Immunologic regulatory effects of human umbilical cord blood-derived mesenchymal stem cells in a murine ovalbumin asthma model.

BACKGROUND: Mesenchymal stem cells (MSCs) have multiple immunomodulatory properties and hold therapeutic potential for inflammatory diseases. However, the therapeutic and immunologic effects of human umbilical cord blood-derived MSCs (huMSCs) remain largely unexamined for asthma. OBJECTIVE: This study was to investigate the immunomodulatory properties of huMSCs in an ovalbumin (OVA)-induced murine asthma model. METHODS: Mice were injected intraperitoneally with OVA and an aluminium hydroxide adjuvant. huMSCs were administered via the tail vein (5×105 cells/100 uL) to female BALB/c mice prior to the initial OVA challenge. The effects of huMSCs were assessed by investigating airway hyperresponsiveness, histological changes, inflammatory cell numbers, serum allergen-specific antibodies, cytokine production in spleen, lung tissue, and bronchoalveolar lavage (BAL) fluid as well as expansion of regulatory T cells. RESULTS: Administration of huMSCs significantly reduced methacholine bronchial hyperresponsiveness and eosinophil counts in BAL cells. Similarly, there was a significant decrease in serum OVA-specific IgE and IgG1 levels along with Th2 cytokine production (IL-4, IL-5, and IL-13) in the lung and spleen tissues, whereas increased percentage of regulatory T cells was observed after treatment with huMSCs. CONCLUSIONS: Our results suggest that huMSC treatment reduces OVA-induced allergic inflammation, which could be mediated by regulatory T cells.

Google unveils a glimpse of allergic rhinitis in the real world.

Google Trends (GT) is a Web-based surveillance tool used to explore the searching trends of specific queries on Google. Recent studies have suggested the utility of GT in predicting outbreaks of influenza and other diseases. However, this utility has not been thoroughly evaluated for allergic diseases. Therefore, we investigated the utility of GT for predicting the epidemiology of allergic rhinitis. In the USA, GT for allergic rhinitis showed repetitive seasonality that peaked in late April and early May and then rapidly decreased, and a second small peak occurred in September. These trends are highly correlated with the searching trends for other queries such as 'pollen count', antihistamines such as loratadine and cetirizine (all r > 0.88 and all P < 0.001), and even the total pollen count collected from 21 pollen counters across the USA (r = 0.928, P < 0.001). Google Trends for allergic rhinitis was similar to the monthly changes in rhinitis symptoms according to the US National Health and Nutrition Examination Survey III, sales for Claritin(®) and all over-the-counter antihistamines, and the number of monthly page views of 'claritin.com'. In conclusion, GT closely reflects the real-world epidemiology of allergic rhinitis in the USA and could potentially be used as a monitoring tool for allergic rhinitis.

Staphylococcal enterotoxin sensitization in a community-based population: a potential role in adult-onset asthma.

BACKGROUND: Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult-onset asthma in community-based populations. OBJECTIVE: We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community-based adult populations. METHODS: The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age = 60.2 years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin-specific IgE using ImmunoCAP. RESULTS: Staphylococcal enterotoxin sensitization (≥ 0.35 kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (≥ 61 years), and inhalant allergen sensitization. Current asthma was mostly adult onset (≥ 18 years old) and showed independent associations with high enterotoxin-specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin-specific IgE level was identified as the major determinant factor for total IgE level. CONCLUSIONS AND CLINICAL RELEVANCE: Staphylococcal enterotoxin sensitization was independently associated with adult-onset asthma in adult community populations. Strong correlations between the enterotoxin-specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis.

The role of high-mobility group box-1 (HMGB1) in the pathogenesis of asthma.

