Evaluation of selected IL6/STAT3 pathway molecules and miRNA expression in chronic obstructive pulmonary disease.

COPD has been regarded as a global epidemic due to an increase in pollution and tobacco exposure. Therefore, the study of molecular mechanism as the basis for modern therapy is important. The aim of the study was the assessment of gene expression levels, IL-6, IL-6ST, PIAS3, STAT3, and miRNAs, miRNA-1, miRNA-106b, miRNA-155, in patients with COPD. Induced sputum as well as PBMC were collected from 40 patients clinically verified according to the GOLD 2021 (A-D) classification and from the control group (n = 20). The levels of gene and miRNA expression were analysed by qPCR. In induced sputum IL6 was significantly down-regulated in COPD group compared with control (p = 0.0008), while IL6ST were up-regulated (p = 0.05). The results were also statistically significant for STAT3 (p = 0.04) and miRNA-155 (p = 0.03) with higher expression in the current smokers compared to ex-smokers. Higher expression levels for IL6ST (p = 0.03) in COPD patients with the exacerbation history compared to COPD patients without the exacerbation history were noted. Compared induced sputum and PB lymphocytes we observed higher expression of IL6 (p = 0.0003), STAT3 (p = 0.000001) miRNA-106b (p = 0.000069 and miRNA-155 (p = 0.000016) in induced sputum with lower expression of PIAS3 (p = 0.006), IL6ST (p = 0.002) and miRNA-1 (p = 0.001). Differences in gene expression levels of the IL-6/IL6ST/STAT3 pathway and miRNA depending on the smoking status and classification of patients according to GOLD suggest the importance of these genes in the pathogenesis of COPD and may indicate their potential utility in monitoring the course of the disease.

DNA methylation across the genome in aged human skeletal muscle tissue and muscle-derived cells: the role of HOX genes and physical activity.

Skeletal muscle tissue demonstrates global hypermethylation with age. However, methylome changes across the time-course of differentiation in aged human muscle derived cells, and larger coverage arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged heterogenous muscle-derived human primary cells (HDMCs) over several time points of differentiation (0, 72 h, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; pathways-in-cancer (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), rap1-signaling, axon-guidance and hippo-signalling. Aged cells also demonstrated a hypermethylated profile in pathways; axon-guidance, adherens-junction and calcium-signaling, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alterations in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in focal adhesion and PI3K-AKT signalling pathways. While the methylomes were vastly different between muscle tissue and HDMCs, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle tissue and cells on genes KIF15, DYRK2, FHL2, MRPS33, ABCA17P. Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6-8 CpGs in the HOX family of genes altered with age. With HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2 and HOXC10 all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionally HOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and HDMCs and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.

Development of resistance to eprinomectin in gastrointestinal nematodes in a goat herd with pre-existing resistance to benzimidazoles.

We described a first case of resistance to eprinomectin in goat herd in Poland in which resistance to benzimidazoles had been previously reported. The herd was established in 2011 by purchasing several goats from a single herd in south-eastern Poland. Resistance to benzimidazoles in the herd was first reported in 2017. Shortly after the owner started to signal low effectiveness of the treatment with eprinomectin. In June 2018 the larval development test from pooled faecal sample was performed and the results indicated the presence of resistance to macrocyclic lactones and levamisole. In July 2018 a faecal egg count (FEC) reduction test was performed in 39 animals with levamisole, eprinomectin and one untreated control group. Drugs were used in doses recommended for goats. Three methods of calculation of FEC reduction were compared. After eprinomectin treatment, FEC reduction ranged from 0 to 20%, depending on the method of calculation. FEC reduction following levamisole treatment was 100%. Main species present in the faecal samples after treatment and in larvicidal concentrations in larval development test was Haemonchus contortus. This is the first report of anthelminthic resistance to macrocylic lactones (eprinomectin) in goats in Poland.

Expression analysis of three miRNAs, miR-26a, miR-29b and miR-519d, in relation to MMP-2 expression level in non-small cell lung cancer patients: a pilot study.

