Occupational bronchitis.

Occupational asthma.

Assoc. Prof. Vladimir Milanov, MD, PhD

Department of Occupational Diseases
Faculty of Medicine, Medical University – Sofia
University Hospital “St. Ivan Rilski”
Occupational bronchitis
 Definitions
 Chronic bronchitis – a productive cough of more
than 3 months occurring within 2 consecutive
years.
 Lung emphysema – an abnormal permanent
enlargement of air spaces distal to the terminal
bronchioles, accompanied by the destruction of
alveolar walls and without obvious fibrosis. This
process leads to reduced gas exchange, changes
in airway dynamics that impair expiratory airflow,
and progressive air trapping
 Chronic Obstructive Pulmonary Disease
(COPD) – a heterogeneous lung condition
characterized by chronic respiratory symptoms
(dyspnea, cough, expectoration, exacerbations)
due to abnormalities of the airways (bronchitis,
bronchiolitis) and/or alveoli (emphysema) that
cause persistent, often progressive, airflow
obstruction (GOLD 2023).
 The role of occupational exposures in COPD
etiopathogenesis
 Coal miners’ studies – relationship between dust exposure and decreased lung
function, regardless of smoking habits, remaining even after reduction in the
exposure:
 USA: 7.7% prevalence of airway obstruction in never-smokers, 16.4% among

cases with coal workers’ pneumoconiosis; 32.3% - with progressive massive

fibrosis;
 China: 8% of coal miners exposed for 35 years at respirable dust were expected

to develop a clinically important loss of FEV1;

 Silica dust could cause airflow limitation even without silicosis;
 Canada: obstructive lung function impairment in asbestos-exposed workers;
 Reduced lung function in workers exposed to cement inorganic dust;
 Recent studies in farmers have associated lifelong exposure to organic dust with
the occurrence of COPD;
 Exposure to other types of organic dust in the textile sector or in paper mills has
been associated with COPD or accelerated lung function decline;
 Other chemicals: welding fumes, cadmium and irritant gases (nitrous fumes,
sulphur dioxide and chlorine);
 Increased incidence of COPD among nurses, associated with the use of irritant
cleaning agents;
The role of occupational exposures in causing COPD

ROS – reactive oxygen species; SHS – second-hand smoke

 Occupations that may pose at risk of COPD

Industry and agriculture Tertiary sector

Cement workers Armed forces
Coke oven workers Building services and sales workers
Construction and trade workers Cleaners
Farming and agriculture workers Freight, stock and material handlers
Food products manufacturing Gardeners, park keepers
Highway and tunnel workers Healthcare workers
Inorganic dust-exposed workers Records processing and distribution clerks
Iron, steel and ferrochrome workers Repair services/gas station workers
Mechanic and repair jobs Sculptors, painters, engravers and art restorers
Miners Warehouse stock handlers, stackers
Paper mill workers
Pottery workers
Railroad workers
Rubber, plastics and leather manufacturing
workers
Silicon carbide smelter workers
Spray painters
Welders
Wood workers
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 Occupational COPD prevention

 Primary prevention of occupational risk factors – risk evaluation and

then elimination, or if this is not possible, mitigation of the noxious
exposure.
 Secondary prevention, to intercept the disease in the early stages –
through medical surveillance and screening programmes.
 Tertiary prevention, focused on management of the disease –
reducing health and social consequences.
 Other interventions at the primary care and specialist level –
important role of the occupational physician – to advise the
employer to adapt the patient’s occupational tasks and working time
to the disease and to its consequences.
 From the clinical point of view, occupational COPD has no specific
hallmarks compared to COPD in general. This complicates the
diagnosis in clinical settings and is responsible underdiagnosis of
COPD, together with a lack of education in occupational medicine.
 Questions to gather information from
occupational history

1. Have you ever been exposed regularly to vapours,

gases, dusts and fumes at work?
2. How long have you been exposed?
3. When it was the first time?
4. In which job/jobs?
5. Are you currently exposed?
6. Did you/do you wore/wear personal protective
equipment during the exposure?
It’s never too late to stop
smoking!
Stopping
smoking and
avoiding
second-hand
smoke is the
best way to
reduce the
rate of decline
in lung
function.
Smoking
cessation
reduces
death and
disability in
long-term
follow-up.
Occupational asthma
Definition, description and diagnosis
of asthma

