OCCUPATIONAL ASTHMA - PowerPoint by d2GZxfv

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									OCCUPATION ASTHMA

MALCOLM NOLAN BLUMENTHAL
      PROFESSOR
 DEPARTMENT OF MEDICINE,
           PEDIATRICS
  LABORATORY MEDICINE
 OCCUPATION ASTHMA (OA)

   ASTHMA ASSOCIATED WITH WORK
            EXPOSURE

  FOCUS IS ON THE HETEROGENEITY OF
WORK EXACERBATED ASTHMA AND A NEED
       FOR A BETTER DEFINITION
WORK RELATED ASTHMA (WRA)
• OCCUPATIONAL ASTHMA (OA): INDUCED
  BY SENSITIZER OR IRRITANTS AT WORK

• WORK–EXACERVATED ASTHMA (WEA):
  ASTHMA PROVOKED BY TRIGGERS AT
  WORK IN INDIVIDUALS WITH CONCURRENT
  OR PRE EXISITING ASTHMA.
               ASTHMA
• SYMPTOMS:   COUGHING
              WHEEZING
              SHORTNESS OF BREATH
• PHYSIOLOGIC CHANGES
              REVERSIBILITY
              BRONCHIAL HYPER-REACTIVITY
• PHYSICIANS DIAGNOSIS OF ASTHMA
• INFLAMMATORY DISEASE OF THE LUNG
  TYPICAL CLINICAL PICTURE
• SYMPTOMS WORSEN THROUGH THE WORK
  WEEK
• SYMPTOMS IMPROVE ON THE WEEKEND
• SYMPTOMS RECUR WHEN THE WORKER
  RETURNS TO THE JOB
                  OR
• AN ACCIDENT AT WORK INVOLVING A HIGH
  EXPOSURE CAUSE ASTHMA SYMPTOMS
    FACTORS INVOLVED IN ASTHMA
•   GENETIC
•   SUBSTANCE
•   EXPOSURE: TYPE, LEVELS AND ROUTE
•   HOST
•   GENETIC-ENVIRIONMENTAL INTERACTION
•   ATOPY
•   SMOKE
•   RHINOCONJUNCTIVITIS
    PREVALENCE AND INCIDENCE OF
             ASTHMA
• 5-10% of the general population have asthma
• 10-25% of asthma is due to OA
• Vocation cohorts are being studied and their
  prevalence will vary.
• Problems of epidemiological studies include
  classification, type of exposure, new or
  exacerbated asthma, genetic factors, age. race,
  sex and other risk factors.
MECHANISMS OF OCCUPATION
        ASTHMA
• IMMUNOLOGIC
  IgE MEDIATED
  NON IgE MEDIATED
• NON IMMUNOLOGIC
• IMMUNOLOGIC AND NON
  IMMUNOLOGIC
    MECHANISMS INVOLVED IN
     OCCUPATIONAL ASTHMA
• T CELL RESPONSE
• NONLINEAR EXPOSURE REPONSE
  RELATIONSHIPS AND TOLERANCE
• BASOPHILS AND MONCYTES ROLE
• AIRWAY REMODELING WHEN
  ASYMPTOMATIC
• POSSIBLE ROLE FOR IRRITANT EXPOSURE
   RISK FACTORS OF OA

RESULTS FROM THE INTERACTION

       HOST FACTORS
     GENETIC FACTORS
    LEVELS OF EXPOSURE
    ROUTE OF EXPOSURE
PATHOPHYSIOLOGY OF
IMMUNOLOGIC ASTHMA
      NON IMMUNOLOGIC
PATHOPHYSIOLOGICAL HYPOTHESIS
     MANAGEMENT OF WRA

• DEPEND ON ACCURATE DIAGNOSIS
  AND CHARACTERIZATION OF WRA
• POTENTIAL SENSIZERS CAUSING OA
       (WWW.ASMANET.COM)
  HMW PROTEINS CAUSES ~400
  LMW PROTIEN CAUSES ~30
COMMON AGENTS THAT CAUSE OA
        HIGH MOLECULAR WEIGHT AGENTS
ANIMAL AND INSECT           ANIMAL HANDLERS
  BIRD,CRUSTAEANS,EGGS      FOOD HANDLERS
  INSECTS, PHARMACEUTICAL   HEALTH CARE WORKERS