Lung cancer is the most common cause of death in men and second only to breast cancer in women. MicroRNAs (miRNAs) are involved in tumorigenesis and function as oncogenes or tumor suppressor genes. Among other genes, miRNAs regulate matrix metalloproteinases (MMPs), the proteolytic enzymes playing a significant role in the degradation of extracellular matrix, enhancing tumor invasion and metastasis. The aim of the study was to evaluate the expression levels of selected miRNAs: miR-26a, miR-29b and miR-519d, and their target gene, matrix metalloproteinase-2 (MMP-2) in patients with non-small cell lung cancer (NSCLC). The results were correlated with tumor staging, NSCLC histopathological subtypes and patients' demographical features to assess the possible diagnostic/prognostic value of the studied miRNAs and MMP-2. Total RNA was isolated from 38 NSCLC tissue samples, and the expression analysis was performed using TaqMan(®) probes in qPCR assay. The results indicated underexpression of selected miRNAs and overexpression of MMP-2. The decrease in miRNA-29b expression was statistically significant and differentiated NSCLC histopathological subtypes. Additionally, statistically significant negative correlation was found between MMP-2 expression and its regulatory miR-26a. There are very few studies reporting miRNA-MMPs analysis on mRNA level in lung cancer, and no similar reports are available from Polish population. The results of our pilot study indicated the diagnostic potential of miR-29b and MMP-2, an inverse association between miR-26a and MMP-2, and proved the role of MMP-2 and the studied miRNAs in lung carcinogenesis. Further studies are needed to verify their potential usefulness for the treatment of lung cancer.

RARß Promoter Methylation as an Epigenetic Mechanism of Gene Silencing in Non-small Cell Lung Cancer.

The retinoid acid receptor-p (RARß) gene is one of the tumor suppressor genes (TSGs), which is frequently deleted or epigenetically silenced at an early stage of tumor progression. In this study we investigated the promoter methylation and expression status of the RARß gene in 60 surgically resected non-small cell lung cancer (NSCLC) tissue samples and 60 corresponding unchanged lung tissue samples, using methylation-specific PCR and real-time-polymerase chain reaction (qPCR) techniques. We correlated the results with the pathological features of tumors and clinical characteristics of patients. qPCR analysis detected a significantly lower RARß expression in the patients with adenocarcinoma (AC) and large cell carcinoma (LCC) than in those with squamous cell carcinoma (SCC) (AC vs. SCC, p = 0.032; AC and LCC vs. SCC, p = 0.0 13). Additionally, significantly lower expression of the RARß gene was revealed in the patients with non-squamous cell cancer with a history of smoking assessed as pack-years (PY < 40 vs. PY ≥ 40, p = 0.045). Regarding RARß promoter methylation, we found significant differences in the methylation index in the SCC group when considering pTNM staging; with higher index values in T1a + T1b compared with T2a + T2b and T3 + T4 groups (p = 0.024). There was no correlation between the methylation status and expression level of the RARß gene, which suggests that other molecular mechanisms influence the RARß expression in NSCLC patients. In conclusion, different expression of the RARß gene in SCC and NSCC makes the RARß gene a valuable diagnostic marker for differentiating the NSCLC subtypes.

Expression of HIF-1A/VEGF/ING-4 Axis in Pulmonary Sarcoidosis.

