The Association of Skin Test Reactivity,Total Serum IgE Levels,and Peripheral Blood Eosinophilia with Asthma in Kuwait

There is evidence that elevated serum immunoglobulin E (IgE) and eosinophilia correlate well with allergic skin test reactivity. These parameters have been used as alternative methods to characterize atopic subjects. Skin test reactivity is the only measure used routinely in clinical practice in Kuwait to reflect atopy in asthma patients. This study examines the usefulness of the two other parameters of atopy in patients with asthma, and to determine the most common allergens involved in Kuwait. Between 1998 and 1999, 101 asthma patients and 33 healthy controls were recruited for this study. Skin sensitivity test, serum total and specific IgE, total blood eosinophil count (B-EOS), and eosinophil cationic protein (ECP) tests were performed in patients and controls. Nine allergens known to be prevalent in this environment were selected for the skin test and specific IgE test. Spirometry was also measured. These parameters were repeated after 4 weeks of therapy in the patients only. Skin test reaction was positive in 81% of the patients, while total IgE above 200 kU/L was obtained in 63% of cases. B-EOS above 300 ± 10³/L was found in 75% of cases. House dust mite reactivity (positivity) was the most frequently encountered skin allergy, occurring in 28% of the patients. IgE correlated positively with B-EOS and ECP. B-EOS similarly correlated positively with ECP. There was a negative correlation between ECP and forced expiratory volume in 1 sec (FEV₁) (% predicted) as expected. At least one positive parameter of atopy was found in 95% of the patients. In 48% of the patients, all three parameters of atopy were found to be positive. Skin test reactivity and elevated IgE were found together in 62% of the cases. This study reveals a significant degree of allergy among patients with asthma in this environment. Skin testing was found to be the most effective measure of atopy in this environment, and correlates well with the other more sensitive newer tests.     

Increased Plasma Reactive Oxidant Levels and Their Relationship to Blood Cells,Total IgE,and Allergen-specific IgE Levels in Asthmatic Children

Asthma is a disorder characterized by inflammation of the airways. Oxidative stress may play a role in the pathophysiology of several diseases including asthma. Characterizing biomarkers of oxidative stress in the context of other systemic measures of immune function or inflammation could provide insight regarding underlying mechanisms inducing asthma. We evaluated whether oxidative stress in the form of plasma reactive oxidants differs between asthmatic and non-asthmatic children and elucidate relationships between plasma reactive oxidants and other asthma-related immunological markers. Plasma reactive oxidants, white blood cell counts, total serum immunoglobulin E (IgE), and a multi–allergen-specific IgE screen were measured in 74 asthmatic and 74 non-asthmatic children (9 to 13 years of age) from the Detroit, Michigan area. Plasma reactive oxidants were measured using a lucigenin-based chemiluminescence assay. Plasma reactive oxidants, eosinophils, and neutrophils (absolute counts and percent of total white blood cell counts), total IgE, and allergen-specific IgE levels were elevated in asthmatics after adjusting for age, gender, and ethnicity. IgE (total or allergen-specific), eosinophils and neutrophils were not significantly associated with plasma reactive oxidant levels. The association between plasma reactive oxidants and asthma status was similar when eosinophils, neutrophils, total IgE, or allergen-specific IgE were included as possible confounders in multivariate logistic regression models.

In conclusion, plasma reactive oxidants are elevated in asthmatics and appear to be an independent predictor of asthma status. Measurement of plasma reactive oxidants may be a useful adjunct diagnostic tool and potential mechanistic indicator relevant to the study of asthma and asthma exacerbation.     

The Association of Skin Test Reactivity, Total Serum IgE Levels, and Peripheral Blood Eosinophilia with Asthma in Kuwait