BACTERIAL AND FUNGAL        DETERGENTS
  BS, PENNIC C, THERMOPHILC CHEESE AND MUSHROOM

PLANT                       HEALTH CARE WORKERS
  LATEX, RUBBER             BEAUTICIANS
  PLANT ENZYMES             FOOD AND DRUG HANDLERS
  PSYLLIUM                  LAXATIVES
  WHEAT FLOUR               BAKERS
  VEGETABLE GUMS            PRINTERS, FOOD, CARPETS
       LOW MOLECULAR WEIGHT AGENTS
• Isocyanates        Spray painters; insulation
                     installers; manufacturers of plastics,
                     rubbers, and foam
•   Wood dusts       Forest workers, carpenters
•   Anhydrides       Users of plastics, epoxy resins
•   Amines           Shellac and lacquer handlers,solderers
•   Fluxes           Electronic workers
•   Chloramine-T     Janitors, cleaners
•   Dyes             Textile workers
•   Persulfate       Hairdressers
•   Acrylate         Adhesive handlers
•   Drugs            Pharmaceutical +health professionals
•   Metals           Solderers, refiners
•   Formaldehyde     Hospital staff
    glutaraldehyde
 AGENTS: IRRITANT INDUCED ASTHMA
Acids (Acetic acid, Sulfuric acid, HCL
Heated acid                  Bleaching agent
Chlorine                     Chloropicrin
Cleaning agents              Diesel exhaust
Dimethylaminoethanol         Diisocyanates
Epichlorohydrin              Ethylene oxide
Fire/smoke                   Floor sealant
Formalin                     Metal remover
Mustard                      Oxide (calcium)
Paints (heated)              Perchloroethylene
Phosgene                     Phthalic anhydride
Spray paint                  Sulfur dioxide
Ammonia
     FACTORS CONFUSED WITH
          WRA AND WEA
•   VOCAL CORD DYSFUNCTION
•   URI
•   HYPERSENSITIVITY PNEUMONITIS
•   EOSINOPHILIC BRONCHITIS
•   RHINOSINUSITIS
•   PSYCHOGENIC FACTORS
    CURRENT DIAGNOSITIC
     PARADIGM FOR WRD
• OBTAINING A COMPATIBLE MEDICAL
  AND OCCUPATIONAL HISTORY
• CONFIRM AN ASTHMA DIAGNOSIS
• DEMONSTRATE DECREMENTS IN
  SYMPTOMS AND LUNG FUNCTION
  WHEN EXPOSED TO SUBSTANCES
  AND IMPROVEMENT AWAY FROM
  WORK.
CLINICAL INVESTIGATION OF WORK
        RELATED ASTHMA
• DIAGNOSIS OF ASTHMA
     HISTORY
     PHYSIOLOGIC TESTING INVOVING EVIDENCE
           OF REVERSIBILITY AND OR BHR USING
           MC AND HC CHALLANGES
• IDENTIFICATION OF CAUSATIVE AGENT
     HISTORY
     SYMPTOMS WITH EXPOSURE
      AVOIDANCE OF CAUSATIVE AGENT
      MONITORING SYMTOM AT/AWAY FROM WORK
      MONITORING PFT AT/AWAY FROM WORK
      SPECIFIC INHALANTION CHALLENGES
DIRECT AND INDIRECT NON SPECIFIC
     BRONCHIAL CHALLENGES

NON-SELECTIVE DIRECT STIMULI ACTS ON
SMOOTH MUSCLE RECEPTORS
   HISTORY
   ACETYLCHOLINE AND MUSCARINIC ANALOGES
   METHACHOLINE
   HISTAMINE
NON SELECTIVE INDIRECT CHALLENGE (MEDIATOR
RELEASE FROM MAST CELLS/BASOPHILS)
   EXERCISE
   NON-OSMOTIC MEDIATOR RELEASE;AMP
   PROPRANOLOL, BRADYKININ, TACHYKININS
CLINICAL INVESTIGATION OF WORK
        RELATED ASTHMA
• DIAGNOSIS OF ASTHMA
     HISTORY
     PHYSIOLOGIC TESTING INVOVING EVIDENCE
           OF REVERSIBILITY AND OR BHR USING
           MC AND HC CHALLANGES
• IDENTIFICATION OF CAUSATIVE AGENT
     HISTORY
     SYMPTOMS WITH EXPOSURE
      AVOIDANCE OF CASUATIVE AGENT
      MONITORING SYMTOM AT/AWAY FROM WORK
      MONITORING PFT AT/AWAY FROM WORK
      SPECIFIC INHALANTION CHALLENGES
• IDENFICATION OF THE MECHANISM
  SPECIFIC INHALATION CHALLENGE
      TESTS: GOLD STANDARD
           INDICATIONS
• WHEN THE DIAGNOSIS OF OA IS IN DOUBT
• WHEN YOU NEED THE EXACT AGENT
  CAUSING THE PROBLEMS
• WHEN A NEW AGENT IS SUSPECTED
  CAUSING OA
• PROBLEMS OF INITIAL OR FURTHER
  SENSITIZATION
 IDENTIFICATION OF THE MECHANISM