Angiogenesis/angiostasis regulated by hypoxia inducible factor-1A (HIF-1A)/vascular endothelial growth factor (VEGF)/inhibitor of growth protein 4 (ING-4) axis may be crucial for the course and outcome of sarcoidosis. Overexpression of angiogenic factors (activation of VEGF through HIF-1A) may predispose to chronic course and lung fibrosis, whereas immunoangiostasis (related to an overexpression of inhibitory ING-4) may be involved in granuloma formation in early sarcoid inflammation, or sustained or recurrent formation of granulomas. In this work we investigated gene expression of HIF-1A, VEGF and ING-4 in bronchoalveolar fluid (BALF) cells and in peripheral blood (PB) lymphocytes of sarcoidosis patients (n=94), to better understand mechanisms of the disease and to search for its biomarkers. The relative gene expression level (RQ value) was analyzed by qPCR. The results were evaluated according to the presence of lung parenchymal involvement (radiological stage I vs. II-IV), acute vs. insidious onset, lung function tests, calcium metabolism parameters, percentage of lymphocytes (BALL%) and BAL CD4+/CD8+ in BALF, age, and gender. In BALF cells, the ING-4 and VEGF RQ values were increased, while HIF-1A expression was decreased. In PB lymphocytes all studied genes were overexpressed. Higher expression of HIF-1A in PB lymphocytes of patients with abnormal spirometry, and in BALF cells of patients with lung volume restriction was found. VEGF gene expression in BALF cells was also higher in patients with abnormal spirometry. These findings were in line with previous data on the role of HIF-1A/VEGF/ING-4 axis in the pathogenesis of sarcoidosis. Up-regulated HIF-1A and VEGF genes are linked to acknowledged negative prognostics.

TGF-ß and SMADs mRNA Expression in Pulmonary Sarcoidosis.

Lung fibrosis is a complication of sarcoidosis, in which TGF-ß/Smad pathway may play an important role. We evaluated gene expression of TGF-ß1, SMAD2, 3 and 7 in bronchoalveolar lavage (BAL) cells and peripheral blood (PB) lymphocytes of sarcoidosis patients (n=94) to better understand the mechanisms of sarcoid inflammation. The relative gene expression was analyzed by qPCR method. Selected clinical/radiological features and biochemical markers were taken into account in the analysis. We found that TGF-ß1 and SMAD3 expressions in PB lymphocytes were significantly higher in sarcoidosis patients. Up-regulation of SMAD7 (inhibitory Smad) and down-regulation of SMAD3 in BAL cells in all subgroups were found. The expression of TGF-ß1 in PB lymphocytes was the highest in patients with lung parenchymal involvement and in the insidious onset phenotype. The expression of TGF-ß1 in BAL cells was higher in patients with abnormal spirometry (p=0.012), and TGF-ß1 and SMAD3 in patients with restrictive pattern (p=0.034 and 0.031, respectively). Several statistically significant negative correlations were found between the expression levels of SMAD2 and 3 in BAL cells and various LFT parameters. We conclude that TGF-ß/Smad pathway is involved in the pathogenesis of pulmonary sarcoidosis. These biomarkers (especially TGF-ß1, SMAD2 and 3) are of a negative prognostic value.

Decreased FAM107A Expression in Patients with Non-small Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related death in the world. Early detection, based on molecular markers, could decrease mortality from this disease. Tumor development is often associated with inactivation or loss of tumor suppressor genes (TSGs). The aim of the present study was to analyze the expression level of FAM107A gene, a TSG located in 3p21.1, in lung cancer tumors and in tumor adjacent normal lung samples. Promoter methylation status of FAM107A was evaluated as the potential mechanism of its epigenetic silencing. The relationship between gene mRNA expression and tumor staging, metastasis status, and non-small cell lung cancer (NSCLC) histopathological subtypes in 60 patients was analyzed. Total RNA was isolated from tissue samples and gene expression was assessed in qPCR assay. Gene promoter methylation status was evaluated in MSP reactions, using bisulfite converted DNA and two pairs of primers: methylated and unmethylated. We found that the expression of the gene was dramatically decreased in all NSCLC samples and was significantly lower than in tumor adjacent normal lung tissue. Promoter methylation of FAM107A gene was confirmed only in the minority of NSCLCs. The results highlight the importance of FAM107A in lung carcinogenesis, although indicate other than promoter hypermethylation mechanism of the gene decreased expression.

Benefits of ICA in the Case of a Few Channel EEG.

