Influence of vascular endothelial growth factor on neutrophil activation in asthmatics.

Introduction: Asthma is a complex syndrome associated with heterogeneity in the type of inflammation that modulates airway hyperresponsiveness and remodelling. Airway inflammation with neutrophils, cytokines like vascular endothelial growth factor (VEGF) and various gene polymorphisms might be relevant for asthma pathogenesis. Aim: To investigate the expression of CD69 and CD11b markers on peripheral neutrophils after VEGF in vitro stimulation in asthmatics. Furthermore, the possible influence of a genetic factor (del/ins genotype at -2549 -2567 position in the VEGF-promoter gene) was taken into account. Material and methods: 122 subjects (82 asthmatics and 40 controls) participated in our study. CD69 and CD11b presence on peripheral blood neutrophils was detected using the flow cytometric method without exogenous stimulation (negative control), after N-formyl-methionine-leucyl-phenylalanine stimulation (fMLP - positive control) and after VEGF stimulation. Genotyping for the VEGF-promoter region was performed by polymerase chain reaction (PCR). Results: Peripheral neutrophil stimulation with VEGF enhances the activity of these cells and induces CD69 and CD11b expression in a dose-dependent manner compared with unstimulated neutrophils (p > 0.05). CD69 and CD11b markers were slightly presented (p = 0.05 and p = 0.07, respectively) on neutrophils stimulated with fMLP in asthmatics with the ins genotype variant in the VEGF-promoter region. Conclusions: Our results demonstrate that VEGF might insignificantly activate neutrophils in asthmatics. In addition, the modulated expression of CD69 and CD11b on peripheral neutrophils is not related to potential contribution of the VEGF gene polymorphism.

Peripheral blood eosinophils priming and in vitro vascular endothelial growth factor stimulation in asthmatics.

INTRODUCTION: Asthma is a complex airway disease with heterogeneity in molecular pathways. Hypersecretion of many cytokines (e.g. vascular endothelial growth factor - VEGF), inflammatory cells infiltration (e.g. eosinophils) and different genetic factors (e.g. gene polymorphism) might be responsible for physiological and pathological changes in the course of this chronic disease. AIM: To reveal the possible expression of activation marker CD69 on eosinophils unstimulated and stimulated by VEGF in patients with asthma. Additionally, the influence of a genetic factor (del18 genotype at -2549 -2567 position in the promoter of the VEGF gene) was considered. MATERIAL AND METHODS: The study involved 122 participants (82 patients with asthma and 40 healthy controls). CD69 expression on peripheral blood eosinophils was detected by flow cytometry without exogenous stimulation and after in vitro stimulation with VEGF. Genotyping for VEGF-promoter region was performed using the polymerase chain reaction method. RESULTS: CD69 was strongly presented (p < 0.05) on unstimulated eosinophils of patients with asthma and del18 genotype in the promoter of the VEGF gene. Stimulation of peripheral eosinophils with VEGF did not induce CD69 expression in a dose-dependent manner. CONCLUSIONS: Our results may suggest the potential contribution of the VEGF gene polymorphism to the spontaneous increase of eosinophils activity (priming) in patients with asthma. In addition, the results show that VEGF is unlikely to significantly activate eosinophils in asthmatics.

Vascular endothelial growth factor-activated basophils in asthmatics.

INTRODUCTION: Vascular endothelial growth factor (VEGF) is an angiogenic cytokine and a potential stimulator of permeability and lung neovascularization in asthmatics. It also plays an important role in the development of airway remodelling and in activation of many cells, including basophils. AIM: To reveal the possible role of VEGF in the activation of basophils in asthmatics - subgroups with and without irreversible bronchoconstriction. Protein CD203c on the basophils surface was used as the activation marker. To define the possible pathway of basophils VEGF-activation, the influence of a genetic factor (polymorphism del18/ins -2549 -2567 in the VEGF-promoter region) was also considered. MATERIAL AND METHODS: Our study involved 82 patients with asthma (40 patients without and 42 patients with irreversible bronchoconstriction) and a group of 40 controls. The flow cytometric methods with anti-CD203c in the samples of basophils with increasing concentrations of VEGF was used for analysis of their activity. Genotyping for VEGF-promoter region was performed by PCR-based methods. RESULTS: Patients with asthma and del/del genotype showed more significant differences in the basophils activation after stimulation with increasing concentrations of VEGF than asthmatics with ins/ins and ins/del genotype (p = 0.023) and controls with del/del genotype (p = 0.0006). CONCLUSIONS: Raised basophils VEGF-activation is characteristic for examined patients with asthma and might be associated with presence of polymorphism del18/ins -2549 -2567 in the VEGF-promoter region. Furthermore, it may contribute to the development of airways remodelling - this pathway has not been considered yet.

