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 α-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 α-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.     

Immunoglobulin E recognition patterns to purified Kiwifruit (Actinidinia deliciosa) allergens in patients sensitized to Kiwi with different clinical symptoms

Background Green kiwifruit allergy is on the rise. However, no surveys testing purified major kiwi allergens have been carried out in a large population, including both kiwi-sensitized [skin prick test (SPT)-positive] and truly kiwi-allergic patients.
Objective To isolate major kiwifruit allergens, and to explore their relevance by in vitro and in vivo methods in a large kiwi-sensitized and -allergic population.
Methods A large group ( n =92) of kiwi-sensitized patients with different clinical symptoms were selected, and double-blind, placebo-controlled, food challenges to kiwi were performed in 52 of them. The three major IgE-binding proteins from kiwifruit extracts were isolated and characterized by N-terminal amino acid sequencing and molecular size and glycosylation analysis. The allergenic potency of the three kiwi allergens, and of avocado Pers a 1 as a model allergen associated with the latex-fruit syndrome, was tested by specific IgE quantitation, immunodetection assays and SPTs.
Results The isolated kiwifruit allergens were identified as actinidin Act d 1, glycosylated thaumatin-like Act d 2 and a novel 40 kDa glycoprotein designated as Act d 3.02. Specific IgE to each of the three allergens was found in over 60% of sera from kiwi-sensitized patients, and Act d 1 and Act d 2 induced positive SPT responses in over 50% of the tested patients. A significant link between IgE levels to Act d 1 and Act d 3 and anaphylaxis was uncovered. Avocado Pers a 1 showed an in vitro sensitization prevalence of around 45%, but a low in vivo reactivity.
Conclusion Act d 1, Act d 2 and Act d 3 are major allergens in the population studied. Severe symptoms after kiwi ingestion are associated with high IgE levels to Act d 1 and Act d 3.     

The performance of a component‐based allergen microarray for the diagnosis of kiwifruit allergy

Background Allergy to kiwifruit is increasingly reported across Europe. Currently, the reliability of its diagnosis by the measurement of allergen‐specific IgE with extracts or by skin testing with fresh fruits is unsatisfying. Objective To evaluate the usefulness of a component‐based allergen microarray for the diagnosis of kiwifruit allergy in a large group of patients. Methods With an allergen microarray, we measured specific IgE and IgG4 levels to a panel of nine kiwifruit allergens in sera of 237 individuals with kiwifruit allergy. Sera from 198 allergic patients without kiwifruit allergy served as controls. Furthermore, we determined the extent of sensitization to latex. Results The panel of kiwifruit allergens showed a diagnostic sensitivity of 66%, a specificity of 56% and a positive predictive value of 73%. Sera from kiwifruit‐allergic patients contained significantly more frequently Act d 1‐specific IgE than sera from control patients. Furthermore, 51% of the positive sera contained IgE directed to a single allergen, namely Act d 1 (45%), Act d 9 (27%) or Act d 7 (13%). Within the control group, 36% sera recognized a single allergen. Out of those, 48% were positive to the cross‐reactive glycoallergen Act d 7, 43% to the profilin Act d 9 and only 5% to Act d 1. Allergen‐specific IgG4 levels did not differ between kiwifruit‐allergic and ‐tolerant patients. Kiwifruit‐ and latex‐allergic patients contained Hev b 11‐specific IgE significantly more frequently than latex‐allergic patients without kiwifruit allergy. Conclusions Act d 1 can be considered a marker allergen for genuine sensitization to kiwifruit. We demonstrated that a component‐based kiwifruit allergen microarray would improve the prognostic value of in vitro diagnostic tests. Cite this as: M. Bublin, S. Dennstedt, M. Buchegger, M. Antonietta Ciardiello, M. L. Bernardi, L. Tuppo, C. Harwanegg, C. Hafner, C. Ebner, B. K. Ballmer‐Weber, A. Knulst, K. Hoffmann‐Sommergruber, C. Radauer, A. Mari and H. Breiteneder, Clinical & Experimental Allergy, 2011 (41) 129–136.     