Independent Component Analysis (ICA) is often used at the signal preprocessing stage in EEG analysis for its ability to filter out artifacts from the signal. The benefits of using ICA are the most apparent when multi-channel signal is recorded. The question is, however, what kind of benefits (if any) can be obtained when ICA is applied for a few channel recording. We addressed this question in this paper by setting up the hypothesis that even in the case of only three channels, ICA can rearrange the sources to new mixtures in such a way that the true brain sources will be enhanced in some components, and the artifacts will be enhanced in others. To verify our hypothesis we applied three popular ICA algorithms to preprocess data from a benchmark file (motor imagery file from the II BCI Competition). Our results, presented in terms of classification precision, show that all ICA algorithms enhanced the signal to noise ratio for components correlating with signals recorded over C3 and C4 channels (the classification precision was higher in their case) and lessened the signal to noise ratio for components correlating with signals recorded over Cz channels.

ZAP70 expression in regulatory T cells in allergic rhinitis: effect of immunotherapy.

BACKGROUND: Some allergic diseases may be accompanied by inappropriate number or malfunction of regulatory T cells, which seems to be modified by specific immunotherapy (SIT). OBJECTIVES: To assess if immunotherapy affects regulatory T lymphocytes (Tregs) and their expression of zeta chain associated protein kinase (Zap70), which is essential for T cell activation and intracellular signal downstream transduction. METHODS: A 3-year prospective, placebo-controlled, double-blind trial of grass SIT was conducted. Forty-one patients sensitized to grass pollen with intermittent allergic rhinitis were randomized to receive SIT (n = 21) or placebo (n = 20) and 15 healthy were included as a control. Concentration of exhaled nitric oxide (ENO), lung function, symptom scores, the subsets of regulatory T cells (CD4(+)  CD25hiCD127low) which express ZAP70 and the level of ZAP70 expression in this subset were assessed at baseline and during the treatment period: before the onset, at the height of the pollen season and after the end of the pollen season. RESULTS: The concentration of nitric oxide and the symptom score were significantly higher in allergic rhinitis patients as compared with the control group. Natural allergen stimulation diminished both the numbers of regulatory T cells that express ZAP70 and the expression of Zap70 within these cells. In the second year of treatment, immunotherapy reduced significantly the symptom scores, concentrations of ENO (P < 0.01), intensively increased expression of ZAP70 in regulatory T cells (P < 0.001) and the percentage of cells that express ZAP70 (P < 0.05) at the height of the pollen season. Placebo treatment did not reduce scores, ENO (P > 0.05) nor had influence on Zap70 expression (P > 0.05). CONCLUSIONS: SIT with grass pollen effectively reduces rhinitis severity and affects allergic airway inflammation reflected by reduction of ENO. Beneficial role of immunotherapy may result not only from the induction of Treg numbers but especially from cell activation and restitution of Treg intracellular signal transduction.

Detection of the DNA of Borrelia afzelii, Anaplasma phagocytophilum and Babesia canis in blood samples from dogs in Warsaw.

Each month, from March 2003 to February 2004, 34 blood samples from dogs were randomly selected from the blood samples delivered to two veterinary laboratories in Warsaw and tested for the DNA of Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Babesia canis and Hepatozoon canis. Borrelia DNA was detected in seven of the 408 dogs, A phagocytophilum DNA was found in two, and B canis DNA was found in 48 (11.8 per cent). The DNA of H canis was not found in any of the blood samples. Sequencing of the seven Borrelia amplicons showed that only the genospecies Borrelia afzelii was present, the first time it has been detected in dogs in Poland.

New localities of Dermacentor reticulatus tick (vector of Babesia canis canis) in central and eastern Poland.