There is evidence that elevated serum immunoglobulin E (IgE) and eosinophilia correlate well with allergic skin test reactivity. These parameters have been used as alternative methods to characterize atopic subjects. Skin test reactivity is the only measure used routinely in clinical practice in Kuwait to reflect atopy in asthma patients. This study examines the usefulness of the two other parameters of atopy in patients with asthma, and to determine the most common allergens involved in Kuwait. Between 1998 and 1999, 101 asthma patients and 33 healthy controls were recruited for this study. Skin sensitivity test, serum total and specific IgE, total blood eosinophil count (B-EOS), and eosinophil cationic protein (ECP) tests were performed in patients and controls. Nine allergens known to be prevalent in this environment were selected for the skin test and specific IgE test. Spirometry was also measured. These parameters were repeated after 4 weeks of therapy in the patients only. Skin test reaction was positive in 81% of the patients, while total IgE above 200 kU/L was obtained in 63% of cases. B-EOS above 300 ± 10³/L was found in 75% of cases. House dust mite reactivity (positivity) was the most frequently encountered skin allergy, occurring in 28% of the patients. IgE correlated positively with B-EOS and ECP. B-EOS similarly correlated positively with ECP. There was a negative correlation between ECP and forced expiratory volume in 1 sec (FEV₁) (% predicted) as expected. At least one positive parameter of atopy was found in 95% of the patients. In 48% of the patients, all three parameters of atopy were found to be positive. Skin test reactivity and elevated IgE were found together in 62% of the cases. This study reveals a significant degree of allergy among patients with asthma in this environment. Skin testing was found to be the most effective measure of atopy in this environment, and correlates well with the other more sensitive newer tests.     

Increased Plasma Reactive Oxidant Levels and Their Relationship to Blood Cells,Total IgE,and Allergen-specific IgE Levels in Asthmatic Children

Asthma is a disorder characterized by inflammation of the airways. Oxidative stress may play a role in the pathophysiology of several diseases including asthma. Characterizing biomarkers of oxidative stress in the context of other systemic measures of immune function or inflammation could provide insight regarding underlying mechanisms inducing asthma. We evaluated whether oxidative stress in the form of plasma reactive oxidants differs between asthmatic and non-asthmatic children and elucidate relationships between plasma reactive oxidants and other asthma-related immunological markers. Plasma reactive oxidants, white blood cell counts, total serum immunoglobulin E(IgE), and a multi–allergen-specific IgE screen were measured in 74 asthmatic and 74 non-asthmatic children(9 to 13 years of age) from the Detroit, Michigan area. Plasma reactive oxidants were measured using a lucigenin-based chemiluminescence assay. Plasma reactive oxidants, eosinophils, and neutrophils(absolute counts and percent of total white blood cell counts), total IgE, and allergen-specific IgE levels were elevated in asthmatics after adjusting for age, gender, and ethnicity. IgE(total or allergen-specific), eosinophils and neutrophils were not significantly associated with plasma reactive oxidant levels. The association between plasma reactive oxidants and asthma status was similar when eosinophils, neutrophils, total IgE, or allergen-specific IgE were included as possible confounders in multivariate logistic regression models. In conclusion, plasma reactive oxidants are elevated in asthmatics and appear to be an independent predictor of asthma status. Measurement of plasma reactive oxidants may be a useful adjunct diagnostic tool and potential mechanistic indicator relevant to the study of asthma and asthma exacerbation     

白细胞介素13基因-1112C/T多态性与支气管哮喘患者发病及血浆总IgE水平的相关性

目的探讨白细胞介素13(IL13)基因启动子区-1112C/T多态性与支气管哮喘(简称哮喘)的相关性及对血浆总IgE水平的影响。方法将哮喘患者(100例)和健康人(100名)被分为哮喘组和对照组,用聚合酶链反应限制性片段长度多态性(PCRRFLP)方法检测哮喘组与对照组-1112位点多态性,用酶联免疫吸附法(ELISA)测定血浆总IgE水平。结果-1112位点等位基因C、T频率在两组间分布的差异具有显著性(χ2=901,P<001),等位基因T与哮喘关联[OR(T/C)=203,95%CI=127～323,P<001]。两组基因型(TT、CT、CC)频率的分布比较差异有显著性(χ2=719,P<005),其优势比OR(TT/CC)=299,95%CI=106～841(P<005);OR(CT/CC)=204,95%CI=109～381(P<005);OR(TT/CT)=146,95%CI=049～437(P>005);在哮喘组CC、CT及TT基因型患者的血浆总IgE水平分别为(204±89)kU/L、(320±108)kU/L、(376±147)kU/L,而在对照组CC、CT及TT基因型患者的血浆总IgE水平分别为(96±34)kU/L、(122±42)kU/L、(150±36)kU/L。同组内T等位基因携带者血浆总IgE水平高于非携带者;同一基因型中哮喘组总IgE水平高于对照组。结论IL13基因-1112位点多态性是影响哮喘的重要候选基因,T等位基因与哮喘关联,并可能通过增强IL13基因的表达影响血浆总IgE水平。     

