Baker's Asthma

May 4, 2021
Baker's Asthma

Question
I continue to see Baker’s Asthma in Australia. Often, bakers are exposed to multiple allergens, not just wheat. Sometimes it is difficult to obtain details of all potential allergens. What is the minimum allergen work-up you recommend, both in skin testing, and allergen serology?

Answers
From the Editors: Ever since Bernardino Ramazzini (1633-1714), the father of occupational medicine, encouraged us to ask patients "what is your occupation", work-related causes of disease, and specifically of allergic disease, have formed an important niche in our clinical work. Baker's asthma, one of the first described occupational diseases, continues as a problem to this day. Here three experts provide up-to-date information on the allergy work-up for these patients"

By Dr. Alexander Diaz Rodriguez

Baker’s asthma is a frequent occupational allergic disease caused mainly by inhalation of cereal flour, particularly wheat flour. It is considered one of the most common types of occupational asthma. Although wheat is the most commonly involved cereal, others (rye, barley, rice, maize, and oats) also play a role in baker’s asthma. Other allergens like soy, various enzyme additives (amylase, cellulose), storage and house dust mites, yeast and molds have also been involved.

In the work up for the diagnosis, it is recommended to include skin prick test to: storage and house dust mites (Acarus siro, Tyrophagus putrescentiae, Lepidoglyphus destructor, Dermatophagoides pteronyssinus, Dermatophagoides farinae), cereal (wheat, rye, barley, maize, oats, rice), soy, enzymes (amylase, cellulose), yeast, egg and fungi. Skin prick testing is commonly used to identify allergen sensitizations because it is safe, specific and more sensitive than most in vitro assays.

Most occupational allergens are not standardized, thus, in many cases; patients are provisionally tested with noncommercially available, laboratory-made skin test extracts. It is also possible to use in vitro tests, such as the radioallergosorbent test (RAST) or enzyme-linked immunoassay (ELISA), for the detection of allergen-specific IgE antibodies; however, skin tests are usually more sensitive for early detection of sensitization than in vitro tests.

Despite skin tests and determination of specific IgE antibodies are useful to assess the sensitization to occupational allergens, the demonstration of the link between the specific sensitization and work-related changes in lung function is mandatory for the diagnosis of Baker’s Asthma. Other important issues are occupational history and exposure documentation.

References:

1. Moscato G, Pala G, Barnig C, De Blay F, Del Giacco SR, Folletti I, Heffler E, Maestrelli P, Pauli G, Perfetti L, Quirce S, Sastre J, Siracusa A, Walusiak-Skorupa J, Gerth van Wjik R. EAACI consensus statement for investigation of work-related asthma in non-specialized centres. Allergy 2012; 67: 491–501.
2. Salcedo G, Quirce S, Diaz-Perales A. Wheat Allergens Associated with Baker’s Asthma. J Investig Allergol Clin Immunol 2011; Vol. 21(2): 81-92.
3. Alvarez Castello M, Leyva Marquez Y, Castro Almarales RL, et al. Sensitization to storage mites, wheat and yeast allergens in Cuban bakers. World Allergy Organ Journal. Volume 6 (Suppl 1); 2013.
4. Quirce S. Sastre J. Disease Summaries. Diagnosis of Occupational Asthma. World Allergy Organization web page. 

Alexander Diaz Rodriguez, MD
Allergist, Professor of Immunology
Havana, Cuba
WAO Occupational Allergy Committee Member

By Prof Hae Sim Park

Within wheat flour allergen, house dust mite, storage mites and fungus (Aspergillus spp etc.) can be included and induce allergic responses.

Also atopy is a predisposing factor for baker’s asthma; I recommend doing skin test with common inhalant allergens in your environment to screen atopy status and to identify the causative allergens of underlying allergic diseases such as allergic rhinitis.

Also skin prick test or in vitro testing with wheat flour, house dust mite, storage mites and fungus should be checked.

