Drug-specific CD4+ T-cell immune responses are responsible for antituberculosis drug-induced maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms syndrome.

BACKGROUND: A multidrug regimen including isoniazid, rifampicin, pyrazinamide and ethambutol is commonly used as first-line treatment for tuberculosis. However, this regimen can occasionally result in severe adverse drug reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and drug-induced liver injury. The culprit drug and mechanistic basis for the hypersensitive reaction are unknown. OBJECTIVES: To investigate drug-specific T-cell responses in patients with antituberculosis drug (ATD)-induced cutaneous hypersensitivity and its underlying mechanism. METHODS: We enrolled eight patients with ATD-induced maculopapular exanthema and DRESS and performed a lymphocyte transformation test. Subsequently, drug-specific T-cell clones were generated from four of the patients who showed proliferation in response to ATDs. We measured the drug-specific proliferative responses and counted the drug-specific interferon (IFN)-γ/granzyme B-producing cells after drug stimulation. Antihuman leukocyte antigen (HLA) class I and class II blocking antibodies were used to analyse human leukocyte antigen-restricted T-cell responses. RESULTS: Positive proliferative responses to ATDs were mostly found in patients with cutaneous hypersensitivity. Furthermore, we isolated isoniazid/rifampicin-specific T cells from patients, which consisted primarily of CD4+ T cells. Drug-specific CD4+ T cells proliferated and secreted IFN-γ/granzyme B when stimulated with isoniazid or rifampicin, respectively. Isoniazid-responsive T-cell clones did not proliferate in the presence of rifampicin and vice versa. Drug-specific T-cell responses were blocked in the presence of anti-HLA class II antibodies. CONCLUSIONS: This study identifies the presence of isoniazid/rifampicin-specific T cells in patients with ATD-induced maculopapular exanthema and DRESS. Furthermore, it highlights the important role of drug-specific T-cell immune responses in the pathogenesis of these reactions.

Staphylococcal enterotoxin IgE sensitization in late-onset severe eosinophilic asthma in the elderly.

BACKGROUND: Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late-onset asthma. Recent studies suggest staphylococcal enterotoxin IgE (SE-IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late-onset elderly asthma. OBJECTIVE: We aimed to examine the associations of SE-IgE sensitization with late-onset asthma in the elderly, using a database of elderly asthma cohort study. METHODS: A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE-IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12-month follow-up period. RESULTS: At baseline, serum SE-IgE concentrations were significantly higher in patients with asthma than in controls [median 0.16 (interquartile range 0.04-0.53) vs. 0.10 (0.01-0.19), P < 0.001]. Elderly asthma patients with high SE-IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE-IgE levels. In multivariate logistic regression analyses, the associations between serum SE-IgE concentrations and severe asthma were significant, independently of covariables [SE-IgE-high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86-30.03, P = 0.005]. Multiple correspondence analyses also showed that high serum SE-IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first report on the significant associations of SE-IgE sensitization with late-onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late-onset eosinophilic asthma in the elderly.

Decreased diversity of nasal microbiota and their secreted extracellular vesicles in patients with chronic rhinosinusitis based on a metagenomic analysis.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory process in the nasal cavity and paranasal sinuses, and bacteria have been considered to be a cause. Indeed, recent evidence indicates that bacteria-derived extracellular vesicles (EV) appear to be an important causative agent of inflammatory diseases. Here, we aimed to evaluate the diversity of nasal microbiota and their secreted EV in patients with CRS. METHODS: Nasal lavage (NAL) fluid samples were obtained from five patients with CRS with polyposis, three patients with CRS without polyposis, and three non-CRS controls. After preparation of bacteria and EV from samples using differential centrifugation, genomic DNA was extracted and 16S-rDNA amplicons were subjected to high-throughput pyrosequencing on a Roche 454 GS-FLX platform. RESULTS: Metagenomics showed that bacteria composition was positively correlated with EV composition. Samples from patients with CRS had greater bacterial abundance and lower diversity, both from bacteria and the EV portion of samples, compared with non-CRS samples. At each phylogenetic level, Bacteroidetes decreased while Proteobacteria increased in the CRS group at the phylum level. At the genus level, Prevotella spp. decreased in the CRS group, while Staphylococcus spp. increased from both bacteria and EV. Moreover, Staphylococcus aureus and its secreting EV compositions were higher in samples from CRS with polyps compared with CRS without polyps. CONCLUSIONS: These results suggest that patients with CRS have altered nasal microbiota and decreased diversity in bacterial compositions as well as increased S. aureus abundance in those patients with polyps.

