Occupational Asthma

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  • Occupational Asthma

    1. 1. Occupational asthma W.pongsak
    2. 2. scope <ul><li>Definition </li></ul><ul><li>Causative agents </li></ul><ul><li>Pathophysiology </li></ul><ul><li>management </li></ul>
    3. 4. Type of occupational asthma <ul><li>Sensitizer-induce OA ( immunologic ) </li></ul><ul><li>- HMW sensitizers </li></ul><ul><li>- LMW sensitizers </li></ul><ul><li>Irritant-induce OA ( non-immunologic ) </li></ul><ul><li>- RADs </li></ul><ul><li>- Others </li></ul>
    4. 9. Varients <ul><li>Asthmalike disorders ( OTDs) </li></ul><ul><li>- expose to vegetable dust ,animal confinement </li></ul><ul><li>building </li></ul><ul><li>- asoociated with systemic symptoms </li></ul><ul><li>- no latency peroids </li></ul><ul><li>- neutrophillic airway inflammation </li></ul><ul><li>Eosinophillic bronchitis </li></ul><ul><li>- develop chronic airway obstruction later </li></ul>ORGANIC TOXIC DUST SYNDROME
    5. 10. Epidemiology <ul><li>Vary from 9-15% of adult asthma </li></ul><ul><li>Depend on geographic pattern </li></ul><ul><li>Depend on level and duration of exposure </li></ul><ul><li>Atopy ? </li></ul><ul><li>Difficult to definite diagnosis </li></ul>
    6. 11. Agent causing OA <ul><li>HMW agents </li></ul><ul><li>- cereals and flaurs </li></ul><ul><li>- laboratory animals & shellfish allergy </li></ul><ul><li>- latex </li></ul><ul><li>- enzymes </li></ul>
    7. 12. <ul><li>LMW agents </li></ul><ul><li>- anhydrides </li></ul><ul><li>- metals esp. platinum salt </li></ul><ul><li>aluminium smelter </li></ul><ul><li>- di-isocyanates => N=C=O group </li></ul><ul><li>- cleaning agents </li></ul><ul><li>- wood dusts => western red cedar </li></ul><ul><li>- colophony and fluxes </li></ul>
    8. 15. Pathophysiology <ul><li>Sensitizer-induce OA </li></ul><ul><li>- HMW agent act as complete antigens </li></ul><ul><li>and act through IgE mediated mechanism </li></ul><ul><li>- Only some LMW agent act through IgE </li></ul><ul><li>mediated mechanism( anhydride,platinum) </li></ul><ul><li>- others LMW agent act through non-IgE </li></ul><ul><li>mediated mechanism (IgG and cell mediated) </li></ul>
    9. 16. <ul><li>Irritant induce OA </li></ul><ul><li>- chlorine </li></ul><ul><li>- SO2 </li></ul><ul><li>- combustion products </li></ul><ul><li>- ammonia </li></ul><ul><li>- phosgene </li></ul>
    10. 17. Cell mediated immunity <ul><li>In mouse model of HDI => mix Th1&2 </li></ul><ul><li>In human TDI induce asthma were CD8+ T cell </li></ul><ul><li>(Del Prete and Maestrelli) </li></ul><ul><li>HDI can induce peripheration of γδ T cell </li></ul><ul><li>In red cedar induce asthma T cell produce IL-5 and IFN- γ </li></ul>
    11. 18. H HDI induce prolipheration of γδ T cell in OA patients
    12. 20. Increase production of IFN- γ and IL-5 in OA patients
    13. 22. T cell in OA and OR increase both TH1&2 response and decrease Treg
    14. 23. <ul><li>Irritant-induce OA </li></ul><ul><li>- high level of exposure </li></ul><ul><li>- epithelial injury </li></ul><ul><li>- inflammatory mediators </li></ul><ul><li>- activate neurotransmitter </li></ul><ul><li>- Macrophage and mast cell activation ? </li></ul><ul><li>- reflex bronchospasm </li></ul>
    15. 28. Role of exposure <ul><li>Characteristic of the antigen </li></ul><ul><li>Intensity of exposure </li></ul><ul><li>Route of exposure </li></ul>
    16. 29. Characteristic of antigen <ul><li>Mostly HMW Ag ( in the past) </li></ul><ul><li>Recently chemical agent cause OA more than HMW Ag </li></ul><ul><li>Structure-activity relationships </li></ul><ul><li>In carbonyl,chlorine and amine group. 2 or more fragment associate with increase odd ratio to be asthmagens </li></ul>
