rads and irritant induced asthma
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RADS and irritant induced asthma
Dennis Nowak
Institute and Outpatient Clinic for Occupational and Environmental Medicine
Ludwig-Maximilians-University Munich, Germany
RADS and Irritant Induced Asthma
- Overview
- RADS
- Irritant induced asthma
- Internet sources
- Summary
OA and BHR: Pathogenesis, types of disease - typical agents
• 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
Atopic asthma
Workplace exposure
Acute, high
RADS
Chronic, lowhigh
Chronic bronchitisAsthma Asthma-like syndrome
Sensitizer
Atopic asthma
Irritant
Modified from do Pico 2004
RADS and Irritant Induced Asthma
- Overview
- RADS
- Irritant induced asthma
- Internet sources
- Summary
Criteria for the diagnosis of RADS (1)
1. Absence of preceding respiratory complaints2. 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 qualities4. Onset of symptoms occuring within 24 hours after the exposure and persisting for at least three months5. Symptoms consistend with asthma, with cough, wheezing and dyspnoea predominating6. Pulmonary function tests may show airflow obstruction7. Appropriate challenge testing showing increasing airway responsiveness8. Other types of pulmonary diseases excluded
modified from Brooks, 1985
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
RADS: Historic exposures
Chlorine gas exposure in industrial workers during world war I pulmonary edema, death persistent respiratory symptoms
Winternitz, W., JAMA 73 (1919) 689Weill, H., et al., ARRD 99 (1969) 374
Sulfur dioxide exposure longstanding obstruction
Härkönen, H., et al., ARRD 128 (1983) 890
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
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
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
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?
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
RADS case reports of varieties
- classic allergic isocyanate asthma following RADS
- Metal fume fever with RADS
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.,
isocyanateasthma)
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
Probablyoccupational
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 fo
r RADS
RADS and Irritant Induced Asthma
- Overview
- RADS
- Irritant induced asthma
- Internet sources
- Summary
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
Distinguishing RADS and “classical“ irritant asthma (2)
1
2
3P
OR
(95
% C
I)
0 2 3 41 0 2 3 41 0 2 3 41 0 2 3 41Shortness ofbreath
Cough withoutsputum
Wheeze Flu-likesymptoms
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
Cleaners
Job group OR (95% CI)*
1) Farmers 2.6 (1.3-5.4)
2) Painters 2.3 (1.0-5.3)
3) Plastic manufacturing 2.5 (0.6-8.3)
4) Cleaning personell 2.0 (1.3-2.9)
5) Spray painters 2.0 (0.7-5.3)
6) Farm workers 1.8 (1.0-3.2)
...
13) Housewives 1.2 (0.9-1.7)
OR for occupational asthma#: ECRHS
#BHR + symptoms/medication*adjusted for study centre, age, sex and smkoking status
Kogevinas et al. 1999
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
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.,
isocyanateasthma)
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
Probablyoccupational
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 including irritant asthma: Diagnostic approach
mechanic
electronic
Mobile, onsite peak flow monitoring / spirometry
E.P., *15.03.1966 (hairdresser) Peak flow record
Workplace provocation challenge
Variant: potroom asthma
0-0,4 0,4-0,8 >0,8 mg/m3 fluoride0
5
10
15RR (95% CI)
Variant: potroom asthma: RR for potroom asthma in relation to fluoride exposure
Kongerud et al. 1994
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 Foundryworkers
OR
(95
% C
I)
Adjusted for age, smoking, year starting work
RADS and Irritant Induced Asthma
- Overview
- RADS
- Irritant induced asthma
- Internet sources
- Summary
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
www.occupationalasthma.com
www.mak-collection.com
RADS and Irritant Induced Asthma
- Overview
- RADS
- Irritant induced asthma
- Internet sources
- Summary
ATS Statement Occupational asthma 2003
RADS:
RADS infrequent
Magnitude of exposure probably most important risk factor
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
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.
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.
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.