Prevalence, risk factors and underdiagnosis of asthma in the general population aged over 60 years.

INTRODUCTION: Bronchial asthma is one of the frequent chronic diseases in elderly persons. Global data show that 6.5-17% of the elderly suffer from asthma. However, there are no Polish data available on asthma prevalence in this group. AIM: This article is a retrospective analysis of the Polish Multicentre Study of Epidemiology of Allergic Diseases (PMSEAD) results aimed at assessing prevalence and clinical characteristics in the elderly. MATERIAL AND METHODS: The study was conducted in 1998-1999 in 11 research centres in Poland, including the Lodz centre. The study included randomly selected subjects of both sexes. Demographics and prevalence were assessed among adults (aged 16-80 years) based on the nationwide database and the detailed clinical analysis was based on the Lodz centre database. RESULTS: Nationwide data were obtained from 12 970 adults, including 1057 respondents in the Lodz Province; 20.3% of respondents in Poland and 23.6% in the Lodz Province were over 60 years of age. In both groups, elderly participants significantly more frequently suffered from asthma (asthma prevalence in this group was 6.7% for Poland and 12.0% for the Lodz Province). The multivariate analysis demonstrated that age over 60 years (OR = 2.08), residence in the city centre (OR = 3.30), and occurrence of seasonal allergic rhinitis (OR = 3.11) were significant risk factors for asthma occurrence among the residents of the Lodz Province. Among the elderly in Lodz, almost 50% of patients with asthma had not had a proper diagnosis made despite reporting clinical symptoms. CONCLUSIONS: In Poland asthma is a common and frequently underdiagnosed disease in the elderly.

Sex-related clinical aspects in insect venom anaphylaxis.

Experimental studies, epidemiological data, and clinical observations suggest that the gender factor is involved in the development and manifestation of IgE-dependent allergic diseases. We intend to answer the question if sex-related factors may play a role in Hymenoptera venom allergy (HVA). In the majority of recent studies the frequency of HVA symptoms with respect to both LL and SYS reactions is similar for men and women, while proven sensitization to insect venom is less frequent in women. Studies assessing clinical reactivity in HVA indicate that male sex and vespid venom allergy are factors increasing the risk of severe allergic reactions. Regarding the risk of adverse events associated with gender in the course of venom immunotherapy (VIT), the results of two large EAACI multicenter studies are discordant. In the first study, women showed increased risk of VIT adverse events. In the latter, systemic allergic side effects were not associated with gender. Despite theoretical premises and certain clinical observations indicating an important role of estrogens in allergic diseases, their influence on stinging insects' venom hypersensitivity is not unequivocal and remains still open. Further studies on the safety of VIT in females seem to be advisable.

Fractioned exhaled nitric oxide (FE(NO)) is not a sufficiently reliable test for monitoring asthma in pregnancy.

