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Investigation of occupational asthma

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Title: Investigation of occupational asthma


1
Investigation of occupational asthma
  • Catherine Lemiere MD, MSc
  • Associate Professor, University of Montreal
  • Sacré-Cur Hospital, Montreal

Université de Montréal
2
Investigation of occupational asthma
  • History
  • Diagnosis of asthma
  • Skin tests and serology
  • Monitoring of PEF and PC20 off and at work
  • Specific inhalation challenges
  • Monitoring of airway inflammation

3
Chan-Yeung Malo NEJM, 1995
4
History
5
What questions should be asked to a worker with
possible OA?
  • The questionnaire include questions regarding
  • Type of work and work shift, agent that the
    worker identifies as responsible for his/her
    symptoms.
  • 2) Nature of symptoms
  • respiratory
  • systemic
  • nasal
  • ocular
  • cutaneous
  • 3) Temporal relationship between symptoms and
    occupational exposure (at the beginning or at the
    end of exposure, persistence after the work
    shift)
  • 4) Importance of symptoms at work, on weekends,
    on holidays.
  • Berstein et al. Asthma in the workplace 1999

6
Clinical history
Occupational asthma
Final Diagnosis OA (n75) Asthma without
OA (n54) No asthma, No OA (n33)
Very probable-prob
Uncertain
Improbable-No
65
6
4
25
19
10
14
10
9
Negative and positive predictive value of 83 63
  • A history of asthma at work, even in the
    presence of a known sensitizer, does not confirm
    the diagnosis of occupational asthma

Malo JL et al. Am Rev Respir Dis 1991
143528-532
7
Diagnosis of asthma
8
Diagnosis of asthma
  • Reversible airflow limitation improvement in
    FEV1 gt12 and et gt 180ml post-ß2 agonist.
  • PC20 methacholine/histamine
  • A negative PC20 does not exclude the diagnosis of
    occupational asthma in a worker off work, but
    makes it unlikely in a symptomatic worker still
    at work

PC20 concentration of meth./hist. Inducing a
20 fall in FEV1
9
Skin tests serology
10
  • Skin prick tests IgE/IgG ...
  • valid for HMWC rarely for LMWC
  • requires good allergen extracts

a positive test confirms sensitization but not
occupational asthma
Neg. pred. value 76 89 Pos. pred.
value 69 54
11
PEF Monitoring
12
(No Transcript)
13
Poor compliance in PEF monitoring
stored
recorded
correspondence between recorded and reported
values 52
Malo JL et al, JACI 1995
14
Compliance may be good
stored
recorded
Malo JL et al, JACI 1995
15
Non-invasive monitoring of airway
inflammation Use of induced sputum
16
p 0.9
plt0.001
p0.1
p0.006
5.0
64.0
L
L
4.0
8.0

m
,
/
V
g
1
E
m
F

3.0
1.0
,
0
C
2
P
2.0
0.12
1.0
0.015
At
Work
At
At
At
Off
Off
Off
Off
p0.6
p0.2
p0.007
p0.01
10000
100


,
s
l
L
i
/
h
g
p
µ
10
1000
o

,
n
P
i
C
s
o
E
E
1.0
100
0.1
10
Lemière C et al. Eur Respir J, 1999 13 482-8
17
The vast majority of subjects with occupational
asthma show an increase in sputum eosinophils
after exposure to the offending agent which is
not the case in subjects without OA
3.00
2.40
1.80
Sputum eosinophils, 106/ml
1.20
0.60
0.0
B
E
B
E
B
E
Positive SIC
Negative SIC
Asthma without OA
LLemiere et al J Allergy Clin Immunol. 2001 107
1063-8
18
Inflammatory and functional changes in subjects
with and without OA
p lt0.05
(Girard et al, ARJCCM 2004)
19
Sensitivity and specificity of different
diagnostic strategies compared to SIC
1
0.9
0.8
PEF
0.7
PEF/Sputum (1 cutoff)
0.6
Sensitivity
PEF/sputum (2 cutoff)
0.5
0.4
0.3
0.2
0.1
0
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
1- Specificity
(Girard et al, ARJCCM 2004)
20
Specific inhalation challenges (SIC)
  • The reference test to confirm the diagnosis of
    occupational asthma

21
SIC - advantages
  • Safe
  • Fast, easy to perform and allow gradual exposure,
    avoiding too severe reactions (safer than return
    to work in some cases)
  • Allow identification of the responsible agent
  • Can be done on an out-patient basis

22
SIC restrictions precautions
  • Exposure may induce life-threatening asthma
  • Done under close supervision of an expert
    physician
  • Requires well trained and responsible technicians
  • Resuscitation material readily available
  • Need for a control day and PC20 assessment

