Evidence Report/Technology Assessment 

Number 129 

Diagnosis and Management of Work-Related Asthma 

Prepared for: 

Agency for Healthcare Research and Quality 

U.S. Department of Health and Human Services 

540 Gaither Road 

Rockville, MD 20850 

www.ahrq.gov 

Contract No. 290-02-0023 

Prepared by: 

University of Alberta Evidence-based Practice Center 

Edmonton, Alberta, Canada 

Jeremy Beach, MBBS, MD, FRCP (Edin), FFOM, FRCP (C) 

Brian H. Rowe, MD, MSc, CCFP (EM), FCCP 

(Principal Investigators) 

Sandra Blitz, MSc 

Ellen Crumley, MLIS 

Nicola Hooton, BSc 

Kelly Russell, BSc 

Carol Spooner, BScN, MSc 

Terry Klassen, MD, MSc, FRCPC 

(EPC Director)

AHRQ Publication No. 06-E003-2 

November 2005
This report is based on research conducted by the University of Alberta Evidencebased Practice Center (EPC) under contract to the Agency for Healthcare Research 

and Quality (AHRQ), Rockville, MD (Contract No. 290-02-0023). The findings and 

conclusions in this document are those of the author(s), who are responsible for its 

content, and do not necessarily represent the views of AHRQ. No statement in this 

report should be construed as an official position of AHRQ or of the U.S. Department 

of Health and Human Services. 

The information in this report is intended to help clinicians, employers, policymakers, 

and others make informed decisions about the provision of health care services. This 

report is intended as a reference and not as a substitute for clinical judgment. 

This report may be used, in whole or in part, as the basis for the development of 

clinical practice guidelines and other quality enhancement tools, or as a basis for 

reimbursement and coverage policies. AHRQ or U.S. Department of Health and 

Human Services endorsement of such derivative products may not be stated or
ii

This document is in the public domain and may be used and reprinted without permission except 

those copyrighted materials noted for which further reproduction is prohibited without the 

specific permission of copyright holders. 

Suggested Citation: 

Beach J, Rowe BH, Blitz S, Crumley E, Hooton N, Russell K, Spooner C, Klassen T. Evidence 

Report/Technology Assessment No. 129. (Prepared by the University of Alberta Evidence-based 

Practice Center, under Contract No. 290-02-0023.) AHRQ Publication No. 06-E003-2. Rockville, 

MD: Agency for Healthcare Research and Quality. November 2005. 
iii

Preface 

 The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based 

Practice Centers (EPCs), sponsors the development of evidence reports and technology 

assessments to assist public- and private-sector organizations in their efforts to improve the 

quality of health care in the United States. The reports and assessments provide organizations 

with comprehensive, science-based information on common, costly medical conditions and new 

health care technologies. The EPCs systematically review the relevant scientific literature on 

topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to 

developing their reports and assessments. 

 To bring the broadest range of experts into the development of evidence reports and health 

technology assessments, AHRQ encourages the EPCs to form partnerships and enter into 

collaborations with other medical and research organizations. The EPCs work with these partner 

organizations to ensure that the evidence reports and technology assessments they produce will 

become building blocks for health care quality improvement projects throughout the Nation. The 

reports undergo peer review prior to their release. 

 AHRQ expects that the EPC evidence reports and technology assessments will inform 

individual health plans, providers, and purchasers as well as the health care system as a whole by 

providing important information to help improve health care quality. 

 We welcome comments on this evidence report. They may be sent by mail to the Task Order 

Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, 

Rockville, MD 20850, or by email to epc@ahrq.gov. 

Carolyn M. Clancy, M.D. Jean Slutsky, P.A., M.S.P.H. 

Director Director, Center for Outcomes and Evidence 

Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality 

Kenneth S. Fink, M.D., M.G.A., M.P.H. 

Director, EPC Program 

Agency for Healthcare Research and Quality 

Margaret Coopey, R.N., M.G.A., M.P.S. 

EPC Program Task Order Officer 

Agency for Healthcare Research and Quality 
iv

Acknowledgments 

We are grateful to members of the technical expert panel who provided direction to the scope 

and content of the review, the peer-reviewers who provided valuable input into the draft report, 

authors of included studies who identified potentially relevant studies, staff members who 

provided technical assistance, and those who assisted in translating articles not published in 

English. These individuals are listed in Appendix F. In addition, we appreciate Natasha Weibe 

for her statistical advice and Marlene Dorgan for providing expertise regarding the literature 

search strategies, respectively. 

Dr. Rowe is supported by the Canadian Institute of Health Research (CIHR) as a Canada 

Research Chair in Emergency Airway Diseases (Ottawa, Canada). He is also supported by the 

Faculty of Medicine and Dentistry and the Capital Health Authority, Edmonton, Alberta. Dr. 

Beach is supported by the Faculty of Medicine and Dentistry at the University of Alberta, 

Edmonton, Alberta. 
v

Structured Abstract 

Context: Approximately 5 to 15 percent of adult onset asthma is thought to be occupational 

asthma (OA). 

Objectives: To systematically review literature regarding the diagnosis and management of OA, 

and specifically, to compare specific inhalation challenge testing (SIC) with alternative tests, and 

to review management, including reduction or cessation of exposure. 

Search Strategy: Electronic databases and trials registries were searched. Additional references 

were identified by bibliographic searches of included studies, hand searches of conference 

proceedings, and contact with authors. 

Selection Criteria: Population: De-novo OA or a previous diagnosis of asthma that was 

exacerbated at work. Study design: Controlled clinical trials, prospective or retrospective cohort, 

cross-sectional, case-series. Diagnosis: Intervention: At least two diagnostic tests, including one 

or more from a pre-determined hierarchy of ‘reference standard’ tests. Outcomes: 2 x 2 or 2 x 1 

table, sensitivity, specificity, likelihood ratios, time to diagnosis, cost of diagnosis, and adverse 

effects. Management: Intervention: Pharmacological treatment, removal, reduced, or continued 

exposure. Outcomes: Pulmonary function, medication use, quality of life, symptoms, economic 

consequences, and adverse events. 

Data Extraction: Two researchers independently extracted data. 

Data Analysis: Diagnosis: Pooled sensitivities and specificities for sensitizer-induced OA with 

95% confidence intervals (CI) were derived using a random effects model. Management:

Weighted pooling of means and standard deviations to combine results within studies. 

Quantitative analysis was not conducted due to heterogeneity. 

Main Results: One-hundred and twenty-four unique diagnostic studies and 65 unique 

management studies were included. Much of the evidence relates to sensitizer induced OA.

Diagnosis: Among the high molecular weight (HMW) asthmagens compared to SIC, nonspecific bronchial provocation (NSBP) test, skin prick test (SPT), and serum specific IgE had 

sensitivities above 73 percent. The specificity was highest between serum specific IgE versus 

SIC (79.0 percent [95% CI: 50.5 to 93.3 percent]). The highest sensitivity among low molecular 

weight (LMW) asthmagens occurred between SPT and SIC (72.9 percent [95% CI: 59.7 to 83.0 

percent]), but this applied only to LMW sensitizers for which SPT could be performed. When 

compared to SIC, serum specific IgE and SPT had similar specificities (88.9 percent [95% CI: 

84.7 to 92.1 percent] and 86.2 percent [95% CI: 77.4 to 91.9 percent], respectively). For HMW 

asthmagens, a combined positive test result to NSBP test and SPT versus SIC yielded modest 

sensitivity (60.6 percent [95% CI: 21.0 to 89.9 percent]) yet high specificity (82.5 percent [95% 

CI: 54.0 to 95.0 percent]). Management: Removed workers showed improved lung function and 

decreased non-specific broncial responsiveness at follow-up; exposed workers were either no 

better or worse. Lack of data prevented conclusions about the effectiveness of reducing 
vi

exposure. Removed workers suffered from reduced income and/or unemployment. Fully or 

partially exposed workers also appeared to have reduced earnings over time. 

Conclusions: Diagnosis: Single NSBP test, specific SPT, or serum specific IgE testing alone is 

insufficient to diagnose OA. While positive results would increase the likelihood of OA, a 

negative result would not exclude OA. The literature supports the concept of combined testing; 

however, additional research is required to determine which combination of tests would result in 

sufficient sensitivity and specificity that it could replace SIC. Management: OA appears to be 

slow to resolve, and may worsen irrespective of subsequent exposure status. Patients who are 

removed from the workplace rarely experience complete resolution, may require medications, 

and experience continued airflow limitation. Standard treatments for asthma appear to be 

effective in OA; however, there is limited research. 
vii

Contents 

Evidence Report ............................................................................................................................1 

Chapter 1. Introduction.................................................................................................................3 

 The Problem of Work-related Asthma ....................................................................................3 

 What is Occupational/Work-related Asthma?...................................................................3 

 Epidemiology of Occupational/Work-related Asthma......................................................4 

 Diagnosis of Occupational/Work-related Asthma.............................................................5 

 Management of Occupational/Work-related Asthma......................................................10 

 Objectives of this Review......................................................................................................13 

 Key Questions .......................................................................................................................15 

Chapter 2. Methods ....................................................................................................................17 

 Methods for the Systematic Reviews ....................................................................................17 

 Literature Search .............................................................................................................17 

 Selection and Inclusion....................................................................................................18

 Quality Assessment .........................................................................................................19

 Data Extraction................................................................................................................20 

 Data Analysis...................................................................................................................21 

 Peer Review...........................................................................................................................22 

Chapter 3. Results.......................................................................................................................23 

 Literature Search ...................................................................................................................23 

 Diagnosis Review..................................................................................................................25 

 Description of Included Studies ......................................................................................25 

 Methodological Quality of Included Studies...................................................................25 

 Quantitative Results.........................................................................................................26 

 Management Review.............................................................................................................29 

 Description of Included Studies ......................................................................................29 

 Methodological Quality of Included Studies...................................................................30 

 Qualitative Results...........................................................................................................31 

Chapter 4. Discussion.................................................................................................................59 

 Diagnosis Systematic Review ...............................................................................................59 

 Management Systematic Review ..........................................................................................62 

 Cohort..............................................................................................................................62 

 Trials................................................................................................................................63 

 Potential Limitations .............................................................................................................64 

 Diagnosis Review............................................................................................................65 

 Management Review.......................................................................................................67 

 Conclusions ...........................................................................................................................67 

 Future Research Opportunities..............................................................................................69 

References and Included Studies.................................................................................................71 
viii

Excluded Studies .........................................................................................................................83 

 Study Design .........................................................................................................................83 

 Inappropriate Topic ...............................................................................................................89 

 Population..............................................................................................................................95 

 Inadequate Data .....................................................................................................................97 

 No Treatment or Tests.........................................................................................................101 

 Unobtainable........................................................................................................................101 

 Addendum ...........................................................................................................................104 

Abbreviations ...........................................................................................................................105 

Flow Diagram 

Flow Diagram. Study retrieval and selection for diagnosis and management of 

 occupational asthma ..............................................................................................................24 

Tables 

Table 1. Definitions of work-related asthma................................................................................4 

Table 2. Summary of occupational asthma guidelines...............................................................14 

Table 3. Inclusion/exclusion criteria for review on diagnosing and managing 

 occupational asthma ..............................................................................................................18 

Table 4. Summary of components of Downs and Black score...................................................30 

Table 5. Economic consequences of occupational asthma.........................................................34 

Table 6. Description of studies for the diagnosis of OA ............................................................55 

Table 7. Methodological quality of studies for the diagnosis of OA .........................................56 

Table 8. Description of studies for the management of OA.......................................................57 

Table 9. Methodological quality of studies for the management of OA ....................................58 

Figures 

Figure 1. Sensitivity and specificity extracted from studies comparing single NSBP test to 

 SIC among LMW asthmagens...............................................................................................39 

Figure 2. Sensitivity and specificity extracted from studies comparing single NSBP test to 

 SIC among HMW asthmagens ..............................................................................................40 

Figure 3. Sensitivity and specificity extracted from studies comparing single NSBP test to 

 SIC among mixed asthmagens ..............................................................................................41 

Figure 4. Sensitivity and specificity pairs from studies comparing NSBP test with SIC ..........42 

Figure 5. Sensitivity and specificity extracted from studies comparing specific SPT test to 

 SIC among LMW asthmagens...............................................................................................43 

Figure 6. Sensitivity and specificity extracted from studies comparing specific SPT test to 

 SIC among HMW asthmagens ..............................................................................................44 

Figure 7. Sensitivity and specificity extracted from studies comparing specific SPT test to 

 SIC among mixed asthmagens ..............................................................................................45 

Figure 8. Sensitivity and specificity pairs from studies comparing SPT to SIC ........................46 

Figure 9. Sensitivity and specificity extracted from studies comparing serum specific IgE test 

 to SIC among LMW asthmagens ..........................................................................................47 
ix

Figure 10. Sensitivity and specificity extracted from studies comparing serum specific IgE 

 test to SIC among HMW asthmagens ...................................................................................48 

Figure 11. Sensitivity and specificity extracted from studies comparing serum specific IgE 

 test to SIC among mixed asthmagens....................................................................................49 

Figure 12. Sensitivity and specificity pairs from studies comparing specific IgE with SIC......50 

Figure 13. Average percent predicted FEV1 at baseline for groups of patients who remained 

 exposed, were removed from contact, or reduced exposure to the suspected asthmagen.....52 

Figure 14. Difference between average percent predicted FEV1 in follow-up and average 

 percent predicted FEV1 at baseline plotted against average length of follow-up by exposure 

 status in follow-up .................................................................................................................52 

Figure 15. Ratio of mean NSBP test at follow-up visit to mean NSBP test at baseline plotted 

 against average length of follow-up by exposure status in follow-up...................................53 

Figure 16. Percentage of patients taking asthma medications in follow-up plotted against 

 average length of follow-up by exposure status in follow-up ...............................................54 

Appendixes 

Appendix A: Exact Search Strings 

Appendix B: Sample Data Forms 

Appendix C: Levels of Evidence 

Appendix D: Multiple Publications 

Appendix E: Evidence Tables 

Appendix F: Technical Expert Panel, List of Peer Reviewers, and Translators 

Appendix G: Quality Analysis of the Diagnostic Occupational Asthma Studies 

Appendix H: Sensitivity and Specificity of Comparison Tests that Used SIC as a Reference 

Standard 

The Appendixes and Evidence Tables cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/asthmawork/asthwork.pdf
4

Evidence Report 
5
3

Chapter 1. Introduction 

The Problem of Work-Related Asthma 

What is Occupational/Work-Related Asthma? 

Occupational asthma (OA) is a heterogeneous clinical syndrome characterized by workrelated symptoms, airway inflammation (partially or completely reversible), 

bronchoconstriction, and hyper-responsiveness induced by workplace exposures (asthmagens). 

In contrast to non-occupational asthma, the differentiating feature of occupational asthma is the 

causal asthmagen is a substance in the occupational environment.1

 The symptoms of OA are 

similar to non-occupational asthma and include wheezing, cough, dyspnea, and impaired 

quality of work and non-work life. More than 250 asthmagens have been implicated and 

identified as causative agents in the development of OA (e.g., di-isocyanates, western red 

cedar, enzymes, snow crab, latex, flour, and laboratory animals). However, there are likely a 

variety of workplace asthmagens that have yet to be identified. An attempt has been made to 

classify the majority of the known asthmagens into categories based on their molecular weight: 

high molecular weight (HMW; ≥ 5000 Daltons) versus low molecular weight (LMW; <5000 

Daltons) compounds, as this is probably important in their mechanism of action.2

 Due to the 

nature and complexity of workplace exposures, this is not always possible. Examples of HMW 

asthmagens include flour and latex; common LMW asthmagens are di-isocyanates, metals, and 

dyes.1 

OA can be broadly classified into two categories: OA with latency and OA without latency. 

Latency periods are observed in all instances of immunologically mediated asthma, even 

though the immunological mechanism may not yet have been clearly identified.2 The latency 

period, which represents the time between the first exposure and onset of first symptoms, can 

range from weeks to years. When a worker has OA with latency, a specific inhalation test with 

the causal agent will usually be positive and often an immunological response for HMW and 

some LMW asthmagens is identified with specific skin prick tests (SPT) and/or serum specific 

IgE antibody testing. Generally, serum specific IgE antibodies, biomarkers for sensitization to 

the specific asthmagen, have been identified for HMW compounds; serum specific IgE 

antibodies associated with LMW OA have yet to be fully characterized, as the antibodies have 

yet to be discovered or occur in only a small portion of workers.2

 The need to produce 

appropriate hapten-protein conjugates is probably a common reason for the failure to detect 

antibodies to LMW agents. OA with latency for which serum specific IgE antibodies have 

been identified is referred to as IgE associated. 

OA can also exist without a latency period and can occur after a single large exposure to 

irritant gases, fumes, or chemicals, such as nitrogen oxide, ammonia, and chlorine.3 This type 

of exposure results in reactive airways dysfunction syndrome, or RADS. Occupational asthma 

has also been reported to occur in few instances from repeated exposures to lower doses of 

'irritant' or non-sensitizing agents.4

 After exposure to an irritant, the asthmatic reaction occurs 

within a short time.5

 Since there is no sensitization, the battery of diagnostic tests for RADS 

does not include specific immunological tests, and specific inhalation challenge (SIC) is not 
4

used. OA without latency is less common; it is believed to represent between 5 and 15 percent 

of all OA cases.1,6,7

For the purpose of this report, OA with and without latency and work-aggravated asthma 

were defined in concordance with the American College of Chest Physicians (ACCP) and are 

described in Table 1: 

Table 1. Definitions of work-related asthma 

Term Defining Features 

Occupational asthma with latency 

of allergic or presumed 

immunological mechanism 

There is an immunologic/hypersensitivity component and the 

diagnostic tests include measures of specific sensitization (e.g.,SIC, 

skin prick test, serum specific IgE). 

Occupational asthma without 

latency 

There is no allergic component and the worker is not “sensitized” to 

an agent, but rather, the agent causes an inflammatory response 

through an irritant mechanism. 

Work-aggravated asthma (no 

latency period) 

The worker has a previous or concurrent history of asthma that was 

not induced by an exposure found in the workplace. The worker is 

not sensitized to an agent at work, but is irritated by a “non-massive” 

exposure (e.g., cold, exercise, non-sensitising dust, fumes, or sprays) 

that provokes an asthmatic reaction. 

Abbreviations: SIC = specific inhalation challenge

Through the remaining report, the term OA refers to OA with and without a latency period. 

This approach is similar to that of the American Thoracic Society guidelines.8 Where possible, 

we have noted where the results are derived from a RADS population. We recognize that some 

studies may also include individuals with work-aggravated asthma within their study 

population, although it is rarely possible to identify if this is so. When the individual studies 

provide adequate detail, we have included the proportion of workers with a previous history of 

asthma and this may indicate work-aggravated asthma rather than OA. 

Epidemiology of Occupational/Work-Related Asthma 

Amongst developed countries, OA has become one of the most prevalent occupational lung 

diseases.2 The annual incidence of OA is estimated to be 50 per million United Kingdom (UK) 

workers and 140 per million Finnish workers.9

 In France, the mean annual incidence rate was 

24 per million workers.10 Among American workers belonging to a Health Maintenance 

Organization who were at risk for developing OA, the annual incidence of new-onset asthma 

was 1300 per million.11 A review of 43 attributable risk estimates from 19 counties found the 

attributable risk of OA to be 9 percent (interquartile range [IQR] 5–19 percent).12 Because of 

the high prevalence of OA, it has been recommended that OA be considered a diagnostic 

possibility in all adults undergoing initial asthma evaluation. Surveillance programs indicate 

that OA accounts for 26–52 percent of reported occupational lung conditions in the UK13 and 

British Columbia, Canada14. Perhaps of even greater concern is the suggestion that OA is 

potentially more common than studies have previously reported.15 This seems likely, as several 

factors make OA identification difficult: 1) most industries expose workers to a number of 

potential causative agents and exposure may vary widely within the same workplace setting, 

making exposure assessment complex; 2) OA symptoms are variable and non-specific, with 

late reactions often occurring after the working day has been completed; 3) specific diagnostic 

tests have limited availability making exact diagnosis difficult; and, 4) the symptom onset is 

unpredictable.15
5

Greater than 250 synthetic and naturally occurring agents in a variety of work settings have 

been identified as relevant workplace exposures16; one of the most common exposures being 

di-isocyanates used in the production of coatings, adhesives, and foams in a wide variety of 

settings. It is estimated that up to 11 percent of workers exposed to di-isocyanates will develop 

bronchial hyper-reactivity.17 Other commonly reported agents include flour, wood dusts, and 

latex.2 While a large number of the causative agents have been identified, many more 

sensitizers and irritants are not well characterized and/or known, thus making the diagnosis of 

OA even more elusive. 

The contribution of work-aggravated asthma cannot be ignored. Work-aggravated asthma 

occurs in workers with a previous or concurrent history of asthma and is characterized by 

worsening symptoms at work in response to chemicals or physical stimuli encountered at work, 

such as dust or cold air.2

 Among employed asthmatics in a Finnish city, Saarinen et al. found 

the prevalence of work-aggravated asthma to be approximately 30 percent.18 In a recent study, 

the annual incidence rate of work-aggravated asthma among employed workers with current 

asthma was 3.9 cases per 100,000 each year.19 The highest incidence rate occurred among 

workers employed in the public administration industry (14.2 cases per 100,000 each year). 

The most commonly responsible agents were mineral and inorganic dusts. 

Because workers often need to be away from work due to their illness, and the cornerstone 

of treatment is removal from the workplace, OA creates a significant economic burden for 

individuals, industry, health care providers, and society. Using the human capital method, 

Leigh et al. calculated the cost of OA in the United States to be $1.6 billion annually.20 

Sometimes, impaired lung function does not improve or reverse, even after extended periods 

away from the causative agent21 and this can result in permanent unemployment. The United 

Kingdom’s Surveillance of Work-related and Occupational Respiratory Disease program found 

that 30 percent of people reported to have OA between 1989 and 1992 were unemployed when 

contacted later.22

Diagnosis of Occupational/Work-Related Asthma 

An ideal diagnostic test has both a high sensitivity and specificity. Sensitivity refers to the 

test successfully identifying the proportion of the people who truly have the disease, i.e., the 

test detects true positives. A test has high sensitivity when it identifies nearly all of the people 

who truly have the disease. A test has high specificity when it successfully identifies most of 

the people who truly are disease-free as not having the disease, i.e., the test detects true 

negatives. In general, the sensitivities and specificities of diagnostic test comparisons are more 

robust if the test results are reproducible. OA is a difficult diagnosis to make for a variety of 

reasons. The first step is to determine that the patient has asthma and not a similar syndrome, 

such as upper respiratory tract irritation or vocal cord dysfunction. Having diagnosed asthma, 

the next step is to show a causative link with exposure to an asthmagen at work and this process 

often commences with obtaining a history or completing a questionnaire. 

While SIC is often cited as a ‘gold standard’, as yet there is no definitive diagnostic test for 

OA. The applicability of SIC is currently limited by its availability.23 In addition, the 

possibilities of false negative and positive results have been recognized.5

 For example, a false 

negative can occur when a worker with OA is exposed to multiple asthmagens and is 

subsequently challenged with the non-offending asthmagen.2 Further, SIC testing is usually not 
6

considered useful in determining a diagnosis of irritant induced OA. As a result, throughout 

this report we will refer to SIC as a reference standard. 