It has been reported that fractioned exhaled nitric oxide (FENO) can be used for monitoring airway inflammation and for asthma management but conclusions drawn by different researchers are controversial. The aim of our study was to evaluate the clinical usefulness of FENO assessment for monitoring asthma during pregnancy. We monitored 72 pregnant asthmatics aged 18-38years (Me=29 years) who underwent monthly investigations including: the level of asthma control according to GINA (Global Initiative for Asthma), the occurrence of exacerbations, ACT (Asthma Control Test), as well as FENO and spirometry measurements. In 50 women, during all visits, asthma was well-controlled. In the remaining 22 women, asthma was periodically uncontrolled. FENO measured at the beginning of the study did not show significant correlation with retrospectively evaluated asthma severity (r=0.07; p=0.97). An analysis of data collected during all 254 visits showed that FENO correlated significantly but weakly with ACT scores (r=0.25; p=0.0004) and FEV1 (r=0.21; p=0.0014). FENO at consecutive visits in women with well-controlled asthma (N=50) showed large variability expressed by median coefficient of variation (CV)=32.0% (Min 2.4%, Max 121.9%). This concerned both: atopic and nonatopic groups (35.5%; and 26.7%, respectively). Large FENO variability (35.5%) was also found in a subgroup of women (N=11) with ACT=25 constantly throughout the study. FENO measured at visits when women temporarily lost control of asthma (N=22; 38 visits), showed an increasing tendency (64.2 ppb; 9.5 ppb-188.3 ppb), but did not differ significantly (p=0.13) from measurements taken at visits during which asthma was well-controlled (27.6 ppb; 6.2 ppb-103.4 ppb). The comparison of FENO in consecutive months of pregnancy in women who had well-controlled asthma did not show significant differences in FENO values during the time of observation. The assessment of asthma during pregnancy by means of monitoring FENO is of limited practical value due to this parameter's considerable intrasubject variability, regardless of the degree of asthma control.

[The long-term variability of FeNO in pregnant asthmatic women with controlled asthma]. / Dlugoterminowa zmiennosc stezenia tlenku azotu w wydychanympowietrzu (FeNO) w astmie kontrolowanej u kobiet w ciazy.

INTRODUCTION: Fractional exhaled nitric oxide (FeNO) is considered as a useful, noninvasive marker of airway inflammation in asthma and allergic rhinitis. It has also been suggested that anti-inflammatory treatment guided by monitoring of exhaled NO could improve overall asthma control. However, long-term intra-subject variability of this parameter as well as the rate of its change, which can be clinically significant, have not been established yet. The aim of our study was to assess the long-term variability of FeNO in pregnant asthmatic women with controlled asthma. MATERIAL AND METHODS: Pregnant, non-smoking women with asthma were recruited between 3 and 6 months of gestation. Exhaled nitric oxide (FeNO) spirometric parameters were measured, and the asthma control test (ACT) was completed during monthly visits up to delivery. The data of 26 subjects with well-controlled asthma during pregnancy (ACT values within the range 20-25, normal spirometric parameters, stable treatment) were analysed. The variability of FeNO values was assessed using the variation coefficient CV (standard deviation x 100%/arithmetic mean). RESULTS: The median level of FeNO coefficient of variation (CV) was: 33.8% (range 11.3 to 121.9) in all subjects with well-controlled asthma during pregnancy. There were no statistically significant differences in FeNO variability between groups of patients who had at least one measurement of FeNO higher than 50ppb (39%; 11.8-121.9%) and those with all FeNO values below 50ppb (29.9%; 11.3-71.8%), as well as between atopic (35.7%; 11.8-121.9%) and nonatopic (24.2%; 11.3-71.8%) pregnant asthmatics (p = 0.95 and 0.11, respectively). CONCLUSIONS: High long-term variability of fractional exhaled nitric oxide values revealed in pregnant women with well-controlled asthma indicates that changes in this parameter should be interpreted with caution while being used for asthma treatment monitoring.

Investigation of Repeatability of Peak Nasal Inspiratory Flow Rate Measurements Under Baseline Conditions and After Administration of 0.05% Oxymetazoline.

