Occupational Occupational asthmaasthma

W.pongsak

scope

• Definition

• Causative agents

• Pathophysiology

• management

Type of occupational asthma

• Sensitizer-induce OA ( immunologic )

- HMW sensitizers

- LMW sensitizers

• Irritant-induce OA ( non-immunologic )

- RADs

- Others

Varients

• Asthmalike disorders ( OTDs)

- expose to vegetable dust ,animal confinement

building

- asoociated with systemic symptoms

- no latency peroids

- neutrophillic airway inflammation• Eosinophillic bronchitis

- develop chronic airway obstruction later

ORGANIC TOXIC DUST SYNDROME

Epidemiology

• Vary from 9-15% of adult asthma

• Depend on geographic pattern

• Depend on level and duration of exposure

• Atopy ?

• Difficult to definite diagnosis

Agent causing OA

• HMW agents

- cereals and flaurs

- laboratory animals & shellfish allergy

- latex

- enzymes

• LMW agents - anhydrides - metals esp. platinum salt aluminium smelter - di-isocyanates => N=C=O group - cleaning agents - wood dusts => western red cedar - colophony and fluxes

Pathophysiology

• Sensitizer-induce OA

- HMW agent act as complete antigens

and act through IgE mediated mechanism

- Only some LMW agent act through IgE

mediated mechanism( anhydride,platinum)

- others LMW agent act through non-IgE

mediated mechanism (IgG and cell mediated)

• Irritant induce OA

- chlorine

- SO2

- combustion products

- ammonia

- phosgene

Cell mediated immunity

• In mouse model of HDI => mix Th1&2 • In human TDI induce asthma were CD8+ T cell

(Del Prete and Maestrelli) • HDI can induce peripheration of γδ T cell • In red cedar induce asthma T cell produce IL-5

and IFN-γ

H

HDI induce prolipheration of γδT cell in OA patients

Increase production of IFN-γ and IL-5 in OA patients

T cell in OA and OR increase both TH1&2 response and decrease Treg

• Irritant-induce OA

- high level of exposure

- epithelial injury

- inflammatory mediators

- activate neurotransmitter

- Macrophage and mast cell activation ?

- reflex bronchospasm

Role of exposure

• Characteristic of the antigen

• Intensity of exposure

• Route of exposure

Characteristic of antigen

• Mostly HMW Ag ( in the past)

• Recently chemical agent cause OA more than HMW Ag

• Structure-activity relationships

• In carbonyl,chlorine and amine group. 2 or more fragment associate with increase odd ratio to be asthmagens

Intensity of exposure

• Dose response relationships

• Some exception

- laboratory animals

• Natural tolerance was not observe in other occupational allergen

• Level of “ no effect ”

Higher exposure to Fel d1 induce tolerance to cat allergen and increase to specific IgG

Route of exposure

• Respiratory tract is the main route

• Dermal exposure ?

• Lower exposure of skin can sensitization

Diagnosis

• History

- change in work process proceeding symptom

- unusual high exposure within 24 hrs

- different symptom on weekday and holidays

- concomittent with rhinitis and conjuntivitis

ACCP 2008

• Objective testing

- spirometry

- specific inhalation challenge

- immunologic testing

- PEFR monitoring

Spirometry and peakflow

• Record 4 wks including peroid of at least 1 wk away from work

• Diurnal variation

• 64 % sensitivity 77% specificity

• What is disease that has worsening PFT on Monday and improve as the work week progress ?

BYSSINOSIS

• Gene asso. with innate immunity and immune regulation

• Gene asso. withTH2 differentiation

• Gene asso. with epithelium and mucosa

• Gene asso. with lung function ,airway remodeling

Genetic aspects

Gene associated with innate immunity and immune regulation

• HLA class II molecule

• DQA1*0104 and DQB1*0503 associate with diisocyanate

• DQB1*0501 associate with acid anhydride

• sCD14 associate with farmer

Gene asso withTH2 differentiation

• In diisocyanate IL-4Rα ,IL-13

Gene asso with epithelium and mucosa

• To date no data in human

• In mouse model increase expression of keratin 18 susceptibility to OA by HDI

Gene asso with lung function ,airway remodeling

• Glutathione S-transferase and

N-acetyltransferase asso with isocyanate induce asthma

gene Type of OA

HLA-DQA1*0104

HLA-DQB1*0503

IL-4α,IL-13

GST,NAT

diiscyanate

HLA-DQB1*0501 Acid anhydride

sCD14 farmer

Natural course

• Risk of OA highest in 1-2 years after exposure• Association with AR,AC (HMW agents)• Fatal condition in DI, baker, shark cartilage dust• Persistent AHR after remove exposure 70% but

lower in electronic and aluminium potroom workers

Management

• Complete avoidance

• Medication not better than avoidance

• Protective devices?

