www.asthma-workplace.com

Tools in the investigation of

asthma in the workplace

Jean-Luc Malo MD

Hôpital du Sacré-Cœurde Montréal

Université de Montréal

Axe de rechercheen santé respiratoire

Centre asthme et travailCenter for Asthma in the Workplace

1. Review on available tools

2. How to use these tools

Tools

1. Questionnaires

2. Immunologial tests

3. Lung function tests

Standardized epidemiological questionnaire for asthma:

Developed by the EuropeanRespiratory Society*

Addition of questions relevant to theintensity and timing of symptomsin relation to the workplace(not standardized)

* Burney PGJ et al. Eur Respir J 1988

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

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

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?

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 homeOnset of symptoms only on returning homeChange of timing of symptoms over time

Questionnaire items relevant to asthma in the workplace

Is the clinical history a satisfactory means

to diagnose occupational asthma ? *

Sensitivity: 87 %Specificity: 55 %Positive predictive value: 63 %Negative predictive value: 83 %

* Prospective clinical assessment of 162 patients

referred for possible occupational asthma.

Malo JL et al. Am Rev Respir Dis 1991

Symptoms at work OR 95% CI p

Wheezing 3.39 1.43-8.0 0.005Loss of voice 0.39 0.18-0.86 0.02Nasal itching 3.7 1.8-7.8 0.0006Ocular itching 2.37 1.06-5.30 0.03

Subjects exposed to high-molecular-weight agents

Wheezing 6.79 1.53-30.0 0.01Loss of voice 0.14 0.03-0.64 0.01Nasal itching 6.23 1.489-26.1 0.01

Subjects exposed to low-molecular-weight agentsNo symptom significantly associated with occupational asthma

Questionnaire items most likely to be associated tothe presence or absence of occupational asthma *

* Vandenplas O. et al. Eur respir J 2005

Tools

1. Questionnaires

2. Lung function tests

3. Immunological tests

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..

Assessment of bronchial responsiveness (methacholine)

Suggests that someone may have asthmaIf negative test, this virtually excludes current asthmaFalse positive test in rhinitis and COPD.

If negative test while a worker is at work andreports symptoms, this virtually excludes asthma and occupational asthma (butnot eosinophilic bronchitis).

If positive test while a worker is at work, thissuggests either asthma or occupational asthma.

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)

Tools

1. Questionnaires

2. Lung function tests

3. Immunological tests

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)

Sensitivity, specificity, and predictive values of diagnostic tests

compared with specific inhalation challenges *

Diagnostic tests Sensitivity Specificity PPV NPV

(%) (%) (%) (%)

Clinical history 87 14 75 50

Methacholine test 90 7 68 25

Skin prick tests 100 21 74 100

History + 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

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

Sensitivity, specificity, and predictive values of diagnostic tests

compared with specific inhalation challenges *

sen- spe- PPV NPVtivity cificity

(%) (%) (%) (%) history 80 55 30 92

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 *

Girard F et al. Am J Respir Crit Care Med 2004

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

Validity of immunological tests

in workers exposed to isocyanates

1. Review on available tools

2. How to use these tools

Compatible historyand/or exposure to a relevant agent

Immunological tests possible:skin prick tests,

specific antibodies

Methacholine inhalation test(working period)

abnormalnormal

No asthma,no occupational asthma

PEF monitoringand/or referral

Positive:sensitization

Negative:no sensitization

No occupationalasthma

Skin pricktests not feasible(low molecularweight agents)

Surveillance of asthma in the workplace

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: ?