Transcript Diisocyanate OA features in 137 claims

Diagnosis of
Work-related Asthma
Susan M Tarlo, MB BS, FRCP(C)
Professor, Dept Medicine,
and Dalla Lana School of Public Health
University of Toronto,
Respiratory Division, Toronto Western
Hospital
Chest 2008
Work-related asthma
(WRA)
Occupational asthma,
caused by work
(OA)
Sensitizer-induced OA
Work-exacerbated asthma
(WEA)
Irritant-induced OA
(Including reactive airways
dysfunction syndrome, RADS)
These groupings are not mutually exclusive; e.g. OA can be followed by WEA
Guidelines and Statements
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Assessment of Asthma in the Workplace, an
ACCP Consensus Statement. Chest
1995;108:1084-117.
CTS Guidelines on Occupational Asthma. Can
Resp J 1998;5:289-300
British Thoracic Society, Standards of Care for
Occupational Asthma. Thorax 2008;63:240-50.
Diagnosis and Management of Work-related
Asthma. ACCP Consensus Statement. Chest
2008;134:1S-41S.
Consensus Document
Diagnosis and Management of Work-related
Asthma. ACCP Consensus Statement. Chest
2008;134:1S-41S.
http:/www.chestjournal.org/cgi/content/abstract/
134/3_suppl/1S
- Based on an AHRQ evidence-based review, (Agency for
Healthcare Quality and Research) 2005, supplemented
by recent literature review to Dec 2006 and by panel
consensus
WEA
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Work-related worsening of asthma that started before
the job or began incidentally.
Common (up to 25% of working asthmatics)
May be transient and diagnosed on history or may
occur daily at work and may mimic occupational
asthma, requiring similar investigations
May be due to expected asthma triggers such as dusts
or temperature extremes, or to common allergens that
may be in the workplace.
OA
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OA= Asthma due to causes and conditions
which are attributable to a particular workplace
environment and not to stimuli encountered
outside the workplace:
Irritant-induced
 Sensitizer-induced
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OA?
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Some WRA does not clearly fit the definitions
– previous childhood asthma recurring from
sensitization to a specific work agent
- existing asthma that worsens at work from
sensitization to a specific work agent
Clinical implications of these are as for OA
but may/may not be included in compensation
definitions
Differential diagnosis for WRA
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Other asthma (non-occ) coincidentally worse while
working
Non-asthma causes for asthma-like symptoms
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GERD
Upper airway cough syndrome (post nasal drip)
Irritable larynx syndromes (WILS) – Hoy et al Occupational Medicine
2010; 60:546-51 [30 cases vs 90 WRA]
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Hyperventilation/anxiety
Eosinophilic bronchitis
- or any combination of these ± WRA
OA - Irritant-induced
(Reactive Airways Dysfunction Syndrome)
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About 7% of all OA: from a high irritant exposure
Onset typically within 24 h of exposure
 New symptoms of asthma, persist >3mo
 Exposure expected to be a high level irritant
 Asthma confirmed: PFTs / methacholine responses
 documented absence of previous respiratory disease
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No specific diagnostic test available
Most certain = RADS, less certain if criteria not all
met
Sensitizer-induced OA Diagnosis
Value of the history
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Exposures, symptoms: start while working, improve wends/holidays off work
PPV 63%,
NPV 83% (Malo et al ’91)
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Daily wheeze worse at work most sensitive (88%)
 + itchy nose/eyes
 + lack of hoarseness,
- predicted 74% of high MWt OA (Vandenplas et al ERJ ’05)
Nevertheless overall ~50% of specific challenges are negative
even when OA suspected, emphasizing need for objective
tests.
Exposure history for sensitizerinduced OA
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HMWt almost any airborne protein (plant,
animal, fish, fungal, insect, enzymes)
LMWt many reactive chemicals, especially with
double bonds and 2 or more reactive side chains
Seed M, Agius R. Further validation of computerbased prediction of chemical asthma hazard. Occup
Med (Lond) 2010; 60:115-20.
Exposure assessment
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Patient’s history: often limited
MSDS, WHIMIS: have limitations, incomplete
information
Occupational hygienist assessment: company
hygienist, independent private assessment or
public health/government agency, e.g MOL,
NIOSH
Why objective tests are necessary
to diagnose OA
1.
2.
3.
4.
