Diagnosis of Work-related Asthma

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Diagnosis of Diagnosis of Work-related Work-related Asthma Asthma Susan M Tarlo, MB BS, Susan M Tarlo, MB BS, FRCP(C) FRCP(C) Professor, Dept Medicine, Professor, Dept Medicine, and Dalla Lana School of and Dalla Lana School of Public Health Public Health University of Toronto, University of Toronto, Respiratory Division, Toronto Respiratory Division, Toronto Western Hospital Western Hospital

description

Diagnosis of Work-related Asthma. Professor, Dept Medicine, and Dalla Lana School of Public Health University of Toronto, Respiratory Division, Toronto Western Hospital. Susan M Tarlo, MB BS, FRCP(C). Chest 2008. These groupings are not mutually exclusive; e.g. OA can be followed by WEA. - PowerPoint PPT Presentation

Transcript of Diagnosis of Work-related Asthma

Page 1: Diagnosis of  Work-related Asthma

Diagnosis of Diagnosis of Work-related Work-related

AsthmaAsthmaSusan M Tarlo, MB BS, Susan M Tarlo, MB BS,

FRCP(C)FRCP(C)Professor, Dept Medicine,Professor, Dept Medicine,and Dalla Lana School of Public Healthand Dalla Lana School of Public HealthUniversity of Toronto,University of Toronto,Respiratory Division, Toronto Western Respiratory Division, Toronto Western HospitalHospital

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Work-related asthma(WRA)

Occupational asthma, caused by work

(OA)

Work-exacerbated asthma (WEA)

Sensitizer-induced OAIrritant-induced OA(Including reactive airways

dysfunction syndrome, RADS)

These groupings are not mutually exclusive; e.g. OA can be followed by WEA

Chest 2008

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Guidelines and Guidelines and StatementsStatements

Assessment of Asthma in the Assessment of Asthma in the Workplace, an ACCP Consensus Workplace, an ACCP Consensus Statement. Chest 1995;108:1084-117.Statement. Chest 1995;108:1084-117.

CTS Guidelines on Occupational CTS Guidelines on Occupational Asthma. Can Resp J 1998;5:289-300Asthma. Can Resp J 1998;5:289-300

British Thoracic Society, Standards of British Thoracic Society, Standards of Care for Occupational Asthma. Thorax Care for Occupational Asthma. Thorax 2008;63:240-50.2008;63:240-50.

Diagnosis and Management of Work-Diagnosis and Management of Work-related Asthma. ACCP Consensus related Asthma. ACCP Consensus Statement. Chest 2008;134:1S-41S.Statement. Chest 2008;134:1S-41S.

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Consensus DocumentConsensus Document

Diagnosis and Management of Work-Diagnosis and Management of Work-related Asthma. ACCP Consensus related Asthma. ACCP Consensus Statement. Chest 2008;134:1S-41SStatement. Chest 2008;134:1S-41S..

http:/www.chestjournal.org/cgi/content/http:/www.chestjournal.org/cgi/content/abstract/134/3_suppl/1S  abstract/134/3_suppl/1S  

- Based on an AHRQ evidence-based review, - Based on an AHRQ evidence-based review, (Agency for Healthcare Quality and (Agency for Healthcare Quality and Research) 2005, supplemented by recent Research) 2005, supplemented by recent literature review to Dec 2006 and by panel literature review to Dec 2006 and by panel consensusconsensus

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WEAWEA

Work-related worsening of asthma that Work-related worsening of asthma that started before the job or began incidentally. started before the job or began incidentally.

Common (up to 25% of working asthmatics)Common (up to 25% of working asthmatics) May be transient and diagnosed on history or May be transient and diagnosed on history or

may occur daily at work and may mimic may occur daily at work and may mimic occupational asthma, requiring similar occupational asthma, requiring similar investigationsinvestigations

May be due to expected asthma triggers such May be due to expected asthma triggers such as dusts or temperature extremes, or to as dusts or temperature extremes, or to common allergens that may be in the common allergens that may be in the workplace. workplace.

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OAOA

OA= Asthma due to causes and OA= Asthma due to causes and conditions which are attributable to conditions which are attributable to a particular workplace environment a particular workplace environment and not to stimuli encountered and not to stimuli encountered outside the workplace: outside the workplace: Irritant-inducedIrritant-induced Sensitizer-inducedSensitizer-induced

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OA?OA?

