Multiple Allergens Research Articles

Work-Related Allergy and Asthma in Spice Mill Workers – The Impact of Processing Dried Spices on IgE Reactivity Patterns

Background: Three spice mill workers developed work-related allergy and asthma after prolonged exposure to high levels (>10 mg/m³) of inhalable spice dust. Patterns of sensitization to a variety of spices and putative allergens were identified. Methods: Work-related allergy and asthma were assessed on history, clinical evaluation, pulmonary function and fractional exhaled nitric oxide. Specific IgE reactivity to a range of common inhalant, food and spice allergens was evaluated using ImmunoCAP and allergen microarray. The presence of non-IgE-mediated reactions was determined by basophil stimulation (CAST-ELISA). Specific allergens were identified by immunoblotting to extracts of raw and dried processed garlic, onion and chili pepper. Results: Asthma was confirmed in all 3 subjects, with work-related patterns prominent in worker 1 and 3. Sensitization to multiple spices and pollen was observed in both atopic workers 1 and 2, whereas garlic and chili pepper sensitization featured in all 3 workers. Microarray analysis demonstrated prominent profilin reactivity in atopic worker 2. Immunoblotting demonstrated a 50-kDa cross-reactive allergen in garlic and onion, and allergens of approximately 40 and 52 kDa in chili pepper. Dry powdered garlic and onion demonstrated greater IgE binding. Conclusions: This study demonstrated IgE reactivity to multiple spice allergens in workers exposed to high levels of inhalable spice dust. Processed garlic and onion powder demonstrated stronger IgE reactivity than the raw plant. Atopy and polysensitization to various plant profilins, suggesting pollen-food syndrome, represent additional risk factors for sensitizer-induced work-related asthma in spice mill workers.

Assessment of the role of aeroallergens in patients with chronic urticaria

Background The cause of chronic urticaria (CU) remains unidentified in many patients. It may include medications, food and autoimmunity. However, the possible role of inhalant allergens (aeroallergens) has not been confirmed. Objective The purpose of this study was to investigate the possible role of aeroallergens in patients with chronic idiopathic urticaria (CIU), and without allergic respiratory diseases. Patients and methods Two hundred patients with CU and no associated allergic respiratory diseases were recruited over an eight-month period from the Allergy Outpatient Clinic at Ain Shams University Hospital, Egypt. CU was diagnosed by history, physical examination and laboratory tests, which included tests for autoimmunity. Patients who had no obvious etiological factor for CU were further studied for sensitivity to common aeroallergens by skin prick test (SPT); cases that were positive for aeroallergens were further investigated by a specific IgE study. In addition, 200 healthy controls were also subjected to SPT. Results Twenty-six of 200 patients (13%) had an etiological factor for urticaria, and were excluded from the study. The remaining 174 patients (87%) were diagnosed as CIU, and underwent SPT. Skin test positivity to aeroallergens only was significantly higher among patients with CIU than among controls (17.2% as compared to 3.5%). Among patients with CIU, the most common aeroallergens were mites (13.8%), followed by pollens (5.2%), and mixed molds (4%). All these aeroallergens were significantly more prevalent among cases than among healthy controls. Multiple allergen sensitivity was also significantly more prevalent among cases than controls. Specific IgE level was elevated (superior to 0.35 kU/L) to allergens in all cases with positive SPT. Conclusion Aeroallergens should be considered as a possible etiology of CU, even if not associated with allergic respiratory diseases.

