1. Work-related asthma
Spo Kgalamono

2. WRA is common Most common OLD in high income countries
Recent evidence - WRA accounts for up to 1 in 4 new cases (25%) of adult asthma ( a 4-fold increase in 3 decades)
Now probably the commonest in SA
Newer agents being identified
While the number of agents causing OA is increasing, the major causes remain the same (wheat, isocyanates, wood dusts, etc)
Under-reporting and under identification still persist
Sherwood Burge. Recent developments in occupational asthma. 2010
Asthma in the Workplace textbook
AS new agents are identified, more cases of OA are diagnosed

4. Evolving

5. Classification of WRA Work-related asthma Work exacerbated
Latent period Allergic (sensitizer)
Occupational asthma
Caused
Typically without latent period RADS and not-so-sudden (low-dose IIA)
Work-related asthma
Work exacerbated
Pre-existing or coincidental, triggered non- specifically
These groups are not mutually exclusive. OA can be followed by WEA

6. Occupational asthma Definition
“Occupational asthma is a form of work-related asthma characterized by variable airflow obstruction, airway hyperresponsiveness, and airway inflammation attributable to a particular exposure in the workplace and not due to stimuli encountered outside the workplace”
Occupational asthma is a disease characterized by variable airflow limitation and/or airway inflammation and/or nonspecific bronchial hyperresponsiveness due to causes and conditions which are attributable to a particular occupational environment and not to stimuli encountered outside the workplace.
Two types of OA are distinguished:
Immunological OA, that is characterized by a latency period (interval between onset of exposure and symptoms)
Non-immunological OA, that occurs after single or multiple exposures to irritants at high concentrations.
Bernstein IL et al. Asthma in the workplace, 2006. 6

7. Exposure in the workplace
Irritants
high levels
allergens/sensitizers
Occupational asthma is usually due to an allergic response to high or low molecular weight antigens, either through the interaction with specific IgE antibodies or by IgE-independent immunologic mechanisms.
These allergic events lead to chronic and acute airway inflammation.
Less commonly, occupational asthma can result from high level irritant exposures at work.
Sensitization
IgE-dependent
IgE-independent
OCCUPATIONAL ASTHMA 7

8. Work-related asthma Immunologic Occupational asthma Caused
Irritant-induced
Work-related asthma
Work exacerbated
Pre-existing or coincidental, triggered non- specifically

9. Case of immunologic occ asthma
40 year old male
Spray painter for the past 8 years.
No history of childhood asthma
Makeshift Booth – inadequate ventilation.
Respirator – cartridges not changed regularly
Now asthma symptoms . Better away from work. Worse from Wednesday onwards.

10. Natural history

11. Common Sensitizers (Incomplete List!)
Low MW
Isocyanates
Anhydrides
Metal salts
Epoxy resins
Fluxes
Persulfate
Aldehydes
High MW
Pharmaceuticals
Animal proteins
Latex
Cereals
Seafood
Proteolytic enzymes

12. Some newly established causes
Diesel – irritant. Also acts as an adjuvant for sensitisation to aeroallergens. Cases of OA wit latency have been described in bus garage workers where diesel exhaust was the most likely cause
Cleaning materials – some may be sensitizers (ammonium compounds, sodium hypochlorite, wax- removing substances - ethanolamines )
Cobalt (diamond polishing, drill bits – hard metal, metal-working fluids)
Cosmetic products – (Argan powder)

13. Occupational Asthma – sensitizer induced
Characterised by work-related asthma appearing after a latency period
Caused by most high- and certain low-molecular weight agents
After sensitization, low levels may cause symptoms / anaphylaxis
Sensitization increases with continued exposure
If IgE mediated, may correlate with immunological tests
Circular Instruction COID
Most de novo occupational asthma is thought to be caused by sensitization mechanisms which often involve IgE allergic antibody responses. Typically, occupational asthma from sensitizers appears only after repeated exposures over months to years (latent period of sensitization); low, non-irritant levels not sensed by healthy individuals may cause symptoms; sensitivity increases with continued exposure; and symptoms often correlate with levels of IgE antibodies, as measured by skin testing or in vitro tests. Usually only a minority of exposed workers are affected. 13