• Lower exposure?

• Allergen immunotherapy?

corticosteroid

Influence of inhaled steroids on the recovery of occupational asthma after cessation of exposure: an 18-month double-blind cross-over study.

Malo JL, Cartier A, Cote´ J, Milot J, Lablanc C, Paquette L, Ghezzo H, Boulet LP.

Am J Res Crit care Med 1997

N= 32 HMW 13 LMW 19 significant improve in PEFR ,QOL,symptom but magnitude is small

Management

• Complete avoidance

• Medication not better than avoidance

• Protective devices?

• Lower exposure?

• Allergen immunotherapy?

Respiratory protective devices can decrease risk of occupational asthma from Anhydride

Management

• Complete avoidance

• Medication not better than avoidance

• Protective devices?

• Lower exposure?

• Allergen immunotherapy?

OA caused by TDI can persistent worsening of PFT despite discontinue exposure

Management

• Complete avoidance

• Medication not better than avoidance

• Protective devices?

• Lower exposure?

• Allergen immunotherapy?

Allergen immunotherapy

Toci et al 3 pt. (oral) improve

Pereira et al 4 pt. (SCIT) improve

Leynadier et al 20 pt. (SCIT) improve

Sastre et al 24 pt. (SCIT) improve

Cistero et al 26 pt. (SLIT) improve

Latex allergy

Armentia et al 30 pt. (SCIT) improve

Jyo et al - improve

Hansen et al 1 pt. ( case report) improve

Baker asthma

Sea squirt allergy

Laboratory animal

Hinojosa et al 2 pt. (SCIT) improve

Wood dust allergy

Prevention

• Primary prevention

• Secondary prevention

• Tertiary prevention

QUIZ

1. All of the following chemicals have been reported to cause reactive airways dysfunction syndrome (RADS) EXCEPT:

A. Anhydrous ammoniaB. Chlorine gasC. Carbon dioxideD. PhosgeneE. Toluene diisocyanate

2. All of the following agents have been shown to cause both occupational asthma and hypersensitivity pneumonitis EXCEPT:

A. Toluene diisocyanateB. Trimellitic anhydrideC. Micropolyspora faeniD. Bacillus subtilisE. Diphenylmethane diisocyanate

3. Three weeks ago, a 28-year-old woman developed large subcutaneous nodules over the pretibial area of both lower extremities which are quite tender. There is prominent bilateral hilar adenopathy on chest x-ray. The most likely diagnosis is:

A. Hypersensitivity pneumonitisB. Lymphomatoid granulomatosisC. Organic dust toxic syndromeD. SarcoidosisE. Leukocytoclastic vasculitis

4. all of the following are HMW agents except

A. animal proteins

B. latex

C. anhydrides

D. detergent enzymes

E. psyllium

5. A 52-year-old farmer presents with paroxysmal cough, breathlessness, polymyalgia and malaise after extensive cleaning of his hay barn. Examination reveals temperature of 38.6 degrees Celsius and bibasilar crepitant rales. The chest roentgenogram is normal. Hemogram reveals leukocytosis with a predominance of polymorphonuclear leukocytes. Spirometry reveals a restrictive pattern. Precipitating antibody to which of the following antigens would be MOST helpful in establishing a diagnosis?

A. Micropolyspora faeniB. Alternaria tenuisC. Aspergillus clavatusD. Cryptostroma corticaleE. Penicillium frequentans

6.Occupational asthma caused by sensitivity to animal proteins is associated with

A. HLA -A

B. HLA -B

C. HLA -C

D. HLA -D

E. HLA -G

7. Specific antibody testing is most likely to confirm sensitization responsible for occupational asthma from which of the following?

A. formaldehyde

B. plicatic acid

C. toluene diisocyanate

D. trimellitic anhydride

E. colophony

8. Two newly hired workers walk into a grain stroage silo to start the spring chores. Four hours later, both workers complain of fever , tightness and wheezing by examination . What is the most likely diagnosis ?

A. Reactive airway dysfunction syndrome B. Byssinosis C. Hypersensitivity pneumonitis D. Organic toxic dust syndrome E. sensitizer induce occupational sthma

1. Lens Maker2. Detergent Worker3.Printer 4.Carpenter5.Urethane Foam

Worker

A. Bacillus SubtilisB. TragacanthC. Grain DustD. TDI

E. Plicatic AcidF. PapainG. Psyllium

FABED

1.2

conclusion

• Type of WRA

• Agent causing OA

• Mechanism of OA

• genetic susceptibility of OA

• Management of OA

Thank you for your attention

agent

Good 3.25

2.108