Interpretation of managing food allergy: Global Allergy and Asthma European Network guideline (2022) / 中华实用儿科临床杂志

Food allergy is one of the most common chronic non-infectious diseases in many countries and regions, which affects 2%-4% of children and adults.Its prevalence is on the rise worldwide.In 2022, the Global Allergy and Asthma European Network (GA 2LEN) proposed recommendations on managing food allergy to people at different age groups.This review aims to interpret the recommendations, clinical practice, precautions, evidence gaps and research priorities of food allergy management based on the GA 2LEN guideline 2022, thus providing reference for clinical management of food allergy.

The progress of combined therapy of omalizumab and allergen immunotherapy in children with moderate to severe allergic asthma / 国际儿科学杂志

Allergen immunotherapy(AIT)is considered the treatment capable of modifying the natural history of allergic respiratory disorders.The adverse reactions associated with AIT limit its clinical use in moderate to severe allergic asthma.Omalizumab is currently approved for the treatment of allergic asthma, chronic spontaneous urticaria, allergic rhinitis and other allergic diseases.A few trials have demonstrated the clinical efficacy of AIT and omalizumab combination therapy in children with moderate to severe allergic asthma.This review summarizes the research progress, mechanisma and application of omalizumab combined with AIT in children with moderate to severe allergic asthma.

Value of allergen nasal provocation test in assessment of the efficacy of house dust mites specific immunotherapy / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the value of nasal provocation test（NPT） in evaluating the efficacy of allergen immunotherapy（AIT） in patients with dust mite induced allergic rhinitis（AR）. Methods:A total of 83 patients with dust mite induced AR with/without asthma were included. Symptom score（SS）, daily medication score（DMS）, combined symptom and medication score（CSMS）, rhinoconjunctivitis quality of life questionnaire（RQLQ）, NPT and skin prick test（SPT） were assessed before and after 1 year AIT. Results:There were statistical differences in SS（P<0.000 1）, DMS（P<0.000 1）, CSMS（P<0.000 1）, and RQLQ（P<0.000 1） after 1 year of AIT compared with pre-treatment. The effective rate of CSMS was 73.49%, and the effective rate of NPT was 42.17%. CSMS was consistent with NPT in efficacy assessment（Kappa=0.437, P<0.001）; while in 54 patients with pre-treatment NPT concentrations other than the original concentration, CMSM and NPT showed better consistence（Kappa=0.895, P<0.001）. Among the 48 patients with ineffective NPT assessment in the first year, 25 patients completed the second-year follow-up, and 12 patients（48.00%） showed effective in NPT. However, 10 out of 12 patients（83.33%） with NPT concentration other than original solution pre-treatment showed effective NPT at the second year. Conclusion:NPT can be used as one of the indicators for efficacy evaluation for dust mite induced AR patients, especially for patients with positive NPT induced at lower concentrations before treatment.

Progress in allergen immunotherapy in children with allergic diseases / 国际儿科学杂志

The increasing incidence of allergic diseases in children has become a global public health problem, which not only endangers physical health, but also imposes a heavy economic burden on society and families.Allergen immunotherapy is a cause-specific treatment therapy for allergic diseases in children, which can change the natural course of allergic diseases and works by inducing the body to establish immune tolerance to allergens.Allergen immunotherapy can not only reduce the clinical symptoms and medication use of children, but also prevent allergic reactions to new allergens, and has good efficacy and safety.This paper reviews the research progress of allergen immunotherapy in children with allergic diseases, especially respiratory allergic diseases, in order to provide more treatment options and new ideas for clinical practice.

