Diagnostic Strategies for Occupational Asthma Louis-Philippe Boulet, MD, FRCPC Institut de...
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Diagnostic Strategies Diagnostic Strategies for Occupational Asthma for Occupational Asthma Louis-Philippe Boulet, MD, FRCPC Institut de cardiologie et de pneumologie de l’Université Laval, Hôpital Laval Québec, Canada Universi té Laval
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Transcript of Diagnostic Strategies for Occupational Asthma Louis-Philippe Boulet, MD, FRCPC Institut de...
Diagnostic Strategies for Diagnostic Strategies for Occupational AsthmaOccupational Asthma
Diagnostic Strategies for Diagnostic Strategies for Occupational AsthmaOccupational Asthma
Louis-Philippe Boulet, MD, FRCPCInstitut de cardiologie et de pneumologie
de l’Université Laval, Hôpital Laval Québec, Canada
Université Laval
SynopsisSynopsis
Definition Mechanisms
Main causal agents
Diagnostic strategies Conclusion
Prevalence of asthmaPrevalence of asthma
Masoli M et coll. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy. 2004;59:469-78.
EpidemiologyEpidemiology
Asthma : 5-10 % of occupational origin
Incidence of asthma may vary according to:
– Type of agent– Duration and intensity of exposure– Risk factors
• Atopy• Genetic factors (HLA)• Smoking
Estimated prevalence of work related-asthmaEstimated prevalence of work related-asthma
Mapp et al. AJRCCM 2006
“Occupational asthma is a disease characterized by variable airflow limitation and/or hyperresponsiveness and/or inflammation due to causes and conditions attributable to a particular occupational environment and not to stimuli encountered outside the workplace.”
- With a latency period: classical occupational asthma
- Without latency period: irritant induced asthma & RADS
Bernstein IL, Chan-Yeung MMalo JL, Bernstein DI.Asthma in the WorkplaceMarcel Dekker Inc., NY 1993
Occupational asthmaOccupational asthma
Asthma caused byworkplace exposure
(occupational asthma)
After latency period
Withoutlatency period
« Irritant-induced asthma »or
« Reactive airwaysdysfunction syndrome »
Asthma exacerbatedby exposure at the
workplace
Variantsof asthma
e.g. non asthmatic eosinophilic
bronchitis
Asthma at the workplaceAsthma at the workplace
Risk factors, e.g. atopy, genetic markers, smoking, etc.
exposure
concentration,duration of exposureand nature of the sensitized agent;
Other intercurrent factors:viral infection,exposure to pollutants,smoking, etc.
sensitization Occupational asthma
exposure
total duration of exposure, duration of symptoms after exposure, severity of asthma at the time of diagnosis
asthma or healing
???baseline airway hyperreactivity
Natural history of occupational asthmaNatural history of occupational asthma
pharmacologic modulation
development of airway inflammation
PathogenesisPathogenesis
Immune mechanisms– Latency period – Mininal exposure can lead to a severe
bronchospasm– Various mechanisms: mainly production of
specific IgE
Non immune mechanisms
Source : Mapp CE, Boschetto P, Maestrelli P, Fabbri LM. Occupational Asthma.Am J Respir Crit Care Med. 2005
Low molecular weight agentsLow molecular weight agents
High molecular weight agentsHigh molecular weight agents
InvestigationInvestigation
Based on :
Medical & environmental history* Specific bronchoprovocation test (in laboratory or at work) Methacholine test PEF at work and out of work Skin prick test Induced sputum
* http://www.asmanet.com/asmapro/substances.htm
DiagnosisDiagnosis
History– Exposure
• Current or past work• Description of tasks and agents at work
– Symptoms • Initially present at work• May be accompanied by symptoms
of rhino-conjunctivitis• Some may also cause symptoms of alveolitis
DiagnosisDiagnosis
History– Symptoms
• Diagnosis may be difficult: – if the exposure is intermittent– if the patient has not recently been exposed– with progression of the disease
(Fixed Airflow Limitation, severe asthma…)
• Latency period variable– Shorter with LMW agents
(e.g. Isocyanates)
DiagnosisDiagnosis
Diagnosis
– Confirm the presence of asthma
– Establish the relationship between asthma and the workplace
– Identify causal agent and subject’s response to this agent
DiagnosisDiagnosis
Diagnosis– Confirm the presence of asthma
• Significant response to bronchodilator (variable airway obstruction)
OR
• Identification of airway hyperresponsiveness to a pharmacological agent
(e.g. methacholine)
DiagnosisDiagnosis
Diagnosis– Establish the relationship between asthma and
the workplace
• PEF• Spirometry• Repeated measurements of non allergic
airway responsiveness at work and out of work
• Skin prick tests for certain agents (e.g. animal danders)• Change in the eosinophil counts after
exposure
Screening of occupational asthmaScreening of occupational asthma
High molecular weight agents
Skin prick tests
negative positive
Methacholine test during time of work
negative positive
referNo occupational asthma
Screening of occupational asthmaScreening of occupational asthma
Low molecular weight agents
questionnaire and methacholine testduring the time of work
If both are positive, refer
Occupational asthma without latency periodOccupational asthma without latency period(“irritant-induced asthma”)(“irritant-induced asthma”)
Diagnosis based on history : only one event sometimes repeated high exposure event
A diagnostic challenge…A diagnostic challenge…
Differential diagnosis with an exacerbation of preexisting asthma
– Caused by exposure to irritants at the workplace
– E.g. dust, smoke, …
– Treatment is different:• Can continue to work but with changes in
the environment or the level of exposure• Medication should be adjusted
