epithelial cells on the TGF-β1-induced FMT, stronger in the asthmatic bronchial fibroblast populations in comparison to the non-asthmatic ones. Moreover, our results suggest the protective effects of fibroblasts on the structure of the TGF-β1–exposed mucociliary differentiated bronchial epithelial cells and their EMT potential. Conclusions Our data are the first to demonstrate a protective effect of the human bronchial fibroblasts on the properties of the human bronchial epithelial cells, which suggests that intrinsic properties of not only epithelium but also subepithelial fibroblasts affect a proper condition and function of the EMTU in both normal and asthmatic individuals.

Background Pirfenidone is an antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis (IPF). The drug is available for Polish patients with IPF since 2017. The PolExPIR study aimed to describe the real-world data (RWD) on the Polish experience of pirfenidone therapy in IPF with respect to safety and efficacy profiles. Methods This was a multicentre, retrospective, observational study collecting clinical data of patients with IPF receiving pirfenidone from January 2017 to September 2019 across 10 specialized pulmonary centres in Poland. Data collection included baseline characteristics, pulmonary function tests (PFTs) results and six-minute walk test (6MWT). Longitudinal data on PFTs, 6MWT, adverse drug reactions (ADRs), treatment persistence, and survival were also collected up to 24 months post-inclusion. Results A total of 307 patients receiving pirfenidone were identified for analysis. The mean age was 68.83 (8.13) years and 77% were males. The median time from the first symptoms to IPF diagnosis was 15.5 (9.75–30) months and from diagnosis to start of pirfenidone treatment was 6 (2–23) months. Patients were followed on treatment for a median of 17 (12–22.75) months. Seventy-four patients (24.1%) required dose adjustments and 35 (11.4%) were chronically treated with different than the full recommended dose. A total of 141 patients (45.92%) discontinued therapy due to different reasons including ADRs (16.61%), death (8.79%), disease progression (6.51%), patient’s own request (5.54%), neoplastic disease (3.91%) and lung transplantation (0.33%). Over up to 24 months of follow-up, the pulmonary function remained largely stable. The median annual decline in forced vital capacity (FVC) during the first year of pirfenidone therapy was −20 ml (−200–100) and during the second year was −120 ml (−340–30). Over a study period, 33 patients (10.75%) died. Conclusions The PolExPIR study is a source of longitudinal RWD on pirfenidone therapy in the Polish cohort of patients with IPF supporting its long-term acceptable safety and efficacy profiles and reinforce findings from the previous randomised clinical trials and observational studies.

Background: The transmission of tuberculosis may affect the incidence rate of the disease in Poland. Genetic methods are of assistance in tracing the infection transmission, identifying its sources, determining the risk groups, and focusing on the preventive actions. Objectives: The objectives of this study lie in an assessment of tuberculosis transmission by genetic methods with the assistance of the standard epidemiologic interview. Methods: The genome DNA of 275 Mycobacterium tuberculosis (Mtb) strains from tuberculosis patients, inhabitants of the city of Krakow, was subjected to a genetic analysis via the spoligotyping method and the IS6110-Mtb1–Mtb2 polymerase chain reaction (PCR) method. If the DNA profiles were identical in both of the PCRs, they were considered identical and classified within one molecular family. Results: Among 275 strains, 104 genetic patterns (spoligotypes) were identified. Two hundred and three strains were divided into 66 molecular families (clusters) and analyzed with the IS6110- Mtb1–Mtb2 PCR method. Eighteen clusters were separated. In the Mtb1–Mtb2 clusters, 21 patients were in the risk groups (the homeless, prisoners, and nursing home residents). We did not confirm any direct or temporary contacts between the patients constituting the Mtb1–Mtb2 clusters (apart from the risk groups). However, the patients in these clusters often lived in the same parts of Krakow. Conclusions: The standard epidemiologic interview in tuberculosis patients should be combined with genetic methods. Active transmission of tuberculosis occurs largely among the individuals maintaining probably periodic contacts. The patients who are in the risk groups may play an important role in the transmission of tuberculosis.

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.

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 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.

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.

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

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.

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.

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.

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.