Airborne Mouse and Other Indoor Allergens in Inner-City Schools

RATIONALE: Previous studies have shown that children are exposed to multiple allergens at school which can contribute to their asthma symptoms. In order to better understand their risk of exposure, we tested air and dust samples from different schools for levels of known indoor allergens and determined the correlations between the samples.METHODS: Air and vacuumed dust samples were collected from 64 classrooms in 5 urban elementary schools in northeastern US and analyzed for dust mite (Der p1, Der f1), cat (Fel d1), dog (Can f1), mouse (Mus m1), rat (Rat n1), and cockroach (Bla g 2). Statistical analysis was then done to establish correlations.RESULTS: In both the air and vacuumed dust samples, dust mite (Der f1), cat, dog, and mouse allergen were present more than 80% of the time. Mouse allergen demonstrated the highest direct correlation between the samples (100% air, 98% dust; r=0.59, p<0.001). Dog allergen showed a weaker correlation (100% air, 84% dust; r=0.35, p=0.004), as did cat allergen (100% air, 91% dust; r=0.28, p=0.023). Dust mite (Der f1) allergen revealed no correlations at all (100% air, 83% dust; r=0.04, p=0.741). Dust mite (Der p1), rat, and cockroach allergen were present in the samples less than 25% of the time and not analyzed.CONCLUSIONS: In our study of urban schools, mouse allergen demonstrated the strongest correlation between air and dust samples with dog and cat allergens showing weaker correlations. Further studies are needed to determine the effect exposure to these airborne and settled dust allergens has on asthma morbidity. RATIONALE: Previous studies have shown that children are exposed to multiple allergens at school which can contribute to their asthma symptoms. In order to better understand their risk of exposure, we tested air and dust samples from different schools for levels of known indoor allergens and determined the correlations between the samples. METHODS: Air and vacuumed dust samples were collected from 64 classrooms in 5 urban elementary schools in northeastern US and analyzed for dust mite (Der p1, Der f1), cat (Fel d1), dog (Can f1), mouse (Mus m1), rat (Rat n1), and cockroach (Bla g 2). Statistical analysis was then done to establish correlations. RESULTS: In both the air and vacuumed dust samples, dust mite (Der f1), cat, dog, and mouse allergen were present more than 80% of the time. Mouse allergen demonstrated the highest direct correlation between the samples (100% air, 98% dust; r=0.59, p<0.001). Dog allergen showed a weaker correlation (100% air, 84% dust; r=0.35, p=0.004), as did cat allergen (100% air, 91% dust; r=0.28, p=0.023). Dust mite (Der f1) allergen revealed no correlations at all (100% air, 83% dust; r=0.04, p=0.741). Dust mite (Der p1), rat, and cockroach allergen were present in the samples less than 25% of the time and not analyzed. CONCLUSIONS: In our study of urban schools, mouse allergen demonstrated the strongest correlation between air and dust samples with dog and cat allergens showing weaker correlations. Further studies are needed to determine the effect exposure to these airborne and settled dust allergens has on asthma morbidity.

Allergy Risk Is Mediated by Dendritic Cells with Congenital Epigenetic Changes

One factor predisposing toward allergic responses is a maternal history of allergy. In a mouse model of maternal transmission of asthma risk, offspring of asthmatic, but not normal, mothers show increased allergic susceptibility, recreating epidemiologic observations in humans. Dendritic cells (DCs) capture and process antigens, and can skew immune responses toward a pro-allergic T helper 2 phenotype. Genome-wide analysis shows that neonates of allergic mothers are born with substantial changes in DNA methylation in their splenic CD11c(+) DCs, findings observed without any contact with allergens. We demonstrate that these DCs from allergen-naive neonates born to asthmatic mothers, but not DCs from offspring of normal mothers, confer increased allergic susceptibility to multiple allergens when adoptively transferred into normal recipient mice, manifesting as increased airway responsiveness and allergic inflammation. Other immune splenocytes, including macrophages and CD4+ T cells, did not transfer the effect. The "asthma-susceptible" DCs also show enhanced allergen-presentation activity in vitro. Our findings suggest that maternal allergy results in an altered epigenetic profile in neonatal DCs that is independent of encounters with allergens and is linked to pro-allergic function.