BACKGROUND: High-mobility group box 1 protein (HMGB1) belonging to endogenous danger signals prolongs eosinophil survival and acts as a chemoattractant. OBJECTIVE: The authors evaluated the role of HMGB1 in the pathogenesis of asthma characterized by eosinophilic airway inflammation. METHODS: Firstly, HMGB1 expressions in induced sputum obtained from human asthmatics were determined. This was followed by an evaluation of the role of HMGB1 in a murine model of asthma using anti-HMGB1 antibodies. Then the effect of HMGB1 on the receptor of advanced glycation end products (RAGE) expressions on CD11b-CD11c(+) cells isolated from a murine model of asthma were measured to elucidate the mechanisms involved. RESULTS: Sputum HMGB1 expressions were markedly higher in asthmatics than in normal controls, and were positively correlated with sputum eosinophilia and sputum TNF-α, IL-5 and IL-13 expressions. In a murine model of asthma, HMGB1 expressions in lung tissue and HMGB1 levels in bronchoalveolar lavage fluid were significantly elevated and eosinophilic airway inflammation, non-specific airway hyperresponsiveness, and pathological changes were attenuated by blocking HMGB1 activity. Furthermore, we found that enhanced RAGE expressions on CD11b-CD11c(+) also significantly decreased when HMGB1 activity was blocked. CONCLUSION AND CLINICAL RELEVANCE: Our findings suggest that HMGB1 plays a key role in the pathogenesis of clinical and experimental asthma characterized by eosinophilic airway inflammation.

Clonorchis sinensis infection is positively associated with atopy in endemic area.

BACKGROUND: Epidemiologic studies have suggested that helminth infections play a protective role against allergy; this inverse association, however, has not been consistent. Clonorchis sinensis, the liver fluke of human, is prevalent in the Far East. The association between C. sinensis infection and allergy has not yet been reported. OBJECTIVE: We evaluated the association between clonorchiasis and atopy or allergic diseases in adults in endemic areas of clonorchiasis. METHODS: A total of 1116 subjects (males 419, females 697; age range, 30-86; mean age=61 years) were recruited from two endemic areas of C. sinensis in Korea. Clonorchiasis was confirmed by stool examination. Allergic symptoms were evaluated with a modified ISAAC questionnaire, and atopy was defined by skin prick test for common inhalant allergens. Total serum IgE and C. sinensis-specific IgE level was measured by ELISA and methacholine bronchial provocation test was performed to evaluate airway hyperresponsiveness (AHR). RESULTS: Clonorchiasis was positively associated with atopy [odds ratio (OR), 1.856; 95% confidence interval (CI), 1.199-2.873] and high levels of total serum IgE (OR, 1.455; 95% CI, 1.050-2.016). Higher association with clonorchiasis was shown in subjects who showed both atopy and high total serum IgE levels (OR, 2.540; 95% CI, 1.448-4.455). Clonorchiasis had no association with wheezing, AHR, asthma or allergic rhinitis. CONCLUSION AND CLINICAL RELEVANCE: Clonorchiasis was positively associated with atopy in adults in endemic area.

Allelic variants of CD40 and CD40L genes interact to promote antibiotic-induced cutaneous allergic reactions.

BACKGROUND: The danger hypothesis provides a new perspective of the mechanisms underlying drug allergy. In this study, we evaluated associations between variations in the genes involved in danger signal pathways and antibiotic-induced cutaneous allergic reactions (AICARs). METHODS: Two hundred cases with urticaria, angio-oedema, maculopapular rash, and erythema multiforme caused by antibiotics were extracted from the database of the Adverse Drug Reaction Research Group in Korea. All cases were confirmed by an allergy specialist. Causative antibiotics included penicillin, cephalosporin, quinolone, and others (approximately 40 different types). Ten single nucleotide polymorphisms (SNPs) in seven genes (-318C>T, +49A>G, and +6230G>A in CTLA4, IVS+17T>C in CD28, -3479T>G and I170V in CD86, -1C>T in CD40, -3458A>G in CD40LG, -308G>A in TNF, and -31T>C in IL1B) were scored for cases and for healthy subjects without a history of AICARs. RESULTS: Our analysis failed to reveal differences in the distribution of the 10 SNPs between cases and controls. However, we could find a gene-gene interaction between -1C>T in CD40 and -3458A>G in CD40L using multifactor dimensionality reduction analysis. Subjects with minor alleles of both SNPs showed a significant risk for developing AICARs [P=0.017, odds ratio (OR) (95% confidence interval)=2.93 (1.20-7.97)]. CONCLUSION: Our findings suggest that a genetic interaction between CD40 and CD40L favours the development of AICARs.