OBJECTIVES: Peak nasal inspiratory flow (PNIF) measurement is an inexpensive and user-friendly method to assess nasal patency. However, the repeatability of PNIF measurements, as well as the threshold value of a change in PNIF, which can be considered significant remain unclear. This study aims to investigate the repeatability of PNIF measurements and the change in PNIF after the administration of 0.05% oxymetazoline. METHODS: Repeated measurements of PNIF (Clement Clarke In-Check nasal inspiratory flow meter; Clement Clarke International, Ltd, Harlow, Essex, UK) were obtained in 333 healthy volunteers (174 women). Based on age, participants were categorized into three groups (6-7 years, 13-14 years, and 20-45 years). We obtained five measurements in each participant. PNIF was remeasured in 294 subjects 30 min after administration of 0.05% oxymetazoline. The variability in PNIF measurements was assessed using the coefficient of variation (CV = standard deviation × 100%/mean). RESULTS: The first four PNIF measurements significantly differed from each other. The difference in PNIF measurements ceased to be statistically significant only between the fourth and fifth measurements (p = 0.19). PNIF repeatability was acceptable; the median CV was 15.5% (0-66), which did not significantly differ between age groups. The administration of 0.05% oxymetazoline led to a statistically significant increase in the PNIF value by 14.3% (-45, 157%) (p = 0.000000). CONCLUSIONS: 1. No statistically significant difference was observed in PNIF values only between the fourth and fifth measurements; therefore, at least three measurements are essential to draw meaningful conclusions. 2. PNIF measurements were satisfactorily characterized by a relatively low CV (15%). 3. The administration of 0.05% oxymetazoline led to an increase in PNIF by approximately 14% over the baseline value.

[Exhaled nitric oxide in patients with esophagitis]. / Stezenie tlenku azotu w wydychanym powietrzuu chorych na zapalenie przelyku.

INTRODUCTION: Assessment of nitric oxide (NO) concentration in exhaled air is broadly used to monitor the airway inflammation in asthma. High level of NO are also observed in paranasal sinuses and gastrointestinal tract (GT). The intact esopahageal sphincters are responsible for maintain the NO within the GT. It is not known how much the GT and especially esophageal motility disorders can affect the FeNO measurements. The aim of the study was to assess if the gastroesophageal reflux disease has any impact on level of NO in exhaled air in patients who do not suffer from any airway disease. MATERIAL AND METHODS: In 51 patients, in whom asthma, nasal polyps or atopy were excluded, gastroscopy with biopsy was performed. In 13 of them no esophageal pathology was found and they were considered as the control group. In the other 38 patients the esophagitis was diagnosed based on Los Angeles classification. RESULTS: The concentration of NO in exhaled air in patients with endoscopical gastro-esophageal changes did not differ significantly from the NO concentration in patients without inflammatory changes in stomach and esophagus (p = 0.68). Moreover, the presence of hiatal hernia did not affect the FeNO (p = 0.67). There was also no significant dependence between NO level and infection with Helicobacter pylori (p = 0.18). CONCLUSIONS: The gastroesophageal pathologies did not significantly affect NO concentration in exhaled air.

[An attempt to estimate potentially useful parameters to evaluate the normal range of nasal peak inspiratory flow]. / Próba oceny parametrów przydatnych do wyznaczenia normy dla nosowego szczytowego przeplywu wdechowego.

INTRODUCTION: Measurement of peak nasal inspiratory flow (PNIF, peak nasal inspiratory flow) seems to be a cheap and simple method to assess nasal patency. Unfortunately, due to the lack of reference values a single measurement does not take any information about the degree of nasal obstruction. Therefore, the purpose of this study was to establish parameters useful for estimating PNIF reference values. MATERIAL AND METHODS: 221 respondents, from Wroclaw, answered a questionnaire based on ECRHS II and ISAAC. Sample was randomized based on the personal number, stratified and representative of age and sex. Subjects were divided into three groups on the basis of their age (6-7, 13-14 and 20-45 years). The PNIF was measured using an In-Check portable nasal inspiratory flow meter (In-Check's Clement-Clark). The highest of the five PNIF values was used as the measure of PNIF for each subject in subsequent analyses (PNIF MAX). Patients with rhinitis and/or asthma were withdrawn from the study. RESULTS: Repeated measurements of PNIF were performed in 221 healthy volunteers. PNIF values were higher in males compared to women and this difference was statistically significant. There was a statistically significant correlation between height and PNIF MAX, and there was no such correlation between age and PNIF MAX. Stepwise linear regression that included gender, height, age revealed that only sex and height were independent significant predictors of PNIF. Obtained dependence PNIF MAX = -137.7 - 22.5 x + 1.7 y, where x is the sex (a woman, 0 - male) and the y - height. Coefficient of determination (R(2)) was 0.45 which means that regression equation explains about 45% of the observed PNIF MAX variability. CONCLUSIONS: A correlation was found between PNIF value and sex and height of the patients, while age is irrelevant in this regard. Difficulty of establishing standards for the PNIF parameter are probably due to anatomical differences in the construction of the nose.