Efficacy of local conjunctival immunotherapy in allergic conjunctivitis

Allergic conjunctivitis was a chronic inflammatory disease, usually associated with rhinitis. Several modalities of treatment were available, but few studies mentioned of immunotherapy which might had benefits in chronic and severe cases. To evaluate efficacy and safety of local conjunctival immunotherapy (LCIT) using a mixed Dermatophagoides extracts for treatment of allergic conjunctivitis (AC) METHODS: A prospective, double-blind and randomized controlled trial (RCT) was performed on eighteen patients with positive skin prick test (SPT) reactions to house dust mites. They were randomized into 2 groups: 1) treated with LCIT and 2) treated with balanced salt solution (BSS) as a control for a 6-month period. Allergen extracts were prepared in eyedrops and given once daily in LCIT group. Efficacy was assessed by clinical scores and conjunctival provocation test (CPT). At 6 months, the CPT scores for the LCIT group reached statistical significance compared to the control group (p = 0.038), but there were no statistically significant differences in signs (p = 0.591), symptoms (p = 0.885) and medication scores (p = 0.338) between both groups. Patients in LCIT group were able to tolerate the allergen without developing any serious adverse events. LCIT treatment significantly reduced CPT scores which indicated that the patients were able to tolerate the antigen better than their counterparts. However, LCIT alone at short period did not alleviate symptoms and signs of allergic conjunctivitis from multiple allergens.

Common Causes of Anaphylaxis in Children: The First Report of Anaphylaxis Registry in Iran

Background Anaphylaxis is an acute, systemic, and potentially fatal allergic reaction. Many things can cause anaphylaxis potentially but some agents are more common like some foods (milk, egg, soy, wheat, peanut, tree nut, shellfish, and fish), insect stings, medications, latex, and food-dependent exercise-induced anaphylaxis. The goal of this study is to show the common causes of anaphylaxis among the children with anaphylaxis history who were referred to the Immunology, Asthma and Allergy Research Institute (IAARI) during a 4-year period (2005-2009).Methods and Materials During those 4 years, we registered all children (<14 years old) with a history of anaphylactic reaction. To prove the cause of anaphylaxis, we performed skin prick tests with suspected agents according to their history and measured specific IgE against them by the ImmunoCAP test. Recognition of common allergens was based on having a positive history for 1 allergen and positive skin prick test or specific IgE for that at the same time, or having positive results from both tests when the allergen was unclear. Idiopathic anaphylaxis was a reaction when any known allergen and positive tests were not obtained.Results One hundred ninety-three nonfatal anaphylactic attacks among 63 children were recognized. In total, the most current cause of anaphylaxis in children was food (89.7%). Milk (49.3%) and wheat (26.1%) were the most common. Other foods were egg (8.7%), nuts (2.8%), and spices (2.8%). Six children (8.7%) were sensitive to multiple food allergens like milk, egg, and wheat. Five (7.1%) of 63 patients had anaphylactic attack because of stinging. Wasp was the trigger in 3 (4.3%) of them and honeybee was the cause in 1 (1.4%). The last one was because of unknown hymenoptera. There were 2 idiopathic cases of all 63 patients.Conclusions Food allergens, especially milk and wheat, are the most common cause of anaphylaxis in children. Because anaphylaxis can be fatal, it is advisable to recognize its causes in different communities to prevent recurrent attacks.

Protease Allergens Induce the Expression of IL-25 via Erk and p38 MAPK Pathway

Allergic diseases, including asthma, are characterized by T helper type 2 (Th2) cell-mediated inflammations, coupled with tissue infiltration by eosinophils. In this study, we demonstrate that multiple protease allergens, including papain and DerP1, efficiently induce interleukin (IL)-25 and thymic stromal lymphopoietin (TSLP) gene expression, and this phenomenon is dependent on the protease activities of these allergens. The IL-25 cytokine level in bronchial alveolar lavage (BAL) was also profoundly and significantly increased after treatment with papain. Additionally, the levels of Th2 cytokines were significantly increased, as compared to those in the OVA-only treatment group. The various protease allergens triggered the expression of IL-25 and TSLP mRNA in mouse lung epithelial cells (MLE12) and primary mouse lung epithelial cells; these effects were inhibited by the deactivation of the protease activity of papain. The allergen papain activates the ErK and p38 MAP pathways; the inhibition of these pathways, but not the NFκB or PI-3 kinase pathways, impairs the induction of IL-25 and TSLP expression by proteases. In this study, we demonstrate that the protease allergens induce IL-25 and TSLP via the MAP kinase signal pathways, and their protease activities are essential to this pathway.

