Transcript Prevalence of OA - Center for Asthma in the Workplace

Investigation of occupational
asthma
Catherine Lemiere MD, MSc
Associate Professor, University of Montreal
Sacré-Cœur Hospital, Montreal
Hôpital du Sacré-Cœur
de Montréal
Université
de Montréal
Investigation of occupational asthma
1.
2.
3.
4.
5.
6.
History
Diagnosis of asthma
Skin tests and serology
Monitoring of PEF and PC20 off and at work
Specific inhalation challenges
Monitoring of airway inflammation
Chan-Yeung &
Malo; NEJM, 1995
History
What questions should be asked to a worker with possible OA?
The questionnaire include questions regarding:
1) Type of work and work shift, agent that the worker identifies as
responsible for his/her symptoms.
2) Nature of symptoms:
a) respiratory
b) systemic
c) nasal
d) ocular
e) 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
Clinical history
Occupational asthma *
Final Diagnosis
Very probable-prob Uncertain
Improbable-No
OA (n=75)
65
6
4
Asthma without OA
(n=54)
No asthma, No OA
(n=33)
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; 143:528-532
Diagnosis of asthma
Diagnosis of asthma
1. Reversible airflow limitation: improvement in FEV1
>12% and et > 180ml post-ß2 agonist.
2. 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
Skin tests & serology
 Skin
prick tests ± IgE/IgG ...
 valid for HMWC & rarely for LMWC
 requires good allergen extracts
a positive test confirms sensitization but not occupational asthma
OA
Skin test - water-84
RAST Water-84
Ratio >4.5
+
-
Total
+
-
Total
+
37
11
48
25
12
37
-
17
35
52
11
62
74
Total
54
46
110
36
74
111
Neg. pred. value:
Pos. pred. value:
76%
69%
89%
54%
PEF Monitoring
Poor compliance in PEF monitoring
stored
False negative
recorded
Malo JL et al, JACI 1995
correspondence between recorded
and reported values: 52%
Compliance may be good…
stored
recorded
Malo JL et al, JACI 1995
True negative
Non-invasive monitoring of airway inflammation:
Use of induced sputum
p= 0.9
p=0.006
p<0.001
PC , mg/mL
64.0
4.0
1
FEV , L
5.0
p=0.1
1.0
20
3.0
8.0
2.0
1.0
100
10
0.015
At
Off
p=0.6
At
Off
At
p=0.007
10000
ECP, µg/L
Eosinophils, %
Work
0.12
p=0.2
Off
At
Off
p=0.01
1000
1.0
100
0.1
10
Lemière C et al. Eur Respir J, 1999; 13: 482-8
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
1.20
0.60
0.0
B
E
Negative SIC
B
E
Positive SIC
B
E
Asthma without OA
LLemiere et al J Allergy Clin Immunol. 2001; 107: 10638
Inflammatory and functional changes in subjects with and
without OA
Negative SIC (n =26)
Symptom
score
2 use
Off work
4.65.6
At work
14.7 9.8*
Positive SIC (n = 23)
Off work
4.5 4.6
At work
18.0 12.0*
FEV1, % pred
PC20, mg/ml
0.4 0.7
1.2 1.6*
88.2 16.9 82.4 20.6*
6.0 5.2
3.5 3.0*
0.3 0.6
1.8 1.9*
90.8 17.2 84.6 22.3*
2.9 2.3
1.6 1.2*
TCC, 106.ml
Neutro,%
Eosino,%
1.8(2.4)
37.7(32.3)
0.8(1.5)
1.8(4.3)
35.3(43.0)
0.5(3.0)
* p <0.05
2.3(2.7)
59.5(41.6)*
1.0(3.6)
2.5(4.3)
33.2(41.2)
2.8(9.1)*
(Girard et al, ARJCCM 2004)
Sensitivity and specificity of different diagnostic
strategies compared to SIC
1
0.9
0.8
PEF
0.7
PEF/Sputum (1% cutoff)
0.6
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)
Specific inhalation challenges (SIC)
The reference test to confirm the
diagnosis of occupational asthma
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
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
Methods- realistic exposure
Flour
Dust generator – safe & controlled exposure
Flour
SIC - procedure
Control day to ensure that spirometry is stable
(lactose, diluent…), from 8:00 to 16:00, 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
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 > 20% - confirms
the diagnosis of OA
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
Typical patterns of response
Eosinophilic Bronchitis
Diagnosis and Treatment
Eosinophilic bronchitis
 Sputum eosinophilia can be observed in subjects without
airflow limitation or airway responsiveness. (Gibson et al.
Lancet 1989:1346-8)
 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).
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
Occupational eosinophilic bronchitis
Three subjects referred for possible OA
Exposed to low-molecular weight agents
• cyanoacrylates
• isocyanates (MDI)
• Platinum salts
Clinical characteristics
Age, Sex Atopy
y
Smoking
(pack/y)
Treatment
Symptoms Agent
at work
1
50
F
-
Ex(15)
IS: 200µg/d
2 agonist;

C,S,D
,
W,CT
Cyano acrylates
2
64
M
-
No
IS:1000µg/d
2 agonist;

C,S,D
,
W,CT
MDI
3
44
M
A
24
0
C,S
Platinum
salts
Functional and inflammatory characteristics
Status FEV 1,L
VC,L
PC 20 ,
(%pred ) (% pred ) mg/ml
1
2
3
TCC
x10 6/ml
Eos
%
Neu
%
At W 2.3(100) 3.0(111)
24
1
13
16.3
Off W 2.5(108) 3.1(114)
>64
1.3
0
26.7
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
At W
3.8(90) 5.8(111)
57
2
27
26.3
Off W
4.0(95) 5.3(103)
>64
1.3
0.5
19
Normal Control
values Inhalation
Test
7 h after
Glue Inhalation Test
30 min exposure
7 h after
24 h after
Chest symptoms
Nose symptoms
+
0
++
0
+
0
Treatment
0
0
0
FEV1, L (% pred )
2.2
2.4 (105)
2.4 (103)
2.6 (114)
VC, L (% pred )
2.7
3.3 (120)
ND
3.3 (120)
PC20, mg/ml
>16
>64
ND
>64
<4.5
<35
<2
<0.07
2.7
28.7
0
0
3
65.5
5.8
1.5
1.4
54.2
5
0.26
<0.4
0.2
ND
0.4
Induced sputum
TCC, 10 6 /ml :
Neutrophils, %:
Eosinophils, %
Metachromatic cells %:
Blood eosinophils ,10
9
/L
Lemière C et al. J Allergy Clin Immunol 1997; 100:852-3
Patient 1
Patient 2
Age
48
38
Duration of symptoms (yrs)
3
1
Smoking habits
ex-Smoker (15p/y)
non smoker
FEV1/FVC ,%
78
85
Atopy
Atopic
Non atopic
PC20, mg/ml
>32
56
Agents
stainless steel and
aluminium
Formaldehyde
13.5%
50.8
2.8%
22.3%
Sputum eosinophils
Pre-SIC:
Post-SIC:
Yacoub MR et al Allergy, 60 2005 1542
Diagnostic criteria for occupational eosinophilic bronchitis
Quirce: Curr Opin Allergy Clin Immunol, Volume 4(2).April 2004.87-91
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.