Occupational module

Gianna Moscato

Department of Public Health, Experimental and Forensic Medicine University of Pavia, Italy

Investigating allergic effects of environmental exposures

2 - 5 July 2014 Brindisi, Italy

Allergy School

• Occupational exposures play an important role in allergic respiratory diseases.

• The work-related diseases of major interest in allergy are: – Work-related asthma and variants – Work-related rhinitis

• Others conditions are – Hypersensitivity pneumonitis – Allergic Bronchopulmonary Aspergillosis (ABPA) – Respiratory symptoms variously related to work:

work-related cough, other aspecific symptoms and signs

– Irritable larynx syndrome

Work-related asthma

• Occupational exposures account for 10-25% of adult asthma in the general population (Kogevinas, 2007).

• Occupational exposure can cause or exacerbate asthma (work-related asthma, WRA), and can also be associated with asthma variants (eosinophilic bronchitis, aluminium potroom asthma) or to symptoms that mimic asthma (e.g. the irritable larynx syndrome).

• WRA has health, social and economic costs

– USA, 1996: PAR 15% 1.6 billion dollars (Leigh, Chest 2002),

– Europe € 1.2 billion (Jinhai, 2010),

– UK £ 135 million (Ayres 2011)

• It is a burden for the society

Bernstein,2013

Allergic OA

• The most frequent form of OA (almost 80% of cases)

• Characterized by a latency period between the beginning of exposure and onset of symptoms

• Caused by workplaces sensitizers: i) Most high-molecular weight (HMW) agents (e.g.

flours) and some low-molecular weight (LMW) (e.g. Platinum salts) agents for which an IgE-mediated mechanism similar to non-WRA has been proven, and

ii) Some specific LMW-agents in which the allergic mechanisms responsible have not yet been fully characterized (e.g. Isocyanates)

Irritant-induced OA • Less frequent form of OA

• The most definite form of IIOA is the “Reactive Airways Dysfunction Syndrome” (RADS), which occurs as an acute onset of asthma after a single exposure to high concentrations of an irritating gas, vapour, fume or smoke.

• A less definite form, due to the paucity of reports and case studies, is non-acute irritant-induced OA where the onset of asthma is delayed and follows multiple, less massive exposures to irritants. It has been recently re-classified (Vandenplas et al, EAACI Pos Paper, Accepted Allergy)

No latency period

Close temporal

relationship

between exposure

and onset of

asthma

“Acute-onset IIA”,

“RADS”

Latency period

Epidemiological

evidence of an

excess incidence

of asthma in high-

risk occupations/

or jobs

“Low-dose IIA”,

“Not-so-sudden

IIA”, “IIA with

latency”

Latency period

Documentation of

repeated

symptomatic

exposures

“Sub-acute IIA”

Acute Delayed/insidious

IRRITANT-INDUCED ASTHMA?

Single, high-level Multiple, high-level Chronic, moderate

Delayed/insidious

* **

DEFINITE IIA PROBABLE IIA POSSIBLE IIA

ONSET OF ASTHMA

MODE OF

EXPOSURE

CLINICAL

CHARACTERISTICS

DIAGNOSTIC

LIKELIHOOD

Vandenplas et al, EAACI Pos Paper, Allergy, “Accepted Article”; doi: 10.1111/all.12448

Bernstein,2013

9

• Work-exacerbated asthma (WEA) is defined as preexisting or concurrent asthma that is worsened by workplace conditions.

• Recognizing and preventing asthma exacerbations is important, since the occurrence of severe asthma exacerbations is associated with an accelerated decline of respiratory function

• In non-work related asthma environmental exposure

factors appear to have a lesser role than host factors

when compared with OA.

• Occupational factors that potentially increase the risk of

asthma include

– high-risk jobs

– exposure to sensitizing agents

– exposure to low-level irritants in the workplace

– the mode and route of exposure

– the level of exposure

– concomitant exposures to pollutants at the workplace.

Curr Opin Allergy Clin Immunol 2014, 14:84–94

Hairdressers

Chest 2005;128;3590-3598

2010; 65: 784

AM J Ind Med 2011 Jul;54(7):565-8.

