Review Club Department of Medicine Maulana Azad Medical College Occupational Asthma Occupational Asthma Presenter: Dr. Rajiv Singla Moderator: Dr. M. K. Daga
Review ClubDepartment of Medicine
Maulana Azad Medical College
Occupational AsthmaOccupational 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
P n eu m o con ioses
Ir r i ta n t R ea c tio ns
A s thm a tic R e a ctio ns
H ype rsen s it iv ity d iso rde rs
M a lign an cies
O ccu pa tion a l L un g D iso rd er
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 PerspectiveBernardino 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.
CLASSIFICATION
1. With a latency period (Sensitizer-induced occupational Asthma).
2. 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
80
1130
50
187
0
50
100
150
200
Sweden USA UK Canada Finland
Cases/Million (average estimate)
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:
PrevalenceThe 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 of Irritant-induced Asthma
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.
Symptoms
Most common symptoms of occupational asthma are: Coughing Wheezing Chest tightness Chest pain Prolonged shortness of breath Extreme fatigue
Symptoms
Allergy symptoms
Eyes - Itchy, burning, or watery
Nose - Itchy or stuffy, sneezing
Skin - Itchy, red, or irritated
Patterns of development 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
Environmentalinfluences.
Genetic influences.
Behavioral influences.
Environmental Factors
High molecular weight Ag.Long latencyLess efficientAre usually proteins
Directly act as sensitizer
Low molecular weight Ag.Small latent periodMore efficientAre usually chemicalsAct as haptens
Environmental: LMW Antigens Responsible for Work-Related Asthma
Low molecular weight chemicals
Occupation at risk
I socyanates (e.g. toluene diisocyanate, diphenylmethane, diisocyanate, hexamethylene diisocyanate, naphthalene diisocyanate)
Polyurethane workers, roofers, insulators, painters
Anhydrides (e.g. trimellitic anhydride, phthalic anhydride)
Manufacturers of paint, plastics, epoxy resins
Metals (e.g. chromic acid, potassium dichromate, nickel sulfate, vanadium, platinum salts)
Platers, welders, metal and chemical workers
Environmental: LMW Antigens Responsible for Work-Related Asthma
Low molecular weight chemicals
Occupation at risk
Drugs (e.g. beta lactam agents, piperazine derivatives, psyllium, sulphathiazole, organophosphate)
Pharmaceutical workers, farm workers
Miscellaneous (e.g. formaldehyde, dimethylethanolamine, ethylene oxide, pyrethrin, polyvinyl chloride vapour)
Laboratory workers, textile workers, paint sprayers
Environmental: HMW Antigens Responsible for Work-Related Asthma
High molecular weight organic chemicals
Animal proteins (e.g. domestic animals, birds, mice, fish glue)
Farmers, veterinarians, poultry processors, laboratory workers, bookbinders, postal workers
Plant proteins (e.g. wheat, grain dust, coffee beans, tobacco dust, cotton, tea)
Farmers, bakers, textile workers, food processors
Wood dust (e.g. Western cedar, mahogany, oak, redwood)
Carpenters, woodworkers
Environmental: HMW Antigens Responsible for Work-Related Asthma
High molecular weight organic chemicals Dyes (e.g. anthraquinone, carmine, paraphenyl diamine, henna extract)
Fabric and fur dyers, beauticians
Fluxes (e.g. colophony, soft core solder)
Solderers, electrical workers
Enzymes (e.g. pancreatic extracts, trypsin, Bacillus subtilis, bromelain pectinase)
Pharmaceutical workers, food processors, plastic workers, detergent manufacturers
Important Causes
Eight target agents for occupational asthma strategy
Genetic Determinants
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
Reactive Airways Dysfunction Syndrome (RADS)
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
Reactive Airways Dysfunction Syndrome (RADS)
Symptoms (cough, wheeze and/or dyspnea) persist at least 3 months
Presence of airflow obstruction on pulmonary function testing
Other pulmonary diseases ruled out
Models of human irritant-induced asthma
Smoke inhalation
-Firefighters, smoke inhalation victims
Chlorine exposure
Pot room asthma in the primary aluminum smelting industry
Differences b/w sensitizer- and irritant-induced OA
Sensitizer-induced asthma 1. requires a latency period 2. is immunologic, manifesting an anamnestic response by definition 3. is marked by specific airway responsiveness upon appropriate challenge with the causative agent.
Irritant-induced asthma, 1. is of immediate onset
2. does not involve specific sensitization
3. is characterized by
nonspecific airway hyper-responsiveness
DIAGNOSIS
OA remains largely unsuspected by health care providers
Only 15% of medical records documented asking about work-related symptoms by general practitioners
Evaluation of a Patient for Possible Work-related 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 Patient for Possible Work-related Asthma
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
Evaluation of a Patient for Possible Work-related Asthma
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
Algorithm for the Clinical Investigation of Occupational Asthma
A methacholine or histamine challenge
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 measurementsComparison 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
MANAGEMENT
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.
Pharmacologic Treatment (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 of Exposure
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 19872.Côté J, Kennedy S, Chan-Yeung M. Am Rev Respir Dis 1990
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.
Prevention of Occupational Asthma
PRIMARY PREVENTION Risk identification Dissemination of information Relevant safety data sheets Medicolegal statistics Hazard surveillance Wearing masks and respirators Cigarette smokers
Prevention of Occupational Asthma
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
Prevention of Occupational Asthma
TERTIARY PREVENTION Referral to experts should be done
quickly.Worker should be assessed by
medicolegal agencies immediately after confirmation of diagnosis.
Occupational asthma in healthcare workers
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 asthma in healthcare 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.
Occupational asthma in healthcare workers
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.
Indian perspective
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.
Indian perspectiveRastogi 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
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