The Predictive Value of IgE as Biomarker in Asthma

Background. The evidence for a causal relationship between allergens and asthma depends on epidemiologic findings showing a strong association between specific immunoglobulin E (IgE) antibodies or total IgE and asthma. Objective. To clarify the relationship between total serum IgE levels and asthma. Study design. A cross–sectional study. Patients and methods. A total of 562 asthmatic patients were included in the study, and their age range was from 17 to 52 years. The subjects included in the study were outpatients from the Asthma and Allergy Centre or Samara General Hospital outpatients Clinic. The diagnosis of asthma was performed by a specialist physician and was established according to the National Heart Blood and Lung Institute/World Health Organization (NHLBI/WHO) workshop on the Global Strategy for Asthma. Results. This study indicated that mean serum IgE level was 554 ± 447 IU/mL in asthmatic patients, while that of the control population was 69 ± 33 IU/mL. There was no overlap in the values of 95% confidence interval (CI) of higher control limit and lower asthmatic limit values. Addition of two standard deviations to the mean IgE value of the control group (134 IU/mL) does not overlap with the lower 95% CI of the asthmatic group. However, serum IgE was within normal values in 5.9% of asthmatic patients in our study population. There was an inverse correlation between serum IgE levels and forced expiratory volume in 1 second (FEV₁) predicted percent for patients with asthma (r = ?0.73, p < 0.0001). The predictive value of serum IgE in asthma was determined using Receiver Operating Characteristics (ROC) curve method. From the ROC curve, it can be seen that it is possible to get both high sensitivity and high specificity if the right cut–off value was chosen. In fact, a cut–off of 200 IU/mL would indicate sensitivity of 93% and specificity of 91% in this group of patients and control subjects. Following immunotherapy there was 36% reduction in total serum IgE level. The value of IgE was significantly reduced (p < 0.001) from 956 ± 378 IU/mL at baseline to 613 ± 194 IU/mL after treatment. Conclusion. Serum IgE level was predictive in asthma, and it may be used to differentiate between asthmatic and non-asthmatic individuals in conjunction with other biomarkers. Specific immunotherapy reduced serum total IgE level in 36% of patients with asthma.     

ORMDL3/GSDMB genotype as a risk factor for early-onset adult asthma is linked to total serum IgE levels but not to allergic sensitization

BackgroundAn orosomucoid-like 3 (ORMDL3)/gasdermin B (GSDMB) gene locus on chromosome 17q is consistently associated with childhood-onset asthma, which is highly atopic. As some evidence suggests the relationship between asthma and allergic sensitization reflects asthma patient susceptibility to augmented IgE responses driven by common environmental allergens rather than an increased asthma risk after allergen exposure, we aimed to determine any relationships between this locus region and childhood-onset adult asthma with regard to serum total IgE levels or allergic sensitization.MethodsWe conducted a case–control association study using three independent Japanese populations (3869 total adults) and analyzed the ORs for association of rs7216389, an expression quantitative trait locus for ORMDL3/GSDMB, with adult asthma according to onset age. Additionally, associations between the rs7216389 genotype and total serum IgE levels or allergic sensitization was examined.ResultsRs7216389 was associated with both childhood-onset adult asthma (OR for asthmatic patients afflicted at the age of 10 years or younger = 1.61, p = 0.00021) and asthmatic patients with higher levels of total serum IgE (OR for asthmatic patients with IgE ≥1000IU/mL = 1.55, p = 0.0033). In both healthy controls and in the combined healthy and asthmatic individuals, rs7216389 was correlated with increased total serum IgE levels (p < 0.0005), but not allergic sensitization (p > 0.1).ConclusionsORMDL3/GSDMB is an important susceptibility gene for childhood-onset adult asthma in Japanese populations and this association is linked to elevated total serum IgE levels but not to allergic sensitization.     