    17. 30. Intensity of exposure <ul><li>Dose response relationships </li></ul><ul><li>Some exception </li></ul><ul><li>- laboratory animals </li></ul><ul><li>Natural tolerance was not observe in other occupational allergen </li></ul><ul><li>Level of “ no effect ” </li></ul>
    18. 32. Higher exposure to Fel d1 induce tolerance to cat allergen and increase to specific IgG
    19. 33. Route of exposure <ul><li>Respiratory tract is the main route </li></ul><ul><li>Dermal exposure ? </li></ul><ul><li>Lower exposure of skin can sensitization </li></ul>
    20. 34. Diagnosis <ul><li>History </li></ul><ul><li>- change in work process proceeding symptom </li></ul><ul><li>- unusual high exposure within 24 hrs </li></ul><ul><li>- different symptom on weekday and holidays </li></ul><ul><li>- concomittent with rhinitis and conjunt ivitis </li></ul>ACCP 2008
    21. 35. <ul><li>Objective testing </li></ul><ul><li>- spirometry </li></ul><ul><li>- specific inhalation challenge </li></ul><ul><li>- immunologic testing </li></ul><ul><li>- PEFR monitoring </li></ul>
    22. 36. Spirometry and peakflow <ul><li>Record 4 wks including peroid of at least 1 wk away from work </li></ul><ul><li>Diurnal variation </li></ul><ul><li>64 % sensitivity 77% specificity </li></ul><ul><li>What is disease that has worsening PFT on Monday and improve as the work week progress ? </li></ul>BYSSINOSIS
    23. 37. <ul><li>Gene asso. with innate immunity and immune regulation </li></ul><ul><li>Gene asso. withTH2 differentiation </li></ul><ul><li>Gene asso. with epithelium and mucosa </li></ul><ul><li>Gene asso. with lung function ,airway remodeling </li></ul>Genetic aspects
    24. 38. Gene associated with innate immunity and immune regulation <ul><li>HLA class II molecule </li></ul><ul><li>DQA1*0104 and DQB1*0503 associate with diisocyanate </li></ul><ul><li>DQB1*0501 associate with acid anhydride </li></ul><ul><li>sCD14 associate with farmer </li></ul>
    25. 39. Gene asso withTH2 differentiation <ul><li>In diisocyanate IL-4R α ,IL-13 </li></ul>
    26. 40. Gene asso with epithelium and mucosa <ul><li>To date no data in human </li></ul><ul><li>In mouse model increase expression of keratin 18 susceptibility to OA by HDI </li></ul>
    27. 41. Gene asso with lung function ,airway remodeling <ul><li>Glutathione S-transferase and </li></ul><ul><li>N-acetyltransferase asso with isocyanate induce asthma </li></ul>
    28. 42. farmer sCD14 Acid anhydride HLA-DQB1 *0501 diiscyanate HLA-DQA1*0104 HLA-DQB1*0503 IL-4 α ,IL-13 GST,NAT Type of OA gene
    29. 46. N atural course <ul><li>Risk of OA highest in 1-2 years after exposure </li></ul><ul><li>Association with AR,AC (HMW agents) </li></ul><ul><li>Fatal condition in DI, baker, shark cartilage dust </li></ul><ul><li>Persistent AHR after remove exposure 70% but lower in electronic and aluminium potroom workers </li></ul>
    30. 47. Management <ul><li>Complete avoidance </li></ul><ul><li>Medication not better than avoidance </li></ul><ul><li>Protective devices? </li></ul><ul><li>Lower exposure? </li></ul><ul><li>Allergen immunotherapy? </li></ul>
    31. 48. corticosteroid <ul><li>Influence of inhaled steroids on the recovery of occupational asthma after cessation of exposure: an 18-month double-blind cross-over study . </li></ul><ul><li>Malo JL, Cartier A, Cote´ J, Milot J, Lablanc C, Paquette L, Ghezzo H, Boulet LP. </li></ul><ul><li>Am J Res Crit care Med 1997 </li></ul><ul><li>N= 32 HMW 13 LMW 19 significant improve in PEFR ,QOL,symptom but magnitude is small </li></ul>
    32. 49. Management <ul><li>Complete avoidance </li></ul><ul><li>Medication not better than avoidance </li></ul><ul><li>Protective devices? </li></ul><ul><li>Lower exposure? </li></ul><ul><li>Allergen immunotherapy? </li></ul>
    33. 50. Respiratory protective devices can decrease risk of occupational asthma from Anhydride
    34. 51. Management <ul><li>Complete avoidance </li></ul><ul><li>Medication not better than avoidance </li></ul><ul><li>Protective devices? </li></ul><ul><li>Lower exposure? </li></ul><ul><li>Allergen immunotherapy? </li></ul>