Clinical characteristics of adult asthma.

Allergen sensitization and Th2 responses are the major factors predisposing to the development of allergic asthma.1,2 This was confirmed by a Korean cohort study that enrolled subjects living in urban (Seoul) or rural areas.3 The present study summarized the clinical features of adult patients with asthma who were admitted to a single university hospital in an urban area (Seoul) over a 6-year period.4 The authors reported that the atopy rate was 50%, which was higher than that reported several years earlier in the same city.5,6 However, asthma has heterogeneous phenotypes, and the atopy rate in Korea is increasing7 and differs according to patient age, with significantly higher atopy rates in the younger population.3 Therefore, if the authors were to dissect the clinical features according to the age of the study subjects, the results may differ. The skin prick test is an essential method for screening atopy status and identifying the causative agents. The authors used 45 antigens to identify the causative agents. Although the authors did not list the skin prick test antigens, 45 inhalant allergens are not enough to identify the causative agents in adult asthmatic patients considering the major causative allergens in our environment.8 The clinical features of asthmatic patients may differ depending on the sensitizing allergens. In this study, the authors grouped all pollens into one group, which may give wrong information, as three seasonal pollen groups exist in Korea-tree, grass, and weed pollens- and sensitive patients show increased eosinophil counts with symptom exacerbation during the corresponding pollen season. Moreover, the results may differ depending on whether the patients are sensitive to multiple indoor and outdoor allergens or to a single allergen. We suggest comparing the patients sensitive to house dust mites alone with those who have combined sensitivity to one specific pollen or animal dander independently. More ideally, in most studies, the enrolled subjects were identified by positive bronchial challenge tests to the corresponding allergen.8 No published data suggest that asthmatic patients sensitized to fungal allergens present with a more severe phenotype. From this study, it is not clear whether the patients were sensitized fungal allergens alone or to multiple allergens, including house dust mites and pollens. Considering the cross-reactivity between Alternaria and Cladosporium spp,9,10 the same study subjects may have been sensitive to both groups. Moreover, the clinical severity of asthma depends on various other clinical parameters, such as smoking, the duration of asthma, and co-morbid conditions, especially chronic rhinitis.11 Furthermore, the severity of asthma can be determined by asthma control status, episodes of asthma exacerbations, and anti-asthmatic medication requirements.12,13 A Korean cohort study suggested that smoking status, male gender, and longer duration of asthma are significant predisposing factors for severe asthma.14 This study provides recent data on the clinical characteristics of adult asthma in a single university hospital for a 6-year period. Further studies are needed in a larger multicenter cohort that dissects the clinical phenotypes, including the clinical course and therapeutic response.

Allergic skin diseases

The skin is one of the largest immunologic organs and is affected by both external and internal factors, as well as innate and adaptive immune responses. Many skin disorders, such as atopic dermatitis, contact dermatitis, urticaria, angioedema, psoriasis, and autoimmune blistering disorders, are immune mediated. Most of these diseases are chronic, inflammatory, and proliferative, in which both genetic and environmental factors play important roles. These immunologic mechanisms might have implications for potential targets of future therapeutic interventions.