白细胞介素4和13基因多态性对支气管哮喘患者易感性及血清总IgE水平的影响

目的 探讨白细胞介素(IL)-4基因启动子区+33C/T位点和IL-13内含子+1923C/T位点单核苷酸多态性与支气管哮喘(简称哮喘)患者易感性的相关性及其对血清总IgE水平的影响.方法 2003年12月至2007年6月应用聚合酶链反应和限制性片段长度多态性(PCR/RFLP)方法对山东的150例汉族哮喘患者(哮喘组)与160名健康人(健康对照组)IL-4基因+33C/T位点和IL-13基因+1923C/T位点的单核苷酸多态性进行检测,应用酶联免疫吸附法(ELISA)测定两组血清总IgE含量.两组各等位基因及基因型频率的比较用X2检验,不同基因型间IgE水平的比较采用两样本t检验.结果 IL-4基因+33C/T位点基因型CC、CT和TT在健康对照组中分布频率分别为43%(68/160)、35%(56/160)和22%(36/160),在哮喘组分布频率分别为18%(27/150)、36%(54/150)和46%(69/150);IL-13基因+1923C/T位点基因型CC、CT和TT在健康对照组中分布频率分别为41%(66/160)、43%(68/160)和16%(26/160),在哮喘组分布频率分别为21%(31/150)、38%(57/150)和41%(61/150).IL-4基因+33C/T位点和IL-13基因+1923C/T位点的各基因型在两组间的分布差异有统计学意义(X2值分别为27.821和26.544,均P<0.01).CT、TT基因型患哮喘的危险性高于CC基因型(X2值分别为21.870和14.206,均P<0.01).IL-4基因+33C/T位点基因型CC、CT和TT在健康对照组中血清总IgE水平分别为(92±37)KU/L、(122±45)KU/L和(146±44)KU/L,哮喘组血清总IgE水平分别为(179±40)KU/L、(294±51)KU/L和(341±80)KU/L;IL-13基因+1923C/T位点基因型CC、CT和TT在健康对照组中血清总IgE水平分别为(85±31)KU/L、(102±38)KU/L和(144±49)KU/L,哮喘组血清总IgE水平分别为(186±65)KU/L、(297±87)KU/L和(363±140)KU/L.在两基因位点中,相同基因型的血清总IgE水平比较,哮喘组高于对照组,差异有统计学意义(t值分别为4.653、6.547、7.754和4.673、6.784、8.157,均P<0.01).同组内的CT、TT基因型血清总IgE水平高于CC基因型,差异有统计学意义(t值分别为5.748和6.253,均P<0.01).结论 IL-4基因启动子区+33C/T和IL-13内含子+1923C/T多态性位点与哮喘易感性和血清总IgE浓度升高相关联.IL-4基因和IL-13基因是影响哮喘的重要候选基因.     

Total IgE in the sputum and serum of patients with asthma

BackgroundThe correlation between total IgE in induced sputum (IS) and serum is not well defined. The aim of this study was to investigate the relationship between total IgE in IS and total IgE in serum and airway inflammation.MethodsTwenty-one patients with stable asthma and thirteen healthy controls were studied. Clinical and spirometric data were collected and a skin prick test to the 13 most common aeroallergens in our area was performed in all subjects. Total IgE in IS and serum was determined by the UNICAP immunoanalysis system (Pharmacia Uppsala, Sweden) while albumin concentration in IS and serum was determined using the Cobas Integra^® turbidimetric method (Roche Diagnostics, Basel, Switzerland).ResultsThe percentage of eosinophils in EI was 8.7 (11.8) in asthmatic subjects and was 0.5 (1) in healthy controls. Total IgE (KU/L) was 43.2 (23) in asthmatics vs 25.6 (3) in healthy controls in IS, and was 329 (413) in asthmatics vs 57 (78) in controls in serum. Total IgE in IS was significantly correlated with total IgE in serum; r = 0.71 (p = 0.048), but not with the albumin relative index. No correlation was found between IgE and the number of eosinophils in IS.ConclusionsTotal IgE can be measured in IS. Total IgE in IS is mildly correlated with total IgE measured in serum. The lack of correlation between total IgE and albumin in IS suggests that IgE in IS could be locally produced, at least in part.     

