1. 07_pepys -1- 3rd Jack Pepys Workshop BGFA Prevention of work-related asthma − Focus: Exposure reduction Rolf Merget merget@bgfa.de 3rd Jack Pepys Workshop

2. 07_pepys -2- 3rd Jack Pepys Workshop BGFA Questions 68 and 73 No. 68 Allergens in wheat flour? Thresholds for sensitization of key occupational allergens? No. 73 Relationships between exposure and sensitization for specific occupational agents, role of atopy?

3. 07_pepys -3- 3rd Jack Pepys Workshop BGFA Absence of analytical methods?

4. 07_pepys -4- 3rd Jack Pepys Workshop BGFA New information about sample processing Conclusion  Addition of Tween-20 → 3-100fold increased allergen recovery  Allergens were stable at -20 o C for 4 months  Stabilizing proteins not required

5. 07_pepys -5- 3rd Jack Pepys Workshop BGFA New information about analytical methods Conclusion  Rabbit IgG inhibition assay recommended for routine wheat allergen measurements.  Sandwich EIA more sensitive (e.g. for short task-related measurements)

6. 07_pepys -6- 3rd Jack Pepys Workshop BGFA Sander et al. J Allergy Clin Immunol 2001;107:907-13 Two-dimensional IgE immunoblot of baker (a) Old information about wheat allergens

7. 07_pepys -7- 3rd Jack Pepys Workshop BGFA 13 21 1a 1b 11 10 97.4 67 45 29 21 12.5 6.5 pH 4 - 8 Sander et al. J Allergy Clin Immunol 2001;107:907-13 Old information about wheat allergens Two-dimensional IgE immunoblot of baker (b)

8. 07_pepys -8- 3rd Jack Pepys Workshop BGFA pH 4 - 8 97.4 67 45 29 21 12.5 6.5 50% 30- 40% 20% 10% Sander et al. J Allergy Clin Immunol 2001;107:907-13 Old information about wheat allergens Frequencies of IgE-binding wheat proteins

9. 07_pepys -9- 3rd Jack Pepys Workshop BGFA New information about dose-response relationship

10. 07_pepys -10- 3rd Jack Pepys Workshop BGFA Estimated additional sensitization risk for wheat flour dust Dutch Expert Committee on Occupational Standards (DECOS)  0.1 % for an occupational exposure to 0.012 mg/m³ inhalable dust  1.0% for an occupational exposure to 0.12 mg/m³ inhalable dust  10.0 % for an occupational exposure to 1.2 mg/m³ inhalable dust as a time-weighted average concentration under normal working conditions of eight hours a day and five days a week, during a life-long employment exposure

11. 07_pepys -11- 3rd Jack Pepys Workshop BGFA …….The available literature does not demonstrate a thrustworthy threshold for any of the flour dust-induced effects……. Provisional recommendation of Scientific Committee for Occupational Exposure Limits (SCOEL) April 2007

12. 07_pepys -12- 3rd Jack Pepys Workshop BGFA Answer to questions 68/73  Wheat flour contains a great number of single allergens  Atopy is a strong risk factor for wheat allergy  Despite progress in exposure assessment thresholds possibly cannot be determined.

13. 07_pepys -13- 3rd Jack Pepys Workshop BGFA Question 32 Exposure control (e.g. NRL, detergent enzymes) or nonsensitizing substitutes for primary prevention?

14. 07_pepys -14- 3rd Jack Pepys Workshop BGFA Two reviews on NRL allergy in healthcare workers  Bousquet et al. JACI 2006;118:447-54 ……Although powder-free gloves allow a reduction in the level of airborne NRL allergens and glove-related symptoms, the lack of appropriate study does not allow any conclusions to be reached on powder-free gloves……  La Montagne et al. Occup Environ Med 2006; 63:359-364 …….Substitution of powdered latex gloves with low protein powder-free NRL gloves or latex-free gloves greatly reduces NRL aeroallergens, NRL sensitization and NRL asthma among healthcare workers (sign level 2+)……… New information about the prevention of latex allergy

15. 07_pepys -15- 3rd Jack Pepys Workshop BGFA Since 2004 2 longitudinal cohort studies (together >1000 person-years) without new sensitizations  Jones et al. Ann occup Hyg 2004;48:455-457  Filon et al. Occup Environ Med 2006;63:121-125 New information about the prevention of latex allergy