Background: Air trapping evaluated in high-resolution computed tomography (HRCT) reflects changes in small bronchi. We simultaneously evaluated focal and diffuse air trapping in asthmatic patients. Objectives: (1) To evaluate air trapping and bronchial wall thickness in asthmatics. (2) To estimate the relationship between air trapping and bronchial wall thickness, pulmonary function tests (PFTs), age, gender and asthma severity. (3) To compare air trapping between subgroups of asthmatic patients with normal FEV1 % pred. and FEV1/FVC % and controls. (4) To compare air trapping and bronchial wall thickness between aspirin-induced asthmatics (AIA) and aspirin-tolerant asthmatics (ATA). Methods: Both groups (asthmatics and controls) included 30 patients. All patients underwent HRCT and PFTs. Results: Focal (p < 0.0001) and diffuse (p = 0.0004) air trappings and bronchial wall thickness (T: p < 0.0001; T/D: p < 0.0001; WA%: p < 0.0001) were significantly greater in asthmatics. Focal and diffuse air trappings were inversely correlated (p = 0.021). Diffuse air trapping correlated with bronchial wall thickness: T/D (p = 0.047), T (p = 0.037), and WA% (p = 0.048). There was a significant difference in the extent of focal air trapping between a subgroup of asthmatics with normal FEV1 % pred. and FEV1/FVC % and controls (p < 0.0001). There were no significant differences in focal (p = 0.095) and diffuse air trapping (p = 0.186) and bronchial wall thickness (T: p = 0.086; T/D: p = 0.428; WA%: p = 0.428) between AIA and ATA patients. Conclusions: Both focal and diffuse air trappings provide valuable diagnostic information and therefore deserve to be estimated. The lack of significant differences in air trapping and bronchial wall thickness between AIA and ATA patients needs further investigation.

Objective Videothoracoscopic sympathecomy is a widely used treatment modality in patients with severe Raynaud disease, but the reported late results are less than favorable. There have been no direct studies of the long-term effect of sympathectomy on microcirculation in the hands of these patients. Methods In 25 patients with Raynaud disease treated with videothoracoscopic Th2-Th4 sympathectomy, we performed basal laser-Doppler flowmetry and measured the maximal refilling time after 1-minute occlusion measurements preoperatively and at 1 week, 6 months, and 1, 2, 3, and 5 years after the sympathectomy. The results were compared with the same measurements obtained in the group of 50 healthy individuals. Results The patients' symptom severity was assessed by using the visual analogue scale. The basal capillary flow and the maximal refilling time improved after the sympathectomy to a level not different from that seen in the healthy population, and the effect was maintained during the 5-year follow-up period. The patients' symptom severity scores diminished to zero in the early postoperative period and increased to 28% of their initial value 5 years after the operation. Conclusions The videothoracoscopic Th2-Th4 sympathectomy produces excellent and long-lasting improvement of microcirculation function in patients with Raynaud disease. The mild return of symptoms might be due to factors other than the capillary blood flow alterations.

Pulmonary emphysema is anatomically defined as abnormal persistent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of alveolar walls, without evident fibrosis. High-resolution computer tomography (HRCT) imaging is a valuable tool for diagnosis of this disease. The presence of minute cysts distributed evenly through all lung zones is rarely observed in pulmonary emphysema. In such cases, emphysema should be differentiated from other cystic lung diseases. We present a case of a 45-year-old women admitted to our Department with dyspnoea on exertion. Physical examination revealed no abnormalities. A chest radiograph showed diffused interstitial lesions in both lungs; HRCT revealed multiple oval-shaped cysts equally dispersed in all lung areas. The pulmonary function tests revealed increased lung volumes (total lung capacity 114.6% predicted, residual volume 200.6% of predicted), while both vital capacity and FEV1 were decreased (73.6% and 54.0% of predicted volumes, respectively). Diffused lung capacity was normal. Trans-bronchial biopsy was non contributory. Histiological examination of lung tissue obtained by videothoraco-scopy (VTS) was diagnostic for bullous emphysema. The patient had prescribed ipratropium bromide and teophyline. Differential diagnosis, apart from pulmonary emphysema, should take into consideration lymphangioleiomyomatosis, histiocytosis and sarcoidosis.

The aim of the study was to assess the diagnostic yield of transbronchial lung biopsy (TBLB) without fluoroscopic guidance in peripheral lesions of diameter 2,5-6 cm. TBLB was performed in 65 consecutive patients without abnormalities in bronchial tree in standard bronchofiberoscopy and preceded by computed tomography (CT). The CT guidance helped to select the segment of lung to be biopsied. In 39 patients (60%) TBLB enabled to diagnose 36 cases of lung cancer, 2 cases of carcinoid and 1 case of malignant lymphoma. There were 26 cases (including 21 cases of lung cancer) undiagnosed by means of TBLB. In 24 patients the diagnosis was established by means of other methods like transbronchial needle aspiration (TBNA)--5 cases, thin needle biopsy (TNB)--12 cases, open lung biopsy (OLB)--7 cases and in the remaining 2 patients a regression of clinical and radiological features was observed. Transbronchial lung biopsy was found to be efficient diagnostic method in peripheral lesions higher than 2,5cm. However, in 40% of cases this technique doesn't allow to establish a diagnosis. This, in turn implicates the necessity for further diagnostic procedures including TBNA, TNB or even OLB.

