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www.asthma-workplace.com
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Hôpital du Sacré-Cœur de Montréal
Tools in the investigation of asthma in the
workplace Jean-Luc Malo MD
Axe de recherche en santé respiratoire
Centre asthme et travail Center for Asthma in the
Workplace
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• Review on available tools
• 2. How to use these tools

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• Tools
• Questionnaires
• 2. Immunologial tests
• 3. Lung function tests

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Standardized epidemiological questionnaire for
asthma Developed by the European Respiratory
Society Addition of questions relevant to
the intensity and timing of symptoms in
relation to the workplace (not standardized)
Burney PGJ et al. Eur Respir J 1988
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Content of the ERS Asthma Questionnaire
Nature of symptoms shortness of breath,
wheezing, cough, sputum, tightness in the
chest Timing of symptoms in the past
year seasonal vs perennial Provoking
factors Relevant personal and familial atopic
history Symptoms at the workplace (nose, eyes,
chest) Other chest conditions, smoking
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Questionnaire items relevant to asthma in the
workplace
Occupational data Job title Duration of work
under the same job title Products made by the
company Workshift Products causing
symptoms Nature of symptoms Respiratory Systemic
Rhinitis Conjunctivitis Cough Fever Nasal
obstruction Ocular itching Sputum Chills Runny
nose Watery eyes Chest tightness Muscle or joint
aches Sneezing Redness of the eyes Wheezing Nasal
/pharyngeal itching Shortness of breath at
rest Shortness of breath on exercise Skin Loss of
voice Rash/urticaria/eczema
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Questionnaire items relevant to asthma in the
workplace
Timing of symptoms in relation to work Interval
between onset of exposure at work and onset of
symptoms Interval between onset of symptoms and
current questionnaire Interval between last
occupational exposure and current
questionnaire Relationship of work and
respiratory symptoms Status of respiratory
symptoms on working days as compared with days
away from work Better, Worse, The same If better
or worse Every day progressively over the
week as a function of working conditions. On
physical exertion On exposure to mist, hot or
cold temperature On exposure to dust, fumes,
gas Possibility to identify a process or a
product that is responsible for respiratory
symptoms If yes, identify the process or
product If yes, is this exposure regular or
intermittent?
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Questionnaire items relevant to asthma in the
workplace
Status of respiratory symptoms on weekends They
disappear They improve No change Status of
respiratory symptoms on vacations (more than one
week) They disappear They improve No change If
they disappear or improve, after how many
days? Timing of respiratory symptoms in relation
to work Interval between onset of work and onset
of symptoms Persistence or reappearance of
symptoms on return to home Onset of symptoms only
on returning home Change of timing of symptoms
over time
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Is the clinical history a satisfactory means to
diagnose occupational asthma ?
Sensitivity 87 Specificity 55 Positive
predictive value 63 Negative predictive value
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Prospective clinical assessment of 162
patients referred for possible occupational
asthma. Malo JL et al. Am Rev Respir Dis 1991
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Questionnaire items most likely to be associated
to the presence or absence of occupational asthma

Symptoms at work OR 95 CI p Wheezing 3.39 1.43-8
.0 0.005 Loss of voice 0.39 0.18-0.86 0.02 Nasal
itching 3.7 1.8-7.8 0.0006 Ocular
itching 2.37 1.06-5.30 0.03 Subjects exposed to
high-molecular-weight agents Wheezing 6.79 1.53-3
0.0 0.01 Loss of voice 0.14 0.03-0.64 0.01 Nasal
itching 6.23 1.489-26.1 0.01 Subjects exposed to
low-molecular-weight agents No symptom
significantly associated with occupational asthma
Vandenplas O. et al. Eur respir J 2005
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• Tools
• Questionnaires
• 2. Lung function tests
• 3. Immunological tests

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Assessment of bronchial caliber and responsiveness
Bronchial obstruction present in a minority of
asthmatic subjects but bronchial
hyperresponsiveness present in all at the time
they have symptoms. Various means to assess
bronchial hyperresponsiveness but inhaled
methacholine the standard one dose that causes
a 20 change in FEV1 and that is equal or less
than 8-16 mg/ml..
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Assessment of bronchial responsiveness
(methacholine)
Suggests that someone may have asthma If
negative test, this virtually excludes current
asthma False positive test in rhinitis and
COPD. If negative test while a worker is at work
and reports symptoms, this virtually excludes
asthma and occupational asthma (but not
eosinophilic bronchitis). If positive test while
a worker is at work, this suggests either asthma
or occupational asthma.
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Serial assessment of peak flow rates

• Interest, advantages
• assessment with portable, cheap instruments
• provides serial assessment of airway caliber
• (relevant for asthma diagnosis and
  management)
• Pitfalls
• compliance poor (50) in asthma and in
• occupational asthma
• falsification of data 20 of values are
  invented
• interpretation of data visual vs computed-
• assisted method (OASYS) ?
• contamination of results in field studies
• variable figures for sensitivity and specificity
  by comparison
• with specific inhalation challenges (gold
  standard)

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• Tools
• Questionnaires
• 2. Lung function tests
• 3. Immunological tests

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Immunological assessment of specific antibodies
Highly sensitive for high-molecular-weight
agents to develop the disease, one has to be
sensitized Interesting for some
low-molecular-weight agents (metal salts,
isocyanates)
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Sensitivity, specificity, and predictive values
of diagnostic tests compared with specific
inhalation challenges Diagnostic tests
Sensitivity Specificity PPV NPV () () () () C
linical history 87 14 75 50 Methacholine
test 90 7 68 25 Skin prick tests 100 21 74 100 His
tory skin prick tests 94 36 76 71 PPV,
positive predictive value NPV, negative
predictive value. Nurses exposed to latex.
From Vandenplas O et al. J Allergy Clin Immunol
2001
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Skin prick tests and methacholine inhalation test
If positive skin prick test with an
aeroallergen positive methacholine test, 80
likelihood that an asthmatic reaction will occur
if exposure to this aeroallergen
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Sensitivity, specificity, and predictive values
of diagnostic tests compared with specific
inhalation challenges sen- spe- PPV NPV tiv
ity cificity () () () () history 80 55 30 9
2 methacholine testing 73 51 27 92 PPV,
positive predictive value NPV, negative
predictive value. 204 workers exposed to latex
(62), flour(28) and isocyanates (114) Baur X et
al. Am J Ind Med 1998
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Girard F et al. Am J Respir Crit Care Med 2004
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Validity of immunological tests in workers
exposed to isocyanates

• Diagnostic tests
• Sensitivity Specificity PPV NPV
• () () () ()
• Specific IgE 21 89 67 50
• Specific IgG 47 74 72 50
• MCP-1 79 91 89 83
• MCP-1 Monocyte chemoattractant protein-1
• Bernstein DI et al. Am J Respir Crit Care Med
  2002

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• Review on available tools
• 2. How to use these tools

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Surveillance of asthma in the workplace
Compatible history and/or exposure to a relevant
agent
Immunological tests possible skin prick tests,
specific antibodies
Skin prick tests not feasible (low
molecular weight agents)
Positive sensitization
Negative no sensitization
Methacholine inhalation test (working period)
abnormal
normal
No asthma, no occupational asthma
No occupational asthma
PEF monitoring and/or referral
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Conclusion
Several tools to be used in combination in
surveillance programs or investigation of
individual cases of possible workplace
asthma. For high-molecular-weight agents and
some low-molecular-weight agents skin prick
tests and methacholine test while at work For
most low-molecular-weight agents ?