Skip to main content
Occupational and Environmental Medicine logoLink to Occupational and Environmental Medicine
. 1999 Nov;56(11):735–741. doi: 10.1136/oem.56.11.735

Exposure assessment of high molecular weight sensitisers: contribution to occupational epidemiology and disease prevention

D Heederik, G Doekes, M J Nieuwenhuijsen
PMCID: PMC1757674  PMID: 10658558

Abstract

An important group of sensitising agents are so called high molecular weight sensitisers--proteins or glycoproteins with molecular weights in the 5-70 kDa range that can provoke a specific IgE response in workers exposed to these agents. Exposure to high molecular weight sensitisers could only be evaluated indirectly in the recent past. Few measurement techniques existed that made it possible to measure the allergens directly. As a result, few studies focused on establishing exposure- response relations, and exposure standards have not been established for high molecular weight sensitisers, or those that have are of doubtful scientific basis. Recent use of immunoassays changed this perspective dramatically. Antibodies used in the assays can originate from human serum (sensitized workers), serum from sensitised animals (rabbits producing polyclonal antibodies), or animal derived cell cultures producing monoclonal antibodies. Although few comparative studies exist, the available evidence suggests that although the correlation of allergen concentrations obtained with different assays is good, large systematic differences occur. The use of conversion factors to make data from previously performed allergen measurements comparable or exchangeable is limited and thorough standardization of assays is preferred. Validation and comparison of different assays by comparisons between laboratories seem important issues that have not received the attention needed. Epidemiological studies in several industries that used immunoassay for the exposure characterisation have shown that risk of sensitisation increases with increasing exposure to allergens. Several studies have also shown that clear differences in potency seem to exist. Sensitisation to rat urinary allergens and fungal alpha-amylase occurred in the pg/m3 and ng/m3 range. The main research questions of the near future have to focus on the prevention of occupational sensitisation. Standard setting seems possible for some allergenson the basis of the available scientific evidence for the existence of exposure response relations. However, assays for characterising exposure to allergens have to be rigorously standardised before they can be used under field conditions.

 

