Occupational

Asthma

Dr. Basim Safi Al-Mgoterصافي باسم الدكتور

المكوطر

IntroductionIntroductionOccupational Asthma (OA) is a form of Occupational Asthma (OA) is a form of asthma associated with work associated with work involving inhalation of a chemical, allergen, or irritant which is aerosolized as involving inhalation of a chemical, allergen, or irritant which is aerosolized as dust or fumes. Occupational asthma symptoms have been observed among dust or fumes. Occupational asthma symptoms have been observed among workers (e.g., bakers, grain workers), even dating back to ancient times. OA workers (e.g., bakers, grain workers), even dating back to ancient times. OA may only affect a small percentage of the population; however, it is a serious may only affect a small percentage of the population; however, it is a serious problem which can lead to permanent lung damage.problem which can lead to permanent lung damage.

Occupational asthma affects the bronchial tree, resulting in symptoms that Occupational asthma affects the bronchial tree, resulting in symptoms that mimic those of bronchial asthma (e.g., coughing, wheezing, dyspnea, and mimic those of bronchial asthma (e.g., coughing, wheezing, dyspnea, and chest congestion) and is associated with airway obstruction and/or airway chest congestion) and is associated with airway obstruction and/or airway hyper-responsiveness. These symptoms may also be accompanied by hyper-responsiveness. These symptoms may also be accompanied by typical allergy symptoms such as itchy eyes, itchy nose and sneezing when typical allergy symptoms such as itchy eyes, itchy nose and sneezing when OA is IgE-mediated.OA is IgE-mediated.There are many types of OA, and it is now understood that there is more There are many types of OA, and it is now understood that there is more than one possible mechanism involved in its development. Unlike most than one possible mechanism involved in its development. Unlike most cases of bronchial asthma, OA with long-term exposure to workplace cases of bronchial asthma, OA with long-term exposure to workplace allergens and irritants can lead to a chronic, irreversible form of asthma that allergens and irritants can lead to a chronic, irreversible form of asthma that is unresponsive to medication, even when the patient is no longer exposed is unresponsive to medication, even when the patient is no longer exposed to the original offending agent. to the original offending agent.

The common form of allergic bronchial asthma is often provoked by The common form of allergic bronchial asthma is often provoked by common aeroallergens found at home and outdoors during the pollen common aeroallergens found at home and outdoors during the pollen season. In contrast, OA is associated with the inhalation of specific and season. In contrast, OA is associated with the inhalation of specific and potent airborne agents unique to the workplace. potent airborne agents unique to the workplace.

Up to 20% of all adult asthma cases Up to 20% of all adult asthma cases maybe work-related asthmamaybe work-related asthma

Of those diagnosed with work-related Of those diagnosed with work-related asthma:asthma:

20-27% are individuals with pre-existing 20-27% are individuals with pre-existing asthma who react to substances in the asthma who react to substances in the workplaceworkplace

Up to 80% develop asthma due to work-Up to 80% develop asthma due to work-place exposuresplace exposures

““Occupational asthma is a disease Occupational asthma is a disease characterized by variable airflow characterized by variable airflow limitation and / or airway hyper-limitation and / or airway hyper-responsiveness and / or inflammationresponsiveness and / or inflammationdue to causes and conditions due to causes and conditions attributable to a particular attributable to a particular occupational environment and not to occupational environment and not to stimuli encountered outside the stimuli encountered outside the workplace.“workplace.“

(Centers for Disease Control and Prevention, 2004)

What clues suggest that asthma What clues suggest that asthma is work-related?is work-related?

Do symptoms:Do symptoms:– Occur only at work or Occur only at work or

regularly after a work-regularly after a work-shift?shift?

– Improve on weekends Improve on weekends or vacations?or vacations?

– Increase over the Increase over the course of the work course of the work week?week?

– Improve after changes Improve after changes in the work in the work environment?environment?

Work-related asthma(WRA)

Occupational asthma, caused by work

(OA)

Work-exacerbated asthma (WEA)

Sensitizer-induced OAIrritant-induced OA(Including reactive airways

dysfunction syndrome, RADS)

Causes of OACauses of OA There are at least two major mechanisms involved in the development of OA:There are at least two major mechanisms involved in the development of OA:

