Occupational and work-aggravated asthma

Institut and Outpatient Clinic for Occupational and Environmental Medicine

Ludwig-Maximilians-Universität Münchendennis.nowak@med.uni-muenchen.de

Dennis Nowak

LMU

Site & intensity of the injury Physico-chemical properties

Particle size…<5u go deeper Concentration… Solubility Density… lighter (as) go deeper Reactivity… higher (NH4) more damage

Duration of exposure Signs of alertness Rate / depth of breathing Host response variability / susceptibility Host defense mechanisms

MechanismsToxic Inflammatory • Irritant : farm dust, chemicals• Allergic : flour (bakers)• Sensitizers : toluene di-isocyanates • Infectious : brucellosisCarcinogenic uranium

Symptoms• Cough• Expectoration• Hemoptysis• Dyspnea at rest and/or on exertion• Wheezing• Chest tightness / pain• Upper airways symptoms• Fever, chills, other

EXPOSURE

AIRWAYS

ALVEOLI

NEUROTOXINSFEVERS

UPPER ITIS BRONCHITIS ASTHMA-LIKE ASTHMABRONCHIOLITIS BOOPPULM. EDEMAPNEUMONITISFIBROSIS

Airways exposure

Acute massive

chemical bronchitis

RADS

Chronic low

Chronic BronchitisAsthma-like disease

Acute low

Allergic asthma

Definition Occupational asthmaA. AsthmaB. Onset after entering workplaceC. Association of symptoms to workplaceD1. Agent known to cause OA orD2. Work-related changes in FEV1 or PEFs +/orD3. “ “ “ “ hyperreactivity +/orD4. Positive specific challenge test +/orD5. Clear sx onset after irritant exposure

OA and BHR: Definition (1)

e.g.,“Occupational asthma is a disease characterized by variable airflow limitation and / or airway hyper-responsiveness due to causes and conditions attributable to a particularoccupational environment and not to stimuli encountered outside the workplace.“Bernstein, I.L., Asthma in the workplace, 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, 1993

Work-aggravated asthma

Pre-existing or concurrent asthma that isaggravated by irritants or physicalstimuli at the workplace

Tarlo S. et al., Chest 118 (2000) 1309: 16 % of asthmaticsSaarinen K. et al., ERJ 22 (2003) 305:

21 % of asthmatics

OA and BHR: Pathogenesis, types of disease

Inducers: common aeroallergens EAR, LARLAR inflammation , BHR Even if no obstruction: inflam. , BHR may require removal from work

Inciters: exercise, cold air, etc.no change in inflammation or BHR may require exposure or therapy

Occupational Asthma

NO LATENCY IRRITANT-INDUCED

LATENCY IgE MEDIATEDSPECIFIC NON-IgE

Etiology Mechanism: InducersImmunologic • IgE mediated

– High molecular wght

– Low molecular haptens

• ? Cell mediated– Low molecular

Nonimmunologic– Irritant-toxic

• Grain, crab, castor beans• Woods, gum acacia• Animal dander, urine• Epoxy resins• Chloramine T• Platinum salts• di-isocyanates• Red Cedar• Cobalt• Ammonia, chlorine

History Exam Lung Function Skin tests Blood:

eosinophils, serology-RAST

Radiology Therapeutic trial

Obstructive pattern FEV1,FVC,FEV1/FVC FEF, PEFR RAW, RV/TLC

Bronchodilators Provocation tests

OA and BHR: Types of disease

Occupational asthma - immunological - non-immunological including RADSWork-aggravated asthmaVariant syndromes - eosinophilic bronchitis - potroom asthma - asthma-like syndrome (e.g., organic dusts)

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

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

OA and BHR: Diagnostic approach (1)

Questionnaire: good primary toolwork-relatednessrhinoconjunctivitis?sensitivity good, spec. +/-

Skin prick test: quick, simple, safelimited by lack of available/

standardized extractsSpecific IgE: bit less sensitive,

bit more specificsame limits as SPT

OA and BHR: Diagnostic approach (2)

Spirometry: routine spirometry far less sensitive than questionnaire!

Cross-shift spirometry: sensitivity better, but much better on multiple days!

MCh challenge: if negative, mostly excludes OAChange in BHR: +++, > 2 doubling concentrations

Induced sputum: HMW agents: eosinophils LMW agents: eos. , neutro.

Exhaled NO: usefulness questionable for OA

mechanic

electronic

Mobile, onsite peak flow monitoring / spirometry

4

4

4

4380

360

340

320

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180

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Pea

k E

xpira

tory

Flo

w (P

EF)

Litr

es /

Min

ute

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

Workplace provocation challenge

OA and BHR: Exposure-response relationship

- Exposure intensity (dose?)- Isocyanate asthma: peak levels!- No effect level? Flour dust < 0.5 mg/m3

Alpha-amylase 0.25 ng/m3

Rat urin protein 0.7 µg/m3

Latex allergens 0.6 ng/m3

cow allergen 20-30 µg/g dust- Upper end of dose-response curve flattens

- Atopy, atopic rhinitis, atopic asthma

- Smoking: only risk factor for platinum salt asthma

FEV1IMMEDIATE REACTION LATE REACTION

DUAL REACTION PROGRESSIVE-PROLONGED

O

HOME-------------WORK-----HOME—WORK--HOMEWORK

Rx

Reactive Airways DysfunctionSyndrome

Asthma-like syndrome Abrupt onset within 12-24 hrs After high irritant exposure Recurrent and persistant > 3 months No preexisting respiratory complaints Airflow obstruction or Non-specific airways hyperreactivity

PrognosisCan not be predicted by severity, exposure, type,...

Progress

Persistent Recurrent

Resolves

Exposure ceases

RADS

Odor-triggered Irritant-assoc. Panic attacks Vocal Cord Dysfunction

K.B., *13.03.71 Peak flow protocol

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

U.M., *21.08.48 Peak flow record

OA and BHR: Prognosis (1)

Inducer

Red cedarRed cedarColophony

IsocyanatesIsocyanatesIsocyanatesIsocyanates

CrabsCrabsVariaVaria

Subjects(n)

3875201250202231313228

Duration offollow-up (J)

0,5-41-9

1,3-3,81-3>4

0,5-41

0,5-24,8-60,5-44-11

Persistence ofsymptoms (%)

2949906682507761

10093

100

Persistenceof BHR

38/28 (100%)25/33 (76%)7/20 (35%)7/12 (58%)12/19 (63%)9/12 (75%)17/22 (77%)28/31 (91%)26/31 (84%)31/32 (97%)25/2 (96%)

OA and BHR: Prognosis (2)

Cessation of exposure: Persistence of symptoms: 61 %Persistence of BHR: 75 %

Reduction of exposure:Persistence of symptoms: 93 %Persistence of BHR: 95 %

Vandenplas, O., et al., ERJ 22 (2003) 689-697

Cullinan, P., et al., ERJ 22 (2003) 853,from: Cathcart, M., et al., Occup. Med. 47 (1997) 473

OA and BHR: Prevention (1)

Cullinan, P., et al., ERJ 22 (2003) 853,from: Allmers, H., et al., JACI 110 (2002) 318

OA and BHR: Prevention (2)

Work-aggravated asthma: Prevention

Work environment plays an importantrole in the aggravation of symptomsof established asthma.

Tertiary prevention!!!