Diagnosis of an affected worker

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Occupational asthma should be considered in all workers with symptoms of airflow limitation. Much of the evidence relating to its diagnosis emanates from specialist settings where the prior probability of disease is high; positive predictive values of tests may be lower in other settings. The diagnosis of occupational asthma is an iterative process. The best screening question to ask is whether symptoms improve on days away from work. This is more sensitive than asking whether symptoms are worse at work, as many symptoms deteriorate in the hours after work or during sleep. Occupational asthma can be present when tests of lung function are normal, making these less useful in screening for occupational asthma. Asthmatic symptoms improving away from work can produce false positive diagnoses, so further validation of occupational asthma is needed. The diagnosis is made most easily before exposures or treatments are modified. Serial measurement of peak expiratory flow is the most available initial investigation. When done and interpreted to validated standards there are very few false positive results, but about 20% are false negatives. Skin prick tests or blood tests for specific IgE are available for most high molecular weight allergens, and a few low molecular weight agents but there are few standardised allergens commercially available which limits their use . A positive test denotes sensitisation, which can occur with or without disease. The diagnosis of occupational asthma can usually be made without specific bronchial provocation testing, considered to be the gold standard diagnostic test. The availability of centres with expertise and facilities for specific provocation testing is very limited in the UK and the test is time-consuming. Specific provocation is particularly indicated when the precise cause of the occupational asthma is unclear, but this knowledge is needed for the management of an employee.

What is the sensitivity and specificity of respiratory questionnaires in the diagnosis of validated cases of occupational asthma?

The sensitivity of asthma symptoms has high sensitivity but lower specificity, whereas the question "have you been told by a doctor that you have asthma" has a high specificity but low sensitivity. (Schlunssen 2004). Asthma symptoms better on days away from work derived from questionnaires have a sensitivity of 58-100% for validated occupational asthma. The sensitivity was below 90% in only one study from Quebec. The sensitivity was 100% in only one study of five latex-exposed nurses. The most common symptoms used were wheeze and shortness of breath. No cases of occupational asthma due to latex were asymptomatic (two studies). The Quebec study showed some improvement in sensitivity to 66% when symptoms improved on holiday. Work-related asthma symptoms were common in those with negative specific challenge tests, the specificity of the questionnaires ranged from 45-100%, only one small study being over 70%.

** 2+ In the clinical setting questionnaires that identify symptoms of wheeze and/or shortness of breath which improve on days away from work or on holiday have a high sensitivity, but relatively low specificity for occupational asthma.

(Abstract Available for: Relation Between Occupational Asthma Case History, Bronchial Methachlorine Challenge, And Specific Challenge Test In Patients With Suspected Occupational Asthma Baur 1998, Abstract Available for: Quantitative Versus Qualitative Analysis Of Peak Expiratory Flow In Occupational Asthma Cote 1993, Full Text Available for: Is The Clinical History A Satisfactory Means Of Diagnosing Occupational Asthma? Malo 1991, Abstract Available for: Asthma Due To The Complex Salts Of Platinum: A Cross-Sectional Survey Of Workers In A Platinum Refinery Merget 1988, Abstract Available for: Prevalence of occupational asthma due to latex among hospital personnel Vandenplas 1995, Abstract Available for: Occupational Asthma In Symptomatic Workers Exposed To Natural Rubber Latex: Evaluation Of Diagnostic Procedures Vandenplas 2001)

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What are the sensitivity and the specificity of an expert medical history and examination in the diagnosis of validated occupational asthma?

There are fewer studies with expert medical histories than questionnaires. The symptoms of occupational asthma are indistinguishable from those of non-occupational asthma . Asking about deterioration at work was an insensitive method of making the diagnosis of occupational asthma (sensitivity 42% in one small study). Seasonal variation was more common in non-occupational asthma. Two experts from Quebec achieved sensitivities of 83% and 95%, substantially more than obtained by the same group from different patients by questionnaire. Expert histories have poor specificity compared with specific challenge testing.

* 3 Free histories taken by experts have high sensitivity, but their specificity may be lower.