• SKIN TESTING FOR IGE INVOLMENT
• NON IGE PARAMETERS OF THE
  IMMUNE RESPONSE.
• MONITORING OF EXHALED NO
• SPUTUM ANALYSIS INCLUDING
  EOSINOPHILS
 IDENTIFICATION OF THE MECHANISM

• TOXINS: IDENTIFICATION
• INFECTIONS: CULTURES, TITERS
• BIOPSY: STAINING OF CELLS,
  FIBROSIS, VASCULITIS,
  IMMUNOGLOBULINS
• GENETIC MARKERS
    Summary of characteristics of the more
relevant workplace agents associated with OA
                                   Mechanisms
Agent             MW* IgE Non-        Innate    Genetic        RF Exposure
                          IgE           IR

Polyisocyanate    low     +    +        +       HLA, IL-4RA.   +    +
                                                IL-13, GST
Acid Anhyrdire     low    +                     HLA            +    +
Animal,            high   +                     HLA, TL R      +    +
Latex              high   +                     HLA            +    +
Plicatic acid     Low     +    +                HLA            +    +
Wood dusts        Low     +    +
Flour dust        high    +
Complex platin    Low     +                     HLA            +    +
Detergent         high     +                    HLA            +     +
Cleaning agents   low     +                                    +    +
    NEEDS OF STUDIES OF OA
•   STANDARDIZATION OF METHODOLOGY
•   STANDARDIZATION OF TESTING REAGENTS
•   PREVENTIVE STUDIES
•   EPIDEMIOLOGIC STUDIES
  MEDICAL LEGAL ASPECTS, SOCIAL
  IMPACT AND SURVEILLANCE OF OA
• NEED OBJECTIVE TESTING IN ADDITION TO
  QUESTIONAIRES
• IMPLICATION OF OA IS GREAT MEDICALLY,
  SOCIALLY AND ECONOMICALLY
    MEDICAL COSTS ARE GREAT
    SOCIAL IMPLICATION ARE A PROBLEM
    ECONOMIC NEEDS OF THE PATIENT ARE
    COMPROMISED
• APPROXIMATELY 75% OF WORKERS WITH
  OA ARE LEFT WITH PERMANENT
  PROBLEMS.
    PSYCHO-SOCIO-ECONOMIC
        IMPACT OF WEA
• THERE IS A MAJOR DIRECT AND INDIRECT
  COST OF OA AND WEA
• PSCHOLOGICAL OUTCOMES EXIST
• VARIABILITY OF DIFFERENT
  COMPENSATION SYSTEMS
• RELATIVELY POOR AVERAGE ASTHMA
  OUTCOME
     PREVENTION OF OA:
    SCREENING METHODS
HOST FACTORS POSSIBLE RISK FACTORS
 PRESENCE OF ASTHMA, ATOPY, FAMILY
    HISTORY OF ALLERGY
 HISTORY OF SENSITIZATION TO AN AGENT
    THAT CROSS REACTS TO THE AGENT
    USED IN INDUSTRY
 PRESENCE OF A DIRECT OR INDIRECT
    CHALLENGE
 PRESENCE OF BHR
PREVENTION OF OA: SCREENING
         METHODS
AVOID COMMON SENSITIZING AGENTS
 ACRYLATE       ADHESIVE HANDLERS
 AMINES         SHELLAC AND LACQUER
                HANDLERS, BEAUTICIAMS
 ANHYDRIDES     PLASTICS AND EPOXY RESINS
 ANIMALS        ANIMAL HANDLERS, VETS,
                FARMERS
 CEREAL GRAIN   BAKERS, MILLERS
 CHLORAMINE-T   JANITORS, CLEANING STAFF
 DRUGS/MEDS     HEALTH CARAE WORKERS
PREVENTION OF OA: SCREENING
         METHODS
 AVOID COMMON SENSITIZING AGENTS

