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Hôpital du Sacré-Cœur de Montréal

Hôpital du Sacré-Cœur de Montréal. Diagnosis of occupational asthma Catherine Lemiere MD, MSc Hôpital du Sacré-Cœur Université de Montréal. Université de Montréal. Investigation of occupational asthma. Chan-Yeung & Malo. N Engl J Med 1995; 333:107-12. Clinical history.

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Hôpital du Sacré-Cœur de Montréal

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  1. Hôpital du Sacré-Cœur de Montréal Diagnosis of occupational asthmaCatherine Lemiere MD, MScHôpital du Sacré-CœurUniversité de Montréal Université de Montréal

  2. Investigation of occupational asthma Chan-Yeung & Malo. N Engl J Med 1995; 333:107-12.

  3. Clinical history Occupational asthma * • Final diagnosis • OA (n=75) • Asthma without OA • (n=54) • No asthma, No OA • (n=33) Very probable-prob Uncertain Unlikely-No 65 6 4 25 19 10 14 10 9 Only 65 subjects (63%) out of 104 with a history suggestive of OA had actual OA * Malo JL et al. Am Rev Respir Dis 1991; 143:528-532

  4. Skin tests & RAST • Skin prick tests ± IgE/IgG ... • valid for HMWC & rarely for LMWC • requires good allergen extracts a positive test confirms sensitization but not occupational asthma Neg. pred. value:76% 89% Pos. pred. value:69% 54% Cartier A, JACI 78: 344-8

  5. Serial monitoring of Peak Expiratory Flow rates • When interpreted visually: Sensitivity: 81 à 86%, specificity: 74 à 89%. • Compliance is often bad, effort dependent test, reading of the graphs subjective. • Computerized interpretation of PEF monitoring: Oasys 2 and 3 (sensitivity 75%,82%), specificity: 94% compared to a method of diagnosis independant of PEF (SIC, IgE, or BHR) (Gannon, Thorax 1996; 51:484-9) (Bright et al. Monaldi Arch Chest Dis. 2001 Jun;56(3):281-8).

  6. Specific Inhalation Challenges • Still considered as the gold standard • Require well-trained personnel and are time consuming. • Available in a limited numbers of centers in worldwide. • A negative test does not entirely rule out the diagnosis of OA. The results may be misinterpreted if the wrong agent or process are used; patient has undergone desensitization, or the patient uses a medication inhibiting an asthmatic reaction.

  7. Future diagnostic tools? • Non invasive measurements of airway inflammation (induced sputum, exhaled NO) • In vitro testing (MCP-1)

  8. Induced sputum and occupational asthma

  9. Changes in induced sputum after specific inhalation challenges

  10. Induced sputum and occupational asthma p = 0.03 p < 0.01 3.00 2.40 1.80 Sputum eosinophils, 106/ml 1.20 0.60 0.0 B E B E B E Negative SIC Positive SIC Asthma without OA Lemiere et al JACI 2001; 107: 1063-8

  11. Changes in induced sputum at the workplace

  12. Induced sputum and occupational asthma p= 0.9 p<0.001 p=0.1 p=0.006 5.0 64.0 L L 4.0 8.0 m , / V g 1 E m F 3.0 1.0 , 0 C 2 P 2.0 0.12 1.0 0.015 Work At Off At Off At Off At Off p=0.6 p=0.007 p=0.2 p=0.01 10000 100 % , s l L i / h g p 10 1000 µ o , n P i C s o E E 100 1.0 0.1 10 Lemière C et al. Eur Respir J, 1999; 13: 482-8

  13. With sputum eosinophilia (n=14) Without sputum eosinophilia (n=24) p value SIC 3 9 – % with increased NSBR at presentation 92.9 50 0.012* FEV1 (% predicted) 61.4 (21.2) 0.001* 83 (16) Bronchodilator reversibility (ml) 397 (265) 161 (197) 0.003 * Exhaled nitric oxide (NO) ppb, 10.4 (5.6–17.4) 5.1 (3.7–6.6) 0.001* Subjects with raised NO >9.6 ppb (%) 64.3 4.2 <0.001* Sputum eosinophils (median %) 6.5 0.3 – Sputum neutrophil count (%) 59.5 (19.6) 55.1 (18.8) 0.5 Sputum macrophage (%) 24.6 (9) 43.2 (19.2) 0.002* Anees et al Thorax, 2002 57:231-6

  14. Inflammatory and functional changes in subjects with and without OA * p <0.05 (Girard et al, ATS 2004)

  15. PC20 and Sputum

  16. Sputum andPEF

  17. Occupational asthma and exhaled NO

  18. Exhaled NO and occupational asthma Pipari et al ERJ, 2002;20:1532-7

  19. Exhaled NO and occupational asthma Lund et al Occup Environ Med. 2000;57:274-8.

  20. In vitro testing (MCP-1)

  21. Rationale • Enhanced secretion of monocyte chemoattractant protein-1(MCP-1) by blood mononuclear cells after co-incubation with diisocyanate HSA (DIISO-HSA) is associated with isocyanate-induced asthma (Lummus et al, JACI, 1998102:265-74)

  22. Isocyanate-induced asthma Bersntein et al Am J Respir Crit Care Med 2002;166:445-50

  23. Isocyanate-induced asthma Bersntein et al Am J Respir Crit Care Med 2002;166:445-50

  24. Conclusions • The diagnosis of occupational asthma is difficult. • New diagnosis tools are needed to make an accurate diagnosis based upon objective measurements. • Non invasive measurements of airway inflammation are promising additional tools in the investigation of OA.

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