Dermacentor reticulatus tick is a vector and final host of Babesia canis canis, protozoan parasite of the dog. In Poland and other European countries, endemic regions for canine babesiosis caused by B. canis canis are the same as endemic regions for D. reticulatus. In many of these regions, canine babesiosis is the most prevalent tick-borne disease in dogs. In Europe, increasing range of geographical distribution of D. reticulatus is observed. A consequence of this fact may be increasing range of canine babesiosis. D. reticulatus is one of the most common ticks occurring in Poland, however, it occurs mainly in the north-eastern and eastern part of the country, and there are many areas in which this species has not been reported yet. In this study, D. reticulatus ticks were collected from March 2007 to November 2008 in central and eastern Mazowsze region, and in some localities in Bialystok and Lublin regions. Twenty four new sites for D. reticulatus, mainly in central and eastern regions of Mazowsze Province have been found. 18 localities are placed on banks of the fishing ponds or in river valleys and 6 are forests borders or barren lands and meadows, not situated near rivers or other water reservoirs. All tick-rich sites are localized in river valleys or on pond banks. However, statistical analysis showed that there were no differences in the density of ticks between groups of areas. These results show that the occurrence of D. reticulatus in newly detected areas has became endemic. Probably woodless, unregulated river valleys are important migration tracts for this species of tick and enable them to penetrate new territories. It seems likely that geographical range of D. reticulatus is widening from east to west of Poland what can induce an increase in the number of canine babesiosis cases in areas non-endemic for B. canis canis and its vector. Climate change may be also partially responsible for earlier beginning of tick's seasonal activity as well as for bigger faunal diversity (more potential host species both for adults and immature stages).

Changes in the prevalence of parasitic nematode infections in dogs from animal asylums in Warsaw and sourroundings.

The distribution of parasitic nematodes of dogs from three shelters for homeless animals in the Warsaw region (Celestynów and Milanówek near Warsaw, Paluch in Warsaw) was investigated. It was found that since our previous investigations (1993-1995) the prevalence of nematode infections had increased in Celestynów and Milanówek and decreased in the municipal shelter in Warsaw (Paluch). The highest percentage of infected animals was found in Celestynów (as in 1993-1995). What can be the importance of local environmental conditions for the prevalence of nematode infections.

Quality of life in patients with persistent allergic rhinitis treated with montelukast alone or in combination with levocetirizine or desloratadine.

BACKGROUND: Persistent allergic rhinitis often impairs quality of life. OBJECTIVE: We assessed the extent to which treating persistent allergic rhinitis with montelukast, desloratadine, and levocetirizine alone or in combination improved quality of life. METHODS: A 32-week randomized, double-blind, placebo-controlled, crossover study was performed in 2 arms: 20 patients received montelukast 10 mg/d and/or desloratadine 5 mg/d or placebo; 20 patients received montelukast 10 mg/d and/or levocetirizine 5 mg/d or placebo. The treatment periods were separated by 2-week washout periods. Quality of life was assessed on the day before starting treatment and on the last day of each treatment period using the Rhinoconjunctivitis Quality of Life Questionnaire. Sleep problems were also assessed. RESULTS: In the desloratadine plus montelukast arm, the mean (SEM) quality of life score before treatment was 3.1 (0.41). After placebo, this score was 2.16 (0.43), after desloratadine it was 1.79 (0.38), after montelukast it was 1.48 (0.37), and after montelukast plus desloratadine it was 1.59 (0.37). In the montelukast plus levocetirizine arm, the mean quality of life score before treatment was 2.58 (0.49). After placebo it was 1.78 (0.46), after levocetirizine it was 1.38 (0.42), after montelukast it was 1.36 (0.37), and after montelukast plus levocetirizine it was 1.26 (0.39). CONCLUSIONS: Placebo, montelukast, desloratadine and levocetirizine significantly improved quality of life. Combining montelukast with either levocetirizine or desloratadine gave additional benefits in comparison to each agent alone and could be considered for patients whose quality of life is impaired by persistent allergic rhinitis.

Influence of natural dissolved organic carbon on the bioavailability of mercury to a freshwater alga.

Bioavailability of mercury (Hg) to Selenastrum capricornutum was assessed in bioassays containing field-collected freshwater of varying dissolved organic carbon (DOC) concentrations. Bioconcentration factor (BCF) was measured using stable isotopes of methylmercury (MeHg) and inorganic Hg(II). BCFs for MeHg in low-DOC lake water were significantly larger than those in mixtures of lake water and high-DOC river water. The BCF for MeHg in rainwater (lowest DOC) was the largest of any treatment. Rainwater and lake water also had larger BCFs for Hg(II) than river water. Moreover, in freshwater collected from several US and Canadian field sites, BCFs for Hg(II) and MeHg were low when DOC concentrations were >5mg L(-1). These results suggest high concentrations of DOC inhibit bioavailability, while low concentrations may provide optimal conditions for algal uptake of Hg. However, variability of BCFs at low DOC indicates that DOC composition or other ligands may determine site-specific bioavailability of Hg.

