RADS and irritant induced asthma

1. RADS and irritant induced asthma Dennis Nowak Institute and Outpatient Clinic for Occupational and Environmental Medicine Ludwig-Maximilians-University Munich, Germany

2. RADS and Irritant Induced Asthma • Overview • RADS • Irritant induced asthma • Internet sources • Summary

3. OA and BHR: Pathogenesis, types of disease - typical agents Atopic asthma • High molecular weight agents flour, latex • Low molecular weight agentsplatinum salts • Irritants (RADS)chlorine, phosgen • Potroom AsthmaHF, SO2, (aluminium chloride? fluoride?) • Asthma-like Syndromeendotoxin, NH3

4. Workplace exposure Irritant Sensitizer Chronic, lowhigh Acute, high RADS Chronic bronchitis Asthma Asthma-like syndrome Atopic asthma Modified from do Pico 2004

5. RADS and Irritant Induced Asthma • Overview • RADS • Irritant induced asthma • Internet sources • Summary

6. Criteria for the diagnosis of RADS (1) 1. Absence of preceding respiratory complaints 2. Onset of symptoms occurring after a single specific exposure incident or accident 3. Exposure was to a gas, smoke, fume or vapour that was present in very high concentrations and had irritant qualities 4. Onset of symptoms occuring within 24 hours after the exposure and persisting for at least three months 5. Symptoms consistend with asthma, with cough, wheezing and dyspnoea predominating 6. Pulmonary function tests may show airflow obstruction 7. Appropriate challenge testing showing increasing airway responsiveness 8. Other types of pulmonary diseases excluded modified from Brooks, 1985

7. Criteria for the diagnosis of RADS (2) • asthma-like syndrome • abrupt start 12-24 h following end of exposure • following high irritant exposure • duration > 3 months • no pre-existing airway disease • obstruction and/or • BHR do Pico 2004

8. RADS: Historic exposures Chlorine gas exposure in industrial workers during world war I  pulmonary edema, death  persistent respiratory symptoms Winternitz, W., JAMA 73 (1919) 689 Weill, H., et al., ARRD 99 (1969) 374 Sulfur dioxide exposure  longstanding obstruction Härkönen, H., et al., ARRD 128 (1983) 890

9. RADS Epidemiology (1) - Onset at home possible - Typically occupational setting - Frequent with industrial accidents, e.g., BhopalNemery, B., ERJ 9 (1996) 1973 - Incidence? - Acetic acid in hospital: 8/51 within 2.5 h Kern, ARRD 144 (1991) 1058- Chlorine: 53/75 developed BHR Bhérer, L., et al., OEM 51 (1994) 225

10. RADS Epidemiology (2) - Chlorine: Follow up of 239 subjects for 3 yrs: BHR dose-dependent Gautrin, D., ERJ 8 (1995) 2046- Mustard gas (Iran / Iraq war): 11 % of 197 developed asthma symptoms and variable obstruction, 68 % developed bronchitis and bronchiectasis Emad, A., Chest 112 (1997) 734

11. Acute Exposure to Chlorine Gas in excess of an estimated 28 ppm for 30 minutes is associated with significant deficits in FVC and FEV1 at 8-10 months post-exposure Erik R. Svendsen, PhD MS ATS Mini-Symposium A13, 2007

12. RADS Clinical manifestation • - Negative previous history • - Mucosal symptoms, burning sensation in upper respiratory tract, thoracic pain, dyspnea, cough, wheezing < 24 h • Patients can identify exact date • Risk factors • Dose • Pre-existing BHR? • Smoking?

13. RADS Spirometry and therapy - BHR improves up to 3 yrs later - Obstruction often with low reversibility 6 out of 15 patients showed increase in FEV1 of > 15 % in Gautrin, D., et al., ERJ 8 (1995) 2046 Therapy: Steroids frequently used Steroids no substitute for environmental control

14. RADS case reports of varieties - classic allergic isocyanate asthma following RADS - Metal fume fever with RADS

15. OA and BHR: Diagnostic approach History, questionnaire, SPT, specific IgE (if possible) Non-specific provocation challenge (e.g., MCh) if possible at the end of a working week after at least two weeks with relevant exposure positive negative Lung function monitoring by the patientfor at least 3 wks with / withoutworkplace exposure Specific challenge under laboratory conditions with suspected agent / extract and / or Not true for RADS suspicious un-suspicious positive negative Lung function monitoring at the workplace vs. non-exposure Mostly no asthma (exception: e.g., isocyanateasthma) suspicious un-suspicious Probably occupational asthma Probably non-occupational asthma

16. RADS and Irritant Induced Asthma • Overview • RADS • Irritant induced asthma • Internet sources • Summary

17. Distinguishing RADS and “classical“ irritant asthma (1) „Irritant asthma“ is broader wording Multiple exposures also possible with RADS RADS typically follows “big bang“ „Low-dose RADS“ (Kipen et al., JOM 36 (1994) 1133) is problematic wording since it suggests no excess over thresholds