 Asthma is a heterogeneous disease defined by the history of respiratory

symptoms (e.g. wheeze, shortness of breath, chest tightness, and cough)
that vary over time and in intensity, together with variable expiratory
airflow limitation. Airflow limitation may later become persistent.
 Asthma is usually associated with airway hyperresponsiveness and
airway inflammation, but these are not necessary or sufficient for
diagnosis. Clinical phenotypes (e.g. childhood onset versus late onset,
allergic versus nonallergic) do not correlate strongly with specific
pathological processes or treatment responses.
 The diagnosis of asthma is based on a history of characteristic symptom
patterns and evidence of variable expiratory airflow limitation obtained from
bronchodilator reversibility testing or from other tests, such as a positive
bronchial provocation test result, excessive variability during PEF monitoring,
excessive variation in FEV1 between visits, or a significant increase in
FEV1 after ICS treatment. Results from clinical examination, including
chest auscultation, may be completely normal.
 Definition of occupational asthma

 Occupational asthma (OA) 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 (Bernstein IL, et al. Asthma
in the workplace, 2006).
 Two types of OA are distinguished:
 Immunological OA characterized by a latency period
(interval between onset of exposure and symptoms);
 Non-immunological OA occuring after single or multiple
exposures to irritants at high concentrations.
 Asthma Phenotypes

Allergic (40-50%)

Non-allergic

Fahy Nat Rev Immunol 2015

 Significance of occupational asthma

 Occupational exposures cause significant worsening in up to

15% of cases with asthma worldwide.
 Estimated 15% of de novo adult asthma cases in U.S. are with
occupational asthma.
 Although de novo occupational asthma (asthma that would
never have developed without workplace exposure) is
estimated to be about 2-5% of all cases of bronchial asthma in
the U.S., failure to diagnose and manage these cases in a
timely manner can lead to long-term, irreversible sequelae.
 The frequency of work-related asthma (WRA) is unknown, but it is
relatively common, affecting around 20-25% of working individuals with
asthma.
 WRA is subdivided into three main phenotypes – work-aggravated asthma
(WAA), allergic occupational asthma (OA) due to sensitisation and
irritant-induced asthma (IIA).
 Patients with WAA either have pre-existing asthma or develop coincidental
adult-onset asthma and report symptoms that are made worse by non-
specific factors in the workplace. Common causes of WAA include extremes
of workplace temperature or humidity, exertion from manual work tasks,
workplace stress or anxiety and exposure to non-specific dusts, fumes, or air
pollution.
 In contrast, occupational asthma (OA) is caused by airborne exposures in
the working environment and accounts for around one in six cases of adult
asthma. OA is further subdivided into 2 separate conditions; IIA and OA due
to allergic sensitisation
Classification of work-related asthma
 Classification of occupational asthma

 “Work-sensitized” (HMW, high molecular weight > 5,000 Da)

IgE-mediated “asthma with latency”
 “Irritant-induced” (LMW, low molecular weight < 5,000 Da)
Non IgE-mediated “asthma without latency”
Irritant asthma
Reactive airways dysfunction syndrome (RADS)
“Low-dose RADS”
Reactive Airways Dysfunction Syndrome (RADS)

 No previous history of asthma

 Acute, high level exposure to toxic/irritant
 Respiratory symptoms within 24 hrs of exposure
 Persistent respiratory symptoms, non-specific bronchial
hyperreactivity
 Pulmonary function may be normal or show reversible
obstruction:
 but obstruction less reversible than sensitizer induced
asthma
 Eosinophilic infiltration not characteristic
 Worse outcome than sensitizer induced OA
Cold Air / Exercise-Induced Asthma

 May be associated with:

 dry cold air;

 exertion;

 hyperventilation;

 Work in cold, dry climates;

 Immediate response, short duration;
 Further exercise may improve airflow!
 Mechanism: airway drying and cooling
 stimulates vagal receptors

 histamine, mediator release from mast cells.

Occupations at risk of occupational asthma
 Causes of occupational asthma
 There are over 400 known causes of OA (known as
asthmagens);
 Most of the cases are related to exposure to a small number
of workplace allergens, most commonly flour dust or
isocyanates;
 Asthmagens are usually divided into HMW or LMW
sensitisers;
 OA caused by repeated exposure to HMW proteins is an IgE-
associated response, involving T-helper cells (Th2).
 This immune mechanism is also known to be relevant to a
small number of LMW causes (e.g., acid anhydrides and
platinum salts), but for the majority, the immune pathways
responsible for sensitisation remain to be determined.
 Frequently reported causes of occupational
asthma, by molecular weight
Agents and source Workers at risk
High Animal urine and proteins (e.g., mice, rats, cows, Laboratory work, veterinarians, farmers,
molecular horses, insects). animal handlers, greenhouse workers.
weight
Cereal grains and flour (e.g., wheat, rye, barley). Bakers, pizza and pastry makers, grain
agents
storage handlers, millers.
Enzymes (e.g., amylase, protease, lipase). Bakers, pastry makers, food process
workers (amylase), cleaners, healthcare
workers, detergent manufacturers.
Natural rubber latex. Healthcare workers, rubber glove
makers.
Other animal or plant-derived products: milk and egg Food producers and processors,
protein, beans (eg, green coffee, castor, soy), spices, bakers, cooks. Pharmaceutical industry,
gums (eg, acacia, guar). printing, carpet making (gums).
Seafood proteins (eg, fish, crustaceans, molluscs). Fish and seafood processing.
 Frequently reported causes of occupational
asthma, by molecular weight
Agents and source Workers at risk