History could be influenced by other factors
Management differs for OA vs. WEA
Early correct diagnosis of sensitizer-OA with
removal from exposure leads to the best
asthma prognosis
Objective diagnosis may lead to changes to
prevent sensitization and OA in other workers
Diagnostic recommendations
(from ACCP Consensus 2008)
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In patients with a hx of possible OA:
Confirm a diagnosis of asthma objectively
Review MSDS
Skin test where feasible
PEFR and Methacholine responses work and
off work, considering possible confounding
factors
Add induced sputum if available
Consider specific challenges if available,
especially if the diagnosis is in doubt
Objective diagnosis of asthma
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FEV1 pre/post bronchodilator
Methacholine/histamine challenge
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sensitive for asthma if patient is still working and
symptomatic
positive findings do not confirm a work relationship
negative findings do not exclude OA if not recently
exposure to the sensitizer
occasional reports of normal responsiveness in
diisocyanate-OA
Skin tests/ immunologic tests
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Limited skin test extracts commercially available for
occupational allergens
 Few are standardized
 Immunologic sensitization is more common than OA
in exposed workers
 Skin tests are unhelpful for most low-molecular-weight
sensitizers
In-vitro immunologic tests
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In-vitro immunologic tests only reliable in a few centres.
 Generally less diagnostic value than skin tests for high
molecular weight sensitizers, eg natural rubber latex
 Limited sensitivity/specificity for low molecular-weight
sensitizers at present, eg diisocyanates
Evidence-based medicine
Diagnosis and Management of OA (AHRQ ’05)
HMWt
Methacholine
Sensitivity
79%
Specificity
51%
Specific IgE
(skin/serum)
Both
81/ 73%
60 / 79%
61%
83%
67%
64%
LMWt
Methacholine
Specific IgE
(skin/serum)
73 / 31%
86 /89%
(very select studies, (often not feasible)
often not feasible)
B
NSBP Test Alone
NSBP Test with
SPT or Specific IgE
1
99
1
99
2
98
2
98
5
95
5
95
90
10
80
70
60
50
40
30
20
20
30
40
50
60
70
80
10
90
95
5
95
5
98
2
98
2
99
Pre-test
Probability
1
Post-test
Probability
99
Pre-test
Probability
1
Post-test
Probability
10
20
30
40
50
60
70
80
90
100
50
20
10
5
2
1
0.5
0.2
0.1
0.05
0.02
0.01
Likelihood
Ratio
+
-
100
50
20
10
5
2
1
0.5
0.2
0.1
0.05
0.02
0.01
Likelihood
Ratio
90
+
-
80
70
60
50
40
30
20
10
A
NSBP Test Alone
NSBP Test with
SPT or Specific IgE
1
99
1
99
2
98
2
98
5
95
5
95
90
10
80
70
60
50
40
30
20
20
30
40
50
60
70
80
10
90
95
5
95
5
98
2
98
2
99
Pre-test
Probability
1
Post-test
Probability
99
Pre-test
Probability
1
Post-test
Probability
10
20
30
40
50
60
70
80
90
100
50
20
10
5
2
1
0.5
0.2
0.1
0.05
0.02
0.01
Likelihood
Ratio
+
-
100
50
20
10
5
2
1
0.5
0.2
0.1
0.05
0.02
0.01
Likelihood
Ratio
+
-
90
80
70
60
50
40
30
20
10
Beach J et al Chest 2007
C
NSBP Test Alone
NSBP Test with
SPT or Specific IgE
1
99
1
99
2
98
2
98
5
95
5
95
90
10
80
70
60
50
40
30
20
20
30
40
50
60
70
80
10
90
5
95
98
2
98
2
99
Pre-test
Probability
1
Post-test
Probability
99
Pre-test
Probability
1
Post-test
Probability
10
20
30
40
50
60
70
80
90
100
50
20
10
5
2
1
0.5
0.2
0.1
0.05
0.02
0.01
+
-
95
Likelihood
Ratio
100
50
20
10
5
2
1
0.5
0.2
0.1
0.05
0.02
0.01
Likelihood
Ratio
90
+
-
80
70
60
50
40
30
20
10
5
Beach J et al Chest 2007
Objective documentation of work-related
changes in asthma
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Serial peak expiratory peak flow monitoring (PEF)
with sx and med diary
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at least 4x per day, several weeks at work and off
work
requires careful patient instruction
needs compliance
effort-dependent
no generally accepted objective criteria for
interpretation
by themselves, positive results do not distinguish OA
from work-exacerbated asthma
A 42 year old polyurethane foam worker
PEFR (L/min), 4 x per day
700
600
500
400
300
200
Working weeks
Off work
100
0
Methacholine PC20
0.07mg/ml
days
Methacholine PC20
11.6 mg/ml
A 50 year old dry cleaner
PEFR (L/min), 4 x per day
500
450
400
350
300
250
200
150
100
50
0
Working weeks
Off work
days
Methacholine PC20 0.03 mg/ml
Methacholine PC20 0.02 mg/ml
PEFs
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Also record symptoms and prn medication use.