Posicionamento da Associação Brasileira de Alergia e Imunologia sobre o manejo da imunoterapia específica com alérgenos (ITA) em pacientes vacinados contra COVID­19 / Position statement of the Brazilian Association of Allergy and Immunology on the management of allergen-specific immunotherapy (AIT) in patients vaccinated against COVID­19

A pandemia de COVID-19 representa um grande desafio para todas as especialidades médicas. A imunoterapia com alérgenos (ITA) é considerada o único procedimento terapêutico capaz de modificar a história natural das doenças alérgicas, e caracteriza o estado da arte na área de Alergia e Imunologia. Esta estratégia terapêutica de imunomodulação é capaz de promover a remissão e controle das doenças alérgicas por períodos prolongados, mesmo após o seu término. Existem poucos dados em relação ao emprego da ITA em pacientes vacinados contra COVID-19, e até o momento não há um posicionamento oficial das sociedades internacionais da área de Alergia e Imunologia Clínica. Este documento tem como objetivo estabelecer recomendações práticas para o manejo da ITA em pacientes que receberam a vacina contra COVID-19. Os fenômenos imunológicos envolvidos na imunoprofilaxia vacinal e no mecanismo de ação da ITA foram comparados, proporcionando o estabelecimento de recomendações precisas.

The COVID-19 pandemic represents a serious challenge for all medical specialties. Allergen-specific immunotherapy (AIT) is considered the only therapeutic procedure capable of modifying the natural history of allergic diseases and characterizes the state of the art in the field of allergy and immunology. This therapeutic strategy of immunomodulation is able to promote remission and control of allergic diseases for prolonged periods, even after cessation. There are few data regarding use of AIT in patients vaccinated against COVID-19 and, to date, there is no official position statement published by international allergy and clinical immunology societies. This document aims to establish practical recommendations for the management of AIT in patients who have received the COVID-19 vaccine. The immunological mechanisms involved in immunoprophylaxis with vaccines and the mechanism of action of AIT have been compared to provide a solid basis for establishing precise recommendations.

Clinical Efficacy of Allergen-Specific Immunotherapy from Patient and Physician Perspectives

PURPOSE: Allergen-specific immunotherapy (AIT) is the only curative treatment for allergic diseases, but a few allergic patients receive AIT. In this multicenter cross-sectional study, we aimed to explore patient and physician perspectives on AIT through a questionnaire survey. MATERIALS AND METHODS: Allergic patients who received subcutaneous immunotherapy for at least 1 year were asked to answer a questionnaire developed by an expert panel of allergen and immunotherapy workgroup in Korea. RESULTS: A total of 267 patients (adults, 60.3%) with allergic rhinitis (91.4%), asthma (42.7%), or atopic dermatitis (20.2%) from referred hospitals completed the survey. Among patients and physicians, respectively, the overall rates of satisfaction with AIT for allergic rhinitis were 86.4% and 83.3% (kappa agreement=0.234, p<0.001), and those for asthma were 85.3% and 72.9% (kappa agreement=0.373, p<0.001). Moreover, pediatric asthmatic patients reported a significantly higher satisfaction rate than adult asthmatic patients after AIT (p=0.040). Symptom severity (p<0.001, respectively) and drug use for allergic rhinitis and asthma decreased after AIT. However, there was no significant difference in satisfaction rates between children and adults in allergic rhinitis (p=0.736). Interestingly, 35.7% and 35% of allergic rhinitis and asthma patients, respectively, reported experiencing improvement in their symptoms within 6 months of starting AIT. CONCLUSION: In this study evaluating the perspectives of patients and physicians on AIT, the majority of patients were satisfied with the efficacy and safety of AIT, but not its cost. AIT should be recommended for AR and allergic patients.

The Role of the Level of Interleukin-33 in the Therapeutic Outcomes of Immunotherapy in Patients with Allergic Rhinitis

Abstract Introduction Allergic rhinitis (AR) affects up to 40% of the population and results in nasal itching, congestion, sneezing, and clear rhinorrhea. Objectives This study aimed to evaluate the changes in the clinical symptoms and in the level of serum interleukin (IL)-33 before and after pollen immunotherapy (IT) in patients with AR. Methods The total symptomscore and the levels of total immunoglobulin E (IgE) and IL-33 were determined in the serum of 10 non-allergic healthy controls and 45 patients with AR who were equally divided into 3 groups: GI (patients did not receive IT), GII (patients had received IT for 6 months) and GIII (patients had received IT for 2 years). Results There was a significantly higher concentration of IgE and IL-33 in the serum of patients with AR than in that of non-allergic patients. Furthermore, serum level of IL-33 decreased significantly after pollen IT. But, there was no significant reduction in the serum level of IL-33 between GII and GIII patients. Conclusion Our results show a clinical improvement associated with a decrease in serum level of IL-33 after pollen IT.

