Prevalence of anthelmintic resistance of gastrointestinal nematodes in Polish goat herds assessed by the larval development test.

BACKGROUND: Helminthic infections, in particular those caused by gastrointestinal nematodes (GIN), are found worldwide and are among the most economically important diseases of goats. Anthelmintic resistance (AR) in GIN of goats is currently present worldwide, and single- or multidrug resistant species are widespread. The aim of this study was to determine the prevalence of AR to benzimidazoles (BZ), macrocyclic lactones (ML) and imidazothiazoles represented by levamisole (LEV) in the Polish goat herds by using an in vitro larval development test, which is useful especially in large-scale epidemiological surveys. RESULTS: This cross-sectional study was conducted from September 2018 to June 2019 and enrolled 42 dairy goat herds scattered over the entire country. The most commonly used anthelmintic class in goat herds in Poland were BZ (92%), followed by ML (85%) and LEV (13%). BZ-resistant GIN populations were found in 37 herds (88%, CI 95%: 75 to 95%), ML-resistant GIN populations in 40 herds (95%, CI 95, 84 to 99%), and LEV-resistant GIN populations in 5 herds (12%, CI 95%: 5 to 25%). Multidrug resistance involving all three anthelmintic classes was found in 5 herds (12%, CI 95, 5 to 25%). Based on the morphological features of stage 3 larvae the main resistant GIN turned out to be Haemonchus contortus and Trichostrongylus spp. The use of BZ and frequency of anthelmintic treatments were significantly related to the presence of AR to BZ in Polish goat herds. CONCLUSIONS: This cross-sectional study demonstrates the existence of AR to BZ, ML and LEV on Polish goat farms. Resistance to BZ and ML is widespread, while AR to LEV is currently at a low level. A considerable proportion of herds harbours multidrug resistant GIN, which requires further consideration. An effective anthelmintic treatment strategy, reasonable preventive measures and better understanding of the resistance-related management practices by farmers and veterinarians may delay further development of AR.

Assessment of microvascular function in vivo using flow mediated skin fluorescence (FMSF) in patients with obstructive lung diseases: A preliminary study.

BACKGROUND: Cardiovascular diseases play an important role in the morbidity and mortality of patients with obstructive lung diseases. Impaired vascular endothelial function seems to be a key element linking obstructive lung disease and cardiovascular disease. Recently developed technique named flow mediated skin fluorescence (FMSF) is a novel, non-invasive tool to study microvascular function. METHODS: Total of 69 volunteers including 26 patients with chronic obstructive pulmonary disease (COPD), 23 patients with asthma and 20 healthy subjects underwent microvascular function assessments using FMSF. FMSF assessments were composed of measurements of reduced form of nicotinamide adenine dinucleotide (NADH) fluorescence intensity signal during brachial artery occlusion - ischemic response (IRmax) and immediately after release of occlusion - hyperemic response (HRmax). Associations of microvascular function with clinical and biochemical characteristics of studied subjects were also evaluated. RESULTS: The median value of IRmax was significantly lower in COPD subjects (2.4 [1.0-6.7] %) compared with healthy subjects (9.6 [3.7-13.5] %; p < 0.01). The mean value of HRmax was also significantly reduced in COPD subjects (9.7 (4.5) %) compared with both asthma subjects (12.1 (3.5) %; p < 0.05) and healthy control subjects (13.4 (2.9) %; p < 0.01). CONCLUSIONS: The FMSF technique makes it possible to identify impairments of the microvascular function in patients with COPD, but not in asthma patients. These exploratory findings require further validation in a larger patients cohort.

The first report of multidrug resistance in gastrointestinal nematodes in goat population in Poland.

BACKGROUND: Prophylactic anthelmintic treatment with one of three basic classes of anthelmintics (benzimidazoles, macrocyclic lactones and imidazothiazoles) is still the mainstay of control of gastrointestinal nematode infections in small ruminants worldwide. As a consequence, anthelmintic resistance is a serious threat to small ruminant health and production. While the resistance to one class of anthelmintics has already been reported in most of countries, the newly-emerging problem is the resistance to two or even all of classes referred to as multidrug resistance. This study aimed to evidence the presence of multidrug resistance of gastrointestinal nematodes in goats in Poland. RESULTS: The combination of one in vivo method (fecal egg count reduction test) and two in vitro methods (egg hatch test and larval development test) performed in two goat herds in the southern Poland showed the presence of gastrointestinal nematodes resistant to fenbendazole and ivermectin in both herds. Moreover, in one herd it revealed the development of resistance to the last effective anthelmintic, levamisole, in response to one-year intensive use. Haemonchus contortus was the most prevalent gastrointestinal nematode in samples in which resistance to benzimidazoles and ivermectin was found, whereas Trichostrongylus colubriformis predominated when resistance to levamisole was observed. CONCLUSION: This study shows for the first time that multidrug resistance of gastrointestinal nematodes to three basic classes of anthelmintics is already present in goat population in Poland. Moreover, it may indicate that different species or genera of gastrointestinal nematodes are responsible for the resistance to specific anthelmintics.

