DIAGNOSIS OF OCCUPATIONAL ASTHMA

1. DIAGNOSIS OF OCCUPATIONAL ASTHMA Assoc. Prof. Can Sevinc Dokuz Eylul University School of Medicine Pulmonary Medicine Department Izmir - Turkiye TTS X. ANNUAL CONGRESS

2. Presantation Plan • Clinical history • PEFR monitoring • Spirometry • Skin prick test • IgE, sIgE • Induced sputum • Nonspesific bronchial challenge test • Spesific bronchial challenge test • Algorhytm

3. Occupational asthma caused by immunological sensitisation • Symptom-free latent period • Reaction to low amounts • Minority of exposed workers Asthma in the workplace (2nd Ed.) Marcel Dekker, 1999

4. Occupational asthma caused by irritation: “irritant-induced asthma” • After a single inhalation accident • RADS • “Reactive Airways Dysfunction Syndrome” Brooks S, Weiss MA, Bernstein IL. Chest, 1985, 88, 376-84

5. Occupational asthma caused by irritation: “irritant-induced asthma” • After multiple peaks of chemical irritants • Cl2, SO2, formaldehyde

6. Clinical diagnosis of asthma • Variable dyspnoea and wheezing • Nonspecific bronchial hyperresponsiveness • Cough,mucus hypersecretion • Repeated episodes of “bronchitis” *document by pulmonary function tests

7. History • Sometimes: asthma-attacks at work • Usually: more asthma symptoms in the evening or at night • (delayed reactions)

8. History • Nonspecific bronchial hyperresponsiveness causes intolerance to inhaled irritants • cigarette smoke, engine exhaust, strong odours, fog, cold air, exercise • The patient often believes that these triggers are the “cause” of the asthma

9. Symptoms • Few symptoms during work • Most symptoms after work • is common and • does not exclude occupational asthma !

10. History • Intolerance to irritants outside the workplace • Does not exclude occupational asthma !

11. Definition • Occupational asthma doesnot necessarily mean “asthma at work”, • but “asthma from work”

12. Which question? • To detect occupational asthma it is not appropriate, nor sufficient to ask • “is your asthma worse at work?” • it is more efficient to ask • “does your breathing get better during the week-end or holiday?” Burge PS, Br J Dis Chest1987; 81: 105-15.

13. Typical history • Occupational history (potential exposure to occupational agents) • Same other cases at this workplace • Allergic findings related to other systems • Concurrent new event at the same time of onset of the symptoms (new work, agent, accident) • Uncontrolled asthma in spite of appropriate treatment • Improvement of symptoms during holiday

14. Does help history of “Improvement of symptoms during holiday” • One study of 162 patients found that • 66 of 75 patients (88%) with OA stated that • their symptoms improved during holidays, • but 66 of 87 patients (76%) without occupational asthma reported a similar improvement Malo, JL, Ghezzo, H, L'Archevêque, J, et al. Am Rev Respir Dis 1991; 143:528.

15. Repeated bronchitis ??? • Repeated absence from work because of “bronchitis” may be a sign of occupational asthma • even if these episodes appear to be responsive to treatment with antibiotics, • it is the temporary removal from exposure that is most beneficial

16. Value of history • Clinical history alone is inadequate to confirm or exclude the diagnosis of OA, • although the negative predictive value is better than the positive predictive value. Malo, JL, Ghezzo, H, L'Archevêque, J, et al. Am Rev Respir Dis 1991; 143:528.

17. Allergy • Documenting allergy to common allergens does not exclude occupational asthma • house dust mite, pets, pollen • atopy is a risk factor for some forms of occupational asthma

18. Atopy • Atopy is clearly associated with OA due to HMW agents, • but because atopy is present in almost 50% of young adults, • it cannot satisfactorily predict the development of OA, • which affects less than 5% of subjects in high-risk workplaces.

19. Allergy • Although the clinician should take a history of preexisting asthma and atopy, • these characteristics have poor positive predictive values. • In one study found that • only approximately one-third of atopic subjects developed rhinoconjunctivitis or asthma symptoms in the five years following onset of exposure to laboratory animals. Slovak, AJM, Hill, RN. Br J Ind Med 1987; 44:129.

20. Always consider ! • Always consider the possibility that asthma may have an occupational aetiology • in new patients • in well-known asthmatics

21. Relation with work • Latent period (weeks-years) • Improvement when off-work • Fellow workers

22. The latency period between the onset of exposure and the onset of symptoms is highly variable. • Generally, • the latency period is shorter • with exposure to low-molecular-weight (LMW) agents, • such as isocyanates and plicatic acid (Western red cedar), • than with HMW agents. Malo, JL, Ghezzo, H, D'Aquino, C, et al. J Allergy Clin Immunol 1992; 90:937.

23. ~ 50% of subjects who develop OA due to isocyanates experience symptoms within the first two years after the onset of exposure, • whereas the median latency period after exposure to HMW agents is approximately five years.

24. Identification of cause • Exposure to known asthma-inducing agent • Type of work • Product information • Contact occupational physician • May be very difficult • Do not always rely on Material Safety Data Sheets • Beware of recent changes in work processes, suppliers of materials & ingredients, etc.