Role of staphylococcal superantigen-specific IgE antibodies in aspirin-intolerant asthma.

IgE antibodies specific for staphylococcal superantigens (SAg) have been implicated in the pathology of several allergic diseases such as rhinosinusitis, nasal polyposis, asthma, and aspirin intolerance. We sought to determine whether SAg-specific IgE levels associate with clinical parameters in patients with aspirin-intolerant asthma (AIA), as compared with patients with aspirin-tolerant asthma (ATA) and nonatopic controls. Eighty patients with AIA, 62 patients with ATA, and 52 normal controls were enrolled in this study. Total serum IgE and IgE specific for staphylococcal enterotoxin A, staphylococcal enterotoxin B, and staphylococcal toxic shock syndrome toxin 1 (TSST-1) were measured using the CAP system (Pharmacia, Uppsala, Sweden). The prevalence of staphylococcal enterotoxin B-specific IgE and TSST-1-specific IgE was significantly higher in the asthma patients than in the healthy controls. The prevalence of SEB-specific IgE was slightly higher in patients with AIA than in those with ATA (22.5% versus 14.5%), although this difference was not statistically significant. No significant difference in staphylococcal enterotoxin A-specific or TSST-1-specific IgE was found between AIA and ATA subjects. Total serum IgE levels were higher in asthma patients with detectable SAg-specific serum IgE than in those without. Airway hyperresponsiveness, as measured by PC20 methacholine, was significantly increased in asthma patients with detectable SAg-specific IgE than in asthma patients without (p = 0.038). There were no significant differences in other clinical parameters between AIA and ATA patients with and without detectable SAg-specific antibody responses. These findings suggest that the staphylococcal SAg may contribute to airway inflammation and the development of airway hyperresponsiveness in asthma.     

Serum levels of soluble CD23 in patients with asthma or rhinitis monosensitive to Parietaria. Its relation to total serum IgE levels and eosinophil cationic protein during and out of the pollen season.

The diagnostic value for allergies of the low affinity IgE receptor and its soluble circulating fragment (sCD23) remains unclear. In particular, little is know about seasonal influences on serum sCD23 levels in subjects with pollen allergy. In the present study, to gain insight into pathophysiological role of sCD23, we have analyzed, in blood from patients allergic to Parietaria sCD23, IgE, and eosinophil cationic protein (ECP) serum levels. IgE were assessed as atopy markers and ECP as an inflammation marker. Patients were studied during and out of pollen season, and results were compared to those obtained in nonallergic subjects. The study population included 42 nonsmoking outpatients, living in Palermo (Sicily, Italy) or in other west Sicilian towns, with a clinical diagnosis of seasonal asthma or rhinitis and monopositive skin test to Parietaria pollen. The group of asthmatic subjects consisted of 25 patients who had one or more of the usual asthma symptoms (wheezing, dyspnea, and cough) only during the pollen season. The group of rhinitis patients consisted of 17 patients, who, during pollen season, had the nasal symptoms (nasal blockage, sneezing, nasal itching, and rhinorrhoea) but no signs of asthma. As a control group, we studied 10 nonatopic subjects from laboratory staff. They had no history of seasonal or perennial rhinitis, asthma, or urticaria and had negative skin tests to a panel of allergens. Soluble CD23, IgE, and ECP were assessed in blood during and out of pollen season. Total serum IgE levels were clearly higher in atopic patients, as classically established. Concerning sCD23 serum levels, a similar pattern of results was obtained. Accordingly, significant correlations were shown between the levels of sCD23 and IgE in all groups of patients. A completely different pattern was observed by analyzing serum ECP levels because ECP levels were significantly increased only in asthmatic patients during pollen season. Accordingly, no significant correlations were observed between the levels of sCD23 and those of ECP. Identifying immune factors associated with the development of atopy can enhance our understanding of the in vivo mechanisms involved and may have utility in paradigms designed to prevent diseases. As demonstrated by the close correlation with total serum IgE values and the lack of correlation with serum ECP values, serum levels of sCD23 appear to be an additional marker for the diagnosis of atopy but not for the follow-up of allergic diseases.     