An important role of tumor necrosis factor receptor-2 on natural killer T cells on the development of dsRNA-enhanced Th2 cell response to inhaled allergens.

BACKGROUND: Recent evidence indicates that TNF-α is a key mediator of the development of dsRNA-enhanced Th2 cell response to inhaled allergens. Natural killer T (NKT) cells may be a candidate source of Th2-polarizing cytokines. OBJECTIVE: The objective of this study was to evaluate the role of lung NKT cells on the development of TNF-α-mediated Th2 cell response. METHODS: A virus-associated asthma mouse model was generated by the administration of ovalbumin (OVA, 75 µg) and poly[I:C] (0.1 µg). Role of NKT and type I NKT cells was evaluated using CD1d- and Jα18-deficient mice. TNF-α receptors (TNFRs) were antagonized by using TNFR blocking peptides. RESULTS: The number of infiltrated NKT cells was increased in a virus-associated asthma mouse model. Increase in Th2 and Th17 cytokine levels in wild-type mice were abolished in both CD1d- and Jα18-deficient mice. In vitro co-culture experiments with alveolar macrophages and NKT cells showed that TNF-α produced by macrophages in the presence of poly[I:C] acts on NKT cells, inducing production of Th2-polarizing cytokines. Moreover, the induction of Th2-polarizing cytokines by poly[I:C] or recombinant TNF-α was impaired in both CD1d- and Jα18-deficient mice and that the above effect was reversed by a TNF-α receptor-2 (TNFR2) blocking peptide, but not by a TNFR1 blocker. CONCLUSIONS: These findings suggest that NKT cells play a key role in the development of Th2 cell response to inhaled allergens and that TNF-α produced by alveolar macrophages induces Th2 cell response, via TNFR2 on NKT cells.

Extracellular vesicles, especially derived from Gram-negative bacteria, in indoor dust induce neutrophilic pulmonary inflammation associated with both Th1 and Th17 cell responses.

BACKGROUND: Many bacterial components in indoor dust can evoke inflammatory pulmonary diseases. Bacteria secrete nanometre-sized vesicles into the extracellular milieu, but it remains to be determined whether bacteria-derived extracellular vesicles in indoor dust are pathophysiologically related to inflammatory pulmonary diseases. OBJECTIVE: To evaluate whether extracellular vesicles (EV) in indoor air are related to the pathogenesis of pulmonary inflammation and/or asthma. METHODS: Indoor dust was collected from a bed mattress in an apartment. EV were prepared by sequential ultrafiltration and ultracentrifugation. Innate and adaptive immune responses were evaluated after airway exposure of EV. RESULTS: Repeated intranasal application of indoor-dust-induced neutrophilic pulmonary inflammation accompanied by lung infiltration of both Th1 and Th17 cells. EV 50-200 nm in diameter were present (102.5 µg protein concentration/g dust) in indoor dust. These vesicles were internalized by airway epithelial cells and alveolar macrophages, and this process was blocked by treatment of polymyxin B (an antagonist of lipopolysaccharide, an outer-membrane component of Gram-negative bacteria). Intranasal application of 0.1 or 1 µg of these vesicles for 4 weeks elicited neutrophilic pulmonary inflammation. This phenotype was accompanied by lung infiltration of both Th1 and Th17 cells, which were reversed by treatment of polymyxin B. Serum dust EV-reactive IgG1 levels were significantly higher in atopic children with asthma than in atopic healthy children and those with rhinitis or dermatitis. CONCLUSION & CLINICAL RELEVANCE: Indoor dust EV, especially derived from Gram-negative bacteria, is a possible causative agent of neutrophilic airway diseases.