The Safety of Sublingual Immunotherapy With One or Multiple Pollen Allergens in Children

Agostinis F, Foglia C, Landi M, et al. Allergy. 2008;63(12):1637–1639 PURPOSE OF THE STUDY. To evaluate the rate and type of adverse events experienced by children receiving sublingual immunotherapy (SLIT) for pollen allergy with either single or multiple allergen extracts. STUDY POPULATION. Prospective postmarketing survey of 433 children receiving SLIT for respiratory allergies attributable to pollen. METHODS. Consecutive children with respiratory allergies attributable to pollens who were receiving SLIT with multiple or single allergens were enrolled. Parents recorded adverse events (eye symptoms, rhinitis/ear …

Genetic allergen modification in the development of novel approaches to specific immunotherapy

In the recent past, multiple allergens from relevant allergen sources have been cloned, sequenced and produced as recombinant proteins. The availability of recombinant allergens with immunological characteristics similar to their natural counterparts has improved the diagnosis of allergic disorders and increased our knowledge of the biochemical, structural and immunological characteristics of proteins with allergenic potential. Moreover, the use of defined recombinant proteins as vaccines substituting currently used total protein extracts from allergen sources may improve specific immunotherapy (SIT) of Type I allergy. In addition to producing well-defined batches of wild-type allergens, the recombinant technology offers the possibility to easily and selectively modify their properties or functions. Diverse modifications of allergens can be genetically engineered, e.g. variants with reduced IgE-binding capacity, multi-mers of single allergens or hybrids consisting of different allergens. Furthermore, allergens can be genetically fused with proteins that promote immune responses, which counterregulate the disease-eliciting T-helper type 2-dominated immune response in allergic individuals and may therefore, improve the efficacy of SIT. This review will introduce different concepts of allergen modification using genetic engineering to improve vaccines for SIT of Type I allergy.

Allergen Specific IgE Measurement with Polycheck Allergy: Comparison of Three Multiple Allergen Simultaneous Tests

The in vivo skin prick test (SPT) or in vitro detection of allergen specific IgE in serum is commonly used for the diagnosis of allergic disease. In this study, we evaluated the usefulness of a new multiple allergen simultaneous test (MAST) immunoblot assay, Polycheck Allergy (Biocheck GmbH, Germany). A total of 100 patients with clinical findings of allergic diseases were tested by SPT and three different MAST assays: Polycheck Allergy (Biocheck GmbH, Germany), MAST CLA allergy system (Hitachi Chemical Diagnostics, USA) and Allergy Screen (R-biopharm, Germany). The results of MAST assays were compared with those of SPT. Concordance rates of MAST assays with SPT were 79-100% for Polycheck Allergy, 88.9-100% for MAST CLA and 72.7-98.3% for Allergy Screen. In ROC curve analysis, significant differences were observed in four of 25 allergens analysed: Alternaria, Birch, Hazelnut and D. farinae. For Alternaria and Birch, Polycheck Allergy (P<0.001) and Allergy Screen (P=0.0075) showed significantly larger AUC (area under the curve) than MAST CLA. For Hazelnut, Polycheck Allergy (P=0.0021), and for D. farinae, MAST CLA (P=0.015) showed significantly larger AUCs than the other two tests. The ROC analysis for overall 16 food allergens showed better results in Polycheck Allergy (P<0.001), and that for overall 21 inhalants did not show significant differences among three MAST assays (P>0.05). Since Polycheck Allergy showed similar or superior result to the others, it can be used for the detection of allergen specific IgE antibodies.

Mono and multifaceted inhalant and/or food allergen reduction interventions for preventing asthma in children at high risk of developing asthma