Full Text

The Full Text of this article is available as a PDF (111.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aalberse R. C., Van Milligen F., Tan K. Y., Stapel S. O. Allergen-specific IgG4 in atopic disease. Allergy. 1993 Nov;48(8):559–569. doi: 10.1111/j.1398-9995.1993.tb00749.x. [DOI] [PubMed] [Google Scholar]
  2. Baur X., Chen Z., Liebers V. Exposure-response relationships of occupational inhalative allergens. Clin Exp Allergy. 1998 May;28(5):537–544. doi: 10.1046/j.1365-2222.1998.00276.x. [DOI] [PubMed] [Google Scholar]
  3. Baur X., Chen Z., Sander I. Isolation and denomination of an important allergen in baking additives: alpha-amylase from Aspergillus oryzae (Asp o II). Clin Exp Allergy. 1994 May;24(5):465–470. doi: 10.1111/j.1365-2222.1994.tb00935.x. [DOI] [PubMed] [Google Scholar]
  4. Baur X., Czuppon A. B., Sander I. Heating inactivates the enzymatic activity and partially inactivates the allergenic activity of Asp o 2. Clin Exp Allergy. 1996 Feb;26(2):232–234. doi: 10.1111/j.1365-2222.1996.tb00084.x. [DOI] [PubMed] [Google Scholar]
  5. Blands J., Diamant B., Kallós P., Kallós-Deffner L., Lowenstein H. Flour allergy in bakers. I. Identification of allergenic fractions in flour and comparison of diagnostic methods. Int Arch Allergy Appl Immunol. 1976;52(1-4):392–406. [PubMed] [Google Scholar]
  6. Burney P. G. Strategy for asthma. BMJ. 1991 Sep 7;303(6802):571–573. doi: 10.1136/bmj.303.6802.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Burstyn I., Teschke K., Bartlett K., Kennedy S. M. Determinants of wheat antigen and fungal alpha-amylase exposure in bakeries. Am Ind Hyg Assoc J. 1998 May;59(5):313–320. doi: 10.1080/15428119891010569. [DOI] [PubMed] [Google Scholar]
  8. Burstyn I., Teschke K., Kennedy S. M. Exposure levels and determinants of inhalable dust exposure in bakeries. Ann Occup Hyg. 1997 Dec;41(6):609–624. doi: 10.1016/S0003-4878(97)00031-8. [DOI] [PubMed] [Google Scholar]
  9. Burstyn I., Teschke K. Studying the determinants of exposure: a review of methods. Am Ind Hyg Assoc J. 1999 Jan-Feb;60(1):57–72. doi: 10.1080/00028899908984423. [DOI] [PubMed] [Google Scholar]
  10. Cullinan P., Lowson D., Nieuwenhuijsen M. J., Gordon S., Tee R. D., Venables K. M., McDonald J. C., Newman Taylor A. J. Work related symptoms, sensitisation, and estimated exposure in workers not previously exposed to laboratory rats. Occup Environ Med. 1994 Sep;51(9):589–592. doi: 10.1136/oem.51.9.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cullinan P., Lowson D., Nieuwenhuijsen M. J., Sandiford C., Tee R. D., Venables K. M., McDonald J. C., Newman Taylor A. J. Work related symptoms, sensitisation, and estimated exposure in workers not previously exposed to flour. Occup Environ Med. 1994 Sep;51(9):579–583. doi: 10.1136/oem.51.9.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Doekes G., Kamminga N., Helwegen L., Heederik D. Occupational IgE sensitisation to phytase, a phosphatase derived from Aspergillus niger. Occup Environ Med. 1999 Jul;56(7):454–459. doi: 10.1136/oem.56.7.454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Heederik D., Venables K. M., Malmberg P., Hollander A., Karlsson A. S., Renström A., Doekes G., Nieuwenhijsen M., Gordon S. Exposure-response relationships for work-related sensitization in workers exposed to rat urinary allergens: results from a pooled study. J Allergy Clin Immunol. 1999 Apr;103(4):678–684. doi: 10.1016/s0091-6749(99)70242-3. [DOI] [PubMed] [Google Scholar]
  14. Hollander A., Gordon S., Renström A., Thissen J., Doekes G., Larsson P. H., Malmberg P., Venables K. M., Heederik D. Comparison of methods to assess airborne rat and mouse allergen levels. I. Analysis of air samples. Allergy. 1999 Feb;54(2):142–149. doi: 10.1034/j.1398-9995.1999.00630.x. [DOI] [PubMed] [Google Scholar]
  15. Hollander A., Heederik D., Doekes G., Kromhout H. Determinants of airborne rat and mouse urinary allergen exposure. Scand J Work Environ Health. 1998 Jun;24(3):228–235. doi: 10.5271/sjweh.303. [DOI] [PubMed] [Google Scholar]
  16. Hollander A., Heederik D., Doekes G. Respiratory allergy to rats: exposure-response relationships in laboratory animal workers. Am J Respir Crit Care Med. 1997 Feb;155(2):562–567. doi: 10.1164/ajrccm.155.2.9032195. [DOI] [PubMed] [Google Scholar]
  17. Hollander A., Heederik D., Kauffman H. Acute respiratory effects in the potato processing industry due to a bioaerosol exposure. Occup Environ Med. 1994 Feb;51(2):73–78. doi: 10.1136/oem.51.2.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Houba R., Heederik D. J., Doekes G., van Run P. E. Exposure-sensitization relationship for alpha-amylase allergens in the baking industry. Am J Respir Crit Care Med. 1996 Jul;154(1):130–136. doi: 10.1164/ajrccm.154.1.8680668. [DOI] [PubMed] [Google Scholar]
  19. Houba R., Heederik D., Doekes G. Wheat sensitization and work-related symptoms in the baking industry are preventable. An epidemiologic study. Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1499–1503. doi: 10.1164/ajrccm.158.5.9803055. [DOI] [PubMed] [Google Scholar]
  20. Houba R., Van Run P., Heederik D., Doekes G. Wheat antigen exposure assessment for epidemiological studies in bakeries using personal dust sampling and inhibition ELISA. Clin Exp Allergy. 1996 Feb;26(2):154–163. doi: 10.1111/j.1365-2222.1996.tb00074.x. [DOI] [PubMed] [Google Scholar]
