Interleukin 1 Gene Polymorphisms Presumably Participate in the Pathogenesis of Chronic Spontaneous Autoreactive Urticaria.

Recent studies underline a potential role of autoimmune and genetic disturbances in this disorder pathogenesis. Variants in genes related to inflammatory processes may possibly predispose to chronic spontaneous urticaria (CSU) occurrence. The objective of this study was to search for an association of Il1 genes polymorphisms with the pathogenesis of CSU. The examined group consisted of 153 unrelated chronic spontaneous autoreactive urticaria patients. The control group consisted of 104 unrelated healthy volunteers. In all studied subjects, IL1 rs1304037 and rs180058 polymorphisms were examined. The Urticaria Activity Score was used to assess disease intensity. The age of disease onset was also analyzed. Statistically significantly higher prevalence of Il1 rs1304037 TT genotype and T allele among CSU was proved. Similarly, the prevalence of Il1 rs1800587 GG genotype and G allele was statistically significantly higher in the CSU group. Haplotype combination rs1304037C/rs1800587G was statistically significantly more frequent in CSU, whereas rs1304037C/rs1800587A revealed statistically significantly less frequent occurrence in CSU. We did not observe any relationship between Il1 genotypes and the disease severity or age of disease onset. We are the first to suggest a significant role of IL1 gene polymorphisms in the susceptibility to CSU. This observation may lead to a better pathogenesis understanding and more effective treatment. We recommend further studies on other polymorphisms in chronic urticaria to analyze the role of the genetic mechanisms in the pathogenesis of this disorder.

Serum levels of interleukin 33 and its receptor ST2 in patients treated with subcutaneous allergen immunotherapy in intermittent allergic rhinitis.

INTRODUCTION: Interleukin 33 (IL-33) is a pleiotropic cytokine involved in pathological processes in seasonal allergic rhinitis. IL-33 binds to ST2 receptor, which is highly expressed on mast cells and selectively on Th2 cells. Information is lacking on the role of IL-33/ST2 axis in allergen subcutaneous immunotherapy. AIM OF THE STUDY: To determine if allergen immunotherapy changes the IL-33/ST2l axis in seasonal allergic rhinitis patients. MATERIAL AND METHODS: 40 patients with intermittent allergic rhinitis sensitive to grass and/or tree pollen were studied. Among these, 10 patients were longitudinally assessed in the follow-up visit after completing the first course of immunotherapy. Twenty-two healthy subjects were included as controls. Immunotherapy was applied according to a perennial schedule comprising up-building and maintenance phases. Serum levels of ST2/IL-33 R and IL-33 were measured by ELISA (R&D Systems). RESULTS: Serum levels of IL-33 significantly rose after the first course of immunotherapy and reached the controls levels. Serum levels of ST2 were comparable before the pollen season and after the first course of immunotherapy. CONCLUSIONS: Increase in serum levels of IL-33 after the first course of immunotherapy may suggest it is too short period to prevent the expected raise in serum IL-33 levels in the pollen season, and longer treatment is required to observe significant changes of this cytokine. ST2 serum levels are independent of immunotherapy and pollen season.

Dietary patterns and respiratory health in adults from nine European countries-Evidence from the GA2 LEN study.

BACKGROUND: Dietary patterns defined using principal component analysis (PCA) offer an alternative to the analysis of individual foods and nutrients and have been linked with asthma and allergic disease. However, results have not been reproducible in different settings. OBJECTIVE: To identify dietary patterns common to different European countries and examine their associations with asthma and allergic symptoms. METHODS: In sixteen study centers in nine European countries, 3206 individuals aged 15-77 years completed a common, internationally validated, food frequency questionnaire and a respiratory symptoms questionnaire. The outcomes of interest were current asthma, asthma symptoms score (derived based on responses to 5 asthma symptom-related questions), atopy (positive skin prick test). Spirometry was used to estimate forced expiratory volume in 1 second (FEV1 ), forced vital capacity (FVC), the FEV1 /FVC, spirometric restriction (FVC below the lower limit of normal (

Dietary Intake of Flavonoids and Ventilatory Function in European Adults: A GA²LEN Study.