Allergen exposure is one of the environmental factors seemingly associated with the development of asthma. If asthma is a multi-factorial disease, it is hypothesised that prevention might only prove effective if most or all relevant environmental factors are simultaneously avoided. To assess effect(s) of monofaceted and multifaceted interventions compared with control interventions in preventing asthma and asthma symptoms in high risk children. We searched the Cochrane Airways Trials Register (December 2008). Randomised controlled trials of allergen exposure reduction for the primary prevention of asthma in children. Interventions were multifaceted (reducing exposure to both inhalant and food allergens) or monofaceted (reducing exposure to either inhalant or food allergens) Follow up had to be from birth (or during pregnancy) up to a minimum of two years of age. We included in the analysis studies assessing the primary outcome (current diagnosis: asthma) and/or one of the secondary outcomes (current respiratory symptoms: wheezing, nocturnal coughing and dyspnoea). We pooled multifaceted and monofaceted intervention trials separately. We made an indirect comparison of their effects using tests for interaction to calculate relative odds ratios. We included three multifaceted and six monofaceted intervention studies (3271 children). Physician diagnosed asthma in children less than five years, and asthma as defined by respiratory symptoms and lung function criteria in children aged five years and older, both favoured treatment with a multifaceted intervention compared to usual care (< 5 years: odds ratio (OR) 0.72, 95% confidence interval (CI) 0.54 to 0.96, and > 5 years: OR 0.52, 95% CI 0.32 to 0.85). However, there was no significant difference in outcome between monofaceted intervention and control interventions (< 5 years: OR 1.12, 95% CI 0.76 to 1.64, and > 5 years: OR 0.83, 95% CI 0.59 to 1.16). Indirect comparison between these treatments did not demonstrate a significant difference between multiple interventions and mono-interventions in reducing the frequency of asthma diagnosis in children under five years (relative OR 0.64 (95% CI 0.40 to 1.04, P = 0.07) or five years and older (relative OR 0.63, 95% CI 0.35 to 1.13, P = 0.12). There was also no significant difference between either mono- and multifaceted intervention and control in reducing the likelihood of symptoms of nocturnal coughing at follow up. Wheezing, however, showed a significant difference between multifaceted and mono-interventions (relative OR 0.59, 95% CI 0.35 to 0.99, P = 0.04), but the significance was lost when data on treatment only was analysed. The available evidence suggests that the reduction of exposure to multiple allergens compared to usual care reduces the likelihood of a current diagnosis of asthma in children (at ages < 5 years and 5 years and older). Mono-intervention studies have not produced effects which are statistically significant compared with control. In children who are at risk of developing childhood asthma, multifaceted interventions, characterised by dietary allergen reduction and environmental remediation, reduce the odds of a physician diagnosis of asthma later in childhood by half. This translates to a number needed to treat (NNT) of 17. The effect of multi-faceted interventions on parent reported wheeze was inconsistent and had no significant impact on nocturnal coughing or dyspnoea. Data from monofaceted intervention exposed children studies were not significantly different from those of control groups for all outcomes. There remains uncertainty as to whether multiple interventions are more effective than mono-component interventions. The comparisons made were indirect, making the conclusions drawn uncertain. To our knowledge there are no ongoing studies in which both intervention strategies are randomly compared. The findings, however, warrant further direct comparison between multiple- and monofaceted interventions aimed at reducing the prevalence of asthma in children.

The Role of Neuroinflammation in Severe Acquired Brain Injuries. Preliminary Results on Subacute and Chronic Patients

Allergen extracts for sublingual immunotherapy (SLIT) are currently marketed by several manufacturers, with administration schedules and amount of allergen(s) quite variable in the different products, although almost all are standardized biologically or immunologically. The allergen extracts for SLIT are available in two main pharmaceutical forms: solution to be delivered by drop-counters, pre-dosed actuators (mini-pumps) or disposable single-dose vials; tablets with appropriate composition that allows a slow (1-2 minutes) dissolution in the mouth in contact with saliva. In Europe, SLIT is prescribed in general for one or a few allergens, and mixtures are less used, though there is no immunological contraindication to give multiple allergens. SLIT traditionally involves a build-up phase and a maintenance phase with the top dose. The build-up phase has usually the duration of 4 - 6 weeks. The patient must start with the lowest concentration and gradually increase, using the different dosage preparations, until the maintenance dose is reached. Rush and ultra-rush inductions have been introduced, based on the safety profile of SLIT that is very favorable. For these reasons it has been suggested that an updosing phase maybe even not necessary. The no-updosing approach would result in a treatment that is more patient-friendly and convenient to manage. Indeed, the most recent randomized trials were performed with the no-updosing regimen and their results in term of safety were as favorable as the studies performed with the traditional updosing approach. The currently recommended duration of SLIT is comprised between 3 and 4 years depending on the clinical response in single patients.