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.

Pharmacogenetic study of the effects of NK2R G231E G>A and TBX21 H33Q C>G polymorphisms on asthma control with inhaled corticosteroid treatment.

BACKGROUND AND OBJECTIVE: Inhaled corticosteroids (ICS) are widely used as maintenance regimens for asthma patients. However, response to ICS shows marked inter-individual variability. Genetic factors have been shown to be potential predictors of responsiveness to ICS. We aimed to evaluate those pharmacogenetic effects on asthma control in further detail. METHODS: Fifty-three mild-to-moderate asthmatics were genotyped for four genetic polymorphisms of four genes: beta2-adrenergic receptor (ADRB2), adenylate cyclase 9 (ADCY9), neurokinin receptor 2 (NK2R) and T-box 21 (TBX21). The principal clinical outcome was the achievement of asthma control, as assessed using the Global Initiative for Asthma (GINA) guidelines. During treatment with ICS, the forced expiratory volume in 1 second (FEV(1)), maximal mid-expiratory flow (MMEF) and peak expiratory flow rate (PEFR) were monitored every 4 weeks and twice daily. RESULTS: Forty-eight of the 53 patients with asthma were in a controlled or partly controlled state after 12 weeks of treatment with ICS, whereas five asthmatics were in an uncontrolled state even after active treatment. Of the four genetic polymorphisms examined, NK2R G231E G>A and TBX21 H33Q C>G were significantly associated with asthma control status (P = 0.041 and P = 0.006). The subjects with wild-type alleles at each polymorphism showed a significant association with the well-controlled or partly controlled state, as compared to those with mutant alleles. At 5-12 weeks after ICS treatment, the NK2R G231E G>A was associated with therapeutic response to ICS, as reflected by improvement in predicted FEV(1)%. CONCLUSION: Our results suggest that NK2R G231E G>A and TBX21 H33Q C>G are genetic predictors of response to ICS, at least with respect to asthma control status and changes in FEV(1)%, in Korean patients with asthma. Further prospective validation of those associations is necessary.

Interleukin-8 production in tuberculous pleurisy: role of mesothelial cells stimulated by cytokine network involving tumour necrosis factor-alpha and interleukin-1 beta.

Interleukin-8 (IL-8) plays an important role in the host immune response to Mycobacterium tuberculosis by recruiting inflammatory cells to the site of infection. Here, we investigated the role of pleural macrophages and mesothelial cells in the production of IL-8 in tuberculous pleurisy. Large concentrations of IL-8 were detected in tuberculous pleural effusions, but not in pleural effusions associated with congestive heart failure (CHF). Tuberculous pleural macrophages and M. tuberculosis-infected CHF pleural macrophages produced large concentrations of IL-8. When immunohistochemistry was performed on pleural tissues, antigenic IL-8 was detected in the mesothelial cells lining the tuberculous pleura. Direct stimulation of cultured CHF pleural mesothelial cells with M. tuberculosis induced IL-8 secretion. However, conditioned media from M. tuberculosis-infected pleural macrophages (CoMTB) induced greater mesothelial cell IL-8 secretion. Tumour necrosis factor-alpha (TNF-alpha) and IL-1beta induced mesothelial cell IL-8 mRNA expression, and neutralizing anti-TNF-alpha antibody and IL-1 receptor antagonist nearly completely obliterated CoMTB-induced mesothelial cell IL-8 mRNA expression and protein secretion. These findings demonstrate that both pleural macrophages and mesothelial cells produce IL-8 in tuberculous pleurisy, and cytokines produced by M. tuberculosis-infected macrophages mediate mesothelial cell IL-8 production.