BACKGROUND: Flavonoids exert anti-inflammatory properties and modulate oxidative stress in vitro, suggesting a protective effect on lung function, but epidemiological studies examining this association are scarce. METHODS: A stratified random sample was drawn from the GA²LEN screening survey, in which 55,000 adults aged 15 to 75 answered a questionnaire on respiratory symptoms. Post-bronchodilator spirometry was obtained from 2850 subjects. Forced vital capacity (FVC), the ratio between the forced exhaled volume in 1 second (FEV1) and FVC (FEV1/FVC), FVC below lower limit of normal (FVC < LLN), and FEV1/FVC < LLN were calculated. Intake of the six main subclasses of flavonoids was estimated using the GA²LEN Food Frequency Questionnaire. Adjusted associations between outcomes and each subclass of flavonoids were examined with multivariate regressions. Simes' procedure was used to test for multiple comparisons. RESULTS: A total of 2599 subjects had valid lung function and dietary data. A lower prevalence of FVC < LLN (airway restriction) was observed in those with higher total flavonoid (adjusted odds ratio (aOR), higher vs. lowest quintile intake 0.58; 95% Confidence Interval (CI) 0.36, 0.94), and pro-anthocyanidin intakes (aOR 0.47; 95% CI 0.27, 0.81). A higher FEV1/FVC was associated with higher intakes of total flavonoids and pro-anthocyanidins (adjusted correlation coefficient (a ß-coeff 0.33; 0.10, 0.57 and a ß-coeff 0.44; 95% CI 0.19, 0.69, respectively). After Simes' procedure, the statistical significance of each of these associations was attenuated but remained below 0.05, with the exception of total flavonoids and airway restriction. CONCLUSIONS: This population-based study in European adults provides cross-sectional evidence of a positive association of total flavonoid intake and pro-anthocyanidins and ventilatory function, and a negative association with spirometric restriction in European adults.

Is fruit and vegetable intake associated with asthma or chronic rhino-sinusitis in European adults? Results from the Global Allergy and Asthma Network of Excellence (GA2LEN) Survey.

BACKGROUND: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases. OBJECTIVE: We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults. METHODS: A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA2LEN) screening survey, in which 55,000 adults aged 15-75 answered a questionnaire on respiratory symptoms. Asthma score (derived from self-reported asthma symptoms) and CRS were the outcomes of interest. Dietary intake of 22 subgroups of fruits and vegetables was ascertained using the internationally validated GA2LEN Food Frequency Questionnaire. Adjusted associations were examined with negative binomial and multiple regressions. Simes procedure was used to control for multiple testing. RESULTS: A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8% reported having at least 1 asthma symptom (asthma score ≥1), whilst 19.5% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (ß-coefficient -2.34; 95% confidence interval [CI] -4.09, -0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and alliums vegetables (adjusted ß-coefficient 0.23; 95% CI 0.06, 0.40). None of these associations remained statistically significant after controlling for multiple testing. CONCLUSION AND CLINICAL RELEVANCE: There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults.

Increased Levels of Interleukin-33 and Thymic Stromal Lymphopoietin in Exhaled Breath Condensate in Chronic Bronchial Asthma.

BACKGROUND: Epithelium-derived cytokines such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33 are important contributors to inflammation in asthma. Exhaled breath condensate (EBC) is a noninvasive method used to assess the inflammation of airways. Our aim was to assess the levels of TSLP, IL-25, IL-33, and its receptor ST2l/IL-1 R4 in EBC in patients with asthma and to correlate these with serum levels and asthma control. METHODS: EBC and serum levels of TSLP, IL-25, IL-33, and ST2l/IL-1 R4 were measured in 44 patients with chronic bronchial asthma (14 in the uncontrolled phase) and 19 healthy control participants. RESULTS: EBC levels of IL-33 and TSLP and serum levels of IL-33 were statistically higher in patients with asthma than in controls. IL-25 and ST2l/IL-1 R4 were present in EBC at barely detectable levels and were not analyzed. The EBC and serum levels of all studied mediators did not differ between controlled and uncontrolled asthma patients, except for the serum level of ST2l/IL-1 R4, which was higher in uncontrolled asthma. There were no correlations between serum and EBC levels of TSLP and IL-33 or between either serum and EBC levels and the forced expiratory volume in 1 s or the total IgE level. CONCLUSIONS: Higher levels of IL-33 and TSLP in EBC provide evidence supporting a role for these mediators in asthma. Their levels do not discriminate between controlled and uncontrolled asthma. The local reaction within the epithelium is independent of the systemic reaction.

Chemokine receptors expression on CD3+ blood cells in bronchial asthma.