23
Methods- realistic exposure
24
Dust generator safe controlled exposure
25
SIC - procedure
  • Control day to ensure that spirometry is stable
  • (lactose, diluent), from 800 to 1600, PC20 at
    end of day
  • Progressive and careful exposure
  • In one day if positive skin tests (HMWC)
  • On several days for LMWC (1-4, 30 120 min)
  • FEV1 q. 10 min. X 1 h., q. 30 min. X 1 h., then
    hourly for a total of 8 hours ( FVC, T)
  • PC20 at end of tests

26
SIC - In the workplace
  • Less controlled exposure
  • Process involved may not be active
  • More difficult to exclude irritant effect
  • FEV1 at 30-60 min. interval FVC T
  • Combine if possible with monitoring of PC20
  • Positive test Fall in FEV1 gt 20 - confirms the
    diagnosis of OA

27
SIC - at work - indications
  • No known sensitizer
  • Unable to reproduce work condition in the lab
  • Too many potential sensitizers
  • To "exclude" asthma at work (legal issues)
  • Requires trained personnel...
  • no previous history of severe asthma at work

28
Typical patterns of response
29
Eosinophilic Bronchitis
Diagnosis and Treatment
30
Eosinophilic bronchitis
  • Sputum eosinophilia can be observed in subjects
    without airflow limitation or airway
    responsiveness. (Gibson et al. Lancet
    19891346-8)
  • This has been described in chronic cough and
    labeled eosinophilic bronchitis.
  • Chronic cough with eosinophilic bronchitis is
    controlled with ICS. (Gibson PG et al. 1994 Clin
    Exp Allergy 1994 127-32).

31
CAUSES OF ISOLATED CHRONIC COUGH (n  91)
Primary Cause of Cough
No. of Patients ()
Rhinitis
20 (24)
Asthma
16 (17.6)
Postviral
12 (13.2)
Eosinophilic bronchitis
12 (13.2)
Gastroesophageal reflux
7 (7.7)
Unexplained
6 (6.6)
COPD
6 (6.6)
Bronchiectasis
5 (5.5)
ACE inhibitor-induced cough
4 (4.4)
Lung cancer
2 (2.2)
Cryptogenic fibrosing alveolitis
1 (1.1)
Brightling et al. Am. J. Respir. Crit. Care Med.,
1999 160 406-10
32
Occupational eosinophilic bronchitis
  • Three subjects referred for possible OA
  • Exposed to low-molecular weight agents
  • cyanoacrylates
  • isocyanates (MDI)
  • Platinum salts

33
Clinical characteristics
Age,
Sex
Atopy
Smoking
Treatment
Symptoms
Agent
y
(pack/y)
at work
1
50
F
-
Ex(15)
IS 200µg/d
C,S,D
,
Cyano
-
2
agonist

W,CT
acrylates

IS1000µg/d
2
64
M
-
No
C,S,D
,
MDI
2
agonist

W,CT

3
44
M
A
24
0
C,S
Platinum
salts
34
Functional and inflammatory characteristics
Status
FEV
,L
VC,L
PC
,
TCC
Eos
Neu
1
20
(
pred
)
(
pred
)
mg/ml
x10
6
/ml


1
At W
2.3(100)
3.0(111)
24
1
13
16.3
Off W
2.5(108)
3.1(114)
gt64
1.3
0
26.7
2
At W
2.6(76)
4.0(92)
16
15.7
11
79
Off W
2.8(82)
4.2(97)
25
7.8
0.8
80.4
3
At W
3.8(90)
5.8(111)
57
2
27
26.3
Off W
4.0(95)
5.3(103)
gt64
1.3
0.5
19
35
Normal
Control
Glue
Inhalation Test
values
Inhalation
30 min
exposure
Test
7 h
after

24 h
after

7 h
after
Chest

symptoms



Nose

symptoms
0
0
0
Treatment
0
0
0
FEV
, L (
pred
)
2.2
2.4 (105)
2.4 (103)
2.6 (114)
1
VC
, L (
pred
)
2.7
3.3 (120)
ND
3.3 (120)
PC
, mg/ml
gt16
gt64
ND
gt64
20
Induced

sputum

TCC
, 10
6
/ml
lt4.5
2.7
3
1.4
Neutrophils,
lt35
28.7
65.5
54.2
Eosinophils,
lt2
0
5.8
5
Metachromatic

cells

lt0.07
0
1.5
0.26
9
/L
lt0.4
0.2
ND
0.4
Blood eosinophils ,10
Lemière C et al. J Allergy Clin Immunol 1997
100852-3
36
Yacoub MR et al Allergy, 60 2005 1542
37
Diagnostic criteria for occupational eosinophilic
bronchitis
Quirce Curr Opin Allergy Clin Immunol, Volume
4(2).April 2004.87-91
38
Conclusions
  • The diagnosis of OA is often difficult to make.
  • A comprehensive investigation needs to be
    performed. The diagnosis of OA must rely on
    respiratory function changes induced by the
    exposure to the suspected occupational agent.
  • History alone is not sufficient to make a
    diagnosis of OA.
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