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Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
Rads and irritant induced asthma
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Rads and irritant induced asthma

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  • 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.
  • 4. RADS and Irritant Induced Asthma <ul><li>Overview </li></ul><ul><li>RADS </li></ul><ul><li>Irritant induced asthma </li></ul><ul><li>Internet sources </li></ul><ul><li>Summary </li></ul>
  • 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)
  • 9. OA and BHR: Pathogenesis, types of disease - typical agents <ul><li>High molecular weight agents flour, latex </li></ul><ul><li>Low molecular weight agents platinum salts </li></ul><ul><li>Irritants (RADS) chlorine, phosgen </li></ul><ul><li>Potroom Asthma HF, SO 2 , (aluminium chloride? fluoride?) </li></ul><ul><li>Asthma-like Syndrome endotoxin, NH 3 </li></ul>Atopic asthma
  • 10. Workplace exposure Acute, high RADS Chronic, low  high Chronic bronchitis Asthma Asthma-like syndrome Sensitizer Atopic asthma Irritant Modified from do Pico 2004
  • 11. RADS and Irritant Induced Asthma <ul><li>Overview </li></ul><ul><li>RADS </li></ul><ul><li>Irritant induced asthma </li></ul><ul><li>Internet sources </li></ul><ul><li>Summary </li></ul>
  • 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
  • 13. Criteria for the diagnosis of RADS (2) <ul><li>asthma-like syndrome </li></ul><ul><li>abrupt start 12-24 h following end of exposure </li></ul><ul><li>following high irritant exposure </li></ul><ul><li>duration &gt; 3 months </li></ul><ul><li>no pre-existing airway disease </li></ul><ul><li>obstruction and/or </li></ul><ul><li>BHR </li></ul>do Pico 2004
  • 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
  • 17. RADS Clinical manifestation <ul><li>- Negative previous history </li></ul><ul><li>- Mucosal symptoms, burning sensation in upper respiratory tract, thoracic pain, dyspnea, cough, wheezing &lt; 24 h </li></ul><ul><li>Patients can identify exact date </li></ul><ul><li>Risk factors </li></ul><ul><li>Dose </li></ul><ul><li>Pre-existing BHR? </li></ul><ul><li>Smoking? </li></ul>
  • 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 &gt; 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
  • 21. RADS and Irritant Induced Asthma <ul><li>Overview </li></ul><ul><li>RADS </li></ul><ul><li>Irritant induced asthma </li></ul><ul><li>Internet sources </li></ul><ul><li>Summary </li></ul>
  • 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
  • 23. Distinguishing RADS and “classical“ irritant asthma (2)
  • 24. &nbsp;
  • 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
  • 26. Cleaners
  • 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
  • 28. Incidence of asthma (doctor’s diagnosis) in Finnish cleaners Karjalainen et al. 2002 <ul><li>5 % of all females working as cleaners </li></ul><ul><li>3.4 cases per 1.000 per year </li></ul><ul><li>age adjusted RR vs office workers: 1.5 (1.4-1.6) </li></ul><ul><li>Risk  in all industrial areas </li></ul><ul><li>Attributable fraction: 33 % (30-36 %) </li></ul>
  • 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
  • 30. Summary of new data on cleaners <ul><li>Enhanced risk for obstructive airway diseases </li></ul><ul><li>High number of exposed people </li></ul><ul><li>Job attributable fraction probably high </li></ul><ul><li>Sprays at home seem to be risky </li></ul>
  • 31. mechanic electronic Mobile, onsite peak flow monitoring / spirometry
  • 32. Workplace provocation challenge
  • 33. Variant: potroom asthma
  • 34. &nbsp;
  • 35. &nbsp;