There are several alternative techniques, used in isolation or in combination, which can be 

used to diagnose occupational and work-related asthma. We have summarized SIC and the 

alternative techniques in the categories below: 

Specific inhalation challenge (SIC). There are several methodologies used to perform 

SIC; however, in general the approach is designed to expose the worker to a suspected 

asthmagen in a controlled, non-work, test environment. When a suspected asthmagen is a 

water-soluble compound, the test subject may inhale it in its nebulized form.24 Initially, low 

concentrations are administered for safety reasons until a response is obtained or a maximum 

concentration has been tested. When the asthmagen cannot be nebulized because of low 

solubility, some have proposed tipping powders of the suspected asthmagen from one tray to 

another in an attempt to mimic the work environment and generate a dry aerosol.25 More 

recently standardized techniques have been developed to deliver dry powder aerosols. Another 

method is to conduct a simulated occupational-type specific provocation test.26 For example, 

when colophony (e.g., used as a solder flux by electronics workers) is suspected to cause OA, 

the worker is exposed to simulated work tasks in a controlled laboratory environment while 

lung function monitoring is conducted in an attempt to determine changes in flow volumes or 

hyper-responsiveness. 

The first step of SIC is to perform a control challenge with a substance similar in physical 

characteristics to the suspected asthmagen, but not likely to cross-react immunologically. 

When the fluctuations in forced expiratory volume in one second (FEV1) following the control 

challenge are less than 10 percent, it is generally considered safe for the worker to undergo 

formal SIC testing with the suspected agent.27 The duration or intensity of exposure is 

increased progressively, usually commencing with a small dose. Lung function is measured for 

a period of time after each incremental challenge dose. When challenging with LMW agents, 

challenges of increasing time durations should occur on separate days, as LMW agents often 

produce isolated, late asthmatic reactions. When challenging with an HMW agent several 

doses may be given on the same day as they more typically produce an early asthmatic 

reaction.27 Conducting SIC in a blinded fashion and ensuring that the results are reproducible 

can minimize false positive results. A typical definition of a positive response is a decrease 

from baseline FEV1 (i.e., control exposure) of 15–20 percent. 

The greatest advantage of SIC is that a positive test confirms a diagnosis of OA caused by 

the particular agent. When the appropriate agent is applied and the test is positive in workers 

with respiratory symptoms that are thought to be work-related asthma, SIC testing is considered 

confirmatory. However, there are several disadvantages to SIC. First, the suspected workplace 

agent may not have been identified, which precludes testing. Second, SIC can only be 

conducted in specialty facilities and these are rare. For example, a survey conducted in 2000 

indicated that only 15 centers capable of performing SIC exist in the USA and Canada.23 

Moreover, there are many complexities associated with developing a SIC laboratory. These 

include the expense of purchasing and operating the laboratory and the ability to generate the 

appropriate concentrations of the putative asthmagens. Third, SIC can only be performed in 

relatively stable workers (FEV1 >60–70 percent of predicted and/or >2L28) because SIC may 

induce a very severe asthma attack.29 A fourth disadvantage is the potential for false positives 

that can occur when SIC is performed in a worker with unstable asthma or when the worker 
7

suffers from marked non-specific bronchial hyper-reactiveness, as the non-specific irritant 

reaction can masquerade as an early reaction to SIC.27 Finally, SIC testing can take several 

days. While SIC can be performed as an outpatient procedure, carefully monitoring is required 

for several hours after the challenge and oxygen, bronchodilators, steroids, and intubation 

equipment should be available.15 

History and questionnaires. There are several questionnaires used to assess respiratory 

health.30-33 Questionnaires and histories may focus on specific job duties and work processes 

and inquire about improvement during weekends and/or holidays and worsening when 

returning to work.2 The 1995 ACCP guidelines recommend three components of history 

taking: 1) history detailing onset of illness, temporal relationship between exposure and 

exacerbation, description of airway disease, and severity of asthma; 2) medical history 

describing pre- and co-morbidities and associated symptoms; and, 3) occupational and 

environmental history.15 In addition, material safety data sheets (MSDSs) can be collected for 

the chemicals used in the workplace. MSDSs describe the ingredients, concentration, and toxic 

properties of chemicals in the workplace. 

Questionnaires and histories are easily administered. However, respiratory symptoms are a 

common complaint among all workers, thus questionnaires and histories tend to lack 

specificity. They may also lack sensitivity. The following circumstances can produce falsely 

negative results: exposure to the agent is indirect and/or sporadic; workers may be reluctant to 

disclose symptoms for fear of losing employment; or, the worker does not relate progression of 

OA to a workplace exposure.5 While the utility of history and questionnaires has been 

established for surveillance purposes and case finding in the event of symptoms of rhinitis 

and/or asthma, little research exists that examines their usefulness as a diagnostic test. 

History and questionnaires are used to identify patients with relevant symptoms and 

workplace exposures known to cause OA. These patients will have a higher pre-test 

probability of testing positive to other tests of OA, as the subsequent test is being conducted in 

a pre-screened population. This is of importance in the later considerations in this review. 

Serial lung function testing. Comparing serial lung function at work and away from work 

has previously been used to diagnose OA, especially when SIC test is unavailable. Until the 

advent of modern compact flow based spirometers, there were practical problems with the 

portability of the required equipment. Modern compact spirometers will allow for the 

measurement of lung function parameters including FEV1 and forced vital capacity (FVC). 

One solution to this was to measure serial peak expiratory flow rate (PEFR) as portable and 

inexpensive equipment to measure this has been available for many years. The current ACCP 

guidelines recommend that PEFR be measured at least four times each day: upon waking, at 

noon, at the end of the working day, and at bedtime.15 During each measurement, three PEFR 

measures are performed and recorded once all three readings are within 20 L/min.15 The 

optimal duration of PEFR recording appears to be at least 4 weeks with a minimum of eight 

readings each day and at least 4 consecutive days in each work period.34 However, obtaining 

records of that quality for that period of time is cumbersome. It is noteworthy that the 

sensitivity and specificity of this procedure was similar to records that were collected for at 

least four readings per day and at least 3 consecutive days at work for approximately 18 days.34

Serial lung function testing is an inexpensive diagnostic test that may show a temporal 

association between lung function and occupational exposure.35 Despite these advantages, 
8

serial lung function testing is still associated with a number of difficulties. Unfortunately, this 

test is dependent upon the worker’s effort, requires them to reliably perform a forced expiratory 

maneuver and record the results accurately, and assumes worker honesty in performing and 

recording the results of the test.2

 Spirometers and peak flow meters incorporating a data 

recording device have helped with this to some extent. Another disadvantage of serial lung 

function testing is that it may be difficult to measure lung function for long enough periods 

while the worker is not at work to exclude OA. It is important the worker understands that late 

asthmatic reactions may occur several hours after exposure ceases, and they may not be 

detected during the monitoring period if only cross-shift measurements are made. In addition, 

serial lung function testing may be of no value among patients who are no longer exposed to 

the causative agent, as an asthmatic response should not occur, and when a patient has 

advanced OA, their lung function may become relatively fixed and not substantially improve 

during fairly short periods away from work. Finally, there are no universally accepted, 

standardized methods, for interpreting the results.15

Non-specific bronchial provocation (NSBP) testing. There are several different 

protocols used to measure bronchial hyper-responsiveness (BHR).15 In general, the first step of 

an NSBP test is to measure baseline lung function. Then, a worker inhales increasing doses of 

a bronchoconstrictor agent; the most commonly used agent in North America is 

methacholine.15 Numerous other agents have been used for NSBP testing, including histamine, 

acetylcholine, hypertonic saline, bethanechol, and distilled water. In the most frequently 

described test method (used in North America) the inhalation of methacholine or histamine 

begins at a concentration of 0.03 mg/mL for 2 minutes and is typically increased in a doubling 

fashion up to 32 mg/mL.15 Following each inhalation, the worker’s FEV1 is measured. The 

predicted concentration causing a 20 percent decrement (PC20) in FEV1 can then be estimated 

by linear interpolation.36 There is no standardized definition of a positive response; however, a 

commonly used definition is a decrease from baseline FEV1 of 20 percent or more at a 

methacholine concentration of 8 mg/mL or less.37 For other techniques, a predicted dose 

causing a 20 percent decrement (PD20) in FEV1 can be similarly estimated. 

 When compared to SIC, the main advantages of NSBP testing approaches are that they are 

reasonably inexpensive, easier to perform, available in a larger number of facilities, and have 

proven safety records. In addition, the test can usually be completed in an hour, or 

considerably less if using an abbreviated protocol. However, a positive NSBP test only proves 

that the worker has hyper-reactive airways, which is typical of asthma due to any cause and it is 

not a definitive test for OA.27 Serial NSBP testing can be performed at work and away from 

work. If the test demonstrates airways hyper-reactivity while an individual is at work and a 

significant reduction after the worker has been away from work for several weeks, then it is 

more likely the worker suffers from OA. From consensus recommendations, a threefold or 

greater increase in PC20 or PD20 when away from work as compared to at work is often 

considered a positive test result for OA38, while a twofold change is suspicious, but not 

universally accepted as definitive of OA.5

Immunological testing. Classically, asthma is often thought of as a specific IgE mediated 

disease, most prevalent in atopic individuals. Common immunological tests include SPT and 

estimation of specific IgE/IgG, which is often measured by using the enzyme-linked immuno 

sorbent assay (ELISA) or radio allergo sorbent test (RAST) techniques. For SPT, a positive 
9

response is often defined as a 3mm or greater wheal reaction to a skin prick.39 SPT can be used 

to identify responses to common allergens, which would signify atopy, or responses to specific 

antigens. Similarly, a high total IgE would be used to signify atopy, while increased specific 

IgE or IgG can also be measured. OA caused by the majority of HMW agents is specific IgE 

mediated and a positive SPT or raised specific IgE will be present. In contrast, LMW-induced 

OA is generally not specific IgE mediated, and consequently SPT or a measurement of specific 

IgE in this situation is not usually helpful40, nor is it useful for irritant induced asthma or workaggravated asthma. 

Further, while specific immunological testing confirms that a worker is sensitized to a 

particular workplace allergen, sensitization is not synonymous with asthma, since sensitization 

to a workplace exposure can exist in the absence of OA. A further disadvantage of 

immunological testing is that few allergens known to cause OA are available in a standardized 

commercial form to be used for allergy testing. Importantly, there is no immunological test 

available for the majority of LMW compounds. 

Total IgE and atopic status are used as screening tools but are not specific for OA or a 

particular workplace exposure, but rather identify atopy. Atopy is a risk factor for developing 

some types of sensitizer-induced OA.41

Measures of airway inflammation. Nitrous oxide is produced by a number of cells 

located in the respiratory tract, such as inflammatory and epithelial cells, and is detectable in 

exhaled air.42 It is hypothesized that asthmatic workers have higher levels of exhaled nitrous 

oxide (eNO) caused by airway inflammation than the normal population. Measuring eNO is a 

non-invasive procedure; however, it has yet to be fully validated as an effective diagnostic test 

for OA, as eNO seems to be increased in a number of inflammatory lung disorders.43 Also, 

eNO testing is confounded by inhaled corticosteroid usage, as workers receiving inhaled steroid 

treatment tend not to have increased eNO.42,44 Finally, it is a difficult test to perform for 

workers, is costly, and its availability in North American is limited. Perhaps, once techniques 

to measure and record eNO are widely available and fully validated, such a method may be 

more appealing. 

A second measure of airway inflammation is sputum induction with identification of 

eosinophils and other cells or inflammatory markers in the expectorated material. The direct 

cellular and chemical evaluation of airway inflammation has traditionally been undertaken 

using bronchial biopsies and bronchial alveolar lavage. In both these latter techniques, 

individuals are usually sedated and bronchoscopes are used to sample the airways either 

through biopsy or saline lavages, respectively. Given the cost, inconvenience, and invasive 

nature of these tests, other methods of identifying and quantifying airway inflammation have 

been developed. One alternative is the use of sputum to examine the cellular and chemical 

agents responsible for inflammation. In many cases, asthmatic workers cannot produce 

sufficient sputum for examination, and so induction is performed using nebulized saline. Once 

a sample is expectorated, it is prepared and examined microscopically for cellular composition 

and chemically analyzed using a variety of techniques. The most important cells in the sputum 

include eosinophils and neutrophils. Standard normal concentrations of both have been 

reported45 and these can be used to evaluate the samples. 

This technique is safe and the repeatability of the technique has now been shown.46 In the 

correct setting (qualified technologist, laboratory, and interpretation) this technique has been 
10

shown to provide useful information about the underlying inflammatory activities in the airway 

and may be incorporated into the diagnostic testing options available for OA.47,48 

In OA, induced sputum markers have been used to determine changes in cellular make-up 

between pre- and post-exposure samples.49 This technique shows some promise for agents or 

circumstances in which SIC cannot be performed. A significant change in eosinophil and/or 

neutrophil concentration post-exposure signifies an airway response related to the asthmagen. 

Management of Occupational/Work-Related Asthma 

Once OA is identified, the general recommendation has been to remove workers from the 

workplace rather than introduce medications to control their symptoms.15 There are, however, 

several different approaches used to manage OA. Firstly, workers can be treated 

pharmacologically in a manner that is similar to those with non-occupationally induced asthma. 

However, additional lung function deterioration may not be prevented in workers who receive 

pharmacological treatment and yet remain exposed to the causative agent.50 Secondly, various 

mechanisms can alter the worker’s environment to reduce exposures to an “acceptable” level 

by using personal protective equipment (PPE), making engineering changes to the workplace 

(e.g., improved ventilation, changing production materials or processes, etc.), or administrative 

changes to work tasks. Additionally, the worker can be relocated to a different job, or to a 

different area of the workplace, or it may be possible to substitute a non-hazardous agent for 

the causative agent in use. The final, and most drastic, management option is to remove the 

worker entirely from workplace. Removal from the workplace should ensure that exposure to 

the causative agent is ended completely which is considered by many to be the cornerstone of 

therapy; however, workers may not wish to be removed for financial and social reasons. In 

practice, it seems that many workers need to be removed from the workplace. Within 6 years, 

approximately one-third of workers are unemployed after their initial confirmed diagnosis of 

OA.22,41 For those who are able to return to work, close medical follow-up is required to ensure 

that lung function does not continue to deteriorate at a rate quicker than would be anticipated as 

due to age alone.2

Reducing exposure. Reducing workplace exposures may benefit not only workers with 

OA, but also those that may go on to develop OA in the future40; however, not all workers with 

OA benefit similarly from this approach. Reducing exposure levels has been hypothesized to 

be of particular use in irritant-based OA where there is no allergic component and hence a more 

linear and predictable dose response relationship.40 Workers with OA with latency (i.e., 

immunologically mediated) may often react to very low concentrations of the aetiological 

agent, and therefore effective management by reducing exposure levels is questionable.2

 The 

American Thoracic Society analyzed five studies that examined the effects of reducing 

workplace exposure on occupational and work-related asthma.5

 They found that OA improved 

or remained unchanged in approximately two-thirds of workers when exposure was reduced, 

while the other workers’ asthma worsened. 

One method to decrease exposure in the workplace is to reduce or eliminate the use of 

potential asthmagens from the workplace.8 Compared to engineering changes, this method is 

advantageous because it does not require mechanical maintenance.8

 Examples of this method 

include using latex-free rubber gloves, latex gloves with lower protein content, or switching to 
11

a spray paint that is di-isocyanate-free. However, it is not frequently applicable in practice as 

the substances used in a workplace rarely have an alternative that can easily be substituted. 

Engineering or structural changes can decrease workplace exposure to an asthmagen. Such 

changes include building an enclosure for the process where the asthmagen is used, or the 

establishment of local ventilation that clears the asthmagen away from the worker’s breathing 

space.8

 Administrative changes, such as job rotation, may also be useful in reducing exposure. 

A third way to reduce exposure is to relocate the workers to a new job in an area of the 

building where the exposure is not present (or present in very low concentrations). The 

Americans with Disabilities Act recommends that large companies with adequate resources go 

to considerable effort to relocate workers with OA into an area or job with decreased 

exposure.51

Finally, exposure concentration can be reduced by the proper use of PPE. In order to be of 

value, PPE must be correctly worn, safely removed, properly maintained, and replaced as 

needed.41 By creating a better atmospheric breathing environment for the worker, air-supplying 

respirators provide the highest level of protection.52 The self-contained breathing respirator can 

protect against most exposures; however, it is cumbersome, expensive, and can not be 

comfortably worn for an entire work shift.52 There is general consensus that PPE is more 

appropriate for managing irritant-induced OA with brief and infrequent exposure than 

sensitizer-induced OA for the reasons mentioned above.8 PPE will reduce but not eliminate 

exposure and consequently is only recommended for short-term use.8 

Removal from exposure. There have been numerous deaths reported among workers with 

OA who were not removed from exposure suggesting that complete asthmagen avoidance is 

important.53 Previous authors have also suggested that for workers suffering from OA with 

latency (immunologically mediated OA), there is consistent evidence concluding that removal 

from the exposure results in an improved health outcome.2,54 In addition, it appears that 

compared to late removal, earlier removal is associated with greater improvement in lung 

function and symptoms.55,56 In contrast, workers with irritant-induced OA are more likely to be 

able to return to work and manage asthma pharmacologically.5 

However, removal from the workplace has significant deleterious effects on the income and 

financial stability of the individual affected, as well imposing costs on the employer.57,58 OA 

claims are also a financial burden to the government; the average accepted claim in Quebec, 

Canada in the early 1990’s was approximately $50,000.59

Pharmacological treatments. Pharmacological treatment of OA does not differ from 

chronic non-occupational asthma treatment. Asthma is managed through a variety of methods 

including trigger avoidance (reduction of trigger or complete avoidance), education, and 

pharmacological measures. Asthma is managed pharmacologically using two large groups of 

agents: relievers (bronchodilators) and preventers (anti-inflammatory agents). 

Relievers. Relievers generally act on the beta-receptors in the airway to dilate the airways and 

relieve symptoms. Examples of these agents include short-acting beta-agonists (SABA) such 

as salbutamol (Ventolin®) or terbutaline, long acting beta-agonists (LABA) such as salmeterol 

(Serevent®) and formoterol (Oxese®, Foradil®), and anticholinergic agents such as 

ipratropium bromide (Atrovent®) and tiotropium (Spiriva®). These agents may be taken for 

relief of symptoms or prior to work to avoid the drop in FEV1 that normally occurs in workers 
12

suffering from OA. There is some evidence that regular use of LABA agents, when 

administered with inhaled corticosteroids, can improve chronic asthma control.60 Monotreatment with LABA is not recommended. There is limited evidence that regular use of 

anticholinergic agents improve chronic asthma control.61

Preventers. Broadly, there are a number of preventers from which physicians and workers may 

choose to decide upon for therapy (corticosteroids, combination agents, leukotriene receptor 

antagonists or modifiers, and mast cell stabilizers): 

• Corticosteroids (CS). Corticosteroids work by reducing inflammation, up-regulating 

beta-receptors, and decreasing airway edema by reducing capillary permeability. There 

are a variety of agents and delivery methods and doses of corticosteroids; however, the 

two main methods of delivery are systemic and inhaled. Systemic corticosteroids are 

effective in intravenous, intramuscular, and oral forms; oral is clearly the preferred 

method of delivery due to convenience, cost, and worker’s adherence. However, long 

term systemic CS are associated with severe adverse effects, such as osteoporosis, skin 

changes, cataracts, impaired glucose regulation, and fluid retention (so called: moonface and buffalo hump appearance). Prior to the introduction of inhaled corticosteroids 

(ICS), systemic CS agents were the mainstay for control of moderate-severe asthma. 

Since the introduction of ICS, these agents have largely replaced systemic CS as a 

treatment of choice. 

• Combination agents. ICS and LABA agents may be taken separately as individual 

inhalational agents, or as new combination inhalers. The current recommendation states 

that LABAs should not be used without an ICS. Fluticasone combined with salmeterol 

(Serevent®) has been marketed as Advair® (Seritide® in Europe); budesonide in 

combination with formoterol (Oxese®) has been marketed as Symbicort®. These 

agents deliver both ICS + LABA in each inhalation and have the benefit of increased 

compliance and ease of use. In general, these agents are reserved for the treatment of 

moderate-severe work-related asthma unresponsive to increasing doses of ICS. 

• Leukotriene receptor antagonists (LKTRA) or modifiers. Discovery of the cystenyl 

leukotriene pathway has been an important advancement in asthma care over the past 

decade. The pathway is particularly important in the inflammatory cascade involved in 

asthma, especially for children and in aspirin-sensitive workers. Agents that inhibit or 

block cystenyl leukotriene pathway, called LKTRA, have been marketed and are 

available for mild-moderate asthma in adults and children. In general, these agents are 

restricted to add-on treatment of moderate-severe work-related asthma unresponsive to 

increasing doses of ICS. 

• Mast cell stabilizers. Infrequently, mast cell stabilizers are used to control asthma. 

These agents are often used in exercise-induced bronchoconstriction (EIB) and in 

children, due to their non-steroidal nature. Given the availability of more effective 

agents, these agents are infrequently used now and generally restricted to EIB and mild 

asthma in children. 

• Other agents. A variety of other agents are available to treat asthma including methylxanthines, antibiotics (especially newer macrolides) and a non-traditional agents. Due 

to their general lack of effectiveness, these agents will not be described in detail in this 

report. 
13

Objectives of this Review 

OA is a common respiratory disease that is difficult to diagnose and treat. Several societies 

have created clinical practice guidelines for OA (Table 2). However, many do not address or 

there is not consensus on the key components identified for this review. In summary; the 

guidelines do not agree upon the role of SIC testing for diagnosing OA; when removal from 

work is mentioned, it appears to be the recommended treatment. 
14

Table 2. Summary of occupational asthma guidelines 

Guideline Year Location Reccomendations: SIC Reccomendations: Removal 

The Asthma 

Management 

Handbook 62 2002 Australia 

SIC is rarely available in Australia. 

All workers with suspected OA 

should have spirometry. 

The cornerstone of effective 

management is cessation of further 

exposure. Assessment of 

permanent respiratory impairment 

and disability should be deferred 

until two years after exposure 

cessation. 

British Guideline 

on the 

Management of 

Asthma 63

2003 United 

Kingdom 

Carefully controlled exposures to 

workplace agents and suitable 

controls is the gold standard for 

diagnosis. SIC should only be 

conducted in specialized units. 

Removal from exposure should 

occur within 12 months of the first 

work-related symptoms of asthma. 

Delay assessment of long-term 

impairment for at least 2 years 

following removal from exposure. 

British 

Occupational 

Health Research 

Foundation 41 

2004 United 

Kingdom 

A diagnosis of OA can generally 

be made without SIC testing. SIC 

is indicated when the worker’s 

management is dependent upon 

knowing the exact cause of OA. 

Symptoms and bronchial hyperresponsiveness may or may not 

improve when the worker is 

removed from exposure. Potential 

for a completely recovery is highest 

when the worker is removed early 

from exposure (relcoation or 

substitution of the hazard). 

Canadian Asthma 

Consensus 

Report 64 1999 Canada Not mentioned 

Once the diagnosis of OA has been 

confirmed, the worker should be 

removed from exposure to the 

causative substance. 

Canadian 

Thoracic Society 

Guidelines for 

Occupational 

Asthma 54

1998 Canada 

Use of challenge tests are 

included as part of the diagnostic 

tests when needed. 

Workers with confirmed OA due to a 

sensitizer should have no further 

respiratory exposure. The best 

medical prognosis occurs with early 

and complete removal from 

exposure. 

The Diagnosis 

and Treatment of 

Adult Asthma 65 2002 New 

Zealand Not mentioned Not mentioned 

Global Initiative 

for Asthma 66 1996 United 

States 

Confirmation of OA should ideally 

be made with measurements such 

as PEF monitoring at home and at 

work or with supervised inhalation 

challenge. 

Complete avoidance of exposure is 

mandatory to permit remission of 

OA. 

Guidelines for 

Assessing and 

Managing 

Asthma Risk at 

Work, School and 

Recreation 8

2004 United 

States 

Assessing the impact of 

workplace exposures includes 

determining the pattern of 

symptoms, specific immunologic 

responses, and airway physiology. 

When a pattern of symptoms or 

airflow limitation in relation to work 

is not clearly identified, 

specialized tests including SIC 

may be essential for diagnosis. 

Prompt and strict exposure control 

should be recommended when OA 

is induced by a workplace sensitizer, 

In some circumstances, such as 

LMW isocyanates, the individual 

should be removed from the 

workplace. 