Some WRA does not clearly fit the Some WRA does not clearly fit the definitions definitions

– – previous childhood asthma recurring previous childhood asthma recurring from sensitization to a specific work agentfrom sensitization to a specific work agent

- existing asthma that worsens at work - existing asthma that worsens at work from sensitization to a specific work agentfrom sensitization to a specific work agent

Clinical implications of these are as for OA Clinical implications of these are as for OA but may/may not be included in but may/may not be included in compensation definitionscompensation definitions

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Differential diagnosis for Differential diagnosis for WRAWRA

Other asthma (non-occ) coincidentally Other asthma (non-occ) coincidentally worse while workingworse while working

Non-asthma causes for asthma-like Non-asthma causes for asthma-like symptomssymptoms GERDGERD Upper airway cough syndrome (post nasal drip)Upper airway cough syndrome (post nasal drip) Irritable larynx syndromes (WILS) Irritable larynx syndromes (WILS) – Hoy et al – Hoy et al

Occupational Medicine 2010; 60:546-51Occupational Medicine 2010; 60:546-51 [30 cases vs 90 WRA][30 cases vs 90 WRA] Hyperventilation/anxietyHyperventilation/anxiety Eosinophilic bronchitisEosinophilic bronchitis

- or any combination of these ± WRA- or any combination of these ± WRA

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OA - Irritant-induced OA - Irritant-induced (Reactive Airways Dysfunction (Reactive Airways Dysfunction

Syndrome)Syndrome) About 7% of all OA: from a high irritant exposureAbout 7% of all OA: from a high irritant exposure

Onset typically within 24 h of exposureOnset typically within 24 h of exposure New symptoms of asthma, persist >3moNew symptoms of asthma, persist >3mo Exposure expected to be a high level irritantExposure expected to be a high level irritant Asthma confirmed: PFTs / methacholine responsesAsthma confirmed: PFTs / methacholine responses documented absence of previous respiratory diseasedocumented absence of previous respiratory disease

No specific diagnostic test availableNo specific diagnostic test available Most certain = RADS, less certain if criteria not Most certain = RADS, less certain if criteria not

all metall met

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Sensitizer-induced OA Sensitizer-induced OA DiagnosisDiagnosis

Value of the historyValue of the history Exposures, symptoms: start while working, Exposures, symptoms: start while working,

improve w-ends/holidays off workimprove w-ends/holidays off work PPV 63%, PPV 63%, NPV 83% NPV 83% (Malo et al ’91)(Malo et al ’91)

Daily wheeze worse at workDaily wheeze worse at work most sensitive (88%) most sensitive (88%)

+ itchy nose/eyes+ itchy nose/eyes + + lacklack of hoarseness of hoarseness, , - predicted 74% of - predicted 74% of high MWt OAhigh MWt OA (Vandenplas et al (Vandenplas et al

ERJ ’05)ERJ ’05)

Nevertheless overall ~50% of specific challenges Nevertheless overall ~50% of specific challenges are negative even when OA suspected, are negative even when OA suspected, emphasizing need for objective tests. emphasizing need for objective tests.

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Exposure history for Exposure history for sensitizer-induced OAsensitizer-induced OA

HMWt almost any airborne protein HMWt almost any airborne protein (plant, animal, fish, fungal, insect, (plant, animal, fish, fungal, insect, enzymes)enzymes)

LMWt many reactive chemicals, LMWt many reactive chemicals, especially with double bonds and 2 or especially with double bonds and 2 or more reactive side chains more reactive side chains

Seed M, Agius R. Seed M, Agius R. Further validation of Further validation of computer-based prediction of chemical computer-based prediction of chemical asthma hazardasthma hazard. . Occup Med (Lond)Occup Med (Lond) 2010; 2010; 60:60:115-20.115-20.