18. Distinguishing RADS and “classical“ irritant asthma (2)

20. Work-related respiratory symptomsin relation to daily work in swine confinement house (in quartiles) 3 n = 4420 2 POR (95% CI) 1 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 0 1 2 3 4 Shortness ofbreath Cough without Wheeze Flu-like sputum symptoms Adjusted for study centre, age, sex and smoking history Radon et al. 2001

21. Cleaners

22. OR for occupational asthma#: ECRHS #BHR + symptoms/medication*adjusted for study centre, age, sex and smkoking status Kogevinas et al. 1999

23. ECRHS OA cohort (n = 3543) Kaplan Meier curve for physician-diagnosed asthma according tothe number of sprays used at least weekly Zock JP, … K Radon, … submitted

24. OA including irritant asthma: Diagnostic approach History, questionnaire, SPT, specific IgE (if possible) Non-specific provocation challenge (e.g., MCh) if possible at the end of a working week after at least two weeks with relevant exposure positive negative Lung function monitoring by the patientfor at least 3 wks with / withoutworkplace exposure Specific challenge under laboratory conditions with suspected agent / extract and / or suspicious un-suspicious positive negative Lung function monitoring at the workplace vs. non-exposure Mostly no asthma (exception: e.g., isocyanateasthma) suspicious un-suspicious Probably occupational asthma Probably non-occupational asthma

25. Mobile, onsite peak flow monitoring / spirometry mechanic electronic

26. E.P., *15.03.1966 (hairdresser) Peak flow record

27. Workplace provocation challenge

28. Variant: potroom asthma

30. Variant: potroom asthma: RR for potroom asthma in relation to fluoride exposure 15 RR (95% CI) 10 5 0 0-0,4 0,4-0,8 >0,8 mg/m3 fluoride Kongerud et al. 1994

31. Don’t forget COPD! Case control study in occupational outpatient clinic 1000 100 OR (95% CI) 10 1 0,1 Farmers Welders Wood Textile Builders Foundryworkers Adjusted for age, smoking, year starting work Mastrangelo et al. 2003

32. RADS and Irritant Induced Asthma • Overview • RADS • Irritant induced asthma • Internet sources • Summary

33. Internet sources www.asmanet.com http://www.remcomp.ft/asmanet/asmapro/asmawork.htm http://epa.gov/ttn/atw/urban/asthmatable.pdf http://www.occupationalasthma.com www.acgih.org www.cdc.gov/niosh/ipcs/cstart.html www.networm-online.net

34. www.occupationalasthma.com

35. www.mak-collection.com

38. RADS and Irritant Induced Asthma • Overview • RADS • Irritant induced asthma • Internet sources • Summary

39. ATS Statement Occupational asthma 2003 RADS: • RADS infrequent • Magnitude of exposure probably most important risk factor

40. Vandenplas, Malo ERJ 2003 Non immunological occupational asthma: • Was attributed to multiple low-dose exposures. • Evidence for “low-dose RADS“ or „not-so-sudden RADS“ very weak

41. Bardana JACI 2003 • There is a chronic occupational asthma induced by low to moderate irritant doses. • Unprobable that new cases of asthma are induced by this.

42. Banks Allergy Clin Immunol 2001 • Low-level RADS has little to do with RADS and presents mostly as asthma-like syndrome. • The role of non-sensitizing low level irritants in the development of asthma ist still unknown.

43. Summary • Occupational exposure to low level irritants is associated with obstructive airway diseases. • This can be demonstrated in, e.g., primary aluminum industry, farmers, cleaning personell.

44. Ilginiz için çok teşekkür ediyorum

46. OA and BHR: Definition (1) e.g.,“Occupational asthma is a disease characterized by variable airflow limitation and / or airway hyper-responsiveness and / or inflammationdue to causes and conditions attributable to a particularoccupational environment and not to stimuli encountered outside the workplace.“ Bernstein, I.L., et al., Asthma in the workplace, 2006 (new versus 1993)

47. OA and BHR: Definition (2) Generally:Inducers: cause airway inflammation and BHR Inciters: trigger airway narrowing in patients with BHR, increase frequency of symptoms in pts. with pre-existing asthmaThus, only inducers should be considered causal agents Bernstein, I.L., Asthma in the workplace, 2006

48. OA and BHR: Pathogenesis, types of disease High molecular weight compounds: mostly IgE-mediated, latency period Low molecular weight compounds: some (e.g. acid anhydrides, platinum salts, reactive dyes) IgE-mediated mostly non-IgE mediated but may combine with airway proteins T-cells frequently involved

49. OA and BHR: Types of disease Occupational asthma - immunological - non-immunological including RADS Work-aggravated asthma Variant syndromes - eosinophilic bronchitis - potroom asthma - asthma-like syndrome (e.g., organic dusts)

50. RADS or iiA: Case report (1) 55 yr old pool attendant who had to add chlorine tablets to swimming pools several times per week No documented excesses of TLVs No accidental exposures documented Work-related respiratory symptoms Normal spirometry and bodyplethysmography Mild BHR, work-related PEF not conclusive