The prevalence of atopy and atopic diseases in Behçet's disease.

OBJECTIVE: The prevalence of Th-2 cell-mediated diseases, such as atopic diseases, has been noted to be low in Th-1 cell-mediated diseases. This study was undertaken to assess the prevalence of atopy and atopic diseases in Behçet's disease (BD), a Th-1 cell-mediated disease, and to investigate the clinical association between the atopy and the development of severe manifestations in BD. METHODS: We examined 70 consecutive BD patients and 113 controls without BD or other inflammatory rheumatic diseases. The cumulative history of severe manifestations in BD patients was investigated during the disease course. A skin prick test was performed in all the subjects, and atopy was defined as present when the size of one or more allergen-induced wheals was equal to or larger than that caused by histamine. Atopic diseases were defined as present when there were relevant responses for atopic diseases on the questionnaires in the subjects with atopy. In addition, serum IgE levels and peripheral blood eosinophil counts were measured. RESULTS: The prevalence of atopy and atopic diseases was significantly lower in BD patients than in controls. Other atopy parameters, such as serum IgE levels and peripheral blood eosinophil counts, were also significantly lower in BD patients when compared with controls. However, atopy, serum IgE levels, and peripheral blood eosinophil counts did not differ significantly between BD patients with and without severe manifestations. CONCLUSION: The prevalence of Th-2 cell-mediated conditions, such as atopy and atopic diseases, appeared to be lower in BD, a Th-1 cell-mediated disease. In addition, a Th-1 and Th-2 balance may not influence the development of severe manifestations in BD.

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.

High prevalence of current asthma and active smoking effect among the elderly.

BACKGROUND: Although asthma is a common cause of morbidity in adults, relatively few objectively measured population studies of asthma prevalence in adult populations have been conducted. OBJECTIVE: To evaluate the prevalence of asthma, based on both a questionnaire and methacholine bronchial provocation test, and to determine the risk factors of asthma prevalence in an adult population. METHODS: A total of 2,467 adults, who were randomly selected from metropolitan urban, non-metropolitan urban and rural areas, responded to the modified ISAAC questionnaire, and underwent methacholine bronchial provocation tests and skin prick tests to locally common aeroallergens. RESULTS: The prevalence of current asthma based on the questionnaire and the methacholine challenge was 2.0% in adults younger than 40, 3.8% in 40- to 54-year-olds, 7.7% in 55- to 64-year-olds and 12.7% in those aged 65 or higher. For subjects of 55-64 years, active smoking was found to be significantly related with the prevalence of current asthma and bronchial hyper-responsiveness, although smoking was positively associated with percentage predictive value of forced expiratory volume of 1 s (FEV1). CONCLUSION: The prevalence of current asthma is common among the elderly, and active smoking may play an important role in the development of asthma and bronchial hyper-responsiveness among the elderly.

Suppression of granulocyte-macrophage colony-stimulating factor expression by glucocorticoids involves inhibition of enhancer function by the glucocorticoid receptor binding to composite NF-AT/activator protein-1 elements.

Increased expression of a number of cytokines including GM-CSF is associated with chronic inflammatory conditions such as bronchial asthma. Glucocorticoid therapy results in suppression of cytokine levels by a mechanism(s) not yet fully understood. We have examined regulation of GM-CSF expression by the synthetic glucocorticoid dexamethasone in human T cells. Transient transfection assays with reporter constructs revealed that dexamethasone inhibited the function of the GM-CSF enhancer, but had no effect on regulation of GM-CSF expression occurring through the proximal promoter. Activation of the GM-CSF enhancer involves cooperative interaction between the transcription factors NF-AT and AP-1. We demonstrate here that glucocorticoid-mediated inhibition of enhancer function involves glucocorticoid receptor (GR) binding to the NF-AT/AP-1 sites. These elements, which do not constitute recognizable glucocorticoid response elements, support binding of the GR, primarily as a dimer. This binding correlates with the ability of dexamethasone to inhibit enhancer activity of the NF-AT/AP-1 elements, suggesting a competition between NF-AT/AP-1 proteins and GR.