DYES            TEXTILE WORKERS
ENZYMES         DETERGENT WORKERS,
                PHARM. WORKER
FLUXES          ELECTRONIC WORKERS
FORMALDEHYDE    HOSPITAL STAFF
GUMS            CARPET, PHARM
     PREVENTION OF OA: SCREENING
              METHODS
AVOID COMMON SENSITIZING AGENTS
ISOCYANATES     SPRAY PAINTERS,INSULATION,
                RUBBER
LATEX           HEALTH PROFESSIONALS
METALS          SODERERS, REFINERS, PRINTERS
PERSULFATE      HAIRDRESSERS
SEAFOOD         SEAFOOD WORKERS
WOOD DUST       FOREST AND WOOD WORKERS
PESTICIDES/     FARMERS, GRAIN WORKERS
  FERTILIZERS
       PREVENTION

PE-EMPLOYMENT SURVEILLANCE


 EFECTIVENESS IN SCREENING
SUBJECTS BEFORE HIRING THEM
     PREVENTION INVOLVES
     EXPOSURE REDUCTION
• IDENTIFY AND ASSESS A HIGH RISK WORK
  ENVIORMENT
• ADVISE THE EMPLOYER REGARDING CONTROL
  MEASURES THAT MAY PREVENT NEW CASES.
• REMOVE THE CAUSATIVE AGENT AND SUBSITUTE
  A SAFER ALTERNATIVE METHOD
• IDENTIFY THRESHOLD EXPOSURE LIMITS TO
  DEFINE A LEVEL BELOW WHICH OA IS UNLIKELY TO
  DEVELOP.
• REDUCE AMBIENT EXPOSURE TO ALLERGENS AND
  IDENTIFY WORKERS WITH OA AND ALLERGIC
  RHINITIS.
 REDUCTION OF EXPOSURE TO
         AGENTS
AGENT ISOLATION
    EXPOSURE LEVELS KEPT AT A MINIMUM
    USE AN EQUALLY GOOD AGENT
    KEEP AGENT IN A ISOLATED AREA WITH A
          MINIMAL EXPOSURE OF THE SUBJECT

HOST ISOLATION
     MASK USE
     KEEP SUBJECT IN AN ENVIRONMENT
          ISOLATED FROM THE AGENT
MANAGEMENT OF WRA CAUSED BY
       SENSITIZERS
          PHAMACOLOGIC   EXPOSURE      REMAIN
            TREAMENT                   AT WORK
OA-HMW     CONTROL       PREVENT        NO(EC)
                         EXPOSURE
OA-LMW     CONTROL       PREVENT        NO
                         EXPOSURE
HA-RADS    CONTROL       PREVENT        YES
                         HI EXPOSURE    MEDM
WEA        CONTROL       PREVENT        YES
                         EXPOSURE       MEDM
SYMPTOMATIC TREATMENT
      OF ASTHMA

 BASED ON ASTHMA TREATMENT
         GUIDELINES
OTHER TREATMENT OF WRA/WEA

• PREVENT AMBIENT EXPOSURE IN OA-HMW
  AND LMW CHEMICAL SENTIZIER
• PREVENT HIGH EXPOSURE TO IRRITANTS
  IN HYPER REACTIVE/REACTIVE AIRWAY
  DISEASE
• WEA PREVENT EXPOSURE TO IRRITANTS,
  ALLERGENS AND RELEVANT TRIGGERS
• PHAMACOTHERAPY OPTIMIZED
• ADMINISTRATIVE MANAGEMENT OF WRA
    SPECIFIC ALLERGEN
      MANAGEMENT
• PRIMARY TREATMENT FOR OA IS
  ELIMINATION OF TRIGGER
• ALLERGEN IMMUNOTHERAPY HAS
  LIMITED EVIDENCE FOR ITS USE
   MANAGEMENT OF WORK
     RELATED ASTHMA

• THERE IS NOT A SINGLE CORRECT
  APPROACH IN VIEW OF THE
  MULTIPLE FACTORS AND MECHANISM
• STRATEGIES ARE TEMPERED BY
  SOCIAL AND ECONOMIC
  CONSIDERATIONS
 HUMAN MODELS OF WORK
    RELATED ASTHMA
• HIGH MOLECULAR WEIGHT AGENTS
     BAKING PRODUCTS
     LATEX
• LOW MOLECULAR WEIGHT AGENTS
     DIISOCYTANATES
     WOOD DUST
       BAKING PRODUCE AND OA

