Bronchial Hyperresponsiveness to Methacholine and AMP in Children With Atopic Asthma

PURPOSE: Bronchial hyperresponsiveness (BHR) is typically measured by bronchial challenge tests that employ direct stimulation by methacholine or indirect stimulation by adenosine 5'-monophosphate (AMP). Some studies have shown that the AMP challenge test provides a better reflection of airway inflammation, but few studies have examined the relationship between the AMP and methacholine challenge tests in children with asthma. We investigated the relationship between AMP and methacholine testing in children and adolescents with atopic asthma. METHODS: The medical records of 130 children with atopic asthma (mean age, 10.63 years) were reviewed retrospectively. Methacholine and AMP test results, spirometry, skin prick test results, and blood tests for inflammatory markers (total IgE, eosinophils [total count, percent of white blood cells]) were analyzed. RESULTS: The concentration of AMP that induces a 20% decline in forced expiratory volume in 1 second [FEV1] (PC20) of methacholine correlated with the PC20 of AMP (r2=0.189, P<0.001). No significant differences were observed in the levels of inflammatory markers (total eosinophil count, eosinophil percentage, and total IgE) between groups that were positive and negative for BHR to methacholine. However, significant differences in inflammatory markers were observed in groups that were positive and negative for BHR to AMP (log total eosinophil count, P=0.023; log total IgE, P=0.020, eosinophil percentage, P<0.001). In contrast, body mass index (BMI) was significantly different in the methacholine positive and negative groups (P=0.027), but not in the AMP positive and negative groups (P=0.62). The PC20 of methacholine correlated with FEV1, FEV1/forced vital capacity (FVC), and maximum mid-expiratory flow (MMEF) (P=0.001, 0.011, 0.001, respectively), and the PC20 of AMP correlated with FEV1, FEV1/FVC, and MMEF (P=0.008, 0.046, 0.001, respectively). CONCLUSIONS: Our results suggest that the AMP and methacholine challenge test results correlated well with respect to determining BHR. The BHR to AMP more likely implicated airway inflammation in children with atopic asthma. In contrast, the BHR to methacholine was related to BMI.

Long-term monotherapy with suplatast tosilate in patients with mild atopic asthma: A pilot comparison with low-dose inhaled fluticasone.

Background and objective: Suplatast tosilate is a Th2 cytokine inhibitor that is effective for controlling persistent asthma. However, the long-term efficacy of suplatast is unknown. We compared the clinical efficacy of long-term monotherapy with suplatast tosilate with a low dose of inhaled steroids in patients with mild atopic asthma. Methods: A total of 32 patients with mild atopic asthma were randomly assigned to receive suplatast (n = 15) or fluticasone (n = 17). In the suplatast group, 100 mg of suplatast was given orally 3 times a day (total daily dose = 300 mg) for 2 years. In the fluticasone group, 100 mg of fluticasone was inhaled twice a day (total daily dose = 200 µg) for 2 years. Results: In the suplatast group, the improvements in peak expiratory flow (PEF) rate and forced expiratory volume in 1 second (FEV1) and the changes in the symptom diary scale and frequency of β2 stimulant inhalation were generally similar to those in the fluticasone group, and efficacy was maintained for 2 years. Improvements in inflammatory indices, such as the sputum eosinophil cationic protein (ECP) level and exhaled nitric oxide concentration, were comparable in the suplatast and fluticasone groups. The improvement in airway hyper-responsiveness was also similar in the 2 groups. The peripheral blood eosinophil percent change, serum ECP level, and total IgE antibody titer improved only in the suplatast group. Conclusions: Long-term treatment with suplatast significantly improved symptoms and inflammatory indices in patients with mild atopic asthma. Along with fluticasone, suplatast is considered a useful drug for the management of mild atopic asthma.

Factors for high-risk asthma in Taiwanese children.