Hae Sim Park, MD, PhD
Dept of Allergy and Clinical Immunology
Ajou University School of Medicine
Suwon, South Korea

By Prof Brett J Green

Occupational exposure to cereal flour and associated additives has been identified as determinants of allergic sensitization and work-related respiratory symptoms (baker’s asthma) among bakery workers [1]. During the last several decades, research has focused on sensitization to wheat (Triticum aestivum) due to the prevalence of this flour in bakery operations [2, 3]. Rye (Secale cereale), barley (Hordeum vulgare), buckwheat (Fagopyrum esculentum), and cereal malt flours are also utilized in bakeries and have been implicated in cases of baker’s asthma [1, 4-6]. To date, the role of other commercially available cereals such as maize, rice, sorghum, triticale, millet, and oats as determinants of occupational sensitization among bakery workers requires further clinical evaluation.

More than 30 cereal allergens have been identified, characterized, and submitted to the International Union of Immunological Societies Allergen Nomenclature Committee (http://www.allergen.org). The most prominent allergens reported in cases of baker’s asthma belong to the group of α-amylase/trypsin inhibitor family [7]. These proteins are common in wheat, rye, and barley [4, 7-9]. In addition to α-amylase/trypsin inhibitors, other proteins have also been identified to bind worker serum IgE and include thioredoxin, peroxidase, lipid transfer protein, serine protease inhibitor, thaumatin-like protein, gliadins, and glycerinaldehyde-3-phosphate dehydrogenase [4, 7, 10, 11]. To date, Phadia ImmunoCap and microarray technologies such as Phadia’s Immuno Solid-phase Allergen Chip (ISAC) have provided new approaches to measure serum specific IgE to individual recombinant and naturally purified cereal and bakery additive allergens [12, 13]. A list of allergens that can be evaluated using these technologies can be referred to in Olivieri et al. [12] and Sander et al. [13].

In addition to cereal flours, other additives such as enzyme-based dough improvers have been identified as respiratory sensitizers in bakeries [1, 6, 14]. Fungal α-amylase derived from Aspergillus oryzae is an enzyme that breaks down starch into simple sugars for yeast during bread proofing [1]. Workers in large scale bakeries that handle bread improvers such as α-amylase, are susceptible to occupational asthma, rhinitis, and other allergic symptoms [15]. In addition to fungal α-amylase, xylanases derived from Aspergillus and Trichoderma species can also be present as an additive to break down high molecular xylans in baking flour to make dough rise faster [16-18]. Other enzymes have also been reported as sensitizers in commercial bakery operations and include cellulase [17, 19], β-xylosidase [20], and glucoamylase [21]. Bacterial enzymes have also been reported and include amylase and amyloglucosidase [22].

Soy (Glycine max) is another common additive used to bleach dough carotinoids [23]. Sensitization to soy has been identified in bakery workers [6, 24] and workers serum IgE has been shown to bind high molecular weight allergens in soybean flour but not Gly m 1 hull allergens associated with community asthma epidemics [23]. Soybean allergens include trypsin inhibitor, lipoxygenase [25] and soybean lecithin [26]. Other high molecular weight protein additives that have been associated with occupational sensitization include egg white [27, 28], egg yolk [1], sesame seed, milk, cacao, chocolate, hazelnut, and almond [1]. Sensitization to insect contaminants including grain weevils [29], storage mites [1], flour beetles [30] and excreta [31] have also been identified among bakery workers. To date, the role of fermentation yeasts (Saccharomyces cerevisiae) and other microbial contaminants such as Alternaria and Aspergillus species requires further clinical evaluation [32-34].

Bakery workers at risk of sensitization include those that are atopic and have job categories that weigh, sieve, and mix ingredients such as dough makers, bread formers, and bread bakers [1, 3, 35-37]. Allergen workups should include wheat, rye, and barley flour extracts as well as a selection of enzyme and protein additives such as fungal α-amylase and soy. The clinician could consider testing additional products used in the workers’ specific environment or job category. For example, if the worker suspects exposure to contaminants, one could consider testing a panel of insect (dust and storage mite) and fungal extracts. To date, skin testing and allergen serology extracts are commercially available for many of the additives that are associated with bakery operations. For a more detailed review of important allergens encountered in bakery occupations please refer Houber et al. [1].