  • 36. 0-0,4 0,4-0,8 &gt;0,8 mg/m 3 fluoride 0 5 10 15 RR (95% CI) Variant: potroom asthma: RR for potroom asthma in relation to fluoride exposure Kongerud et al. 1994
  • 37. Spirometry in non-smoking potroom workers and controls Radon et al. 1999
  • 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
  • 39. RADS and Irritant Induced Asthma <ul><li>Overview </li></ul><ul><li>RADS </li></ul><ul><li>Irritant induced asthma </li></ul><ul><li>Internet sources </li></ul><ul><li>Summary </li></ul>
  • 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
  • 41. www.occupationalasthma.com
  • 42. www.acgih.org
  • 43. www.cdc.gov/niosh/ipcs/cstart.html
  • 44. www.mak-collection.com
  • 45. &nbsp;
  • 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
  • 47. &nbsp;
  • 48. <ul><li>Bakers´Asthma </li></ul><ul><li>Bronchus Carcinoma, Claim for compensation </li></ul><ul><li>Occupational screening in miners </li></ul><ul><li>Asbestosis </li></ul><ul><li>Tuberculosis in a healthcare worker </li></ul><ul><li>Latex allergy in a healthcare worker </li></ul><ul><li>Needle stick injury (Hepatitis) in a healthcare worker </li></ul><ul><li>Forestry worker with white fingers (Vasospastic Syndrom) </li></ul><ul><li>Carpal Tunnel Syndrom </li></ul><ul><li>Bladder cancer due to aromatic amines </li></ul><ul><li>Nasal septum perforation due to Chromium </li></ul><ul><li>Halogen hydrocarbonates/ liver cirrhosis </li></ul><ul><li>Lead intoxication </li></ul><ul><li>Occupational accident </li></ul><ul><li>Flight attendant with Diabetes mellitus </li></ul><ul><li>Radiation protection </li></ul><ul><li>Epidemiologic study </li></ul><ul><li>Preventive medical check-up </li></ul>Cases so far available Lung Healthcare worker Musculosceletal „ Classical“ OM Methods
  • 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 _________________________________________
  • 50. Worldwide participants of NetWoRM
  • 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
  • 52. RADS and Irritant Induced Asthma <ul><li>Overview </li></ul><ul><li>RADS </li></ul><ul><li>Irritant induced asthma </li></ul><ul><li>Internet sources </li></ul><ul><li>Summary </li></ul>
  • 53. Summary: ATS Statement Occupational asthma 2003 <ul><li>RADS : </li></ul><ul><li>RADS infrequent </li></ul><ul><li>Magnitude of exposure probably most important risk factor </li></ul>
  • 54. Summary: ATS Statement Occupational asthma 2003 <ul><li>Organic Dust-induced Asthma-like Disorder : </li></ul><ul><li>Workers chronically exposed to organic dust have increased risk for cough and sputum </li></ul><ul><li>Magnitude of endotoxin exposure probably relevant </li></ul>
  • 55. Conclusion: Vandenplas, Malo ERJ 2003 <ul><li>Non immunological occupational asthma: </li></ul><ul><li>Was attributed to multiple low-dose exposures. </li></ul><ul><li>Evidence for “low-dose RADS“ or „not-so-sudden RADS“ very weak </li></ul>
  • 56. Conclusion: Bardana JACI 2003 <ul><li>There is a chronic occupational asthma induced by low to moderate irritant doses. </li></ul><ul><li>Unprobable that new cases of asthma are induced by this. </li></ul>
  • 57. Conclusion: Banks Allergy Clin Immunol 2001 <ul><li>Low-level RADS has little to do with RADS and presents mostly as asthma-like syndrome. </li></ul><ul><li>The role of non-sensitizing low level irritants in the development of asthma ist still unknown. </li></ul>
  • 58. Summary <ul><li>Occupational exposure to low level irritants is associated with obstructive airway diseases. </li></ul><ul><li>This can be demonstrated in, e.g., primary aluminum industry, farmers, cleaning personell. </li></ul>
  • 59. Ilginiz için çok teşekkür ediyorum

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