Long-term 

Management of 

Asthma 67 

2001 Finland Not mentioned Not mentioned 

National Asthma 

Education and 

Prevention 

Program 68 

2003 United 

States Not mentioned Not mentioned 
15

Table 2. Summary of occupational asthma guidelines 

(continued) 

Guideline Year Location Reccomendations: SIC Reccomendations: Removal 

The Primary 

Care 

Management of 

Asthma in 

Adults 69 

1999 United 

Kingdom Not mentioned Not mentioned 

Abbreviations: OA = occupational asthma; PEF = peak expiratory flow; SIC = specific inhalation challenge; LMW = 

low molecular weight 

The first aim was to review the diagnostic approaches for occupational asthma. Many 

studies have examined the utility of various diagnostic techniques that attempt to differentiate 

OA from non-occupational asthma. However, there is variability in study methodology and 

definitions of what constitutes a positive test, and a systematic review and meta-analysis of the 

existing literature is required to determine the most appropriate diagnostic technique and 

identify which workers should be undergoing SIC testing. The objective of this review was not 

to examine the utility of the different tests in screening for OA, such as might be performed in a 

working population potentially exposed to an asthmagen, but rather to reflect how the tests 

might be used in the clinical diagnosis of OA. 

Similarly, the best methods for managing OA have yet to be established. As discussed 

above, there are various techniques for treating OA and many studies have followed cohorts of 

workers suffering from OA and measured markers of disease progression. Thus far, it is 

unclear which treatment option best improves lung function and symptoms. Also, it has yet to 

be established whether complete removal from exposure, with its attendant social and 

economic consequences, is imperative in all types of OA. 

It was our objective to systematically gather the existing evidence to determine which 

diagnostic methods are effective at determining a case of OA and what the optimal treatment is 

for such workers. 

Key Questions 

The American College of Chest Physicians put forth the following four questions: 

1. What is the best diagnostic approach for a patient with suspected occupational asthma? 

What are the advantages of SIC testing versus peak flow monitoring, serial 

methacholine challenges, immunological testing, or spirometry in making the diagnosis 

of occupational asthma? 

2. In what situations would specific inhalation challenge testing provide additional useful 

diagnostic information? 

3. Which treatment is most effective for asthma that is occupationally caused, such as 

removal from work environment versus reduced exposure through modification and 

treatment with optimal asthma anti-inflammatory medications (e.g., inhaled steroids)? 

4. Must patients with asthma that is occupationally caused or aggravated be removed from 

the workplace environment to control symptoms and/or disease progression?

17

Chapter 2. Methods 

Methods for the Systematic Reviews 

Literature Search 

Two medical librarians identified appropriate databases to search and developed search 

strategies based on the following terms: asthma, lung disease, respiratory disease, occupational 

disease, occupational exposure, worker, work-related, leave work, reduce exposure, personal 

protective equipment, pharmacological treatment, inhalation challenge, peak flow, forced 

expiratory flow rates, bronchial provocation test, medical history taking, diagnostic techniques, 

sensitivity, specificity, predictive value, and, likelihood function. A filter was applied to the 

search output to remove studies pertaining to children (defined as those under the age of 18 

years). 

These search terms were adapted appropriately to search the following electronic resources: 

MEDLINE®, EMBASE®, Dissertation Abstracts®, Expanded Academic®, National Agricultural 

and Safety Database®, CINHAL®, Biological Abstracts®, Agricola®, and trials registries 

(http://clinicaltrials.gov/; http://www.centerwatch.com/; http://www.cochrane.org/index0.htm; 

http://www.controlled-trials.com/; http://www.update-software.com/National/; 

http://www.trialscentral.org/). Web of Science® was searched by tracking the most sentinel 

articles forward. The Cochrane Airways Review Group has developed an "Asthma and 

Wheez* RCT" register through a comprehensive search of EMBASE®, MEDLINE®, and 

CINAHL®. In addition, hand searching of 20 common respiratory care journals has been 

completed and relevant randomized controlled trials (RCT) have been added to the register. 

This database was examined for articles pertaining to therapy for OA. The detailed search 

strategies appear in Appendix A.♦

Authors of included studies that had published at least two papers were contacted regarding 

any missing studies. The reference lists of all included articles and an internal report that was 

recently prepared for the Workplace Safety & Insurance Board of Ontario, Canada entitled 

“The Diagnosis of Occupational Asthma” were searched for any new studies we might have 

missed. Conference proceedings from ACCP, American Thoracic Society, and European 

Respiratory Society scientific meetings were hand searched for the years 2001–2003. In 

addition, clinical practice guidelines were examined for the following organizations: ACCP, 

American Thoracic Society, Canadian Asthma Consensus Guidelines, European Respiratory 

Society, Thoracic Society of Australia and New Zealand, British Thoracic Society, World 

Health Organization, International Labor Organization, International Commission on 

Occupational Health, and the Canadian Thoracic Society Guidelines on Occupational Asthma. 

The search was not limited by language or publication status and is considered current until 

February 2004. If potentially relevant studies were identified as part of the review process and 

met the inclusion criteria, they were included. 

Selection and Inclusion 

 

♦ The Appendices and Evidence Tables cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/asthmawork/asthwork.pdf
18

All duplicate references were removed from the initial electronic searches. Each title, and 

when available, abstract was independently screened by two reviewers. Using general 

inclusion criteria, that is, primary research describing the diagnosis and/or management of OA, 

each study was classified as “include”, “exclude”, or “unclear”. An occupational medicine 

specialist with an interest in occupational asthma and an asthma researcher then screened the 

references identified as “include” and “unclear” and the full text of the potentially relevant 

articles were retrieved. Specific inclusion criteria pertaining to the diagnosis and management 

of OA were developed (Table 3, Appendix B). For example, articles involving workers with 

respiratory symptoms who were referred for assessment of OA at a pulmonary clinic were 

included. Similarly, if a group of workers were screened using a survey method, and only 

those with respiratory symptoms were reported (for diagnostic or treatment studies), the study 

was eligible. In the event a screening study of workers at a work site was identified and if 

those with respiratory symptoms could not be ascertained from the publication or author 

communication, the article was excluded. In this manner, this systematic review excluded 

studies designed to screen for workplace respiratory symptoms. 

Using standard data forms, two reviewers independently applied the inclusion criteria. 

Disagreements were resolved through discussion and consultation with an occupational and 

asthma researcher. In situations where the studies were attempting to diagnose or manage 

workers with OA, respiratory symptoms, and/or rhinitis, studies were included if the results 

were stratified by specific disease and data for those with OA extractable, or if >90 percent of 

the included workers suffered from suspected OA, and data for just those subjects with OA 

could not be identified, all data were included. Case-reports and series involving less than two 

workers were excluded, as were studies that exclusively examine two different ways of 

measuring the same diagnostic test (e.g., Occupational Asthma System computer system versus 

visual assessment of PEFR records). 

If needed, the investigators contacted the authors to clarify that individual publications 

reported on discrete workers. In cases where multiple publications involving the same or a 

portion of the same workers were identified, the most recent publication of the largest cohort 

was selected and any additional, unique information from previous publications was 

incorporated. If a study was published within the last 10 years and relevant health outcomes 

were not presented by ongoing exposure status, but the authors presented exposure status as an 

outcome (e.g., number remaining at same workplace), the authors were asked to provide 

outcome data by exposure status. 

Table 3. Inclusion/exclusion criteria for review on diagnosing and managing occupational asthma 

Criterion Diagnosis Review Management Review 

Study Design 

Include: RCT, CCT, prospective or 

retrospective cohort, cross-sectional, 

case-series (>2 subjects) 

Exclude: case studies 

Include: RCT, CCT, prospective or 

retrospective cohort, cross-sectional, 

case-series (>2 subjects) 

Exclude: case studies 

Participants 

Include: de-novo asthma or a previous 

diagnosis of occupational asthma that is 

exacerbated at work 

Include: de-novo asthma or a previous 

diagnosis of occupational asthma that is 

exacerbated at work 
19

Table 3. Inclusion/exclusion criteria for review on diagnosing and managing occupational asthma 

(continued)

Intervention / 

Control 

Reference Standard: SIC, supervised 

workplace challenge, serial lung function 

tests, serial measurement of non-specific 

airway reactivity, immunological testing, 

clinical expert diagnosis and exposure to 

an “asthmagen”. 

Other Comparison: above tests and/or 

sputum, metabonomics, nitrous oxide. 

Removal from the workplace, relocated 

to a position with decreased exposure to 

the “asthmagen” within the same 

workplace, PPE, engineering controls, or 

pharmacological treatment. 

Outcome 

Measures 

Absolute numbers to construct a 2 x 2 

(comparing two diagnostic techniques) or 

2 x 1 (assessing one diagnostic technique 

in workers with a previous diagnoses of 

occupational asthma) table, sensitivity, 

specificity, or likelihood ratios, cost, time 

to complete diagnosis, adverse effects. 

Pulmonary function, use of medication, 

healthcare utilization, frequency of 

exacerbations, QOL, symptoms, 

economic consequences, adverse 

events. 

Abbreviations: RCT = randomized controlled trial; CCT = clinical controlled trial; SIC = specific inhalation 

challenge; PPE = personal protective equipment; QOL = quality of life 

Quality Assessment 

Assessment of the methodological quality of included studies was completed independently 

by two reviewers, using a variety of methods of assessment based on the review topic as 

follows: 

Diagnosis review. The methodological quality of each included diagnostic study was 

completed using a quality tool developed from Lijmer’s empirical research examining biases in 

diagnostic studies (Appendix B). The quality tool was comprised of 12 questions and pilot 

tested by the research team prior to employment. Empirically validated questions included 

study design (case control versus cohort), levels of blinding of measurements, use of 

appropriate reference or gold standard, an adequate description of the reference standard and 

test(s), thorough description of the study population, and the occurrence of differential 

reference bias.70 In addition, information regarding the occurrence of partial verification bias, 

timing of data collection, method of worker selection, reporting of inter-rater reliability, and the 

method of reporting results was also captured. Discrepancies were resolved through discussion. 

Whether or not the authors mentioned that medication was terminated (or attempted) before 

testing was considered an additional marker of methodological quality. 

Management review. The quality of each included cohort therapy study was independently 

assessed using Downs and Black’s partially validated “Checklist of the assessment of 

methodological quality of both randomized and non-randomized studies of health care 

interventions” (Appendix B).71 This tool is composed of 28 questions that evaluate reporting 

(10 questions, total score 11), external validity (three questions, total score three), internal 

validity-bias (seven questions, total score seven), internal validity-confounding (six questions, 

total score six), and power (two questions, total score two). The maximum total score was 29 

indicating high quality and the lowest possible score was 0 indicating low quality. The 

reviewers, asthma researchers, and occupational health specialist developed a priori guidelines 

regarding the application and implementation of the quality tool. In the event that a question 

was not applicable to the study design, the question was answered “no”. Also, the funding 
20

source was recorded for each study. Controlled clinical trials (CCT) were assessed with a 

second tool, the Jadad scale.72 This validated five-point scale assesses randomization, doubleblinding, and the reporting of withdrawals and dropouts. In addition, concealment of allocation 

was evaluated to be “adequate”, “inadequate”, or “unclear”.73 When there were multiple 

publications of the same workers, methodological quality was assessed on the most recent or 

largest study. Discrepancies were resolved through discussion. 

Data Extraction 

Two data extraction forms were developed, piloted, and used to extract data from the group 

of diagnostic or therapy studies (Appendix B). Data were extracted by one reviewer and 

checked for completeness and accuracy by a second reviewer. When data were presented 

graphically, the graphs were scanned into CorelDraw® (Version 9; Ottawa, Canada) to 

facilitate extracting the data points with greater accuracy. Discrepancies were resolved through 

discussion and input from the task leaders. Whenever possible, a task leader classified the 

exposures as high and low molecular weight based on published information.74

Diagnosis review. Data were extracted regarding the study population characteristics, 

diagnostic tests, and results (e.g., sensitivity, specificity, likelihood ratios [LR], etc.). The 

following patient characteristics were recorded: probable cause of OA, patient source, sex, race, 

duration of exposure and symptoms, history of atopy/allergy diagnosis, smoking status, history 

of asthma, medication usage, and baseline pulmonary function. For each diagnostic test, the 

methodology, timing, inclusion/exclusion criteria, medication use, and definition of a positive 

test result were extracted. 

The reference standard was assigned an ‘evidence grade’ as per our Levels of Evidence 

(Appendix C) designed in consultation with the technical expert panel (TEP). Additional 

outcomes included cost of diagnosis, time to complete diagnosis, and presence of adverse 

events. Where possible, a 2 x 2 diagnostic table was constructed for the reference standard 

versus the comparison test(s). Where a comparison involved two ‘reference’ tests the highest 

ranked test for evidence grade (see Appendix C) was used as the reference test. The sensitivity 

and specificity were extracted or calculated from the 2 x 2 table. 

Management review. Details concerning worker characteristics, interventions, tests used to 

measure outcomes, and outcomes were recorded. Workers were described by their sex, age, 

race, smoking status, history of asthma, history of atopy, probable cause of OA, diagnostic tests 

used to determine OA, duration or exposure and symptoms, current medication, and severity of 

asthma. Where applicable, appropriate workers characteristics, such as smoking status, at 

follow-up were documented. Interventions were described by change in exposure (decreased 

or removal from exposure), type of protective equipment employed, or the type, dosage, route, 

and timing of pharmaceutical treatment. The type of test, method followed, and when 

appropriate, definition of a positive test (e.g., follow-up NSBP test) was recorded for each of 

the tests used to measure outcomes. Outcomes extracted included lung function, symptoms and 

medication scores, and economic status. The length of follow-up was also recorded. 
21

Data Analysis 

All data analyses were performed using SAS® (Version 8.2, Cary, USA). Graphics were 

produced using S-Plus® (Version 6.0, Seattle, USA). 

Diagnosis review. Whenever possible we re-created a standard 2 x 2 table (or 2 x 1 if only 

reference standard positive or reference standard negative subjects were included) for each 

comparison test or combination of tests. This was not possible when individual patient data 

(IPD) was presented without a documented cut-off value indicating the presence (i.e., a positive 

result) or absence of OA. When sensitivity and specificity could be calculated for more than 

one cut-off value or definition for the same diagnostic test, we included the table that produced 

the highest test efficiency defined as the proportion of correctly identified patients (reference 

standard positive and reference standard negative) by the comparison test.75

Sensitivity and specificity were calculated for each study using standard formulas. Results 

were pooled using the inverse variance method for random effects to calculate an overall 

estimate of sensitivity and specificity.1

 We pooled data from 2 x 1 tables separately (reference 

standard positive or reference standard negative only) from studies that presented data from 

which a 2 x 2 table could be generated (both reference standard positive and negative). 

Furthermore, results were only pooled for studies of similar molecular weight (HMW or LMW) 

asthmagens. When sensitivity and specificity could both be calculated, these values were 

plotted in receiver operator curve (ROC) space. When there were a sufficient number of 

studies (n>10), a summary ROC (SROC) curve was derived and added to the plot. 

One drawback of pooling sensitivity and specificity is that it does not take between study 

heterogeneity into account. There are many sources of heterogeneity in any review, and a 

specific source for diagnostic reviews is that variation in sensitivity and specificity that results 

from heterogeneous definitions of a positive test result.76,77 When the information was 

reported, we recorded the exact definition used to define a positive test and this information is 

presented in an evidence table (Appendix E). The inclusion of different asthmagens within 

each molecular weight category was an additional source of heterogeneity in this review. The 

study specific asthmagen is listed with the results on the test specific plots described later in 

this report. 

Management review. Due to the extreme heterogeneity of the reporting of outcomes in the 

treatment articles, no meta-analytic techniques were employed and the summaries are 

descriptive in nature. Nonetheless, some re-organization of the data as reported was required to 

homogenize the information provided in the descriptive summary. 

For continuous outcomes such as FEV1 and some measures of BHR, a mean was used as 

the measure of central tendency when available. In cases where the mean was not reported or 

could not be obtained from an accompanying graph, the following substitutions (in order of 

preference) were used: median and midpoint of the range or IQR. When possible, a mean was 

calculated from IPD when it was available in a tabular format or plotted on a graph. 

Similarly, standard deviation (SD) was used as the measure of variation. In cases where the 

SD was not reported or could not be determined from a graph, the following substitutions were 

used: (75th percentile – 25th percentile)/1.35 when IQR was reported; (maximum – minimum)/4 

 

1

The following software was used for these calculations: Lau J. Meta-Test version 0.9. Tufts-New England Medical 

Center, Boston, 2003 and the Meta package for R (http://cran.r-project.org/). 
22

when range was reported and sqrt(n)*standard error of the mean (SEM) when SEM was 

reported. If individual data were available in tabular or graphic form, the SD was directly 

calculated. 

Baseline characteristics and outcomes were grouped in various ways for the studies. When 

possible the data were grouped according to exposure status in follow-up as follows: continued 

exposure, reduced exposure, or ceased exposure. We used the following formulas to combine 

data when necessary: 

Exposure Group mean=(n1*mean1)+(n2*mean2 )+...(nk*meank )/(n1+n2...nk) 

Exposure Group SD=sqrt(((n1-1)*(SD1)

2

+(n2-1)*(SD2)

2

+...(nk-1)*(SDk)

2

)/(n1+n2...+nk–k)) 

Because it was usually not reported, the mean difference between baseline (diagnosis) and 

follow-up was calculated as the difference between the mean at follow-up and the mean at 

baseline. Standard deviation of the difference was estimated assuming a between patient 

correlation of rho=0.5 between the baseline and follow-up values using the formula: 

 Var(A-B)=sqrt(VarA+VarB–2*rho*sqrt(VarA*VarB)) where Var(X)=SD(X) 2

For economic outcomes, currency measures were converted into US dollar (USD) 

equivalents based on exchange rates for the reported currency in the year of the studies’ 

publication (http://www.oanda.com/convert/classic).

Peer Review 

Twenty-six occupational asthma and/or methodological experts were approached to peerreview the draft of this report. Twelve experts agreed to do so and 11 provided comments 

within the allocated time period. We considered their comments and amended this report 

accordingly. Peer reviewers are listed in Appendix F and will be available on the AHRQ Web 

site.
23

Chapter 3. Results 

Literature Search 

Using database specific search strategies, the following electronic bibliographic databases 

were searched: MEDLINE®, EMBASE®, CINHAL®, Web of Science®, Biological Abstracts®, 

Agricultural Index®, Expanded Academia®, Dissertation Abstracts®, Clinical Trials Registry®, 

National Agricultural Safety Database®, and the Cochrane Airways Group Trials Registry. 

Contact with the authors (Drs. Alvarez, Burge, Lemiere, Malo, Palczynski, and Park) generated 

an additional 33 potential studies. Eleven potentially relevant studies were found hand 

searching pertinent conference proceedings (ACCP, American Thoracic Society, and the 

European Respiratory Society). Additional studies were found in the reference lists of included 

studies. In total, 671 unique studies were reviewed. Study retrieval and selection is outlined in 

the flow diagram. 

Studies were excluded for the following reasons: inappropriate study design (n=164); 

inappropriate topic (n=124); incorrect study population (n=63); inadequate data (n=58); or no 

tests or treatment (n=13). Upon further examination, seven studies within the diagnosis review 

did not provide sufficient detail to calculate a sensitivity and/or specificity, and subsequently 

were excluded.78-84

The majority of the included studies were of subjects with OA with latency (i.e., 

immunologically mediated). There are few studies examining the diagnosis or management of 

OA without latency (i.e., caused by irritants). Therefore, the bulk of the results pertain to 

diagnosis and management of sensitizer induced OA. 

Within the diagnosis and management review, there were several cases where there 

appeared to be multiple publications involving the same, or a portion of the same, cohort of 

workers. In such situations, the most complete study was included, and where unique 

information was presented, additional outcomes were extracted from the other papers. A 

description of these cohorts and the main outcomes reported in each publication are detailed in 

Appendix D.♦

 

♦ The Appendices and Evidence Tables cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/asthmawork/asthwork.pdf
24 

Flow Diagram. Study retrieval and selection for diagnosis and management of occupational asthma 

Initial independent references 

from all databases 

(n=11366) 

Citations with potential 

relevance 

(n=671) 

Second screening 

with specific criteria 

Met inclusion criteria 

(n=65) 

Reference lists, 

authors’ lists, 

conference presentations 

First screening of titles and abstracts 

using general criteria 

 Diagnosis Review Management Review 

* 38 studies were unobtainable or not translated 

13 studfor diagmanage

Met inclusion criteria 

(n=124) 
25 

Diagnosis Review 

Description of Included Studies 

One hundred twenty-four unique cohorts were included in the diagnosis review (Appendix 

E: Evidence Table E-1; Table 6). The median year of publication was 1991 and all but 20 

studies were published in English. Twenty-two studies were conducted in the UK, followed by 

19 studies in each of Canada and Italy. The baseline characteristics of the patients are outlined 

in Evidence Table E-2. Excluding studies that only included patients with a confirmed 

diagnosis of OA, the prevalence of OA among studies including suspected OA cases ranged 

from 5 to 88 percent; the median prevalence of OA was 54 percent. 

Evidence Table E-3 describes the reference and comparison tests. SIC was the most 

commonly identified reference standard; it was performed in 105 of the studies. The next most 

commonly used reference standard was clinical diagnosis. Over half of the studies (67) 

included workers exposed to LMW agents; HMW agents were investigated in 33 studies and 

the probable cause could not be classified in one study. Various chemicals were most often 

believed to be the agent responsible for OA, of which di-isocyanates were the most represented 

chemical. The second most commonly identified agent was wood dust. Not all studies had 

workers with a uniform exposure and/or type of OA: 23 studies included workers from several 

different occupations with various probable causes of OA. Eighty-five studies reported single 

NSBP test as one of their outcome measures. Other frequently reported outcomes were: atopy 

and/or specific SPT, serum specific IgE, eosinophil counts obtained either from serum or 

sputum, and serial PEFR. Only one study examined workers with RADS. 

Methodological Quality of Included Studies 

 

The methodological quality is described in Appendix E: Evidence Table E-4; Table 7. 

Workers were infrequently selected consecutively or randomly; 37 studies failed to report the 

selection method and the remaining studies used alternative methods, such as choosing some 

workers in a factory or some clinic patients. The majority of the included studies collected data 

prospectively. Data were collected retrospectively in 14 studies and whether the study was 

prospective or retrospective could not be established in six other studies. Blinded assessment 

of either the reference standard or comparison test occurred in 21 trials; however, only three 

studies reported that both the reference standard and comparison test results were assessed 

blindly. Partial blinding was inadequate in four trials. The remaining studies did not mention 

blinding status. The methodology used for the reference standard test, most commonly SIC, 

was adequately described in approximately 73 percent of the studies; the description was 

inadequate in the remaining studies. 

Differential bias is likely to have occurred in 26 of the studies and could not be assessed in 

18 studies; the other studies did not have this bias. Partial verification bias was present in 31 

studies and it was unclear if it had occurred in a further 18 studies. Partial verification bias did 

not occur in the remaining 75 studies. Forty-one of the studies reported that workers stopped, 

or attempted to stop, asthma medication prior to diagnostic testing. Funding was not reported 

in 78 of the 124 studies. Among studies with one source of funding, funding was most 

commonly provided by a government agency; 10 studies had multiple sources of funding. 
26

Quantitative Results 

One hundred thirty-one publications reporting data on 124 cohorts met the inclusion criteria 

for the diagnostic component of this review. After selecting the most efficient comparison 

within a study for each comparison test, and ensuring that a comparison test was only reported 

once for a cohort, the most frequently reported comparison tests included single NSBP test 

(n=61), specific SPT (n=47), serum specific IgE antibodies (n=41), clinical diagnoses (n=9), 

serial pulmonary function tests (generally PEFR) (n=9), eosinophil count (n=6), and serial 

NSBP test (n=6). 