Response to sublingual immunotherapy with grass pollen extract: Monotherapy versus combination in a multiallergen extract

To date, there have been no randomized, double-blind studies showing the effectiveness of sublingual immunotherapy with multiple allergens. The purpose of this study was to examine whether the efficacy of sublingual immunotherapy (SLIT) with standardized timothy extract was reduced by combination with other allergen extracts. A single-center, randomized, double-blind, placebo-controlled trial with SLIT was conducted. After an observational grass season, SLIT was administered for 10 months to 54 patients randomized to 1 of 3 treatment arms: placebo, timothy extract (19 microg Phl p 5 daily) as monotherapy, or the same dose of timothy extract plus 9 additional pollen extracts. Symptom and medication scores were collected and titrated nasal challenges, titrated skin prick tests, specific IgE, IgG4 and cytokines release by timothy-stimulated lymphocyte proliferation were performed. Perhaps because of a very low grass pollen season in 2008, there were no significant differences in medication or symptom scores in either treatment group compared with placebo. Compared with placebo, in the timothy monotherapy group, thresholds for titrated nasal challenge and skin prick tests (P = .03 and P = .001, respectively), and serum-specific IgG4 levels (P = .005) significantly increased, and IFN- gamma levels decreased (P = .02), whereas in the multiallergen group, there was significant improvement only in the titrated skin prick tests (P = .04) which was less than in the monotherapy group. There were no significant differences between the 2 active groups in any outcome measure, and both active groups experienced more adverse events than placebo. There were no systemic reactions. Improvement in multiple relevant outcomes strongly suggests that SLIT with timothy extract alone was effective; however, the results for symptom and medication scores were not significant. The differences between multiple allergen SLIT and placebo only in skin sensitivity to timothy suggest a reduction in SLIT efficacy in this group. However, further studies are required to confirm these observations.

A multicentre study assessing the prevalence of sensitizations in patients with asthma and/or rhinitis in China

The prevalence of sensitization in patients with asthma and rhinitis in mainland China remains unclear. Our aim was to estimate the prevalence of allergy in patients with respiratory allergic diseases such as asthma and/or rhinitis attending respiratory clinics within mainland China. The study also investigated regional and annual differences in the prevalence and pattern of sensitization among the patients in China. A cross-sectional survey was performed in 6304 patients suffering from asthma and/or rhinitis in 17 cities from 4 regions of China. Patients completed a standardized questionnaire asking for the presence of respiratory and allergic symptoms. They also underwent skin prick tests with 13 common aeroallergens. Among the 6304 patients, 4545 (72.1%) had at least one positive skin prick reaction. The overall prevalence of positive skin prick responses was 59.0% for Dermatophagoides farinae, 57.6% for Dermatophagoides pteronyssinus, 40.7% for Blomia tropicalis, 16.1% for American cockroach, 14.0% for dog, 11.5% for Blatella germanica, 11.3% for Artemisia vulgaris, 10.3% for cat, 6.5% for Ambrosia artemisifolia, 6.3% for mixed mould I, 4.4% for mixed mould IV, 3.5% for mixed grass pollen and 2.2% for mixed tree pollen. Sensitizations to common allergens varied widely between geographical areas and demonstrated unique pattern in patients by stratification with age groups, with asthma and/or rhinitis. Severity of rhinitis and asthma was significantly correlated with skin index of reactivity to Artemisia vulgaris, Ambrosia artemisifolia and to D. pteronyssinus, D. farinae and Blomia tropicalis respectively (P < 0.001). Positive reactivity to the tested allergens and concomitant reactivity to multiple allergens including to house dust mites and Blomia tropicalis was markedly increased in patients with both asthma and rhinitis. House dust mites were the most prevalent allergens in patients with asthma and/or rhinitis in China. There were significant differences in patterns of sensitizations in patients from different geographical areas, age groups as well as asthma and/or rhinitis.