Videothoracoscopy is a useful diagnostic tool in patients with suspicion of malignant pleural effusion, because of both: the high accuracy in diagnosis and the possibility of assessing the extent of pleural involvement and producing the pleurodesis. An analysis of characteristics of 110 patients with suspected pleural dissemination is presented, including final diagnosis established with the use of VTS. In patients with confirmed malignant pleural effusion following characteristics were analyzed: the extent of pleural metastatic involvement, type of the primary malignancy, possibility of re-expansion of the lung and patients survival according to the primary tumor and extent of involvement of the pleura.

The aim of the study was to assess the diagnostic yield of transbronchial needle aspiration (TBNA) in mediastinal or hilar adenopathy in: sarcoidosis, tuberculosis and malignancy. Transbronchial needle aspiration was performed in 53 patients, preeceded by computed tomography (CT). In 22 patients (41,5%) TBNA enabled to diagnose 10 cases of sarcoidosis, 12 cases of neoplastic infiltrates of the lung. There were 31 cases undiagnosed by means of TBNA. In 24 patients the diagnosis was established by means of other methods like bronchoscopy with mucose biopsy (8 cases of sarcoidosis), transbronchial lung biopsy (4 cases of squamous cell carcinoma and adenocarcinoma, 2 cases of sarcoidosis), mediastinoscopy (3 cases of sarcoidosis and 2 cases of Hodgkin's disease), and videothoracoscopy (2 cases of sarcoidosis), transthoracic needle biopsy (1 case of squamous cell carcinoma) and lymph node biopsy (1 case of adenocarcinoma and 1 case of sarcoidosis). In the remaining 7 patients who were followed-up for a period of one year the diagnosis of sarcoidosis was confirmed by clinical, radiological and cytological (BAL) examinations. Transbronchial needle aspiration was shown to be efficient diagnostic method in mediastinal or hilar adenopathy in sarcoidosis and malignancy except lymphoma. Moreover in approximately 60% of cases this technique doesn't allow to establish a diagnosis and in turn implicates the necessity for further diagnostic procedures like mediastinoscopy, or transbronchial or thoracoscopic lung biopsy.

The aim of the study was to assess the diagnostic yield of transbronchial lung biopsy (TBLB) in some of diffuse pulmonary diseases, like: sarcoidosis, organizing pneumonia--(OP), tuberculosis and neoplasmatic infiltrates of the lung. Transbronchial lung biopsy was performed in 123 patients, preceded by high resolution computed tomography (HRCT). The HRCT guidance helped to select the area of lung to be biopsied. In 80 patients (65%) TBLB enabled to diagnose 40 cases of sarcoidosis, 15 cases of OP, 13 cases of neoplasmatic infiltrates of the lung and 5 cases of tuberculosis. There were 43 cases undiagnosed by means of TBLB. In 19 patients the diagnosis was established by means of other methods like videothoracoscopy (8 cases), bronchoscopy with bronchial mucose biopsy (7 cases of sarcoidosis), mediastinoscopy (2 cases of Hodgkin's disease), transthoracic needle biopsy (2 cases of adenocarcinoma). Moreover sarcoidosis was diagnosed in 15 cases by means of clinical, radiological examination and BAL. 9 patients didn't agree for further invasive diagnostics. Transbronchial lung biopsy was shown to be efficient diagnostic method especially in sarcoidosis, OP and neoplasmatic infiltrates of the lung. However, in approximately 35% of cases of diffuse pulmonary diseases this technique doesn't allow to establish a diagnosis. This in turn implicates the necessity for further diagnostic procedures including videothoracoscopic or open lung biopsy.

We have described a case of a 70-year-old woman, treated for a pancreas cancer, which was diagnosed for many months because of atypical skin lesions, lymphadenopathy and progressing cachexia. Despite many autoimmunological, serological, histopathological, bacteriological and mycological examinations there was no diagnosis. Finally the case of extrapulmonary tuberculosis involving skin, lymph nodes, kidneys and bones was diagnosed. After the introduction of antituberculotic therapy we are observing some clinical improvement and regression of symptoms.

