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

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1011

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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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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