Diagnosis in occupational asthma by liuqingyan



Assoc. Prof. Can Sevinc

Dokuz Eylul University
School of Medicine
Pulmonary Medicine Department
Izmir - Turkiye

Presantation Plan

   Clinical history
   PEFR monitoring
   Spirometry
   Skin prick test
   IgE, sIgE
   Induced sputum
   Nonspesific bronchial challenge test
   Spesific bronchial challenge test
   Algorhytm
Occupational asthma caused by
immunological sensitisation

   Symptom-free latent period
   Reaction to low amounts
   Minority of exposed workers

  Asthma in the workplace (2nd Ed.) Marcel Dekker, 1999
Occupational asthma caused by
irritation: “irritant-induced asthma”

    After a single inhalation accident
       RADS
         “Reactive Airways Dysfunction Syndrome”

Brooks S, Weiss MA, Bernstein IL. Chest, 1985, 88, 376-84
Occupational asthma caused by
irritation: “irritant-induced asthma”

 After multiple peaks of chemical
   Cl2, SO2, formaldehyde
Clinical diagnosis of asthma

   Variable dyspnoea and wheezing
   Nonspecific bronchial
   Cough,mucus hypersecretion
   Repeated episodes of “bronchitis”

  *document by pulmonary function tests

 Sometimes: asthma-attacks at work
 Usually: more asthma symptoms in the
 evening or at night
  • (delayed reactions)

 Nonspecific bronchial hyperresponsiveness
 causes intolerance to inhaled irritants
   cigarette smoke, engine exhaust, strong odours,
   fog, cold air, exercise

 The patient often believes that these triggers
 are the “cause” of the asthma

   Few symptoms during work
   Most symptoms after work
     iscommon and
     does not exclude occupational
      asthma !

   Intolerance to irritants outside the
       Does not exclude occupational
        asthma !

   Occupational asthma does not
    necessarily mean “asthma at work”,
     but “asthma from work”
 Which question?

 To detect occupational asthma it is
  not appropriate, nor sufficient to ask
    “is   your asthma worse at work?”
 it   is more efficient to ask
    “does   your breathing get better
       during the week-end or holiday?”

           Burge PS, Br J Dis Chest 1987; 81: 105-15.
    Typical history

   Occupational history (potential exposure to
    occupational agents)
   Same other cases at this workplace
   Allergic findings related to other systems
   Concurrent new event at the same time of
    onset of the symptoms (new work, agent,
   Uncontrolled asthma in spite of appropriate
   Improvement of symptoms during holiday
    Does help history of “Improvement
    of symptoms during holiday”
One study of 162 patients found that
  66 of 75 patients (88%) with OA stated
       their symptoms improved during holidays,
  but 66 of 87 patients (76%) without
   occupational asthma reported a similar

   Malo, JL, Ghezzo, H, L'Archevêque, J, et al. Am Rev Respir Dis 1991; 143:528.
 Repeated bronchitis ???

 Repeated absence from work because
 of “bronchitis” may be a sign of
 occupational asthma
   even if these episodes appear to be
    responsive to treatment with
   it is the temporary removal from
    exposure that is most beneficial
Value of history

 Clinical history alone is inadequate to
 confirm or exclude the diagnosis of
       although the negative predictive
       value is better than the positive
       predictive value.

Malo, JL, Ghezzo, H, L'Archevêque, J, et al. Am Rev Respir Dis 1991; 143:528.

 Documenting allergy to common
 allergens does not exclude
 occupational asthma
     house dust mite, pets, pollen
   atopy is a risk factor for some forms
   of occupational asthma

 Atopy is clearly associated with OA due
 to HMW agents,
   but because atopy is present in almost
   50% of young adults,
   it cannot satisfactorily predict the
   development of OA,
   which affects less than 5% of subjects
   in high-risk workplaces.

 Although the clinician should take a history
  of preexisting asthma and atopy,
   these characteristics have poor positive
    predictive values.
 In one study found that
   only approximately one-third of atopic
    subjects developed rhinoconjunctivitis or
    asthma symptoms in the five years following
    onset of exposure to laboratory animals.

          Slovak, AJM, Hill, RN. Br J Ind Med 1987; 44:129.
Always consider !

 Always consider the possibility that
 asthma may have an occupational
   in new patients
   in well-known asthmatics
Relation with work

 Latent period (weeks-years)
 Improvement when off-work
 Fellow workers
The latency period between the onset
 of exposure and the onset of
 symptoms is highly variable.
  the latency period is shorter
       with exposure to low-molecular-weight
        (LMW) agents,
             such as isocyanates and plicatic acid
              (Western red cedar),
       than with HMW agents.