The findings and the conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.

References:

1. Houba R, Doekes G, Heederik D, Occupational respiratory allergy in bakery workers: a review of the literature. Am J Ind Med 1998;34: 529-46.
2.  Sander I, Flagge A, Merget R, Halder TM, Meyer HE, Baur X, Identification of wheat flour allergens by means of 2-dimensional immunoblotting. J Allergy Clin Immunol 2001;107: 907-13.
3. Smith TA, Smith PW, Respiratory symptoms and sensitization in bread and cake bakers. Occup Med (Lond) 1998;48: 321-8.
4. Tatham AS, Shewry PR, Allergens to wheat and related cereals. Clin Exp Allergy 2008;38: 1712-26.
5. Valdivieso R, Moneo I, Pola J, Munoz T, Zapata C, Hinojosa M, Losada E, Occupational asthma and contact urticaria caused by buckwheat flour. Ann Allergy 1989;63: 149-52.
6. Baur X, Degens PO, Sander I, Baker’s asthma: still among the most frequent occupational respiratory disorders. J Allergy Clin Immunol 1998;102: 984-97.
7. Salcedo G, Quirce S, Diaz-Perales A, Wheat allergens associated with Baker’s asthma. J Investig Allergol Clin Immunol 2011;21: 81-92; quiz 94.
8. Letran A, Palacin A, Barranco P, Salcedo G, Pascual C, Quirce S, Rye flour allergens: an emerging role in baker’s asthma. Am J Ind Med 2008;51: 324-8.
9. Franken J, Stephan U, Neuber K, Bujanowski-Weber J, Ulmer WT, Konig W, Characterization of allergenic components of rye and wheat flour (Secale, Triticum vulgaris) by western blot with sera of bakers: their effects on CD23 expression. Int Arch Allergy Appl Immunol 1991;96: 76-83.
10. Weichel M, Glaser AG, Ballmer-Weber BK, Schmid-Grendelmeier P, Crameri R, Wheat and maize thioredoxins: a novel cross-reactive cereal allergen family related to baker’s asthma. J Allergy Clin Immunol 2006;117: 676-81.
11. Bittner C, Grassau B, Frenzel K, Baur X, Identification of wheat gliadins as an allergen family related to baker’s asthma. J Allergy Clin Immunol 2008;121: 744-9.
12. Olivieri M, Biscardo CA, Palazzo P, Pahr S, Malerba G, Ferrara R, Zennaro D, Zanoni G, Xumerle L, Valenta R, Mari A, Wheat IgE profiling and wheat IgE levels in bakers with allergic occupational phenotypes. Occup Environ Med 2013;70: 617-22.
13. Sander I, Rozynek P, Rihs HP, van Kampen V, Chew FT, Lee WS, Kotschy-Lang N, Merget R, Bruning T, Raulf-Heimsoth M, Multiple wheat flour allergens and cross-reactive carbohydrate determinants bind IgE in baker’s asthma. Allergy 2011;66: 1208-15.
14. Harris-Roberts J, Robinson E, Waterhouse JC, Billings CG, Proctor AR, Stocks-Greaves M, Rahman S, Evans G, Garrod A, Curran AD, Fishwick D, Sensitization to wheat flour and enzymes and associated respiratory symptoms in British bakers. Am J Ind Med 2009;52: 133-40.
15. Sander I, Raulf-Heimsoth M, Van Kampen V, Baur X, Is fungal alpha-amylase in bread an allergen? Clin Exp Allergy 2000;30: 560-5.
16. Baur X, Sander I, Posch A, Raulf-Heimsoth M, Baker’s asthma due to the enzyme xylanase—a new occupational allergen. Clin Exp Allergy 1998;28: 1591-3.
17. Elms J, Fishwick D, Walker J, Rawbone R, Jeffrey P, Griffin P, Gibson M, Curran AD, Prevalence of sensitisation to cellulase and xylanase in bakery workers. Occup Environ Med 2003;60: 802-4.