25. Identification of cause • Immunological tests • skin prick tests • specific IgE (RAST) • for macromolecular agents • usually not available and not valid for LMW agents, except for some • complex Pt salts • some reactive chemicals (organic dyes) • only indicative of sensitization, not cause

26. Skin testing • Skin test reagents are not available for documenting hypersensitivity to most occupational agents, • but the technique is feasible for some HMW agents, • such as animal or plant proteins.

27. The presence of immediate skin test reactivity reflects • IgE-specific sensitization.

28. Excessive dermal reaction to pectin İn a jam production worker

29. Negative skin prick test • A negative test virtually excludes the possibility that OA is caused by that specific antigen.

30. Specific BCT • These tests consist of intentionally exposing subjects to occupational agents in a hospital laboratory or, occasionally, at work.

31. In the case of HMW agents, bronchoprovocation testing • can be carried out in a single day, • because an immediate reaction that is maximal during the first hour following exposure is expected.

32. Identification of cause - SBCT • Specific bronchial provocation testing considered as the Gold Standard, but: • not so easy to perform • not always feasible • time-consuming and expensive • potentially dangerous (specialized centres) • not always necessary • “false negative” if challenge with wrong agent

33. SBCT • Can be done in the workplace under medical supervision, • but time-consuming and • often difficult to organize

34. Baker’s asthma Immediate response to soya and wheat flour in specific bronchial challenge test

35. Hairdresser’s asthma Dual asthmatic response to sodium persulphate in specific bronchial challange test

36. Nonspecific bronchoprovocation testing • To obtain more objective evidence of an occupational relationship of symptoms, • nonspecific bronchial hyperresponsiveness can be measured • at the end of the work period and • at the end of the period away from work.

37. The absence of bronchial hyperresponsiveness • when the subject is at work and has symptoms • virtually excludes OA.

38. LMW agents • LMW agents often cause nonimmediate or late reactions and • require daily challenges of escalating doses of antigen on sequential days. • During testing, • assessment of nonspecific bronchial hyperresponsiveness is carried out • toward the end of the challenge day or • at 24 hours after inhalation.

39. NSBCT • Increase in nonspecific bronchial responsiveness • can precede the onset of asthmatic reactions and • is an early and sensitive marker of airway responsiveness to occupational agents. Vandenplas, O, Delwiche, JP, Jamart, J, Van de Weyer, R. Thorax 1996; 51:472.

40. Relation with work • “stop-and-resume-work test” • changes in symptoms and medication need • changes in lung function • spirometry (FEV1) • nonspecific bronchial responsiveness • (histamine or methacholine PC20) • self-recorded peak-flow measurements

41. PULMONARY FUNCTION TESTS • Before assessing whether asthma is caused by workplace exposure, one should confirm that the patient indeed has asthma. • The diagnosis of asthma from history alone may not be accurate, and therefore pulmonary function testing is warranted.

42. Spirometry in the workplace • Monitoring of FEV1 in the workplace by a skilled technician should be encouraged, and • comparison with data from a non-exposure day can confirm work-related exacerbations of asthma, • But, this technique does not identify the causal agent.

43. Spirometry in the workplace • Measurement of single FEV1 values when the subject is at work and again when he/she is not at work • does not have sufficient sensitivity to detect a relationship between work and asthma. Bardy, JD, Malo, JL, Seguin, P, et al. Am Rev Respir Dis 1987; 135:1033. Burge, PS. Eur J Respir Dis Suppl 1982; 123:47.

44. PEF monitoring • Simple and inexpensive • Good specificity & sensitivity (> 80%) • Nearly always feasible • Empowerment of patient (falsification is rare) • Success depends on motivation of patient and physician • oral + written explanation

45. PEF monitoring • At least 4 x per day: 3 forced expirations • Note on form (not on graph) • time of day • 3 values of PEF • activities (home, work, exposure) • symptoms • medication • Allow missing values • Aat least 4 weeks, workdays + free days

46. PEF monitoring • Graphical analysis = essential • best of 3 PEF values • plot daily mean, maximum, minimum • day = 10 a.m. to 10 a.m. • indicate exposure • Interpretation: daily/weekly pattern is more important than magnitude of changes • “subjective” interpretation • expert system (OASYS) P.S. Burge (Birmingham)

47. PEFR monitoring • Serial measurement of PEFR’s is a useful method in the investigation and assessment of OA. Burge, PS, O'Brien, IM, Harries, MG. Thorax 1979; 34:308. Burge, PS, O'Brien, IM, Harries, MG. Thorax 1979; 34:317. Moscato, G, Godnic-Cvar, J, Maestrelli, P, et al. J Allergy Clin Immunol 1995; 96:295.

48. PEFR monitoring • Monitoring is generally carried out by asking the subject to record his or her PEF • The diagnostic period should be shortened if the patient develops pronounced airway obstruction or has severe symptoms.

50. PEFR monitoring • There are a number of potential problems inherent to this approach, including • the reproducibility of readings, • compliance and honesty of subjects, • interpretation of results, and • sensitivity and specificity compared with specific inhalation challenges.