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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 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
3. RADS or iiA: Case report (2) 52 yr old chemical factory worker During smouldering fire unable to find door, approximately 10 min exposure to plastic pyrolysis products Previously healthy. Physician after accident saw conjunctivitis, nothing else. Starting this day, variable respiratory symptoms. Mild obstruction with 6 % reversibility, moderate BHR.
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5. OA and BHR: Definition (1) e.g., “Occupational asthma is a disease characterized by variable airflow limitation and / or airway hyper- responsiveness and / or inflammation due to causes and conditions attributable to a particular occupational environment and not to stimuli encountered outside the workplace.“ Bernstein, I.L., et al., Asthma in the workplace, 2006 (new versus 1993)
6. 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 asthma Thus, only inducers should be considered causal agents Bernstein, I.L., Asthma in the workplace, 2006
7. 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
8. 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)
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10. Workplace exposure Acute, high RADS Chronic, low high Chronic bronchitis Asthma Asthma-like syndrome Sensitizer Atopic asthma Irritant Modified from do Pico 2004
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12. 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
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14. 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
15. RADS Epidemiology (1) - Onset at home possible - Typically occupational setting - Frequent with industrial accidents, e.g., Bhopal Nemery, 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
16. 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 % von 197 developed asthma symptoms and variable obstruction, 68 % developed bronchitis and bronchiectasis Emad, A., Chest 112 (1997) 734
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18. RADS Spirometry and therapy - BHR improves up to 3 yrs later - Obstruction often with low reversibility 6 out of 15 patients showed increase in FEV 1 of > 15 % in Gautrin, D., et al., ERJ 8 (1995) 2046 Therapy: Steroids frequently used Steroids no substitute for environmental control
19. RADS case reports of varieties - classic allergic isocyanate asthma following RADS - Metal fume fever with RADS
20. 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 Mostly no asthma (exception: e.g., isocyanate asthma) Specific challenge under laboratory conditions with suspected agent / extract Lung function monitoring by the patient for at least 3 wks with / without workplace exposure positive Probably occupational asthma Lung function monitoring at the workplace vs. non-exposure Probably non-occupational asthma negative suspicious un-suspicious suspicious un-suspicious and / or negative positive OA and BHR: Diagnostic approach Not true for RADS
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22. 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
25. 1 2 3 POR (95% CI) 0 2 3 4 1 0 2 3 4 1 0 2 3 4 1 0 2 3 4 1 Shortness of breath Cough without sputum Wheeze Flu-like symptoms n = 4420 Work-related respiratory symptoms in relation to daily work in swine confinement house (in quartiles) Radon et al. 2001 Adjusted for study centre, age, sex and smoking history
27. OR for occupational asthma # : ECRHS # BHR + symptoms/medication *adjusted for study centre, age, sex and smkoking status Kogevinas et al. 1999 ... 1.2 (0.9-1.7) 13) Housewives 1.8 (1.0-3.2) 6) Farm workers 2.0 (0.7-5.3) 5) Spray painters 2.0 (1.3-2.9) 4) Cleaning personell 2.5 (0.6-8.3) 3) Plastic manufacturing 2.3 (1.0-5.3) 2) Painters 2.6 (1.3-5.4) 1) Farmers OR (95% CI)* Job group
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29. ECRHS OA cohort (n = 3543) Kaplan Meier curve for physician-diagnosed asthma according to the number of sprays used at least weekly Zock JP, … K Radon, … submitted
38. Don’t forget COPD! Case control study in occupational outpatient clinic Mastrangelo et al. 2003 0,1 1 10 100 1000 Farmers Welders Wood Textile Builders Foundry workers OR (95% CI) Adjusted for age, smoking, year starting work
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40. 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
46. Computer-oriented case based e-learning Story Chief complaint History taking, Occupational history Medical and technical examinations Background information: Workplaces, legal aspects Medical estimate
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49. Mr. Bun, a 52-year old patient, attends your outpatient clinic. For three years he has been suffering from sneezing, an itching and running nose , red, itching eyes , and swelling of eyelids. Since last year he has developed a cough with breathlessness and wheeze. What is the most likely diagnosis with these symptoms? Free text entry: Please type your answer in the box _________________________________________
51. New cases Construction worker with skin carcinoma Workplace survey Protection of the unborn child Pleura mesothelioma Occupational health nurses Silicosis Psychosocial problems at work Hypersensitivity pneumonitis (HP) Welder with maculopathy Workplace accident due to alcohol Occupational asthma / HP Trichloroethanol intoxication Salt workers Surveillance programm for asbestos