In addition, some studies reported sufficient information to investigate the utility of 

combining comparison tests. These combinations primarily consisted of single NSBP test with 

SPT and/or serum specific IgE. For the most frequently reported comparisons, results based on 

the molecular weight of the suspected agent are summarized below and individual study results 

have been plotted in figures. In addition, pooled results from less frequently reported 

comparisons and combinations of comparison tests are reported. However, due to the betweenstudy heterogeneity, which can be seen in the figures, pooled results should be interpreted with 

caution. Finally, because the majority of the workers included in the individual studies were 

screened-in, the results presented below are probably best interpreted as the patients also being 

“positive” for history, questionnaire, and/or referral to a specialist. For example, the 

comparison should be interpreted as screening and single NSBP test versus screening and SIC. 

A summary of sensitivity and specificity of comparison tests that used SIC as the reference 

test is provided in Appendix H. 

Single NSBP test versus SIC. Sixty-one studies reported sensitivity and/or specificity for 

single readings of NSBP testing compared to SIC. Individual study results for LMW, HMW 

and mixed agents are shown in Figures 1, 2, and 3 respectively. The sensitivity/specificity 

pairs are plotted in Figure 4. When we considered the methodological parameters of the 

studies, no clear patterns emerged (Appendix G).

Among the 37 studies that investigated patients exposed to LMW agents, 24 reported both 

sensitivity and specificity. The pooled estimate of sensitivity was 66.7 percent (95% 

confidence interval [CI]: 58.4 to 74.0 percent) and of specificity was 63.9 percent (95% CI: 

56.1 to 71.0 percent). Pooled estimates for studies that reported only sensitivity were higher 

(n=13; 76.6 percent; 95% CI: 59.0 to 88.2 percent).

Of the 13 studies that reported results from investigations of HMW agents, 10 reported 

sensitivity and specificity. The pooled estimate for sensitivity was 79.3 percent (95% CI: 67.7 

to 87.6 percent) and for specificity was 51.3 percent (95% CI: 35.2 to 67.2 percent). The 

estimated sensitivity in the five studies reporting only this data was similar (75.5 percent; 95% 

CI: 56.4 to 88.1 percent). 

Nine studies reported results for various suspected agents of differing molecular weights 

and five studies reporting both sensitivity and specificity. For these mixed populations, the 

pooled estimate of sensitivity was 83.7 percent (95% CI: 66.8 to 92.9 percent) and specificity 

was 48.4 percent (95% CI: 25.9 to 71.6 percent). Sensitivity was lower in the three studies 

reporting only this value (43.7 percent; 95% CI: 10.9 to 83.0 percent). 
27

Specific skin prick test versus SIC. Forty-seven studies reported comparisons of specific 

SPT to SIC. 

Sixteen studies reported results of SPT using the following LMW agents: bleaching 

powder, reactive dyes, wood dust (exotic and western red cedar), chemicals, and di-isocyanates 

(see Figure 5). Among the five studies reporting both sensitivity and specificity, the pooled 

estimate of sensitivity was 72.9 percent (95% CI: 59.7 to 83.0 percent) and of specificity was 

86.2 percent (95% CI: 77.4 to 91.9 percent). Sensitivity was lower in the 11 studies reporting 

only this result (51.8 percent; 95% CI: 28.5 to 74.4 percent). 

Of the 16 studies that reported both sensitivity and specificity for patients exposed to HMW 

agents, the pooled estimate of sensitivity was 80.6 percent (95% CI: 69.8 to 88.1- percent) and 

of specificity was 59.6 percent (95% CI: 41.7 to 75.3 percent). Sensitivity was similar (80.9 

percent; 95% CI: 60.5 to 92.1 percent) in the 10 studies reporting only that result. Results are 

shown in Figure 6. 

Among the five studies that included patients exposed to various agents, the pooled 

estimates for sensitivity and specificity were lower than either high or low molecular weight 

agents. The pooled estimate of sensitivity was 63.0 percent (95% CI: 41.5 to 80.3 percent) and 

specificity was 59.2 percent (95% CI: 45.4 to 71.7 percent). Results are shown in Figure 7. 

The sensitivity/specificity pairs for each molecular weight group are plotted in Figure 8. 

Serum specific IgE antibodies versus SIC. Forty studies reported sensitivity and 19 

reported specificity for serum specific IgE compared to SIC. Of those, 21 studies included 

patients exposed to LMW substances such as bleaching powder, reactive dyes, wood dust 

(exotic and western red cedar), chemicals, and, di-isocyanates (see Figure 9); 16 included 

patients exposed to HMW agents (see Figure 10); and three included patients exposed to 

substances with variable molecular weights (see Figure 11). The sensitivity/specificity pairs 

are plotted in Figure 12. 

Eleven out of the 21 studies considering LMW agents reported both sensitivity and 

specificity; the pooled estimate of sensitivity was 31.2 percent (95% CI: 22.9 to 40.8 percent) 

and of specificity was 88.9 percent (95% CI: 84.7 to 92.1 percent). Of the 10 studies that only 

reported sensitivity, the pooled estimate was 35.9 percent (95% CI: 23.2 to 50.9 percent). 

Sensitivity was higher in the studies where HMW agents were examined; the pooled 

estimate of sensitivity was 73.7 percent (95% CI: 63.9 to 81.0 percent) for the nine studies 

reporting sensitivity and specificity and 81.7 percent (95% CI: 57.8 to 93.5 percent) for the nine 

studies reporting sensitivity alone. The pooled estimate of specificity was 79.0 percent (95% 

CI: 50.5 to 93.3 percent). 

The two studies using a variety of molecular weight agents reported both sensitivity and 

specificity. The pooled estimate for sensitivity was 85.1 percent (95% CI: 40.3to 98.0 percent) 

and of specificity was 61.2 percent (95% CI: 7.0 to 97.1 percent). 

Combined results with single NSBP test, serum specific IgE, and specific SPT 

compared to SIC. When possible, results were combined for the most frequently reported 

comparison tests. In the first assessment, all tests in combination had to be positive for the 

combined result to be considered positive. If any result was negative, the combination testing 

was considered negative. We report results from studies reporting sensitivity and specificity 

for LMW and HMW agents. 
28

When a single NSBP test and specific SPT were considered in combination, four studies 

investigated patients exposed to HMW agents.85-88 The pooled estimate of sensitivity was 60.6 

percent (95% CI: 21.0 to 89.9 percent) and of specificity was 82.5 percent (95% CI: 54.0 to 

95.0 percent) respectively. Sensitivity was 100 percent (95% CI: 74.1 to 100 percent) and 

specificity was 80 percent (95% CI: 49.0 to 94.3 percent) in the one study that investigated 

green tea (a LMW agent).89

Single NSBP test and serum specific IgE results could be combined for only three studies 

reporting both sensitivity and specificity. For two studies of HMW agents, the pooled 

sensitivity was 35.6 percent (95% CI: 1.2 to 96.1 percent) and 84.6 percent specificity (95% CI: 

48.2 to 97.0 percent). 86,87 The third study examined OA caused by isocyanates and resulted in 

0 percent sensitivity (95% CI: 0 to 49.0 percent) and 100 percent specificity (95% CI: 61.0 to 

100 percent).90

In a second analysis, the combination of a positive single NSBP test and either a positive 

specific SPT or positive serum specific IgE was considered positive. Three studies of HMW 

agents yielded results which could be combined in this manner 86-87 The pooled estimate of 

sensitivity was 60.4 percent (95% CI: 11.8 to 94.5 percent) and specificity 81.5 percent (95% 

CI: 47.8 to 95.5 percent). 

Other comparisons. Nine studies reported serial pulmonary function tests versus SIC; all 

but one study91 recorded PEFR. Of these, five studies investigated mixed agents and reported 

both sensitivity and specificity.35,92-95 The pooled estimate of sensitivity was 63.6 percent (95% 

CI: 43.4 to 79.9 percent) and of specificity was 77.2 percent (95% CI: 66.5 to 85.2 percent). 

One study of a LMW agent reported 86.7 percent (95% CI: 59.5 to 96.6 percent) sensitivity and 

90 percent (95% CI: 53.3 to 98.6 percent) specificity.96 Two other studies only reported 

sensitivity resulting in a pooled estimate of 56.2 percent (95% CI: 17.2 to 88.8 percent).91,97 

Finally, one study of a HMW agent reported 100 percent (95% CI: 56.6 to 100 percent) 

sensitivity and no results for specificity.98

All nine studies that compared clinical diagnosis to SIC reported both sensitivity and 

specificity. Clinical diagnosis ranged from physician assessment to a combination of tests, 

which may have included pulmonary function tests, NSBP test, symptom questionnaires, etc. 

Five studies investigated LMW agents and the pooled estimate of sensitivity was 93.6 percent 

(95% CI: 85.0 to 97.5 percent) and of specificity was 68.9 percent (95% CI: 54.7 to 80.3 

percent).99-103 The pooled estimates of sensitivity and specificity were 93.7 percent (95% CI: 

69.3 to 99.0 percent) and 32.3 percent (95% CI: 7.5 to 73.8 percent) respectively in the two 

studies reporting results for HMW agents.104,105 Combined results of the two studies 

considering agents of various molecular weight yielded a sensitivity of 95.1 percent (95% CI: 

86.8 to 98.3 percent) and specificity of 47.7 percent (95% CI: 26.7 to 69.7 percent).106,107

Six studies reported serial NSBP tests compared to SIC and all reported sensitivity and 

specificity. Pooled results from the three studies investigating mixed agents yielded 50 percent 

sensitivity (95% CI: 35.5 to 64.5 percent) and 66.8 percent specificity (95% CI: 53.3 to 78.0 

percent).92,95,108 Two studies involved only patients exposed to LMW agents; pooled sensitivity 

was 67.5 percent (95% CI: 42.6 to 85.3 percent) and specificity was 65.6 percent (95% CI: 41.1 

to 84.0 percent).109,110 A study of OA caused by oil seed rape flour (a HMW agent) yielded 100 

percent sensitivity and specificity.87 

Six studies reported eosinophil counts from sputum, blood, or broncho-alveolar lavage 

versus SIC of which four considered various agents causing OA. Of these, three94,111,112
29

reported sensitivity and specificity. The pooled estimate of sensitivity was 54.9 percent (95% 

CI: 23.7 to 82.7 percent) and of specificity was 72.3 percent (95% CI: 54.1 to 85.3 percent); 

one study reported 100 percent sensitivity only.113 Two studies of LMW agents reported 

sensitivity only.26,114 The pooled estimate of sensitivity was 53.1 percent (95% CI: 10.3 to 91.8 

percent). 

RADS. Only one study examined workers with RADS.115 Fifty-six hospital workers were 

exposed to 100 percent acetic acid; within 24 hours eight workers met the RADS criteria. 

Eight months later, a questionnaire was administered to determine the degree to which workers 

experienced respiratory symptoms after the chemical spill. Fifty-one workers completed the 

survey. Approximately 9 months after the spill, a NSBP test was performed among 24 of the 

exposed workers, including seven of the eight workers who met the criteria for RADS 

(persistent respiratory symptoms). Four of the seven workers had a positive methacholine 

challenge, defined as provocative dose causing a 20 percent drop in FEV1 [(PD20) FEV1] >20 

percent (no dose cut-off was reported). 

None of the included studies reported cost of diagnosis, time to complete diagnosis, or the 

presence of adverse events. 

Management Review 

Description of Included Studies 

Cohort. There were 67 publications referring to 52 cohorts included in the review (Appendix 

E: Evidence Table E-5; Table 8). The median year of publication was 1996. Eleven studies 

were conducted in the UK, followed in decreasing order by Italy, Canada, and the United 

States. Two studies examined workers with RADS; the workers were exposed to sulfur dioxide 

in a pyrite mine explosion in one study116 and pipefitters were exposed to chlorine at a paper 

mill over a 3 month period.4

 The baseline characteristics of the included workers are described 

in Evidence Table E-6. 

The most commonly identified asthmagens in these studies were chemicals, of which 14 of 

the studies examined di-isocyanates. Thirteen studies included workers with OA caused by 

various agents. Workers were most often recruited from an OA clinic or the workplace. The 

median sample size of the included studies was 26 workers (range: 3–1011). Length of followup was variable within and between studies. 

The interventions and outcomes are outlined in Evidence Table E-7. Twenty-nine cohorts 

reported results on one group of workers who all received the same intervention. Seventeen 

cohorts reported results from two intervention groups; three cohort studies reported on three 

intervention groups; and three cohorts reported on four intervention groups. The most common 

intervention was removal from the workplace (n=42 [81%]). Fourteen studies reported results 

for subjects who continued exposure and, reduced exposure was assessed in 18 studies. Eight 

studies examined the effectiveness of PPE, while two studies compared the use of medication. 

The most commonly reported outcomes were NSBP tests and pulmonary function tests. Other 

tests reportedly completed at follow-up visits included: questionnaires, SPT, SIC, and serum 

specific IgE. 
30

Trials. Thirteen trials were included in this review (Appendix E: Evidence Table E-8). The 

median year of publication was 1990 and all but two trials117,118 were conducted in Europe. 

Patients were not randomized to the treatment groups in four of the trials119-122 and eight 

employed a crossover design.117,119,120,123-127 The most common asthmagen studied was diisocyanates120,122,124-128, followed by flour121,129. Evidence Table E-9 describes the baseline 

characteristics of workers. 

Evidence Table E-10 depicts the interventions and outcomes examined in the trials. Two 

trials assessed methods to reduce the level of asthmagen exposure119,123, including using a 

respirator and using hypo-allergenic latex gloves. The remaining studies examined the efficacy 

of various drugs, including anti-inflammatory agents, bronchochodilators, and immunotherapy. 

Specifically, the types of drugs tested included: beclomethasone (four trials117,125,126,128), 

theophylline (two trials124,126), salbutamol (one trial118), indomethacin (one trial122), atropine 

(one trial120), nifedipine (one trial127), verapamil (one trial126), cromolyn (one trial126), fenoterol 

(one trial129), prednisone (one trial122), and immunotherapy (one trial121). All but one of the 

pharmacological trials was placebo controlled.122 The length of study intervention and followup varied; three studies followed patients for at least 6 months117,121,128 and the remaining 

studies were shorter. Response to SIC was a commonly assessed outcome and was measured in 

ten (77 percent) trials.118,119,122-127,129,130

Methodological Quality of Included Studies 

Cohort. The mean Downs and Black score of the 52 included studies was 16.4 (SD 4.0) 

(Appendix E: Evidence Table E-11; Table 9) of a total possible score of 29. Table 4 depicts the 

mean scores within each component of the quality assessment tool. 

Table 4. Summary of components of Downs and Black score 

Reporting External 

Validity 

Bias Confounding Power Overall 

Maximum 

Score 

11 3 7 6 2 29 

Actual 

Score 

Mean (SD) 

8.2 (1.8) 1.6 (1.0) 3.9 (1.1) 2.3 (1.1) 0.5 (0.5) 16.4 (4.0) 

Abbreviations: SD = standard deviation 

Apart from one study, data were collected prospectively. Approximately half (27/52) of the 

studies provided some IPD. When reported, the most common funding source was provided by 

a government agency; 31 of the studies did not disclose their funding source and few were 

industry sponsored. 

Trials. Of the thirteen clinical trials, the median Jadad score was 2 (IQR: 2, 3) (Appendix E: 

Evidence Table E-12). Concealment of allocation was adequately reported in two of the 

trials117,129, and inadequately in four trials119-122. The method of concealing allocation was 

unclear in the remaining seven trials.118,123-128 Six trials did not report their source of 

funding118,119,121,123,127,129 and two trials were supported solely by government grants.126,128 The 

remaining trials received grants from at least two different types of sources, including private 
31

industry, government bodies, foundations, or other sources. Eight of the studies reported that 

workers stopped medication prior to the beginning of the trial.118-120,122,124-126,128 

Qualitative Results 

Cohort Studies 

Lung function. Twenty-seven studies reported FEV1 at diagnosis (see Appendix E: Evidence 

Table E-7) and we attempted to synthesize the change in lung function over time. In order to 

assess this outcome, we examined the difference between the mean percent predicted FEV1 at 

follow-up and baseline in relation to average length of follow-up. Baseline mean percent 

predicted FEV1 of the included studies is shown in Figure 13. 

55,58,130-147

Severity at diagnosis. Of the 17 studies (n=666 patients) where patients were completely 

removed from exposure to the offending asthmagen, 16 reported a mean baseline percent 

predicted FEV1 >80 percent, indicating primarily mild impairment to normal pulmonary 

function. Among the studies examining patients who remained fully exposed, six of seven 

studies reported mean baseline percent predicted FEV1 >80 percent. Four of the five studies 

describing subjects with reduced exposure reported mean baseline percent predicted FEV1 >80 

percent. Based on these findings, it does not appear that lung function at diagnosis was 

associated with exposure status during follow-up. No specific pattern emerged when we 

considered the molecular weight of the asthmagen studied. 

Follow-up. Less than half of the studies where patients were removed from exposure58,132,138-

140,144,146 or had reduced their exposure131,138,139, had improved FEV1 over time (change >0) 

(Figure 14). Only one study where patients remained exposed to the work environment had a 

positive change in mean percent predicted FEV1.

144 No specific pattern emerged when we 

considered the molecular weight of the asthmagen studied. 

NSBP test. A variety of test characteristics were used to describe non-specific BHR. 

Generally, hyper-responsiveness was defined as the provocative concentration or dose of 

histamine or methacholine required to elicit a pre-determined change in FEV1, usually a 15 or 

20 percent decline (PC15/20 and PD15/20, respectively). In most cases, PC20 values <16 mg/mL 

were considered to reflect significantBHR; however, cutoff levels of <8 mg/mL and <32 

mg/mL were also reported. These results were eventually reported as either the number of 

patients who were hyper-responsive at a specified concentration cut-off value (e.g., <8 mg/mL, 

<16 mg/mL, <32 mg/mL) or as the mean or geometric mean of the concentrations that 

produced the required FEV1 drop. Of the 13 studies that reported the presence of hyperresponsiveness at diagnosis, between 36 percent and 100 percent of patients with OA were 

classified as hyper-responsive.56,130,132,134,135,141,144,148-152 

Follow-up. The change in hyper-responsiveness over time (i.e., from baseline) was 

investigated by calculating the ratio of average hyper-responsive concentration at follow-up to 

the average baseline concentration. This measure was chosen because it is independent of the 

measurement unit and because the baseline measures of NSBP test varied. Therefore, all 

studies that reported or provided sufficient information to calculate a mean or geometric mean 
32

of a hyper-responsiveness measure at baseline and at follow-up were included. A ratio greater 

than 1.0 indicates improved hyper-responsiveness (follow-up/baseline) because the average 

concentration to achieve the specified bronchial response was greater at follow-up than at 

diagnosis. Conversely, a ratio less than 1.0 indicates worsening hyper-responsiveness because 

the average concentration to elicit a bronchial response was lower at the follow-up visit, 

signifying that the airways of patients were more hyper-responsive.

Figure 15 demonstrates that 14 of 15 studies of individuals who were removed from 

exposure had decreased hyper-responsiveness at follow-up.130-133,135-137,143,148,153-157 

Conversely, patients who remained exposed were overall more hyper-responsive at follow-up 

testing, although two of the five studies showed improved hyper-responsiveness at followup.133,150 There were insufficient data (three studies) to draw conclusions about change in 

hyper-responsiveness among patients with reduced exposure. No specific pattern emerged 

when we considered the molecular weight of the asthmagen studied. 

Medications. Medication needs were used as a proxy measure for disease severity and 

continued asthma symptoms. Twenty-two studies reported some medication data at baseline or 

diagnosis. The number of patients taking specific types of medications (bronchodilators, 

corticosteroids, etc.) was most frequently reported in insufficient detail to form an analytic 

approach.58,134,136,146,158-162 Eight studies reported the percent of patients using asthma 

medications at baseline; however, did not specify type.49,123,131,132,141-143,163 Two studies 

categorized patients by frequency of medication use130,138 and three studies reported a mean 

score based on the frequency of medication use.56,100,137 Follow-up data were reported in a 

similar manner. 

There was no clinically meaningful way to combine the continuous measure outcomes with 

the frequency data. In addition, not all studies reported medication use at baseline and followup, thus we explored the percent of patients taking medications at follow-up. When the usage 

level was specified, only those that reported daily or frequent use of medications were 

counted.138,141,142,147,158,164

Follow-up. Of the patients removed from exposure, the percentage of patients using 

medication at follow-up ranged from 17 to 100 percent (Figure 16).56,98,116,130-132,134-

136,138,141,147,154,158,162,165-168 Within this group of 17 studies, there was no indication that fewer 

patients were using medication as time from removal increased. Only nine studies reported 

medication use among patients who remained exposed131,139,141,157,162 or had reduced exposure 

to the asthmagen131,138,139,142,165; no clear pattern of changes in medication use emerged. 

Symptoms/improvement. Thirty publications reported a variety of symptom outcomes by 

intervention status of continued exposure, reduced exposure, and cessation of exposure. 

Outcome measures included mean symptom scores137,138,145, categorical symptom scores164,166, 

and the number of subjects who were asymptomatic or recovered, remained symptomatic, or 

had specific symptoms.50,56,58,131-133,139,142,144,148,157-159,169-176 Four studies included statements 

regarding non-quantified “improvement”.136,149,154,163 Due to the disparity of outcomes, only a 

qualitative assessment was possible. 

Among the studies that examined workers removed from exposure the majority reported 

some improvement in workers’ symptoms following removal.50,56,58,131-133,136-138,144,148,154,157-

159,163,164,166,169-174 This was measured by either a symptom score or reporting that the majority 
33

of patients had improved symptoms or were considered “asymptomatic”. The same pattern 

emerged in the nine studies describing symptoms for subjects whose exposure had been 

reduced by a workplace intervention.131,138,139,142,149,163,170,175,176 Very few studies reported a 

complete resolution of symptoms among the majority of workers.148,159,174

Three groups examined the effectiveness of respiratory protective equipment in reducing 

symptoms caused by workplace exposures. In general, these papers reported that while 

respiratory protective equipment did reduce the severity of acute symptoms, they did not 

eliminate symptoms altogether.152,169,177,178

Finally, most of the studies of workers who remained exposed to the asthmagen at work 

showed that symptoms either remained stable or deteriorated with continued 

exposure.50,58,133,137,139,144,145,157,163 Only two studies reported improved symptoms among those 

who remained exposed to the asthmagen.166,176

Socioeconomic consequences. Seven studies examined socioeconomic outcomes among 

workers with OA (Table 5). In all but three studies138,164,179, the subjects were comprised of a 

group primarily removed from workplace exposure and a continued exposure group. 

Vandenplas et al.138 compared two groups of workers: reduced or removed from exposure. In 

two instances, all of the workers were removed from the offending workplace.164,179 Five of the 

studies included mixed causes of OA, while one study examined latex-induced OA138, and the 

other included patients with red cedar asthma.50 Time since OA diagnosis ranged from 1 year 

to 5.5 years. 

Of the four studies that measured financial situation after OA diagnosis, all found that 

workers who were removed from the workplace causing their OA suffered a loss in income. In 

one study conducted, 85 workers who were removed from exposure were compared to 117 

workers who continued to work for the same employer (46 used PPE, 20 had the same job, 38 

workers were relocated, and 13 were on chronic sick leave).57 The response rate to economic 

questions was high (89 percent). When compared to workers who were completely removed 

from the causative workplace, exposed workers were less likely to have suffered diminished 

earnings; the mean loss of annual income was significantly less among the exposed workers. 