Inhalations of 5-ALA in photodynamic diagnosis of bronchial cancer.

BACKGROUND: Photodynamic bronchoscopy (PDD) allows for early detection of bronchial cancer. Adverse effects and high costs, partly related to general application of photosensitisers, are important limitations of the method. The local application of a photosensitiser could help to minimize these problems. In this study the validity and safety of inhaled 5-ALA have been tested. METHODS: We examined 49 patients (age 59 +/- 11, cigarette consumption 36 +/- 17 pack-years) with present or past respiratory neoplasms and other with increased risk of bronchial cancer by photodynamic bronchoscopy (Storz-D-light) after inhaled 5-ALA. Biopsies were taken from the fluorescence-positive and negative foci (control). Symptoms and pre-/post-inhalation spirometry were analysed. RESULTS: The overall sensitivity was 82%, specificity 62%, positive predicted value (PPV) 45% and negative predictive value (NPV) 90%. Specificity decreased to 53% and PPV to 15% when visible tumours were excluded. PDD, when added to white light bronchoscopy increased sensitivity by 2.1% and NPV by 6%, but decreased specificity by 35.4% and PPV by 53.1%. In a group of actual or past tumours the sensitivity increased by 22% and NPV by 34%, whereas specificity decreased by 26% and PPV by 35%. In 2 cases a drop in FEV1 above 10% of pre-inhalation value was observed but no clinically relevant symptoms were reported. CONCLUSIONS: Photodynamic bronchoscopy with inhalation of 5-ALA is a relatively safe diagnostic method. The main disadvantage is high percentage of false positive results. Nevertheless, we believe, that it may be a useful adjunct to conventional diagnostic modes, especially in the detection of early lesions in patients operated due to cancer (stump control and detection of metachronous lesions) and those prepared for operation (synchronous lesions and detection of infiltration margins). However all suspected lesions must be verified by histo-pathological examination.

Genetic variants of FcepsilonRIbeta and Il-4 and atopy in a Polish population.

BACKGROUND: Atopy results from the interaction between genetic and environmental factors. The aim of our study was to clarify the association between the FcRIint2 polymorphic variant, the Glu237Gly mutation in exon 7 of FcepsilonRIbeta and (-590 C/T) Il-4 gene promoter polymorphism with atopy in a randomized Polish sample. SUBJECTS AND METHODS: Unrelated subjects aged 18-45 years who were residents of an urban area (Lodz, Poland) were included in the study: 98 patients with asthma and/or allergic rhinitis, and 87 non-atopic, non-asthmatic controls. We used common criteria for atopy and asthma. Atopic status was determined by positive skin prick tests (SPT) and IgE levels. The severity of asthma was assessed in spirometric measurements; SPTs to house dust mite (HDM) and mixed grass pollen (MGP) were performed. Total and specific IgE were measured in each subject. Genotypic analysis was performed by PCR for FcRIint2 and (590 C/T) Il-4 gene promoter polymorphism and ARMS-PCR was performed for the Glu237Gly mutation. RESULTS: We found a statistically significant association between atopy and FcRIint2 variant polymorphism (OR = 2.96), a correlation between positive skin prick tests to MGP and raised MGP-specific IgE concentrations in patients bearing this variant (OR = 4.0). We did not observe that the FcRIint2 variant was associated with positive SPTs to HDM or high levels of HDM-specific IgE (OR = 1.0). The intronic variant of FcepsilonRIbeta was strongly correlated with elevated total serum IgE (OR = 4.74). No statistically significant association was found between atopy and the Glu237Gly mutation of FcepsilonRIbeta(OR = 1.36) or (-590 C/T) Il-4 gene promoter polymorphism (OR = 0.88). CONCLUSIONS: The results suggest that FcRIint2 polymorphism is related to atopy and may influence its development.

Respiratory allergy in apprentice bakers: do occupational allergies follow the allergic march?

