Tools in the investigation of asthma in the workplace Jean-Luc Malo MD Hôpital du Sacré-Cœur de Montréal Université de Montréal Axe de recherche en santé respiratoire Centre asthme et travail Center 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 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

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 RespiratorySystemicRhinitisConjunctivitis CoughFeverNasal obstructionOcular itching SputumChillsRunny noseWatery eyes Chest tightnessMuscle or joint achesSneezingRedness of the eyes WheezingNasal/pharyngeal itching Shortness of breath at rest Shortness of breath on exerciseSkin Loss of voiceRash/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 home Onset of symptoms only on returning home Change 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 workOR95% CIp Wheezing Loss of voice Nasal itching Ocular itching Subjects exposed to high-molecular-weight agents Wheezing Loss of voice Nasal itching Subjects exposed to low-molecular-weight agents No symptom significantly associated with occupational asthma Questionnaire items most likely to be associated to the 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 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.

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 SensitivitySpecificityPPVNPV (%)(%)(%)(%) Clinical history Methacholine test Skin prick tests History + skin prick tests 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-PPVNPV tivitycificity (%)(%)(%)(%) history methacholine testing 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 SensitivitySpecificityPPVNPV (%)(%)(%)(%) Specific IgE Specific IgG MCP-1 * 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 history and/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 monitoring and/or referral Positive: sensitization Negative: no sensitization No occupational asthma Skin prick tests not feasible (low molecular weight 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: ?