Another study examined 25 workers with SIC-confirmed OA; 13 workers were removed from 

exposure and 12 workers continued their exposure.166 After one year, a significantly greater 

number of removed workers reported deterioration in their economic situation. Compared to 1 

year earlier, both monthly and annual income significantly decreased among the removed 

workers. Earnings also decreased in the workers with continued exposure; however, this 

difference was not significant. Interestingly, this study also reported that pharmaceutical 

expenses significantly decreased for those removed from exposure, while they increased among 

workers with continued exposure. A third study compared 78 workers with OA removed from 

the workplace to 34 workers with OA who continued to be exposed.58 While 140 participants 

were identified, 112 completed the follow-up questionnaire. Fewer workers who were still 

exposed felt they had lost money than workers who were removed. The perceived median 

annual loss of income and the perceived percentage loss of annual income were higher among 

the workers who ceased workplace exposure. The authors did not perform any tests of 

statistical significance. The final study examined red cedar asthma workers who were exposed 

workers (48), non-exposed workers (27), and unemployed workers (53).50 Monthly income 

among the unemployed cohort was significantly less than the working exposed and working 

non-exposed groups. 
34

Vandenplas et al. compared 20 workers who had reduced levels of latex exposure to 16 

workers who were removed from latex.138 Among the reduced exposure group, 7/20 workers 

reported work disability, defined as changed or left work, while 11/16 of workers removed 

from latex exposure reported work disability and the remaining five workers were not working 

because of their latex-induced OA. More workers who were removed from latex reported a 

decrease in income compared with workers with reduced latex exposure. The actual reduction 

in earning was 20 percent among the non-exposed workers, while there was no reduction in 

earnings for the workers with reduced exposure. 

Two studies assessed the rate of worker’s compensation claims and associated 

acceptance.50,138 In Vandenplas’ et al. study, only 12 of the 36 workers stated they had 

attempted to seek compensation. The Belgian Workers’ Compensation Board (WCB) more 

frequently approved claims among workers who were removed from the workplace than those 

who reduced their exposure. In contrast, the Canadian WCB approved more claims than its 

Belgian equivalent. Among those who filed for compensation, the acceptance rate was similar 

between workers with continued exposure, workers who ceased exposure, and the 

unemployed.50

Two studies followed a cohort of workers who were removed from exposure. Gassert et al. 

conducted a study of 55 patients with “definite/probable” OA of mixed origins.164 Seventy-two 

patients were identified and 55 were interviewed. At follow-up, approximately one-third of the 

subjects were employed and their exposure was reduced (17/55). The remaining subjects were 

unemployed. Prior to a diagnosis of OA, 54 workers had health insurance; at follow-up, 49/55 

patients were not insured and had to pay for their asthma medication and care. The final study 

reported findings on 211 Quebec workers with OA caused by mixed exposures were awarded 

workers’ compensation between 1986 and 1988. One hundred and thirty-four of the 211 

eligible workers were followed up 2 years after removal from exposure. The average cost of 

disability/impairment for each worker was $35,529 USD. A significant portion of the workers 

were either unemployed (11/134) or took an early retirement (22/134). 

Table 5. Economic consequences of occupational asthma 

Citation Removed/Unemployed Exposed or Reduced 

Employment 

Gassert et al. 164

Dewitte et al.59 

38*/55 

33*/134 

17+/55 

Income 

Ameille et al.57 

Moscato et al.166 

Gannon et al.58 

Gannon et al.58 

Marabini et al.50 

Marabini et al 50

-50 percent (69/82^) 

-$4,203.72 USD/year 

-$5,863.88 USD/year 

-54 percent (56/78^) 

-$368.14 USD/month 

-$609.96 USD/month* 

-20 percent (10/16^) 

-19 percent (20/104^) 

-$268.71 USD/year 

-$3,820.27 USD/year 

-35 percent (14/34^) 

-$256.38 USD/month 

0 percent (6/20^+) 

Insured 

Gassert et al. 164 49/55 

WCB Claim Acceptance 

Vandenplas et al.138

Marabini et al.50 3/7 

17/20 / 42/45 

1/5 

31/33 

Pharmaceutical Costs/Month 

Moscato et al.166 -$12.46 USD +$13.17 USD 

Abbreviations: USD = United States dollars; WCB = Workers’ Compensation Board 

Note: * = unemployed; + = reduced exposure; ^ = perception of reduced income 
35

Quality of life (QOL). Two studies measured quality of life. Vandenplas et al. examined 36 

subjects with SIC confirmed latex induced OA.138 At a median follow-up time of 56 months, 

16 subjects were no longer exposed to latex and 20 subjects had reduced their exposure. Two 

methods to reduce latex exposure were employed: using less than 20 pairs of latex gloves in the 

room or department each week; and using low allergen sterile and latex-free examination 

gloves. QOL was measured using a French version of the Asthma Quality of Life 

Questionnaire (AQOL). AQOL did not significantly differ among those removed from 

exposure versus those who reduced their exposure. 

In the second study, 211 workers with OA, 134 participated in a follow-up survey assessing 

QOL.93 SIC or serial PEFR was used to diagnose Quebec workers with OA; all the workers 

were removed from the exposure and received compensation from the WCB. Ninety-one 

workers with OA were matched to 91 similar patients with non-occupational asthma. This 

study also utilized the AQOL that considers five components of asthma: self-determined 

activities that were limited by OA, other activities, symptoms, emotional function, and 

exposure to environmental stimuli. When compared to the control group, both the total and 

component scores of the QOL survey were significantly lower among workers with OA than 

those with non-occupational asthma. 

RADS. Piirila et al. followed six men who were exposed to sulfur dioxide during an explosion 

at a pyrite mine.116 At follow-up, three patients continued to work in the same workplace, two 

had retrained and no longer worked underground, and one had retired because of respiratory 

disability sustained after the explosion; 13 years later, chest radiographs, spirometry, and NSBP 

testing were assessed. All of the workers, except one of the men who was retrained, continued 

to suffer from non-specific BHR. NSBP testing was not performed in one worker who 

continued in the same workplace because of dyspnea, wheezing, and moderate obstructive 

ventilatory impairment. There were no changes in chest radiographs. 

A second study reported findings among a group of 29 men who were repeatedly exposed 

to chlorine over three months and subsequently diagnosed with RADS.4

 The men were no 

longer exposed to chlorine and 20 men were assessed one-year post diagnosis. While percent 

predicted FEV1 was not significantly different between diagnosis and follow-up, some of the 

workers showed improvement in non-specific BHR. Six workers had a significant 

improvement in PC20 (3.2 fold difference from baseline to follow-up); non-specific BHR 

significantly deteriorated in one worker. Compared to diagnosis, significantly fewer workers 

required medication to control their OA symptoms. 

Trials 

Pharmacological outcomes. Ten trials examined the effectiveness of various 

pharmaceutical interventions for preventing exacerbations of OA. 

Prednisone, but not indomethacin, was found to be effective in preventing late asthmatic 

responses among workers with toluene di-isocyanates (TDI)-induced OA.122 Five workers 

completed four SIC and NSBP tests in the following order: 1) before treatment to establish 

baseline airway responsiveness; 2) after prednisone treatment (50 mg/d for 3 days); 3) after 

indomethacin (50 mg four times a day for 3 days); and 4) no treatment to assess reproducibility 

of baseline lung function values. After prednisone treatment, there was no significant decrease 

in FEV1 measured 4 and 8 hours post-SIC. There was also no significant change in PD20 FEV1. 
36

Conversely, treatment with indomethacin resulted in FEV1 and PD20 FEV1 significantly 

decreasing 4 and 8 hours after SIC and NSBP test. 

Two trials studied the effect of inhaled beclomethasone versus placebo among workers who 

had been removed from exposure.117,128 The first study, conducted by Malo et al., compared 

beclomethasone (dose: 500 μg twice daily) to placebo; workers were randomized to the first 

treatment for 1 year and then crossed over to the other for 6 months117. Forty-four workers 

exposed to HMW and LMW agents were randomized; however, 12 refused to continue 

treatment for reasons not related to OA and thus, 32 completed the study. When taking 

beclomethasone, there was a significant reduction in nocturnal symptoms and cough. FEV1 and 

FVC also significantly decreased during both the beclomethasone and placebo periods. 

However, when compared to placebo, PEF and global QOL significantly improved when taking 

beclomethasone; no such difference was observed when taking placebo. Greater improvement 

was noted among those who were first randomized to beclomethasone. The second trial 

compared beclomethasone (1000 μg daily for 5 months) to placebo among 15 workers who 

were SIC positive to TDI; seven workers received the active treatment.128 Outcomes were 

measured at diagnosis, 2, 4, and 6 months. At 6 months, both groups still exhibited a 

significant late fall in FEV1 during SIC; workers randomized to beclomethasone no longer had 

an early fall in FEV1. Among workers receiving beclomethasone, PD20 measured using FEV1 

significantly improved at 2 months and continued to improve at 6 months. PD20 measured 

using FEV1 did not change among those receiving placebo. 

De Marzo et al. conducted a three-way randomized crossover trial of TDI-sensitive workers 

who had had not been exposed for 2 weeks prior to the trial beginning.125 The treatment arms 

consisted of high dose (2000 μg) beclomethasone, low dose (400 μg) beclomethasone, and 

placebo; the washout period was at least 1 week. SIC and NSBP tests were performed on the 

seventh day. When receiving placebo and low dose beclomethasone, FEV1 was significantly 

lower after SIC; FEV1 did not change among the workers when they were taking high dose 

beclomethasone. Neither high-dose nor low-dose beclomethasone improved BHR and the 

hyper-responsiveness decreased over time among all three groups. 

Mapp et al. examined the effectiveness of four drugs for the treatment of TDI-induced 

OA.126 Twenty-four workers received one of the following drugs for 7 days: aerosolized 

beclomethasone (1 mg/kg twice a day), oral theophylline (6.5 mg/kg twice a day), verapamil 

(120 mg twice a day), or aerosolized cromolyn (20 mg/kg four times a day). Each worker was 

also crossed-over to placebo; placebo and active treatment ordering were assigned randomly. 

NSBP test was performed on the sixth day and 8 hours post-SIC, which was conducted on the 

seventh day. Workers randomized to beclomethasone experienced less airway responsiveness 

and did not suffer an asthma exacerbation after SIC. Theophylline reduced the severity of 

asthma exacerbations after SIC; however, airway responsiveness did not decrease. FEV1 

decreased and airway responsiveness increased among workers receiving verapamil, cromolyn, 

or placebo. 

Crescioli et al. compared theophylline to placebo in a randomized crossover trial of six 

male workers with TDI-induced OA.124 In random order, workers received theophylline (5 +/- 

1 mg/kg twice daily) or placebo for 7 days; the washout period was 1 week. SIC was 

performed on the seventh day and airway hyper-responsiveness was measured on day 6 and 8 

hours after SIC. Theophylline had no effect on airway hyper-responsiveness; however, it did 

significantly reduce the severity of late asthmatic reactions. After placebo, three of the six 
37

workers required salbutamol after SIC; when treated with theophylline, none of the workers 

needed salbutamol after SIC. 

To determine if atropine was effective in reducing asthmatic reactions, Paggiaro et al. 

performed SIC before and after administering atropine to 10 workers with TDI-induced OA.120 

Workers with hyper-responsive airways (PD15 FEV1<0.200 mg) received 0.012 mg/kg of 

subcutaneous atropine; the remaining workers received 0.008 mg/kg. Atropine was delivered 

30 minutes prior to SIC and in 90-minute intervals for 6.5 hours. While atropine did inhibit an 

immediate asthma reaction in one worker, the severity of late asthma reactions was unchanged 

in the other nine workers. All workers suffered side effects commonly associated with 

atropine, such as dry mouth, cycloplegia, and increased heart rate. 

Eighteen male workers suffering from flour-induced OA were randomized to two 0.4 mg 

aerosol doses of Fenoterol®.129 Body plethysmography was used to measure airway resistance 

and end expiratory thoracic gas volume. Woitowitz et al. found that workers randomized to 

Fenoterol® experienced a significantly normalized airway resistance within 5 minutes. End 

expiratory thoracic gas volume also improved with the use of Fenoterol®, however this 

difference was not significant. The drug remained effective for 4 hours and the maximum 

effect was achieved within 30–120 minutes. There was no significant change in pulse rate or 

blood pressure. 

Moscato et al. compared the effects of nifedipine and placebo on bronchial responsiveness 

to TDI among five workers with TDI-induced OA.127 In a crossover trial, five patients received 

two capsules of nifedipine (20 mg sublingually) or placebo 45 minutes before SIC. The test 

was repeated with alternate treatment 1 week later. Placebo did not prevent asthmatic 

exacerbations. Immediate asthmatic reactions and reactions within 1 hour were prevented by 

nifedipine. Two patients required a second dose of 10 mg of nifedipine at 2 hours to prevent a 

late response. 

Malo et al. examined 25 workers who had SIC confirmed OA and displayed late asthmatic 

reactions; three workers refused to continue and were excluded from the analysis.118 Post SIC, 

workers were given either salbutamol (200 μg) or placebo and spirometry was measured to 

determine recovery in FEV1. When compared to placebo, workers receiving salbutamol 

consistently showed greater improvement in FEV1, measured by percent FEV1 improvement, 

improvement of ≥20 percent FEV1, and return of FEV1 as percent of baseline. 

Immunotherapy. Armentia et al. conducted a double-blind trial examining the effectiveness 

of wheat flour extract immunotherapy.121 Thirty workers with bakers’ asthma were included, 

however four withdrew because they left their job and their symptoms improved. Ten workers 

received injections of placebo, eight received immunotherapy for 10 months, and the remaining 

eight workers received immunotherapy for 20 months; immunotherapy was administered 

weekly. Compared to workers in the placebo group, immunotherapy resulted in significantly 

less skin prick sensitivity and non-specific bronchial reactivity; significant subjective clinical 

improvement was also noted among the treatment groups. Workers receiving immunotherapy 

for 20 months experienced a significant decrease in serum specific IgE levels. Overall, the 

immunotherapy appeared to be safe; a single worker had urticaria after a dose of 

immunotherapy. 

Reducing workplace exposure. Two trials examined the effect of reducing exposure on 

asthma outcomes in workers with OA. The first study was a crossover trial examining the 
38

efficacy of respiratory devices among 26 farmers with SIC-verified OA.119 The farmers wore 

various respiratory devices with P2 filters (21 Dustmasters®, 4 Airstream®, 1 Airlite®), and 

SIC was repeated approximately 21 weeks later. Both airway resistance and specific airway 

resistance were significantly improved when SIC was performed while wearing the respiratory 

device. During the SIC without respiratory devices, all of the farmers required bronchodilator 

treatment; only six farmers needed bronchodilator treatment when SIC was performed while 

wearing a respiratory device. While the respiratory devices did reduce bronchial obstruction, 

they failed to provide complete protection. 

The second study compared healthcare workers’ asthmatic reactions to various latex 

gloves.27 Eight healthcare workers with latex-induced OA were included; all of the workers 

were SIC positive to the latex powdered gloves (Triflex®) used in their workplace. Each 

worker had SIC performed in random order while handling at least two of the three types of 

hypoallergenic latex gloves: low-powdered Triflex®, non-powdered Nutex®, and/or powdered 

SensiTouch®. Two of the seven workers tested were SIC positive to low-powdered Triflex® 

gloves. The other two hypoallergenic gloves did not elicit an SIC response. Non-specific BHR 

to hypoallergenic gloves occurred in two of the eight workers. Among the eight healthcare 

workers, the use of hypoallergenic gloves reduced the risk of latex asthma exacerbations. 
39

Figure 1. Sensitivity and specificity extracted from studies comparing single NSBP test to SIC among LMW 

asthmagens 

Data extracted as 2x2 table

Schwaiblmair, 1997 (Bleaching powder) 7/9 32/37

Lozewicz, 1985 (Chemical: acrylates) 0/3 1/1

Burge, 1980 (Colophony) 16/31 14/15

Burge, 1985 (Formaldehyde) 3/6 7/8

Nordman, 1985 (Formaldehyde) 8/11 127/198

Shirai, 2003 (Green tea) 11/11 4/10

Behr, 1990 (Isocyanates) 13/25 13/20

Bernstein, 2002 (Isocyanates) 12/18 19/34

Burge, 1982b (Isocyanates) 22/31 12/14

Cartier, 1989 (Isocyanates) 27/29 14/33

Dente, 1986 (Isocyanates) 14/16 8/26

Ferguson, 1996 (Isocyanates) 22/27 38/48

Karol, 1994 (Isocyanates) 23/34 20/29

Mapp, 1986 (Isocyanates) 0/4 2/2

Moller, 1986 (Isocyanates) 6/7 2/5

Moscato, 1993 (Isocyanates) 12/30 37/45

O'Brien, 1979a (Isocyanates) 6/8 10/16

O'Brien, 1979b (Isocyanates) 17/31 13/21

Paggiaro, 1984c (Isocyanates) 31/53 34/49

Sastre, 2003 (Isocyanates) 11/11 1/9

Vogelmeier, 1991 (Isocyanates) 6/13 3/6

Malo, 1988a (Spiromycin) 2/3 5/10

Obata, 1999 (Wood dust: cedar) 9/9 4/8

DeZotti, 1996a (Wood dust: exotic) 4/4 3/3

Pooled Estimate 282/424

66.7% (95%CI: 58.4% to 74%)

423/647

63.9% (95%CI: 56.1% to 71%)

Data extracted as 2x1 table

Howe, 1983 (Chemical: TCPA) 0/4

Park, 1994 (Chemical: chromium) 3/4

Coutts, 1984 (Chemical: cimetidine) 1/3

Munoz, 2004 (Chemical: persulfate) 6/8

Merget, 1996 (Chemical: platinum salts) 52/57

Kopferschmitt-Kubler, 1998 (Isocyanates) 3/11

Mapp, 1979 (Isocyanates) 12/15

Paggiaro, 1986 (Isocyanates) 21/27

Pezzini, 1984 (Isocyanates) 9/23

Park, 1989 (Reactive dyes) 9/9

Park, 1991 (Reactive dyes) 6/13

Lam, 1979 (Wood dust: cedar) 10/11

Lam, 1983 (Wood dust: cedar) 83/83

Ricciardi, 2003 (Wood dust: iroko) 9/9

Pooled Estimate 221/266

76.6% (95%CI: 59% to 88.2%)

3/11

27.3% (95%CI: 9% to 56.6%)

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Specificity

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Specificity
40

Figure 2. Sensitivity and specificity extracted from studies comparing single NSBP test to SIC among HMW 

asthmagens 

Data extracted as 2x2 table

Koskela, 2003 (Animal/bird: cow dander) 9/11 17/26

Vanhanen, 2000 (Cellulase) 6/8 2/3

Alvarez, 1996 (Cereals) 4/4 1/1

Merget, 1993 (Enzymes) 12/13 12/29

Carletti, 1997 (Flour) 12/20 7/17

Park, 1998 (Grain dust) 3/6 5/9

Jager, 1993 (Latex) 4/6 3/3

Schuermans, 2003 (Latex) 18/20 15/19

Vandenplas, 1995b (Latex) 7/7 0/5

Vandenplas, 2001 (Latex) 28/31 1/14

Pooled Estimate 103/126

79.3% (95%CI: 67.7% to 87.6%)

63/126

Data extracted as 2x1 table 51.3% (95%CI: 35.2% to 67.2%)

Quirce, 1992 (Alpha amylase) 5/5

Zeiler, 2002 (Animal/bird: cow dander) 6/9

Kim, 1999 (Citrus red mite) 7/7

Paggiaro, 1984b (Enzymes: proteolytic) 4/6

Cartier, 1987 (Psyllium) 4/5

Pooled Estimate 26/32

75.5% (95%CI: 56.4% to 88.1%)

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Specificity
41

Figure 3. Sensitivity and specificity extracted from studies comparing single NSBP test to SIC among 

mixed asthmagens 

Data extracted as 2x2 table

Baur, 1998 (Mixed) 2/2 13/23

Dellabianca, 1996 (Mixed) 18/20 12/20

Grosclaude, 1980 (Mixed) 8/15 13/14

Larbanois, 2003 (Mixed) 84/90 12/84

Malo, 1991 (Mixed) 63/75 33/85

Pooled Estimate 175/202

83.7% (95%CI: 66.8% to 92.9%)

83/226

48.4% (95%CI: 25.9% to 71.6%)

Data extracted as 2x1 table

Biot, 1980 (Mixed) 5/12

Graneek, 1987 (Mixed) 8/9

Malo, 1990 (Mixed) 24/164

Pooled Estimate 37/185

43.7% (95%CI: 10.9% to 83%)

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Specificity
42

Figure 4. Sensitivity and specificity pairs from studies comparing NSBP test with SIC 

The size of the plotting character is proportional to the number of patients in the group and the color indicates the 

molecular weight of the suspected asthmagen (white=HMW, black=LMW, grey=mixed).

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1-Specificity

Sensitivity

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1-Specificity

Sensitivity

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1-Specificity

Sensitivity
43

Figure 5. Sensitivity and specificity extracted from studies comparing specific SPT test to SIC among LMW 

asthmagens 

Data extracted as 2x2 table

Schwaiblmair, 1997 (Bleaching powder) 5/9 31/37

Shirai, 2003 (Green tea) 11/11 8/10

Park, 2001 (Reactive dyes) 32/42 85/93

Colas, 1985 (Wood dust: exotic) 3/5 4/5

Paggiaro, 1981 (Wood dust: tanganyika aningre) 2/2 0/1

Pooled Estimate 53/69

72.9% (95%CI: 59.7% to 83%)

128/146

86.2% (95%CI: 77.4% to 91.9%)

Data extracted as 2x1 table

Howe, 1983 (Chemical: TCPA) 4/4

Park, 1994 (Chemical: chromium) 2/4

Coutts, 1984 (Chemical: cimetidine) 0/4

Munoz, 2004 (Chemical: persulfate) 4/8

Merget, 1996 (Chemical: platinum salts) 41/57

Palczynski, 2003 (Chloramine) 6/6

Cirla, 1975 (Isocyanates) 18/33

Duan, 1989 (Isocyanates) 11/12

Hinojosa, 1986 (Wood dust: african maple/ramin) 4/4

Lam, 1983 (Wood dust: cedar) 0/206

Ricciardi, 2003 (Wood dust: iroko) 0/9

Pooled Estimate 90/347

51.8% (95%CI: 28.5% to 74.4%)

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Specificity
44

Figure 6. Sensitivity and specificity extracted from studies comparing specific SPT test to SIC among HMW 

asthmagens 

Data extracted as 2x2 table

Koskela, 2003 (Animal/bird: cow dander) 11/11 13/26

Taivainen, 1994 (Animal/bird: cow dander) 32/49 51/51

Tabar, 2004 (Asparagus) 8/8 0/2

Vanhanen, 2000 (Cellulase) 7/8 0/3

Merget, 1993 (Enzymes) 13/13 27/29

Carletti, 1997 (Flour) 14/20 10/17

Alvarez, 2001 (Flour: oilseed rape) 2/2 0/1

Choudat, 1999 (Flour: wheat) 8/8 6/11

Merget, 1997 (Flour: wheat) 11/11 17/23

Block, 1983 (Flour: wheat and rye) 4/4 1/3

Sander, 2001 (Flour: wheat and rye) 16/24 19/21

Park, 1998 (Grain dust) 2/6 8/9

Jager, 1993 (Latex) 6/6 0/3

Vandenplas, 1995b (Latex) 7/7 0/5

Vandenplas, 2001 (Latex) 31/31 3/14

Symington, 1981 (Mushroom dust) 3/4 2/4

Pooled Estimate 175/212

80.6% (95%CI: 69.8% to 88.1%)

157/222

59.6% (95%CI: 41.7% to 75.3%)

Data extracted as 2x1 table

Park, 2002b (Alpha amylase) 4/4

Quirce, 1992 (Alpha amylase) 5/5

Zeiler, 2002 (Animal/bird: cow dander) 9/9

Krakowiak, 2003 (Animal/bird: lab animals) 13/25

Alvarez, 1996 (Cereals) 4/4

Kim, 1999 (Citrus red mite) 16/16

Paggiaro, 1984b (Enzymes: proteolytic) 5/6

Wurzinger, 1997 (Flour) 1/5

Baur, 1979 (Papain) 5/5

Cartier, 1987 (Psyllium) 4/4

Pooled Estimate 66/83

80.9% (95%CI: 60.5% to 92.1%)

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Specificity
45

Figure 7. Sensitivity and specificity extracted from studies comparing specific SPT test to SIC among 

mixed asthmagens 

Data extracted as 2x2 table

DeZotti, 1996b (Mixed) 10/12 5/10

Grosclaude, 1980 (Mixed) 1/7 4/8

Harries, 1980 (Mixed) 18/24 10/13

Obtulowicz, 1998 (Mixed) 13/25 13/24

Rasanen, 1994 (Mixed) 5/7 5/5

Pooled Estimate 47/75

63% (95%CI: 41.5% to 80.3%)

37/60

59.2% (95%CI: 45.4% to 71.7%)

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Specificity

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Specificity
46

Figure 8. Sensitivity and specificity pairs from studies comparing SPT to SIC 

The size of the plotting character is proportional to the number of patients in the group and the color indicates the 

molecular weight of the suspected asthmagen (white=HMW, black=LMW, grey=mixed). 