Allergen standardization

Allergen immunotherapy (AIT) and diagnostic tests are based on well qualified allergen extracts, which are derived from biologic organisms. The allergenicity of the extracts is markedly affected by the climate, soil, year of production, storage methods, and manufacturing processes. Thus, standardization is a crucial process to guarantee the clinical efficacy and safety of the treatment and diagnostic reagents in allergic diseases. There are 2 different standardization processes, one is In vivo and the other is in vitro standardization. In vivo standardization is done by skin prick or intradermal tests. For in vitro standardization, measurements of weight/volume and protein nitrogen units have been widely used since the early period of AIT. In the 1970s, immunological methods such as radial immunodiffusion, enzyme-linked immunosorbent assay (ELISA) inhibition test and basophil activation test were developed. Allergen potency measured by ELISA inhibition test reflects the potency measured by skin tests and has been widely used for quality control of batch-to-batch variation. Recently, standardizations focused on the major allergen content of extracts have developed. Standardization for major allergens requires reliable reference materials (RMs) made of recombinant allergens and 2-site ELISA kits. However, only a few reliable RM and 2-site ELISA kits are available. For the standardization process, allergen RMs are essential. The Center for Biologics Evaluation and Research of the U.S. Food and Drug Administration provides 19 allergen RMs, and our research team also proved 9 RMs which are important in Korea. In conclusion, allergen standardization is an essential process for the development of reliable treatment and diagnostic reagents, and allergy specialist should be familiar with the concept of allergen standardization.

Decreased CRTH2 Expression and Response to Allergen Re-stimulation on Innate Lymphoid Cells in Patients With Allergen-Specific Immunotherapy

PURPOSE: Group 2 innate lymphoid cells (ILC2s) have been implicated in the pathogenesis of allergic disease. However, the effect of allergen-specific immunotherapy (AIT) on ILCs remains to be clarified. The aim of this study was to evaluate the levels of ILC subsets in allergic rhinitis (AR) patients in response to house dust mite (HDM)-specific immunotherapy. METHODS: We enrolled 37 AR patients undergoing AIT (16 responders and 11 non-responders) for 2 years, 35 HDM AR patients and 28 healthy subjects. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry to identify ILC subsets. Stimulation of ILC2s with recombinant allergen-specific protein was used to determine ILC2's activation (CD69 expression). RESULTS: Responder AIT patients and healthy subjects had a decreased frequency of circulating ILC2s compared to non-responder AIT and AR patients. Conversely, ILC1s from responder AIT patients and healthy subjects showed increased frequency compared to non-responder AIT and AR patients. The frequency of ILC3s natural cytotoxicity receptor (NCR)+ and NCR− in responder AIT patients was significantly lower compared to AR patients and healthy subjects. The ILC1: ILC2 proportion in responder AIT patients was similar to that of healthy subjects. PBMCs from patients who were responders to AIT had a significantly lower expression of the activation marker CD69 on ILC2s in response to allergen re-stimulation compared to AR patients, but no difference compared to non-responder AIT patients and healthy subjects. CONCLUSIONS: We propose that AIT might affect ILC responses. The activation of ILC2s was reduced in AR patients treated with AIT. Our results indicate that a relative ILC1/ILC2 skewed response is a possible key to successful AIT.