Vascular Endothelial Growth Factor as a Putative Biomarker of Depression in Asthmatics with Reversible Airway Narrowing.

The vascular endothelial growth factor (VEGF) plays a pivotal role in process of angiogenesis in adults. If angiogenesis is not properly controlled, its deregulation may implicate it in various psychosomatic diseases states. The aim of our study was to reveal possible correlation between severity of depression in asthmatics with different degrees of airway narrowing and serum vascular endothelial growth factor levels. The study population included a total of 122 adult subjects: 82 patients with asthma (among them 42 patients with irreversible bronchoconstriction and 40 patients with reversible bronchoconstriction) and 40 healthy participants as a control group. The standardized Beck Depression Inventory (BDI) was used to estimate the depression symptoms. Enzyme-linked immunosorbent assay (ELISA) was used to assess the VEGF serum concentration in all participants. There was a significant difference in depression symptoms in asthmatics with reversible (p = 0.0432) and irreversible airway obstruction (p = 0.00005) in comparison to control group and between these two subgroups of asthmatics (p = 0.0233). Obtained results revealed significant correlation between level of depression and mean VEGF serum concentration in asthmatics with reversible airway obstruction (p = 0.0202). There was no difference between enhanced depression symptoms and VEGF serum concentration in patients with irreversible airway obstruction nor in the total group of asthmatics (in both p > 0.05). The relationship between asthma severity and depression symptoms seems to be certain. VEGF might be considered as a putative biomarker of depression in asthmatics, mainly those with reversible airway narrowing.

[Vascular endothelial growth factor - structure, function and role in airways inflammation and the clinical course of asthma]. / Czynnik wzrostu sródblonka naczyniowego - struktura, funkcje oraz rola w zapaleniu oskrzeli i przebiegu klinicznym astmy.

Vascular endothelial growth factor (VEGF) is produced by a wide range of cells and plays an important role in normal and pathological angiogenesis. The formation of the vascular system is essential for inflammatory process in airways, especially in the course of chronic lung diseases - for example bronchial asthma. Increased level of VEGF in serum and induced sputum has been demonstrated in patients with stable asthma, as well as during the exacerbation of this disease. VEGF end VEGF-receptor's expressions is closely correlated with neovascularization and seems to be an important predictor of the lung's remodeling. Due to direct causative relationship between inflammatory process and angiogenesis in airways, it was suggested, that inhibiting VEGF's activity would have an anti-inflammatory effect on airways. In this article the potential role of vascular endothelial growth factor in airways inflammation, remodeling and the clinical course of bronchial asthma is presented.

VEGF serum concentration and irreversible bronchoconstriction in adult asthmatics.

BACKGROUND: Vascular endothelial growth factor (VEGF) is an angiogenic, heparin-binding glycoprotein playing an important role in the pathogenesis of many diseases and disorders, including asthma. It has been reported that increased VEGF serum concentration is a biomarker of neovascularization, which could suggest that higher VEGF expression may be relevant to asthmatics with airway remodeling and irreversible bronchoconstriction. OBJECTIVES: The aim of this study was to assess the possible association between VEGF serum concentration and irreversible bronchoconstriction in adult patients with a diagnosis of asthma. MATERIAL AND METHODS: This study involved 82 adult patients with asthma (42 persons with and 40 persons without irreversible bronchoconstriction) and 40 healthy adult controls. Vascular endothelial growth factor serum concentration was analyzed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Vascular endothelial growth factor serum concentration in patients with asthma was higher than in healthy controls (p = 0.0131), particularly in those from the subgroup of irreversible bronchoconstriction (p = 0.0133). The rising tendency was confirmed using the Kruskal­Wallis rank sum test that showed a significant difference (p = 0.0374) in VEGF values among the 3 groups examined: healthy controls (Me = 246.6 pg/mL), asthmatics with reversible bronchoconstriction (Me = 288.6 pg/mL) and asthmatics with irreversible bronchoconstriction (Me = 340.6 pg/mL). However, the direct comparison between the 2 asthmatics groups (reversible vs irreversible bronchoconstriction) did not show a statistically significant difference (p = 0.5521). CONCLUSIONS: Increased VEGF serum concentration is characteristic of patients with asthma, especially those with irreversible bronchoconstriction.