  Malo, JL, Ghezzo, H, D'Aquino, C, et al. J Allergy Clin Immunol 1992; 90:937.
~ 50% of subjects who develop OA
 due to isocyanates experience
 symptoms within the first two years
 after the onset of exposure,
  whereas the median latency period
   after exposure to HMW agents is
   approximately five years.
    Identification of cause
 Exposure to known asthma-inducing agent
     Type of work
     Product information
     Contact occupational physician
   May be very difficult
     Do not always rely on Material Safety Data
     Beware of recent changes in work processes,
     suppliers of materials & ingredients, etc.
    Identification of cause

 Immunological tests
     skin prick tests
     specific IgE (RAST)
     for macromolecular agents
     usually not available and not valid for
     LMW agents, except for some
        complex Pt salts
        some reactive chemicals (organic dyes)
   only indicative of sensitization, not cause
Skin testing

Skin test reagents are not available
 for documenting hypersensitivity to
 most occupational agents,
  but the technique is feasible for some
   HMW agents,
     such as animal or plant proteins.
The presence of immediate skin test
 reactivity reflects
  IgE-specific sensitization.
Excessive dermal reaction to pectin
    İn a jam production worker
Negative skin prick test

   A negative test virtually excludes the
    possibility that OA is caused by that
    specific antigen.
Specific BCT

   These tests consist of intentionally
    exposing subjects to occupational
    agents in a hospital laboratory or,
    occasionally, at work.
 In the case of HMW agents,
 bronchoprovocation testing
   can be carried out in a single day,
   because an immediate reaction that
   is maximal during the first hour
   following exposure is expected.
      Identification of cause -
     Specific bronchial provocation testing
      considered as the Gold Standard, but:
       not so easy to perform
       not always feasible
       time-consuming and expensive
       potentially dangerous (specialized centres)
       not always necessary
     “false negative” if challenge with wrong agent

 Can be done in the workplace under medical
   but time-consuming and
   often difficult to organize
                                        Baker’s asthma

Immediate response to soya and wheat flour in specific bronchial challenge test
                                           Hairdresser’s asthma

Dual asthmatic response to sodium persulphate in specific bronchial challange test
  Nonspecific bronchoprovocation testing

 To obtain more objective evidence of an
 occupational relationship of symptoms,
 nonspecific bronchial
 hyperresponsiveness can be measured
   at the end of the work period and
   at the end of the period away from work.
 The absence of bronchial
 when the subject is at work and has
   virtually excludes OA.
LMW agents

LMW agents often cause
 nonimmediate or late reactions and
  require daily challenges of escalating
   doses of antigen on sequential days.
During testing,
  assessment of nonspecific bronchial
   hyperresponsiveness is carried out
     toward the end of the challenge
      day or
     at 24 hours after inhalation.

      Increase in nonspecific bronchial
          can precede the onset of asthmatic reactions
          is an early and sensitive marker of airway
           responsiveness to occupational agents.

Vandenplas, O, Delwiche, JP, Jamart, J, Van de Weyer, R. Thorax 1996; 51:472.
      Relation with work
     “stop-and-resume-work test”
       changes in symptoms and medication need
       changes in lung function
          spirometry (FEV1)
          nonspecific bronchial responsiveness
            (histamine or methacholine PC20)
    self-recorded peak-flow measurements

 Before assessing whether asthma is
  caused by workplace exposure, one
  should confirm that the patient indeed
  has asthma.
 The diagnosis of asthma from history
  alone may not be accurate, and
  therefore pulmonary function testing is
   Spirometry in the workplace

 Monitoring of FEV1 in the workplace by a
 skilled technician should be encouraged,
 comparison with data from a non-exposure
 day can confirm work-related exacerbations
 of asthma,
   But, this technique does not identify the
   causal agent.
Spirometry in the workplace

   Measurement of single FEV1 values
   when the subject is at work and
   again when he/she is not at work
        does not have sufficient
        sensitivity to detect a relationship
        between work and asthma.

 Bardy, JD, Malo, JL, Seguin, P, et al. Am Rev Respir Dis 1987; 135:1033.
 Burge, PS. Eur J Respir Dis Suppl 1982; 123:47.
     PEF monitoring
 Simple and inexpensive
 Good specificity & sensitivity (> 80%)
 Nearly always feasible
 Empowerment of patient (falsification is rare)
 Success depends on motivation of patient
 and physician
  oral + written explanation
     PEF monitoring
 At least 4 x per day: 3 forced expirations
 Note on form (not on graph)
   time of day
   3 values of PEF
   activities (home, work, exposure)
   symptoms
   medication
 Allow missing values
 Aat least 4 weeks, workdays + free days
     PEF monitoring
 Graphical analysis = essential
   best of 3 PEF values
   plot daily mean, maximum, minimum
   day = 10 a.m. to 10 a.m.
   indicate exposure
 Interpretation: daily/weekly pattern is more
 important than magnitude of changes
   “subjective” interpretation
   expert system (OASYS) P.S. Burge (Birmingham)
            PEFR monitoring

                Serial measurement of PEFR’s is a
                 useful method in the investigation and
                 assessment of OA.