  21. Houba R., van Run P., Doekes G., Heederik D., Spithoven J. Airborne levels of alpha-amylase allergens in bakeries. J Allergy Clin Immunol. 1997 Mar;99(3):286–292. doi: 10.1016/s0091-6749(97)70044-7. [DOI] [PubMed] [Google Scholar]
  22. Jensen J., Poulsen L. K., Mygind K., Weeke E. R., Weeke B. Immunochemical estimations of allergenic activities from outdoor aero-allergens, collected by a high-volume air sampler. Allergy. 1989 Jan;44(1):52–59. doi: 10.1111/j.1398-9995.1989.tb00446.x. [DOI] [PubMed] [Google Scholar]
  23. Kruize H., Post W., Heederik D., Martens B., Hollander A., van der Beek E. Respiratory allergy in laboratory animal workers: a retrospective cohort study using pre-employment screening data. Occup Environ Med. 1997 Nov;54(11):830–835. doi: 10.1136/oem.54.11.830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Musk A. W., Venables K. M., Crook B., Nunn A. J., Hawkins R., Crook G. D., Graneek B. J., Tee R. D., Farrer N., Johnson D. A. Respiratory symptoms, lung function, and sensitisation to flour in a British bakery. Br J Ind Med. 1989 Sep;46(9):636–642. doi: 10.1136/oem.46.9.636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nieuwenhuijsen M. J., Gordon S., Harris J. M., Tee R. D., Venables K. M., Newman Taylor A. J. Variation in rat urinary aeroallergen levels explained by differences in site, task and exposure group. Ann Occup Hyg. 1995 Dec;39(6):819–825. doi: 10.1016/0003-4878(95)00042-9. [DOI] [PubMed] [Google Scholar]
  26. Nieuwenhuijsen M. J., Gordon S., Tee R. D., Venables K. M., McDonald J. C., Newman Taylor A. J. Exposure to dust and rat urinary aeroallergens in research establishments. Occup Environ Med. 1994 Sep;51(9):593–596. doi: 10.1136/oem.51.9.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nieuwenhuijsen M. J., Heederik D., Doekes G., Venables K. M., Newman Taylor A. J. Exposure-response relations of alpha-amylase sensitisation in British bakeries and flour mills. Occup Environ Med. 1999 Mar;56(3):197–201. doi: 10.1136/oem.56.3.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nieuwenhuijsen M. J., Lowson D., Venables K. M., Newman Taylor A. J. Correlation between different measures of exposure in a cohort of bakery workers and flour millers. Ann Occup Hyg. 1995 Jun;39(3):291–298. [PubMed] [Google Scholar]
  29. Nieuwenhuijsen M. J., Sandiford C. P., Lowson D., Tee R. D., Venables K. M., McDonald J. C., Newman Taylor A. J. Dust and flour aeroallergen exposure in flour mills and bakeries. Occup Environ Med. 1994 Sep;51(9):584–588. doi: 10.1136/oem.51.9.584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Renström A., Gordon S., Hollander A., Spithoven J., Larsson P. H., Venables K. M., Heederik D., Malmberg P. Comparison of methods to assess airborne rat and mouse allergen levels. II. Factors influencing antigen detection. Allergy. 1999 Feb;54(2):150–157. doi: 10.1034/j.1398-9995.1999.00631.x. [DOI] [PubMed] [Google Scholar]
  31. Renström A., Gordon S., Larsson P. H., Tee R. D., Newman Taylor A. J., Malmberg P. Comparison of a radioallergosorbent (RAST) inhibition method and a monoclonal enzyme linked immunosorbent assay (ELISA) for aeroallergen measurement. Clin Exp Allergy. 1997 Nov;27(11):1314–1321. [PubMed] [Google Scholar]
  32. Renström A., Larsson P. H., Malmberg P., Bayard C. A new amplified monoclonal rat allergen assay used for evaluation of ventilation improvements in animal rooms. J Allergy Clin Immunol. 1997 Nov;100(5):649–655. doi: 10.1016/s0091-6749(97)70169-6. [DOI] [PubMed] [Google Scholar]
  33. Sander I., Neuhaus-Schröder C., Raulf-Heimsoth M., Doekes G., Heederik D., Baur X. Quantifizierung der inhalativen Belastung mit alpha-Amylase in zwei Bäckereien. Pneumologie. 1998 Aug;52(8):440–443. [PubMed] [Google Scholar]
  34. Sandiford C. P., Nieuwenhuijsen M. J., Tee R. D., Taylor A. J. Determination of the size of airborne flour particles. Allergy. 1994 Dec;49(10):891–893. doi: 10.1111/j.1398-9995.1994.tb00795.x. [DOI] [PubMed] [Google Scholar]
  35. Sandiford C. P., Nieuwenhuijsen M. J., Tee R. D., Taylor A. J. Measurement of airborne proteins involved in Bakers' asthma. Clin Exp Allergy. 1994 May;24(5):450–456. doi: 10.1111/j.1365-2222.1994.tb00933.x. [DOI] [PubMed] [Google Scholar]
  36. Sandiford C. P., Tee R. D., Newman-Taylor A. J. Identification of crossreacting wheat, rye, barley and soya flour allergens using sera from individuals with wheat-induced asthma. Clin Exp Allergy. 1995 Apr;25(4):340–349. doi: 10.1111/j.1365-2222.1995.tb01052.x. [DOI] [PubMed] [Google Scholar]
  37. Smith T. A., Smith P. W. Respiratory symptoms and sensitization in bread and cake bakers. Occup Med (Lond) 1998 Jul;48(5):321–328. doi: 10.1093/occmed/48.5.321. [DOI] [PubMed] [Google Scholar]
  38. Virtanen T., Eskelinen T., Husman K., Mäntyjärvi R. Long- and short-term variability of airborne bovine epithelial antigen concentrations in cowsheds. Int Arch Allergy Immunol. 1992;98(3):252–255. doi: 10.1159/000236193. [DOI] [PubMed] [Google Scholar]
  39. Virtanen T., Kalliokoski P., Vilhunen P., Taivainen A., Mäntyjärvi R. Concentrations of specific dusts in swineries and the humoral response of swinery workers. Allergy. 1990 Jul;45(5):354–362. doi: 10.1111/j.1398-9995.1990.tb00511.x. [DOI] [PubMed] [Google Scholar]
  40. Zock J. P., Doekes G., Heederik D., Van Zuylen M., Wielaard P. Airborne dust antigen exposure and specific IgG response in the potato processing industry. Clin Exp Allergy. 1996 May;26(5):542–548. [PubMed] [Google Scholar]

Articles from Occupational and Environmental Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES