Occupational asthma Presented by Theerapan Songnuy, MD. On May 10, 2013

1. Theerapan Songnuy M.D.

2. Overview
 Definition
 Etiology
 Diagnosis
 Conclusion

3. Occupational Asthma ( OA)
Jean Luc Malo & Moira Chan-Yeung. Occupational Asthma. In Middleton 7th edition. 939-953.
-A type of asthma caused by the workplace
-Classified into 2 types:
1. OA with a latency period need to get
sensitized to an agent in the workplace
2. OA without a latency period, occur after
accidentally inhale at work
-Of the first type, mostly caused by high ( protein)
molecular-weight agents
-High-molecular weight agent induced by IgE-
mediated mechanism
- LMW agents act as hapten

4. Jean Luc Malo & Moira Chan-Yeung. Occupational Asthma. In Middleton 7th edition.
939-953.

5. l
Jean Luc Malo & Moira Chan-Yeung. Occupational Asthma. In Middleton 7th edition. 939-953.

6. JACI 2013; 131: 704-10

7. Aims
1. Compare the clinical , functional and inflammatory
characteristics of workers with work-exacerbated
asthma and occupational asthma
2. Compare health care use and related costs between
work-exacerbated asthma and occupational asthma,
work-related asthma and non-work-related asthma
JACI 2013; 131: 704-10

8. Materials & Methods
 A prospective cohort study with a 2-year follow-
up
 Subjects:
- Asthmatic patients referred for suspected
work-related asthma
- Two tertiary centers in Quebec, Canada
- From 2003-2008
JACI 2013; 131: 704-10

9. Materials & Methods
 Subjects :
- At first visit ; questionnaires, SPT, PFT,
methacholine inhalation challenge test,
sputum induction
- Be classified as ; inflammatory phenotypes
- Eosiophilic ( sputum EO > 3%)
- Nutrophilic ( sputum N > 61%)
- Paucigranulocytic ( sputum EO< 3%,N < 61%)
- Mixed ( sputum EO> 3% , N > 61%)

10. Materials & Methods
 Severe asthma: an ER visit or a hospitalization
 Specific inhalation challenges to occupational agents
were done when asthma possibly related to work
 Asthma diagnosis:
- FEV1<80% of predicted value
- FEV1/FVC < 0.7
- improvement in FEV1 > 12% after bronchodilator
- If absence of reversible airflow limitation,
PC20 value should < 16 mg/ml
JACI 2013; 131: 704-10

11. Materials & Methods
 Diagnosis of occupational asthma:
- Positive specific inhalation challenge test
- Worsening asthma symptoms while at work
Diagnosis of work-exacerbation asthma:
- Negative specific inhalation challenge test
- Worsening asthma symptoms while at work

12. Materials & Methods
 Health care use and related costs
- From administrative database
- Focusing on physician’s cost, ER visit &
hospitalization

13. JACI 2013; 131: 704-10

14. JACI 2013; 131: 704-10

15. JACI 2013; 131: 704-10

16. JACI 2013; 131: 704-10

17. JACI 2013; 131: 704-10

18. JACI 2013; 131: 704-10

19. Conclusion
 Workers with WEA have more severe clinical
than workers with occupational asthma
 WEA is associated with a non-eosinophilic
phenotype
 Both WEA & occupational asthma have
greater health care use & 10-fold higher direct
costs than NWRA

20. Diagnostic tools for
Occupational Asthma
 Specific inhalation challenge ( standard test)
 Combination of Peak Expiratory Flow Rate &
sputum eosinophil count
 Exhaled Breath Condensate pH test

21. l

22. Aims
 To characterize the threshold duration of
exposure needed to elicit an asthmatic
reaction during specific inhalation challenge
with various occupational agents
 To determine the duration of exposure that
should be complete before the test can be
considered negative

23. Materials & Methods
 A retrospective study
 Centre Hospitalier Universitaire de Mont-
Godinne, Universite Catholique de Louvain,
Yvain,Belgium
 From Jan 1992-Dec 2011
 Data records were reviewed
 All subjects investigated for possible occupational
asthma with positive test for specific inhalation
challenge

24. Materials & Methods
 Specific Inhalation Challenge:
- Occupational agents were generated in five-cubic-
meter cubicles using a realistic approach
- Asthma medications were stopped according to their
duration of action
- Inhaled steroid was halted 72 hr prior to the test
- The level of exposure during SICs was monitored
only for isocyanates using an MDA 7100 monitor
( MDA Scienctific Inc, Glenview, IL) & was kept below
the ceiling value of 20 ppb.