18. Merget R, Sander I, Raulf-Heimsoth M, Baur X, Baker’s asthma due to xylanase and cellulase without sensitization to alpha-amylase and only weak sensitization to flour. Int Arch Allergy Immunol 2001;124: 502-5.
19. Quirce S, Cuevas M, Diez-Gomez M, Fernandez-Rivas M, Hinojosa M, Gonzalez R, Losada E, Respiratory allergy to Aspergillus-derived enzymes in bakers’ asthma. J Allergy Clin Immunol 1992;90: 970-8.
20. Sander I, Raulf-Heimsoth M, Siethoff C, Lohaus C, Meyer HE, Baur X, Allergy to Aspergillus-derived enzymes in the baking industry: identification of beta-xylosidase from Aspergillus niger as a new allergen (Asp n 14). J Allergy Clin Immunol 1998;102: 256-64.
21. Quirce S, Fernandez-Nieto M, Bartolome B, Bombin C, Cuevas M, Sastre J, Glucoamylase: another fungal enzyme associated with baker’s asthma. Ann Allergy Asthma Immunol 2002;89: 197-202.
22. Elms J, Robinson E, Mason H, Iqbal S, Garrod A, Evans GS, Enzyme exposure in the British baking industry. Ann Occup Hyg 2006;50: 379-84.
23. Quirce S, Polo F, Figueredo E, Gonzalez R, Sastre J, Occupational asthma caused by soybean flour in bakers—differences with soybean-induced epidemic asthma. Clin Exp Allergy 2000;30: 839-46.
24. Baur X, Sauer W, Weiss W, Baking additives as new allergens in baker’s asthma. Respiration 1988;54: 70-2.
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27. Escudero C, Quirce S, Fernandez-Nieto M, Miguel J, Cuesta J, Sastre J, Egg white proteins as inhalant allergens associated with baker’s asthma. Allergy 2003;58: 616-20.
28. DeMasi JM, A unique cause of asthma in a baker. J Asthma 2006;43: 333-4.
29. Frankland AW, Lunn JA, Asthma caused by the grain weevil. Br J Ind Med 1965;22: 157-9.
30. Schultze-Werninghaus G, Zachgo W, Rotermund H, Wiewrodt R, Merget R, Wahl R, Burow G, zur Strassen R, Tribolium confusum (confused flour beetle, rice flour beetle)—an occupational allergen in bakers: demonstration of IgE antibodies. Int Arch Allergy Appl Immunol 1991;94: 371-2.
31. Popescu IG, Ulmeanu V, Murariu D, Atopic and non-atopic sensitivity in a large bakery. Allergol Immunopathol (Madr) 1981;9: 307-12.
32. Baldo BA, Baker RS, Inhalant allergies to fungi: reactions to bakers’ yeast (Saccharomyces cerevisiae) and identification of bakers’ yeast enolase as an important allergen. Int Arch Allergy Appl Immunol 1988;86: 201-8.
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35. Baatjies R, Meijster T, Lopata A, Sander I, Raulf-Heimsoth M, Heederik D, Jeebhay M, Exposure to flour dust in South African supermarket bakeries: modeling of baseline measurements of an intervention study. Ann Occup Hyg 2010;54: 309-18.
36. Prichard MG, Ryan G, Musk AW, Wheat flour sensitisation and airways disease in urban bakers. Br J Ind Med 1984;41: 450-4.
37. Elms J, Beckett P, Griffin P, Evans P, Sams C, Roff M, Curran AD, Job categories and their effect on exposure to fungal alpha-amylase and inhalable dust in the U.K. baking industry. AIHA J (Fairfax, Va) 2003;64: 467-71.

Brett J. Green, PhD
Team Lead, Allergen Characterization
Allergy and Clinical Immunology Branch
Health Effects Laboratory Division
National Institute for Occupational Safety and Health
Centers for Disease Control and Prevention
Morgantown, West Virginia, USA

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