Polymorphisms in the neurokinin-2 receptor gene are associated with angiotensin-converting enzyme inhibitor-induced cough.

BACKGROUND AND OBJECTIVE: Treatment with angiotensin-converting enzyme (ACE) inhibitors can induce chronic cough in many patients. Genetic variations in the neurokinin 2 receptor gene (NK2R) are significantly associated with cough sensitivity to capsaicin. METHODS: This study assessed the relationship between genetic polymorphisms in the NK2R gene and chronic cough in 91 patients taking ACE inhibitors. Patients included in the study did not have chest abnormalities, postnasal drip, gastroesophageal reflux or a recent history of upper respiratory infection. RESULTS: We detected two single nucleotide polymorphisms in the NK2R gene (i.e., Gly231Glu and Arg375His). The allelic frequencies at amino acid 231 were 36.3% for Gly/Gly, 49.5% for Gly/Glu and 14.3% for Glu/Glu. The allelic frequencies at amino acid 375 were 74.7% for Arg/Arg, 24.2% for Arg/His and 1.1% for His/His. The prevalence of chronic cough in patients with the amino acid 231 genotype was 33.3% in Gly/Gly homozygotes, 24.4% in Gly/Glu heterozygotes and 0% in Glu/Glu homozygotes. There was a statistically significant association between chronic cough and the Glu/Glu allele (P = 0.028) when the data were analyzed with a recessive model. In addition, there was a significant inverse linear association between the number of Glu231 alleles and ACE inhibitor-related cough (P = 0.026). The prevalence of chronic cough in patients with the amino acid 375 genotype was 22.1% in Arg/Arg homozygotes, 31.8% in Arg/His heterozygotes and 0% in His/His homozygotes, although none of these association were statistically significant. CONCLUSION: Our findings indicate that the Gly231Glu polymorphism is associated with a lower prevalence of ACE inhibitor-related cough.

Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict response.

BACKGROUND: Recent findings have raised new interests about the use of anticholinergics, especially tiotropium, for the treatment of asthma. This study was performed to determine whether an additional improvement in lung function is obtained when tiotropium is administrated in addition to conventional therapies in severe asthmatics, and to identify factors capable of predicting the response to tiotropium, using a pharmacogenetic approach. METHODS: A total of 138 severe asthmatics on conventional medications and with decreased lung function were randomly recruited. Tiotropium 18 microg was added once a day and lung functions were measured every 4 weeks. Responders were defined as those with an improvement of > or = 15% (or 200 ml) in the forced expiratory volume in 1 s (FEV1) that was maintained for at least 8 successive weeks. Eleven single nucleotide polymorphisms (SNPs) in CHRM1-3 (coding muscarinic receptors one to three) which were identified by re-sequencing, and Arg16Gly and Gln27Glu in ADRB2 (coding beta(2) adrenoreceptor) were scored in 80 of the 138 asthmatics. RESULTS: Forty-six of the 138 asthmatics (33.3%) responded to tiotropium treatment. Logistic regression analyses (controlled for age, gender, and smoking status) showed that Arg16Gly in ADRB2 [P = 0.003, OR (95% CI) = 0.21 (0.07-0.59) in a minor allele-dominant model] was significantly associated with response to tiotropium. CONCLUSIONS: As many as 30% of severe asthmatics on conventional medications with reduced lung function were found to respond to adjuvant tiotropium. The presence of Arg16Gly in ADRB2 may predict response to tiotropium.

Evaluation of cytokine mRNA in induced sputum from patients with allergic rhinitis: relationship to airway hyperresponsiveness.