Serum levels of eosinophil cationic protein and eosinophils in asthmatic children during a course of prednisolone therapy

Eosinophils play an important role in the inflammatory events of allergic asthma. Serum eosinophil cationic protein (ECP) is a marker of disease activity and of treatment efficacy in bronchial asthma. To understand the role of ECP concentrations in disease activity of acute asthma, we determined changes in serum concentrations of ECP elaborated by activated eosinophil before and after prednisolone therapy. Circulating levels of ECP in 15 normal control subjects, and in sera of 20 asthmatic children who were allergic to house dust mites, were measured during an acute exacerbation and when the children were in stable condition, using commercially available assay kits. The mean concentrations of serum ECP were significantly higher during an acute asthma exacerbation than when the children were stable (26.41 +/- 21.66 microg/L vs 15.74 +/- 11.36 microg/L P < 0.01) or when compared to control subjects (7.50 +/- 1.42 microg/L; P < 0.001). The mean eosinophil counts (EC) during acute asthma attacks (575 +/- 286/mm3) and when stable (467 +/- 204/mm3) were higher than in the control group (181 +/- 164/mm3). The differences were statistically significant among the three groups (P < 0.05). A significant correlation was found between serum levels of ECP and EC (r = 0.788, P = 0.001) in asthmatic children; there were also significant correlations between ECP and EC in nonallergic normal control subjects (r = 0.662; P = 0.007). In conclusion, this study provides further evidence that changes in serum ECP may serve as an objective indicator for clinical activity and results of treatment in allergic asthmatics.     

Association of the expression of IL-4 and IL-13 genes, IL-4 and IgE serum levels with allergic asthma

Immune and inflammatory responses mediated by cytokines, play important roles in the pathophysiology of asthma. These responses are associated with overexpression of Th2 cytokines such as IL-4 and IL-13. These two cytokines use common receptors for signaling that lead to identical immunological effects and regulation of the Th1/Th2 balance. The aim of this study was to determine whether patients with allergic asthma display overexpression of IL-4 and IL-13 genes. Using RT-PCR, we examined the expression of IL-4 and IL-13 genes in twenty asthmatic cases and twenty normal individuals. Total levels of serum IgE and IL-4 were also determined by ELISA method. Expression of IL-13 gene in 70% of patients with allergic asthma was higher than controls (P=0.01). There was no correlation between the expression of IL-13 gene and total level of serum IgE (P=0.07). Expression of IL-4 gene was detected in 30% of the patients and none of the normal individuals as determined by RT-PCR (P=0.01). Mean of serum IgE levels in patients and controls were 84.9 IU/ml and 62.2 IU/ml, respectively. Level of serum IgE was more than 100 IU/ml in 30% of patients (P=0.03). Mean of serum IL-4 levels in patients and controls were 15.73 pg/ml and 13.07 pg/ml, respectively. There was a relation between levels of serum IgE and IL-4 in 73% of cases. The results showed that there was a correlation between the expression of IL-4 gene and the level of serum IL-4. Levels of serum IgE and IL-4 were considerably higher in asthmatics than non-asthmatic controls.     

Correlation between serum IgE and specific IgE antibody titer to house dust mite in children with asthma

Using the enzyme-linked immunosorbent assay (ELISA) for IgE specific to mites, we evaluated the relationship between total serum IgE levels and IgE antibodies specific to mite in 58 asthmatic children. Our results showed that there was a positive correlation between total serum IgE and IgE antibody specific to Dermatophagoides pteronyssinus (r = 0.57; p less than 0.001) and Dermatophagoides farinae (r = 0.59; p less than 0.001). There was also a significant correlation between D. pteronyssinus-specific IgE and D. farinae-specific IgE (r = 0.68; p less than 0.001). This suggests that there are common allergens between the two species. The close correlation between the ELISA assay and skin test suggests that the former will be useful for the diagnosis of mite allergy in asthma.     