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1-Specificity

Sensitivity

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1-Specificity

Sensitivity

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1-Specificity

Sensitivity
47

Figure 9. Sensitivity and specificity extracted from studies comparing serum specific IgE test to SIC 

among LMW asthmagens 

Data extracted as 2x2 table

Schwaiblmair, 1997 (Bleaching powder) 5/9 31/37

Shirai, 2003 (Green tea) 11/11 8/10

Park, 2001 (Reactive dyes) 32/42 85/93

Colas, 1985 (Wood dust: exotic) 3/5 4/5

Paggiaro, 1981 (Wood dust: tanganyika aningre) 2/2 0/1

Pooled Estimate 53/69

72.9% (95%CI: 59.7% to 83%)

128/146

86.2% (95%CI: 77.4% to 91.9%)

Data extracted as 2x1 table

Howe, 1983 (Chemical: TCPA) 4/4

Park, 1994 (Chemical: chromium) 2/4

Coutts, 1984 (Chemical: cimetidine) 0/4

Munoz, 2004 (Chemical: persulfate) 4/8

Merget, 1996 (Chemical: platinum salts) 41/57

Palczynski, 2003 (Chloramine) 6/6

Cirla, 1975 (Isocyanates) 18/33

Duan, 1989 (Isocyanates) 11/12

Hinojosa, 1986 (Wood dust: african maple/ramin) 4/4

Lam, 1983 (Wood dust: cedar) 0/206

Ricciardi, 2003 (Wood dust: iroko) 0/9

Pooled Estimate 90/347

51.8% (95%CI: 28.5% to 74.4%)

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Specificity
48

Figure 10. Sensitivity and specificity extracted from studies comparing serum specific IgE test to SIC 

among HMW asthmagens 

Data extracted as 2x2 table

Koskela, 2003 (Animal/bird: cow dander) 9/11 26/26

Taivainen, 1994 (Animal/bird: cow dander) 40/49 48/51

Tabar, 2004 (Asparagus) 8/8 1/2

Davison, 1983 (Caster beans) 2/2 0/1

Vanhanen, 2000 (Cellulase) 5/8 0/3

Merget, 1993 (Enzymes) 8/13 28/29

Schwarting, 1979 (Flour) 9/14 11/11

Alvarez, 2001 (Flour: oilseed rape) 2/2 0/1

Park, 1998 (Grain dust) 3/6 5/9

Pooled Estimate 86/113

73.3% (95%CI: 63.9% to 81%)

119/133

79% (95%CI: 50.5% to 93.3%)

Data extracted as 2x1 table

Park, 2002b (Alpha amylase) 4/4

Quirce, 1992 (Alpha amylase) 5/5

Krakowiak, 2003 (Animal/bird: lab animals) 8/25

Alvarez, 1996 (Cereals) 3/4

Kim, 1999 (Citrus red mite) 16/16

Paggiaro, 1984b (Enzymes: proteolytic) 5/6

Wurzinger, 1997 (Flour) 4/5

Baur, 1979 (Papain) 5/5

Cartier, 1987 (Psyllium) 5/5

Pooled Estimate 55/75

81.7% (95%CI: 57.8% to 93.5%)

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Specificity
49

Figure 11. Sensitivity and specificity extracted from studies comparing serum specific IgE test to SIC 

among mixed asthmagens 

Data extracted as 2x2 table

DeZotti, 1996b (Mixed) 12/12 3/10

Rasanen, 1994 (Mixed) 5/7 5/5

Pooled Estimate 17/19

85.1% (95%CI: 40.3% to 98%)

8/15

61.2% (95%CI: 7% to 97.1%)

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Specificity

0 20 40 60 80 100

Sensitivity

0 20 40 60 80 100

Specificity
50

Figure 12. Sensitivity and specificity pairs from studies comparing specific IgE with SIC 

The size of the plotting character is proportional to the number of patients in the group and the color indicates the 

molecular weight of the suspected asthmagen (white=HMW, black=LMW, grey=mixed). 

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1-Specificity

Sensitivity

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1-Specificity

Sensitivity

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1-Specificity

Sensitivity
51

Figure 13. Average percent predicted FEV1 at baseline for groups of patients who remained exposed, were 

removed from contact, or reduced exposure to the suspected asthmagen 

The size of the plotting character is proportional to the number of patients in the group and the color indicates the 

molecular weight of the suspected asthmagen (white=HMW, black=LMW, grey=mixed). 

Removed Exposed Reduced

Exposure Status in Follow-up

70

80

90

100

110

Average Baseline %predicted FEV1
52

Figure 14. Difference between average percent predicted FEV1 in follow-up and average percent predicted 

FEV1 at baseline plotted against average length of follow-up by exposure status in follow-up 

Improved percent predicted FEV1 over time is indicated by values greater than zero (0). No change in percent 

predicted FEV1 in indicated by a dashed line at percent predicted FEV1=0. Observations from cohorts with multiple 

follow-up visits are joined by a dotted line. The size of the plotting character is proportional to the number of 

patients in the group and the color indicates the molecular weight of the suspected asthmagen (white=HMW, 

black=LMW, grey=mixed). 

02468

-20

-10

0

10

20 Removed

02468

-20

-10

0

10

20 Exposed

02468

-20

-10

0

10

Change in Average %predicted FEV

20 Reduced

1

Length of Follow-up (years)
53

Figure 15. Ratio of mean NSBP test at follow-up visit to mean NSBP test at baseline plotted against 

average length of follow-up by exposure status in follow-up 

Improved hyper-responsiveness is indicated by values greater than 1. No change in responsiveness is indicated by 

a dashed line where the ratio=1. Observations from cohorts with multiple follow-up visits are joined by a dotted line. 

The size of the plotting character is proportional to the number of patients in the group and the color indicates the 

molecular weight of the suspected asthmagen (white=HMW, black=LMW, grey=mixed). 

02468

0

1

2

3

4

5

Removed

02468

0

1

2

3

4

5 Exposed

02468

0

1

2

3

4

5

Reduced

Ratio of Follow-up and Baseline Mean Hyperesponsiveness

Length of Follow-up (years)
54

Figure 16. Percentage of patients taking asthma medications in follow-up plotted against average length of 

follow-up by exposure status in follow-up 

Using medication need as a surrogate for disease severity, decreasing percentages of subjects on medication over 

time may indicate decreasing disease severity. Observations from cohorts with multiple follow-up visits are joined 

by a dotted line. The size of the plotting character is proportional to the number of patients in the group and the 

color indicates the molecular weight of the suspected asthmagen (white=HMW, black=LMW, grey=mixed). 

0 2 4 6 8 10 12 14

0

20

40

60

80

100

Removed

0 2 4 6 8 10 12 14

0

20

40

60

80

100 Exposed

0 2 4 6 8 10 12 14

0

20

40

60

80

100

Reduced

Length of Follow-up (years)

Percent of Patients on Medications
55

Table 6. Description of studies for the diagnosis of OA 

 References 

Published in language other than English 

 Italian 180, 181, 182, 107, 183, 184, 185, 186

 German 103, 85, 187, 188, 189

 French 190, 191, 192, 193

 Chinese 194

 Finnish 104

Country of study origin 

 United Kingdom 34, 195, 101, 99, 196, 197, 198, 102, 199, 91, 200, 201, 202, 203, 98, 204, 205, 206,

207, 208, 209

 Canada 210, 211, 212, 213, 214, 96, 215, 94, 216, 111, 35, 110, 146, 217, 93, 43, 218, 95, 219

 Italy 180, 181, 182, 220, 221, 222, 113, 107, 183, 223, 184, 224, 225, 185, 186, 226, 227, 228

 Germany 106, 103, 85, 229, 230, 187, 231, 188, 232

 Korea 233, 234, 235, 236, 151, 86, 237, 236, 238

 Spain 88, 87, 239, 97, 240, 241, 90, 242

 United States 243, 244, 245, 115, 246, 247, 114, 248

 Finland 249, 250, 251, 104, 252, 160, 253

 France 190, 191, 254, 192, 193, 255

Reference standard other than SIC 

 Clinical diagnosis 34, 243, 182, 91, 200, 98, 233, 184, 256, 257, 241, 209, 160, 248, 102, 115, 246, 207

 Serial PEFR 258

Suspected asthmagen 

 Low molecular weight 

 Di-isocyanates 243, 103, 210, 99, 196, 244, 214, 181, 222, 194, 215, 245, 249, 233, 255, 183, 223, 247,

224, 205, 206, 186, 226, 237, 227, 114, 90, 209, 232

 Chemical 198, 102, 91, 203, 115, 204, 230, 246, 97, 256, 151, 259, 207, 248

 Wood dust 192, 96, 260, 239, 216, 43, 225, 218, 241, 228, 219

 High molecular weight 

 Flour 87, 211, 180, 254, 229, 257, 187, 188, 189

 Animal/Bird 261, 262, 104, 160, 253

 Latex 85, 263, 264, 105

 Mixed 34, 190, 106, 191, 265, 220, 221, 113, 200, 94, 201, 193, 202, 107, 266, 111, 35, 146,

217, 93, 184, 112, 95, 251

Comparison tests 

 Single NSBPT 88, 87, 190, 106, 103, 210, 191, 211, 265, 196, 197, 180, 213, 214, 254, 181, 192, 198,

220, 260, 221, 222, 113, 91, 215, 201, 193, 85, 245, 115, 234, 258, 255, 261, 262, 216,

266, 111, 35, 204, 110, 146, 217, 183, 223, 267, 229, 230, 184, 247, 224, 97, 256, 250,

205, 206, 43, 225, 185, 186, 226, 218, 268, 235, 236, 151, 86, 237, 238, 227, 257, 240,

114, 228, 90, 263, 231, 89, 259, 264, 105, 252, 232, 189, 253

 Specific skin prick test 88, 87, 195, 211, 26, 180, 212, 213, 214, 181, 192, 182, 198, 199, 220, 260, 91, 194, 94,

193, 202, 239, 203, 85, 249, 234, 261, 262, 107, 216, 111, 35, 204, 110, 146, 217, 183,

223, 267, 229, 230, 224, 97, 256, 206, 43, 112, 225, 185, 226, 218, 268, 235, 236, 151,

86, 237, 236, 238, 227, 257, 240, 241, 251, 228, 187, 231, 188, 89, 259, 207, 208, 242,

104, 209, 264, 105, 252, 232, 189, 253, 248

 Serum specific IgE 88, 87, 190, 195, 210, 211, 244, 212, 213, 214, 254, 102, 199, 220, 194, 215, 239, 203,

85, 245, 249, 233, 234, 261, 262, 267, 229, 246, 256, 225, 185, 218, 268, 235, 236, 86,

237, 236, 238, 227, 240, 241, 251, 228, 90, 188, 259, 242, 104, 209, 219, 252, 160, 232,

189, 253, 248

 Eosinophil counts 87, 26, 192, 220, 260, 113, 94, 202, 258, 262, 111, 110, 246, 250, 43, 112, 268, 86, 114,

228, 259

 Serial PFT 34, 101, 99, 96, 200, 98, 35, 110, 217, 93, 97, 250, 151, 95, 228, 207, 255, 246
56

Table 7. Methodological quality of studies for the diagnosis of OA 

 References 

Subject selection 

 Random or consecutive 34, 96, 221, 98, 249, 261, 266, 110, 146, 230, 250, 43, 104, 105, 160, 253

 Not reported 190, 195, 103, 191, 197, 244, 180, 213, 192, 182, 220, 222, 194, 193, 239, 107, 183,

223, 184, 256, 206, 185, 186, 226, 235, 151, 95, 227, 251, 114, 187, 90, 263, 219, 252,

232, 189

 Data collection 

 Retrospective 34, 99, 244, 213, 249, 35, 217, 93, 224, 250, 225, 240, 242, 209

 Could not be determined 201, 85, 107, 266, 188, 189

Blinded assessment of outcome 

 Reference standard and comparison 

test 

111, 35, 110

 Reference standard or comparison test 87, 210, 99, 265, 212, 182, 96, 113, 94, 201, 98, 258, 262, 204, 217, 256, 43, 268, 236,

209, 105

 Inadequate 194, 226, 252, 248

Adequately described reference standard 88, 87, 34, 106, 103, 210, 211, 26, 101, 99, 265, 180, 212, 213, 214, 254, 181, 192, 96,

199, 220, 260, 221, 91, 194, 215, 94, 201, 193, 202, 239, 203, 85, 245, 115, 249, 234,

255, 261, 262, 216, 266, 111, 35, 110, 146, 93, 183, 223, 267, 229, 230, 184, 246, 224,

97, 256, 250, 205, 206, 43, 225, 185, 186, 226, 218, 235, 236, 151, 86, 237, 236, 238,

227, 240, 251, 228, 90, 231, 89, 242, 104, 209, 264, 105, 252, 160, 232, 189, 253, 248

Differential bias 

88, 195, 211, 212, 113, 200, 201, 203, 234, 261, 107, 35, 146, 93, 246, 205, 236, 86,

236, 228, 90, 208, 242, 219, 264, 160

 Could not be determined 190, 103, 26, 180, 214, 181, 199, 91, 194, 98, 216, 250, 186, 218, 227, 241, 187, 263

Partial verification bias 

88, 190, 195, 211, 214, 182, 199, 113, 91, 200, 98, 85, 233, 234, 204, 110, 146, 183,

184, 225, 185, 236, 86, 251, 228, 231, 188, 104, 219, 264, 189

 Could not be determined 243, 103, 26, 180, 181, 198, 220, 194, 258, 107, 216, 250, 206, 186, 227, 241, 187, 263

Asthma medication stopped prior to 

testing 88, 87, 265, 254, 96, 220, 221, 113, 91, 215, 94, 202, 245, 115, 255, 261, 216, 35, 146,

223, 267, 229, 230, 247, 224, 97, 250, 43, 226, 218, 268, 237, 227, 240, 251, 90, 231,

89, 242, 104, 253

Source of funding 

 Government 243, 211, 96, 113, 94, 115, 234, 266, 223, 268, 227, 219

 Foundation 195, 216, 111, 256, 43, 240, 160

 Internal 261, 235, 86, 236, 114

 Private 205, 206, 238, 105

 Other (including multiple sources) 34, 210, 244, 212, 214, 200, 245, 247, 253, 248, 88, 254, 203, 229, 237, 257, 264, 232
57

Table 8. Description of studies for the management of OA 

 References 

Published in language other than English 

 German 172

 Italian 140

 Spanish 169

Country of study origin 

 United Kingdom 158, 131, 58, 163, 141, 22, 159, 177, 176, 269, 173

 Canada 134, 136, 143, 55, 147, 132, 179, 4, 270, 135

 Italy 133, 145, 166, 144, 130, 153, 137, 56, 148, 140

 United States 142, 167, 164, 174, 175, 178

 Finland 116, 152

 France 57, 139

 Germany 170, 172

 Korea 151, 171

 Spain 165, 169

 Other 271, 149, 154, 150

Suspected asthmagen 

 Low molecular weight 

 Di-isocyanates 142, 163, 143, 141, 133, 169, 144, 130, 153, 171, 137, 139, 148, 269

 Chemical 158, 174, 175, 4, 170, 165, 151, 116, 56, 173

 Other 131, 150, 172, 149, 55

 High molecular weight 

 Latex 167, 178, 138

 Animal/Bird 177, 152

 Flour 154, 176

 Other 271, 132, 159

 Mixed 134, 57, 58, 164, 136, 147, 179, 270, 145, 166, 135, 22, 140

Subject source 

 Clinic 134, 57, 158, 131, 58, 164, 154, 178, 136, 143, 55, 141, 147, 179, 4, 145, 166, 165, 169,

151, 171, 135, 137, 56, 139, 150, 140, 152, 138

 Workplace 142, 175, 163, 170, 172, 149, 153, 116, 159, 177, 269, 173

 Not reported 167, 174, 271, 132, 270, 133, 144, 130, 22, 148, 176

Exposure Status 

 Removed 134, 57, 158, 167, 131, 58, 164, 154, 174, 175, 163, 136, 143, 55, 141, 147, 132, 179, 4,

270, 133, 170, 172, 166, 165, 169, 144, 130, 153, 151, 171, 135, 116, 137, 56, 139, 22,

148, 159, 150, 138, 173

 Reduced 57, 142, 167, 131, 218, 175, 163, 141, 170, 166, 153, 272, 116, 137, 139, 176, 138, 269

 Continued exposure 57, 167, 58, 55, 133, 145, 170, 166, 149, 144, 56, 139, 150, 176

 Used PPEs 57, 167, 178, 165, 169, 139, 177, 152

 Medications (+/- removal) 271, 140

Outcomes 

 NSBP tests 134, 142, 158, 131, 43, 59, 154, 141, 147, 132, 4, 270, 133, 145, 170, 172, 166, 165,

149, 144, 130, 153, 151, 155, 135, 116, 137, 56, 139, 148, 150, 140, 138, 173

 Pulmonary function tests 134, 142, 158, 131, 59, 154, 174, 175, 163, 55, 141, 147, 132, 4, 133, 145, 170, 166,

165, 144, 135, 116, 137, 56, 139, 150, 177, 140, 152, 138, 269, 173

 Questionnaires 134, 57, 142, 158, 131, 43, 59, 58, 164, 154, 174, 175, 136, 143, 141, 147, 132, 170,

166, 135, 56, 139, 22, 138, 269, 173

 Specific skin prick test 158, 167, 168, 154, 136, 143, 141, 170, 165, 144, 135, 137, 56, 177, 173

 SIC 178, 136, 143, 141

133, 156, 165, 144, 153, 56, 148, 150, 138

 Serum specific IgE 158, 154, 174, 175, 271, 136, 143, 132, 171, 272, 159, 173
58

Table 9. Methodological quality of studies for the management of OA 

 References 

Report IPD 142, 158, 174, 163, 271, 178, 136, 143, 132, 4, 133, 165, 144, 130, 153, 151, 171, 135,

116, 56, 139, 148, 159, 150, 177, 152, 173

Data collection 

 Prospective 134, 57, 142, 158, 167, 131, 55, 58, 164, 154, 174, 175, 163, 271, 178, 136, 143, 141,

147, 132, 179, 4, 270, 133, 145, 170, 172, 166, 165, 149, 169, 144, 130, 153, 151, 171,

135, 116, 137, 56, 139, 148, 159, 150, 177, 176, 140, 152, 138, 269, 173

 Retrospective 22

Source of funding 

 Government 142, 158, 167, 164, 271, 166, 130, 153, 22, 148

 Other 174, 175, 178, 136, 143, 4, 133, 145, 171, 135, 138

 Not reported 134, 57, 131, 55, 58, 154, 163, 141, 147, 132, 179, 270, 170, 172, 165, 149, 169, 144,

151, 116, 137, 56, 139, 159, 150, 177, 176, 140, 152, 269, 173
59 

Chapter 4. Discussion

Diagnosis Systematic Review 

This report summarizes all of the identified available scientific evidence relating to tests 

used for the diagnosis of OA. Before considering the usefulness of diagnostic tests in OA, it is 

important to recognize that perhaps the only unique characteristic of OA is that it is caused by 

workplace exposure. The symptoms, signs, results of many investigations, and the range of 

patho-physiologies encountered are similar to those of non-occupational asthma. 

Consequently, the tests that attempt to specifically diagnose OA must try to identify the 

causative asthmagen. Given that asthma does, by its very nature, demonstrate variability in 

symptoms, signs, and airflow limitation, this is unlikely to ever be a straightforward 

proposition. 

Prior to determining the accuracy of diagnostic tests, a referenced standard must be 

available for comparison. The reference test in OA is SIC, described in detail in a previous 

section of this report. There are a number of issues that make this test problematic. First, SIC 

is not readily available in many countries23, thus, this reference standard diagnostic test is not 

often employed in diagnostic research. Second, testing with some agents may involve 

considerable technical challenges, particularly outside of major centers. In addition, workers 

are often exposed to multiple asthmagens and it may be difficult to determine precisely which 

asthmagen is causing OA. If the worker is challenged with the incorrect asthmagen, a false 

negative test result can occur. 

Further, the criteria used to signify a positive SIC test varies. A 15–20 percent drop in the 

measured airflow (FEV1) generally signifies a “positive” response; however, other outcomes 

have also been used.273-275 It is unclear how this corresponds with some important components 

in the definition of asthma, including inflammatory changes in the airways. Using outcome 

measures such as induced sputum may be one way of circumventing this problem but this is 

not, as yet, widely available.276 Moreover, the reliability of the SIC is hard to determine. It 

seems likely that operator experience and volume-quality relationships are important in 

determining the validity of SIC testing but this has not to our knowledge been formally 

evaluated. Despite these limitations, SIC remains the best test available to use as a reference 

standard and we have elected to use this as our highest ranked “gold standard”. 

Using a comprehensive search strategy and methodologically rigorous approaches to 

identifying diagnostic studies, there were only sufficient data available for us to meaningfully 

analyze the following comparisons: 

• SIC versus NSBP test; 

• SIC versus skin prick testing; 

• SIC versus serum specific IgE. 

There were other comparisons identified in the search, such as serial PEFR, sputum 

eosinophilia, and clinical diagnosis. However, the insufficient volume of evidence comparing 

these diagnostic tests to SIC prevented drawing firm conclusions. From within the available 

evidence, there are some valuable observations that can be made. First, a single measurement 

of NSBP demonstrates moderate sensitivity and a somewhat lower specificity in predicting the 
60

outcome of SIC. For HMW substances, the pooled estimate of sensitivity was 79.3 percent, 

while pooled specificity was 51.3 percent (positive likelihood ratio [LR+]=1.6; negative 

likelihood ratio [LR -]=0.4). It has been suggested that the sensitivity of a single NSBP test can 

be improved by measuring BHR within hours of exposure to the asthmagen.90,105 It is 

important to recognize that these results are primarily derived from highly selected populations 

(usually either referred to a specialty clinic or seen as part of a workplace survey) and these 

results effectively represent a population with a high pre-test probability of disease. 

Presumably, the selection process of referral or participation in a workplace survey identified a 

relevant workplace exposure while NSBP confirmed asthma. Based on these data, we would 

suggest that a positive test would assist the clinician to rule-in OA without being completely 

confirmatory; however, a negative NSBP test would not rule-out OA unlikely, especially in 

lower-risk groups. 

Second, immunological testing may be of importance, depending on the compounds tested. 

Clearly such testing will be more useful for those sensitizers that are known to work via an 

immunological response and may be of little use where immunological sensitizers are either 

unknown or not present. Overall, it appears that when compared to serum specific IgE, SPT 

shows higher sensitivity in comparison with SIC. It appears the converse is perhaps true for 

specificity. However, from these data is appears that SPT and serum specific IgE levels alone 

have limited sensitivity or specificity in at least some settings, and therefore cannot rule-in or 

rule-out OA with sufficient reliability to reassure the patient, the physician, or the employee of 

the presence or absence of OA. 