Low Acid anhydrides (eg, tri-mellitic anhydride, phthalic anhydride). Makers and processors of epoxy resins (adhesives, surface
coatings).
molecular
weight Acrylic monomers (eg, cyanoacrylate, methyl methacrylate). Adhesive work, dental professionals, aestheticians, printing.
agents
Biocides (eg, aldehydes, chlorine releasing agents, quaternary Healthcare workers, cleaners, swimming pool attendants.
ammonium compound).

Colophony (rosin) in solder flux (abietic acid). Electronic soldering, work with adhesives and surface coatings.

Di-isocyanates (eg, toluene di-isocyanate, methylene diphenyl di- Spray painters, foundry workers, makers and processors of
isocyanate, hexa-methylene di-isocyanate). polyurethane substances (eg, adhesives, foams, hard surface
coatings).

Drugs (eg, opiates, penicillins, other antibiotics). Pharmaceutical manufacture, healthcare workers with repeated
exposures.

Metals (eg, chromium, cobalt, nickel, zinc) and metalworking fluids. Welders, metal platers, hard metal manufacturing.
CNC grinders and lathe operators.

Persulphates and henna. Hairdressers.

Platinum and other precious metal salts. Refinery workers.

Some wood dust (eg, iroko, obeche, sapele, western red cedar) Carpenters, joiners, millers, forestry workers.
and MDF (medium-density fibreboard)
 Recommended algorithm for
the assessment and referral of
patients with possible OA
 Beyond History: Testing for Occupational asthma

 History alone insufficient for diagnosis

 Objective testing
 Work-related changes in peak flows &/or non-specific bronchial
responsiveness (NSBR) – repeated and significant (≥ 20%) falls in PEF
with work place exposure support the diagnosis of occupational asthma.
PEF monitoring can be coupled with monitoring of NSBR to
methacholine which can increase its sensitivity and specificity. Pre and
post-shift changes in FEV1 have not been shown to be adequately
sensitive or specific.
 Immunologic testing for occupational allergens – immediate-type
skin testing with appropriate materials may establish sensitization but
does not confirm the diagnosis of OA. In vitro tests for specific IgE
(e.g. RAST) may be useful but are generally less sensitive
 Controlled inhalation challenge with suspect agent – the “reference
standard” for diagnosis, either in the laboratory or in the workplace with
close monitoring of spirometry by a technician over a work-shift period.
 Immunologic assessment

• Skin prick tests to HMW agents

• In vitro tests
 Measurements of specific IgE: radioallergosorbent test
(RAST)/CAP, ELISA
 Immunoblotting, Crossed
radioimmunoelectrophoresis (CRIE)
• Reagents:
 Whole “natural” extracts (not standardized, potency?)
 Purified allergens (e.g. enzymes, isolated proteins)
 Recombinant allergens (e.g. latex allergens)
 Occupational asthma management

 Reduce / avoid exposure in workplace.

 Removal of worker in some cases, particularly if sensitizer
present.
 Surveillance measures:
 Periodic monitoring of work place exposures, spirometry,
tests for immunologic sensitization.
 Medications.
 Address any non-occupational factors.
 Consider the possibility that other exposed workers may have
occupational asthma.
 Occupational asthma prognosis

 Timely removal should result in improvement;

 Residual disease: Isocyanates, red cedar, snow crab, some irritants,
other agents;
 Prognosis worse if:
 longer duration of exposure;
 greater severity/frequency of symptoms;
 airway obstruction or hyper-reactivity, dual bronchial responses;
 Restriction from exposure or removal from the job often has significant
socioeconomic consequences for the worker:
 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.
 Public Health Management

 Treat as “Sentinel event”;

 Surveillance;

 Identification of specific hazard when

possible;
 Hazard Control:

 engineering control;

 personal protective equipment (PPE).

Thank you for the attention!