Background: Asthma is one of the major causes of death in otherwise healthy young individuals. However, many of these deaths may have been prevented by more aggressive treatment. To determine factors correlated with a high risk of death in Taiwanese children with atopic asthma. Methods: Taiwanese children aged 5-18 years, diagnosed with atopic asthma were enrolled in the study. Atopic asthma was diagnosed and immunoglobulin E (IgE) specific to antigens from any 1 of 8 allergens was measured (i.e. Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat and dog dander, cockroach, egg white, milk and fish). High-risk asthma was defined as asthma requiring admission to a hospital or a visit to an emergency department. The study tried to determine the association of high-risk asthma with allergy-related parameters (e.g. asthma severity, asthma score, total serum IgE levels, serum levels of allergenspecific IgE, eosinophil count) and pulmonary function in Taiwanese children. Results: One thousand one hundred and twenty-two Taiwanese children were evaluated. Those with higher asthma severity, asthma symptom score, serum levels of IgE specific to D. pteronyssinus and D. farinae, higher total serum IgE levels, and lower FEF25-75% (forced expiratory flow, 25-75%) values were considered to be members of the highrisk asthma group. Conclusions: The characterization of risk factors has enabled us to identify high-risk asthma in Taiwanese children, which will facilitate the treatment of these children in the future.

A revisit to cockroach allergens.

Among cockroaches (CR) that live in people’shomes, two species, i.e., German CR (Blattella germanica) and American CR (Periplaneta americana) predominate in temperate and tropical areas, respectively. CR is an important source of inhalant indoor allergens that sensitize atopic subjects to (localized) type I hypersensitivity or atopy including allergic rhinitis and atopic asthma. In Thailand the predominant CR species is P. americana. CR allergens are found throughout CR infested houses; the number found in kitchens correlates with the degree of CR infestation while sensitization and reactivation of the allergic morbidity are likely to occur in the living room and bedroom. Levels of the CR allergens in homes of CR allergic Thais, measured by using locally made quantification test kits, revealed that the highest levels occur in dust samples collected from the wooden houses of urban slums and in the cool and dry season. CR allergens are proteins that may be derived from any anatomical part of the insect at any developmental stage. The allergens may be also from CR secretions, excretions, body washes or frass. The proteins may be the insect structural proteins, enzymes or hormones. They may exist as dimers/multimers and/or in different isoforms. Exposure to CR allergens in infancy leads to allergic morbidity later in life. Clinical symptoms of CR allergy are usually more severe and prolonged than those caused by other indoor allergens. The mechanisms of acute and chronic airway inflammation and airway hyper-responsiveness (AHR) have been addressed including specific IgE- and non-IgEmediated mechanisms, i.e., role of proteaseactivated receptor-2 (PAR2). Participation of various allergen activated-CD4+ T cells of different sublineages, i.e., Th2, Th17, Th22, Th9, Th25, Tregs/Th3 as well as invariant NKT cells, in asthma pathogenesis have been mentioned. The diagnosis of CR allergy and the allergy intervention by CR population control are also discussed.

Glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genetic polymorphisms and atopic asthma in children from Southeastern Brazil

Xenobiotics can trigger degranulation of eosinophils and mast cells. In this process, the cells release several substances leading to bronchial hyperactivity, the main feature of atopic asthma (AA). GSTM1 and GSTT1 genes encode enzymes involved in the inactivation of these compounds. Both genes are polymorphic in humans and have a null variant genotype in which both the gene and corresponding enzyme are absent. An increased risk for disease in individuals with the null GST genotypes is therefore, but this issue is controversial. The aim of this study was to investigate the influence of the GSTM1 and GSTT1 genotypes on the occurrence of AA, as well as on its clinical manifestations. Genomic DNA from 86 patients and 258 controls was analyzed by polymerase chain reaction. The frequency of the GSTM1 null genotype in patients was higher than that found in controls (60.5 percent versus 40.3 percent, p = 0.002). In individuals with the GSTM1 null genotype the risk of manifested AA was 2.3-fold higher (95 percentCI: 1.4-3.7) than for others. In contrast, similar frequencies of GSTT1 null and combined GSTM1 plus GSTT1 null genotypes were seen in both groups. No differences in genotype frequencies were perceived in patients stratified by age, gender, ethnic origin, and severity of the disease. These results suggest that the inherited absence of the GSTM1 metabolic pathway may alter the risk of AA in southeastern Brazilian children, although this must be confirmed by further studies with a larger cohort of patients and age-matched controls from the distinct regions of the country.

A study of high-sensitivity c-reactive protein in bronchial asthma.