Diagnosis and management of Diagnosis and management of Occupational AsthmaOccupational Asthma
Clinical investigation of Occupational Clinical investigation of Occupational AsthmaAsthma
Investigation protocolInvestigation protocol
QUESTIONNAIREQUESTIONNAIREPattern of symptomsPattern of symptoms
6 07 0
7 6
8 8
5 1
8 5
0
10
20
30
40
50
60
70
80
90
100
A S T H M E A S T H . P R O F N O R M A L
R e s p ira to ry s ym p to m s
B etter o n w ek-en d B etter o n h o lid ays
Positive predictive value: 63%Negative predictive value: 83%
PEFPEF
8 7 9 0
7 38 0
7 0
9 0 9 3 9 0
0
10
20
30
40
50
60
70
80
90
100
v is u a l w e e k e n d h o l id a ys m a x-m in
P E F d iffe re n c e b e tw e e n th e 2 p e r io d s
s e n s it iv i tys p e c if ic i ty
PEF Circadian variationPEF Circadian variation
8 7 9 0
6 6
9 08 6
8 0
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
v is u a l w e e k e n d h o l id a ys
s e n s it iv i ty
s p e c i f ic i ty
Serial PCSerial PC2020 methacholine tests methacholine tests
2 measures – End of holiday– End of working period
Suggestive of OA:– Improvement by 3.2X out of work– E.G.: 2 to 12 mg /ml
PC20 methacholinePC20 methacholine
6 1
5 2
4 3
6 56 2
7 8
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
O A O A C e d a r a s th m a
s e n s it iv i ty
s p e c if ic i ty
DiagnosisDiagnosis
– Identification of the causal agent
• Bronchoprovocation in specialized centres– HMW: can be done with increasing concentration
over one day– LMW: may require many days with increasing
doses as there are not always early responses
• Skin prick tests– Available for some proteinic agents– When negative: usually exclude OA
Specific bronchoprovocation testSpecific bronchoprovocation test
« Gold-standard for the diagnosis of occupational asthma If asthma is stable (FEV1>60-70% predicted and/or > 2 L)
Control day : – Exposure to a non specific irritant or a spontaneous
variation of expiratory flows measurement– Fall in FEV1< 10%
Exposure days : – Controlled and increasing concentrations / time of
exposure– Different methods for LMW and HMW substances– Positive if FEV1 falls > 20%
Vandenplas O, Malo JL. Inhalation challenges with agents causing occupational asthma. Eur Respir J. 1997
Specific Inhalation Specific Inhalation ChallengeChallenge
Baseline FEV1 After each exposure period:
– FEV1 and FVC at 30 sec and 10 min After last inhalation,
– Each 10-15 min x 1 hr then hourly for 7-8 h PEF measures on return home in the evening
Monitor symptoms, sometimes DLCO and temperature (alveolitis?)
SIC - Early ResponseSIC - Early Response
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
0 1 0 2 0 3 0 4 0 5 0 6 0 1 2 0 1 8 0 2 4 0 3 0 0 3 6 0 4 2 0
s a l in e c ra b
SIC - Dual ResponseSIC - Dual Response
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
0 1 0 2 0 3 0 4 0 5 0 6 0 1 2 0 1 8 0 2 4 0 3 0 0 3 6 0 4 2 0
s a l in e f lo u r
SIC – Atypical ResponseSIC – Atypical Response
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
0 1 0 2 0 3 0 4 0 5 0 6 0 1 2 0 1 8 0 2 4 0 3 0 0 3 6 0 4 2 0
s o lv a n t is o c ya n a te
SIC – Very Late ResponseSIC – Very Late Response
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6
d i lu a n t re d c e d a r
Patterns of response Patterns of response to occupational agentsto occupational agents
206 subjects
More frequent Late or Dual Responses with Low Molecular Weight substances
EAR more frequent un women and smokers
%
0
10
20
30
40
50
60
70
80
EAR LAR DualResponse
AtypicalResponse
HMWLMW
*
*
* p < 0,0001
Role of induced sputum in the Role of induced sputum in the diagnosis of occupational asthmadiagnosis of occupational asthma
Lemière et al.
2000 : 15 subjets with OA• Increase eosinophils after exposure (LMW > HMW)• Early markers of exposure / sensitization ?
2001 : 41 subjets, 17 with positive BPT• ↑ eosinophils + neutrophils with HMW + LMW• Sputum eosinophilia and change in airway responsiveness
could predict the response to occupational agents.
2004 : 49 subjets, 23 with positive BPT• Sputum eosinophils is a valuable tool to support the diagnosis
of OA
Occupational Asthma and Work-Occupational Asthma and Work-Exacerbated Asthma:Exacerbated Asthma:
Factors associated with time delay to diagnosisFactors associated with time delay to diagnosis
Occupational asthma
- Male sex, unmarried, low education, lack of awareness of symptoms association with work, older age, sole income of the family and no knowledge of potential effects of occupational agents
Work-exacerbated asthma
- Lower household income, low education, absence of health and safety program at work, no union, lack of awareness of potential effects of occupational agents and of OA.
Santos et al Chest 2007;131: 1768.
ConclusionConclusion
Occupational asthma is one of the main causes of respiratory diseases at work
It is important to make the diagnosis early to prevent long term consequence on lung function
Patient should be referred to the Workmen’s Compensation Board
Promotion of preventative strategies is important particularly for high-risk workers
Bronchial provocation test with Bronchial provocation test with occupational sensitizersoccupational sensitizers
Bronchial provocation test with Bronchial provocation test with occupational sensitizersoccupational sensitizers
Bronchial provocation test with Bronchial provocation test with occupational sensitizersoccupational sensitizers
Bronchial provocation test with Bronchial provocation test with occupational sensitizersoccupational sensitizers
Bronchial provocation test with Bronchial provocation test with occupational sensitizersoccupational sensitizers
