Revie w C lub

Department of Medicine
Maulana Azad Medical College

Occupational Asthma

Presenter: Dr. Rajiv Singla

Moderator: Dr. M. K. Daga
Date: August 5th, 2005
Occupational Lung Disorder
: Definition

An occupational lung disorder can

be defined as an acute or chronic
lung condition that arises, at least
partly,from the inhalation of airborne
agent in the workplace
Guidelines for Diagnosis of Occupational
Lung Disorder
Exposure to an agent, which can cause an
pulmonary disorder
Appropriate latency from exposure to onset
of symptoms
The clinical syndrome should be consistent
with the syndrome related to the exposure.
No other more likely explanation of the
signs and symptoms
Occupational Lung Disorder
: Classification
O c c u p a t io n a l L u n g D is o r d e r

P n e u m o c o n io s e s

Ir r ita n t R e a c tio n s

A s th m a tic R e a c tio n s

H y p e r s e n s it i v it y d i s o r d e r s

M a lig n a n c ie s
 Occupational Asthma
:Definition
"Occupational asthma is a disease
characterized by variable air flow limitation
and/or airway hyper-responsiveness due to
causes and conditions attributable to a
particular occupational environment and not
to stimuli encountered outside the
workplace"
Bernstein et al 1993
Historical Pe rspective
Bernardino Ramazzini (father of
occupational medicine) described
occupational diseases for the first time in
bakers, handlers of old clothes, and workers
with flax, hemp, and silk.
John Hutchinson's invention of the
spirometer in 1841.
The classic complex of Monday morning
symptoms that occurs in flax and textile
workers was reported by Mareska and
Heyman in 1845.
Dr. Charles Blackley inhaled a grass pollen
extract and, in this, paved the way to the use
of inhalation challenges.
 CL ASSI FICATI ON

With a latency period (Sensitizer-

induced occupational Asthma).

Without a latency period (RADS).

Chan-Yeung M. ACCP Consensus Statement. Chest

1995.
 Problem Statement
Occupational asthma is the most
common work-related lung disease in
developed countries.
Occupational factors are associated
with about 1 in 10 cases of adult
asthma including new onset disease
and reactivation of preexisting
asthma1.

1.Blanc PD, Toren K. Am J Med 1999.

Country-based Estimates of
Incidence

Cases/Million (average estimate)

187
200

150

80
100
50
30
50 11

0
Sweden USA UK Canada Finland
In latest statistics released by SWORD,U.K.
total no. of cases per year are depicted as
below:
In latest statistics released by SWORD,U.K. total no. of cases per year are depicted as below:
 Prevalence
The prevalence rates are more valid if all
suspected cases, whether on the grounds of
questionnaires, lung function tests, or
immunologic investigation, undergo objective
testing that can document lung function
changes in a serial way in relation to
workplace exposure or exposure to the causal
agent in the laboratory.
Studies show prevalence rates of
approximately 5% or less in the case of high-
molecular-weight agents and greater than 5%
for low-molecular-weight agents1.

1. Becklake MR, Malo JL, Chan-Yeung M. Chest 1989.

 Frequency o f Irritant-
induced Ast hma

The SWORD1 and SENSOR2 sentinel

projects estimated that 15% and 11%,
respectively, of OA cases were of the
irritant-induced type.

1.McDonald JC, Keynes HL, Meredith SK. Occup Environ Med 2000.
2. Jajosky RA Romero, Harrison R, Reinisch F et al. MMWR (CDC)1999.
 Sym ptoms
Most common symptoms of occupational
asthma are:
 Coughing
 Wheezing
 Chest tightness
 Chest pain
 Prolonged shortness of breath
 Extreme fatigue
 Sy mp toms

Allergy symptoms
Eyes - Itchy, burning, or watery
Nose - Itchy or stuffy, sneezing
Skin - Itchy, red, or irritated
Pa tterns of dev elop ment of
symptoms
In most people with occupational asthma, the
symptoms appear a short time after beginning
work and subside after leaving work.
In many , the symptoms worsen gradually over the
work week, go away over the weekend, and return
when the new work week starts.
In others, the symptoms are slow to develop and
may not be noticed until after leaving work for the
day.
In the later stages of the disease, after long-term
regular exposure, symptoms may not go away
after leaving the workplace.
 Sensitizer-induced
Occupational Asthma : Etiology
Sensitizer
-induced
Occupational
Asthma