Dust mite sublingual immunotherapy in asthmatic children / 国际儿科学杂志

Bronchial asthma is one of the most common chronic inflammatory disorders in children.Pharmacotherapy can effectively control the chronic airway inflammation,improve the lung function,but it is difficult to improve the underlying immune response and natural progression of allergic diseases.Allergen specific immunotherapy can modify the course of allergic disease,reducing the risk of new allergic sensitizations,deterring the development of clinical asthma in children treated for allergic rhinitis and induce specific immune tolerance.The principal types of AIT are subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT).Dust mite is a common type of allergen.Dust mite SLIT has been widely used in clinic due to its effectiveness and safety.

Changes in basophil activation during immunotherapy with house dust mite and mugwort in patients with allergic rhinitis

BACKGROUND: The basophil activation test (BAT) is a promising tool for monitoring allergen-specific immunotherapy responses. OBJECTIVE: We aimed to investigate the changes in basophil activation in response to the inhalant allergens of house dust mite (HDM) and mugwort pollen during immunotherapy in patients with allergic rhinitis. METHODS: We enrolled patients with allergic rhinitis who were to receive subcutaneous immunotherapy for the inhalant allergens HDM or mugwort. A BAT was performed to assess CD63 upregulation in response to allergen stimulation using peripheral blood collected from the patients prior to immunotherapy and at 3, 6, 12, and 24 months after beginning immunotherapy. Rhinitis symptoms were evaluated using the rhinitis quality of life questionnaire (RQLQ) at 1-year intervals. RESULTS: Seventeen patients (10 with HDM sensitivity, 3 with mugwort sensitivity, and 4 with sensitivity to both HDM and mugwort) were enrolled in the study. Basophil reactivity to HDM did not change significantly during 24 months of immunotherapy. However, a significant reduction in basophil reactivity to mugwort was observed at 24-month follow-up. There was no significant association between the change in clinical symptoms by RQLQ and the change in basophil reactivity to either allergen. The change in allergen-specific basophil reactivity to HDM was well correlated with the change in nonspecific basophil activation induced by anti-FcεRI antibody, although basophil reactivity to anti-FcεRI antibody was not significantly reduced during immunotherapy. CONCLUSION: Suppression of CD63 upregulation in the BAT was only observed with mugwort at 2-year follow-up. However, the basophil response did not reflect the clinical response to immunotherapy.

Allergic conjunctivitis in Asia

Allergic conjunctivitis (AC), which may be acute or chronic, is associated with rhinitis in 30%–70% of affected individuals, hence the term allergic rhinoconjunctivitis (AR/C). Seasonal and perennial AC is generally milder than the more chronic and persistent atopic and vernal keratoconjunctivitis. Natural allergens like house dust mites (HDM), temperate and subtropical grass and tree pollen are important triggers that drive allergic inflammation in AC in the Asia-Pacific region. Climate change, environmental tobacco smoke, pollutants derived from fuel combustion, Asian dust storms originating from central/north Asia and phthalates may also exacerbate AR/C. The Allergies in Asia Pacific study and International Study of Asthma and Allergies in Childhood provide epidemiological data on regional differences in AR/C within the region. AC significantly impacts the quality of life of both children and adults, and these can be measured by validated quality of life questionnaires on AR/C. Management guidelines for AC involve a stepped approach depending on the severity of disease, similar to that for allergic rhinitis and asthma. Topical calcineurin inhibitors are effective in certain types of persistent AC, and sublingual immunotherapy is emerging as an effective treatment option in AR/C to grass pollen and HDM. Translational research predominantly from Japan and Korea involving animal models are important for the potential development of targeted pharmacotherapies for AC.