Background. Relevance of C-reactive protein an acute phase reactant and a sensitive marker of low-grade systemic inflammation in bronchial asthma has not been fully studied. Objective. To evaluate the significance of high-sensitivity C-reactive protein (hs-CRP) in atopic and non-atopic asthma using an ultra sensitive assay. Methods. The levels of hs-CRP of 200 patients with bronchial asthma and 50 non-asthmatic control subjects were measured using a Latex enhanced immunoturbidimetric test. Spirometry with reversibility study, serum immunoglobulin-E (IgE) measurement and skin test for allergy was done in all the patients. Results. There was a significant increase in hs-CRP levels with age in atopic asthmatics but no such association was observed in the non-atopic asthmatics and control subjects. The hs-CRP levels were not influenced by sex in any group. Smokers in all the three groups had a significantly higher hs-CRP levels as compared to non-smokers. Patients with asthma had higher hs-CRP values as compared to controls. Patients with non-allergic asthma had higher mean hs-CRP as compared to atopic asthmatics and control subjects. Conclusions. The study suggests that there exists a certain degree of low-grade systemic inflammation in addition to the local bronchial inflammation in non-atopic asthmatics. Hence, hs-CRP may be used as a surrogate marker for the airway inflammation in non-atopic asthma patients.

Association study of polymorphism in leukotriene C4 synthase and cysteinyl leukotriene receptor 1 genes with phenotype of asthma and clinical parameters in Korean children / 소아과

PURPOSE: Cysteinyl leukotrienes are important proinflammatory mediators in asthma. Recently, it was suggested that a promoter polymorphism in the genes encoding for leukotriene C4 synthase (LTC4S), a key enzyme in the leukotriene synthetic pathway, and cysteinyl leukotriene receptor 1 (CysLTR1) might be associated with aspirin-intolerant asthma. We investigated whether polymorphisms in LTC4S and CysLTR1 genes or their interactions were associated with the asthma phenotype, lung function, or bronchial hyperreactivity (BHR) in Korean children. METHODS: A total of 856 asthmatic children and 254 non-asthmatic controls were enrolled; a skin prick test, lung function test and bronchial provocation test were performed. Of those enrolled, 395 children underwent exercise challenge tests. The LTC4S A(-444)C and CysLTR1 T(+927)C were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Of those enrolled, 699 children were classified as having atopic asthma and 277 children, as having exercise-induced asthma (EIA). LTC4S and CysLTR1 polymorphisms were not associated with atopic asthma, EIA, or asthma per se. Lung function and BHR were not significantly different between the wild type (AA or TT) and the variant (AC+CC or TC+CC) genotypes in asthmatics, atopic asthmatics, and EIA (+) asthmatics, while total eosinophil counts were higher in the variant type of LTC4S than in the wild type in atopic asthmatics. There were no associations between the gene-gene interactions of LTC4S and CysLTR1 genotypes and the asthma phenotypes. CONCLUSION: LTC4S A(-444)C and CysLTR1 T(+927)C polymorphisms and their gene-gene interactions are not associated with asthma phenotype, lung function, or BHR in Korean children.

Comparison of Methacholine and Adenosine 5'-Monophosphate Responsiveness Between Preschool Children with Atopic Asthma and Those with Nonatopic Asthma / 소아알레르기및호흡기학회지

PURPOSE: It is well known that atopy is a major determinant of bronchial hyperresponsiveness (BHR) in both asymptomatic and asthmatic children. However, the relationship between atopy and BHR has not been well studied in preschool children with asthma. The aim of this study was to evaluate and compare BHR to direct and indirect stimuli between young children with atopic asthma and those with nonatopic asthma. METHODS: Methacholine and adenosine 5'-monophosphate (AMP) bronchial challenges were performed on 177 preschool children with asthma (145 atopics and 32 nonatopics) using a modified auscultation method. The endpoint was defined as the appearance of wheezing and/or oxygen desaturation. RESULTS: While the geometric mean of methacholine endpoint concentration was not significantly different between atopics and nonatopics that of the AMP endpoint concentration was significantly lower in atopics than in nonatopics (25.5 vs. 59.4 mg/mL; P=0.032). A positive response to methacholine (an end-point concentration < or =8 mg/mL) was observed in 96.5% (140/145) of patients with atopic asthma and in 84.3% (27/32) with non-atopic asthma. The frequency of a positive response to AMP (an endpoint concentration < or =200 mg/mL) was 86.8% (126/145) in patients with atopic asthma and 75% (24/32) in these with non-atopic asthma. CONCLUSION: Atopics more frequently displayed BHR to AMP and had a higher responsiveness to AMP than nonatopics. These results suggest that atopic and non-atopic asthma in preschool children may be related to the distinctive pathophysiologic pathways.