Environmental Genetic Behavioral

influences. influences. influences.
 Environmental Factors

High molecular Low molecular

weight Ag. weight Ag.
Long latency Small latent period
Less efficient More efficient
Are usually proteins Are usually
chemicals
Directly act as Act as haptens
sensitizer
 Environmental: LMW Antigens
Responsible for Work-Related Asthma

Low molecular Occupation at risk

weight chemicals
Isocyanates (e.g. Polyurethane workers,
toluene diisocyanate, roofers, insulators, painters
diphenylmethane,
diisocyanate,
hexamethylene
diisocyanate, naphthalene
diisocyanate)
Anhydrides (e.g. Manufacturers of paint,
trimellitic anhydride, plastics, epoxy resins
phthalic anhydride)
Metals (e.g. chromic Platers, welders, metal and
acid, potassium chemical workers
dichromate, nickel sulfate,
vanadium, platinum salts)
 Environmental: LMW Antigens
Responsible for Work-Related Asthma

Low molecular Occupation at

weight chemicals risk
Drugs (e.g. beta Pharmaceutical
lactam agents, workers, farm workers
piperazine derivatives,
psyllium,
sulphathiazole,
organophosphate)
Miscellaneous (e.g. Laboratory workers,
formaldehyde, textile workers, paint
dimethylethanolamine, sprayers
ethylene oxide,
pyrethrin, polyvinyl
chloride vapour)
 Environmental: HMW Antigens
Responsible for Work-Related Asthma

High molecular weight organic chemicals

Animal proteins (e.g. Farmers, veterinarians, poultry
domestic animals, birds, processors, laboratory workers,
mice, fish glue) bookbinders, postal workers
Plant proteins (e.g. Farmers, bakers, textile
wheat, grain dust, coffee workers, food processors
beans, tobacco dust,
cotton, tea)
Wood dust (e.g. Carpenters, woodworkers
Western cedar,
mahogany, oak,
redwood)
 Environmental: HMW Antigens
Responsible for Work-Related Asthma
High molecular weight organic
chemicals
Dyes (e.g. Fabric and fur dyers,
anthraquinone, carmine, beauticians
paraphenyl diamine,
henna extract)
Fluxes (e.g. colophony, Solderers, electrical
soft core solder) workers
Enzymes (e.g. Pharmaceutical workers,
pancreatic extracts, food processors, plastic
trypsin, Bacillus subtilis, workers, detergent
bromelain pectinase) manufacturers
 Imp ortant Ca use s
Eight target agents for occupational
asthma strategy
 Genetic
De termin ants
HLA class II molecules
-excess of ‘HLA DR3 and deficit of HLA
DR61.

Glutathione-S-transferase (GST) super

family
-homozygosity for the GSTP1 Val allele
confers protection.

1.Young RP, Barker RD, Pile KD, Cookson WOCM, Taylor AJ Newma Am J Respir Crit
Care Med 1995 .
Behavioral influences.

Tobacco smoking
-increased sensitization to
certain asthma- causing
agents (viz. platinum salts).
Pathophysiology
 Reactiv e A irw ay s
Dys funct ion Syndrome
(RAD S)
Exposure to a high concentration of irritant
gas, smoke, fume, or vapor
Immediate onset of symptoms after single
exposure to the irritant, although
symptoms may not peak for several hours
Presence of non-specific bronchial hyper-
responsiveness
Reacti ve Ai rways Dy sfunct ion
Syndrome (RAD S)
Symptoms (cough, wheeze and/or dyspnea)
persist at least 3 months
Presence of airflow obstruction on
pulmonary function testing
Other pulmonary diseases ruled out
 Mo dels o f huma n
irritant-in duced
ast hma
Smoke inhalation
-Firefighters, smoke inhalation victims
Chlorine exposure
Pot room asthma in the primary
aluminum smelting industry
Di ff erences b/ w sensi ti zer-
an d irri tan t-induced OA
Sensitizer-induced Irritant-induced
asthma asthma,
1. is of immediate onset
1. requires a
latency period
2. does not involve
2. is specific sensitization
immunologic, manifesting
an anamnestic response 3. is characterized by
by definition nonspecific airway hyper-
3. is marked by responsiveness
specific airway
responsiveness upon
appropriate challenge with
the causative agent.
 DIA GNO SI S

OA remains largely unsuspected by

health care providers

Only 15% of medical records

documented asking about work-
related symptoms by general
practitioners
 Evalua tion of a Pati ent f or
Possi ble Work- rel ated Asthma
Every patient
History of the present illness -- emphasis on
temporal relationships between job exposures and
symptoms
Documented information about worker's job and
work environment (if available): occupational
health records; material safety data sheets;
industrial hygiene reports; printed job
descriptions
Worker's past medical and work history --
emphasis on allergies; smoking; other respiratory
illnesses, including sinusitis; hospitalizations and
doctor visits, including pulmonary function tests;
previous work environments
 Evaluation of a P at ient for
Poss ible Work- related A sthm a

Every patient (contd.)