Background: Acetylsalicylic acid (ASA) and other nonsteroid anti-inflammatory drugs (NSAIDs) are reported to account for 21–25% of all adverse drug reactions. Some asthmatics may react to ASA and other NSAIDs with acute bronchoconstriction, profuse rhinorrhea and skin flushing. This is a distinct clinical syndrome called aspirin-induced asthma (AIA). The prevalence of AIA among asthmatic patients in Poland has not been previously assessed. Methods: A questionnaire survey of 12 970 adults of both sexes, randomly selected from the population of Poland. Results: The prevalence of AIA in the general population of Poland was estimated as 0.6%. Thirty patients (4.3%; 95% CI: 2.8–5.8) of 703 asthmatics (5.4% of general population) reported symptoms attesting to hypersensitivity to aspirin. In 27% of them the reactions were precipitated by aspirin, whereas in the remaining subjects by other NSAIDs. Conclusions: The prevalence of AIA in Poland is 4.3%, being somewhat lower than in Finland and Australia, where it was recently reported to account for 8.8 and 10.9% of the adult asthmatics, respectively. These figures indicate that aspirin hypersensitivity might be a significant community problem.

Malignant pleural effusion is a common problem in advanced cancers, contributing to the poor quality of life in this group of patients. The aim of the study was to assess the efficiency of talc powder and doxycycline in pleurodesis in patients with malignant pleural effusion in comparable conditions.Of 52 patients screened, 33 entered the trial. They were randomized to the talc group (n=18) and the doxycycline group (n=15). Both groups were comparable with regard to age, sex and the most important variables influencing effectiveness of the procedure, i.e. primary malignancy and stage of metastatic involvement of the pleura. Efficiency of pleurodesis was prospectively assessed.The analysis of short-term effectiveness of pleurodesis in the first 33 patients has shown a highly significant difference in favor of talc powder (p=0.009); this difference was the reason for terminating the randomization. Further observation has revealed in the doxycycline group an increasing number of patients with fluid reaccumulation, as time went by; this was not observed in the talc group. A statistical analysis of the long-term effectiveness of both agents studied has shown a more significant difference in favor of the talc powder (p=0.00003).Talc powder is superior to doxycycline in achieving pleurodesis in patients with malignant pleural effusion, in both short- and long-term observations.

The treatment of chronic severe asthma is unsatisfactory for many patients. The aim of the study was to determine the effects of treatment of steroid-dependent asthma with cyclosporin. We performed a double-blind, placebo-controlled, randomized, parallel group trial on the effect of cyclosporin on pulmonary function, asthma severity and tapering of prednisone in 34 steroid-dependent asthmatics (mean oral prednisone dose: 16 mg.day-1). The study consisted of: 1) baseline period (12 weeks); 2) experimental period divided into two parts: Part I (12 weeks) cyclosporin or placebo treatment; Part II (22 weeks) cyclosporin or placebo treatment and oral prednisone reduction; and 3) follow-up observation (8 weeks). Asthma symptoms score, pulmonary function tests (daily peak expiratory flow (PEF) and bi-weekly forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid-expiratory flow (MEF50), biochemical profile and blood cyclosporin levels were monitored throughout the study. Following cyclosporin administration, a slight beneficial effect on some subjective parameters of asthma severity was observed. At the same time, no beneficial effect on pulmonary function was noted. The time trends analysis of mean daily prednisone doses between the treatment groups revealed a statistically significant difference indicating that, during prednisone reduction, cyclosporin seemed to be slightly more efficient than placebo in reducing the requirement for systemic corticosteroid, even though the steroid reduction was accompanied by slight impairment of some pulmonary function. However, there was no significant difference in the final dose reduction between the treatment groups. These data and the known toxicity of the drug suggest a limited place for cyclosporin treatment in steroid-dependent bronchial asthma.

We have recently shown that oral aspirin provocation leads to an increase in LTE4 and a reduction in 11-dehydro-TXB2 levels in urine of patients with aspirin induced-asthma (AIA). To test the hypothesis that cyclooxygenase inhibition and an enhancement of cysteinyl-leukotriene production occurs in the lungs of patients with AIA, we examined the eicosanoid levels in bronchoalveolar lavage fluid obtained 30 min after lysine-aspirin or placebo inhalation in 10 patients with AIA. Eosinophil cationic protein (ECP) levels were determined to evaluate eosinophil activation. Six asthmatics nonsensitive to aspirin (NA) underwent challenge with placebo. The dose of lysine-aspirin inhaled by patients with AIA was equal to that which had produced > or = 20% fall in FEV1. Compared with NA, patients with AIA had: (1) eicosanoid levels, particularly PGE2 and TXB2, elevated and (2) higher number of eosinophils and ECP. The overproduction of eicosanoids could be related to a distinct eosinophilic inflammation in airways of patients with AIA. Inhalation of lysine-aspirin had no effects on 12-HETE and 15-HETE levels, but it markedly depressed cyclooxygenase products and significantly enhanced leukotriene production in the lungs of patients with AIA.