Changes in skin reactivity and associated factors in patients sensitized to house dust mites after 1 year of allergen-specific immunotherapy

BACKGROUND: Allergen-specific immunotherapy (SIT) can significantly improve symptoms and reduce the need for symptomatic medication. OBJECTIVE: The aim of this study was to investigate changes in skin reactivity to house dust mites (HDMs) as an immunologic response and associated factors after 1 year of immunotherapy. METHODS: A total of 80 patients with allergic airway diseases who received subcutaneous SIT with HDMs from 2009 to 2014 were evaluated. The investigated parameters were basic demographic characteristics, skin reactivity and specific IgE for HDM, serum total IgE level, blood eosinophil counts, and medication score. RESULTS: The mean levels of skin reactivity to HDMs, blood eosinophil counts, and medication scores after 1 year were significantly reduced from baseline. In univariate comparison of the changes in skin reactivity to HDMs, age ≤30 years, HDMs only as target of immunotherapy, and high initial skin reactivity (≥2) to HDMs were significantly associated with the reduction in skin test reactivity. In multivariate analysis, high initial skin reactivity and HDMs only as target allergens were significantly associated with changes in skin reactivity to HDMs. In the receiver operating characteristic curve of the initial mean skin reactivity to HDMs for more than 50% reduction, the optimal cutoff value was 2.14. CONCLUSION: This study showed significant reductions in allergen skin reactivity to HDMs after 1 year of immunotherapy in patients sensitized to HDMs. The extent of initial allergen skin reactivity and only HDMs as target allergen were important predictive factors for changes in skin reactivity.

Subcutaneous Immunotherapy Improves the Symptomatology of Allergic Rhinitis

Introduction The relevance of allergic rhinitis is unquestionable. This condition affects people s quality of life and its incidence has increased over the last years. Objective Thus, this study aims to analyze the effectiveness of subcutaneous injectable immunotherapy in cases of nasal itching, sneeze, rhinorrhea and nasal congestion in allergic rhinitis patients. Methods In the present study, the same researcher analyzed the records of 281 patients. Furthermore, the researchers identified allergens through puncture cutaneous tests using standardized extracts containing acari, fungi, pet hair, flower pollen, and feathers. Then, the patients underwent treatment with subcutaneous specific immunotherapy, using four vaccine vials for desensitization, associated with environmental hygiene. The authors analyzed conditions of nasal itching, sneeze, rhinorrhea, and nasal congestion throughout the treatment, and assigned them with a score ranging from zero (0), meaning absence of these symptoms to three (3), for severe cases. The symptoms were statistically compared in the beginning, during, and after treatment. Results In this study, authors analyzed the cases distribution according to age and the evolution of symptomatology according to the scores, comparing all phases of treatment. The average score for the entire population studied was 2.08 before treatment and 0.44 at the end. These results represent an overall improvement of ±79% in symptomatology of allergic rhinitis in the studied population. Conclusion The subcutaneous immunotherapy as treatment of allergic rhinitis led to a reduction in all symptoms studied, improving the quality of life of patients, proving itself as an important therapeutic tool for these pathological conditions.

Allergen-specific immunotherapy in pediatric allergic asthma

Allergen-specific immunotherapy (AIT) is the only curative way that can change the immunologic response to allergens and thus can modify the natural progression of allergic diseases. There are some important criteria which contributes significantly on efficacy of AIT, such as the allergen extract used for treatment, the dose and protocol, patient selection in addition to the severity and control of asthma. The initiation of AIT in allergic asthma should be considered in intermittent, mild and moderate cases which coexisting with other allergic diseases such as allergic rhinitis, and in case of unacceptable adverse effects of medications. Two important impact of AIT; steroid sparing effect and preventing from progression to asthma should be taken into account in pediatric asthma when making a decision on starting of AIT. Uncontrolled asthma remains a significant risk factor for adverse events and asthma should be controlled both before and during administration of AIT. The evidence concerning the efficacy of subcutaneous (SCIT) and sublingual immunotherapy (SLIT) for treatment of pediatric asthma suggested that SCIT decreases asthma symptoms and medication scores, whereas SLIT can ameliorate asthma symptoms. Although the effectiveness of SCIT has been shown for both seasonal and perennial allergens, the data for SLIT is less convincing for perennial allergies in pediatric asthma.

