occupational asthma
Upload: chulalongkorn-allergy-and-clinical-immunology-research-group
Post on 26-May-2015
1.591 views
TRANSCRIPT
![Page 1: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/1.jpg)
Occupational Occupational asthmaasthma
W.pongsak
![Page 2: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/2.jpg)
scope
• Definition
• Causative agents
• Pathophysiology
• management
![Page 3: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/3.jpg)
![Page 4: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/4.jpg)
Type of occupational asthma
• Sensitizer-induce OA ( immunologic )
- HMW sensitizers
- LMW sensitizers
• Irritant-induce OA ( non-immunologic )
- RADs
- Others
![Page 5: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/5.jpg)
![Page 6: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/6.jpg)
![Page 7: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/7.jpg)
![Page 8: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/8.jpg)
![Page 9: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/9.jpg)
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
![Page 10: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/10.jpg)
Epidemiology
• Vary from 9-15% of adult asthma
• Depend on geographic pattern
• Depend on level and duration of exposure
• Atopy ?
• Difficult to definite diagnosis
![Page 11: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/11.jpg)
Agent causing OA
• HMW agents
- cereals and flaurs
- laboratory animals & shellfish allergy
- latex
- enzymes
![Page 12: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/12.jpg)
• 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
![Page 13: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/13.jpg)
![Page 14: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/14.jpg)
![Page 15: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/15.jpg)
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)
![Page 16: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/16.jpg)
• Irritant induce OA
- chlorine
- SO2
- combustion products
- ammonia
- phosgene
![Page 17: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/17.jpg)
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
![Page 18: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/18.jpg)
H
HDI induce prolipheration of γδT cell in OA patients
![Page 19: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/19.jpg)
![Page 20: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/20.jpg)
Increase production of IFN-γ and IL-5 in OA patients
![Page 21: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/21.jpg)
![Page 22: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/22.jpg)
T cell in OA and OR increase both TH1&2 response and decrease Treg
![Page 23: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/23.jpg)
• Irritant-induce OA
- high level of exposure
- epithelial injury
- inflammatory mediators
- activate neurotransmitter
- Macrophage and mast cell activation ?
- reflex bronchospasm
![Page 24: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/24.jpg)
![Page 25: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/25.jpg)
![Page 26: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/26.jpg)
![Page 27: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/27.jpg)
![Page 28: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/28.jpg)
Role of exposure
• Characteristic of the antigen
• Intensity of exposure
• Route of exposure
![Page 29: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/29.jpg)
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
![Page 30: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/30.jpg)
Intensity of exposure
• Dose response relationships
• Some exception
- laboratory animals
• Natural tolerance was not observe in other occupational allergen
• Level of “ no effect ”
![Page 31: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/31.jpg)
![Page 32: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/32.jpg)
Higher exposure to Fel d1 induce tolerance to cat allergen and increase to specific IgG
![Page 33: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/33.jpg)
Route of exposure
• Respiratory tract is the main route
• Dermal exposure ?
• Lower exposure of skin can sensitization
![Page 34: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/34.jpg)
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
![Page 35: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/35.jpg)
• Objective testing
- spirometry
- specific inhalation challenge
- immunologic testing
- PEFR monitoring
![Page 36: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/36.jpg)
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
![Page 37: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/37.jpg)
• 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
![Page 38: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/38.jpg)
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
![Page 39: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/39.jpg)
Gene asso withTH2 differentiation
• In diisocyanate IL-4Rα ,IL-13
![Page 40: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/40.jpg)
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
![Page 41: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/41.jpg)
Gene asso with lung function ,airway remodeling
• Glutathione S-transferase and
N-acetyltransferase asso with isocyanate induce asthma
![Page 42: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/42.jpg)
gene Type of OA
HLA-DQA1*0104
HLA-DQB1*0503
IL-4α,IL-13
GST,NAT
diiscyanate
HLA-DQB1*0501 Acid anhydride
sCD14 farmer
![Page 43: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/43.jpg)
![Page 44: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/44.jpg)
![Page 45: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/45.jpg)
![Page 46: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/46.jpg)
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
![Page 47: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/47.jpg)
Management
• Complete avoidance
• Medication not better than avoidance
• Protective devices?
• Lower exposure?
• Allergen immunotherapy?
![Page 48: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/48.jpg)
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
![Page 49: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/49.jpg)
Management
• Complete avoidance
• Medication not better than avoidance
• Protective devices?
• Lower exposure?
• Allergen immunotherapy?
![Page 50: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/50.jpg)
Respiratory protective devices can decrease risk of occupational asthma from Anhydride
![Page 51: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/51.jpg)
Management
• Complete avoidance
• Medication not better than avoidance
• Protective devices?
• Lower exposure?
• Allergen immunotherapy?
![Page 52: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/52.jpg)
![Page 53: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/53.jpg)
OA caused by TDI can persistent worsening of PFT despite discontinue exposure
![Page 54: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/54.jpg)
![Page 55: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/55.jpg)
Management
• Complete avoidance
• Medication not better than avoidance
• Protective devices?
• Lower exposure?
• Allergen immunotherapy?
![Page 56: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/56.jpg)
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
![Page 57: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/57.jpg)
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
![Page 58: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/58.jpg)
![Page 59: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/59.jpg)
Prevention
• Primary prevention
• Secondary prevention
• Tertiary prevention
![Page 60: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/60.jpg)
![Page 61: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/61.jpg)
![Page 62: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/62.jpg)
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
![Page 63: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/63.jpg)
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
![Page 64: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/64.jpg)
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
![Page 65: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/65.jpg)
4. all of the following are HMW agents except
A. animal proteins
B. latex
C. anhydrides
D. detergent enzymes
E. psyllium
![Page 66: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/66.jpg)
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
![Page 67: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/67.jpg)
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
![Page 68: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/68.jpg)
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
![Page 69: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/69.jpg)
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
![Page 70: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/70.jpg)
1. Lens Maker2. Detergent Worker3.Printer 4.Carpenter5.Urethane Foam
Worker
A. Bacillus SubtilisB. TragacanthC. Grain DustD. TDI
E. Plicatic AcidF. PapainG. Psyllium
FABED
![Page 71: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/71.jpg)
1.2
![Page 72: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/72.jpg)
conclusion
• Type of WRA
• Agent causing OA
• Mechanism of OA
• genetic susceptibility of OA
• Management of OA
![Page 73: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/73.jpg)
Thank you for your attention
![Page 74: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/74.jpg)
agent
![Page 75: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/75.jpg)
Good 3.25
![Page 76: Occupational Asthma](https://reader036.vdocument.in/reader036/viewer/2022062319/5563abdbd8b42a79028b47ce/html5/thumbnails/76.jpg)
2.108