Specific IgE density assay: A new reverse enzyme allergosorbent test-based procedure for the quantitative detection of allergen-specific IgE

A new method is described for the quantitative detection of IgE antibodies, based on IgE capture with a specific antibody, reaction with liquid-biotinylated allergens and biotinylated anti-IgE and immunoenzymatic development of the reaction (reverse enzyme allergosorbent test). Using a reference system based on the World Health Organization IgE International standard, this method determines total IgE in the range 2-100kU/L and specific IgE in the range 0.2-100 kU/L, from which the specific/total ratio, called 'specific IgE density', can be calculated. This procedure has been applied to the study of specific IgE in 23 sera from patients polysensitized to pollen and mite allergens: 11 with asthma and 12 with rhinitis. The sensitivity and reproducibility of the method were evaluted. Sera from asthmatic patients showed higher cumulative levels of specific IgE (mean density 57.7%) than sera from rhinitic patients (mean density 32.6%). The clinical significance of specific IgE density in patients with multiple sensitizations is discussed.     

白细胞介素4基因启动子区多态性与新疆维吾尔族人群支气管哮喘患者发病间的关系

目的　探讨白细胞介素 4 (IL 4 )基因启动子区 - 5 89(C/T)位点基因的多态性和新疆维吾尔族人群支气管哮喘 (简称哮喘 )患者及其临床表型间的关系。方法　 93例哮喘患者 (A组 )根据病情轻、重分为轻度组 30例 (A1组 )、中度组 32例 (A2 组 )、重度组 31例 (A3 组 ) ;根据发作情况分为夜间哮喘组 (AⅠ 组 ) 4 1例 ,非夜间哮喘组 (AⅡ 组 ) 5 2例。并与 6 2名正常对照组 (B组 )进行对照。采用聚合酶链反应 限制性片段长度多态性 (PCR RFLP)技术检测各组IL 4基因启动子区 - 5 89(C/T)位点的多态性。应用UniCAP变应原检测系统测定血清嗜酸粒细胞阳离子蛋白 (ECP)、血清总免疫球蛋白E(T IgE)和特异性IgE抗体 (sIgE)水平。记录一秒钟用力呼气容积占预计值百分比 (FEV1占预计值 % )及最大峰流速 (PEF)。结果　A组患者IL 4基因启动子区 - 5 89(C/T)位点多态性分布频率CT杂合子为 4 2例 (4 5 1% ) ,CC纯合子为 2 9例 (31 2 % ) ,TT纯合子为 2 2例 (2 3 7% ) ;B组CT杂合子为 2 6例 (4 1 9% ) ,CC纯合子为 2 1例 (33 9% ) ,TT纯合子为 15例 (2 4 2 % ) ,A组与B组 3种基因型构成比比较差异无显著性 (P >0 0 5 ) ;AⅠ 组CC纯合子基因型的频率为 39 0 % ,AⅡ 组为2 5 0 % ,AⅠ 组与AⅡ 组比较差异有显著性 (P =0     

The relationship of skin test positivity, high serum total IgE levels, and peripheral blood eosinophilia to symptomatic and asymptomatic airway hyperresponsiveness

The relationships of skin test positivity, high serum total IgE levels (> 100 kU/L), and peripheral blood eosinophilia (>/= 275 cells/microliter) to symptomatic (either chronic cough, chronic phlegm, bronchitis episodes, dyspnea, wheeze, or asthma) and asymptomatic bronchial hyperresponsiveness (BHR) were studied cross-sectionally in 620 adult subjects who participated in the Vlagtwedde-Vlaardingen Study of 1989 and 1990. Eosinophilia (OR = 2.06, 95% CI = 1.28 to 3.31) and skin test positivity (OR = 1.66, 95% CI = 1.02 to 2.71) were both significantly associated with BHR independent of age, sex, smoking, and urban area of residence. High serum total IgE levels were not associated with BHR (OR = 1.29, 95% CI = 0.81 to 2.03). Separate analyses for symptomatic and asymptomatic subjects showed that the higher risk of BHR with skin test positivity applied only to symptomatic subjects (OR = 5.78, 95% CI = 1.63 to 20.51), independent of eosinophilia and high serum total IgE levels. The higher risk of BHR with eosinophilia was not different between symptomatic and asymptomatic subjects, and independent of skin test positivity and high serum total IgE levels. The results of this study show that, in the general adult population, eosinophilia is associated with BHR both in symptomatic and asymptomatic persons, whereas skin test positivity is associated with BHR only in symptomatic subjects.     