•Need for preventive strategies •Possible preventive measures encompass the substitution of cleaning sprays, bleach and ammonia, avoidance of mixing products, the use of respiratory protective devices, workers’ education and medical surveillance

Irritant-induced OA

CLEANERS Identified as a population at high risk for both non-

WRA and WRA in developed countries

offices, industrial plants, kitchens and hospitals

home

High-molecular weight agents

Occupation Agent

Baking, milling, pastry making Flour(s), -amylase, other enzymes, egg

white

Laboratory animal researchers and

technicians

Rat, mouse, guinea pig, ferret, etc. proteins,

egg

Health care workers Latex

Detergent enzyme manufactures Detergent protease, amylase, lipase, cellulase

Tea packers, coffee processors Herbal teas, green coffee bean

Sea food processors Prawn, crab, other (shell) fish proteins

Other food processors Garlic, egg, enzymes

Flower and vegetable farmers Pollens, moulds

Moscato et al. EAACI Position Paper on WRA diagnosis, Allergy 2012

ALLERGIC OA Sensitizers and occupations at risk

Low-molecular weight agents

Occupation Agent

Spray painters, French polishers Di-isocyanates

Electronic solderers Colophony fume

Health care workers Glutaraldehyde,methyl/butyl

methacrylate

Plastic and foam manufacturers Diisocyanates, acid anhydrides, epoxy

resins

Woodworkers, lumberjack Red cedar, iroko, other tropical sawdusts

Textile workers Reactive dyes

Hairdressers Persulphates

Pharmaceutical manufacturers Penicillins, morphine, cimetidine

Moscato et al. EAACI Position Paper on WRA diagnosis, Allergy 2012

ALLERGIC OA Sensitizers and occupations at risk

MODE AND ROUTE OF EXPOSURE

•Inhalation is by far the main route for many agents that cause occupational asthma.

•Despite the industry efforts to reduce exposure to chemicals through the inhalation route, occupational asthma continues to occur, suggesting skin exposure causing sensitization

nasopharyngeal region

trachea

primary bronchi

secondary bronchi

terminal bronchioles

respiratory bronchioles

alveoli

Entry and interaction of particles with the respiratory tract

tho

raci

c (4

-10

µm

)

inh

alab

le (

<10

0 µ

m)

resp

irab

le (

<4 µ

m)

Does particle size influence sensitization?

Exposure by inhalation

• The evidence supporting a dose-response relationship between the exposure level to occupational agents and the development of IgE-mediated sensitization and work-related respiratory symptoms for agents acting through an IgE-mediated mechanism is strong (Nicholson 2010; Vandenplas 2011).

• For sensitizers there is no exposure level

which entirely eliminates the risk (Heederik, 2012)

Level of exposure

Work-related asthmaWork-related asthma Work-related rhinitis

Asthma

caused

by work

=

Occupational

Asthma

(OA)

Asthma

exacerbated

by work

=

Work-

Exacerbated

Asthma (WEA)

Rhinitis

caused

by work

=

Occupational

Rhinitis

(OR)

Rhinitis

exacerbated

by work

=

Work-

Exacerbated

Rhinitis (WER)

Allergic OA (with latency period):

IgE-mediated

Non-IgE-mediated

Non-allergic OA (without latency):

Single exposure: RADS*

Multiple exposures: Irritant-

induced OA

Allergic OR (with latency period):

IgE-mediated

Non-IgE-mediated

Non-allergic OR (without latency):

Single exposure: RUDS**

Multiple exposures: Irritant-

induced OR

Corrosive rhinitis* RADS = Reactive Airways Dysfunction Syndrome

** RUDS = Reactive Upper airways Dysfunction Syndrome

Classification of work-related rhinitis and asthma

2008

EAACI POSITION PAPER OCCUPATIONAL RHINITIS

Moscato G et al, Allergy 2008

2008: 969-980

Relationships between OA and occupational rhinitis

• Rhinitis symptoms may be present in up to 92% cases of occupational asthma

• OA and OR share the same etiologic agents and mechanisms

• Rhinitis may precede of 6 - 24 months the onset of OA Occupational rhinitis may be a marker of the likelihood of developing occupational asthma

Moscato, Curr Opin Allergy Clin Immunol 2014; Siracusa, EAACI Pos Paper, submitted to Allergy

OCCUPATIONAL ANAPHYLAXIS

CONCLUSIONS • Work-related diseases are a typical example of the

influence of environment on human health

• Work-related respiratory diseases are the most frequent, however also occupational anaphylaxis may be found

• A recent review has shown that in non-work related asthma environmental exposure factors appear to have a lesser role than host factors when compared with occupational asthma.

• Occupational and non-occupational asthma have common features and OA is an excellent model for studying asthma