Information about current and previous non-
work environments
Physical examination -- with emphasis on
cardiac and respiratory systems
Chest x-ray (if none within past year)
Spirometry before and after inhaled
bronchodilator
 Evaluati on of a Pati ent for
Possi ble Wo rk- rel ated
Ast hma

Selected patients
Bronchoprovocation test (with inhaled non-
specific methacholine or histamine)
Allergy skin tests
Immunologic blood tests
Serial peak flow measurements, self-tested
by the patient
Specific broncho-provocation test with
suspected antigen
Algorit hm for the Cl ini cal I nv esti gati on
of O ccupati onal Asthm a
 A me thacholin e o r
hist amine challe nge
A provocation concentration causing a
20% fall in FEV1 (PC20) that increases
more than threefold after a period of a few
weeks off work, when measured within 8
weeks of the test at work, is significant 1,
whereas a twofold increase is of possible
significance.

1.American Thoracic Society Guidelines. Am J

Respir Crit Care Med 1999
 Allergy skin tests
The presence of immediate skin test reactivity
reflects IgE – specific sensitization.
Skin test reagents are not available for
documenting hypersensitivity to most
occupational agents, but the technique is
feasible for some HMW agents, such as animal
or plant proteins.
A negative test virtually excludes the possibility
that OA is caused by that specific antigen.
 Immunologic blood tests
Immunologic tests to demonstrate IgE
antibodies to a high molecular workplace
allergen when feasible can document
immunologic sensitization to a workplace
allergen with sensitivity and specificity up to
95% and 100%1.

1.Hamilton RG, Adkinson NF. J Allergy Clin Immunol 1998

 Serial peak flow measurements
Comparison of PEF readings with serial FEV1
showed better sensitivity (at 73%) and specificity
(at 100%) for peak flow recordings1.

Monitoring is carried out by recording PEFR at

least four times per day for a period of at least two
weeks at work and during a similar period away
from work.

1.Burge PS, Moscato G. Asthma in the workplace . New York . 1999.

 Serial peak flow measurements
Non-occupational factors, like intercurrent
respiratory viral infections within the preceding
6 weeks, or non-occupational relevant allergen
exposures to which the patient is sensitized,
can confound the interpretation of both PEF
results and methacholine or histamine
challenges1.

1.American Thoracic Society. Guidelines for methacholine and exercise

challenge testing. Am J Respir Crit Care Med 1999
 Investigational Possibilities
Exhaled nitric oxide and induced sputum analysis
have recently been evaluated in diagnosis and
impairment assessment of OA1
Induced sputum eosinophils have been found to
increase in OA with exposure to a relevant
sensitizer at work or in the laboratory2
Exhaled NO has not to date proven useful

1.Obata H, Dittick M, Chan H, Chan-Yeung M. . Eur Respir J 1999

2.Lemière C, Pizzichini MMM, Balkissoon R et al. Eur Respir J 1999
 MANAG EME NT
Pharmacologic Treatment
 Anti-asthma medications are used in the same way as
for patients who have non-occupational asthma
 Pharmacologic treatment is not effective in preventing
lung function deterioration in sensitizer-induced OA
when the subjects remain exposed to the causal agent
1,2
.
 Adding inhaled steroids to removal from exposure result
in a small but significant improvement in asthma
symptoms, quality of life, bronchial responsiveness, and
PEF

1.Marabini A, Ward H, Kwan S . Chest 1993 .

2.Moscato G, Dellabianca A, Perfetti L. Chest 1999.
 Phar macologic T reatment
(cont.)

The beneficial effects of inhaled steroids are

more pronounced if the treatment is started
early after diagnosis1,2.
Patients with RADS/irritant-induced asthma
are treated pharmacologically as for non-
OA, but there are no controlled clinical trials
as to the relative efficacy of specific
medications.
1.Marabini A, Ward H, Kwan S . Chest 1993 .
2.Moscato G, Dellabianca A, Perfetti L. Chest 1999.
Avoidance o f Ex posu re
Complete avoidance of exposure remains
the most effective treatment of sensitizer-
induced OA .
Complete avoidance of exposure is
associated with improvement in asthma
symptoms and functional parameters, non-
specific bronchial reactivity persist in
approximately 70% of affected workers.
Removal from exposure is associated with
the worst socioeconomic outcome.
 Reducing Exposure
Analysis of available data shows that asthma
remained stable or improved in 68% and
worsened in 32% of workers who remained
exposed to "lower" levels of the offending agent
1,2.