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

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

The association between airway eosinophilic inflammation and IL-33 in stable non-atopic COPD.

BACKGROUND: Interleukin(IL)-33 is an epithelial alarmin important for eosinophil maturation, activation and survival. The aim of this study was to examine the association between IL-33, its receptor expression and airway eosinophilic inflammation in non-atopic COPD. METHODS: IL-33 concentrations were measured in exhaled breath condensate (EBC) collected from healthy non-smokers, asthmatics and non-atopic COPD subjects using ELISA. Serum and sputum samples were collected from healthy non-smokers, healthy smokers and non-atopic COPD patients. Based on sputum eosinophil count, COPD subjects were divided into subgroups with airway eosinophilic inflammation (sputum eosinophils > 3%) or without (sputum eosinophils ≤3%). IL-33 and soluble form of IL-33 receptor (sST2) protein concentrations were measured in serum and sputum supernatants using ELISA. ST2 mRNA expression was measured in peripheral mononuclear cells and sputum cells by qPCR. Hemopoietic progenitor cells (HPC) expressing ST2 and intracellular IL-5 were enumerated in blood and induced sputum by means of flow cytometry. RESULTS: IL-33 levels in EBC were increased in COPD patients to a similar extent as in asthma and correlated with blood eosinophil count. Furthermore, serum and sputum IL-33 levels were higher in COPD subjects with sputum eosinophilia than in those with a sputum eosinophil count ≤3% (p < 0.001 for both). ST2 mRNA was overexpressed in sputum cells obtained from COPD patients with airway eosinophilic inflammation compared to those without sputum eosinophilia (p < 0.01). Similarly, ST2 + IL-5+ HPC numbers were increased in the sputum of COPD patients with airway eosinophilia (p < 0.001). CONCLUSIONS: Our results indicate that IL-33 is involved in the development of eosinophilic airway inflammation in non-atopic COPD patients.

Altered miRNA expression in pulmonary sarcoidosis.

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

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

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

Personality traits and styles of coping with stress in physicians.

UNLABELLED: The stress of being a doctor and being responsible for own decisions is one of the most intense feelings the doctors have to cope with. The stress coping styles are determined by the factors dependent on psychological variables such as personality. AIM: The aim of study was to assess the relation between personality traits and stress coping among physicians. MATERIALS AND METHODS: The study group consisted of 50 physicians (males n=25; 50%) employed in Norbert Barlicki Memorial Medical University Teaching Hospital No 1 in Lodz. The stress coping styles were assessed using Coping Inventory for Stressful Situations, whereas the tool used for personality assessment was NEO Five Factor Inventory of Personality. RESULTS: Task-oriented coping (TOC) was the predominant stress coping style among physicians (mean sten value 6.7±2.0; high sten scores - 8-10 in 38%). Among all dimensions of the doctors' personality, extraversion predominated significantly (mean sten value 9.7±0.7). Neuroticism correlated positively with emotional oriented coping (EOC) (r=0.43). Extraversion influenced more infrequent adoption of EOC by males (r=-0.43) and older subjects (≥44years) (r=-0.52). Conscientiousness influenced more frequent adoption of TOC by females (r=0.46). Both the doctors' age (r=-0.49 p<0.05)), and duration of employment (r=-0.49 p<0.05)) significantly correlated negatively with AOC. The doctors' gender did not affect their stress coping styles. CONCLUSIONS: Task oriented coping was the dominant stress coping style among physicians. High levels of neuroticism correlated positively, and those of extraversion negatively with the adoption of emotional oriented coping with stress. The tendency to choose the avoidance oriented coping decreases with the physicians' age and duration of employment.

Preliminary studies: differences in microRNA expression in asthma and chronic obstructive pulmonary disease.