(Abstract Available for: A Comparison Of Some Of The Characteristics Of Patients With Occupational And Non-Occupational Asthma Axon 1995, Abstract Available for: Relation Between Occupational Asthma Case History, Bronchial Methachlorine Challenge, And Specific Challenge Test In Patients With Suspected Occupational Asthma Baur 1998, Full Text Available for: Inhalation challenge with bovine dander allergens: who needs it? Koskela 2003, Full Text Available for: Is The Clinical History A Satisfactory Means Of Diagnosing Occupational Asthma? Malo 1991, Full Text Available for: Prevalence and intensity of rhinoconjunctivitis in subjects with occupational asthma Malo 1997, Abstract Available for: Occupational asthma due to exposure to iroko wood dust Ricciardi 2003, Abstract Available for: Occupational Asthma In Symptomatic Workers Exposed To Natural Rubber Latex: Evaluation Of Diagnostic Procedures Vandenplas 2001)

What are the sensitivity and the specificity of pre and post shift changes in lung function in the diagnosis of occupational asthma?

There are no good studies comparing across shift changes with specific challenge testing. Such testing is unlikely to be either sensitive or specific since measures of airflow obstruction, such as FEV1 or PEF, have a diurnal variation in most normal workers that is increased in most asthmatics. Furthermore, pre- and post-shift spirometry are unhelpful in the case of workers who suffer delayed responses after leaving work or with those who have prolonged bronchoconstriction that extends into the next work shift. In one case-control study of day-shift workers in a factory with many cases of colophony asthma, a fall in FEV1 of >10% post-shift was found in 5% of asymptomatic workers and 32% of those with work-related asthma symptoms.

* 3 Pre to post shift changes in lung function cannot be recommended for the validation or exclusion of occupational asthma.

(Full Text Available for: Peak Flow Rate Records In The Diagnosis Of Occupational Asthma Due To Colophony Burge 1979, Full Text Available for: Peak flow rate records in the diagnosis of occupational asthma due to isocyanates Burge 1979)

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What is the feasibility of obtaining serial measurements of peak flow in workers suspected of having occupational asthma?

Six publications describe small case series of consecutive patients attending specialist clinics. Three describe workplace surveys, in the context of research studies, with lower frequencies of daily recordings. Publication bias is probable, particularly in the latter group. In four clinical series and each of the workforce populations acceptable records were returned by over 70% of subjects.

** 3 Acceptable peak flow series can be obtained in around two thirds of those in whom a diagnosis of occupational asthma is being considered.

(Abstract Available for: Sensitivity And Specificity Of PC20 And Peak Expiratory Flow Rate In Cedar Asthma Cote 1990, Abstract Available for: Quantitative Versus Qualitative Analysis Of Peak Expiratory Flow In Occupational Asthma Cote 1993, Abstract Available for: The use of portable peak flowmeters in the surveillance of occupational asthma Henneberger 1991, Full Text Available for: Work-Related Changes In Peak Expiratory Flow Among Laboratory Animal Workers Hollander 1998, Abstract Available for: Comparison Of Serial Monitoring Of Peak Expiratory Flow And FEV1 In The Diagnosis Of Occupational Asthma Leroyer 1998, Abstract Available for: Do Subjects Investigated For Occupational Asthma Through Serial Peak Expiratory Flow Measurements Falsify Their Results? Malo 1995, Abstract Available for: Peak Expiratory Flow Monitoring Is Not A Reliable Method For Establishing The Diagnosis Of Occupational Asthma Quirce 1995, Abstract Available for: Subclinical Immunologic And Physiologic Responses In Hexamethylene Di-isocyanate - Exposed Auto Body Shop Workers Redlich 2001, Abstract Available for: Diurnal Variation In Peak Expiratory Flow Rate Among Grain Elevator Workers Revsbech 1989)

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What are the minimum criteria for serial measurements of peak flow to maintain a high degree of diagnostic accuracy?

A single case series of 74 patients attending a specialist clinic reports the highest combination of sensitivity and specificity with a measurement frequency of at least four readings a day. Less frequent readings produced a higher specificity but lower sensitivity.

* 3 The diagnostic performance of serial peak flow measurements falls when fewer than four readings a day are made.

(Abstract Available for: How Many Times Per Day Should Peak Expiratory Flow Rates Be Assessed When Investigating Occupational Asthma? Malo 1993)

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Can experts agree on the interpretation of serial measurements of peak flow in the diagnosis of occupational asthma?

Six of seven series report high levels of agreement (averaging 80%) between expert assessors with kappa values of at least 0.6. A single series, where non-expert assessors were used, reports a much lower level of inter-observer agreement. Three series report levels of intra-observer agreement over two occasions. A high level of repeatability was reported in two. The third used non-expert assessors.