PURPOSE: Chemokines and their receptors participate in pathomechanism of bronchial asthma. The aim of the study was to analyze the pattern of chemokine receptor expression on T cells in severe asthmatics and to compare to mild-to-moderate patients and controls. MATERIAL/METHODS: Flow cytometric analysis of CXCR1, CXCR2, CXCR3, CCR3, CCR4, CCR5, CCR7, CCR8 expression on CD3(+)CD8(-) and CD3(+)CD8(+) cells was performed in patients with different severity of chronic asthma and in controls. RESULTS: Percentages of CD3(+)CD8(+) cells expressing CXCR1 were significantly lower in severe asthmatic than in mild-to-moderate asthmatics and in controls. Percentages of CD3(+)CD8(+) cells expressing CCR7 were significantly lower in the severe asthma group than in control group. Percentages of CD3(+)CD8(-) cells expressing CXCR1, CXCR2 and CCR8 were significantly lower in the severe asthma group than in mild-to-moderate asthmatics and in controls. The number of cells CD3(+)CD8(-) and CD3(+)CD8(+) expressing of CXCR1 was significantly lower in the group of patients using more than 800µg of budesonide daily than in the group of patients using less than 400µg of budesonide. Percentages of CD3(+)CD8(-) cells expressing CXCR3, CCR4 and CCR5 were visibly higher (not significantly) in chronic mild-to-moderate asthma than in healthy controls and severe asthmatics. CONCLUSIONS: These results may indicate impairment of some chemokine expression on T cells in severe asthma patients. Moreover participation of both chemokine receptors related to Th1 and Th2 responses in mild-to-moderate asthma and attenuation of these responses in severe asthma has been suggested.

Coexistence of angioedema alone with impaired glucose tolerance.

BACKGROUND: Most patients with chronic spontaneous urticaria (CSU) exhibit recurrent angioedema. As of yet, the pathogenesis of angioedema in CSU is largely unclear, especially when angioedema occurs in patients who do not develop wheals. Over the past years, we and others have repeatedly observed that patients with recurrent angioedema alone exhibit impaired glucose tolerance. AIM: To assess blood glucose levels and glucose tolerance in these patients and to compare the results to those of CSU patients who do not develop angioedema. METHODS: A total of 29 patients with angioedema alone (15 women, mean age 43.2 ± 12.8 years) and 33 CSU patients (17 women, mean age 41.9 ± 17 years) were investigated and compared for clinical features and laboratory values, including fasting and random blood glucose levels, and glycated hemoglobin (HbA1c%). All patients were subjected to oral glucose tolerance testing (OGTT). RESULTS: Fasting plasma glucose levels, random blood glucose levels and OGTT glucose levels were significantly higher in patients with angioedema alone as compared to CSU patients. Glucose tolerance was impaired in 17 of 29 patients with angioedema alone (58.6%) and only in 2 of 33 CSU patients (6.1%). Patients were found to have an increased risk of high glucose (OR 1.74) and HbA1c (OR 1.83) blood levels and of developing a high BMI (OR 1.97). CONCLUSION: Recurrent angioedema in patients who do not develop wheals appears to be associated with impaired glucose tolerance and elevated blood glucose levels. We recommend blood glucose measurements in patients with recurrent angioedema alone.

Serum IL-33 but not ST2 level is elevated in intermittent allergic rhinitis and is a marker of the disease severity.

BACKGROUND: Th2 cells play an important role in intermittent allergic rhinitis (IAR). Interleukin (IL)-33 stimulates the production of Th2-associated cytokines. IL-33 binds to ST2 receptor which is highly expressed on mast cells and selectively on Th2 cells. IL-33 and ST2 might be involved in the Th2-mediated immune response. OBJECTIVE: We analyzed the serum level of IL-33 and its receptor ST2 in patients with IAR sensitive to grass and/or tree pollen to assess if the serum level of IL-33 and/or ST2 may be a marker of the disease severity. METHODS: IL-33, ST2 and total immunoglobulin (Ig) E were measured in sera of patients with IAR sensitive to birch and/or grass pollen and in patients with controlled bronchial asthma and in non-allergic controls. IAR severity was assessed by total nasal symptom score. RESULTS: Serum levels of IL-33 in patients with IAR were comparable with patients with bronchial asthma and were significantly higher in patients with IAR (P=0.0035) and in patients with bronchial asthma (P=0.008) than in controls. Serum levels of IL-33 correlated with disease severity. CONCLUSION: Elevated level of IL-33 in sera of patients with IAR sensitive to tree and/or grass pollen and the correlation of IL-33 with the disease severity suggest that IL-33 is involved in the pathogenesis of intermittent allergic rhinitis.

Coexistence of two types of allergic hypersensitivity to drugs.

Hypersensitivity to drugs is a complex diagnostic challenge. Detailed medical history remains the mainstay of drug hypersensitivity evaluation, which further determines diagnostic procedures, especially the types of skin tests to be performed. The current paper presents the case of a female patient with coexisting features of supposed immunoglobulin E (IgE) dependent allergic hypersensitivity to fluoroquinolones and those of non-IgE dependent allergic hypersensitivity to povidone-iodine. Hypersensitivity was diagnosed based on the appropriately selected skin tests.