BACKGROUND: Although airway hyperresponsiveness (AHR) is a characteristic feature of asthma, it is also frequently present in allergic rhinitis (AR). However, the pathogenesis of AHR is unclear and the roles of cytokines in the airway have not been well established in AR. We sought to compare cytokine mRNA levels in the sputum of AR patients with or without AHR and those of asthma patients, and to evaluate whether differences in cytokine levels are associated with the development of an abnormal airway response and the absence of respiratory symptoms in AR patients with AHR. METHODS: Airway cells were obtained by sputum induction from 18 AR patients with AHR, 58 AR patients without AHR, and 27 asthma patients. Airway cell cytokine levels, interleukin (IL) -4, IL-5, IL-13, vascular endothelial growth factor (VEGF), and interferon-gamma (IFN-gamma), were studied at the mRNA level by RT-PCR. RESULTS: Vascular endothelial growth factor and IL-5 mRNA levels were significantly higher in AR patients with AHR than in AR patients without AHR, but these were lower than those of asthmatic patients. Eosinophils were significantly higher in AR patients with AHR and in asthmatic patients than in AR patients without AHR. Interleukin-4, IL-13, and IFN-gamma levels were not elevated in AR patients with or without AHR vs asthma patients. CONCLUSIONS: These findings suggest that VEGF and IL-5 can be important determinants of the development of AHR in AR patients and that lower levels of other cytokines may be associated with the absence of asthmatic symptoms in AR patients with AHR.

Association between genetic variations in prostaglandin E2 receptor subtype EP3 gene (Ptger3) and asthma in the Korean population.

BACKGROUND: Recent investigations suggest that prostaglandin E2 (PGE2) is important in the pathogenesis of not only aspirin-intolerant asthma but also asthma unrelated to aspirin intolerance. OBJECTIVES: This study was conducted to evaluate the effects of variations in the gene coding PGE2 receptor subtype EP1-4 (Ptger1-4) on the risk of asthma in the Korean population. METHODS: Nineteen single nucleotide polymorphisms (SNPs) were selected after re-sequencing Ptger1-4 and were genotyped in 480 asthmatics and 140 healthy controls, who were randomly recruited. RESULTS: By logistic regression analyses controlling for age and sex, 1388T>C in Ptger3 was found to be significantly associated with asthma [P=0.002, odds ratio (95% confidence interval)=0.63 (0.46-0.85) in the allele model], and this remained significant after applying the Bonferroni correction. In terms of haplotype, the frequency of the C-C-A-A haplotype in Ptger3 was significantly lower in asthmatics than in healthy controls (P=0.004). Moreover, the prevalence of this haplotype was significantly lower in moderate-to-severe asthmatics than in mild asthmatics (P=0.045; mild vs. moderate and P=0.034; mild vs. severe). However, no association was found between any genetic variation in Ptger1, Ptger2, or Ptger4 and asthma. CONCLUSION: The present study demonstrated that genetic variations in Ptger3 are significantly associated with the risk and severity of asthma in the Korean population.

Association and functional relevance of E237G, a polymorphism of the high-affinity immunoglobulin E-receptor beta chain gene, to airway hyper-responsiveness.