Oropharyngeal candidiasis with dry-powdered fluticasone propionate: 500 microg/day versus 200 microg/day

We aimed to determine the frequency of oropharyngeal candidiasis and its clinical correlates in the asthmatic patients who use fluticasone propionate (FP) as a dry powdered inhaler. We selected four groups of patients: 62 asthmatic patients who were taking 200 microg/d FP, 122 asthmatics who were taking 500 microg/d FP, 50 asthmatic patients who had not been on inhaled corticosteroid (ICS) treatment and 40 normal non-asthmatic subjects. The frequency of positive swabs for Candida colonization was higher in 500 microg/d FP group than asthmatics without ICS use (chi2 = 6.8, p < 0.05) and normal controls (chi2 = 4.9, p < 0.05), whereas it wasn't different in the 200 microg/day FP group when compared to controls. When we considered patients who used ICS, the most effective variables affecting the occurrence of Candida colonization were washing of the throat by the patients (OR = 9.4, 95 % Confidence Interval [CI] = 3.9-22.7, p < 0.0001) and duration of ICS use more than 12 months (OR = 2.5, 95 % CI = 1.1-2.6, p < 0.05). The present study showed that in the patients who use ICS, the most important determinants on colonization were not washing the throat regularly and duration of ICS use for more than 12 months.     

Plasma adrenomedullin levels in asthmatic patients.

Adrenomedullin (ADM) is a newly discovered endogenous vasorelaxing peptide isolated from pheochromocytoma. Some experimental studies suggest that ADM plays a role in asthma. The purposes of the present study were to assess the plasma ADM levels in adults with mild to severe asthma and controls and to correlate those with the findings on lung function test results and other clinical indices. We recruited 16 mild, 10 moderate, and 11 severely asthmatic patients and 12 healthy controls. We measured the plasma concentrations of ADM in patients with asthma and in healthy subjects using RIA. We assessed FEV1, FEV1 predicted %, FEV1/FVC, symptom score, IgE, ECP, and morning and evening peak expiratory flow measurements. There was no significant difference between the asthmatic and the control group ADM levels, which were 26.3 +/- 24.2 pg/mL and 22.9 +/- 17.6 pg/mL, respectively. Furthermore, plasma ADM levels increased as the severity of the disease increased in asthmatic patients (20.7 +/- 14.4 pg/mL in mild, 25.2 +/- 24.3 pg/mL in moderate, and 35.5 +/- 33.6 pg/mL in severe asthmatics), although they did not result in any statistical significance. However, the plasma ADM levels correlated negatively with the FEV1 levels in the asthmatic group (p < 0.02, r = -0.37). Peripheral blood eosinophilia, IgE, and ECP levels did not correlate with plasma ADM levels. These results suggest that the measurement of ADM concentration in plasma will not be of diagnostic use in asthma, but may be a reflection of the severity of asthma.     

Association between the IL-4 promoter polymorphisms and asthma or severity of hyperresponsiveness in Taiwanese

BACKGROUND AND OBJECTIVES: Recent family-based studies have revealed a linkage between human chromosome 5q31 and asthma, elevated serum IgE levels and airway hyperresponsiveness (AHR). Among the candidate genes in this region is the gene encoding IL-4. This gene could be a candidate gene for asthma. The aim of this prospective case-control study was to assess the frequency of polymorphisms in the IL-4 gene promoter among asthmatic patients from Taiwan. METHODS: The study consisted of 167 patients with asthma and 111 healthy subjects. PCR amplification followed by Bsm F1 restriction digestion were used to assign genotypes at the IL-4 promoter C-589T locus. Pulmonary function tests, methacholine challenge tests, total IgE, specific IgE antibodies against common inhalant allergens and total eosinophil counts were assessed in asthmatic patients. RESULTS: The T allele frequency for the C-589T IL-4 gene promoter in asthma patients was higher than for normal subjects (P < 0.0001). The frequency discrepancy was found to be even higher for asthmatic patients with severe AHR (P < 0.05). There were no significant differences for the T allele frequency among asthmatic patients with the various other phenotypes such as high versus normal total eosinophil, high versus normal total IgE and high versus normal levels of specific IgE against mite, cockroach or cat dander, or dog dander. CONCLUSIONS: Polymorphism in the promoter of the IL-4 gene is associated with asthma and is a disease modifier in terms of the severity of AHR.