1. The most common type of OA1. The most common type of OA occurs after prolonged exposure to workplace occurs after prolonged exposure to workplace allergens. During this time, the patient becomes sensitized to the inhaled workplace allergens. During this time, the patient becomes sensitized to the inhaled workplace agent. The initial period in which the patient is symptom-free is called the agent. The initial period in which the patient is symptom-free is called the latency latency phasephase, which can sometimes last years. During this period, the patient has no , which can sometimes last years. During this period, the patient has no asthma symptoms as the immunologic hypersensitivity to the workplace allergen is asthma symptoms as the immunologic hypersensitivity to the workplace allergen is developing. The mechanism is mostly IgE-mediated, and the patient may also developing. The mechanism is mostly IgE-mediated, and the patient may also develop typical allergy-like symptoms that include itchy eyes, itchy nose and develop typical allergy-like symptoms that include itchy eyes, itchy nose and sneezing prior to or during the presentation of asthma symptoms. Early in the course sneezing prior to or during the presentation of asthma symptoms. Early in the course of OA, asthma symptoms usually lessen or resolve when the patient is not at work, of OA, asthma symptoms usually lessen or resolve when the patient is not at work, especially during evenings, weekends, and vacations. especially during evenings, weekends, and vacations.

Immunologic sensitization to a workplace agent is mostly due either to Immunologic sensitization to a workplace agent is mostly due either to high high molecular weight (HMW) agentsmolecular weight (HMW) agents (e.g., flour, animal protein), or less often, to (e.g., flour, animal protein), or less often, to low low molecular weight (LMW) agentsmolecular weight (LMW) agents (e.g., chemicals such as isocyanates). The (e.g., chemicals such as isocyanates). The mechanism for HMW sensitization is usually IgE-mediated, while the mechanism for mechanism for HMW sensitization is usually IgE-mediated, while the mechanism for LMW sensitization is often a result of T-cell mediation (cellular hypersensitivity). LMW sensitization is often a result of T-cell mediation (cellular hypersensitivity).

2. The less common type of OA2. The less common type of OA results from exposure to high levels of airborne results from exposure to high levels of airborne irritants in the workplace. Symptoms begin soon after entering the new work irritants in the workplace. Symptoms begin soon after entering the new work environment, with little to no latency period. Since there is no underlying immunologic environment, with little to no latency period. Since there is no underlying immunologic mechanism or sensitization (latency) period, symptoms result from direct irritation or mechanism or sensitization (latency) period, symptoms result from direct irritation or damage to the airway. This presentation is often referred to as reactive airway damage to the airway. This presentation is often referred to as reactive airway dysfunction syndrome (RADS).dysfunction syndrome (RADS).

Sensitizer-induce OASensitizer-induce OA ( immunologic ( immunologic ) )

reversible air-flow obstruction / airway hyper-reversible air-flow obstruction / airway hyper-responsiveness due to a sensitizing agent responsiveness due to a sensitizing agent encountered in the workplace” encountered in the workplace” HMW sensitizersHMW sensitizers LMW sensitizersLMW sensitizers

Irritant-induce OAIrritant-induce OA ( non-immunologic) ( non-immunologic) Reactive airways dysfunction syndrome (RADS)Reactive airways dysfunction syndrome (RADS) Persistent asthma symptoms induced by a one-time, Persistent asthma symptoms induced by a one-time,

high-level irritant.high-level irritant.

Sensitizer Occupational AsthmaSensitizer Occupational Asthma is is caused by caused by sensitization sensitization to a specific chemical to a specific chemical agent in the workplace over a agent in the workplace over a period of timeperiod of time. This . This is the mechanism for the vast majority (>90%) of is the mechanism for the vast majority (>90%) of cases of occupational asthma. The sensitization cases of occupational asthma. The sensitization process does not occur after one exposure but process does not occur after one exposure but develops over time (i.e., develops over time (i.e., latency periodlatency period). ).

Sensitization to a specific antigenSensitization to a specific antigen– low molecular-weight.low molecular-weight.– high molecular weight.high molecular weight.

Low MWLow MW

IsocyanatesIsocyanates AnhydridesAnhydrides Metal saltsMetal salts Epoxy resinsEpoxy resins FluxesFluxes PersulfatePersulfate Aldehydes Aldehydes

LMW AgentsLMW Agents(< 5Kd)(< 5Kd)

– Too small to be complete Too small to be complete allergensallergens

– Immunologic mechanisms Immunologic mechanisms less well characterizedless well characterized

– Specific Ig-E to isocyanates Specific Ig-E to isocyanates & plicatic acid found in only & plicatic acid found in only 15-30% 15-30%

High MWHigh MW Pharmaceuticals Pharmaceuticals Animal proteinsAnimal proteins LatexLatex CerealsCereals SeafoodSeafood Proteolytic enzymesProteolytic enzymes Wood constituentsWood constituents

HMW Agents HMW Agents (> 5Kd)(> 5Kd)– Organic proteins/ Organic proteins/

polysaccharides polysaccharides

– Type-I Hypersensitivity Type-I Hypersensitivity – Often skin or serologic Often skin or serologic

evidence of sensitizationevidence of sensitization– Atopy typically a Atopy typically a

predisposing condition predisposing condition

Irritant Induced Occupational Asthma Irritant Induced Occupational Asthma usually develops after a usually develops after a single, very high single, very high exposure exposure to an irritant chemical. It is a direct to an irritant chemical. It is a direct “burn” effect on the airways and is not related “burn” effect on the airways and is not related to the immune system. to the immune system.

