07_pepys -1- 3rd Jack Pepys Workshop BGFA Prevention of work-related asthma − Focus: Exposure reduction Rolf Merget [email protected] 3rd Jack Pepys Workshop

07_pepys -1-

3rd Jack Pepys Workshop

BGFA

Prevention of work-related asthma − Focus: Exposure

reduction

Rolf [email protected]


07_pepys -2-


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?

07_pepys -3-


BGFA

Absence of analytical methods?

07_pepys -4-


BGFA

New information about sample processing

Conclusion Addition of Tween-20 → 3-100fold increased allergen

recovery

Allergens were stable at -20oC for 4 months

Stabilizing proteins not required

07_pepys -5-


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)

07_pepys -6-


BGFApH 4 - 8

128

717

163220

36

3721

22159

5b5a

23

1a

3c

1b

4b2

3a4a 18

3430

6b

6a

243b

19

67

97.4

45

29

21

12.5

6.5

Sander et al. J Allergy Clin Immunol 2001;107:907-13

Two-dimensional IgE immunoblot of baker (a)

Old information about wheat allergens

07_pepys -7-


BGFA

13

21

1a1b

11 10 97.4

67

45

29

21

12.5

6.5

pH 4 - 8



Two-dimensional IgE immunoblot of baker (b)

07_pepys -8-


BGFApH 4 - 8

97.467

45

29

21

12.5

6.5

2315

16

8018

19

82

7578

83

32

31

39

79

84

87

92

91

77

8889

90

22

85

53

36

52

3721

4451

4250

4348

2054

45

13

65

41

38

46

4758

59

60

35

1

34

2

833

727

34

5772

1774

73

5655

66

6564

11

10 1 10 2

12

25

30

2614

9

1062

61

63

24

69 70 71

86 76

2829

40

49

6768

8193

98

50%30-40%20%10%



Frequencies of IgE-binding wheat proteins

07_pepys -9-


BGFA

New information about dose-response relationship

07_pepys -10-


BGFA

Estimated additional sensitization risk for wheat flour dustDutch 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

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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

07_pepys -12-


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.

07_pepys -13-


BGFA

Question 32

Exposure control (e.g. NRL, detergent enzymes)or nonsensitizing substitutes for primaryprevention?

07_pepys -14-


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

07_pepys -15-


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

07_pepys -16-


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/m3)

New information about exposure to enzymes

07_pepys -17-


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

07_pepys -18-


BGFA

Substitution/avoidance of allergens (summary by RM) Substance Substitution?

HMW

flours no

baking enzymes complete avoidance

detergent enzymes

no

laboratory animals

no

farm animals no

latex (almost) complete avoidance

LMW

Pt salts catalyst replacement by Pd or less halogenated Pt species

Pt salts refinery no

acid anhydrides replacement by other substances

isocyanatesreplacement by other substances; technical modifications (MicroemissionTM)?

07_pepys -19-


BGFA

Answer to question 32

(Almost) complete avoidance or substitutionmay be considered for some allergens.For most allergens exposure reduction willcontinue to be the only choice.

07_pepys -20-


BGFA

Question 98

Should industry label compounds as sensitizers? How can management be improved?

07_pepys -21-


BGFA

Old information on labelling of enzymes

Merget et al. Int Arch Allergy Immunol 2001;124:502-505

07_pepys -22-


BGFA

New information about rapid detection of enzymes

07_pepys -23-


BGFA

Principle of lateral flow immunoassay (LFIA)

Bogdanovic et al.J Allergy Clin Immunol 2006;118:1157-63

07_pepys -24-


BGFA

Good agreement between EIA and LFIA

Bogdanovic et al.J Allergy Clin Immunol 2006;118:1157-63

07_pepys -25-


BGFA


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.

07_pepys -26-


BGFA

Question 69

Exposure standards for isocyanates?Skin absorption of isocyanates?

07_pepys -27-


BGFA

New information about exposure in car body repair shops

Pronk et al. Ann Occup Hyg 2006;50:1-14

07_pepys -28-


BGFA

New information about exposure in car body repair shops

07_pepys -29-


BGFA


07_pepys -30-


BGFA

New information about isocyanate biomonitoring

07_pepys -31-


BGFA

New information about skin exposure to isocyanates

07_pepys -32-


BGFA

Beach et al. 2005Agency for Healthcare Research and Quality www.ahry.gov

New review about exposure cessation/reduction

Difference between FEV1 at follow-up and baseline by exposure status

07_pepys -33-


BGFA

New question

What are the consequences of exposure reduction (without complete exposure cessation) in sensitized subjects?

07_pepys -34-


BGFA

07_pepys -35-


BGFA



Difference between bronchial hyperresponsiveness at follow-up and baseline by exposure status

07_pepys -36-


BGFA



Difference between asthma medication at follow-up and baseline by exposure status

07_pepys -37-


BGFA

FeNO-results at the workplace and at homeN

O [

ppb]

200

150

100

50

0

350

300

250

1 2 3 4 5 6 7 8 9 10 11 12 13 14Week

Budesonide

Salbutamol

07_pepys -38-


BGFA

Peak flow variability

1 2 3 4 5 6 7 8 9 10 11 12 13 14Week

Budesonide

Salbutamol

PEF

[L/m

in]

350

300

250

150

500

450

400

200

Documents

07_pepys -1- 3rd Jack Pepys Workshop BGFA Prevention of work-related asthma − Focus: Exposure reduction Rolf Merget [email protected] 3rd Jack Pepys Workshop