To the Editor: Occupational asthma accounts for more than 10% of all cases of asthma in adults, and baker's asthma (BA) is the leading cause of occupational respiratory disease in Western countries.1 ...Such occupational allergic respiratory disorders are often misdiagnosed, with significant legal, economic, and health impacts for affected patients.1,2 The incidence of BA among young bakers has been reported to range from 0.3 to 2.4 cases per 1000 person-year, and an increasing number of asthma cases are being reported among supermarket bakery workers.3 In recent years, some studies aimed to determine the panel of wheat allergens for diagnosing patients with BA to avoid specific bronchial challenge with wheat due to its potential risk and technical requirements.4,5 Regarding in vitro diagnosis (specific IgE assays), all known diagnostic approaches have poor predictability and specificity.1,2 The introduction of microarray techniques featuring a large panel of purified allergens has been a major advance in the diagnosis of allergic diseases.6,7 However, this technique has been hardly applied to the diagnosis of patients with occupational asthma caused by wheat.7,8 In the present study, the allergen profiles of patients with BA from 3 different regions in Spain (Madrid, Malaga, and Valladolid) with a relevant bakery industry were characterized. Location Median age (y) (range) Sex (M/F) SPT wheat extract (positive) Bronchial challenge test (positive) Aeroallergen sensitization (SPT) Food allergy (SPT) Madrid n = 17 39.2 (28-64) 16/1 17/17 17/17 + Any SPT 88%Olive 35%Grass 29%Dust mites 35%Alternaria 11.7%Alpha-amylase 17.6% 53% No47% Yes18% Nuts6% Barley6% Egg6% Kiwi Malaga n = 10 38 (19-60) 8/2 10/10 10/10 + Any SPT 75%Olive 37.5%Grass 37.5%Dust mites 62.5%Alternaria 12.5%Alpha-amylase 12% 60% No40% Yes50% Peach25% Nuts25% Spices25% Barley Valladolid n = 18 31 (19-66) 14/4 18/18 18/18 + Any SPT 89%Olive 50%Grass 70%Dust mites 20%Alternaria 10%Alpha-amylase 22.4% 62% No38% Yes50% Barley25% Apple25% Peach Table I Clinical data of patients with BA included in the study F, Female; M, male.
Background Cow's milk is the main cause of food allergy in children. Patients allergic to food frequently experience accidental exposure. There are few studies analyzing this problem, most of them ...concerning peanut allergy. Objective We sought to calculate the frequency of accidental exposure reactions in children allergic to cow's milk during a 12-month period, to analyze the clinical characteristics and circumstances surrounding the reactions, and to identify risk factors for severe reactions. Methods Eighty-eight children allergic to cow's milk (44 boys; median age, 32.5 months) were included in the study. A systematized questionnaire about accidental exposure was used. Reactions were classified as mild, moderate, and severe. Cow's milk– and casein-specific IgE antibody titers were determined. Results Thirty-five (40%) children had 53 reactions in the previous year (53% mild, 32% moderate, and 15% severe). Most reactions took place at home (47%) under daily life circumstances (85%). Specific IgE levels to cow's milk were higher in children with severe reactions than in those with moderate (median, 37.70 vs 7.71 KUA/L; P = .04) or mild (3.37 KUA/L; P = .04) reactions. The frequency of severe reactions was 10-fold higher in asthmatic children (odds ratio, 10.2; 95% CI, 1.13-91.54). Conclusions Reactions to accidental exposure are frequent in children with cow's milk allergy. The proportion of severe reactions was 15%. The risk factors for such reactions included very high levels of specific IgE to cow's milk and casein and asthma.