Methacholine and adenosine 5'-monophosphate challenge tests in children with atopic asthma and with nonatopic asthma, and their relationships to blood eosinophil markers / 소아과

PURPOSE: Though atopic and nonatopic asthma have different clinical manifestations, bronchial hyperresponsiveness (BHR) and airway inflammations are common characteristics of them. We investigated BHR to both methacholine and adenosine 5'-monophosphate (AMP), and their relationships with blood eosinophil markers in nonatopic asthma as well as atopic asthma. METHODS: We studied 116 children (82 atopics; 34 nonatopics) with mild to moderate asthma. Methacholine and AMP challenge tests were performed and bronchial responsiveness was expressed as PC20 (provocative concentration causing a 20 percent fall in FEV1); blood eosinopil counts (ETCs) and serum eosinophil cationic protein (ECP) levels were gauged. RESULTS: In atopics, 95.1 percent and 90.2 percent showed hyperreactivity to methacholine (PC20<16 mg/mL) and AMP (PC20<200 mg/mL), respectively. Meanwhile, in nonatopics, 94.1 percent and 52.9 percent displayed hyperreactivity to methacholine and AMP, respectively. The geometric mean of AMP PC20 was lower in atopics (31.6 mg/mL) than in nonatopics (125.9 mg/mL); that of methacholine PC20 was similar in the two groups. AMP PC20 correlated with blood ETCs in both atopics(r=-0.30, P<0.01) and nonatopics (r=-0.57, P<0.01), and correlated with serum ECP levels (r=-0.23, P<0.01) in atopics, but not in nonatopics. Apart from AMP, methacholine PC20 was not associated with blood eosinophil markers in either group. CONCLUSION: Atopics more frequently displayed BHR to AMP than nonatopics. Furthermore, BHR to AMP was associated with not only blood ETCs, but serum ECP levels in atopics but was correlated with only blood ETCs in nonatopics. Those results suggest that BHR to AMP reflects airway inflammation in asthma and is more related to atopy.

IL-4, IFN-gamma, IL-5, IL-12 Production by Peripheral Blood Mononuclear Cells of Moderate Atopic Asthma and Its Relation with Clinical Findings / 소아알레르기및호흡기학회지

PURPOSE: Activation of T helper(Th) cells and secretion of cytokines play a pivotal role in the pathogenesis of asthma. Th2 cells secrete IL-4 and IL-5. IL-4 stimulates IgE production and IL-5 is related with hematopoiesis, chemotaxis and activation of eosinophils. IFN-gamma produced by Th1 cells and IL-12 produced by antigen presenting cells have an inhibitory action on IgE production. We examined the cytokine production by peripheral blood mononuclear cells(PBMCs) of atopic asthmatic children and its relation with clinical findings. METHODS: We measured IL-4, IFN-gamma, IL-5, IL-12 in serum and supernatants of stimulated PBMCs cultures in 32 children with moderate stable asthma and 17 healthy controls. They were compared with number of skin test positive allergens, serum total IgE, peak expiratory flow rate(PEFR), methacholine PD20, sputum eosinophils and eosinophil cationic protein(ECP). RESULTS: No difference in serum cytokines was found between patients and controls, except IL-5. In supernatants of stimulated PBMCs cultures, the concentration of IL-4, IL-5 was significantly increased and IFN-gamma, IL-12 was significantly decreased in patients compared with controls. IL-4 was related with total serum IgE and numbers of skin test positive allergens. IL-5 was related with sputum eosinophils and ECP. The serum total IgE was inversely and PEFR was directly related with IFN-gamma. CONCLUSION: In atopic asthmatics, Th1 cytokines were increased and Th2 were decreased in stimulated PBMCs cultures. IL-4 was related with atopy, IFN-gamma with lung function and IL-5 with airway inflammation.