** 3 There is high level of agreement between expert interpretations of serial peak flow records.

(Full Text Available for: Interpretation Of Occupational Peak Flow Records: Level Agreement Between Expert Clinicians And OASYS-2 Baldwin 2002, Abstract Available for: Comparison Of Serial Monitoring Of Peak Expiratory Flow And FEV1 In The Diagnosis Of Occupational Asthma Leroyer 1998, Abstract Available for: Peak expiratory flow rates in possible occupational asthma Liss 1991, Abstract Available for: How Many Times Per Day Should Peak Expiratory Flow Rates Be Assessed When Investigating Occupational Asthma? Malo 1993, Abstract Available for: Compliance With Peak Expiratory Flow Readings Affects The Within- And Between-Reader Reproducibility Of Interpretation Of Graphs In Subjects Investigated For Occupational Asthma Malo 1996, Abstract Available for: Occupational Asthma: Validity Of Monitoring Of Peak Expiratory Flow Rates And Non-Allergic Bronchial Responsiveness As Compared To Specific Inhalation Challenge Perrin 1992, Abstract Available for: Between- And Within- Observer Agreement For Expert Judgment Of Peak Flow Graphs From A Working Population Zock 1998)

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What are the sensitivity and specificity of serial measurements of peak flow in the diagnosis of occupational asthma?

Eight case series report direct and blinded comparisons of serial peak flow measurement and either specific bronchial provocation testing (five studies) or an expert diagnosis (three studies) based on a combination of other types of evidence. Some cases are reported in more than one publication. Reported sensitivities and (particularly) specificities are consistently high: averaging 80% and 90% respectively.

** 3 The sensitivity and specificity of serial peak flow measurements are high in the diagnosis of occupational asthma

(Full Text Available for: Improved Analysis Of Serial Peak Expiratory Flow In Suspected Occupational Asthma Bright 2001, Abstract Available for: Occupational asthma in electronics workers caused by colophony fumes: Follow-up of affected workers Burge 1982, Abstract Available for: Sensitivity And Specificity Of PC20 And Peak Expiratory Flow Rate In Cedar Asthma Cote 1990, Abstract Available for: Quantitative Versus Qualitative Analysis Of Peak Expiratory Flow In Occupational Asthma Cote 1993, Abstract Available for: Comparison Of Serial Monitoring Of Peak Expiratory Flow And FEV1 In The Diagnosis Of Occupational Asthma Leroyer 1998, Abstract Available for: Peak expiratory flow rates in possible occupational asthma Liss 1991, Abstract Available for: How Many Times Per Day Should Peak Expiratory Flow Rates Be Assessed When Investigating Occupational Asthma? Malo 1993, Abstract Available for: Occupational Asthma: Validity Of Monitoring Of Peak Expiratory Flow Rates And Non-Allergic Bronchial Responsiveness As Compared To Specific Inhalation Challenge Perrin 1992)

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Are statistical or computed methods of peak flow assessment as accurate as expert interpretation in the diagnosis of occupational asthma?

Three case series compare visual inspection of peak flow records by experts with a variety of statistical indices of the same records. In two, visual inspection gave higher values of sensitivity and specificity; in the third an index derived from maximum values away from work and minimum values at work produced a slightly higher value for sensitivity than did visual inspection. Other statistical indices used in the same report were less sensitive and specific than visual inspection. Just one computed method of analysis has been reported. The analysis was calibrated using the diagnostic opinion of a single expert and in cases whose occupational asthma was, for the most part, attributable to low molecular weight agents. A sensitivity of 75% and a specificity of 94% for 67 records (32 cases of occupational asthma) were reported.

** 3 Statistical analysis of serial peak flow measurements is of limited diagnostic value compared to expert interpretation

(Abstract Available for: Quantitative Versus Qualitative Analysis Of Peak Expiratory Flow In Occupational Asthma Cote 1993, Abstract Available for: Comparison Of Serial Monitoring Of Peak Expiratory Flow And FEV1 In The Diagnosis Of Occupational Asthma Leroyer 1998, Abstract Available for: Occupational Asthma: Validity Of Monitoring Of Peak Expiratory Flow Rates And Non-Allergic Bronchial Responsiveness As Compared To Specific Inhalation Challenge Perrin 1992)

** 2+ Computed analysis of peak flow records has good diagnostic performance

(Full Text Available for: Interpretation Of Occupational Peak Flow Records: Level Agreement Between Expert Clinicians And OASYS-2 Baldwin 2002, Full Text Available for: Development Of OASYS-2: A System For The Analysis Of Serial Measurement Of Peak Expiratory Flow In Workers With Suspected Occupational Asthma Gannon 1996)

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What are the sensitivity and the specificity of a normal measurement of non-specific reactivity while at work in the diagnosis of occupational asthma?