BACKGROUND: The hyper-sensitivity reaction of IgE, with its high-affinity receptors (FcepsilonRI), is central to the phenomenon of atopic diseases. OBJECTIVE: To evaluate the genetic effects of non-synonymous single-nucleotide polymorphisms (SNPs) of FcepsilonRI on intermediate phenotypes of asthma, i.e. atopy and airway hyper-responsiveness (AHR), in the Korean general population. SUBJECTS AND METHODS: Atopy and AHR were evaluated in a cohort of 2055 subjects, aged 10-18 years, using skin prick tests (SPTs) for common aeroallergens and total serum IgE and methacholine bronchial provocation tests. All FcepsilonRI-alpha, FcepsilonRI-beta, and FcepsilonRI-gamma gene exons of 24 healthy subjects were sequenced to locate informative non-synonymous SNPs (minor allele frequency>2%). Informative SNPs were then scored, using the high-throughput single base extension method. Relative risk (RR) was determined by multiple logistic regression analysis, after adjusting for confounding factors. The functional relevance of non-synonymous SNPs was analysed using the sorting intolerant from tolerant (SIFT) program. RESULTS: The SNP search found only one informative non-synonymous SNP in FcepsilonRI-beta: E237G (minor allele frequency=0.21). The positive rate of AHR was lower among subjects with the 237*E allele than among those with 237*G [RR (95% confidence interval)=0.41 (0.19-0.89); P=0.01]. However, the E237G substitution was not associated with either a positive SPT response or total serum IgE levels. Sequence evolution analysis predicted that the E237G variation is an intolerant amino acid substitution, with functional importance. CONCLUSION: In the Korean general population, AHR is significantly associated with the E237G polymorphism of FcepsilonRI-beta, which results in an intolerant amino acid substitution.

Outcomes in occupational asthma caused by reactive dye after long-term avoidance.

BACKGROUND: Reactive dye (RD) is known to be a causative agent of occupational asthma (OA). However, to date, no report has been issued concerning the long-term outcomes of RD-induced OA. OBJECTIVES: We sought to evaluate the long-term outcomes in cases of OA caused by RD. METHODS: A total of 11 OA patients confirmed by RD bronchial challenge were enrolled in this study. First and second follow-up examinations were conducted at 4.3+/-2.3 and 13.7+/-2.3 years (means+/-SD) after the initial examinations, respectively. Skin prick test with RD and 11 common inhalant allergens, pulmonary function test, methacholine bronchial provocation testing, symptom and medication scores were determined at each visit. In addition, inflammatory cells in induced sputum were measured at the second follow-up examinations. RESULTS: Reduced lung function at initial examinations did not recover at the first and second examinations despite cessation of exposure and proper pharmacological treatment. In addition, asthma severity (as determined by symptom and medication scores) and non-specific airway hyper-responsiveness to methacholine also did not improve. However, skin reactivity to RD almost disappeared at the second examinations. Interestingly, four of the six patients who showed negative skin responses to all 11 common inhalant allergens at initial examinations were found to be atopic at the second examinations. Moreover, in terms of airway inflammation, seven of the 11 patients showed eosinophilia in induced sputum (> or =3%) at the second examinations despite having been on high-dose inhaled corticosteroid medication. CONCLUSION: The present study demonstrates that reduced lung function and asthmatic symptoms persist in RD-induced OA even after long-term exposure avoidance.

Association of genetic variations in neurokinin-2 receptor with enhanced cough sensitivity to capsaicin in chronic cough.

BACKGROUND: Chronic cough is associated with increased sensitivity to inhaled capsaicin, and both tachykinins and their receptors play important roles in the cough reflex. However, associations between polymorphisms of the tachykinin receptor genes and cough sensitivity in patients with non-productive chronic cough have not been reported. METHODS: Direct sequencing was used to identify single nucleotide polymorphisms (SNPs) in the genes for the neurokinin-1 and neurokinin-2 receptors (NK-1R and NK-2R, respectively). Informative non-synonymous SNPs were scored using the single base extension method for 312 patients with chronic cough and for 100 age matched healthy controls. The cough response to capsaicin was recorded for 312 patients with chronic cough, and the potential genetic association between cough sensitivity to capsaicin and the NK-1R and NK-2R genotypes was evaluated. RESULTS: Two informative SNPs were identified in NK-2R (Gly231Glu and Arg375His), whereas no informative SNP was found in NK-1R. After adjusting for atopy, sex, age, and smoking, the prevalence of enhanced cough sensitivity to capsaicin was higher in the chronic cough patients with the 231Glu allele (p = 0.004; OR 1.69 (95% CI 1.18 to 2.42)) and the 231Glu_375Arg haplotype (p = 0.003; OR 1.71 (95% CI 1.20 to 2.24)). Moreover, the lowest capsaicin concentration to cause five consecutive coughs (C5) was significantly lower in patients with 231Glu (mean (SD) 44.1 (53.2) v 60.9 (55.8) microM/l, p = 0.04) and those with 231Glu_375Arg (43.2 (52.7) v 69.6 (52.0) microM/l, p = 0.03). CONCLUSIONS: The results of this study suggest that NK-2R gene polymorphisms are involved in the enhanced cough sensitivity to capsaicin of patients with chronic cough.