BACKGROUND: This prospective study describes the incidence, risk factors and natural history of occupational respiratory allergy in apprentice bakers. METHODS: Two hundred and eighty-seven apprentice bakers were examined using a questionnaire, skin prick tests (SPTs) to common and occupational allergens, evaluation of total serum IgE level and specific anti-flour and alpha-amylase IgE, before, 1 year and 2 years after the onset of vocational training. To diagnose occupational respiratory disease, spirometry, histamine and allergen-specific inhalation challenge tests were performed. RESULTS: The incidence of work-related chest symptoms was 4.2% in the first year and 8.6% in the second year of exposure. Hypersensitivity to occupational allergens developed in 4.6 and 8.2% of subjects, respectively. The incidence of occupational allergic rhinitis was 8.4% after 1 year and 12.5% after 2 years, and that of occupational asthma/cough-variant asthma 6.1 and 8.7%, respectively. The latency period of work-related rhinitis symptoms was 11.6 +/- 7.1 months and chest symptoms 12.9 +/- 5.5 months. Only in 20% of occupational asthmatics could allergic rhinitis be diagnosed a stage earlier. In 21 out of 25 subjects with occupational asthma, chronic cough was the sole clinical manifestation of the disease. Stepwise logistic regression analysis revealed that positive SPT to common allergens was a significant risk factor of hypersensitivity to occupational allergens (OR = 10.6, 95% CI 5.27; 21.45), occupational rhinitis (OR = 3.9, 95% CI 1.71; 9.14) and occupational asthma (OR = 7.4, 95% CI 3.01; 18.04). Moreover, positive SPT to occupational allergens on entry to the training was a significant risk factor of asthma (OR = 6.9, 95% CI 0.93; 51.38). CONCLUSIONS: The incidence of occupational asthma and rhinitis in apprentice bakers is high and increases z with the duration of exposure. Skin reactivity to common and occupational allergens is the main risk factor of bakers' asthma. Most cases of work-related respiratory symptoms among apprentice bakers are related to a specific sensitization. In most subjects who developed occupational asthma, rhinitis occurred at the same time as the chest symptoms did.

Genetic variants of Fc RI and Il-4 and atopy in a Polish population

Background: Atopy results from the interaction between genetic and environmental factors. The aim of our study was to clarify the association between the FcRIint2 polymorphic variant, the Glu237Gly mutation in exon 7 of FcεRIβ and (-590 C/T) Il-4 gene promoter polymorphism with atopy in a randomized Polish sample. Subjects and methods: Unrelated subjects aged 18-45 years who were residents of an urban area (Lodz, Poland) were included in the study: 98 patients with asthma and/or allergic rhinitis, and 87 non-atopic, non-asthmatic controls. We used common criteria for atopy and asthma. Atopic status was determined by positive skin prick tests (SPT) and IgE levels. The severity of asthma was assessed in spirometric measurements; SPTs to house dust mite (HDM) and mixed grass pollen (MGP) were performed. Total and specific IgE were measured in each subject. Genotypic analysis was performed by PCR for FcRIint2 and (­590 C/T) Il-4 gene promoter polymorphism and ARMS-PCR was performed for the Glu237Gly mutation. Results: We found a statistically significant association between atopy and FcRIint2 variant polymorphism (OR = 2.96), a correlation between positive skin prick tests to MGP and raised MGP-specific IgE concentrations in patients bearing this variant (OR = 4.0). We did not observe that the FcRIint2 variant was associated with positive SPTs to HDM or high levels of HDM-specific IgE (OR = 1.0). The intronic variant of FcεRIβ was strongly correlated with elevated total serum IgE (OR = 4.74). No statistically significant association was found between atopy and the Glu237Gly mutation of FcεRIβ (OR = 1.36) or (-590 C/T) Il-4 gene promoter polymorphism (OR = 0.88). Conclusions: The results suggest that FcRIint2 polymorphism is related to atopy and may influence its development (AU)