Soluble E-selectin as A Clinical Marker of Disease Activity in Atopic Dermatitis / 소아알레르기및호흡기학회지

PURPOSE: Augmentation in the expression of E-selectin on activated vascular endothelial cells regulates leukocyte migration into the tissue. These molecules are also shed into the circulation as a soluble form. The level of soluble forms in the serum has been known to be correlated with those expressed on the endothelial cells, thus it can be used as a marker of inflammation in that tissue. The purpose of this study is to compare the serum levels of soluble E-selectin(sE-selectin) in patients with atopic dermatitis(AD), atopic asthmatics, and healthy non-atopics, and to determine whether sE-selectin levels are correlated with disease activity in patients with atopic dermatitis. METHODS: We examined serum sE-selectin levels, serum total IgE levels, and total eosinophil counts from 18 children with AD, 15 atopic asthmatics and 15 healthy non-atopics. The severity of AD was assessed by clinical scoring(SCORAD index). We compared the sE-selectin levels among the three groups and investigated the correlations with SCORAD index. RESULTS: The children with AD had significantly higher levels of sE-selectin than those of atopic asthmatics(P<0.05) and of healthy non-atopics(P<0.05). There was no difference in the serum sE-selectin levels between the groups of atopic asthmatics and healthy non- atopics. Serum sE-selectin levels were correlated with SCORAD index in patients with AD, (P<0.05) but not significantly correlated with serum total IgE levels and total eosinophil counts. There were no significant correlations among SCORAD index, serum total IgE levels, and total eosinophil counts. CONCLUSION: The serum sE-selectin level is elevated only in patients with AD, not in atopic asthmatics. Therefore, sE-selectin could be considered as a useful marker of the disease activity in AD.

Influence of conventional house-dust-mite immunotherapy on histamine releasability from the basophil / 천식및알레르기

BACKGROUND: Allergen-specific immunotherapy has been shown to be clinically effective in the treatment of patients with atopic asthma, but the mechanisms are still unclear. Some of the immunologic changes include increase of an allergen-specific IgG antibody, decrease of allergen-specific IgE after transient increase, allergen-specific T-cell shift in cytokine expression from Th2 to Th1 cytokines, and decrease of basophil histamine releasability. OBJECTIVE: To investigate the influence of immunotherapy on basophil releasability, we examined the changes of IgE-mediated and non-IgE-mediated basophil histamine releasability during immunotherapy. METHODS: Fourteen Dermatophagoides farinae (D.f) sensitive asthmatic children with conventional immunotherapy were investigated. Basophil histamine releasability was measured prior to immunotherapy and 4 and 9 months after immunotherapy. Basophils were stimulated with D.f and goat antihuman IgE antibody as IgE-mediated stimuli which act on IgE-receptor, and formyl-Met-Leu-Phe (fMLP) as non-IgE-mediated stimuli which acts on non-IgE receptor, and calcium ionophore A23187 as non-IgE-mediated stimuli which does not act on cell surface receptors. Histamine was measured by automated fluorometric technique. RESULTS: Before immunotherapy, there were significant correlations between histamine release by D.f and histamine release by fMLP, and between histamine release by D.f and histamine release by anti-IgE antibody, but no correlation between histamine release by D.f and histamine release by calcium ionophore. Histamine release by D.f and by anti-IgE antibody decreased at and 9 months after immunotherapy compared to those before immunotherapy. Histamine release by fMLP and by calcium ionophore showed no significant changes after immunotherapy. There was no significant change of total histamine release after immunotherapy. CONCLUSION: Conventional immunotherapy has influenced only the IgE-mediated basophil releasability. IgE-mediated and non-IgE-receptor-mediated basophil releasability was correlated before immunotherapy, but only IgE-receptor-mediated basophil releasability decreased after immunotherapy. These findings suggest that a kind of physicochemical change may happen on the IgE receptors of basophil, which may induce decrease of IgE-mediated basophil histamine releasability after immunotherpy.