INTRODUCTION: The asthma- and chronic obstructive pulmonary disease (COPD)-related morbidity has been increasing during the recent years. Both asthma and COPD are diseases of inflammatory etiology. The increasing interest in the pathomechanisms involved in the development of obstructive pulmonary diseases seems to be fully justified. Recent research has attempted to determine the associations of microRNA with the pathogenesis of pulmonary diseases. AIM: To assess the expression of microRNA in the blood sera of patients diagnosed with bronchial asthma and chronic obstructive pulmonary disease in comparison with healthy subjects. MATERIAL AND METHODS: In our study, at the preliminary stage, we compared the expression of miRNA in the groups of patients with asthma and COPD versus the control group of healthy subjects. RESULTS: A significant difference in hsa-miRNA-224, hsa-miRNA-339-5p, hsa-miRNA-382 in patients with asthma and COPD as compared with the controls was noted. CONCLUSIONS: With such difference of expression of specific micro-RNA in serum of patient with asthma and COPD, those small non-coding RNA has to play a significant role in those diseases pathway. Therefore we expect to increase the size and differentation of the study groups in next studies.

Immunoexpression of TGF-ß/Smad and VEGF-A proteins in serum and BAL fluid of sarcoidosis patients.

BACKGROUND: The chronic course of pulmonary sarcoidosis can lead to lung dysfunction due to fibrosis, in which the signalling pathways TGF-ß/Smad and VEGF-A may play a key role. METHODS: We evaluated immunoexpression of TGF-ß1, Smad2, 3, and 7, and VEGF-A in serum and bronchoalveolar lavage (BAL) fluid of patients (n = 57) classified according to the presence of lung parenchymal involvement (radiological stage I vs. II-III), acute vs. insidious onset, lung function test (LFT) results, calcium metabolism parameters, percentage of BAL lymphocytes (BAL-L%), BAL CD4(+)/CD8(+) ratio, age, and gender. Immunoexpression analysis of proteins was performed by ELISA. RESULTS: The immunoexpression of all studied proteins were higher in serum than in BAL fluid of patients (p >0.05). The serum levels of TGF-ß1 (p = 0.03), Smad2 (p = 0.01), and VEGF-A (p = 0.0002) were significantly higher in sarcoidosis patients compared to healthy controls. There were no differences within the sarcoidosis group between patients with vs. without parenchymal involvement, acute vs. insidious onset, or patients with normal vs. abnormal spirometry results. In patients with abnormal spirometry results a negative correlation was found between forced vital capacity (FVC) % predicted value and TGF-ß1 immunoexpression in BAL fluid, and positive correlations were observed between the intensity of lung parenchymal changes estimated by high-resolution computed tomography (HRCT scores) and Smad 2 level in serum. CONCLUSIONS: TGF-ß/Smad signalling pathway and VEGF-A participate in the pathogenesis of sarcoidosis. BAL TGF-ß1, and Smad 2 in serum seem to be promising biomarkers with negative prognostic value, but further studies are required to confirmed our observations.

Oxidative stress and damage to erythrocytes in patients with chronic obstructive pulmonary disease--changes in ATPase and acetylcholinesterase activity.

The study indicates, for the first time, the changes in both ATPase and AChE activities in the membrane of red blood cells of patients diagnosed with COPD. Chronic obstructive pulmonary disease (COPD) is one of the most common and severe lung disorders. We examined the impact of COPD on redox balance and properties of the membrane of red blood cells. The study involved 30 patients with COPD and 18 healthy subjects. An increase in lipid peroxidation products and a decrease in the content of -SH groups in the membrane of red blood cells in patients with COPD were observed. Moreover, an increase in the activity of glutathione peroxidase and a decrease in superoxide dismutase, but not in catalase activity, were found as well. Significant changes in activities of erythrocyte membrane enzymes in COPD patients were also evident demonstrated by a considerably lowered ATPase activity and elevated AChE activity. Changes in the structure and function of red blood cells observed in COPD patients, together with changes in the activity of the key membrane enzymes (ATPases and AChE), can result from the imbalance of redox status of these cells due to extensive oxidative stress induced by COPD disease.

Quantitative analysis of mRNA expression levels and DNA methylation profiles of three neighboring genes: FUS1, NPRL2/G21 and RASSF1A in non-small cell lung cancer patients.