Studies of non-specific reactivity are confounded by different methods used, different cut-offs for normality and the interval between last occupational exposure and the performance of the test (increasing time may allow recovery of initial hyper-reactors). There are however a large number of studies using different methods from many centres showing that non-specific bronchial hyper-reactivity may be normal in 5-40% of specific challenge positive workers. Testing with higher concentrations of methacholine or histamine at which some non-asthmatics react reduces the number of non-reacting occupational asthmatics, but still leaves some non-reactors. One study showed no additional benefit of non-specific bronchial reactivity measurement over and above a history and specific IgE to inhaled antigens. A normal test of non-specific reactivity is not sufficiently specific to exclude occupational asthma in clinical practice.

*** 2++ A large number of concordant studies from different centres using different methodologies demonstrated that increased non-specific reactivity is often found in workers with occupational asthma. There are however many reports of normal methacholine or histamine reactivity within 24 hours of exposure in workers with confirmed occupational asthma.

(Full Text Available for: Occupational Asthma Due To Low Molecular Weight Agents : Eosinophilic And Non-Eosinophilic Variants Anees 2002, Abstract Available for: Relation Between Occupational Asthma Case History, Bronchial Methachlorine Challenge, And Specific Challenge Test In Patients With Suspected Occupational Asthma Baur 1998, Abstract Available for: Sensitisation To Occupational Allergens In Bakers' Asthma And Rhinitis: A Case-Referent Study Brisman 2003, Abstract Available for: Occupational asthma in electronics workers caused by colophony fumes: Follow-up of affected workers Burge 1982, Abstract Available for: Specific Serum Antibodies Against Isocyanates: Association With Occupational Asthma Cartier 1989, Abstract Available for: Occupational Asthma Without Bronchial Hyper-responsiveness Hargreave 1984, Full Text Available for: Inhalation challenge with bovine dander allergens: who needs it? Koskela 2003, Full Text Available for: Persistent specific bronchial reactivity to occupational agents in workers with normal nonspecific bronchial reactivity Lemiere 2000, Abstract Available for: New Method For An Occupational Dust Challenge Test Lin 1995, Full Text Available for: Is The Clinical History A Satisfactory Means Of Diagnosing Occupational Asthma? Malo 1991, Abstract Available for: Quantitative Skin Prick And Bronchial Provocation Tests With Platinum Salt Merget 1991, Abstract Available for: Absence Of Relationship Between Degree Of Nonspecific And Specific Bronchial Responsiveness In Occupational Asthma Due To Platinum Salts Merget 1996, No Abstract Available for: Toluene Di-isocyanate-Induced Asthma : Clinical Findings And Bronchial Responsiveness Studies In 113 Exposed Subjects With Work-Related Respiratory Symptoms Moscato 1991, Abstract Available for: Occupational Asthma: Validity Of Monitoring Of Peak Expiratory Flow Rates And Non-Allergic Bronchial Responsiveness As Compared To Specific Inhalation Challenge Perrin 1992, Abstract Available for: Occupational asthma due to exposure to iroko wood dust Ricciardi 2003, Abstract Available for: Outcome of assessment for occupational asthma Tarlo 1991, Abstract Available for: Prevalence of occupational asthma due to latex among hospital personnel Vandenplas 1995, Abstract Available for: Occupational Asthma In Symptomatic Workers Exposed To Natural Rubber Latex: Evaluation Of Diagnostic Procedures Vandenplas 2001)

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What are the sensitivity and the specificity of changes in non-specific reactivity at work and away from work in the diagnosis of validated cases of occupational asthma?

Three studies were identified where pre and post exposure measurements were attempted. One did not investigate workers further when the at-work reactivity was normal, limiting its interpretation. Using a 3.2 fold change in reactivity (the 95% confidence interval for between test reproducibility), one study found a sensitivity of 48% and a specificity of 64%. Reducing the required change to twofold increased the sensitivity to 67%, reducing specificity to 54%. A smaller study with 14 workers with occupational asthma showed a sensitivity of 62% and specificity of 78%.

** 2- Changes in non-specific reactivity at and away from work alone have only moderate sensitivity and specificity for diagnosis.

(Abstract Available for: Sensitivity And Specificity Of PC20 And Peak Expiratory Flow Rate In Cedar Asthma Cote 1990, Abstract Available for: Occupational Asthma: Validity Of Monitoring Of Peak Expiratory Flow Rates And Non-Allergic Bronchial Responsiveness As Compared To Specific Inhalation Challenge Perrin 1992, Abstract Available for: Outcome of assessment for occupational asthma Tarlo 1991)

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What is the feasibility of obtaining paired measurements of non-specific reactivity at and away from work?