Third, combining tests may enhance the specificity of testing and may be a suitable 

alternative to SIC in the diagnosis of OA in some people. The highest specificity seems to arise 

from a combination of a single measurement of NSBP test along with SPT or specific IgE in 

pre-screened patients. In a single study of a LMW asthmagen, combined tests provided a 

sensitivity of 100 percent and a specificity of 80.0 percent (LR+ = 4.2; LR- = 0.05). For NSBP 

test and SPT, the pooled sensitivity in HMW asthmagens is 60.6 percent and the specificity is 

82.5 percent (LR+ = 3.5; LR- = 0.5). If it is assumed that clinical referral or participation in a 

workplace survey for suspected OA due to HMW asthmagen produces a high pre-test 

probability of disease (~50%), a positive combined test would support a diagnosis of OA (78% 

probability); negative combined testing would provide the clinician with limited certainty that 

OA was absent (33% probability). Further, in the setting of a lower pre-test probability (such 

as an un-screened sample of workers), the combined test is less confirmatory and more likely to 

rule-out OA. 

Unfortunately, the body of research identified is insufficient to support other combinations 

as accurate substitutes for SIC. For example, the combination of a clinic referral, positive 

NSBP test, positive SPT, and positive serial peak flow monitoring has not been compared to 

SIC in sufficient detail to draw any conclusions. Moreover, serial testing has not been 

examined in sufficient detail to draw firm conclusions. While clinical diagnosis versus SIC 

resulted in high sensitivities among LMW, HMW, and mixed asthmagens, the specificity was 

lower. Moreover, due to the small number of studies for other relevant comparisons, we would 

be cautious in interpreting pooled estimates of sensitivity and specificity for some relevant 

comparisons such as serial peak flow recordings versus SIC. 

A large number of different tests have been reported and used in an effort to reliably 

diagnose OA. In addition to SIC, these include single and serial NSBP test, serial peak flow 

recording, lung function testing, immunological testing, and inflammatory markers. 
61

Unfortunately, there are few comparisons that are repeated with sufficient frequency to allow a 

meaningful analysis. There has been considerable interest in the use of serial PEFR in the 

diagnosis of OA. Surprisingly, a low sensitivity (63.6 percent; 95% CI: 43.4 to 79.9 percent) 

and specificity (77.2 percent; 95% CI: 66.5 to 85.2 percent) was reported for serial PEFR 

versus SIC among a number of mixed asthmagens. The sensitivity and specificity were higher 

among the one study that evaluated serial PEFR versus SIC in LMW asthmagens. This may 

have been related to technical issues in making the recordings, such as the timing of serial 

measurements and the proximity of these measurements to the on/off work cycle. Further, 

some combinations of these tests have been suggested as useful methods for diagnosing OA. 

For example, combining serial PEFR and symptom diaries is recommended as a method to 

diagnose OA8

; however, few studies have specifically evaluated this method. 

Although we had anticipated that there might be comparisons involving reference standards 

other than SIC, we were not able to identify sufficient comparisons utilizing these to undertake 

analyses that we would consider statistically meaningful. In some instances the paucity of 

comparative data were further compounded by the use of non-standardized methodology and 

the use of various end points. In addition, these studies related to different putative asthmagens 

and it is likely that these are associated with different mechanisms in causing OA; the 

performance of each of the tests may vary depending upon the agents involved in causing the 

asthma originally. 

Further, within diagnostic test comparisons that included many studies, the sensitivity and 

specificity was inconsistent at predicting the outcome of SIC. Thus, although we have 

estimated a pooled sensitivity and specificity for some combinations of these tests we 

recommend caution in their interpretation. The pooled estimates of sensitivity and specificity 

tend to have wide confidence intervals and often the sensitivities and or specificities from 

individual tests ranged from 0 to 100 percent. The variation may reflect the wide range of 

agents that were causing OA, and hence the true reason for the tests’ performance may be that 

the underlying mechanisms of OA are different. 

Although the sensitivity and specificity of some of these tests appear to provide some value 

in assisting in the diagnosis of OA, it must be recognized that these results are generally 

produced from a very select population, as the majority of the included workers had been 

screened by either a questionnaire, referral to a specialist, or a medical/occupational history 

compatible with OA. Essentially, all the subjects who were involved in comparisons of SIC 

against other diagnostic techniques were pre-screened and therefore, had a high pre-test 

probability for testing positive to SIC. These data cannot and should not be generalized to an 

unselected, or unscreened population of workers. However, in a clinical setting where patients 

are being investigated for OA, most patients have undergone screening that is similar to that of 

subjects included in the studies. Alternatively, patients seen in specialty clinics by OA experts 

would require similar screening and that would produce similar high pretest probabilities of 

disease. Consequently, it may seem reasonable to apply the pooled estimates of sensitivity and 

specificity derived from these analyses to those groups. 

The second question the diagnostic review tried to address was “in what situations would 

specific inhalation challenge testing provide additional useful diagnostic information?”. 

Unfortunately we were unable to identify sufficient relevant studies that addressed the 

comparative usefulness of SIC as a diagnostic tool with different agents and in different 

settings. Consequently any advice about the situations where SIC should be applied must 

remain based on expert opinion and consensus until further evidence is available. 
62

Management Systematic Review 

This systematic review examined the best available evidence upon which to base 

management decisions for OA. From nearly 15,000 references, we identified 52 cohort studies 

and 13 CCT examining the treatment of OA. In general, the populations studied (etiological 

agents), study designs and quality, and outcomes reported varied considerably. Moreover, the 

majority of the interventions were non-randomized, so the rationale for the intervention 

decision was largely unknown. Overall, the primary questions proved too disparate and the 

results too heterogeneous to pool. Not withstanding the above concerns, some valuable general 

information does arise from this review. 

Cohort 

First, most OA reports indicate patients have mild-moderate airflow limitation, with most 

studies reporting >80 percent predicted FEV1 at the time of initial assessment. We attempted to 

compare the different treatment groups using baseline percent predicted FEV1 data as it related 

to exposure status (e.g., removed from exposure, reduced exposure, and remaining exposed) to 

ensure that selection for the various treatments was not unduly influenced by severity of disease 

at baseline (time of diagnosis). We had anticipated that patient groups removed from exposure 

at work might demonstrate the lowest group FEV1 and those who continued exposure at work 

would demonstrate the highest group FEV1. It does not appear, however, that a selection bias 

occurred with respect to subsequent work exposure based on baseline FEV1 status. While 

formal statistical testing cannot be completed on these data, we argue that the display in Figure 

10 demonstrates similar FEV1 irrespective of subsequent exposure risk. Conclusions based on 

reduced exposure groups are complicated by the paucity of studies included in this comparison. 

Second, given the available data on follow-up, the review team constructed a picture of the 

outcomes of workers with OA, based on their exposure status and duration of follow-up. Once 

again, due to the vagaries of reporting we have not been able to produce statistical analyses; 

however, the graphic display in Figure 11 suggests several important general summary 

comments. Most importantly, those who remain exposed (either partially or fully) experience 

continued deterioration in FEV1 status compared to baseline and over time. In addition, most 

of those groups who are removed from their workplace appear to generally report improvement 

compared to baseline lung function at diagnosis. Despite removal, improvement does not 

appear to be dramatic nor progressive with time. Moreover, while most studies reported group 

improvement, some indicated deterioration, suggesting that the impact of OA is long-lived and 

difficult to “cure”. Finally, in contradistinction to the diagnosis review, no clear trends were 

identified based on the LMW versus HMW sensitizer agent division with respect to clinical 

outcomes. 

Third, similar results are demonstrated for the small group of studies where NSBP were 

recorded at baseline and at follow-up. Once again, those groups who remained exposed 

experienced continued deterioration in NSBP test results compared to baseline and over time. 

Almost all of those groups who report being removed from their workplace appeared to have 

improved compared to NSBP test results at the time of diagnosis. Improvement in non-specific 

BHR appears to be more impressive and progressive with time than FEV1 results. Few groups 
63

appeared to deteriorate, suggesting that continued exposure may be required for non-specific 

BHR to continue to decline. Conclusions based on reduced exposure groups are complicated 

by the paucity of studies included in this comparison. No clear trend was identified based on 

the LMW versus HMW asthmagen division. 

Fourth, while many studies reported symptoms and/or improvement, the definitions and 

measurements were too variable to analyze quantitatively. Symptoms appeared to persist and 

potentially worsen among workers who continued exposure. The picture is less certain among 

workers who were removed; there was evidence that while some workers’ symptoms improve 

after removal from exposure, other workers failed to improve. Among workers who reduced 

their exposure, symptoms abated in some workers but the overall effect seemed to be 

persistence of symptoms. Because symptoms were often measured subjectively and using 

different methods, this outcome is problematic in determining the effect of removal, reduction, 

and continuation of exposure. 

Medication use was a confounder and outcome that was incompletely reported in the 

majority of studies; however, using available data, we attempted to examine the three exposure 

status groups based on their medication use at follow-up. The conclusions from these studies 

are harder to draw, due to small study numbers. Overall, workers with OA, irrespective of 

subsequent exposure, often require medication treatment long after diagnosis. No clear trend 

was identified based on the LMW versus HMW asthmagen division. 

Finally, the economic consequences of developing OA are impressive. From the published 

literature, those who leave the workplace clearly suffer economic repercussions of reduced 

income and/or unemployment. Workers who reduce their exposure or stay employed at the 

same workplace still appear to lose income over time, and their costs of medication increase. 

Furthermore, medical insurance coverage among workers, an important consideration in the 

United States, is reduced after the diagnosis of OA. 

Trials 

There were a limited number of clinical trials performed in the OA field. Overall, the 13 

included clinical trials were of only moderate methodological quality. For example, while 

eight (62 percent) were randomized, none reported their method of randomization; seven (54 

percent) were double-blinded, yet none described their methods of ensuring double-blinding; 

and only two (15 percent) demonstrated adequate concealment of allocation. All studies 

reported losses to follow-up and withdrawals. 

From the 13 clinical trials examining OA interventions, the total number of study patients is 

210, with the largest trial enrolling only 32 patients. One study involved immunotherapy, two 

involved reducing exposure via protective measures and the remaining were medication 

studies. Overall, the immunotherapy results, based on a small overall sample (n=30 patients) 

examining wheat flour antigen, suggest spirometric, immunological, and symptomatic 

improvement when workers experiencing OA are treated with immunotherapy. A 

comprehensive Cochrane Review supports benefit from this therapeutic approach. From 75 

trials involving 3,188 patients with asthma, Abramson et al. demonstrated that immunotherapy 

reduced asthma symptoms and the use of asthma medications and improved bronchial hyperreactivity.277 While this therapy may be as effective as ICS, it is complicated by its long 

duration (10–20 months), limited availability, and that many OA patients have a disease for 

which the relevant antigen for immunotherapy has yet to be identified. Finally, the possibility 
64

of adverse effects, such as allergic reactions and anaphylaxis, is a concern for some patients. It 

is likely most patients either would not qualify or elect to use other forms of therapy. 

Trial evidence examining reduction in exposure is limited to only two clinical trials. 

Evidence does suggest that protective devices can reduce bronchial obstruction; however, they 

failed to provide complete protection and workers were required to be compliant with their use. 

In the situation of latex allergy-induced OA, the use of non-latex or low protein, powder-free 

latex gloves in the work environment appears to be a successful method of improving OA 

symptoms and outcome measures.123

Finally, medication research in OA is limited and conclusions are difficult to draw. These 

medication trials suffer from small sample sizes, limited duration of treatment, and various 

dissimilar comparisons. Consequently, statistical pooling was not possible. In general, there is 

evidence that corticosteroid agents (both systemic and inhaled) are effective in the treatment of 

OA, although this was primarily evaluated in patients with di-isocyanate induced OA. Well 

recognized and parallel evidence is available regarding the effectiveness of corticosteroid 

treatments for chronic asthma from a variety of resources including guidelines and the 

Cochrane Library. Theophylline, a weak bronchodilator, reduced the severity of asthma 

exacerbations after SIC; however, airway responsiveness did not decrease. Other agents such 

as non-steroidal anti-inflammatories, calcium channel blockers, cromolyn, or placebo 

demonstrated limited or no benefit in the acute treatment of OA. Once again, these general 

effectiveness trends appear to be similar for OA and chronic asthma. 

Potential Limitations

There is a possibility of publication bias in this systematic review. For example, by missing 

unpublished and/or poor performing diagnostic test studies, we may be over-estimating the 

psychometric properties of diagnostic tests. Also, by missing unpublished negative studies we 

may be over-estimating the effect of OA treatment. However, a comprehensive search of the 

published literature for potentially relevant studies was conducted, using a systematic strategy 

to avoid bias. This was followed by attempts to contact corresponding and first authors. Grey 

(i.e., unpublished or difficult to find) literature was repeatedly searched; some unpublished 

studies were identified and several negative studies were uncovered. Despite these efforts, we 

do recognize that more of these types of studies may exist. 

There is also a possibility of study selection bias; however, we employed at least two 

independent reviewers, and feel confident that the studies excluded were done so for consistent 

and appropriate reasons. Our search was comprehensive, so it is unlikely that there are many 

studies in press or publication that were missed. 

Overall, OA literature is not indexed well and authors are not consistently using the term 

"occupational asthma" in article titles or abstracts. Using the subject heading “occupational 

diseases” will pick up many relevant articles; however, this is a very sensitive heading and 

includes almost 75,000 references. A second issue is that some of the relevant articles do not 

mention the word “asthma” or any of the terms used to describe OA in lines 1–18 of the search 

strategy (see Appendix A♦). There are also a huge variety of allergens, such as chemicals, 

animals, and trees, which can potentially cause OA. It is impossible to account for every 

variation and term within the search strategy. Knowing this, the strategy was designed to be 

 

♦ The Appendices and Evidence Tables cited in this report are provided electronically at 

http://www.ahrq.gov/downloads/pub/evidence/pdf/asthmawork/asthwork.pdf
65

highly sensitive in order to avoid missing any potentially relevant articles. In addition, 10 

databases were searched in order to retrieve as many pertinent studies as possible. 

The classification of agents into HMW and LMW is of relevance because of their likely 

differing mechanisms and the implications this has for diagnostic tests. While for many agents 

the relevant allergens are well characterized, this classification was not without problems. For 

example, while grain dust contains a number of HMW agents, it likely also contains other 

constituents that may be LMW, or that work by other mechanisms. There was one study 

included in the diagnosis section of this review that examined grain dust; there is some 

controversy regarding the classification of grain dust as a HMW or mixed asthmagen. It is 

noteworthy that when this study is included with other HMW asthmagens for comparisons to 

SIC with NSBP test and SPT, estimates yielded a pooled sensitivity of 60.6 and specificity of 

82.5. When this study is excluded from the comparison, the sensitivity and specificity improve 

to 83 and 100, respectively. Further combination testing research is needed to resolve this 

debate. 

For other agents, such as platinum, their mechanism of action may be a more important 

characteristic than their molecular weight, but characterization by molecular weight seemed the 

best categorization available. Analyses of results by other methods of categorization were not 

undertaken. The results are presented to allow for the calculation of an individual asthmagen’s 

sensitivity and specificity. 

Diagnosis Review 

The evidence concerning the harms (false positive and false negative) of diagnosis of OA is 

even less developed than the evidence for the benefits. Essentially, these patients have not 

been followed for the anxiety of an incorrect diagnosis, nor have the consequences been 

followed in any comprehensive manner. Costs of asthma care are largely borne by the patients, 

families, and the employers, and the costs of OA care are largely borne by the same groups. 

Falsely diagnosing respiratory symptoms as OA may force patients to inappropriately change 

work or become unemployed. Not diagnosing respiratory symptoms as OA when such is the 

case may lead patients to further asthmagen exposure, worsening health, impaired QOL, and 

later unemployment without compensation. 

While SIC is considered the reference standard test in the diagnosis of OA, some studies 

did not have this result available for all patients, if at all. Some studies used a clinical 

“consensus” diagnosis to determine the presence of OA, which may or may not have included 

SIC in the diagnostic process, and it was usually not clear which patients had undergone SIC 

and why. In other studies, only data from patients who had a positive SIC result were reported. 

Two forms of bias may be present as a result of these characteristics: different reference 

standard bias and partial verification bias.70 For HMW agents, we noted that the sensitivity 

generated from SIC positive subjects was similar to that generated from workers with suspected 

OA in two of the three comparison tests we considered in depth (single NSBP testing and 

specific SPT). Among LMW asthmagens, the sensitivity of SPT was substantially lower in 

studies when only SIC positive subjects were included in the study. 

The studies included in the diagnosis review display considerable heterogeneity. This 

heterogeneity likely arises because many different asthmagens can cause OA and the diagnostic 

tests do not behave identically among the various asthmagens. Unfortunately, there were not 

enough studies to pool sensitivities and specificities by the specific asthmagen; however, in an 
66

effort to reduce heterogeneity, the results are presented by HMW and LMW and subgrouped by 

the specific asthmagen. Because of the heterogeneity between studies, pooled results for 

sensitivity and specificity are presented separately for each of the comparison tests. A 

drawback to this approach is that because the calculations are done independently, the pooled 

results of sensitivity and specificity are not explicitly paired as they are for each of the 

contributing studies. The plots of sensitivity/specificity pairs in ROC space demonstrate this 

artifact but do not allow for a link to the detail on specific asthmagen which we believe is 

valuable to the reader. Controversy exists with respect to pooling of heterogeneous data. Some 

would argue that the pooling in this setting is unhelpful and potentially misleading, while 

others believe this approach provides the best estimate of the test property. We have utilized 

random effects modeling, as appropriate for pooling heterogenous studies. However, we advise 

the reader to use caution in interpreting the results presented in this report, but believe that the 

utility of these values should be judged by the reader. We have provided sufficient data to 

recalculate the sensitivity and specificity for a number of specific asthmagens. This will allow 

clinicians to calculate the most appropriate pooled result for use in their practice. 

Among the included studies, there were various definitions of a positive test result and 

different protocols were used to conduct the same test. For example, a positive test result for a 

single NSBP test was frequently reported as PC20 or PD20 FEV1 ≤ 8 or 16 mg. Similarly for 

SPT, studies reported a positive SPT as ≥ 3 mm or compared the size of the reaction among 

workers with suspected OA to the size among a control population. For the purpose of this 

review, we treated one SIC methodology to be equivalent to another; this report does not 

attempt to evaluate the various methodologies used to conduct SIC. 

A further limitation was that not all studies we identified were designed to be diagnostic 

studies and the data presented were not in a useful form to evaluate the diagnostic accuracy of a 

comparison test. That is, it had to be possible to generate a 2 x 2 or 2 x 1 table of the reference 

standard test result with a comparison test result based on one or more cut-offs of the 

comparison test. It is not possible to use results presented as a difference between mean values 

of the comparison test when grouped by the reference test result. In other cases, IPD data were 

available; however, the absence of an established cut-off value to define a “positive” test 

excluded these results. Resources and/or the long length of time between the publication of the 

results to the writing of this report precluded contact with most authors to obtain the necessary 

data in a usable form. This would have increased the number of studies that could be pooled in 

some of the comparisons. 

Management Review 

The main limitation of the management review is that the design of the included studies 

was weak. For example we found very few RCTs and the methodological quality of these was, 

at best, moderate. Most importantly, the interventions were generally divided into removal, 

reduced exposure, or continued exposure; however, the definition of these approaches differed 

and allocation was non-randomized. 

Another limitation of the management studies is that the populations differed considerably. 

For example, while all groups attempted to confirm the diagnosis of OA, the methods used 

varied and the types of asthmagens that workers were exposed to differed. We attempted to 

retain the HMW versus LMW division employed in the diagnostic section of the review to 
67

investigate the heterogeneity of the results; however, this was not helpful. Treatment cointerventions were also incompletely reported in these studies. 

Finally, the outcome assessments were often not comparable and tended to focus on shortterm spirometric results (e.g., pulmonary function tests, NSBP test, SIC, etc.) rather than QOL. 

There was variability in length of follow-up within and between studies, making pooling 

difficult. Only four studies had repeated outcome measurements at different follow-up times 

for the same cohort. 

Conclusions 

OA is an important health care problem, particularly in certain work settings: paint use and 

production (di-isocyanates), the lumber industry (red cedar), bakers (flour), health care workers 

(latex), and other occupations. Workers with this disease generally present with respiratory 

symptoms such as cough, wheeze, shortness of breath, and exercise intolerance. Diagnosis and 

management of OA is designed to reduce morbidity and improve QOL; fortunately, mortality is 

rare, unless severe sensitivities exist. 

Diagnosing OA is a contentious and hotly debated issue, largely because of the social and 

economic implications of the diagnosis to the employer and the employee. Furthermore, 

controversy exists because of the relative paucity of high-quality research in this field. Until 

such time as there is considerable more high quality information on which to base decisions, 

the findings from this systematic review may be unsatisfying to some.

Following a comprehensive search and selection of the electronic and grey literature using 

English and foreign language literature, we identified a large number of studies examining 

diagnostic tests in OA. Based on the evidence, the following conclusions can be made: 

• The general weaknesses associated with the quality and quantity of the research 

evidence suggests that caution should be used in interpreting these results; 

• In the diagnosis review, the sensitivities and specificities varied widely for some of the 

comparison tests. We elected to pool heterogeneous data from individual studies, but 

would encourage clinicians to interpret these results cautiously and conservatively. 

Moreover, we have provided sufficient data to allow clinicians to calculate values that 

would be most useful in their practice. 

• Overall, SIC appears to be the main reference standard for the diagnosis of OA; 

however, its availability is limited where studied; 

• If SIC is not available and the population has a high pre-test probability (e.g., screened 

by history, questionnaire, and/or referral to a specialist), a single NSBP testing is a 

common test that assists in supporting the diagnosis and is of some use in excluding 

OA. Its sensitivity and specificity alone are insufficiently discriminative to definitively 

diagnose OA; 

• In isolation, none of the diagnostic tests (NSBP test, SPT, serum specific IgE, serial 

PEFR, serial NSBP test, etc.) yielded a sufficiently high combination of sensitivity and 

specificity which would be required for a test to be a used routinely as a substitute for 

the reference standard used in this report (SIC); 

• The specificity of NSBP testing can be enhanced by the addition of other testing, 

especially SPT or serum specific IgE; 
68

• Many other combination tests (e.g., repeat of the NSBP testing which demonstrates 

decreases associated with removal from the workplace, serum specific IgE, serial peak 

flow, etc.) have not be evaluated in sufficient detail to provide recommendations; 

• While current clinical recommendations suggest a diagnosis be made by examining the 

results of a number of sequential tests, we did not find sufficient data to evaluate this 

option. 

Following a similar comprehensive search, we identified a moderate number of studies 

examining the treatment of OA. Based on the evidence, the following conclusions can be 

drawn: 

• The general, weaknesses associated with the methodological quality of the research 

evidence suggests that caution should be used in interpreting these results; 

• Overall, the baseline FEV1 does not appear to predict which worker groups will leave 

the workplace or remain exposed (either partially or fully); 

• Workers with OA who remain exposed to the workplace asthmagens tend to experience 

decreased FEV1 over time, increased non-specific BHR, and will continue to require 

medications to control their symptoms; 

• Most workers with OA who cease being exposed to the workplace sensitizer appear to 

experience improved FEV1 over time and less non-specific BHR; despite these 

improvements, many workers will continue to require medications to control their 

symptoms; 

• Some workers with OA can be expected to continue to experience a decrease in their 

FEV1 over time despite ceasing sensitizer exposure; 

• The evidence of outcome for workers who reduce their exposure is insufficient to draw 

firm conclusions but from the limited evidence, it seems likely they continue to have 

ongoing disease; 

• In general, the anti-inflammatory agents (i.e., preventers) appear to be effective shortterm therapy for OA; however, limited OA-specific research has been performed. 