BACKGROUND: Tumor suppressor gene (TSG) inactivation plays a crucial role in carcinogenesis. FUS1, NPRL2/G21 and RASSF1A are TSGs from LUCA region at 3p21.3, a critical chromosomal region in lung cancer development. The aim of the study was to analyze and compare the expression levels of these 3 TSGs in NSCLC, as well as in macroscopically unchanged lung tissue surrounding the primary lesion, and to look for the possible epigenetic mechanism of TSG inactivation via gene promoter methylation. METHODS: Expression levels of 3 TSGs and 2 DNA methyltransferases, DNMT1 and DNMT3B, were assessed using real-time PCR method (qPCR) in 59 primary non-small cell lung tumors and the matched macroscopically unchanged lung tissue samples. Promoter methylation status of TSGs was analyzed using methylation-specific PCRs (MSP method) and Methylation Index (MI) value was calculated for each gene. RESULTS: The expression of all three TSGs were significantly different between NSCLC subtypes: RASSF1A and FUS1 expression levels were significantly lower in squamous cell carcinoma (SCC), and NPRL2/G21 in adenocarcinoma (AC). RASSF1A showed significantly lower expression in tumors vs macroscopically unchanged lung tissues. Methylation frequency was 38-76%, depending on the gene. The highest MI value was found for RASSF1A (52%) and the lowest for NPRL2/G21 (5%). The simultaneous decreased expression and methylation of at least one RASSF1A allele was observed in 71% tumor samples. Inverse correlation between gene expression and promoter methylation was found for FUS1 (rs = -0.41) in SCC subtype. Expression levels of DNMTs were significantly increased in 75-92% NSCLCs and were significantly higher in tumors than in normal lung tissue. However, no correlation between mRNA expression levels of DNMTs and DNA methylation status of the studied TSGs was found. CONCLUSIONS: The results indicate the potential role of the studied TSGs in the differentiation of NSCLC histopathological subtypes. The significant differences in RASSF1A expression levels between NSCLC and macroscopically unchanged lung tissue highlight its possible diagnostic role in lung cancer in situ recognition. High percentage of lung tumor samples with simultaneous RASSF1A decreased expression and gene promoter methylation indicates its epigenetic silencing. However, DNMT overexpression doesn't seem to be a critical determinate of its promoter hypermethylation.

Short-term reproducibility of the inflammatory phenotype in different subgroups of adult asthma cohort.

Inflammatory phenotype classification using induced sputum appears attractive as it can be applied to inflammation-based management of the patients with asthma. The aim of the study was to determine the reproducibility of inflammatory phenotype over time in patients with asthma. In 66 adults asthma was categorized as steroid-naïve (SN, n = 17), mild to moderate (MMA, n = 33), and refractory treated with oral corticosteroids (RA, n = 16). Clinical assessment, skin prick testing, spirometry, and two sputum inductions in 4-6-week interval were done. Inflammatory phenotypes were classified as eosinophilic (EA), consisting of eosinophilic and mixed granulocytic phenotypes, and noneosinophilic (NEA) consisting of paucigranulocytic and neutrophilic phenotypes. During study asthma treatment remained constant. In SN group 25% of patients changed phenotype from EA to NEA and 44% changed phenotype from NEA to EA. In MMA group 26% of patients changed phenotype from EA to NEA and 50% changed phenotype from NEA to EA. In 29% of RA patients inflammatory phenotype changed from EA to NEA and in 22% it changed from NEA to EA. Inflammatory classification, using induced sputum, is not fully reproducible in adults with asthma in short-term evaluation. EA seems to be more stable phenotype across all subgroups whereas NEA remained stable only in RA group.

Association between asthma control test, pulmonary function tests and non-specific bronchial hyperresponsiveness in assessing the level of asthma control.

INTRODUCTION: Global Initiative for Asthma (GINA) reports emphasize the use of validated and simple tools in order to assess the level of asthma control, as the Asthma Control Test (ACT). However, an ACT does not include assessment of airway inflammation, which is better reflected when measuring nonspecific bronchial hyperresponsiveness (BHR). The authors aimed to find out if the level of asthma control quantified by an ACT correlates with BHR and pulmonary function tests. MATERIAL AND METHODS: 118 asthmatics participated in the study. All patients completed an ACT. The scores of the ACTs were compared with pulmonary function tests and BHR assessed with the methacholine challenge test and expressed as a provocative concentration of methacholine, inducing a 20% decline in the FEV1 (PC20 M in mg/ml). RESULTS: Patients with controlled asthma amounted to 52 (44%) while those with uncontrolled asthma amounted to 66 (56%). In patients with controlled asthma (ACT score ≥ 20) the mean geometric value of PC20M was 2.72 mg/ml (range from 0.25 to > 8.0), whereas 0.94 mg/ml (range from 0.28 to 8.0) (p = 0.02) was observed in patients with uncontrolled asthma (ACT score < 20). Almost 64% (21/33) of uncontrolled asthmatics achieved normal lung function (FEV1 > 80% pred. value) while 19% (5/26) patients with controlled asthma presented an FEV1 < 80% predicted value. Asthma duration in years in controlled asthmatics was significantly shorter than in uncontrolled patients (6.2 ± 8.9 vs. 12.0 ± 11.4, p = 0.005) CONCLUSION: In determining the most accurate level of asthma control it is reasonable to use an ACT in conjunction with BHR, which provides more accurate assessment of bronchial inflammation than ventilatory parameters alone.