The G/G genotype of transforming growth factor beta 1 (TGF-beta1) single nucleotide (+915G/C) polymorphism coincident with other host and environmental factors is associated with irreversible bronchoconstriction in asthmatics.

Irreversible airflow obstruction may develop in some cases of asthma even in absence of known risk factors such as smoking and environmental insults and despite implementing apparently appropriate therapy. This implies that genetic factors may significantly contribute to determining the severity in the course of the disease. The published reports on genetic predisposition to irreversible bronchoconstriction in asthma, however, are relatively scarce, and disregard its potential association with transforming growth factor (TGF)-beta1 gene polymorphism despite established role that TGF-beta1 plays in airway remodelling. We tested TGF-beta1 single-nucleotide polymorphisms (SNPs) at position +869 of codon 10 (leucine or proline) and position +915 of codon 25 (arginine or proline) for association with irreversible bronchoconstriction in a case-control study involving 110 patients with asthma and 109 controls. Multivariate logistic regression analysis revealed that genotype G/G at codon 25 was significantly associated with irreversible bronchoconstriction in asthmatics (odds ratio = 4.44; 95% confidence interval: 1.00-19.61; P = 0.05), but only after adjustment for gender, disease duration and smoking index. The influence of SNPs at codon 10 on irreversible airway obstruction was not significant. Our results suggest that presence of SNP (+915G/G) at codon 25 in TGF-beta1 gene may predispose to the development of irreversible bronchoconstriction in asthmatic patients, but only when coincident with the male gender, habitual smoking and relevant duration of the disease.

Diverse production of interferons alpha, beta, and gamma by airway leukocytes of asthmatics with regard to cigarette smoking and corticosteroid treatment.

The production of interferon-alpha(IFN-alpha), IFN-beta, and IFN-gamma by airway leukocytes from induced sputa (IS) of asthmatics was investigated. The groups consisted of 32 corticosteroid-free asthmatics (A), with 13 nonsmokers (nS) and 19 smokers (S), and 30 inhaled corticosteroid-treated asthmatics (cA) with 14 nS and 16 S. The control healthy group (H) comprised 11 nS and 15 S. The levels of IFNs in media from cultures of IS leukocytes were assessed by ELISA. The cells of the smokers produced lower amounts of IFN-alpha than those of nonsmokers in groups H, A, and cA (p = 0.0417, 0.0002, 0.0495, respectively) and significantly higher amounts of IFNbeta than nonsmokers in groups H (p = 0.0044) and cA (p = 0.0007). No differences in the levels of IFN-gamma were observed between S and nS in groups H (p = 0.8148), A (p = 0.8339), and cA (p = 0.0722). In the entire group of smokers, smoking indices correlated negatively with IFN-alpha (R(S) = -0.4374, p = 0.0006), and positively with IFN-beta (R(S) = 0.4239, p = 0.0009). There was no correlation with IFN-gamma (R(S) = 0.0471, p = 0.7004). The results suggest that production of IFNs by the airway leukocytes of cA may be modified by cigarette smoking toward deficient production of IFN-alpha and excess production of IFN-beta, which may have implications in the pathophysiology of asthma.

Serum concentration of C-reactive protein is not a good marker of bronchial hyperresponsiveness.