Citrus red mite (Panonychus citri) may be an important allergen in the development of asthma among exposed children.

BACKGROUND: Recent investigations have demonstrated that spider mites are important allergens in the development of asthma in fruit-cultivating farmers. OBJECTIVE: The aim of this study was to evaluate the sensitization rate to the citrus red mite (Panonychus citri) in children living in rural areas, and to determine the allergenic cross-reactivity with other mites. METHODS: A total of 7254 children (ages 7-15 years) living in rural areas were enrolled, and each subject was evaluated by a questionnaire and a skin prick test. Allergenic cross-reactivity was evaluated by ELISA inhibition tests. RESULTS: The most common sensitizing allergens were house dust mites, followed by citrus red mite and cockroach. High serum-specific IgE bindings to the citrus red mite were detected in 21 of 100 randomly selected subjects. The prevalence of asthma was higher among those with positive skin responses to the citrus red mite than with negative skin responses to this mite. ELISA inhibition tests showed that IgE bindings to this mite were minimally inhibited with additions of domestic mites. CONCLUSION: Spider mites such as the citrus red mite may be important outdoor allergens among children living in rural areas, and spider mite-derived allergens have unique allergenic determinants compared with domestic mites.

Acute respiratory distress syndrome associated with scrub typhus: diffuse alveolar damage without pulmonary vasculitis.

Pathologic findings of scrub typhus have been characterized by vasculitis of the microvasculature of the involved organ resulting from a direct invasion by Orientia tsutsugamushi. We experienced a case of acute respiratory distress syndrome (ARDS) associated with scrub typhus. The case was proven by eschar and high titer of serum IgM antibody (positive at 1:1280). Open lung biopsy showed diffuse alveolar damage (DAD) in the organizing stage without evidence of vasculitis. Immunofluorescent antibody staining and polymerase chain reaction for O. tsutsugamushi failed to demonstrate the organism in the lung tissue. The patient expired due to progressive respiratory failure despite doxycycline therapy. Immunologic mechanism, without direct invasion of the organism, may participate in the pathogenesis of ARDS associated with scrub typhus.

Two-spotted spider mite (Tetranychus urticae): an important allergen in asthmatic non-farmers symtomatic in summer and fall months.

BACKGROUND: The Tetranychus urticae (two-spotted spider mite, TSM) is a spider mite commonly found on fruit trees, herbaceous plants, and greenhouse flowers. OBJECTIVE: To evaluate the clinical significance of TSM-derived allergens in non-farmers with asthma living around pear orchards, and to assess the allergenic relationship with house dust mite. METHODS: Skin prick tests with TSM were performed in 50 asthmatic non-farmers living around pear orchards. The serum TSM-specific IgE was measured in the 16 asthmatics with a positive skin response to TSM. To diagnose TSM-induced asthma, specific bronchial challenges with TSM were performed in the 16 asthmatics. ELISA inhibition tests were performed to assess the allergenic cross-reactivity with house dust mites. RESULTS: Ten of the 16 asthmatics with positive skin responses to TSM showed a significant bronchoconstriction following inhalation of TSM. Eight of the ten TSM-induced asthmatics had high serum TSM-specific IgE and one showed a positive skin response only to TSM. Their asthmatic symptoms were aggravated seasonally, especially in summer and early fall. On ELISA inhibition tests, partial inhibitions with D. pteronyssinus antigens were noted in sera from five asthmatics with positive skin responses to both TSM and D. pteronyssinus, although no inhibition was noted in serum from an asthmatic with a positive skin response only to TSM. CONCLUSION: Tetranychus urticae may be an important allergen in asthmatic non-farmers living around pear orchards and TSM extracts contain species-specific allergens as well as commonly shared allergens with house dust mite.