Extrabronchial symptoms and late phase reaction enhance the diagnostic value of aspirin bronchial challenge.

INTRODUCTION: Lysine aspirin (l-ASA) bronchial challenge can be used in the diagnostics of aspirin exacerbated respiratory disease. It is safer than oral challenge, however it is characterized by a lower sensitivity. AIM: We sought to investigate whether additional indicators of the positive result of l-ASA bronchial challenge, i.e. late phase reaction (LPR) and extrabronchial symptoms (EBS), may enhance its diagnostic value. MATERIAL AND METHODS: Sixty-seven patients with a positive history of asthma exacerbated by aspirin and/or other non-steroidal inflammatory drugs underwent l-ASA bronchial challenge. The control groups comprised 15 aspirin tolerant asthmatics and 15 healthy subjects. Forced expiratory volume in 1 s (FEV1) and 24-hour peak expiratory flow (PEF) measurements were performed in all subjects in order to recognize early and late response to l-ASA. All subjects underwent oral ASA challenge 2 weeks after l-ASA bronchial challenge. RESULTS: Basing on FEV1 and PEF results, early reaction was present in 50.7% of patients, early and LPR in 29.9% and LPR in only 10.4% of aspirin exacerbated respiratory disease patients. The EBS were noted in 31.3% of subjects. Inclusion of LPR and EBS as positive criteria of the challenge increased sensitivity to 94.0%. CONCLUSIONS: These results indicate that both LPR and EBS should be considered as positive criteria of aspirin bronchial challenge as they enhance its diagnostic value.

Concentration of angiopoietins 1 and 2 and their receptor Tie-2 in peripheral blood in patients with chronic obstructive pulmonary disease.

INTRODUCTION: Both angiopoietins (angiopoietin 1 - Ang-1, angiopoietin 2 - Ang-2) and angiopoietin receptors (Tie) are involved in angiogenesis and vascular remodeling. AIM: To assess concentrations of Ang-1, Ang-2 and Tie-2 in blood of patients with chronic obstructive pulmonary disease (COPD) and evaluate if their concentrations depend on the severity of the disease. MATERIAL AND METHODS: Thirty patients with COPD (stage II-IV) and 8 healthy smokers as well as 8 healthy non-smokers were included in the study. Detailed history was taken, physical examination and spirometry tests were done and blood samples were taken for evaluation of serum concentrations of Ang-1, Ang-2 and Tie. RESULTS: Among COPD patients, 8 patients suffered from moderate disease, 8 patients had severe, while 14 patients had very severe disease. The concentrations of Ang-1 and Ang-2 were not significantly greater in patients with COPD than in healthy controls. The highest concentrations of Ang-1 and Ang-2 were observed in patients with moderate COPD, and levels of Ang-2 correlated with Tie-2 in this group of patients. The levels of Ang-1 were the lowest in healthy non-smokers and in patients with severe COPD, where they inversely correlated with Tie-2. The concentrations of Ang-2 were not significantly higher in patients with moderate COPD when compared with those with severe and very severe disease and healthy smokers, and were significantly higher than in healthy non-smokers. CONCLUSIONS: It is possible that Ang-1, Ang-2 and Tie-2 play an important role especially in the early stage of COPD but not in the late phase when vascular complications of the disease occur.

Risk factors associated with irreversible airway obstruction in nonsmoking adult patients with severe asthma.