[Coexistence of chronic obstructive pulmonary disease - retrospective analysis]. / Wspólwystepowanie POChP z cukrzyca typu 2- analiza retrospektywna.

INTRODUCTION: The incidence of chronic obstructive pulmonary disease and type 2 diabetes mellitus tends to rise in old populations. The coincidence of these two diseases seems to be quite frequent. The aim of the study was the retrospective analysis of all patients hospitalized in the Department and Clinic of Internal Diseases, Allergology and Clinical Immunology, Medical University of Silesia in 2000-2004 due to the diagnosis of COPD and the assessment of the coincidence of that chronic disease with glucose metabolic disturbances. MATERIAL AND METHODS: In 213 (135 men and 78 women, mean age 66.3) hospitalized patients due to the COPD the glucose tolerance was assessed. Diabetes mellitus was diagnosed according to WHO criteria of 1985 and COPD was diagnosed with the use of GOLD 2005 criteria. RESULTS: The coexistence of COPD and glucose metabolic disturbances (diabetes mellitus, impaired glucose tolerance test, impaired fasting glucose) were diagnosed in 74 patients (34.7% of all COPD group). In 22 (29.7%) patients the symptoms of COPD preceded the diagnosis of diabetes mellitus by 5.4 years (1 month-15 years). In 18 (8.4%) the diagnosis of diabetes was established during hospitalization. 16 (7.5%) had impaired fasting glucose level, 18 (8.4%) revealed impaired glucose tolerance test. All the cases were heterogenous in terms of the duration of both diseases, clinical features and therapeutical approaches. CONCLUSIONS: The coexistence of both diseases were independent of the corticosteroids use. The exact analysis of the processes involved in etiopathogenesis of both diseases offers a promise of newer treatment approaches.

[Allergen specific-IgG4 in circulating immune complexes in patients with inhalant allergy undergoing specific immunotherapy]. / Wplyw swoistej immunoterapii alergii wziewnej na stezenie IgG4 w krazacych kompleksach immunologicznych.

The mechanism of action of specific immunotherapy (SIT) is still not definitely clear. The problem of the presence of allergen specific-IgG4 in circulating immune complexes (CIC) of patients with inhalant allergy is being discussed. The aim of the study was to determine the allergen specific-IgG4 serum levels and concentration in CIC in patients with inhalant allergy who underwent specific immunotherapy with relevance to its clinical benefits. The trial was carried out on 57 patients with seasonal allergic rhinitis (SAR) and 55 with perennial allergic rhinitis (PAR). Each of them underwent 3-year specific immunotherapy with Allergovit (Nexter-Allergopharma) or Novo Helisen Depot (Nexter-Allergopharma). 56 patients with pharmacologically treated allergic rhinitis served as a control group. Serum levels of allergen specific-IgG4 (as-IgG4), IgE, as-IgE and as-IgG4 concentration in CIC were measured in each patient and correlated with the clinical score of the disease activity. Nonparametric tests (the U Mann-Whitney test, Kruskall-Wallis test and Spearman's correlation rang test) were used. Serum levels of as-IgG4 and bound in CIC were statistically higher in the SIT group than in the control group and differed significantly between SAR and PAR groups. Immunotherapy caused significantly higher concentrations of as-IgG4 in CIC in PAR group than in SAR patients. No significant associations were found between studied immunological indices and clinical effects of SIT. Specific immunotherapy of allergic rhinitis is connected with the increase of as-IgG4 serum level and its concentration in circulating immune complexes.

[Hyperserotoninemia as a cause of symptomatic bronchial asthma]. / Hiperserotoninemia jako przyczyna objawowej astmy oskrzelowej.

Asthma-like symptoms, infrequently, may be secondary to other diseases like: gastro-esophageal reflux, allergic bronchial-pulmonary aspergillosis, Churg-Strauss syndrome, sarcoidosis or carcinoid syndrome. The diagnosis is often made after months of unsuccessful treatment. The authors discuss clinical picture and diagnostic problems in case of symptomatic bronchial asthma in course of hyperserotoninemia.

[The impact of environmental factors in atopic disorders]. / Znaczenie zanieczyszczen srodowiska a choroby alergiczne.

The widely understood environmental influence plays an important role in the formation of atopic phenotype. The manifestation of clinical symptoms and signs of asthma is the resultant of the effects of many genes and gene-gene and gene-environment interactions. Based on recent literature data the main environmental factors are analysed, such as tobacco smoke, viral infections, living conditions, moisture and moulds, diet and air pollution. Understanding of these genetic determinants and the role of environmental factors would make possible to improve the methods of diagnosis and treatment.