Atopic status and level of bronchial responsiveness in parents of children with acute bronchiolitis.

To examine whether children with a genetic predisposition to asthma are more likely to be afflicted with bronchiolitis, we studied 122 parents of infants who were hospitalized with the diagnosis of acute bronchiolitis (index group) and 120 parents of children who had never suffered from this disease (control group). The parents underwent bronchial challenge testing with methacholine and skin prick testing with common airborne allergens, and gave blood specimens for measurement of serum total IgE. There was no difference in atopic status, as assessed by the prevalence of atopy (at least one positive response to the allergens tested) or by serum total IgE levels, between index and control parents. The prevalence of bronchial hyperresponsiveness (BHR) (concentration of methacholine causing a 20% reduction in forced expiratory volume in 1 sec [PC20] < 18 mg/mL) was higher in index parents than in control parents (17.2% vs. 7.5%, p = 0.02). Bronchial responsiveness (BR) index was significantly higher in index parents than in control parents (1.135 +/- 0.088 vs. 1.104 +/- 0.071, p < 0.01). Parents of children who were hospitalized with acute bronchiolitis showed a higher level of BR, but not atopy. This suggests that in terms of BHR, there may be a genetic predisposition to the development of bronchiolitis.

Spider mite allergy in apple-cultivating farmers: European red mite (Panonychus ulmi) and two-spotted spider mite (Tetranychus urticae) may be important allergens in the development of work-related asthma and rhinitis symptoms.

BACKGROUND: Recent investigations have suggested that the citrus red mite (Panonychus citri) is the most important allergen affecting citrus-cultivating farmers with asthma, allergic rhinitis, or both. OBJECTIVE: We sought to evaluate type I hypersensitivity to spider mites, particularly the European red mite (Panonychus ulmi) and the two-spotted spider mite (Tetranychus urticae), and to determine the relationship between hypersensitivity to spider mites and respiratory dysfunction. METHODS: We performed a cross-sectional survey. Questionnaires were given, and skin prick tests for 11 inhalant allergens common in Korea and 2 species of spider mites (European red mite and two-spotted spider mite) were performed in 725 apple-cultivating farmers in Korea. RESULTS: Results of skin prick tests in the apple farmers indicated that European red mite (23.2%) was the most common sensitizing allergen, followed by Tyrophagus putrescentiae (21.2%), two-spotted spider mite (16.6%), Dermatophagoides farinae (16.3%), D pteronyssinus (14.4%), cockroach (13.1%), and Hop Japanese (Humulus Japonicus) pollen (12.0%). Positive skin responses (mean wheal size >/=3 mm) to one or more of 13 inhalant allergens were found in 48.2% of farmers tested, whereas 40 subjects (8.6%) had an isolated skin response to the spider mites. Among 119 farmers with work-related asthmatic symptoms, the positive skin response rates to European red mite and two-spotted spider mite were 40.4% and 27.0%, respectively. These figures were significantly higher than those found among farmers without work-related symptoms (19.1% and 14.1%, respectively; P <.01). The prevalence of work-related asthma symptoms was higher in farmers with positive skin responses to spider mites than in those with negative skin responses to spider mites and those with positive skin responses to any allergen tested (31.4% vs 15.0% vs 21.0%, respectively; P <.05). CONCLUSION: Spider mites, particularly European red mite and 2-spotted spider mite, are common sensitizing allergens in apple-cultivating farmers. These spider mites may be important causative allergens in the development of work-related respiratory symptoms in these workers.

Skin reactivity to inhalant allergens, total serum IgE levels, and bronchial responsiveness to methacholine are increased in parents of nonatopic asthmatic children.