Información básica: Resultados de atopia de la interacción de factores genéticos y ambientales. El objetivo de nuestro estudio era esclarecer la asociación entre la Fc€RIBeta variante polimorfa de Fc int2, la mutación Glu237Gly en el exón 7 de Fc€RIBeta y el polimorfismo del promotor génico (-590 C/T) Il-4 con atopia en una muestra polaca aleatorizada. Sujetos y métodos: Se incluyó en el estudio a sujetos de 18-45 años no emparentados, residentes en el área urbana (Lodz, Polonia): 98 pacientes con asma, rinitis alérgica o ambas y 87 controles no asmáticos y no atópicos. Utilizamos los criterios habituales para la atopia y el asma. El estado atópico se determinó por pruebas de punción cutánea positivas (spts) y las concentraciones de IgE. La gravedad del asma se evaluó con mediciones espirométricas; se realizaron spts frente a ácaros del polvo doméstico (hdm) y mezcla de polen de gramíneas (mgp). Se cuantificaron en cada sujeto los valores de IgE total y específica. Se efectuó un análisis de genotipo mediante PCR para Fc€RIBetaint2 y el polimorfismo del promotor génico (-590 C/T) Il-4, y ARMS-PCR para la mutación Glu237Gly. Resultados: Observamos una asociación estadísticamente significativa entre la atopia y el polimorfismo variante FcRIint2 (razón de posibilidades (RP = 2,96) y una correlación entre las pruebas de punción cutánea positivas frente a mgp y el aumento de las concentraciones de IgE específica para mgp en pacientes que albergaban la variante (RP = 4,0). No observamos que la variante FcRIint2 se asociase a spts positivas frente a hdm ni a concentraciones elevadas de IgE para hdm (RP = 1,0). La variante intrónica de Fc€RIBeta guardó una estrecha relación con la elevación de la IgE sérica total (RP = 4,74). No hubo una asociación estadísticamente significativa entre la atopia y la mutación Glu237Gly de Fc€RIBeta (RP = 1,36) o el polimorfismo del promotor génico (-590 C/T) Il-4 (RP = 0,88). Conclusiones: Los resultados indican que el polimorfismo de Fc€RIBeta int2 se relaciona con la atopia y puede influir en su desarrollo (AU)

Montelukast plus cetirizine in the prophylactic treatment of seasonal allergic rhinitis: influence on clinical symptoms and nasal allergic inflammation.

BACKGROUND: The aim of our study was to investigate effects of 6-week pretreatment of seasonal allergic rhinitis (AR) with cetirizine, and montelukast, alone and in combination. Antihistamine/antileukotriene treatment is effective in AR. Antihistamines may prevent AR symptoms while prophylactic activity of antileukotrienes remains unclear. METHODS: Sixty AR patients, aged 18-35 years, were randomized to receive placebo, montelukast only, cetirizine only, or montelukast plus cetirizine, 6 weeks prior and 6 weeks after the beginning of grass pollen season. Mean self-recorded in-season symptom scores and mean weekly all-symptom scores were analyzed. In 31 patients, nasal lavages were performed before treatment, and at the end of the study, i.e. 12 weeks after the treatment initiation. Eosinophil and basophil counts, eosinophil cationic protein (ECP), and mast cell tryptase (MCT) levels were evaluated in lavage samples. RESULTS: Combined montelukast/cetirizine pretreatment significantly reduced in-season symptom score for sneezing, eye itching, nasal itching, rhinorrhea, and congestion. Montelukast plus cetirizine were more effective than cetirizine alone in preventing eye itching, rhinorrhea, and nasal itching. Moreover, combined pretreatment with montelukast and cetirizine delayed appearance of AR symptoms. Eosinophil nasal lavage fluid counts were significantly increased during pollen season in placebo and montelukast-only groups. No differences were observed in basophil counts. The in-season ECP level was significantly increased in all groups except montelukast-plus-cetirizine group. In-season MCT levels were not increased. CONCLUSION: Combined antihistamine and antileukotriene treatment started 6 weeks before the pollen season is effective in preventing AR symptoms and reduces allergic inflammation in nasal mucosa during natural allergen exposure.