14. Factors modifying risk for sensitizer induced Occupational Asthma
Industrial factors
Nature of occupational agent
Molecular weight, reactivity
Level of exposure (spills, etc)
Duration of exposure
 Host factors
Atopy – atopic ind more likely to develop asthma
Genetic susceptibility - Limited studies in terms of what genes exactly are implicated
Occupational rhinitis and conjunctivitis – upper and lower airways share a common and possibly interconnected inflammatory process - united airways
Cigarette smoking in some
This slide illustrates some of the multiple factors that are known to modify the risk of occupational asthma.
Higher molecular weight, protein agents are more likely to sensitize than are low molecular weight agents. However, some low molecular agents such as trimellitic anhydride (TMA) can readily react with airway proteins (e.g., albumin) to form hapten-protein conjugates that induce IgE antibody-mediated occupational asthma.
Some low molecular agents such as isocyanates, red cedar and various acrylates are also very potent sensitizers.
High level of exposures, particularly spills have been associated with an increase prevalence of occupational asthma.
In addition, longer period of exposure to sensitizing agents are more likely to result in occupational asthma.
Host factors may also influence development of occupational asthma, although their effect may vary according to the type of occupational exposure. Atopic individuals generally are more likely to develop asthma and specific IgE antibodies from high molecular weight (>1000 daltons) agents (e.g. latex, flour), but not from most low molecular weight occupational agents with a few notable exceptions (eg. Platinum salts). Individuals with pre-existing bronchial hyperreactivity may be more susceptible to developing occupational asthma from some agents but generally not to low molecular weights chemicals. Cigarette smokers are more likely to develop asthma from some occupational agents. 14

15. Work-related asthma Immunologic Occupational asthma Caused
Irritant-induced
Work-related asthma
Work exacerbated
Pre-existing or coincidental, triggered non- specifically

16. Irritant-Induced Asthma (IIA)
RADS – OA without latency OR non-immunological OA that occurs after a single high level exposure to irritants
ACCP recommends inclusion of “Not-so-sudden IIA” (repeated low dose exposure to irritants) as part of IIA
Clinical classification of IIA is proposed
Experts formalluy acknowledged that RADS should be considered a form of OA. RECEntly, ACCP erecommended that the term IIA be used to include delayed onsed of asthma after multiple low levels of irritant exposure. IIA is a subtype of occupational asthma without immunologic sensitization and includes the typical reactive airway dysfunction syndrome (RADS) and a more gradual form called not-so-sudden IIA, when onset of asthma follows repeated low-dose exposure to irritants.

17. EAACI position paper: irritant‐induced asthma
Proposed diagnostic algorithm for identifying the various clinical phenotypes of irritant‐related asthma. IIA, irritant‐induced asthma; RADS, reactive airways dysfunction syndrome. *Onset of asthma symptoms often occurs after one more severe high‐level exposure incident . **There is some evidence that asthma may develop within days to weeks after an acute high‐level exposure incident .
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Allergy. Volume 69, Issue 9, pages , 4 JUL 2014 DOI: /all.12448

18. Reactive Airways Dysfunction Syndrome (RADS) Circular Instruction 177 - COID
No previous history of asthma
Acute, high level exposure to toxic/irritant
Respiratory symptoms within 24 hrs of exposure
Pulmonary function showing reversible obstruction or positive non-specific bronchial hyperactivity (methacholine challenge test)
Persistent respiratory symptoms and bronchial hyperreactivity for at least 3 months
The reactive airways dysfunction syndrome (RADS) is the term which refers to the development of cough, wheezing and dyspnea after an acute, single exposure to a high level of an irritant agent such as ammonia or fumes (often in a workplace accident) in a patient without a prior history of airway disease. Patients develop symptoms within 24 hours of exposure and have bronchial hyperreactivity (e.g. to methacholine, cold air or exercise) that may persist for years after exposure. Results of pulmonary function tests may be normal or show reversible (often partly irreversible) air flow obstruction. Compared to patients with occupational asthma developing after a latency period, patients with RADS evaluated in the chronic stage have airway obstruction that is less reversible after inhalation of beta agonists, and have airways with more subepithelial thickening with fibrosis. Bronchial biopsies from RADS patients typically show epithelial desquamation and lymphocytic infiltrates, but not an increased number of eosinophils, a feature generally present in asthma.
See: Brooks SM, Weiss MA, Bernstein IL. Reactive airways dysfunction syndrome (RADS). Persistent asthma syndrome after high level irritant exposures. Chest 1985; 88: 18

19. Work-related asthma Work exacerbated Latent period Allergic
Occupational asthma
Caused by work
Without latent
Irritant-induced RADS
Chronic low exposure
Work-related asthma
Work exacerbated
Pre-existing or coincidental, triggered non- specifically
The distinction between the two is important, since the outcome for the affected worker, the way in which the problem is managed at work, and the advice to the worker and employer are likely to be very different.