BACKGROUND: Family studies suggest that asthma has an increased familial occurrence, but the hypothesis of a genetic predisposition to IgE response and bronchial hyperresponsiveness (BHR) on the expression of nonatopic asthma is controversial. OBJECTIVE: The aim of this study was to evaluate familial predisposition to IgE response and BHR on expression of nonatopic asthma. METHODS: One hundred four parents of nonatopic asthmatic children, 154 parents of atopic asthmatic children, 78 parents of atopic nonasthmatic control children, and 80 parents of nonatopic control children provided questionnaire data and underwent allergy skin prick tests with 10 inhalant allergens and methacholine bronchial provocation tests. Total serum IgE levels were determined in 352 parents (134 with atopic asthmatic children, 87 with nonatopic asthmatic children, 65 with atopic control children, and 66 with nonatopic control children). RESULTS: Prevalence of asthma, based on questionnaire data and on BHR to methacholine, was higher among parents of nonatopic asthmatic children (10.6%) and atopic asthmatic children (9.1%) than among those of nonatopic control children (1.3%). BHR to methacholine was higher among parents of nonatopic asthmatic children (19.2%) and atopic asthmatic children (16.2%) than among those of atopic and nonatopic control children (5.1% and 1.3%, respectively). The percentage of positive skin test responses to 10 inhalant allergens was higher among parents of atopic asthmatic children (43.9%), nonatopic asthmatic children (39.4%), and atopic control children (38.5%) than among those of nonatopic control children (23.7%). Geometric means (IU/mL +/- SEM) of total serum IgE were higher among parents of atopic and nonatopic control children than among those of nonatopic control children (2.11 +/- 0.05 vs 2. 20 +/- 0.06 vs 2.09 +/- 0.07 vs 1.92 +/- 0.06). CONCLUSION: Nonatopic asthma runs in families. The prevalence of positive skin test responses to inhalant allergens, BHR to methacholine, and total serum IgE levels is higher among the parents of nonatopic and atopic asthmatic children than among those of nonatopic control children.

Prevalence of childhood asthma based on questionnaires and methacholine bronchial provocation test in Korea.

BACKGROUND: In most epidemiological survey studies, only subjective symptoms and past medical history of asthma have been used as diagnostic criteria. Even though a questionnaire survey can be performed in a large population study at low cost, limitations such as lack of objectivity and poor predictability in non-specific bronchial hyperresponsiveness cannot be avoided. OBJECTIVES: The purpose of this study was to elucidate the prevalence of current asthma based on questionnaires and methacholine bronchial provocation test, and the prevalence of atopy in Korea. METHODS: We performed modified ATS respiratory questionnaires and allergen skin-prick test with 10 common inhalant allergens among 3219 subjects aged 7-19 years in Seoul and a rural part of a small city, Chungju in Korea. Methacholine bronchial provocation tests were also performed among those who had asthma symptoms according to the questionnaire. The criteria of asthma was presence of both asthma symptoms and non-specific bronchial hyperresponsiveness. Atopy was defined as when an allergen induced weal size is same or larger than that caused by histamine. RESULTS: The prevalence of asthma based on questionnaires and methacholine bronchial provocation tests was 4.6%, while the prevalence of wheeze was 8.2% and 19.3% of total population complained of one or more respiratory symptoms related to asthma on the questionnaires. There was no significant difference according to age, sex and living area. The mean prevalence of atopy was 35.0% and the most common allergens were Dermatophagoides farinae (30.9%), Dermatophagoides pteronyssinus (27.5%), cat fur (20.4%) and cockroach (11.8%). The atopy prevalence in Chungju area was higher than that in Seoul and males showed a higher prevalence than females. The asthma prevalence was higher among atopics (6.8%) than among non-atopics (2.7%). None of questionnaire items were enough to predict the presence of bronchial hyperresponsiveness in terms of sensitivity, specificity and positive predictive value. CONCLUSION: The prevalence rate of current asthma in Korea was 4.6% and the prevalence rate of atopy in Korea was 35.0%. Questionnaire-based surveys are not enough to predict the actual prevalence of asthma.