The Relationship between Total Serum IgE, Allergen-Specific IgE, and Skin Prick Test in Children with Atopic Asthma

PURPOSE: Skin prick test and determination of allergen-specific IgE antibodies in serum are methods commonly used to diagnose allergies. Several studies indicate that skin test and specific IgE have roughly the same diagnostic precision, although discrepancies exist. The objective of this study was to evaluate the influence of total serum IgE on the relation between skin prick test and allergen-specific IgE antibody. METHODS: We performed skin prick tests using 14 major inhalant allergens and measured total IgE and specific IgE for two major allergens [Dermatophagoides farinae(D.f.) and Dermatophagoides pteronyssinus (D.p.)] in serum of 230 children with atopic asthma. RESULTS: Positivity of skin prick test was 92.2% for D.f., 89.6% for D.p., and 22.6% for cockroach. Allergen/Histamine(A/H) ratio and allergen-specific IgE score showed a positive correlation for D.f.(r=0.39, P<0.01), and for D.p.(r=0.38, P<0.01). Total serum IgE and allergen-specific antibody score showed a positive correlation for D.f.(r=0.50, P<0.01), and for D.p.(r=0.53, P<0.01). There was no correlation between total serum IgE and A/H ratio on skin prick test for the two allergens. However, total serum IgE had the tendency to increase according to the number of positive allergens on skin prick test. At each level of A/H ratio for D.f. and D.p. on skin prick test, patients with high total IgE had higher antigen-specific IgE scores than patients with low total IgE. CONCLUSION: Our results show that the relationship between skin prick test and antigen-specific IgE was influenced by the level of serum total IgE. This indicates that the level of serum total IgE should be taken into account when skin prick test and allergen-specific IgE are compared.

The Effect of Allergen-Specific Immunotherapy on IL-10 and IL-13 mRNA Expression in Peripheral Blood Mononuclear Cells from Patients with Atopic Asthma / 소아알레르기및호흡기학회지

PURPOSE: Allergen-specific immunotherapy (IT) has been shown to be effective in the treatment for allergic diseases. But the immunologic mechanism of IT effect has not been fully elucidated. We studied house dust mite (HDM)-specific cytokine mRNA expression in peripheral blood mononuclear cells (PBMC) from patient with HDM- sensitive asthma and determined whether alterations in cytokine mRNA expression correlated with the clinical outcome of IT. METHODS: PBMC were obtained from 64 children with mite-sensitive asthma : 25 had never received HDM-IT (NIT), 39 had been receiving HDM-IT for more than 12 months. The 39 patients were divided into two groups according to the clinical response based on the asthma scores (symptom and medication scores) before and after IT. Good responders were those patients who showed an improvement greater than 50%, whereas poor responders were those who showed an improvement less than 50%. After a 18 hr culture with HDM, cytokine mRNA expression was analysed by RT-PCR and densitometry. RESULTS: 1) IL-10 mRNA expression in NIT was significantly lower than that in the normal controls and was significantly increased by IT. IL-10 mRNA expression in the good responders was significantly higher than that in the poor responders and NIT. 2) Little or no IL-13 mRNA were detected in the good responders and the normal controls. IL-13 mRNA expression in the good responders was significantly lower than that in the poor responders and NIT. 3) IFN-gamma mRNA expression in NIT was significantly lower than that in the normal controls and was significantly increased with IT. IFN-gamma mRNA expression in the good responders was significantly higher than that in the poor responders and NIT. 4) Little IL-4 mRNA were detected in the good responders and the normal controls. IL-4 mRNA expression in the good responders was significantly lower than that in the poor responders and NIT. CONCLUSION: These results show that IT not only induces a shift in cytokine expression from TH2 (IL-4 and IL-13) to TH1 cytokines (IFN-gamma), but also leads to induction of the antiinflammatory cytokine IL-10. These changes in cytokine expression may be responsible for clinical effects by immunotherapy.