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Exposure assessmentExposure assessment

Patient’s history: often limitedPatient’s history: often limited MSDS, WHIMIS: have limitations, MSDS, WHIMIS: have limitations,

incomplete informationincomplete information Occupational hygienist assessment: Occupational hygienist assessment:

company hygienist, independent company hygienist, independent private assessment or public private assessment or public health/government agency, e.g MOL, health/government agency, e.g MOL, NIOSH NIOSH

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Why objective tests are Why objective tests are necessary to diagnose OAnecessary to diagnose OA1.1. History could be influenced by other History could be influenced by other

factors factors

2.2. Management differs for OA vs. WEA Management differs for OA vs. WEA

3.3. Early correct diagnosis of sensitizer-Early correct diagnosis of sensitizer-OA with removal from exposure leads OA with removal from exposure leads to the best asthma prognosisto the best asthma prognosis

4.4. Objective diagnosis may lead to Objective diagnosis may lead to changes to prevent sensitization and changes to prevent sensitization and OA in other workersOA in other workers

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Diagnostic recommendationsDiagnostic recommendations (from ACCP Consensus 2008)(from ACCP Consensus 2008)

In patients with a hx of possible OA:In patients with a hx of possible OA: Confirm a diagnosis of asthma Confirm a diagnosis of asthma

objectivelyobjectively Review MSDSReview MSDS Skin test where feasibleSkin test where feasible PEFR and Methacholine responses work PEFR and Methacholine responses work

and off work, considering possible and off work, considering possible confounding factorsconfounding factors

Add induced sputum if availableAdd induced sputum if available Consider specific challenges if available, Consider specific challenges if available,

especially if the diagnosis is in doubtespecially if the diagnosis is in doubt

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Objective diagnosis of Objective diagnosis of asthmaasthma

FEV1 pre/post bronchodilatorFEV1 pre/post bronchodilator Methacholine/histamine challengeMethacholine/histamine challenge

sensitive for sensitive for asthmaasthma if patient is still if patient is still working and symptomaticworking and symptomatic

positive findings do not confirm a work positive findings do not confirm a work relationship relationship

negative findings do not exclude OA if negative findings do not exclude OA if not recently exposure to the sensitizernot recently exposure to the sensitizer

occasional reports of normal occasional reports of normal responsiveness in diisocyanate-OA responsiveness in diisocyanate-OA

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Skin tests/ immunologic Skin tests/ immunologic teststests

Limited skin test extracts commercially Limited skin test extracts commercially available for occupational allergensavailable for occupational allergens Few are standardizedFew are standardized Immunologic sensitization is more Immunologic sensitization is more

common than OA in exposed workerscommon than OA in exposed workers Skin tests are unhelpful for most low-Skin tests are unhelpful for most low-

molecular-weight sensitizersmolecular-weight sensitizers

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In-vitro immunologic In-vitro immunologic teststests

In-vitro immunologic tests only reliable in In-vitro immunologic tests only reliable in a few centres. a few centres. Generally less diagnostic value than skin Generally less diagnostic value than skin

tests for high molecular weight tests for high molecular weight sensitizers, eg natural rubber latexsensitizers, eg natural rubber latex

Limited sensitivity/specificity for low Limited sensitivity/specificity for low molecular-weight sensitizers at present, molecular-weight sensitizers at present, eg diisocyanateseg diisocyanates

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Evidence-based medicineEvidence-based medicine Diagnosis and Management of OA Diagnosis and Management of OA

(AHRQ ’05)(AHRQ ’05)HMWtHMWt SensitivitySensitivity SpecificitySpecificity

Methacholine Methacholine 79%79% 51%51%

Specific IgE Specific IgE (skin/serum)(skin/serum)

81/ 73%81/ 73% 60 / 79%60 / 79%

BothBoth 61%61% 83%83%

LMWtLMWt

MethacholineMethacholine 67%67% 64%64%

Specific IgE Specific IgE (skin/serum)(skin/serum)

73 / 31%73 / 31%

(very select (very select studies, often studies, often not feasible)not feasible)

86 /89%86 /89%

(often not (often not feasible)feasible)

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Beach J et al Chest 2007

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99 1 99 1

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80 20 80 2070 30 70 3060 40 60 4050 50 50 5040 60 40 6030 70 30 7020 80 20 80

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5 95 5 95

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Post-testProbability

Pre-testProbability

LikelihoodRatio

Post-testProbability

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+

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99 1 99 1

98 2 98 2

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80 20 80 2070 30 70 3060 40 60 4050 50 50 5040 60 40 6030 70 30 7020 80 20 80

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Objective documentation of work-Objective documentation of work-

related changes in asthmarelated changes in asthma Serial peak expiratory peak flow Serial peak expiratory peak flow

monitoring (PEF) with sx and med diarymonitoring (PEF) with sx and med diary at least 4x per day, several weeks at at least 4x per day, several weeks at

work and off workwork and off work requires careful patient instruction requires careful patient instruction needs complianceneeds compliance effort-dependenteffort-dependent no generally accepted objective criteria no generally accepted objective criteria

for interpretationfor interpretation by themselves, positive results do not by themselves, positive results do not

distinguish OA from work-exacerbated distinguish OA from work-exacerbated asthmaasthma