Normal C1 inhibitor mRNA expression level in type I hereditary angioedema patients: newly found C1 inhibitor gene mutations.

BACKGROUND: C1 esterase inhibitor (C1INH) plays a key role in the classical pathway of the complement cascade. Mutations in this gene cause a decreased level of antigenic (type I hereditary angioedema, HAE) or functional (type II HAE) C1INH. OBJECTIVE: To find novel mutations in C1INH and evaluate the expression of C1INH gene in HAE patients. METHODS: Direct sequencing mutation analysis was performed for genomic DNA from three unrelated families (14 HAE patients and 18 family members). Genomic DNA from one family was also analyzed for larger genomic rearrangements, using Southern blotting analysis. We used real-time quantitative polymerase chain reaction (PCR) to evaluate C1INH mRNA expression level. RESULTS: Four mutations in exons (2,311 T-->C, 14,034 G-->A, 16,830 G-->A, and 16,979-16,980 G insertion) and four in introns (738 G-->A, 8,531 A-->G, 14,254 A-->G, and 14,337-14,378 TT deletion) were found. Interestingly, all of the nine patients in one family share the same mutation of Gly345Arg (14,034 G-->A) in the seventh exon. In another family, a single base mutation near the splice site (14,254 A-->G) was found in all of the three patients. In the last family, although a significant mutation was not found by direct sequencing, patients showed an abnormal 16 kb fragment in addition to the normal allele (21 kb Bcl I fragment). The C1INH mRNA expression of HAE patients in two families was not significantly different compared with that of normal controls. CONCLUSION: The two novel exonal mutations (G-->A and A-->G) and one large gene deletion were associated with the clinical phenotypes of HAE. Considering the normal C1INH mRNA levels but below normal protein levels in two families, their phenotypes would be associated with the post-translational defect.

Association between bronchodilating response to short-acting beta-agonist and non-synonymous single-nucleotide polymorphisms of beta-adrenoceptor gene.

BACKGROUND: With beta-agonists being the most widely used agents in the treatment of asthma, in vitro studies reported that beta(2)-adrenergic receptor (ADRB2) polymorphisms are associated with agonist-promoted down-regulation. OBJECTIVE: The present population-based study aimed to evaluate the association between bronchodilating response to inhaled short-acting beta-agonist and two non-synonymous single-nucleotide polymorphisms (SNPs) of ADRB2 (ADRB2-16 and ADRB2-27). METHODS: Two hundred and nine children with reduction in forced expiratory volume in 1 s of more than 20% on methacholine bronchial challenge underwent bronchodilating response testing 5 min after the inhalation of 200 mug of albuterol. Of these 209, 195 gave peripheral blood for genotyping of ADRB2 polymorphisms. RESULTS: The bronchodilating response was significantly higher in subjects with the homozygous Arg16 than in those with the homozygous Gly16. It was further demonstrated that haplotype pairs of the homozygous Arg16Gln27 and of the heterozygous Arg16Gln27/Gly16Glu27 showed the highest bronchodilating responses, and the haplotype pairs of the homozygous Gly16Gln27 the lowest response. As a whole, the bronchodilating response was more positively associated with the combined quantity of Arg16 and Glu27 polymorphisms than with that of Arg16 alone. CONCLUSION: Non-synonymous SNPs of ADRB2 at codons 16 and 27 is significantly associated with bronchodilating response to inhaled short acting beta-agonists.