Reducing exposure to the offending agent

 through relocation to less exposed jobs.
 improvement in workplace hygiene.
 use of modified materials.

 and/or use of personal protective devices.

1.Rosenberg N, Garnier R, Rousselin X . Clin Allergy 1987

 Exposure : in RADS
Patients with RADS/irritant-induced OA
without concurrent sensitization to the
exposure agent can usually return to
the same workplace if they have
adequate pharmacologic control of their
asthma and if there are appropriate
occupational hygiene controls in place
to prevent the likelihood of a repeat
high-level respiratory irritant exposure.
 Pr eve ntio n o f
Occupatio nal Ast hma
PRIMARY PREVENTION
 Risk identification
 Dissemination of information

 Relevant safety data sheets

 Medicolegal statistics

 Hazard surveillance

 Wearing masks and respirators

 Cigarette smokers
 Pr eve ntio n o f
Occupatio nal Ast hma
SECONDARY PREVENTION
 Skin-testing
 Regular questionnaires or assessment of bronchial
responsiveness
 Rhino-conjunctivitis can be used as a predictor of the later
development of OA 1.
 For RADS, it is recommended that a respiratory
questionnaire and bronchial responsiveness should be
assessed before employment and after every visit to the
first-aid unit with respiratory symptoms 2.

1.Malo JL, Lemière C, Desjardins A, Cartier A. Eur Respir J 1997.

2. Leroyer C, Malo JL . Occup Med 1998
 Pr eve ntio n o f
Occupatio nal Ast hma
TERTIARY PREVENTION
 Referral to experts should be done
quickly.
 Worker should be assessed by
medicolegal agencies immediately after
confirmation of diagnosis.
Occupatio nal a st hma in
healt hcare wo rkers
Over a 5-year period,1,879 confirmed cases
of occupational asthma were reported to the
four SENSOR states. Sixteen percent of
these cases (n=305) were among health care
workers, who constituted only 8 percent of
total workforce.
Most of the cases were new-onset asthma
(68%), although aggravation of pre-existing
asthma was not uncommon (23%) and 10%
were reactive airways dysfunction syndrome
(RADS).
 Occupational ast hma
in h ealt hcare
workers
Cleaning products were the agents most
frequently reported by cases (74/305, 24%).
But the exposures that triggered asthma varied
by occupation.
 Nurses most commonly reported latex
 Office workers in health care settings most often
identified miscellaneous chemicals, paints, solvents
and glues
 Laboratory workers and technicians reported
aldehydes (glutaraldehyde and formaldehyde) most
often
 dental workers reported latex.
 Oc cupational ast hma
in h ealt hcare
wo rkers
Cleaning where possible, instead of
disinfection, will reduce hazardous chemical
exposures.
Latex products should be replaced with safer
alternatives
Indoor air quality may be improved by
prevention of moisture incursion, caution with
construction, and better ventilation design and
maintenance.
 India n p ersp ective

Occupational asthma has been listed in

Workmen's Compensation Act - Schedule 3
section III part B.
Patient can report to zonal occupational
disease centre for compensation.
But there is no institutionalized surveillance
system in place for occupational asthma in
India.
 In dian persp ective
Rastogi SK, Gupta BN, Husain T, Mathur N, Pangtey BS,
Garg N. Respiratory symptoms and ventilatory capacity
in metal polishers ( Hum Exp Toxicol. 1992
Nov;11(6):466-72.) showed a prevalence of 4.8% for
occupational asthma among 104 polishers and 90
unexposed controls
Harindranath N, Prakash O, Subba Rao PV . Prevalence
of occupational asthma in silk filatures (Ann Allergy.
1985 Sep;55(3):511-5). showed 16.9% of the total subjects
had asthma of occupational origin. And 28.8% showed allergy
to silk worm antigens by skin prick test.
Conclusion: Why Should We
Study Occupational asthma
Occupational asthma is preventable
Diagnosis is frequently overlooked
Prevalence of OA is quite significant
OA can give much better insight into
pathophysiology of asthma as
1. population at risk is defined

2. culprit antigen is known

Thank You