20. Case
32 year old man.
18 months photocopier in poorly ventilated room. Fugitive ammonia exposure from factory floor. No sensitizers.
Asthma from high school. Well controlled until a year ago.
Now triggered by ammonia and photocopying; in past 6 months two emergency room treatments, increased medication and 8 days sick absence. Better on holiday.
Lung function test

21. Work-exacerbated asthma
Very common
Worsening of pre-existing asthma (not necessarily occupational) due to causes and conditions attributable to a particular occupational environment and not to stimuli encountered outside the workplace
Aggravation is typically due to an occupational irritant but can be due to allergens

22. Work-aggravated asthma Instruction 118 - COID
Medical history indicating pre-existing asthma
Presence of workplace exposures (cold air, strenuous work, dust, etc) associated with onset of asthma or worsening symptoms
Increase in symptoms or medication requirements or work-related changes in PEFR
Pulmonary function showing reversible obstruction or positive non-specific bronchial hyperactivity (methacholine challenge test)

23. Evaluation of work-related asthma
Diagnosis
Two basic questions
First, does the patient have asthma?
Is the asthma caused or exacerbated by the work place, or by some other explanation

24. Diagnosis Asthma – objective evidence. History important
Exposure to an established cause
Chronological relation with work
After 1st exposure
Symptoms/airflow/airway responsiveness worse at work, better away
Immediate, late, dual
Challenge testing before and after work
Serial peak flow measurements - OASYS

25. Established cause
Serial Peak flow measurements 2 hourly – at least 4X a day several weeks on and off work
Challenges:
Literacy level
Fabrication of results
Consistency – days away from work
The OASYS system developed by Burge is freely available

27. Supporting evidence Tests of sensitization Specific IgE
(Total IgE not useful – waste of money)
Specific skin prick tests

28. Tests of sensitization -SPT
Demonstrates an allergic response to a specific allergen. In conjunction with hx and exam, SPT can help confirm presence of allergy

29. Alternative explanations for asthma
Upper respiratory infection at onset of symptoms
COPD – could this explain the sx
Smoking
Medications (beta blockers, NSAIDs) – can precipitate asthma and drug abuse (heroin, cocaine can cause asthma exacerbations)
Gastro-0esophageal reflux symptoms 
In the assessment of whether occupational asthma is present, it is important to determine whether there are alternative or confounding non-occupational explanations for asthma. Questions as follow may assist in this assessment.
Is there a poor relationship between acute work place exposure and symptoms?
Were there previous respiratory problems before work place exposure, such as prolonged wheezing, coughing after previous respiratory infections (suggesting preexisting asthma)? One must keep in mind however that the pre-existence of asthma does not exclude the diagnosis of occupational asthma.
Was there an upper respiratory infection at onset of symptoms (a common first presentation for adult-onset, non-occupational asthma)?
Are there non-occupational allergic factors (e.g. pets, symptoms with house dust or mold exposure, seasonal variation of symptoms coinciding with aeroallergen pollen seasons)?
Is there a smoking history that could predispose to COPD which could explain the symptoms of the worker?
Is there a family history of asthma or allergies?
Is there a family history of alpha 1-antitrypsin deficiency (that could predispose to COPD)?
Is there a history of recreational drug use? (e.g. heroin insufflation can cause asthma exacerbations, smoking crack cocaine can cause other lung disease, and injected drugs can cause talc pneumoconiosis that may complicate pulmonary status).
Are medications being used that could precipitate asthma (e.g. aspirin, non-steroidal anti-inflammatory drugs, beta blockers)?
Does the patient have a history of gastroesphogeal reflux symptoms?
Review of medical records may provide information about pre-existing respiratory problems and documentation when respiratory problems associated with work exposure first occurred. 29