Wheat and maize thioredoxins: a novel cross-reactive cereal allergen family related to baker's asthma

BACKGROUND: Baker's asthma is a serious problem for a significant proportion of workers in bakeries, confectionaries, and the food industry. Although several wheat allergens related to baker's asthma have been described, standardized reagents for a reliable diagnosis are not yet available. OBJECTIVE: To clone novel wheat allergens related to baker's asthma and investigate the cross-reactive potential of their maize and human homologues. METHODS: A wheat cDNA phage display library was screened with sera from bakers with occupational asthma for IgE-binding structures. Homologous sequences from maize and human thioredoxins were amplified from corresponding cDNA libraries. RESULTS: Within the enriched wheat cDNA repertoire we identified, among others, the sequence encoding wheat thioredoxin-hB (Triticum aestivum allergen 25 [Tri a 25]). The recombinant protein displayed enzymatic activity, and we observed a sensitization rate of 47% among bakers with occupational asthma and of 35% among patients with grass pollen allergy, but without a clinical history of cereal allergy. Furthermore, the previously characterized maize thioredoxin-h1 (Zea mays allergen 25 [Zea m 25]), sharing 74% identity with Tri a 25, exhibited distinct IgE cross-reactivity with its wheat homologue. Two bakers also showed sensitization to human thioredoxin, which shares 29% identity with Tri a 25. In a comparative study, we included recombinant alpha-amylase inhibitor 0.19, showing a sensitization rate of 65% in individuals with baker's asthma. CONCLUSION: Thioredoxins represent a novel family of cross-reactive allergens that might contribute to the symptoms of baker's asthma and might in addition be related to grass pollen allergy, as indicated by the reactivity of grass pollen allergic patients to cereal thioredoxins. CLINICAL IMPLICATIONS: The recombinant cereal thioredoxins will, together with the already reported wheat allergens, contribute to a more reliable diagnosis of baker's asthma and, perhaps, become a tool for the development of component-resolved immunotherapy.     

Micro‐arrayed wheat seed and grass pollen allergens for component‐resolved diagnosis

Background: Wheat is a potent allergen source and can cause baker’s asthma, food and pollen allergy. The aim of the study was to develop an allergen micro‐array for differential diagnosis of baker’s asthma, wheat‐induced food allergy and grass pollen allergy. Methods: We analysed the immunoglobulin‐E reactivity profiles of patients suffering from baker’s asthma, wheat‐induced food allergy and grass pollen allergy to micro‐arrayed recombinant wheat flour allergens and grass pollen allergens and compared these results with clinical results and diagnostic tests based on crude wheat flour, wheat pollen and grass pollen allergen extracts. Results: We identified recombinant wheat flour allergens, which are specifically recognized by patients suffering from baker’s asthma, but not from patients with food allergy to wheat or pollen allergy. rPhl p 1 and rPhl p 5 were identified as marker allergens specific for grass pollen allergy. They can be used to replace grass pollen extracts for allergy diagnosis and to identify grass pollen allergic patients among patients suffering from baker’s asthma and wheat‐induced food allergy. Profilin was identified as a cross‐reactive allergen recognized by patients suffering from baker’s asthma, food and pollen allergy. Conclusions: Our results indicate that it will be possible to design serological tests based on micro‐arrayed recombinant wheat seed and grass pollen allergens for the discrimination of baker’s asthma, wheat‐induced food allergy and grass pollen allergy.     

Immunoglobulin E antibodies to ingested cereal flour components: studies with sera from subjects with asthma and eczema

The specificity of immunoglobulin E for different cereal grain proteins was investigated using sera from twenty paedialric patients with asthma and/or eczema. Close correlations were observed between radioallergosorbent test values for grain extracts of wheat, rye and barley, and, to a lesser extent, oats. Of the different wheat flour fractions tested, the globulins and glutenins consistently bound higher levels of IgE than the gliadins and albumins. This is in contrast both with bakers' asthma (an allergy to inhaled flour where the albumins are important allergens) and with coeliac disease (in which gliadin is the most toxic fraction). Partial digestion of the flour proteins largely removed their ability to bind IgE, An analytical technique of identifying allergens after gel isoelectric focusing demonstrated that many different flour proteins were involved.     

Western blot analysis of water-soluble wheat flour (Triticum vulgaris) allergens.

