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- Materials and methods
Background: Wheat and rye flours are among the most important allergens causing occupational asthma. Usually, the diagnosis of baker’s asthma is based on inhalation challenge tests with flours.
Aims of the study: To evaluate the relevance of flour-specific serum immunoglobulin E (IgE) and skin prick test (SPT) in the diagnosis of baker’s asthma and to define flour-specific IgE concentrations and wheal sizes that allow a prediction of the outcome of challenge testing.
Methods: Bronchial and nasal challenge tests with wheat (rye) flour were performed in 71 (95) symptomatic bakers. Determinations of flour-specific IgE as well as SPTs were performed in all subjects. Analyses included the calculation of sensitivity, specificity, positive (PPV) and negative predictive values (NPV) at different IgE concentrations and different wheal sizes, and receiver-operating characteristics (ROC) plots with the challenge result as gold standard.
Results: Thirty-seven bakers were positive in the challenge with wheat flour, while 63 were positive with rye flour. Depending on the flour-specific IgE concentrations (wheal size), PPV was 74–100% (74–100%) for wheat and 82–100% (91–100%) for rye flour, respectively. The minimal cut-off values with a PPV of 100% were 2.32 kU/l (5.0 mm) for wheat flour and 9.64 kU/l (4.5 mm) for rye flour. The shapes of the ROC plots were similar for wheat and rye flour.
Conclusion: High concentrations of flour-specific IgE and clear SPT results in symptomatic bakers are good predictors for a positive challenge test. Challenge tests with flours may be avoided in strongly sensitized bakers.
Baker’s asthma is one of the most frequent forms of occupational asthma. In 2005 49% of 571 confirmed cases of occupational asthma in Germany were caused by bakery-derived allergens (1). In general, for diagnosis of occupational asthma, especially within the scope of compensation claims, the specific challenge to suspected occupational agents is considered the gold standard (2, 3). Because there are relatively few specialized centers, and challenge tests are time-consuming, unpleasant for patients and may cause severe reactions, it was the aim of this study to investigate whether the concentration of flour-specific immunoglobulin E (IgE) or the results of skin prick test (SPT) can act as predictors for the outcome of the specific challenge tests.
While the general associations between the degree of bronchial responsiveness to allergens and the degree of sensitization as assessed by SPT and/or in vitro tests are well known, it was shown only for some allergens, especially food allergens, that the results of specific IgE determination or SPT are useful to predict the result of the challenge test (4, 5). In this connection little is known about occupational allergens.
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- Materials and methods
The results of this study demonstrate that both, flour-specific IgE and SPT with flours, can be used effectively for the prediction of the outcome of specific challenge tests with flours in symptomatic bakers. It was shown that all bakers with flour-specific IgE or wheal sizes in SPT with flours above a defined cut-off had a positive challenge test.
Even if the predictive values were not clearly higher with a combination of specific IgE and SPT as positive criterion than with the single criteria alone, we recommend both diagnostic tests for reasons of quality control. Our findings indicate that SPT provide little, although additional diagnostic information compared with specific IgE. While specific IgE determination is the more sensitive test, SPT reached at least in the case of rye flour a higher PPV using the minimal cut-off values.
As already indicated by the fact that NPV in no case reached a value higher than 82%, IgE concentrations and wheal sizes below the minimal cut-off values did not exclude a positive reaction in the challenge. Using the lowest cut-off values (0.35 kU/l; 2 mm), five bakers without specific IgE and 13 bakers with negative SPT to wheat, as well as eight bakers without specific IgE and 14 bakers with negative SPT to rye flour showed a positive challenge test. This could be either due to insufficient sensitivity of determination procedure (specific IgE test or SPT) or to irritative effects (7).
There are a number of reports about predictive values of specific IgE concentrations for the outcome of oral food challenges, predominantly performed in children. For egg, milk, peanut, and fish allergy, the diagnostic levels of specific IgE which were shown to predict clinical reactivity in a group of 196 children and adolescents with greater than 95% certainty were 6, 32, 15 and 20 kU/l, respectively (8). In another study group, neither with specific IgE (9) nor with SPT (4) a predictive probability of 95% for wheat and soy was reached.
Little is known about the relationship between specific IgE or SPT and the outcome of challenge tests with inhalation allergens. For cat allergy it could be shown in 49 asthmatic subjects that a probability of a positive bronchial challenge of ≥93% could be reached at a cut-off value of ≥17 kU/l. Using SPT results, a maximum PPV of 71% at an 8 mm cut-off could be reached (10). In a further study, cat-exposed persons with a history of asthma and a positive methacholine test were investigated. Positive challenge tests occurred in all 27 participants with cat-specific IgE, compared with 12 of 44 subjects with negative IgE result. This analysis revealed also that 38 of 41 subjects with positive SPT to cat, but only 10 of 39 with negative SPT had a positive challenge result (11).
The relationship between specific IgE concentration or SPT and the outcome of the specific challenge test has been rarely investigated with occupational allergens. Out of 27 dairy farmers with suspected occupational asthma due to bovine allergens, 11 farmers showed a positive result in the specific challenge test. The minimal cut-off value for bovine-specific IgE, at which a PPV of 100% could be obtained, was 5 kU/l. All farmers with higher IgE concentrations (n = 9) had positive challenge tests. However, PPV of SPT with bovine dander solution calculated for a cut-off value of ≥3 mm was only 46% (12).
A small number of studies found correlations between the degree of sensitization as assessed by SPT and the degree of the bronchial reactions during challenge tests with occupational allergens. The authors of a study including 24 bakers with positive SPT to different bakery-derived allergens and bronchial hyperresponsiveness described a formula showing the allergen concentration causing a 20% fall in FEV1 during inhalative challenge test (allergen PC20) as a function of skin sensitivity to allergen and methacholine PC20. A highly significant correlation (r = 0.92, P < 0.001) was found between the measured allergen PC20 and the predicted allergen PC20 calculated with this formula. A similar formula using specific IgE instead of skin sensitivity could not be established (13). Shirai et al. demonstrated also a correlation (r = 0.796, P < 0.05) among allergen PC20, methacholine PC20 and skin reactivity to epigallocatechine gallate, the causative agent of green tea-induced asthma (14).
In a study with 57 workers with occupational asthma due to platinum salts, an univariate correlation between skin reactivity and bronchial responsiveness due to platinum salts (r = 0.6, P < 0.0001) could be observed. However, responsiveness to platinum was not correlated with the degree of bronchial hyperresponsiveness (15).
Because of its multicentre design we could rely in our study on a rather large group of subjects and therefore we accepted heterogeneity in challenge test procedures. However, a PPV of 100% was reached at relatively low cut-off values: 2.32 kU/l for wheat and 9.64 kU/l for rye within specific IgE determination and ≥5.0 mm (wheat) and ≥4.5 mm (rye) within SPT, respectively. The difference between the specific IgE cut-off values for so similar allergens like wheat and rye flour could be explained by one single subject with higher concentration of rye flour-specific IgE, but a negative challenge. However, analysis of cut-off values has to be carried out for each allergen separately.
In conclusion, a high concentration of flour-specific IgE in the sera of bakers suffering from work-related symptoms is a good indicator for a positive inhalation challenge test with flours. Also clearly positive SPT results with flour extracts in symptomatic bakers indicate a great likelihood that a subject will show a positive reaction in specific challenge test. Thus, in such cases specific challenges may be dispensable. On the other hand, positive challenges with flours may occur also at low-grade sensitization, and in rare instances also without sensitization. Challenge tests with flours should be considered preferably in these subjects.