Keep regular meds stable at the lowest dose to
adequately control symptoms but not to mask
PEF changes
Record at least 2 weeks at work and 10 days off
work
PEF interpretation confounders
Inadequate technique
 Poor compliance with recordings
 Fabrication of results
 Intercurrent cold or non-occupational exposure
to asthma triggers
 Work exposures not representative of those
causing symptoms
 Changes masked by medications
Any of these may need further repeat PEFS
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PEF Interpretation
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Expert visual interpretation
Formula e.g. ≥20% variability from maximum
occurring relatively more frequently working days vs
off work (93% sens 77% specificity when variability >1
day) (Liss, Tarlo ’91)
OASYS: 2-hourly PEFs analyzed to score 1-4, a cut-off
2.5 for OA: 75% sensitivity, 94% specificity
(www.occupationalasthma.com)
ABC (area between the curves) uses OASYS2 for
curves work days vs days off work with readings >6
times per day, reported 72% sensitive, 100% specific at
ABC 15 L/min/hour (Moore VC et al Chest, 2009;
135: 307- 14)
PEFs
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Electronic spirometers allow assessment of
compliance but expensive (~$500)
Despite problems with compliance, a recent
systematic review showed 61% had interpretable
recordings and of those, a pooled sensitivity for
OA 82%, specificity 88% (Moore et al Ann Resp
Med ’10)
Methacholine challenges
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Serial inhalation of increasing concentrations of
nebulized methacholine
Spirometry pre- and post- each dose.
Test is stopped with at least a 20% drop in
FEV1
PC20 calculated (lower = more hyperresponsive, cut-off 8mg/ml, borderline 416mg/ml)
A ≥3-fold worsening in PC20 at work is
significant
Methacholine challenge
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A single test is useful to diagnose asthma – with
current asthma symptoms/exposures
Paired tests (one at the end of a work week and
one after a period off work) is useful to assess
work-related changes (e.g. OA)
Confounders: lab technique, intercurrent colds
or other non-occupational exposures,
insufficient time away from work exposure
Peak flows and methacholine
responses
Combinations of tests
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A combination of investigations has been advocated
in OA guidelines/consensus statements, as far as is
feasible.
However, skin tests/immunologic tests often
cannot be performed, patients often cannot
adequately comply with PEFRs, and
methacholine/histamine challenges may require
travelling a long distance for the tests.
Despite recommendations, patients may have
stopped work before assessment and be
unwilling/unable to return on a trial basis
Specific laboratory challenges
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Labour-intensive and expensive
Require specialized facilities with exposuremonitoring as well as prolonged responsemonitoring
Although referred to as a “gold standard”, there can
be false positive and false negative responses
In some countries, medicolegal concerns regarding
positive responses have also limited use
Laboratory challenges
Limitations to specific challenge
interpretations (? how frequent)
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False positive:
irritant exposure levels
 uncontrolled asthma or unrelated exacerbation
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False negative responses:
wrong “sensitizer”
 insufficient exposure (concentration/duration),
especially after a prolonged period away from exposure
 failure to monitor for late responses or airway
responsiveness changes
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Workplace challenge
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Open challenge in suspected work area compared with
an expected unexposed area
Objective monitoring at work (e.g. hourly spirometry,
preferably with laboratory quality equipment and
personnel)
Expensive, employer may not permit access, exposures
not blinded
Most effective for hospital workers who can have the
tests on-site in the PFT lab (including methacholine
tests)
Induced sputum eosinophilia as
a diagnostic test
(Girard et al AJRCCM ’04)
Induced sputum working and off work
(Confounders include inhaled steroid use, URIs and coincidental allergen exposures)
OA vs WEA Diagnosis
OA
WEA
Asthma history
No preceding
asthma
Preceding
asthma
Work sensitizer
+
-
Objective asthma
+
+
PEF worse with work
+
+
Methacholine PC20 better off work
+
+/-
Sputum eos increase with work
+/-
+/-
Work agent immunologic tests
+ if feasible
-
Specific challenge
+
-
Diagnostic Summary
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In patients with a hx of possible OA:
Confirm an objective diagnosis of asthma
Review MSDS / exposures
Skin test where feasible
PEFR and Methacholine responses work and
off work, considering possible confounding
factors
Consider specific challenges if diagnosis is in
doubt
Consider addition of induced sputum if
available
A combination of tests is most useful