Water-soluble wheat flour allergens were analyzed using the western blot technique. The sera of 130 bakers (42 with wheat flour allergy, 88 without allergy) were analyzed for IgE, IgG, and IgG4 binding towards wheat flour allergens. Three major allergens with molecular weights of 47, 17, and 15 kD were identified (Tri v Bd 47, Tri v Bd 17, and Tri v Bd 15; IUIS allergen nomenclature) by their ability to bind IgE from approximately 50% of the allergic sera. The specificity of the IgG was mostly directed against three high molecular weight components (134, 122, and 98 kD). In contrast, IgE and IgG4 was found frequently against the major allergens. 40% of healthy donors versus 12% of the asthmatic bakers had no detectable IgG4 against wheat flour extract. The biological activity of the water-soluble wheat flour components has been shown by their ability to induce histamine release from basophil leukocytes obtained from patients with bakers' asthma. The release of histamine from basophil leukocytes significantly correlated with the presence of IgE antibodies against wheat flour components of 47, 17 and 15 kD. A regulatory role of wheat flour specific IgG4 in allergic diseases could not be evaluated by western blot analysis.     

Clinical presentation,allergens, and management of wheat allergy

IgE-mediated allergy to wheat proteins can be caused by exposure through ingestion, inhalation, or skin/mucosal contact, and can affect various populations and age groups. Respiratory allergy to wheat proteins is commonly observed in adult patients occupationally exposed to flour, whereas wheat food allergy is more common in children. Wheat allergy is of growing importance for patients with recurrent anaphylaxis, especially when exercise related. The diagnosis of wheat allergy relies on a consistent clinical history, skin prick testing with well-characterized extracts and specific IgE tests. The accuracy of wheat allergy diagnosis may be improved by measuring IgE responses to several wheat components. However, a high degree of heterogeneity has been found in the recognition pattern of allergens among patient groups with different clinical profiles, as well as within each group. Thus, oral provocation with wheat or the implicated cereal is the reference test for the definitive diagnosis of ingested wheat/cereal allergy.     

Asthma induced by inhalation of flour in adults with food allergy to wheat

Background Wheat is one of the major food allergens and it is also an inhalant allergen in workers exposed to flour dusts. Food allergy to wheat in adulthood seems to be rare and has never been reported to be associated with asthma induced by flour inhalation.
Objective The study aimed at detecting adults with food allergy to wheat and screening them for the presence of specific bronchial reactivity to inhaled wheat proteins.
Methods Adults with a history of adverse reactions to ingestion of wheat underwent skin prick test with commercial wheat extract and were assessed for the presence of specific wheat IgE in the sera. Food sensitivity to wheat was confirmed by double-blind, placebo-controlled food challenge (DBPCFC). Specific bronchial reactivity was investigated through a specific bronchial challenge with wheat proteins.
Results In nine patients with evidence of specific IgE response to wheat, a diagnosis of food allergy was made by DBPCFC. Only two subjects had asthma as disease induced by ingestion of wheat. Seven subjects reported a history of respiratory symptoms when exposed to flour dusts. A significant reduction of forced expiratory volume in 1 s (FEV₁) was detected in these seven patients when a specific bronchial challenge with flour proteins was performed. Only three out of seven subjects with asthma induced by flour could be considered occupationally exposed to flour dusts.
Conclusion For the first time, it has been shown that specific bronchial reactivity to wheat proteins can be detected in patients with different disorders associated with food allergy to wheat. The presence of asthma induced by inhaled flour is not strictly related to occupational exposure and it may also occur in subjects not displaying asthma among symptoms induced by wheat ingestion.     

IgE sensitization profiles toward green and gold kiwifruits differ among patients allergic to kiwifruit from 3 European countries