Ilginiz için çok teşekkür ediyorum
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)
OA and BHR: Definition (2)
Generally:Inducers: cause airway inflammation and BHRInciters: trigger airway narrowing in patients with BHR, increase frequency of symptoms in pts. with pre-existing asthma
Thus, only inducers should be considered causal agentsBernstein, I.L., Asthma in the workplace, 2006
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
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)
RADS or iiA: Case report (1)
55 yr old pool attendant who had to add chlorinetablets to swimming pools several timesper week
No documented excesses of TLVsNo accidental exposures documented
Work-related respiratory symptomsNormal spirometry and bodyplethysmographyMild BHR, work-related PEF not conclusive
52 yr old chemical factory workerDuring smouldering fire unable to find door,approximately 10 min exposure to plasticpyrolysis products
Previously healthy. Physician after accident saw conjunctivitis, nothing else. Starting this day,variable respiratory symptoms. Mild obstruction with 6 % reversibility, moderate BHR.
RADS or iiA: Case report (2)
Incidence of asthma (doctor’s diagnosis) in Finnish cleaners
Karjalainen et al. 2002
• 5 % of all females working as cleaners
• 3.4 cases per 1.000 per year
• age adjusted RR vs office workers: 1.5 (1.4-1.6)
• Risk in all industrial areas
• Attributable fraction: 33 % (30-36 %)
Summary of new data on cleaners
Enhanced risk for obstructive airway diseases
High number of exposed people
Job attributable fraction probably high
Sprays at home seem to be risky
4
4
4
4380
360
340
320
300
280
260
240
220
200
180
160
Peak E
xpirato
ry F
low
(P
EF
) Litre
s / M
inute
20%
50%
D.V
.By Whole Record Mean
Date
ReadingsWork Hours
Additional
W0304October, 20011011
T0405
1111
F0507
1411
S0708
8
M0809
8
T0910
8
W1011
9
T1111
7
T1112
1011
F1213
1011
S1315
1411
M1516
8
T1617
8
W1718
8
T1818
7
T1819
1011
F1920
1011
S2022
1411
M2223
8
T2324
8
W
cewW
Daily MaxDaily MeanDaily MinOasys 2b score for periodPatient restedPatient worked a day shiftPatient worked an afternoon shiftPatient worked a night shiftPatient workedPatient recorded no dataDay excludedThere are comments for dayDay is marked for exclusionMissing waking reading(s)Waking reading(s) created
P.S. Burge, W. Anees
Spirometry in non-smoking potroom workers and controls
60
70
80
90
100
110
120
130
140
150
IVC FVC FEV1 Tiffeneau PEF
% v
om S
oll
Elektrolyse (n = 37)
Gießerei (n = 11)
Anodenfertigung (n = 19)
Kontrolle (n = 35)
**
** **
Radon et al. 1999
1. Bakers´Asthma 2. Bronchus Carcinoma, Claim for compensation3. Occupational screening in miners 4. Asbestosis5. Tuberculosis in a healthcare worker6. Latex allergy in a healthcare worker7. Needle stick injury (Hepatitis) in a healthcare worker8. Forestry worker with white fingers (Vasospastic
Syndrom)9. Carpal Tunnel Syndrom10. Bladder cancer due to aromatic amines11. Nasal septum perforation due to Chromium12. Halogen hydrocarbonates/ liver cirrhosis 13. Lead intoxication14. Occupational accident15. Flight attendant with Diabetes mellitus16. Radiation protection17. Epidemiologic study18. Preventive medical check-up
Cases so far availableLungHealthcare workerMusculosceletal„Classical“ OMMethods
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
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Co-ordinating centre:Unit for Occupational andEnvironmental Epidemiology & Net Teaching Munich
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New cases
Construction worker with skin carcinoma
Workplace surveyProtection of the unborn child
Pleura mesothelioma
Occupational health nursesSilicosis
Psychosocial problems at work
Hypersensitivity pneumonitis (HP)Welder with maculopathy
Workplace accident due to alcohol
Occupational asthma / HPTrichloroethanol intoxication
Salt workers
Surveillance programm for asbestos
Summary: ATS Statement Occupational asthma 2003
Organic Dust-induced Asthma-like Disorder:
Workers chronically exposed to organic dust have
increased risk for cough and sputum
Magnitude of endotoxin exposure probably relevant
www.acgih.org
www.cdc.gov/niosh/ipcs/cstart.html
Computer-oriented case based e-learning
Story
Chief complaint
History taking, Occupational history
Medical and technical examinations
Background information:Workplaces, legal aspects
Medical estimate
U.M. *21.08.48 (colophony worker) Peak flow record
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