Effect on quality of life of the mixed house dust mite/weed pollen extract immunotherapy

BACKGROUND: Although many patients with allergic rhinitis have symptoms due to sensitization to more than one kind of allergens, and mixed allergen extracts are widely used for immunotherapy, there are few published trials. OBJECTIVE: Our study aimed to evaluate the effect of multiple-allergen immunotherapy on improving the symptoms and quality of life of allergic rhinitis patients. METHODS: We performed a 1-year single-center observation study of subcutaneous immunotherapy using house dust mite extract (n = 12), weed pollen extract (n = 21), or mixed house dust mite/weed pollen extract (n = 11) in 44 allergic rhinitis patients. All the allergens responsible for the symptom of each patient were included in his immunotherapy. Symptom score, medication score, and quality of life of the patients were evaluated before and after 1-year immunotherapy. Quality of life was evaluated with the Rhinoconjunctivitis Quality of Life Questionnaire. RESULTS: In all 3 groups receiving subcutaneous immunotherapy, significant improvement of symptom score, medication score, and quality of life was found vs. baseline at 1 year, irrespective of the allergen used. In the weed pollen season, the changes of quality of life questionnaire score after 1-year treatment were not significantly different between the weed pollen group (1.55 ± 1.24) and the mixed house dust mite/weed pollen group (1.14 ± 1.01). The same happened in the nonpollen seasons, during which dust mite immunotherapy (1.23 ± 1.63) and mixed immunotherapy (0.60 ± 0.47) did not show significantly different effect on the quality of life. CONCLUSION: The multiple-allergen immunotherapy might be effective in polysensitized allergic rhinitis patients, and could improve their quality of life. Our result did not show significant difference between the effects of multiple-allergen immunotherapy and mono-allergen immunotherapy.

Allergen Immunotherapy: Past, Present, and Future

Allergen-specific immunotherapy (AIT), although in clinical use for more than a century, is still the only causal treatment of allergic diseases. The safety and efficacy of AIT has been demonstrated in a large number of clinical trials. In addition to allergy symptom reduction AIT plays an essential role in preventing new allergies and asthma and shows long-term effects after discontinuation of treatment. Ideally, it is capable of curing allergy. However, AIT is not effective in all allergic individuals and is not equally effective in the treatment of various hypersensitivities to different allergens. For many years, the route of administration and the vaccine compositions have been evolving. Still there is a strong need for research in the field of new AIT modalities to increase its effectiveness and safety. Growing evidence on immunological effects of AIT, especially new T cell subsets involved in antigen/allergen tolerance, provides novel concepts for safer and more effective vaccination. Pharmacoeconomic studies have demonstrated a clear advantage of AIT over pharmacologic therapies.

A Survey of the Prescription Patterns of Allergen Immunotherapy in Korea

PURPOSE: Allergen immunotherapy (AIT) has been used as a curative and specific treatment of allergic diseases. However, no data on the prescription patterns of AIT in Korea is available. Therefore, we surveyed the prescription patterns of AIT by allergy specialists in Korea. METHODS: We emailed a questionnaire on AIT prescription patterns to the 690 members of the Korean Academy of Asthma, Allergy and Clinical Immunology with clinical practice experience. All returned answers were evaluated. RESULTS: The response rate was 21.0%. Only 69.0% of the respondents performed AIT in practice. Hindrance factors for performing AIT in the practice included a lack of facilities (21%), lack of practical experience during their subspecialty or postgraduate educational training programs (15.8%), no need for AIT because of sufficient pharmacotherapy (14.5%), insufficient economic profits (14.5%), and risks for adverse reactions (13.2%). Ninety-two allergy specialists (82%) performed AIT subcutaneously subcutaneous immunotherapy (SCIT) and 20 allergy specialists (18%) performed it sublingually sublingual immunotherapy (SLIT). Only 8 specialists performed both SCIT and SLIT. The allergens used for SCIT were house dust mites (98.9%), pollens (72.8%), and animal dander (23.9%). SLIT was prescribed only for house dust mites. Twenty-eight physicians (30.4%) observed anaphylactic reactions during SCIT. Eight physicians (40.0%) who prescribed SLIT observed adverse reactions, including local reactions, but none of them observed anaphylactic reactions. CONCLUSIONS: In this survey, 69.0% of the respondents performed AIT in clinical practice. SCIT prescription is more popular than SLIT. The Lack of facilities and clinical education is a critical barrier to performing AIT. Therefore, proper clinical education of AIT is necessary for Korean allergists.

Diagnosis and Management of Grain-Induced Asthma

Grain-induced asthma is a frequent occupational allergic disease mainly caused by inhalation of cereal flour or powder. The main professions affected are bakers, confectioners, pastry factory workers, millers, farmers, and cereal handlers. This disorder is usually due to an IgE-mediated allergic response to inhalation of cereal flour proteins. The major causative allergens of grain-related asthma are proteins derived from wheat, rye and barley flour, although baking additives, such as fungal alpha-amylase are also important. This review deals with the current diagnosis and treatment of grain-induced asthma, emphasizing the role of cereal allergens as molecular tools to enhance diagnosis and management of this disorder. Asthma-like symptoms caused by endotoxin exposure among grain workers are beyond the scope of this review. Progress is being made in the characterization of grain and bakery allergens, particularly cereal-derived allergens, as well as in the standardization of allergy tests. Salt-soluble proteins (albumins plus globulins), particularly members of the alpha-amylase/trypsin inhibitor family, thioredoxins, peroxidase, lipid transfer protein and other soluble enzymes show the strongest IgE reactivities in wheat flour. In addition, prolamins (not extractable by salt solutions) have also been claimed as potential allergens. However, the large variability of IgE-binding patterns of cereal proteins among patients with grain-induced asthma, together with the great differences in the concentrations of potential allergens observed in commercial cereal extracts used for diagnosis, highlight the necessity to standardize and improve the diagnostic tools. Removal from exposure to the offending agents is the cornerstone of the management of grain-induced asthma. The availability of purified allergens should be very helpful for a more refined diagnosis, and new immunomodulatory treatments, including allergen immunotherapy and biological drugs, should aid in the management of patients with this disorder.

Diagnosis and Management of Grain-Induced Asthma

Grain-induced asthma is a frequent occupational allergic disease mainly caused by inhalation of cereal flour or powder. The main professions affected are bakers, confectioners, pastry factory workers, millers, farmers, and cereal handlers. This disorder is usually due to an IgE-mediated allergic response to inhalation of cereal flour proteins. The major causative allergens of grain-related asthma are proteins derived from wheat, rye and barley flour, although baking additives, such as fungal alpha-amylase are also important. This review deals with the current diagnosis and treatment of grain-induced asthma, emphasizing the role of cereal allergens as molecular tools to enhance diagnosis and management of this disorder. Asthma-like symptoms caused by endotoxin exposure among grain workers are beyond the scope of this review. Progress is being made in the characterization of grain and bakery allergens, particularly cereal-derived allergens, as well as in the standardization of allergy tests. Salt-soluble proteins (albumins plus globulins), particularly members of the alpha-amylase/trypsin inhibitor family, thioredoxins, peroxidase, lipid transfer protein and other soluble enzymes show the strongest IgE reactivities in wheat flour. In addition, prolamins (not extractable by salt solutions) have also been claimed as potential allergens. However, the large variability of IgE-binding patterns of cereal proteins among patients with grain-induced asthma, together with the great differences in the concentrations of potential allergens observed in commercial cereal extracts used for diagnosis, highlight the necessity to standardize and improve the diagnostic tools. Removal from exposure to the offending agents is the cornerstone of the management of grain-induced asthma. The availability of purified allergens should be very helpful for a more refined diagnosis, and new immunomodulatory treatments, including allergen immunotherapy and biological drugs, should aid in the management of patients with this disorder.