BACKGROUND: Kiwifruits have become a major elicitor of plant food allergy. Until recently, the only species of kiwifruit grown commercially was the common green-fleshed Actinidia deliciosa cv Hayward. In 1999, the yellow-fleshed cultivar Actinidia chinensis cv Hort16A was introduced into the international market. OBJECTIVE: We compared the allergen compositions of green and gold kiwifruits and assessed the sensitization patterns of patients with kiwifruit allergy toward both varieties. METHODS: Sera from 90 patients with kiwifruit allergy from Austria, central Italy, and the Netherlands were tested for IgE binding to green and gold kiwifruit protein extracts and to purified actinidin, the major kiwifruit allergen, by ELISA. In addition, ELISA inhibitions and immunoblots were performed with selected sera. Relevant allergens were identified by N-terminal sequencing and immunoblotting with allergen-specific antibodies. RESULTS: IgE immunoblotting showed marked differences in the allergen compositions of green and gold kiwifruit extracts. Phytocystatin, a novel plant food allergen, and a thaumatin-like protein were identified as allergens common for both cultivars. Two allergens with homologies to chitinases were found in gold kiwifruits, whereas actinidin was detected exclusively in green kiwifruits. Patients from Central Europe and central Italy showed distinct sensitization profiles toward green and gold kiwifruit extracts as well as actinidin. Whereas sera from Austrian and Dutch patients mainly recognized green kiwifruit extract and actinidin, almost all Italian sera showed IgE binding to both kiwifruit species, but only half of them contained actinidin-specific IgE. Green and gold kiwifruit extracts were shown to be highly cross-reactive as determined by IgE ELISA inhibition. CONCLUSION: The presence of common allergens and the IgE cross-reactivity to green kiwifruit qualifies gold kiwifruit as a potential new allergen source for patients allergic to green kiwifruits.     

Occupational asthma caused by soybean flour in bakers—differences with soybean-induced epidemic asthma

BACKGROUND: Soybean dust has been identified as the causative agent of occupational asthma and asthma epidemics. Two main soybean hull allergens responsible for asthma outbreaks, Gly m 1 and Gly m 2, have been identified and purified. OBJECTIVE: The soybean allergens causing occupational asthma in exposed bakers were investigated and compared with those involved in epidemic asthma. METHODS: We report four bakers or confectioners with work-related respiratory symptoms who were exposed to soybean flour used as a baking additive. The causative role of soybean flour was investigated by immunological tests and specific inhalation challenge tests. Soybean flour allergens causing occupational asthma were characterized by immunoblotting. Immunoglobulin (Ig) E-reactivity to Gly m 1 and Gly m 2 was assessed using enzyme-linked immunosorbent assay. RESULTS: Sensitization to soybean flour was demonstrated by skin and serological tests and was confirmed by positive inhalation tests. Bronchial challenge test to soybean flour extract elicited immediate or dual asthmatic responses. Immunoblotting with soybean flour and soybean hull extracts showed IgE-binding mainly to high molecular weight (MW) allergens. There was an important individually different allergic response to inhalant soybean components. None of the patients showed IgE-reactivity against Gly m 1 and only one patient showed IgE-reactivity to the soybean hull allergen Gly m 2. CONCLUSION: These bakery workers had developed IgE-mediated occupational asthma to soybean flour. The allergens involved in occupational asthma caused by soybean flour are predominantly high MW proteins that are present both in soybean hull and flour, and they are different from the allergens causing asthma outbreaks, which are mainly low MW proteins concentrated in the hull.     

Sensitization to the storage mite Lepidoglyphus destructor in wheat flour respiratory allergy.

Occupational allergy due to hypersensitivity to cereal flours is relatively common among bakers and grain-store workers. Storage mites can contaminate wheat flour and could be an important cause of allergic symptoms due to inhalation. Forty-three patients with criteria for allergic sensitization to wheat flour (skin tests, specific IgE to wheat flour and positive challenge tests) were included in a study to investigate the prevalence of cosensitization to Lepidoglyphus destructor (Ld). This mite was the predominant species in the wheat flour samples supplied by our patients. We found that 30% of the patients had IgE-mediated hypersensitivity of Ld. Of these, 23% did not have a relationship with any bakery or agriculture. We conclude that the prevalence of sensitization to Ld in patients sensitized to wheat flour is important.     