Persistent airways obstruction (PAO) may affect some patients with severe asthma and may significantly worsen the prognosis. This study was designed to detect risk factors associated with persistent airflow limitation in nonsmoking adult patients with severe asthma. A total of 68 adults with severe asthma were recruited and followed prospectively for four to six weeks during the stable phase of disease. For all patients, at every visit spirometry with reversibility test was performed. Based on the results, patients were stratified into group 1 (reversible obstruction) or group 2 (PAO). In both cohorts, associations of postbronchodilatator forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC) with patients' age, gender, asthma duration, history of atopy and allergy, family history, medications, frequency of previous exacerbations, infections, hospitalizations, and artificial ventilation due to the asthma attack-related respiratory failure were investigated. Using a univariate logistic regression analysis, we have shown that older age, more than six exacerbations per year, artificial ventilation in the past, at least one hospitalization per year, the presence of atopic dermatitis, and exposure to domestic visible mold were all independent risk factors of PAO. Furthermore, multivariate regression analysis demonstrated that especially those with domestic exposure to visible molds, with very frequent exacerbations and with at least one hospitalization throughout the last year, were at risk for developing PAO. Domestic exposure to molds, hospitalization during the last year, and very frequent exacerbations were associated with PAO in patients with severe asthma. These factors may help in predicting fixed airflow limitation in nonsmoking patients with severe asthma.

Occupational exposure to noise from authorized emergency vehicle sirens.

Warning signals generated by sirens of authorized emergency vehicles should be audible and recognizable to all road users. Currently, there is no legislation in Poland defining sound pressure levels (SPLs) of audible warning signals generated by sirens of authorized emergency vehicles. Measured A-weighted SPLs of those signals range between 104 and 108 dB. While for road users, an audible warning signal is a source of important information and its A-weighted SPL is acceptable, it may be a source of annoying noise to an emergency vehicle crew. That is why, it is necessary to find a method of improving the acoustic comfort of the crew and, at the same time, maintaining the informational function of audible warning signals.

Stratification of patients with COPD according to the 2011 GOLD report.

INTRODUCTION: The authors aimed to compare the distribution of COPD based on the new GOLD grading with stadium based exclusively on spirometry. MATERIAL AND METHODS: Eligible patients had an average age of 64.8 years and smoked at least 10 pack-years. COPD was defined according to GOLD fixed cut-off criterion FEV1/FVC < 0.70. In all patients postbronchodilator spirometry was performed. Categories were defined with the mMRC dyspnoea scale and CAT scale. COPD exacerbations in the previous year and lung function were evaluated. Statistical comparisons were done using t-student test. RESULTS: 315 COPD patients, 99 (31.4%) women and 216 (68.6%) men, were examined. Mean pack-years in the whole group was 47.1 ± 17.8. In women this figure was less than in men, 43.7 ± 19.2 vs 49.5 ± 16.5 (p > 0.05), respectively. At study entry, 144 subjects (45.7%) were current smokers, and the majority of them (n-87, 60.4%) belonged to category D - 26/66 (54.5%) women and 51/102 (50%) men. Based on spirometry alone, the patients were classified as moderate COPD 144 (45.71%), severe - 154 (48.89%), and very severe 17 (5.4%). According to the 2011 GOLD report stratification, 60 patients (19.04%) were graded as category A, 63 (20%) as category B, 24 (7.62%) as category C, and 168 (53.33%) as category D, although 21 (12.5% of them) were in category B, but the number of exacerbations classified them as category D. CONCLUSIONS: The COPD population is heterogeneous in reference to the symptoms, value of FEV1, and susceptibility to exacerbations. Clinical symptoms assessed using validated questionnaires characterized COPD patients better than the value of spirometric parameters (which are necessary for diagnosis of this disease). Some patients were difficult to classify, especially those belonging to category C.

[A 24-year-old male patient with pulmonary veno-occlusive disease - case report]. / 24-letni pacjent z choroba zarostowa zyl plucnych - opis przypadku.

Pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension characterised by poor prognosis. We report the case of a 24-year-old male patient with increasing dyspnea and exercise intolerance treated with calcium channel blockers and glucocorticosteroids, due to suspicion of pulmonary hypertension and interstitial lung disease, until lung biopsy was performed and a diagnosis of PVOD was established on the basis of the histological analysis of the lung biopsy sample. This case highlights that pulmonary veno-occlusive disease is a disorder that is difficult to diagnose and resistant to medical treatment, which is particularly poor prognostic factor. Due to poor response to medical therapy and high mortality in patients with PVOD, understanding the pathogenesis, differentiation with pulmonary arterial hypertension and the search for a new methods of treatment should be the key challenges for modern medicine.