25. Materials & Methods
 Spirometry was obtained at:
- baseline, q 15 min * 4 times
q 30 min * 2 times
q 1 hr for a total of 6 hr after the end of exposure
- The baseline level of BHR to histamine & sputum eosinophil
count were assessed at the end of control day
- Re-assessed 6 & 24 hr after the active challenge
- Degree of non-specific BHR was assessed as provocative
concentration of histamine causing a 20% fall in FEV1 ( PC20)
- Positive SIC : sustained > 20% fall in FEV1 was recorded on 2
consecutive assessments

26. Materials & Methods
 On the first day :
- Using “ control” agent for 30 min to ensure
FEV1 fluctuation < 12% of baseline
- “ control” agent according to the nature of
occupational agent suspected causing asthma
( ie ; use lactose powder for flour)

27. Materials & Methods
 The second day:
- Use a suspected agent
- A duration of exposure gradually increased
from 1 , 4, 10, 15, 30, 60 min until a > 20%
fall in FEV1 occurred or 2 hr was reached
- Who did not show a >20% fall in FEV1, had to
repeat for 3 hr on the next day
- Negative test : challenging at least 240 min
without significant change
- If > 3-fold decrease in post-challenge PC20 or
increase in sputum > 3% compared to control
value, further challenge will be repeated

30. Conclusion
 Sensitivity of Specific Inhalation
Challenge for diagnosis occupational
asthma depend on duration of challenge
exposure
 Need markers such as post-challenge
level of non-specific bronchial
responsiveness to histamine , sputum
eosinophil count

32. Aim
 To evaluate the utility of exhaled breath
condensate ( EBC) pH for the diagnosis
of occupational asthma

33. Materials & Methods
 A prospective study
 Total of 37 patients suspected
occupational asthma
 Exclusion criteria:
- Seasonal asthma
- Can not join PEF, SIC, EBC pH
* Allow to take asthma medication but
don’t change type or dose

35. Materials & Methods
 Spirometry & Methacholine Test
- A Datospir 200 system ( Sibel, Barcelona, Spain) used for spirometry
- A Mefar MB3 dosimeter ( Ele H2O, Medically, Brescia, Italy) for
Methacholine test
- Increasing dose of methacholine ( 0.03-16 mg/ml) were inhaled at 3-
min intervals until FEV1 fell by 20% of baseline or max dose was
inhaled ( PC 20)
- Negative test defined as PC20 > 16 mg/ml
- Dose response rate : last FEV1 decline ( %) / last dose administered

36. Materials & Methods
 Monitoring Peak Expiratory Flow Rates
- Serial PEF during 2 wk at work & 2 wk off work
- A Mini-Wright portable peak flow meter ( Clement
Clarke International, UK) & diary cards
- Record 4 times a day
- PEF graphs were interpreted by 3 experienced
independent readers
- Positive test : evidence changes between exposure
period
- PEF recording was computerized by Oasys-2 software
- Suggestive Occupational asthma : score > 2.51

37. Materials & Methods
 Exhaled Breath Condensate Collection & pH Measurement
- Collecting during tidal breating with a commercially
condensor ( EcoScreen; Jaeger,Wurzburg, Germany)
- To determine ventilatory pattern, spirometer
( EcoVent; Jaeger ) was connected
- Patients were prohibited from foods 2 hr before sample
collection
- A fixed volume of 150 liters of exhaled breath was collected
per patient
- Sample was divided into 500 ul aliquots in 2-4 plastic tubes

39. Materials & Methods
 pH was measured in 1 aliquot after collection
immediately
 Another one was measured after de-aeration
with helium ( 350ml/min for 10 min)
 Using a model GLP 21 calibrated Ph meter
( Crison Instruments SA, Barcelona, Spain)
with an accuracy of +- 0.01 pH
 A probe ( Crison 5028) was calibrated daily
with standard Ph 7.02 & 4.00 buffers

40. Materials & Methods
 Specific Inhalation Challenge:
- Standard test for diagnosis
- Using substances suspected the cause of the patient’s
asthma*
- A placebo was done before an actual test
- Measuring FEV1, FVC q 10 min during first hr following
exposure & q 1 hr until 15 hr post-inhalation
- Positive test : FEV1 decrease > 20% baseline

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45. Conclusion
 SIC is a gold standard to diagnosis
occupational asthma
 EBC pH is an easily performed,
inexpensive, & noninvasive method
 If SIC can’t be done, PEF & induced
sputum eosinophil count are chosen
 EBC pH alone or combine with PEF may
be a good option

46. Thank You Very Much