To the Editor: Bakers are repeatedly exposed to wheat flour (WF) and may develop sensitization and occupational rhinoconjunctivitis and/or asthma to WF allergens.1 Several wheat proteins have been ...identified as causative allergens of occupational respiratory allergy in bakery workers.1 Testing of IgE reactivity in patients with different clinical profiles of wheat allergy (food allergy, wheat-dependent exercise-induced anaphylaxis, and baker's asthma) to salt-soluble and salt-insoluble protein fractions from WF revealed a high degree of heterogeneity in the recognized allergens. When she was removed from the workplace, not only asthma symptoms significantly improved but also EoE went into remission, even when she was allowed to eat cereals. ...we have ruled out the involvement of cereal ingestion as an eliciting factor of occupational EoE, despite the fact that gliadins are stable to heat and gastric enzymes and exhibit low solubility in gastric and duodenal fluids.10 Nevertheless, patients with baker's asthma, including those allergic to gliadins, almost invariably tolerate ingestion of cereal products without any ill effect.1,2 In summary, we report the first case of occupational EoE due to WF gliadin triggered by inhalation and not by ingestion, associated with rhinoconjunctivitis and asthma.
Background Baker's asthma is a frequent occupational allergic disorder mainly caused by inhalation of cereal flours. Lipid transfer proteins (LTPs) constitute a family of plant food panallergens, but ...their role as inhalant and wheat allergens is still unclear. Objective We sought to explore the involvement of wheat LTPs in baker's asthma caused by wheat flour sensitization. Methods Forty patients with occupational asthma caused by wheat flour inhalation were studied. Wheat LTP, Tri a 14, was purified by using a 2-step chromatographic protocol and characterized by N-terminal amino acid sequencing and 3-dimensional modeling. Its reactivity was confirmed by means of IgE immunodetection, ELISA and ELISA-inhibition assays, and skin prick tests. Results Specific IgE to Tri a 14 was found in 60% of 40 individual sera from patients with baker's asthma, and the purified allergen elicited positive skin prick test reactions in 62% of 24 of these patients. Tri a 14 and peach LTP, Pru p 3, showed a sequence identity of 45%, but the low cross-reactivity between both allergens detected in several individual sera reflected great differences in their 3-dimensional IgE-binding regions. Conclusions Wheat LTP is a major inhalant allergen associated with baker's asthma caused by wheat flour sensitization. Poor cross-reactivity with its peach homolog was found in some patients. Clinical implications LTPs can be considered relevant inhalant allergens linked to respiratory disorders. LTP from wheat (Tri a 14) can be used as a helpful tool for the diagnosis of baker's asthma.
Specific IgE to Ara h 2 has been shown to be useful in the diagnosis of peanut allergy, whereas the peanut lipid transfer protein, Ara h 9, has been suggested to be responsible for peanut allergy in ...the Mediterranean population.
To better characterize peanut allergy in children from a Mediterranean area and determine the value of specific IgE to Ara h 6 (conglutinin, 2S albumin) for the diagnosis of peanut allergy.
Ninety-one children with suspected allergy to edible vegetables were included in the study. They were classified as allergic or tolerant to peanut. Specific IgE to peanut allergens was measured by a commercially available microarray (ImmunoCAP ISAC 112, ThermoFisher, Uppsala, Sweden).
Patients allergic to peanut showed positive specific IgE changes to peanut seed storage proteins (Ara h 1, Ara h 2, Ara h 3, and Ara h 6) more frequently than tolerant subjects. Ara h 9 showed a similar frequency of reactivity in the 2 groups. Ara h 6 was the allergen most frequently recognized by patients with allergy. Four patients with allergy were found to be mono-sensitized to Ara h 6. Ara h 2 and Ara h 6 showed similar diagnostic accuracy (areas under the curve 0.792 and 0.852). A combined cutoff point for Ara h 2 (≥0.1 ISU) and Ara h 6 (≥2 ISU) yielded the best diagnostic performance (sensitivity 0.77, specificity 0.97, positive predictive value 0.89, negative predictive value 0.93).
Peanut allergy cannot be ruled out without obtaining a negative determination of Ara h 6.