Allergen-specific conventional immunotherapy decreases immunoglobulin E-mediated basophil histamine releasability.

BACKGROUND: Allergen-specific immunotherapy has proven to be clinically effective in the treatment of patients with atopic asthma; however, the mechanisms are still unclear. Several noted immunological changes include an increase of the allergen-specific IgG antibody, a reduction in the allergen-specific IgE antibody subsequent to transient increase, an allergen-specific T cell shift in cytokine production from Th2 to Th1, and a decrease in quantity and activity of basophils and mast cells. OBJECTIVE: To analyse the changes of basophil histamine release in response to IgE-mediated and non-IgE-mediated stimuli before and after conventional house-dust mite immunotherapy in children who suffer from atopic asthma. METHODS: Fourteen Dermatophagoides farinae (Df) sensitive asthmatic children with conventional immunotherapy were examined. Basophil histamine releasability was measured 0 months (just before immunotherapy), 4 months and 9 months after immunotherapy. Basophils were stimulated with Df and goat anti-human IgE antibody as IgE-mediated stimuli; and formyl-Met-Leu-Phe (fMLP) and calcium ionophore A23187 as non-IgE-mediated stimuli. Accordingly, the asthma symptom score was used to assess clinical outcome and the skin test reactivity to Df was measured. RESULTS: In contrast to pre-immunotherapy activity, 4 and 9 months after immunotherapy there were significant decreases in histamine release by Df and by anti-IgE antibody. The histamine release by fMLP and by calcium ionophore showed no significant changes after immunotherapy. Histamine release by Df demonstrated significant correlation to that by anti-IgE antibody and by fMLP, yet there was no observable correlation between histamine release by Df and by calcium ionophore. The asthma symptom score decreased significantly 4 and 9 months after immunotherapy and showed significant correlation with histamine release by Df. The skin test reactivity (allergen/histamine ratio) remained constant 4 months after immunotherapy, but decreased significantly 9 months after immunotherapy. CONCLUSION: Basophils have the potential to play an important role in the early clinical improvement of conventional immunotherapy in children with atopic asthma, which may be a result of the decreased IgE-mediated histamine releasability during immunotherapy.

Role of environmental exposure to spider mites in the sensitization and the clinical manifestation of asthma and rhinitis in children and adolescents living in rural and urban areas.

BACKGROUND: Spider mites such as the citrus red mite and the two-spotted spider mite have been demonstrated to be important allergens for fruit cultivating farmers. OBJECTIVE: To evaluate the role of environmental exposure to spider mites in the sensitization and the clinical manifestations of asthma and rhinitis in children and adolescents living in urban and rural areas. METHODS: A total of 16,624 subjects (aged 7 to 18 years) living in urban (metropolitan and non-metropolitan) and rural areas (apple orchards and citrus orchards) in Korea were evaluated by questionnaire and skin prick test for 11 common aeroallergens, including citrus red mite (CRM) and two-spotted spider mite (TSM). RESULTS: The positive skin response rates to TSM were 4.2% of 1,563 metropolitan subjects, 3.8% of 5,568 non-metropolitan subjects and 6.5% of 1,464 subjects living nearby apple farms, and that to CRM 15.6% of 8,029 living nearby citrus farms. The prevalence of current wheeze and rhinitis as reported on a questionnaire was higher among those with a history of visiting fruit farms once or more per year than among those without it (10% vs. 7.1%, 32.8% vs. 26.7%, for wheezing and rhinitis, respectively). Among those with wheezing or rhinitis, the positive skin responses to TSM or CRM were also higher among those with a history of visiting fruit farms than among those without one (11.2% vs. 6.6%, 13.0% vs. 6.6%, respectively), although the positive skin responses to house dust mites were similar in the both groups. CONCLUSION: Spider mites are common sensitizing allergens in children and adolescents exposed to them, and environmental exposure to these mites may represent an important risk factor in the sensitization and the clinical manifestations of asthma and rhinitis in children and adolescents living in rural and urban areas.