    35. 53. OA caused by TDI can persistent worsening of PFT despite discontinue exposure
    36. 55. Management <ul><li>Complete avoidance </li></ul><ul><li>Medication not better than avoidance </li></ul><ul><li>Protective devices? </li></ul><ul><li>Lower exposure? </li></ul><ul><li>Allergen immunotherapy? </li></ul>
    37. 56. Allergen immunotherapy Latex allergy improve 24 pt. (SCIT) Sastre et al improve 20 pt. (SCIT) Leynadier et al improve 4 pt. (SCIT) Pereira et al improve 3 pt. (or al) Toci et al improve 26 pt. (SLIT) Cistero et al
    38. 57. Baker asthma Sea squirt allergy Laboratory animal Wood dust allergy improve 30 pt. (SCIT) Armentia et al improve - Jyo et a l improve 1 pt. ( case report) Hansen et al improve 2 pt. (SCIT) Hinojosa et al
    39. 59. Prevention <ul><li>Primary prevention </li></ul><ul><li>Secondary prevention </li></ul><ul><li>Tertiary prevention </li></ul>
    40. 62. QUIZ <ul><li>1. All of the following chemicals have been reported to cause reactive airways dysfunction syndrome (RADS) EXCEPT: A. Anhydrous ammonia B. Chlorine gas C. Carbon dioxide D. Phosgene E. Toluene diisocyanate </li></ul>
    41. 63. <ul><li>2. All of the following agents have been shown to cause both occupational asthma and hypersensitivity pneumonitis EXCEPT: A. Toluene diisocyanate B. Trimellitic anhydride C. Micropolyspora faeni D. Bacillus subtilis E. Diphenylmethane diisocyanate </li></ul>
    42. 64. <ul><li>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 pneumonitis B. Lymphomatoid granulomatosis C. Organic dust toxic syndrome D. Sarcoidosis E. Leukocytoclastic vasculitis </li></ul>
    43. 65. <ul><li>4. all of the following are HMW agents except </li></ul><ul><li>A. animal proteins </li></ul><ul><li>B. latex </li></ul><ul><li>C. anhydrides </li></ul><ul><li>D. detergent enzymes </li></ul><ul><li>E. psyllium </li></ul>
    44. 66. <ul><li>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 faeni B. Alternaria tenuis C. Aspergillus clavatus D. Cryptostroma corticale E. Penicillium frequentans </li></ul>
    45. 67. <ul><li>6.Occupational asthma caused by sensitivity to animal proteins is associated with </li></ul><ul><li>A. HLA -A </li></ul><ul><li>B. HLA -B </li></ul><ul><li>C. HLA -C </li></ul><ul><li>D. HLA -D </li></ul><ul><li>E. HLA -G </li></ul>
    46. 68. <ul><li>7. Specific antibody testing is most likely to confirm sensitization responsible for occupational asthma from which of the following? </li></ul><ul><li>A. formaldehyde </li></ul><ul><li>B. plicatic acid </li></ul><ul><li>C. toluene diisocyanate </li></ul><ul><li>D. trimellitic anhydride </li></ul><ul><li>E. colophony </li></ul>
    47. 69. <ul><li>8. Two newly hired workers walk into a grain stroage silo to star t the spring chores. Four hours later, both workers complain of fever , tightness and wheezing by examination . What is the most likely diagnosis ? </li></ul><ul><li>A. Reactive airway dysfunction syndrome </li></ul><ul><li>B. Byssinosis </li></ul><ul><li>C. Hypersensitivity pneumonitis </li></ul><ul><li>D. Organic toxic dust syndrome </li></ul><ul><li>E. sensitizer induce occupational sthma </li></ul>
    48. 70. FABED A. Bacillus Subtilis B. Tragacanth C. Grain Dust D. TDI E. Plicatic Acid F. Papain G. Psyllium <ul><li>Lens Maker </li></ul><ul><li>Detergent Worker </li></ul><ul><li>3.Printer  </li></ul><ul><li>4. Carpenter </li></ul><ul><li>5.Urethane Foam Worker </li></ul>
    49. 71. 1.2
    50. 72. conclusion <ul><li>Type of WRA </li></ul><ul><li>Agent causing OA </li></ul><ul><li>Mechanism of OA </li></ul><ul><li>genetic susceptibility of OA </li></ul><ul><li>Management of OA </li></ul>
    51. 73. Thank you for your attention
    52. 74. agent
    53. 75. Good 3.25
    54. 76. 2.108

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