Basophil Histamine Releasability in Asthmatic Children

PURPOSE: The release of histamine from human basophils is controlled by an intrinsic, as yet unidentified, cellular property termed "releasability." We carried out this study to ascertain whether there was any difference in the releasability of basophils from asthmatic children compared to those from normal children. We intended also to clarify the correlation between the releasability and the atopic status of asthma. METHODS: We selected nineteen atopic asthmatic, eighteen nonatopic asthmatic and fourteen normal children for this study. Suspensions of leukocytes were isolated and stimulated with calcium ionophore A23187, anti-IgE and D. pteronyssinus antigen. After incubation, the supernatant was assayed for histamine with an automated fluorometric technique. RESULTS: Basophil histamine release with anti-IgE was different in three groups. Anti-IgE caused significantly more basophil histamine release in asthmatic children than in nomal children. Atopic asthmatic group showed greater basophil histamine release with anti-IgE than nonatopic asthmatic group. D. pteronyssinus antigen caused the significant amount of histamine release only in atopic asthmatic group. CONCLUSIONS: Our data suggests that basophils from asthmatic children are characterized by a specific increase in IgE mediated histamine releasability. The difference of histamine releasability with anti-IgE between atopic and nonatopic asthmatic children may be due to the heterogeneity of IgE bound to cell surface, or may be due to the degree of the basophil activation by cytokines such as IL3. The specific release of histamine with D. pteronyssinus antigen in atopic asthmatic group suggests that the basophil histamine release test can be used to diagnose the causing antigen.

Studies on familial of basophil histamine releasability / 천식및알레르기

BACKGROUND: Bronchial asthma is a complex genetic disorder. Although serum IgE level and bronchial hyperresponsiveness are well known to be under genetic control, the influence of genetic factors on basophil releasability has been seldom studied. OBJECTIVE: The present study was carried out to investigate whether genetic factors may influence the basophil histamine releasability. MATERIALS AND METHODS: We studied 50 children, 32 with atopic asthma (AA) and 18 normal control (NC), and their parents. Suspensions of leukocytes were isolated and stimulated with Ca ionophore and anti-IgE antibody. Then, histamine in the supernatant was as-sayed by an automated fluorometric analyzer. RESULTS: Among the probands, AA children had a significantly higher anti-IgE induced histamine release than NC children. In contrast, Ca ionophore-induced histamine release was similar between the two groups. Ca ionophore-induced or anti-IgE-induced histamine release was not significantly different between parents of AA children and those of NC children. However, the maximal histamine release by Ca ionophore in parents had a significant correlation with that of probands, whereas the values by anti-IgE were not correlated between probands and their parents. CONCLUSION: We confirmed that basophils from patients with atopic asthma are characterized by a specific increase in IgE-mediated histamine release. The significant correlation of Ca ionophore-induced maximal histamine release between children and their parents suggests that genetic factors may play an important role in the control of non-IgE-mediated relessability from basophils.

Activity of Cytokines and Expression of CD62L in Patients with Bronchial Asthma / 결핵

BACKGROUND: The CD4+ T-helper cells comprise functionally distinct subsets of Th1 and Th2 cells that are distinguished on the basis of differential cytokines production. Th1 cells secrete interferon-gamma, lymphotoxin, interleukin-2. Th2 cells produce interleukin-4, interleukin-5, interleukin-10. A previous study shown that Th2 cells and their cytokines increased in patients with atopic asthma. We compared cytokines(IL-4, IFN-gamma) activity and subpopulation of T-lymphocytes in peripheral blood from atopic asthmatics versus non-asthmatics. METHOD: Fifteen patients with atopic asthma(nine men, six women), twelve patients with chronic bronchitis (six men, six women), five healthy persons(three men, two women) were studied. Activity of IL-4, IFN-gamma and T-cell subpopulation in peripheral blood were estimated. RESULTS: Patients had a median age of 55yr. The mean activity of IL-4 of asthmatics was significantly increased(control 0.75+/-1.1pmol/L, atopic asthmatics 3.50+/-0.75pmol/L, chronic bronchitis 2.01+/-1.2pmol/L), but IFN- was not significantly increased. In the T lymphocyte subsets the percent of CD62L+ T-lymphocytes of asthmatics was not significantly increased(control 16.7+/-16.4 %, atopic asthmatics 24.8+/-23.6 %, chronic bronchitis 17.0+/-16.9%). CONCLUSION: In this study elevated production of IL-4 was observed in atopic asthmatics. CD62L+ T-lymphocytes was not increased in atopic asthma.