Burge, PS, O'Brien, IM, Harries, MG. Thorax 1979; 34:308.
Burge, PS, O'Brien, IM, Harries, MG. Thorax 1979; 34:317.
Moscato, G, Godnic-Cvar, J, Maestrelli, P, et al. J Allergy Clin Immunol 1995; 96:295.
PEFR monitoring

Monitoring is generally carried out by
 asking the subject to record his or her
 The diagnostic period should be
 shortened if the patient develops
 pronounced airway obstruction or has
 severe symptoms.
 PEFR monitoring

 There are a number of potential problems
 inherent to this approach, including
   the reproducibility of readings,
   compliance and honesty of subjects,
   interpretation of results, and
   sensitivity and specificity compared with
   specific inhalation challenges.
       PEFR monitoring

        Newer portable peak flow meters
            store values electronically, enabling
             falsified patient logs to be identified
        PEF monitoring is more useful
             in confirming than
             in excluding OA.

Leroyer, C, Perfetti, L, Trudeau, C, et al. Am J Respir Crit Care Med 1998; 158:827.
        Induced sputum

        Airway inflammation is correlated with
             the presence and
             proportion of eosinophils
                  in induced sputum samples.

Lemière, C, Pizzichini, MM, Balkissoon, R, et al.. Eur Respir J 1999; 13:482.

Lemiere, C, Chaboillez, S, Malo, JL, Cartier, A. J Allergy Clin Immunol 2001; 107:1063.
Induced sputum

 Examining induced sputum for the degree of
  at the end of a period at work and
  following a period away from work
      may also prove useful,
      but is not widely employed at present.

   Lemière, C, Pizzichini, MM, Balkissoon, R, et al. Eur Respir J 1999; 13:482.

   Obata, H, Dittrick, M, Chan, H, Chan-Yeung, M. Eur Respir J 1999; 13:489.
        PEFR and Induced Sputum
        The combination of
             serial PEFR monitoring and
             induced sputum examination
                   may be more useful.

                                +                     =       
Girard, F, Chaboillez, S, Cartier, A, et al. Am J Respir Crit Care Med 2004; 170:845.
PEFR and Induced Sputum
 The presence of >1% increase in
 sputum eosinophils after work
   increased both the sensitivity and
   specificity of OA diagnosis,
      compared to PEF monitoring alone.
             Advantages and Drawbacks of
             Various Diagnostic Tools for Occupational

Tools                       Advantages Drawbacks
Medical questionnaire       Simple, sensitive       Low specificity

Immunological testing       Simple, sensitive       Reserved for HMA and some LMW
Increased bronchial         Simple, sensitive       Not specific for asthma
Pre-post shift FEV1         Simple, cheap           Low sensitivity and specificity, not as
                                                    sensitive as FEV1
PEF monitoring              Relativeley simple,     Need collaboration and honesty, no
                            cheap                   standardized methods
Specific inhalation         If positive, confirms   If negative, does not exclude diagnosis,
challenges in a hospital    diagnosis               expensive, few centers for referral
Serial FEV1 assessment at   If negative,            If positive, “irritant induced asthma” can
work under supervision      excludes diagnosis      not be excluded, needs collaboration
                Diagnosis and management
                of OA
   Initial suspicion        Preliminary evaluation                 Confirmatory                 Management

    All physicins                Physicians who                  Specialists with           Treating physicians,
                              diagnose/treat asthma             specific expertise           consultantsi public
                                                                                            health practitioners

•Routine patients             •Confirm asthma                •Choose confirmatory           Work environment:
                                                                                            Removal (ideal)
•Sentinel cases               •Assess work                   method                         Decrease exposure by
                                                             •Clinical acumen               engineering or respirators
•Workplace surveillance       exposures                                                     Accommodation efforts
                                                             •Immunologic tests
(known hazards)
                                                             •Serial monitoring of airway   Clinical:
                              •Presumptive class:            caliber with portable          Counsel
                              •OA with latency                                              Treat according to
                                                             enstruments                    asthma guidelines
                              •OA without latency (RADS)     •Worksite monitoring of        Monitor course
                              •Work effect on concurrent     airway caliber under           Public health and legal:
                              asthma                         supervision                    Advise about
                                                             •Laboratory specific           Notify public health
                                                             challenge tests                agency
                                                                                            ? Notify employer,
                       Adapted from Chan-Yeung M, et al. NEJM 1995; 333: 107
                              Clinical Investigation of Occupational Asthma

                  Compatible clinical history and exposure to possible causal agents

                                     Skin and RAST tests (if possible)

                 Assessment of bronchial responsiveness to pharmacological agents

                                         Normal                   Increased

Subject still at work                        Subject no longer at work
                                                                                              Subject still at work
                        Lab challenges with the suspected occupational agent

                                       Positive                       Negative

                                                                Consider return to work
                         Workplace or lab challenges with the suspected occupational agent and/or PEF monitoring

                                                            Positive                Negative

       No asthma
                                            Occupational asthma                 Non occupational asthma

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