Paired measurements of non-specific reactivity were possible in 27/54 workers in whom the tests were considered indicated in one study. In another study measurements were made in 194/204 apprentice welders who were there at the time.

* 3 Paired measurements of non-specific reactivity may be achieved in the workplace.

(Full Text Available for: Incidence of probable occupational asthma and changes in airway calibre and responsiveness in apprentice welders El-Zein 2003, Abstract Available for: Outcome of assessment for occupational asthma Tarlo 1991)

What are the sensitivity and the specificity of specific IgE testing in the diagnosis of validated cases of occupational asthma?

The production of specific IgE antibody may be detected by skin prick or serological tests. The respective sensitivities and specificities of the ability of these tests to detect specific IgE vary between allergens but in any case are dependent on the setting of positive cut-offs. Blood testing for specific serum IgE may not be as sensitive as skin prick testing (Park 2001) but may be useful if skin testing cannot be performed. The presence of specific IgE confirms sensitisation to an agent at work, but alone does not confirm the presence of occupational asthma, nor necessarily its cause. In this sense there is a high false positive rate although, with high molecular weight agents, few false negatives. The power of testing for specific IgE is to exclude an allergen as a cause of a worker's asthma. Specific IgE is an insensitive but specific test for isocyanate-induced occupational asthma (Tee 1998) although this is to some extent dependent on the time since last exposure. A small study reported greater sensitivity for MDI (83%) than TDI (27%) (Pezzini 1984).

** 2+ Both skin prick and serological tests are highly sensitive for detecting specific IgE and occupational asthma caused by most high molecular weight agents, but are not specific for diagnosing asthma.

(Abstract Available for: Diagnostic Validation Of Specific Ige Antibody Concentrations, Skin Prick Testing, And Challenge Tests In Chemical Workers With Symptoms Of Sensitivity To Different Anhydrides Baur 1995, Abstract Available for: Occupational asthma and rhinitis related to laboratory rats: serum IgG and IgE antibodies to the rat urinary allergen PlattsMills 1987, Abstract Available for: Prevalence of occupational asthma due to latex among hospital personnel Vandenplas 1995)

** 2+ Both skin prick and serological tests are sensitive for detecting specific IgE and occupational asthma caused by acid anhydrides and some reactive dyes; but have a lower specificity for diagnosing asthma.

(Abstract Available for: Utility of antibody in identifying individuals who have or will develop anhydride-induced respiratory disease Grammer 1998, Abstract Available for: Tetrachlorophthalic anhydride asthma: evidence for specific IgE antibody Howe 1983, Abstract Available for: Occupational asthma and IgE antibodies to reactive dyes Park 1989, Full Text Available for: Role of skin prick test and serological measurement of specific IgE in the diagnosis of occupational asthma resulting from exposure to vinyl sulphone reactive dyes Park 2001)

** 2+ Skin prick tests are highly sensitive but less specific for occupational asthma caused by complex platinum salts.

(Abstract Available for: Asthma Due To The Complex Salts Of Platinum: A Cross-Sectional Survey Of Workers In A Platinum Refinery Merget 1988, Abstract Available for: Quantitative Skin Prick And Bronchial Provocation Tests With Platinum Salt Merget 1991, Abstract Available for: Absence Of Relationship Between Degree Of Nonspecific And Specific Bronchial Responsiveness In Occupational Asthma Due To Platinum Salts Merget 1996, Abstract Available for: Plicatic Acid-Specific Ige And Nonspecific Bronchial Hyper-responsiveness In Western Red-Cedar Workers Vedal 1986)

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What are the sensitivity and the specificity of specific bronchial provocation testing while at work, and after removal from work, in the diagnosis of validated cases of occupational asthma?

Specific provocation challenges are usually used as the gold standard for occupational asthma diagnosis making assessments of their diagnostic validity difficult. There is a lack of standardised methods for many occupational agents. There is evidence that the threshold exposure increases with time since last exposure, making the tests less sensitive after prolonged absence from work. There are individuals who have been shown to have non-specific reactions to specific challenges at concentrations likely to be found in the workplace and negative specific challenges in workers with otherwise good evidence of occupational asthma when challenge concentrations are confined to levels below occupational exposure standards. (Burge 1979a, Burge 1979b, Cartier 1989, Lin 1995, Moscato 1991)

- 4 Carefully controlled specific challenges come closest to a gold standard test for some agents causing occupational asthma.

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- 4 A negative test in a worker with otherwise good evidence of occupational asthma is not sufficient to exclude the diagnosis.

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