30. Management of WRA Prevent /Reduce / avoid exposure in workplace
Once asthmatic – Removal from exposure , particularly if sensitizer still present
Surveillance measures:
Periodic monitoring of work place exposures, questionnaires, spirometry, tests of sensitization
Medications – ICS mainstay
Address any non-occupational factors
In some cases where irritants are involved, a worker with occupational asthma may return to work if there is sufficient modification of the environment to reduce exposure (e.g. by increased ventilation, use of protective gear) and if surveillance measures are followed (e.g. air monitoring to verify low exposure levels and pulmonary function testing to assure no decline of respiratory status after exposure to the modified workplace). When a worker has developed occupational asthma to a sensitizer, even low levels of exposures may be intolerable and the worker should be removed from the work place in order to prevent increased sensitization and more serious disease. In work place environments that have significant potential for causing occupational asthma, medical surveillance of all workers on a periodic basis (e.g. every 6-12 months) can help identify workers who have developed evidence of early sensitization or occupational respiratory disease. Depending on the assessed risk, the worker may need to be reassigned to a different work environment to prevent further sensitization and significant clinical disease.
Although anti-inflammatory and bronchodilator medications used in other forms of asthma are also useful in occupational asthma, the focus of management should always be on avoidance and reduction of harmful occupational exposures.
Reduction or elimination of non-occupational factors in a worker’s asthma should also be pursued. For example, avoidance measures to reduce exposure to concomitant non-occupational allergens of significance (e.g. house dust mite, pets) also should be instituted, as this may help reduce airway hyperreactivity and thereby susceptibility to exposure to work place agents.
Consider the possibility that other exposed workers may have occupational asthma – see Tarlo S.M., Boulet L.P., Cartier A., Cockcroft D., Côté J., Hargreave F.E., Holness L., Liss G., Malo J.L., and Chan-Yeung M. Canadian Thoracic Society. Guidelines for occupational asthma. Can Respir J 1998:5 (4); . 30

31. Workplace considerations
Respirator use
Does the job require use of a respirator?
Is the employee comfortable?
Heavy physical work?
Access to care?
(e.g. severe and underground)
Is the worker fit to work?
ATS Respiratory Protection Guidelines. Am J Crit Care Med 1996;154:

32. Occupational asthma prognosis
Prognosis worse if:
longer duration of exposure,
greater severity / frequency of symptoms
“Early initiation of inhaled steroids yielded greater improvement than later initiation” Nicholson et al. OEM. 2005; 62:
Timely removal should result in improvement – in rare cases resolution of asthma
Restriction from exposure or removal from the job often has significant socioeconomic consequences:
Loss of income
Unemployment
Higher medication costs in those remaining in exposure
Be reasonably sure of the diagnosis and cause of OA before recommending job change 32

33. New entity – Asthma COPD Overlap Syndrome (ACOS)
Are asthma and COPD a continuum of the same disease?
Clinical distinction between severe asthma and COPD is often difficult
Although majority of asthmatics will have reversible airway obstruction, a segment of patients can have severe lung function compromise that looks like COPD
In many patients features of both are seen – ‘’overlap syndrome” is increasingly being recognised
Up to 50% of older patients with obstructive airway disease can be classified as having overlap syndrome (cross between asthma and COPD)
The “united airway disease hypothesis” proposes that upper and lower airway diseases are both manifestations of a single inflammatory process

34. Key messages
Physiologic confirmation of OA is important but remains challenging
Integrated management of allergic rhinitis and asthma highly recommended
Early diagnosis, management and removal from exposure improves prognosis
Prevention is key
All types of OA are compensable in SA
NB: Review literature regularly for updates
Several millennia ago, Hippocrates said that physicians should take into account the environments in which their patients live. Several hundred years ago, Bernadino Ramazzini, the father of occupational medicine, added to the words of Hippocrates by advocating that the physician take one more point into account, namely what is the occupation of his patient. In the case of occupational asthma, taking an occupational history is of great importance in suspecting the diagnosis and initiating appropriate objective evaluation and intervention. Intervention should be focused on reducing or avoiding harmful work place exposures so that permanent lung impairment and need for chronic medical treatment are avoided.
History is key to suspecting OA 34

35. Acknowledgment
Prof D. Rees
NIOH Clinic patients

36. Latest updates on OA www.occupationalasthma.com
In my unbiased opinion, this is the definitive text on OA, Asthma in workplace, now in its 2nd edition
co-edited by Names
and authors that makes up a list of who’s who in the field

38. Current guidelines and consensus statements
Canadian Thoracic Society
BOHRF
ACCP
EAACI

39. Watch out for the red flags!!!!

40. Causes of High IgE Atopy Parasitic infections Auto-immune diseases
Malignancy
Air pollution(cigarette, diesel) stimulate the production of IgE without initiating sensitisation

41. Some sensitizers may also be irritants: TDI

42. Work exacerbated Asthma
in the workplace
Occupational Asthma
(caused by
the workplace)
Work exacerbated Asthma
(pre-existing, coincidental, triggered non-specifically
TWO TYPES OF oa ARE distinguished based on their manifestation after a latency period
Irritant–induced OA
Acute (RADS)
Chronic low- dose
Sensitizer–induced
OA (with latency)
EAACI position paper: irritant induced asthma: Allergy 69 (2014)