Occupational Asthma
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Transcript of Occupational Asthma
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