INTRODUCTION: Asthmatic inflammation is responsible for vital features of the disease, including bronchial hyperresponsiveness (BHR). At present we do not have precise markers for monitoring asthmatic inflammation. C-reactive protein (CRP), a marker of systemic inflammation, seemed to be a factor which could also reflect the level of asthmatic inflammation expressed by BHR. Therefore the relationship between CRP concentration and BHR was evaluated. MATERIALS AND METHODS: One hundred and two patients entered the study. A skin prick test with a broad spectrum of common aeroallergens as well as baseline spirometry and a histamine bronchoprovocation test were performed in each subject. Blood samples for high-sensitivity CRP (hsCRP) measurement were taken before the bronchial challenge tests. RESULTS: Serum hsCRP concentrations ranged from 0.20 to 14.5 mg/l (median: 1.2 mg/l, 25-75% quartiles: 0.6-2.4). Positive skin prick tests were found in 26 subjects. Bronchial hyperresponsiveness was confirmed in 42 patients (first subgroup), while 60 subjects did not demonstrate BHR (second subgroup). Among the patients with BHR, asthma was diagnosed in 33 cases and Corrao syndrome in 9. In both subgroups, serum hsCRP concentrations had similar levels (median: 1.4 mg/l, 25-75% quartiles: 0.8-2.4 and median: 0.9 mg/l, 25-75% quartiles: 0.5-2.8, respectively; p=0.297). There was no statistically significant correlation (r = -0.163, p = 0.302) between serum hsCRP concentration and the level of BHR expressed as the 20% provocative concentration for histamine. In addition, hsCRP serum concentration, after adjustment for age, atopy, body mass index, and gender, was not a significant predictor of positive histamine bronchoprovocation test results (p = 0.22, CONCLUSIONS: Serum hsCRP concentration is not a good marker of BHR, which is mainly dependent on asthmatic inflammation and is measured during bronchial challenge with histamine. This finding is important for interpreting and discussing results obtained from epidemiological and population-based studies on relationships between either CRP concentration and BHR or local and systemic inflammation.

The Impact of Sex and Age on the Prevalence of Clinically Relevant Sensitization and Asymptomatic Sensitization in the General Population.

The objective of our study was to evaluate the impact of sex and age on the prevalence of sensitization to inhalant allergens. The study was performed as a part of Polish Epidemiology of Allergic Diseases study, and data concerning citizens of Wroclaw were analyzed. The participants were divided into three age groups (6-7, 13-14, and 20-44 years) with a subdivision according to sex. We randomly selected 1409 individuals, 439 people complied; the complete set of tests was performed on 421 of them. We found that 37.7 % of the study population demonstrated sensitization to at least one of the allergens tested. Positive skin tests were found more frequently in males than in females (p = 0.003); among 6-7-year-old children, the sensitization was independent of sex (p = 0.26), while in two other groups, it was higher in males (p = 0.002 and p = 0.03, respectively). Clinically asymptomatic sensitization (AS) was found more often in females than in males (p = 0.04). The higher rate of AS in women was observed only in the two younger age groups, while in the 20-44-year-old group AS did not differ between the sexes (p = 0.72). Female sex hormones may contribute to a later change in the nature of sensitization from clinically asymptomatic to symptomatic. Further studies are needed to confirm the results of our study.

Nitric oxide production by pulmonary leukocytes from induced sputum in patients with asthma and its effect on epithelial cell viability.

INTRODUCTION: Nitric oxide (NO) is one of many factors potentially involved in lung remodeling in asthma. The aim of the study was to assess the effect of pulmonary leukocytes from patients with bronchial asthma on alveolar epithelial cell damage in relation to NO production. MATERIALS AND METHODS: Induced sputum samples were obtained from 25 patients with bronchial asthma and 10 healthy volunteers. Twelve asthmatics were on inhaled corticosteroid treatment and 13 were corticosteroid free. Type II-like alveolar epithelial (A549) cells were cultured for 48 h in the presence of cell-free media from a 24-h culture of leukocytes obtained from the induced sputa (IS-Su). The level of NO was measured in supernatants from the cell cultures and the viability of the A549 cells was established. RESULTS: The levels of NO in IS-Su from corticosteroid-free asthmatics were significantly higher (p = 0.001) than those in IS-Su from healthy controls. Furthermore, NO production by A549 cells exposed to IS-Su from steroid-free asthmatics (group A) was significantly higher than that from asthmatics on corticosteroid therapy (group cA) as well as from healthy controls (p = 0.01 and p = 0.001, respectively). Lower viability of the epithelial cells exposed to IS-Su was observed in group A compared with controls (median: 72% vs. 97.5%; p < 0.001). In addition, a negative correlation (R(S) = - 0.706, p < 0.001) was found between the levels of NO produced by pulmonary leukocytes and the viability of epithelial cells. CONCLUSIONS: The results suggest that in the course of asthma, pulmonary leukocytes may interact with alveolar epithelial cells by inducing an excessive production of NO which, in turn, may contribute to epithelium impairment.