Background Asthma guidelines emphasize both maintaining current control and reducing future risk, but the relationship between these 2 targets is not well understood. Objective This retrospective ...analysis of 5 budesonide/formoterol maintenance and reliever therapy (Symbicort SMART Turbuhaler ) studies assessed the relationship between asthma control questionnaire (ACQ-5) and Global Initiative for Asthma-defined clinical asthma control and future risk of instability and exacerbations. Methods The percentage of patients with Global Initiative for Asthma–defined controlled asthma over time was assessed for budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies; higher dose inhaled corticosteroid (ICS), same dose ICS/long-acting β2 -agonist (LABA), and higher dose ICS/LABA plus short-acting β2 -agonist. The relationship between baseline ACQ-5 and exacerbations was investigated. A Markov analysis examined the transitional probability of change in control status throughout the studies. Results The percentage of patients achieving asthma control increased with time, irrespective of treatment; the percentage Controlled/Partly Controlled at study end was at least similar to budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies: higher dose ICS (56% vs 45%), same dose ICS/LABA (56% vs 53%), and higher dose ICS/LABA (54% vs 54%). Baseline ACQ-5 score correlated positively with exacerbation rates. A Controlled or Partly Controlled week predicted at least Partly Controlled asthma the following week (≥80% probability). The better the control, the lower the risk of an Uncontrolled week. The probability of an exacerbation was related to current state and was lower with budesonide/formoterol maintenance and reliever therapy. Conclusions Current control predicts future risk of instability and exacerbations. Budesonide/formoterol maintenance and reliever therapy reduces exacerbations versus comparators and achieves at least similar control.
Oral desensitization in children allergic to cow's milk proteins is not risk free. The analysis of factors that may influence the outcome is of utmost importance.
To analyze the efficacy and safety ...of the oral desensitization according to specific IgE (sIgE) level and adverse events during the maintenance phase.
Thirty-six patients allergic to cow's milk (mean age, 7 years) were included in an oral desensitization protocol. Patients were grouped according to sIgE levels (ImmunoCAP) into groups 1 (sIgE <3.5 kU/L), 2 (3.5-17 kU/L), and 3 (>17-50 kU/L). Nineteen children were included as a control group. Serum sIgE levels to cow's milk and its proteins were determined at inclusion and 6 and 12 months after finishing the desensitization protocol.
Thirty-three of 36 patients were successfully desensitized (200 mL): 100% of group 1 and 88% of groups 2 and 3. Desensitization was achieved in a median of 3 months (range, 1-12 months); 90% of the patients in group 1, 50% of the patients in group 2, and 30% of the patients in group 3 achieved tolerance in less than 3 months (P = .04). In the control group only 1 child tolerated milk in oral food challenge after 1 year. During the induction phase, there were 53 adverse events in 27 patients (75%). Patients of groups 2 and 3 had more severe adverse events compared with group 1. During the maintenance phase, 20 of 33 patients (60%) had an adverse event.
Oral desensitization is efficacious. Tolerance is achieved earlier when sIgE is lower. Severe adverse events are frequent, especially in patients with higher sIgE levels.
Background Identifying patients at risk of future severe asthma exacerbations, those whose asthma might be less treatment responsive, or both might guide treatment selection. Objective We sought to ...investigate predictors for failure to achieve Global Initiative for Asthma (GINA)–defined good current asthma control and severe exacerbations on treatment and to develop a simple risk score for exacerbations (RSE) for clinical use. Methods A large data set from 3 studies comparing budesonide/formoterol maintenance and reliever therapy with fixed-dose inhaled corticosteroid/long-acting β2 -agonist therapy was analyzed. Baseline patient characteristics were investigated to determine dominant predictors for uncontrolled asthma at 3 months and for severe asthma exacerbations within 12 months of commencing treatment. The RSE, right censored at 6 months to include all 3 studies, was based on the dominant predictors for exacerbations in two thirds of the data set and validated in one third. Results Patients (n = 7446) whose symptoms were not controlled on GINA treatment steps 3 and 4 and with 1 or more exacerbations (as judged by a clinician based on patient records, history, or both) in the previous year were included. On multivariate analysis, GINA step, reliever use, postbronchodilator FEV1 , and 5-item Asthma Control Questionnaire score were dominant (all P < .001) predictors for both the risk of uncontrolled asthma and severe exacerbations. Additional dominant predictors for uncontrolled asthma were smoking status and asthma symptom scores and an additional predictor for severe exacerbation was body mass index. An exponential increase in risk was observed with increments in RSE based on 5 selected predictors for exacerbations. Conclusion Risk of uncontrolled asthma at 3 months and a severe exacerbation within 12 months can be estimated from simple clinical assessments. Prospective validation of these predictive factors and the RSE is required. Use of these models might guide the management of asthmatic patients.
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