Often represents clinical expression of Often represents clinical expression of airways hyperactivity + irritant exposureairways hyperactivity + irritant exposure

May be induced by any irritating exposureMay be induced by any irritating exposure Usually history of intolerance to second-hand Usually history of intolerance to second-hand

tobacco smoke tobacco smoke Some irritant exposures may also be Some irritant exposures may also be

sensitizing: Isocyanides .sensitizing: Isocyanides .

Objective testingObjective testing

-PEFR monitoring -PEFR monitoring -- Spirometry-- Spirometry

- Specific inhalation - Specific inhalation challengechallenge

- Immunologic testing- Immunologic testingNew Devices to measure FEV1

a) Deterioration during the a) Deterioration during the working day, such working day, such that on that on returning the following day the returning the following day the patient has completely patient has completely recovered. recovered.

b) Progressive deterioration over b) Progressive deterioration over the course of the week with the course of the week with recovery at the weekend.recovery at the weekend.

c) c) Week-by-week deterioration Week-by-week deterioration with recovery only after at least 3 with recovery only after at least 3 days away from work.days away from work.

d) maximal d) maximal deterioration on deterioration on Monday with recovery over the Monday with recovery over the course of the week.course of the week.

Improvement of PEF when away from work and deterioration of PEF on returning to work

Exposure challenge testing

at and away from work cross-shift

Bronchoprovocation Study: Bronchoprovocation Study: methacholine or histamine induced methacholine or histamine induced fall in FEV1 fall in FEV1 >> 20% 20%

PC20 (PC20 (provocative concentration )provocative concentration ) < 8 < 8 mg/ml (normal >16 mg/ml)mg/ml (normal >16 mg/ml)

Correlates with asthma severityCorrelates with asthma severity

““Gold-standard” Gold-standard” Decrease in FEV1 of Decrease in FEV1 of >> 20% in response to 20% in response to

specific agentspecific agent Performed at specialized centers; limited by Performed at specialized centers; limited by

precise knowledge of the agentprecise knowledge of the agent

IndicationsIndications– Diagnosis in doubtDiagnosis in doubt– Potential “new” agentPotential “new” agent– Finding exact agent in complex workplaceFinding exact agent in complex workplace– Medical-legal purposesMedical-legal purposes

Skin Test: (Skin Test: (IgE )IgE ) Valid for HMW allergens (eg. baker’s Valid for HMW allergens (eg. baker’s

asthma) & rarely for LMW agents (eg. asthma) & rarely for LMW agents (eg. diisocyanates)diisocyanates)

Requires good allergen extractsRequires good allergen extracts Frequently not available commerciallyFrequently not available commercially When positive, means presence of When positive, means presence of

sensitizationsensitization RASTRAST ELISA ELISA

Removal from exposureRemoval from exposure Reducing exposure (Reducing exposure (use of face masks use of face masks

or providing better ventilationor providing better ventilation)) Medical and pharmacological Medical and pharmacological

treatmenttreatment Allergen immunotherapy?Allergen immunotherapy?

Occupational asthma, based on sensitization to agents Occupational asthma, based on sensitization to agents encountered at work, is the best defined and documented encountered at work, is the best defined and documented type of work-related asthma but under diagnosed. type of work-related asthma but under diagnosed.

RADS is a special subgroup of occupational asthma induced RADS is a special subgroup of occupational asthma induced without a latency period by a high level of exposure to without a latency period by a high level of exposure to irritants.irritants.

Prevention (decreasing exposure) is important, because the Prevention (decreasing exposure) is important, because the prognosis is not very good.prognosis is not very good.

Work-related asthma includes also worsening of pre-existing Work-related asthma includes also worsening of pre-existing asthma due to harmful exposure at work, and presumably asthma due to harmful exposure at work, and presumably also asthma developed in long-term but not very high also asthma developed in long-term but not very high exposure to irritants, not defined as occupational diseases exposure to irritants, not defined as occupational diseases to-day. Prevention of exposure is most important. to-day. Prevention of exposure is most important.