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A 42 year old polyurethane A 42 year old polyurethane foam workerfoam worker

0

100

200

300

400

500

600

700PEFR (L/min), 4 x per day

Off workWorking weeks

Methacholine PC20 0.07mg/ml

Methacholine PC20 11.6 mg/ml

days

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A 50 year old dry cleaner A 50 year old dry cleaner

0

50

100

150

200

250

300

350

400

450

500

Methacholine PC20 0.03 mg/ml Methacholine PC20 0.02 mg/ml

Working weeks Off work

days

PEFR (L/min), 4 x per day

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PEFsPEFs Also record symptoms and prn Also record symptoms and prn

medication use.medication use. Keep regular meds stable at the Keep regular meds stable at the

lowest dose to adequately control lowest dose to adequately control symptoms but not to mask PEF symptoms but not to mask PEF changeschanges

Record at least 2 weeks at work and Record at least 2 weeks at work and 10 days off work10 days off work

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PEF interpretation PEF interpretation confoundersconfounders

Inadequate techniqueInadequate technique Poor compliance with recordingsPoor compliance with recordings Fabrication of resultsFabrication of results Intercurrent cold or non-occupational Intercurrent cold or non-occupational

exposure to asthma triggersexposure to asthma triggers Work exposures not representative of Work exposures not representative of

those causing symptomsthose causing symptoms Changes masked by medications Changes masked by medications Any of these may need further repeat Any of these may need further repeat

PEFSPEFS

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PEF InterpretationPEF Interpretation Expert visual interpretationExpert visual interpretation Formula e.g. ≥20% variability from Formula e.g. ≥20% variability from

maximum occurring relatively more maximum occurring relatively more frequently working days vs off work (93% frequently working days vs off work (93% sens 77% specificity when variability >1 day) sens 77% specificity when variability >1 day) (Liss, Tarlo ’91)(Liss, Tarlo ’91)

OASYS: OASYS: 2-hourly PEFs2-hourly PEFs analyzed to score 1-4, analyzed to score 1-4, a cut-off 2.5 for OA: 75% sensitivity, 94% a cut-off 2.5 for OA: 75% sensitivity, 94% specificity (www.occupationalasthma.com)specificity (www.occupationalasthma.com)

ABC (area between the curves) uses OASYS2 ABC (area between the curves) uses OASYS2 for curves work days vs days off work with for curves work days vs days off work with readings readings >6 times per day>6 times per day, reported 72% , reported 72% sensitive, 100% specific at ABC 15 sensitive, 100% specific at ABC 15 L/min/hour (Moore VC et al Chest, 2009; L/min/hour (Moore VC et al Chest, 2009; 135: 307- 14)135: 307- 14)

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PEFsPEFs

Electronic spirometers allow Electronic spirometers allow assessment of compliance but assessment of compliance but expensive (~$500)expensive (~$500)

Despite problems with compliance, a Despite problems with compliance, a recent systematic review showed recent systematic review showed 61% had interpretable recordings 61% had interpretable recordings and of those, a pooled sensitivity for and of those, a pooled sensitivity for OA 82%, specificity 88% (Moore et OA 82%, specificity 88% (Moore et al Ann Resp Med ’10) al Ann Resp Med ’10)

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Methacholine challengesMethacholine challenges

Serial inhalation of increasing Serial inhalation of increasing concentrations of nebulized concentrations of nebulized methacholine methacholine

Spirometry pre- and post- each dose.Spirometry pre- and post- each dose. Test is stopped with at least a 20% Test is stopped with at least a 20%

drop in FEV1drop in FEV1 PC20 calculated (lower = more PC20 calculated (lower = more

hyper-responsive, cut-off 8mg/ml, hyper-responsive, cut-off 8mg/ml, borderline 4-16mg/ml)borderline 4-16mg/ml)

A ≥3-fold worsening in PC20 at work A ≥3-fold worsening in PC20 at work is significantis significant

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Methacholine challengeMethacholine challenge

A single test is useful to diagnose asthma – A single test is useful to diagnose asthma – with current asthma symptoms/exposureswith current asthma symptoms/exposures

Paired tests (one at the end of a work Paired tests (one at the end of a work week and one after a period off work) is week and one after a period off work) is useful to assess work-related changes (e.g. useful to assess work-related changes (e.g. OA)OA)

Confounders: lab technique, intercurrent Confounders: lab technique, intercurrent colds or other non-occupational exposures, colds or other non-occupational exposures, insufficient time away from work exposureinsufficient time away from work exposure

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Peak flows and Peak flows and methacholine responsesmethacholine responses

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Combinations of testsCombinations of tests A combination of investigations has been A combination of investigations has been

advocated in OA guidelines/consensus advocated in OA guidelines/consensus statements, as far as is feasible.statements, as far as is feasible.