[Markers of oxidative balance and concentration of selected metals in pollinotics]. / Markery równowagi oksydacyjnej i stezenia wybranych metali u osób chorych na pylkowice.

It was reported that catalytically active metals are presented in both the soluble and insoluble fractions of ambient air pollution particles. Both catalyses generate and stimulate oxidative stress. There are very few reports on the role of oxidative stress in pollen allergy Theoretical presumptions may suggest that oxidative metabolism can be influenced by the activity of some metals and, on the other hand, pollens could be a carrier of at least catalytic amount of metals. The aim of our study was to evaluate concentrations of some metals (Cd, Cr, Pb, Ni, Mg, Zn) and compare the markers of oxidative balance expressed as malondialde-hyde (MDA) concentration, superoxide dismutase (SOD) and glutathion peroxidase (GPx) activities in the blood of patients with pollinosis. The investigation was performed on the group of 50 individuals, 34 diagnosed as pollen allergic and 16 healthy volunteers. We have found Pb blood concentration higher in pollen allergics group, but only on the verge of statistical significance (p = 0.058). No statistically significant differences in the concentrations of other examined metals between pollen allergics and controls were observed; whereas SOD activity was higher in allergics (p = 0.015), GPx activity lower in allergics (p = 0.045) and MDA concentration higher in allergics (p = 0.044). The positive linear correlations between SOD and Pb (r = 0.492; p < 0.001) as well as between Mg and MDA (r = 0.329; p = 0.02) were observed. On the basis of these results we formulated the following hypotheses, in our opinion worth further investigations: The statistically significant increase in SOD activity in the group of pollen allergics when compared to the group of controls points out the role of oxidative stress in pollen allergic persons. The statistically significant decrease in GPx activity suggests the long-lasting duration of oxidative stress in pollen allergic. The positive correlation between SOD activity and Pb level may suggest the putative role of Pb in oxidative stress. The positive correlation between Mg and MDA may suggest the presence of an additional mechanism in pollen allergy probably connected with the activation of phagocytosis by magnesium.

[TGF-beta1 gene polymorphism in chronic obstructive pulmonary disease]. / Polimorfizm genu TGF-beta1 w przewleklej obturacyjnej chorobie pluc.

Gene polymorphism is often responsible for occurrence of some chronic diseases. It has not been clarified, why only 15-20% of smokers suffer from chronic obstructive pulmonary disease (COPD). TGF-beta1 gene polymorphism has been postulated as one of possible genetic risk factors. The aim of our study was to evaluate TGF-beta1 gene polymorphism in codons 10 and 25 in COPD patients in comparison to healthy controls. Thirty six COPD patients and 60 healthy persons entered the study. The distribution of TGF-beta1 genotypes in codon 10 was as follows in COPD group: T/C--50%, T/T--25% and C/C--25% in control group: 45%, 42% and 13% respectively. The distribution of genotypes in codon 25 in COPD patients was: G/G 86% and G/C 14%, in control group 83% and 17% respectively. There were not statistically significant differences between evaluated groups with regard to both polymorphisms. Moreover, in group of 27 smokers without COPD the distribution of the analysed TGF-beta1 gene polymorphism was similar to that in COPD group. After adjustment to sex, age and smoking index, in the logistic regression model, we can not confirm the hypothesis that TGF-beta1 gene polymorphisms in codons 10 and 25 might be significant risk factors of COPD.