• CAUSES ARE HIGH MOLECLULAR WEIGHT AGENTS
     CEREALS SUCH AS WHEAT
     LATEX
     HIGHLY VOLATILE SOYS DUST
     ENZYMES
     ADDITIVES
     YEAST
     STORAGE MITES
     MOLDS
• RISK FACTORS INCLUDING:
     RHINOCONJUNCTIVITY/ASTHMA
     ATOPY
     LEVELS OF WHEAT DUST EXPOSURE >0.5 MG/M3
                    LATEX

   HIGH MOLECULAR WEIGHT AGENT
ESSENTIAL FUNCTION UNIT IS A RUBBER
PARTICLE
   Housekeeping; Hev b1, Hev b2, Heb b7
   Health care workers: Heb v 6 and Hev b7)
CROSS REACTIONS WITH FOODS
   Avocado            Kiwi Fruit
   Banana             Potatoes
   Tomatoes           Chestnut
   Papaya
         EPIDEMIOLOGY
• PREVELANCE
  5-10% IN GENERAL POPULATION
  2.5-16.9% IN HEALTH PROFESSIONALS
• FOUND IN
  HEALTHCARE WORKERS (0.5-17%)
  PATIENTS WITH SPINA BIFIDA (18-64%)
    CLINICAL PICTURE OF LATEX
             ALLERGY

•   CONTACT DERMATITIS
•   CONTACT URTICARIA
•   RHINITIS AND ASTHMA
•   ANAPHYLAXIS
DIAGNOSIS OF LATEX ALLERGY

• SKIN TESTING
• SPECIFIC LATEX IGE
• CHALLENGE STUDIES
    MANAGEMENT OF LATEX
• AVOIDANCE
 TEAM APPROACH TO DECREASE EXPOSURE
 CENTRALIZED PURCHASING
 AVOID POWDERED LATEX GLOVE
 LOOK FOR ALTERNATIVE FOR LATEX
 EDUCATION
 ESTABLISH POLICIES FOR LATEX SENITIVITY
   SUBJECTS
• PHARMACOLOGIC
• IMMUNOTHERAPY
     DIISOCYANATES (DIC)
• LOW MOLLECULAR WEIGHT AGENTS
• AGENTS INCLUDE TDI. MDI AND HDI
• OCCUPATIONS INCLUDE AUTOMOBILE INDUSTRY,
  FOUNDRIES, PRODUCTION OF RUBBER CUSHIONS,
  SPRAY PAINTS
• GENE SUSCEPTIBILITY SUGGESTIVE FOR THE HLA
  CLASS II ANTIGENS SYSTEM.
• MECHANISM INVOLVED NOT CLEARLY
  ESTABLISHED.
• MOST PATIENTS WITH DIC FAIL TO RECOVER
  YEARS AFTER REMOVAL.
  ACRYLATES AND WOOD DUST ARE
  LOW MOLECULAR WEIGHT AGENTS
ACRYLATES: USED IN QUICK DRYING
 PATIENTS, SEALERS, INKS, ADHESIVE,
 FLOOR WAX ETC.

WOOD DUST:
 PLICATIC ACID IN WESTERN RED CEDAR.
 PREVELENCE BETWEEN 5 – 10%
 SUGGESTION OF A HLA RELATIONSHIP
           WRA SUMMARY
• WRA IS COMMON
• DEFINITIONS OF WRA IS NEEDED
  -NO CURRENT DIAGNOSITIC TESTS FOR OA ARE
  PERFECT
  -PATIENTS STUDIED IN TERTIARY CENTERS DO
  NOT REPRESENT THE FULL SPECTRUM OF OA
• EFFECTS OF REDUCED EXPOSURE NEEDS TO BE
  STUDIED
• NEED TO CONSIDER THE INFLUENCE OF THE
  COMPENSATION SYSTEM FOR OA
• MANY MECHANISMS ARE INVOLVED IN WRA
        WRA SUMMARY
• NEED DEFINITION OF MECHANISMS
• STANDARDIZATION OF METHODS
• STANDARDIZATION OF DIAGNOSTIC
  REAGENTS.
• METHODS OF AVOIDANCE AND USE OF
  ALTERNATIVE MATERIALS
• UNDERSTANDING OF THE MEDICAL,
  ECONOMIC AND LEGAL ASPECT.
       WRA SUMMARY

• KNOWLEDGE GAPS EXIST IN WEA
  AND ITS RELATED DISABILITY

• THERE IS A NEED FOR RESEARCH
  ADDRESSING WRA

								
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