Association analysis of food allergens

Food allergy patients are known to present with allergic reactions to multiple allergens, but extrapolating these associations is difficult. Data mining, a procedure that analyzes characteristic combinations among large amounts of information, is often used to analyze and predict consumer purchasing behaviour. We applied this technique to the extrapolation of food allergen associations in allergy patients. We sent 1510 families our 'Questionnaire survey for the prevention of food allergies'. Responses noting 6549 allergens came from 878 families with 1383 patients, including 402 with anaphylaxis. Some results of the survey have already been published and here we presented the results of our association analysis of combinations of food allergens. Egg, milk, wheat, peanuts, and buckwheat are the most common food allergens. The most common simultaneous combinations of these allergens were 'egg-milk', 'egg-wheat', and 'milk-wheat'. The occurrence probability of a combination (i.e. one person suffering from a certain allergen also suffers from another) is called 'confidence'. Confidence was higher for 'chicken-egg', 'abalone-salmon eggs', and 'matsutake mushroom-milk'. As well, the combinations of 'crab-shrimp', 'squid-shrimp', and 'squid-crab' also indicated higher values in a statistical examination of the occurrence probabilities of these allergen combinations (Z-score). From the results of the association analysis, we speculated that some food allergens, such as abalone, orange, salmon, chicken, pork, matsutake mushroom, peach and apple did not independently induce food allergies. We also found that combinations, such as 'crab-shrimp', 'squid-shrimp', 'squid-crab', 'chicken-beef', and 'salmon-mackerel' had strong associations.

Combined sensitization of mice to extracts of dust mite, ragweed, and Aspergillus species breaks through tolerance and establishes chronic features of asthma

Existing asthma models develop tolerance when chronically exposed to the same allergen. We sought to establish a chronic model that sustains features of asthma long after discontinuation of allergen exposure. We immunized and exposed mice to a combination of single, double, or triple allergens (dust mite, ragweed, and Aspergillus species) intranasally for 8 weeks. Airway hyperreactivity (AHR) and morphologic features of asthma were studied 3 weeks after allergen exposure. Signaling effects of the allergens were studied on dendritic cells. Sensitization and repeated exposure to a single allergen induced tolerance. Sensitization to double and especially triple allergens broke through tolerance and established AHR, eosinophilic inflammation, mast cell and smooth muscle hyperplasia, mucus production, and airway remodeling that persisted at least 3 weeks after allergen exposure. Mucosal exposure to triple allergens in the absence of an adjuvant was sufficient to induce chronic airway inflammation. Anti-IL-5 and anti-IL-13 antibodies inhibited inflammation and AHR in the acute asthma model but not in the chronic triple-allergen model. Multiple allergens produce a synergy in p38 mitogen-activated protein kinase signaling and maturation of dendritic cells, which provides heightened T-cell costimulation at a level that cannot be achieved with a single allergen. Sensitivity to multiple allergens leads to chronic asthma in mice. Multiple allergens synergize in dendritic cell signaling and T-cell stimulation that allows escape from the single allergen-associated tolerance development.

Innovation in immunotherapy

Innovation in immunotherapy

Multiallergen immunotherapy for allergic rhinitis and asthma

The English and non-English language literature on allergen immunotherapy was reviewed for studies simultaneously using 2 or more distinct allergen extracts in either subcutaneous or sublingual immunotherapy. Thirteen studies were identified, 11 using subcutaneous injections, 1 using sublingual administration, and 1 using both. In studies with adequate information, administration of 2 extracts by means of either subcutaneous immunotherapy or sublingual immunotherapy was effective. In studies using multiple allergens, 3 studies showed clear efficacy, whereas in the other 2 studies, lack of efficacy might have been due to inadequate doses of extract or omission of clinically relevant allergens in the treatment regimen. It is concluded that simultaneous administration of more than 1 allergen extract is clinically effective. However, more studies are needed, particularly with more than 2 allergen extracts and with sublingual administration.