16. 07_pepys -16- 3rd Jack Pepys Workshop BGFA Conclusion  195 personal air samples in 55 craft bakeries:  Frequencies of measurable enzyme exposures  Amyloglucosidase 9%  Fungal alpha-amylase 6%  Bacterial alpha-amylase 7%  Similar enzyme air concentrations (about 5-10 ng/m 3 ) New information about exposure to enzymes

17. 07_pepys -17- 3rd Jack Pepys Workshop BGFA Car body repair: …. but none of the managers reported even considering switching to water-based paints until required to do so…. Sparer et al. SPRAY-study. J Occup Environ Hyg 2004;1:570-81 New information about substitution of isocyanates

18. 07_pepys -18- 3rd Jack Pepys Workshop BGFA Substitution/avoidance of allergens (summary by RM) Substance Substitution? HMW floursno baking enzymescomplete avoidance detergent enzymesno laboratory animalsno farm animalsno latex(almost) complete avoidance LMW Pt salts catalystreplacement by Pd or less halogenated Pt species Pt salts refineryno acid anhydridesreplacement by other substances isocyanates replacement by other substances; technical modifications (Microemission TM )?

19. 07_pepys -19- 3rd Jack Pepys Workshop BGFA Answer to question 32 (Almost) complete avoidance or substitution may be considered for some allergens. For most allergens exposure reduction will continue to be the only choice.

20. 07_pepys -20- 3rd Jack Pepys Workshop BGFA Question 98 Should industry label compounds as sensitizers? How can management be improved?

21. 07_pepys -21- 3rd Jack Pepys Workshop BGFA Old information on labelling of enzymes Merget et al. Int Arch Allergy Immunol 2001;124:502-505

22. 07_pepys -22- 3rd Jack Pepys Workshop BGFA New information about rapid detection of enzymes

23. 07_pepys -23- 3rd Jack Pepys Workshop BGFA Principle of lateral flow immunoassay (LFIA) Bogdanovic et al. J Allergy Clin Immunol 2006;118:1157-63

24. 07_pepys -24- 3rd Jack Pepys Workshop BGFA Good agreement between EIA and LFIA Bogdanovic et al. J Allergy Clin Immunol 2006;118:1157-63

25. 07_pepys -25- 3rd Jack Pepys Workshop BGFA Answer to question 98 It should be mandatory for industry to label sensitizing substances (more precisely). Management can be improved by quick and simple tests for the detection of allergens.

26. 07_pepys -26- 3rd Jack Pepys Workshop BGFA Question 69 Exposure standards for isocyanates? Skin absorption of isocyanates?

27. 07_pepys -27- 3rd Jack Pepys Workshop BGFA New information about exposure in car body repair shops Pronk et al. Ann Occup Hyg 2006;50:1-14

28. 07_pepys -28- 3rd Jack Pepys Workshop BGFA New information about exposure in car body repair shops

29. 07_pepys -29- 3rd Jack Pepys Workshop BGFA Answer to question 69

30. 07_pepys -30- 3rd Jack Pepys Workshop BGFA New information about isocyanate biomonitoring

31. 07_pepys -31- 3rd Jack Pepys Workshop BGFA New information about skin exposure to isocyanates

32. 07_pepys -32- 3rd Jack Pepys Workshop BGFA Beach et al. 2005 Agency for Healthcare Research and Quality www.ahry.gov New review about exposure cessation/reduction Difference between FEV 1 at follow-up and baseline by exposure status

33. 07_pepys -33- 3rd Jack Pepys Workshop BGFA New question What are the consequences of exposure reduction (without complete exposure cessation) in sensitized subjects?

34. 07_pepys -34- 3rd Jack Pepys Workshop BGFA

35. 07_pepys -35- 3rd Jack Pepys Workshop BGFA Beach et al. 2005 Agency for Healthcare Research and Quality www.ahry.gov New review about exposure cessation/reduction Difference between bronchial hyperresponsiveness at follow-up and baseline by exposure status

36. 07_pepys -36- 3rd Jack Pepys Workshop BGFA Beach et al. 2005 Agency for Healthcare Research and Quality www.ahry.gov New review about exposure cessation/reduction Difference between asthma medication at follow-up and baseline by exposure status

37. 07_pepys -37- 3rd Jack Pepys Workshop BGFA FeNO-results at the workplace and at home NO [ppb] 200 150 100 50 0 350 300 250 1234567891011121314 Week Budesonide Salbutamol

38. 07_pepys -38- 3rd Jack Pepys Workshop BGFA Peak flow variability 1234567891011121314 Week Budesonide Salbutamol PEF [L/min] 350 300 250 150 500 450 400 200