Allergy after ingestion or inhalation of cereals involves similar allergens in different ages

BACKGROUND: Cereals are among the major foods that account for food hypersensitivity reactions. Salt-soluble proteins appear to be the most important allergens contributing to the asthmatic response. In contrast, very limited information is available regarding cereal allergens responsible for allergic reactions after ingestion of cereal proteins. OBJECTIVE: The aim of this study was to evaluate the allergenic reactivity of ingested and inhaled cereal allergens in different ages, in order to investigate if the response to different allergens would depend on the sensitization route. METHODS: We included 66 patients in three groups. Group 1: 40 children aged 3 to 6 months who suffered from diarrhoea, vomiting, eczema or weight loss after the introduction of cereal formula in their diet and in which a possibility of coeliac disease was discarded. Group 2: 18 adults with food allergy due to cereals tested by prick tests, specific IgE and food challenge. Group 3: eight patients previously diagnosed as having baker's asthma. Sera pool samples were collected from each group of patients and IgE immunoblotting was performed. RESULTS: We found an important sensitization to cereal in the 40 children. The most important allergens were wheat followed by barley and rye. Among the adults with cereal allergy, sensitization to other allergens was common, especially to Lolium perenne (rye grass) pollen. Immunoblotting showed similar allergenic detection in the three groups. CONCLUSION: Clinically significant reactivity to cereal may be observed in early life. Inhalation and ingestion routes causing cereal allergy seem to involve similar allergens. The diet control was more effective in children. The possibility of cereal allergy after the introduction of cereal formula during the lactation period should not be underestimated.     

Baker's asthma

Seven bakers with respiratory symptoms were evaluated by skin tests, RAST assay for specific IgE antibodies to rye and wheat, inhalation challenge with methacholine for the determination of non-specific bronchial reactivity, and bronchoprovocation with rye and wheat extracts for the determination of antigen-specific bronchial reactivity. An immediate asthmatic response to antigen challenge was observed in four subjects and all of them had a high level of flour-specific IgE antibodies. The serum RAST values provided a more accurate predictive value than the degree of cutaneous sensitivity determined by skin testing with respect to the bronchial response to antigenic challenge. Among those who reacted positively to antigenic bronchoprovocation, a much lower antigen dose was required to elicit a positive reaction if the subject also had an increased degree of non-specific bronchial reactivity. An elevated RAST value was not found in thirty-eight asymptomatic bakers or in ten asthmatics who had no occupational exposure to flour. Thus, baker's asthma appears to he a form of allergic asthma to cereal flours mediated by specific IgF antibodies. Both the level of serum IgE antibodies and the degree of non-specific bronchial reactivity are important factors which may influence a baker's bronchial response upon inhalation of cereal flours.     

Bronchial responsiveness to bakery-derived allergens is strongly dependent on specific skin sensitivity

BACKGROUND: Quantitative relationships between immunological reactivity, non-specific bronchial responsiveness and bronchial responsiveness to allergens have scarcely been investigated in occupational asthma. METHODS: We assessed the above relationships in 24 subjects with baker's asthma. The skin endpoint titration to bakery allergens as a measure of immunological reactivity, together with the methacholine PC20 and allergen PC20 during early asthmatic reaction were determined. RESULTS: All patients had positive skin tests to some bakery allergens (wheat and rye flour, soybean flour, fungal enzymes and egg white proteins) and bronchial hyperresponsiveness to methacholine. Specific inhalation challenge (SIC) tests were performed with aqueous allergen extracts of cereal flour (n = 14), soybean (n = 8), baking enzymes (n = 12), and egg white proteins (n = 8) in sensitized workers. A positive asthmatic reaction was observed in 84% of the inhalation challenges. SIC elicited isolated early asthmatic reactions in 62%, dual reactions in 32% and isolated late reactions in 5%. Multiple linear regression analysis showed allergen PC20 as a function of skin sensitivity to allergen and methacholine PC20, yielding the following highly significant regression formula: log-allergen PC20 = 0.18 + 0.99 log(skin sensitivity) + 0.343 log(methacholine PC20) (r = 0.89, P < 0.001). This formula predicted allergen PC20 to within one double concentration in 67%, to within two double concentrations in 85% and within three double concentrations in 97%. CONCLUSION: The main determinant of bronchial responsiveness to allergen in patients with baker's asthma is the degree of sensitization to occupational allergens as determined by skin reactivity, modulated to a lesser extent by non-specific bronchial hyperresponsiveness.     

Occupational Rhinoconjunctivitis due to Maize in a Snack Processor: A Cross-Reactivity Study Between Lipid Transfer Proteins From Different Cereals and Peach

We report the case of a snack processor who developed occupational rhinoconjunctivitis due to maize brand exposure during the extrusion process, and who experienced abdominal pain upon drinking beer. The allergens implicated and the cross-reactivity between non-specific lipid transfer proteins (LTPs) from different cereals and peach were investigated. Skin prick tests and specific IgE to cereal flours, pulmonary functions tests and specific conjunctival and inhalation challenges to maize extract were performed. In vitro studies included IgE immunoblotting and ELISA inhibition assays. Skin prick tests with maize flour, maize brand and wheat flour extracts were positive, whereas serum specific IgE was positive only to maize flour. Specific inhalation challenge (SIC) to maize flour did not elicit an asthmatic reaction; however, conjunctival challenge test with the same extract was positive. Patient''s serum recognized IgE-binding bands in the maize and beer extracts corresponding to LTPs. In the ELISA inhibition assays, a significant degree of allergenic cross-reactivity was found between maize and beer LTPs, whereas no cross-reactivity was observed between maize LTP and wheat and peach LTPs.     

Papain Induced Occupational Asthma with Kiwi and Fig Allergy

Papain is a proteolytic enzyme which is widely used in food industry, pharmaceuticals, and cosmetics. Occupational and non-occupational papain allergies have previously been documented; however, there are limited publications about papain allergy with its relative fruit allergy. Here, we present a case of occupational, IgE-mediated papain allergy with kiwi fruit and fig fruit allergy. A 53-year-old man suffered from rhinitis for several years, with the onset of his symptoms coinciding with the time he started to work at a sausage processing plant where papain is often used as a meat tenderizer. He began to experience symptoms of chest tightness, shortness of breath and wheezing shortly after starting work 5 years ago. Furthermore, he experienced several episodes of oral itching, and tongue and oropharyngeal angioedema after injestion of kiwi fruit and fig fruit. The patient had a lifelong history of allergic conjunctivitis, allergic rhinitis, and childhood asthma. Specific IgE was positive to kiwi fruit, papain and chymopapain (2.95 kUA/L, >100 kUA/L, and 95.0 kUA/L, respectively). Similar bands at 10-15 kDa in blotting with papain and kiwi fruit extracts were found. This patient showed a potential association between papain allergy and sensitization to kiwi fruit. We also reviewed 13 patients with papain allergy published in the literature, with 85% (11/13) of the patients sensitized through the respiratory tract, and 40% (4/11) having atopy. Further studies should focus on the determination of cross-reactive allergens between papain and its fruit relatives, and the prevalence of food allergy in patients with papain allergy should be investigated in a relatively large cohort.     

Respiratory allergy in apprentice bakers: do occupational allergies follow the allergic march?

BACKGROUND: This prospective study describes the incidence, risk factors and natural history of occupational respiratory allergy in apprentice bakers. METHODS: Two hundred and eighty-seven apprentice bakers were examined using a questionnaire, skin prick tests (SPTs) to common and occupational allergens, evaluation of total serum IgE level and specific anti-flour and alpha-amylase IgE, before, 1 year and 2 years after the onset of vocational training. To diagnose occupational respiratory disease, spirometry, histamine and allergen-specific inhalation challenge tests were performed. RESULTS: The incidence of work-related chest symptoms was 4.2% in the first year and 8.6% in the second year of exposure. Hypersensitivity to occupational allergens developed in 4.6 and 8.2% of subjects, respectively. The incidence of occupational allergic rhinitis was 8.4% after 1 year and 12.5% after 2 years, and that of occupational asthma/cough-variant asthma 6.1 and 8.7%, respectively. The latency period of work-related rhinitis symptoms was 11.6 +/- 7.1 months and chest symptoms 12.9 +/- 5.5 months. Only in 20% of occupational asthmatics could allergic rhinitis be diagnosed a stage earlier. In 21 out of 25 subjects with occupational asthma, chronic cough was the sole clinical manifestation of the disease. Stepwise logistic regression analysis revealed that positive SPT to common allergens was a significant risk factor of hypersensitivity to occupational allergens (OR = 10.6, 95% CI 5.27; 21.45), occupational rhinitis (OR = 3.9, 95% CI 1.71; 9.14) and occupational asthma (OR = 7.4, 95% CI 3.01; 18.04). Moreover, positive SPT to occupational allergens on entry to the training was a significant risk factor of asthma (OR = 6.9, 95% CI 0.93; 51.38). CONCLUSIONS: The incidence of occupational asthma and rhinitis in apprentice bakers is high and increases z with the duration of exposure. Skin reactivity to common and occupational allergens is the main risk factor of bakers' asthma. Most cases of work-related respiratory symptoms among apprentice bakers are related to a specific sensitization. In most subjects who developed occupational asthma, rhinitis occurred at the same time as the chest symptoms did.     

Rye flour allergens associated with baker's asthma. Correlation between in vivo and in vitro activities and comparison with their wheat and barley homologues

Background A number of wheat and barley flour proteins that belong to the cereal α-amylase/trypsin inhibitor family have been identified as major allergens associated with baker's asthma. However, the allergenic role of this protein family had not been investigated in rye. Objective To study the allergenicity of flve purified proteins from rye flour which belong to the same inhibitor family, as well as to compare their properties with those of their wheat and barley homologues. Methods In vivo skin-prick tests were carried out in 21 patients with radioallergo-sorbent test (RAST) 2–3 to rye and allergic sensitization mainly to this cereal flour. In addition, sera from all these patients were used to assay the IgE binding capacity of dot blotted purified proteins. Results Three of the rye proteins tested, namely Sec c 1, RDAI-1 and RDAI-3, provoked positive skin-prick tests in more than 50% of patients, although their in vitro reactivity was lower. Different reactivities were found for the rye components compared with their wheat and barley homologues. Statistical analyses showed a significant correlation between the results of in vivo and in vitro tests for seven out of the nine purified proteins considered in this study. Conclusion Members of the rye α-amylase inhibitor family are main allergens involved in allergic reactions to cereal flours. However, different allergenic behaviours were found between homologous allergens from rye, barley, and wheat.     

Diversity of asparagus allergy: clinical and immunological features

BACKGROUND: Asparagus (Asparagus officinalis) is an extensively grown and consumed vegetable. To a lesser extent than other Liliaceae vegetables, allergic contact dermatitis (ACD) due to asparagus has been reported. However, only a few case reports of asparagus IgE-mediated allergy have been published. In a previous study, we demonstrated that two lipid transfer proteins (LTPs) (Aspa o 1.01 and Aspa o 1.02) were relevant allergens of asparagus. OBJECTIVE: We retrospectively analysed the 27 patients diagnosed with asparagus allergy during the last 5 years. All of them reported adverse symptoms after either asparagus ingestion or handling. We describe their clinical features and evaluate whether they were associated to immunological findings (immunoblot pattern and skin reactivity to LTPs). METHODS: Patients underwent skin prick and patch tests with standard panels of vegetables and aeroallergens. Besides crude asparagus extract, two purified LTPs were prick and patch tested. Total and specific IgE measurements and asparagus extract IgE immunoblotting were performed. Patients reporting asthma symptoms underwent specific inhalation challenge to asparagus. RESULTS: Of the 27 subjects, eight had ACD, 17 had IgE-mediated allergy and two had both ACD- and IgE-mediated allergy. Positive patch tests with the crude asparagus extract but not with LTPs were observed in subjects with ACD (n=10). Of 19 patients with IgE-mediated disease, 10 had contact urticaria after asparagus handling. Of them, five subjects and five others without skin allergy showed respiratory symptoms; of them, eight were diagnosed with occupational asthma confirmed by positive asparagus inhalation challenge, whereas the remaining two had isolated rhinitis. Four patients suffered from immediate allergic reactions related to asparagus ingestion (food allergy); three of them reported anaphylaxis whereas the other had oral allergic syndrome. Positive IgE immunoblotting (bands of 15 and 45-70 kDa) was observed in 10 subjects. Of 10 subjects with positive prick test to LTPs, six showed bands at 15 kDa. Either IgE-binding bands or positive prick tests to LTPs were observed in asthma (62%) and anaphylaxis (67%). CONCLUSION: Asparagus is a relevant source of occupational allergy inducing ACD and also IgE-mediated reactions. Severe disease (anaphylaxis or asthma) is common and LTPs seem to play a major role. The clinical relevance of LTP sensitization among patients with mild disease or symptom-free subjects should be addressed in prospective studies.