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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