However, skin tests/immunologic tests often However, skin tests/immunologic tests often cannot be performed, patients often cannot cannot be performed, patients often cannot adequately comply with PEFRs, and adequately comply with PEFRs, and methacholine/histamine challenges may methacholine/histamine challenges may require travelling a long distance for the require travelling a long distance for the tests.tests.

Despite recommendations, patients may Despite recommendations, patients may have stopped work before assessment and be have stopped work before assessment and be unwilling/unable to return on a trial basisunwilling/unable to return on a trial basis

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Specific laboratory Specific laboratory challengeschallenges

Labour-intensive and expensiveLabour-intensive and expensive Require specialized facilities with Require specialized facilities with

exposure-monitoring as well as exposure-monitoring as well as prolonged response-monitoringprolonged response-monitoring

Although referred to as a “gold Although referred to as a “gold standard”, there can be false positive standard”, there can be false positive and false negative responsesand false negative responses

In some countries, medicolegal In some countries, medicolegal concerns regarding positive responses concerns regarding positive responses have also limited use have also limited use

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Laboratory challengesLaboratory challenges

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Limitations to specific challenge Limitations to specific challenge interpretations (? how frequent)interpretations (? how frequent)

False positive:False positive: irritant exposure levelsirritant exposure levels uncontrolled asthma or unrelated exacerbationuncontrolled asthma or unrelated exacerbation

False negative responses:False negative responses: wrong “sensitizer”wrong “sensitizer” insufficient exposure (concentration/duration), insufficient exposure (concentration/duration),

especially after a prolonged period away from especially after a prolonged period away from exposureexposure

failure to monitor for late responses or airway failure to monitor for late responses or airway responsiveness changes responsiveness changes

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Workplace challengeWorkplace challenge Open challenge in suspected work area Open challenge in suspected work area

compared with an expected unexposed compared with an expected unexposed areaarea

Objective monitoring at work (e.g. hourly Objective monitoring at work (e.g. hourly spirometry, preferably with laboratory spirometry, preferably with laboratory quality equipment and personnel) quality equipment and personnel)

Expensive, employer may not permit Expensive, employer may not permit access, exposures not blindedaccess, exposures not blinded

Most effective for hospital workers who Most effective for hospital workers who can have the tests on-site in the PFT lab can have the tests on-site in the PFT lab (including methacholine tests)(including methacholine tests)

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Induced sputum Induced sputum eosinophilia as a eosinophilia as a diagnostic test diagnostic test

(Girard et al AJRCCM ’04)(Girard et al AJRCCM ’04)Induced sputum working and off workInduced sputum working and off work(Confounders include inhaled steroid use, (Confounders include inhaled steroid use, URIs and co-incidental allergen URIs and co-incidental allergen exposures)exposures)

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OA vs WEA DiagnosisOA vs WEA DiagnosisOAOA WEAWEA

Asthma historyAsthma history No preceding No preceding asthmaasthma

Preceding Preceding asthmaasthma

Work sensitizerWork sensitizer ++ --

Objective asthmaObjective asthma ++ ++

PEF worse with workPEF worse with work ++ ++

Methacholine PC20 better Methacholine PC20 better off workoff work

++ +/-+/-

Sputum eos increase with Sputum eos increase with workwork

+/-+/- +/-+/-

Work agent Work agent immunologic tests immunologic tests

+ if feasible+ if feasible --

Specific challengeSpecific challenge ++ --

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Diagnostic SummaryDiagnostic Summary In patients with a hx of possible OA: Confirm an objective diagnosis of asthma Review MSDS / exposures Skin test where feasible PEFR and Methacholine responses work

and off work, considering possible confounding factors

Consider specific challenges if diagnosis is in doubt

Consider addition of induced sputum if available

A combination of tests is most useful