Future Research Opportunities 

Overall, this area is fraught with heterogeneity and methodological problems. It would be 

helpful if the methodology used in this field could be further standardized. Further, given the 

small number of patients reported in each study, perhaps a larger (national) agenda for the 

diagnosis and treatment of OA is needed. Collaborative efforts to resolve the many remaining 

issues will require sufficient funding, multi-centered collaboration, and innovative thinking. 

The following future research priorities are recommended: 

• Future OA studies should use common and internationally accepted definitions for 

asthma severity, other relevant population characteristics, and outcome measures; 

• There in an urgent need for clear comparisons between reference standards (preferably 

SIC) and alternative test approaches, performed independently, and reported using 

standardized diagnostic test methods (sensitivity, specificity, and likelihood ratios). 

Combinations of comparison tests should also be assessed; 
69

• Studies comparing diagnostic tests should ideally collect information regarding the cost 

of diagnosis, time to complete diagnosis, and presence of adverse events; 

• SIC is not widely available and the presence of OA is often determined by nonreference standard testing. A prospective cost-benefit analysis of the non-reference 

standard procedures should be conducted to determine the costs and benefits associated 

with using tests other than SIC to determine the presence or absence of OA; 

• There is an urgent need for prospective long-term outcome studies to further understand 

the outcomes of OA using standardized reporting; 

• Longer-term medication studies are under-represented in the present literature. It is 

imperative to develop an evidence base that supports clinical decision making on the 

intensity of treatment, optimization of medication regimens, and utility of disease 

management interventions for various OA populations; 

• There is limited evidence specifically examining work-aggravated asthma and OA 

without latency. Greater research is needed to determine optimal diagnostic and 

management techniques of these types of OA; 

• Priority should be given to ensuring the highest methodological quality of the research 

and reporting of research conducted to investigate the diagnosis and treatment of OA; 

• Because many workers with OA do not appear to improve, research should also focus 

on the primary prevention of OA. 
70 
71 

References and Included Studies 

 1. Banks DE, Wang ML. Occupational asthma: "the 

big picture". Occup Med 2000;15(2):335-58. 

 2. Chan-Yeung M, Malo JL. Occupational asthma. 

N Engl J Med 1995;333(2):107-12. 

 3. Brooks SM, Weiss MA, Bernstein IL. Reactive 

airways dysfunction syndrome (RADS). 

Persistent asthma syndrome after high level 

irritant exposures. Chest 1985;88:376-84. 

 4. Malo JL, Cartier A, Boulet LP et al. Bronchial 

hyperresponsiveness can improve while 

spirometry plateaus two to three years after 

repeated exposure to chlorine causing respiratory 

symptoms. Am J Respir Crit Care Med 

1994;150(4):1142-5. 

 5. Chan-Yeung M, Malo JL, Tarlo SM et al. 

Proceedings of the first Jack Pepys Occupational 

Asthma Symposium. Am J Respir Crit Care Med 

2003;167(3):450-71. 

 6. McDonald JC, Keynes HL, Meredith SK. 

Reported incidence of occupational asthma in the 

United Kingdom, 1989-97. Occup Environ Med 

2000;57(12):823-9. 

 7. Tarlo SM, Broder I. Irritant-induced occupational 

asthma. Chest 1989;96(2):297-300. 

 8. American Thoracic Society. Guidelines for 

assessing and managing asthma risk at work, 

school, and recreation. Am J Respir Crit Care 

Med 2004;169(7):873-81. 

 9. Meredith S, Nordman H. Occupational asthma: 

measures of frequency from four countries. 

Thorax 1996;51(4):435-40. 

 10. Ameille J, Pauli G, Calastreng-Crinquand A et al. 

Reported incidence of occupational asthma in 

France, 1996-99: the ONAP programme. Occup 

Environ Med 2003;60(2):136-41. 

 11. Milton DK, Solomon GM, Rosiello RA et al. Risk 

and incidence of asthma attributable to 

occupational exposure among HMO members. 

Am J Ind Med 1998;33(1):1-10. 

 12. Blanc PD, Toren K. How much adult asthma can 

be attributed to occupational factors? Am J Med 

1999;107:580-7. 

 13. Meredith SK, Taylor VM, McDonald JC. 

Occupational respiratory disease in the United 

Kingdom 1989: a report to the British Thoracic 

Society and the Society of Occupational Medicine by 

the SWORD project group. Br J Ind Med 

1991;48:292-8. 

 14. Contreras GR, Rousseau R, Chan-Yeung M. 

Occupational respiratory diseases in British Columbia, 

Canada in 1991. Occup Environ Med 1994;51:710-2. 

 15. Chan-Yeung M. Assessment of asthma in the 

workplace. ACCP consensus statement. American 

College of Chest Physicians. Chest 1995;108:1084-

117. 

 16. van Kampen V, Merget R, Baur X. Occupational 

airway sensitizers: an overview on the respective 

literature. Am J Ind Med 2000;38(2):164-218. 

 17. Tarlo SM, Liss G, Corey P et al. A workers' 

compensation claim population for occupational 

asthma. Comparison of subgroups. Chest 

1995;107:643-41. 

 18. Saarinen K, Karjalainen A, Martikainen R et al. 

Prevalence of work-aggravated symptoms in clinically 

established asthma. Eur Respir J 2003;22(2):305-9. 

 19. Goe SK, Henneberger PK, Reilly MJ et al. A 

descriptive study of work aggravated asthma. Occup 

Environ Med 2004;61(6):512-7. 

 20. Leigh JP, Romano PS, Schenker MB et al. Costs of 

Occupational COPD and Asthma. Chest 

2002;121:264-72. 

 21. Chan-Yeung M. Occupational asthma. Chest 

1990;98:148S-61S. 

 22. Ross DJ, Mcdonald JC. Health and employment after 

a diagnosis of occupational asthma: a descriptive 

study. Occup Med (Oxf) 1998;48(4):219-25. 

 23. Ortega HG, Weissman DN, Carter DL et al. Use of 

specific inhalation challenge in the evaluation of 

workers at risk for occupational asthma: a survey of 

pulmonary, allergy, and occupational medicine 

residency training programs in the United States and 

Canada. Chest 2002;121(4):1323-8. 

 24. Sterk PJ, Fabbri LM, Quanjer PH et al. Airway 

responsiveness. Standardized challenge testing with 

pharmacological, physical and sensitizing stimuli in 

adults. Report Working Party Standardization of Lung 

Function Tests, European Community for Steel and 

Coal. Official Statement of the European Respiratory 

Society. Eur Respir J Suppl 1993;16:53-83. 
72

 25. Pepys J, Hutchcroft BJ. Bronchial provocation 

tests in etiologic diagnosis and analysis of asthma. 

Am Rev Respir Dis 1975;112(6):829-59. 

 26. Burge PS, Harries MG, O'Brien IM et al. 

Respiratory disease in workers exposed to solder 

flux fumes containing colophony (pine resin). 

Clin Allergy 1978;8(1):1-14. 

 27. Vandenplas O, Malo JL. Inhalation challenges 

with agents causing occupational asthma. Eur 

Respir J 1997;10:2612-29. 

 28. Cartier A, Bernstein IL, Burge PS et al. 

Guidelines for bronchoprovocation on the 

investigation of occupational asthma. Report of 

the Subcommittee on Bronchoprovocation for 

Occupational Asthma. J Allergy Clin Immunol 

1989;84(5 Pt 2):823-9. 

 29. Malo JL, Cartier A, Lemiere C et al. Exaggerated 

bronchoconstriction due to inhalation challenges 

with occupational agents. Eur Respir J 

2004;23(2):300-3. 

 30. Minette A. Questionnaire of the European 

Community for Coal and Steel (ECSC) on 

respiratory symptoms. 1987--updating of the 1962 

and 1967 questionnaires for studying chronic 

bronchitis and emphysema. Eur Respir J 

1989;2(2):165-77. 

 31. Burney PG, Chinn S, Britton JR et al. What 

symptoms predict the bronchial response to 

histamine? Evaluation in a community survey of 

the bronchial symptoms questionnaire (1984) of 

the International Union Against Tuberculosis and 

Lung Disease. Int J Epidemiol 1989;18(1):165-73. 

 32. Ferris BG. Epidemiology Standardization Project 

(American Thoracic Society). Am Rev Respir Dis 

1978;118(6 Pt 2):1-120. 

 33. Cotes JE. Medical Research Council 

Questionnaire on Respiratory Symptoms (1986). 

Lancet 1987;2:1028. 

 34. Anees W, Gannon PF, Huggins V et al. Effect of 

Peak Expiratory Flow Data Quantity on 

Diagnostic Sensitivity and Specificity in 

Occupational Asthma. Eur Respir J 

2004;23(5):370-4. 

 35. Liss GM, Tarlo SM. Peak expiratory flow rates in 

possible occupational asthma. Chest 

1991;100(1):63-9. 

 36. Cote J, Kennedy S, Chan-Yeung M. Sensitivity 

and specificity of PC20 and peak expiratory flow 

rate in cedar asthma. J Allergy Clin Immunol 

1990;85(3):592-8. 

 37. American Thoracic Society. Medical Section of the 

American Lung Association. Guidelines for the 

evaluation of impairment/disability in patients with 

asthma. Am Rev Respir Dis 1993;147:1056-61. 

 38. Crapo RO, Casaburi R, Coates AL et al. Guidelines 

for methacholine and exercise challenge testing-1999. 

Am J Respir Crit Care Med 2000;161:309-29. 

 39. Dreborg S. Bronchial hyper-reactivity and skin 

sensitivity. Clin Exp Allergy 1991;21(5):529. 

 40. Kuschner WG, Chitkara RK, Sarinas PS. Occupational 

asthma. Practical points for diagnosis and 

management. West J Med 1998;169(6):342-50. 

 41. Newman Taylor AJ, Nicholson PJ (Editors). 

Guidelines for the prevention, identification, and 

management of occupational asthma: Evidence review 

and recommendations. British Occupational Health 

Research Foundation. London 2004. 

 42. Kharitonov SA, Yates D, Robbins RA et al. Increased 

nitric oxide in exhaled air of asthmatic patients. 

Lancet 1994;343:133-5. 

 43. Obata H, Dittrick M, Chan H et al. Sputum 

eosinophils and exhaled nitric oxide during late 

asthmatic reactions in patients with western red cedar 

asthma. Eur Respir J 1999;13(3):489-95. 

 44. Kharitonov SA, Yates DH, Barnes PJ. Inhaled 

glucocorticoids decrease nitric oxide in exhaled air of 

asthmatic patients. Am J Respir Crit Care Med 

1996;153(1):454-7. 

 45. Belda J, Leigh R, Parameswaran K et al. Induced 

sputum cell counts in healthy adults. Am J Respir Crit 

Care Med 2000;161:475-8. 

 46. Pizzichini E, Pizzichini MM, Efthimiadis A et al. 

Indices of airway inflammation in induced sputum: 

reproducibility and validity of cell and fluid-phase 

measurements. Am J Respir Crit Care Med 

1996;154:307-17. 

 47. Vlachos-Mayer H, Leigh R, Sharon RF et al. Success 

and safety of sputum induction in the clinical setting. 

Eur Respir J 2000;16:997-1000. 

 48. Gibson PG. How to measure airway inflammation: 

induced sputum. Can Respir J 1998;5(Suppl A):22A6A. 

 49. Lam S, LeRiche J, Phillips D et al. Cellular and 

protein changes in bronchial lavage fluid after late 

asthmatic reaction in patients with red cedar asthma. J 

Allergy Clin Immunol 1987;80(1):44-50. 
73

 50. Marabini A, Dimich-Ward H, Kwan SY et al. 

Clinical and socioeconomic features of subjects 

with red cedar asthma. A follow-up study. Chest 

1993;104(3):821-4. 

 51. United States of America. American with 

Disabilities Act of 1990. 1990;Pub. L.:101-336. 

 52. Martyny J, Glazer CS, Newman LS. Respiratory 

protection. N Engl J Med 2002;347(11):824-30. 

 53. Ortega HG, Kreiss K, Schill DP et al. Fatal 

asthma from powdering shark cartilage and 

review of fatal occupational asthma literature. Am 

J Ind Med 2002;42(1):50-4. 

 54. Tarlo SM, Boulet LP, Cartier A et al. Canadian 

Thoracic Society guidelines for occupational 

asthma. Can Respir J 1998;5(4):289-300. 

 55. Lin FJ, Dimich-Ward H, Chan-Yeung M. 

Longitudinal decline in lung function in patients 

with occupational asthma due to western red 

cedar. Occup Environ Med 1996;53(11):753-6. 

 56. Pisati G, Zedda S. Outcome of occupational 

asthma due to cobalt hypersensitivity. Sci Total 

Environ 1994;150(1-3):167-71. 

 57. Ameille J, Pairon JC, Bayeux MC et al. 

Consequences of occupational asthma on 

employment and financial status: a follow-up 

study. Eur Respir J 1997;10(1):55-8. 

 58. Gannon PF, Weir DC, Robertson AS et al. Health, 

employment, and financial outcomes in workers 

with occupational asthma. Br J Ind Med 

1993;50(6):491-6. 

 59. Dewitte JD, Chan-Yeung M, Malo JL. 

Medicolegal and compensation aspects of 

occupational asthma. Eur Respir J 1994;7:969-

80. 

 60. Walters EH, Walters JA, Gibson M. Inhaled long 

acting beta agonists for stable chronic asthma. 

The Cochrane Database of Systematic Reviews 

2004, Issue 4. Published by John Wiley & Sons, 

Ltd. 

 61. Westby M, Benson M, Gibson P. Anticholinergic 

agents for chronic asthma in adults. The Cochrane 

Database of Systematic Reviews 2004, Issue 4. 

Published by John Wiley & Sons, Ltd. 

 62. National Asthma Council Australia. Asthma 

Management Handbook 2002. 2002. 

 63. The British Thoracic Society SIGN. British 

Guideline on the Management of Asthma. 

Thorax, i1-94. 2003. London & Edinburgh, UK, 

Scottish Intercollegiate Guidelines Network. 

 64. Boulet LP, Becker A, Berube D et al. Canadian 

asthma consensus report, 1999. CMAJ 161[11 Suppl], 

s1-s62. 1999. 

 65. New Zealand Guidelines Group. The diagnosis and 

treatment of adult asthma. 2002. Wellington, NZ, 

2002 New Zealands Guidelines Group. 

 66. National Institutes of Health. Global Initiative for 

Asthma: Global Strategy for Asthma Management and 

Prevention. NHLBI/WHO Workshop. 1995. National 

Heart, Lung, and Blood Institute (U.S.) World Health 

Organization. 

 67. Keistinen T. Long-term management of asthma 

(Finnish Medical Society). P06031 (006.031), 1-9. 

2001. Duodecim Medical Publications Ltd. 

 68. Williams SG, Schmidt DK, Redd SC et al. 

Recommendations of the National Asthma Education 

and Prevention Program. 1-14. 2003. National Center 

for Environmental Health;National Heart, Lung, and 

Blood Institute. 

 69. North of England Evidence Based Guideline 

Development project. The primary care management 

of asthma in adults. Centre for Health Services 

Research at the University of Newcastle upon Tyne 

1999;99. 

 70. Lijmer JG, Mol BW, Heisterkamp S et al. Empirical 

evidence of design-related bias in studies of diagnostic 

tests. JAMA 1999;282(11):1061-6. 

 71. Downs SH, Black N. The feasibility of creating a 

checklist for the assessment of the methodological 

quality both of randomized and non-randomised 

studies of health care interventions. J Epidemiol 

Community Health 1998;52(6 ):377-84. 

 72. Jadad AR, Moore RA, Carroll D et al. Assessing the 

quality of reports of randomized clinical trials: is 

blinding necessary? Control Clin Trials 1996;17(1):1-

12. 

 73. Schulz KF, Chalmers I, Hayes RJ et al. Empirical 

evidence of bias. Dimensions of methodological 

quality associated with estimates of treatment effects 

in controlled trials. JAMA 1995;273:408-12. 

 74. Chan-Yeung M, Malo JL. Aetiological agents in 

occupational asthma. Eur Respir J 1994;7(2):346-71. 

 75. Glas AS. The diagnostic odds ratio: a single indicator 

of test performance. J Clin Epidemiol 

2003;56(11):1129-35. 
74

 76. Irwig L, Macaskill P, Glasziou P et al. Metaanalytic methods for diagnostic test accuracy. J 

Clin Epidemiol 1995;48(1):119-30. 

 77. Deeks JJ. Systematic reviews in health care: 

Systematic reviews of evaluations of diagnostic 

and screening tests. BMJ 2001;323(7305):157-62. 

 78. Palczynski C, Walusiak J, Ruta U et al. 

Occupational asthma and rhinitis due to 

glutaraldehyde: changes in nasal lavage fluid after 

specific inhalatory challenge test. Allergy 

2001;56(12):1186-91. 

 79. Lemiere C, Chaboilliez S, Trudeau C et al. 

Characterization of airway inflammation after 

repeated exposures to occupational agents. J 

Allergy Clin Immunol 2000; 106(6):1163-70. 

 80. Ucgun I, Ozdemir N, Metintas M et al. Prevalence 

of occupational asthma among automobile and 

furniture painters in the center of Eskisehir 

(Turkey): the effects of atopy and smoking habits 

on occupational asthma. Allergy 

1998;53(11):1096-100. 

 81. Green RH, Brightling CE, Woltmann G et al. The 

use of induced sputum in the diagnosis of 

occupational asthma. ATS meeting 2001. 

 82. Danks JM, Cromwell O, Buckingham JA et al. 

Toluene-diisocyanate induced asthma: evaluation 

of antibodies in the serum of affected workers 

against a tolyl mono-isocyanate protein conjugate. 

Clin Allergy 1981;11(2):161-8. 

 83. Lemiere C, Pizzichini MM, Balkissoon R et al. 

Diagnosing occupational asthma: use of induced 

sputum. Eur Respir J 1999;13(3):482-8. 

 84. Ulrik CS, Backer V, Skov PG. Usefulness of 

repeated measurements of bronchial 

hyperresponsiveness for the diagnosis of 

occupational asthma. J Asthma 1994;31(1):35-42. 

 85. Jager D, Engelke T, Rennert S et al. [Stepwise 

diagnosis of respiratory latex allergy]. 

Pneumologie 1993;47(8):491-6. 

 86. Park HS, Nahm DH, Suh CH et al. Occupational 

asthma and IgE sensitization to grain dust. J 

Korean Med Sci 1998;13(3):275-80. 

 87. Alvarez MJ, Estrada JL, Gozalo F et al. Oilseed 

rape flour: another allergen causing occupational 

asthma among farmers. Allergy 2001;56(2):185-

8. 

 88. Alvarez MJ, Tabar AI, Quirce S et al. Diversity of 

allergens causing occupational asthma among 

cereal workers as demonstrated by exposure 

procedures. Clin Exp Allergy 1996;26(2):147-53. 

 89. Shirai T, Reshad K, Yoshitomi A et al. Green teainduced asthma: relationship between immunological 

reactivity, specific and non-specific bronchial 

responsiveness. Clin Exp Allergy 2003;33(9):1252-5. 

 90. Sastre J, Fernandez-Nieto M, Novalbos A et al. Need 

for monitoring nonspecific bronchial 

hyperresponsiveness before and after isocyanate 

inhalation challenge. Chest 2003;123(4):1276-9. 

 91. Di Stefano F, Siriruttanapruk S, McCoach J et al. 

Glutaraldehyde: an occupational hazard in the hospital 

setting. Allergy 1999;54(10):1105-9. 

 92. Perrin B, Lagier F, L'Archeveque J et al. Occupational 

asthma: validity of monitoring of peak expiratory flow 

rates and non-allergic bronchial responsiveness as 

compared to specific inhalation challenge. Eur Respir 

J 5, 40-8. 1992. 

 93. Malo JL, Cote J, Cartier A et al. How many times per 

day should peak expiratory flow rates be assessed 

when investigating occupational asthma. Thorax 

1993;48:1211-7. 

 94. Girard F, Chaboillez S, Cartier A et al. An Effective 

Strategy for Diagnosing Occupational Asthma: Use of 

Induced Sputum. Am J Respir Crit Care Med 2004.. 

 95. Perrin B, Malo JL, L'Archeveque J et al. Comparison 

of peak expiratory flow rates and bronchial 

responsiveness with specific inhalation challenges in 

occupational asthma. Am Rev Respir Dis 1990;141. 

 96. Cote J, Kennedy S, Chan-Yeung M. Quantitative 

versus qualitative analysis of peak expiratory flow in 

occupational asthma. Thorax 1993;48(1):48-51. 

 97. Munoz X. Validation of specific inhalation challenge 

for the diagnosis of occupational asthma due to 

persulphate salts. Occup Environ Med 

2004;61(10):861-6. 

 98. Huggins V, Hole A, Burge PS et al. Peak expiratory 

flow responses analysed with OASYS in workers 

exposed to detergent enzymes. Eur Respir Soc 2003. 

 99. Burge PS, O'Brien IM, Harries MG. Peak flow rate 

records in the diagnosis of occupational asthma due to 

isocyanates. Thorax 1979;34(3):317-23. 

 100. Cote J, Kennedy S, Chan-Yeung M. Outcome of 

patients with cedar asthma with continuous exposure. 

Am Rev Respir Dis 141, 373-6. 1990. 
75

 101. Burge PS, O'Brien IM, Harries MG. Peak flow 

rate records in the diagnosis of occupational 

asthma due to colophony. Thorax 1979;34:308-

16. 

 102. Curran AD, Burge PS, Wiley K. Clinical and 

immunologic evaluation of workers exposed to 

glutaraldehyde. Allergy 1996;51(11):826-32. 

 103. Behr J, Baur X, Rommelt H et al. [Diagnosis of 

irritative-toxic isocyanate asthma with the 

isocyanate exposure test]. Pneumologie 1990;44 

Suppl 1:229-31. 

 104. Taivainen A, Iivonen E, Kokkarinen J et al. [The 

diagnosis of asthma caused by cow hair 

epithelium]. Duodecim 1994;110( 21):1999-2003. 

 105. Vandenplas O, Van Cangh FB, Brumagne A et al. 

Occupational asthma in symptomatic workers 

exposed to natural rubber latex: evaluation of 

diagnostic procedures. J Allergy Clin Immunol 

2001;107(3):542-7. 

 106. Baur X, Huber H, Degens PO et al. Relation 

between occupational asthma case history, 

bronchial methacholine challenge, and specific 

challenge test in patients with suspected 

occupational asthma. Am J Ind Med 

1998;33(2):114-22. 

 107. La Paglia G, Ruvolo M, Scancarello D et al. 

[Usefulness of specific bronchial provocation 

tests in the diagnosis of compensable 

occupational allergic pneumopathies]. G Ital Med 

Lav 1986;8(3-4):139-44. 

 108. Tarlo SM, Broder I. Outcome of assessments for 

occupational asthma. Chest 100, 329-35. 1991. 

 109. Cote J, Kennedy S, Chan-Yeung M. Sensitivity 

and specificity of PC20 and peak expiratory flow 

rate in cedar asthma. J Allergy Clin Immunol 

1990;85(3):592-8. 

 110. Malo JL, Cartier A. Occupational asthma in 

workers of a pharmaceutical company processing 

spiramycin. Thorax 1988;43:371-7. 

 111. Lemiere C, Chaboillez S, Malo JL et al. Changes 

in sputum cell counts after exposure to 

occupational agents: what do they mean? J 

Allergy Clin Immunol 2001; 107(6):1063-8. 

 112. Obtulowicz K, Laczkowska T, Kolarzyk E et al. 

Obstruction of the small airways in the 

spirometric diagnosis of occupational bronchial 

asthma. J Investig Allergol Clinl Immunol 

1998;8(5):300-3. 

 113. Di Franco A, Vagaggini B, Bacci E et al. Leukocyte 

counts in hypertonic saline-induced sputum in subjects 

with occupational asthma. Respir Med 

1998;92(3):550-7. 

 114. Redlich CA, Homer RJ, Smith BR et al. Immunologic 

responses to isocyanates in sensitized asthmatic 

subjects. Clin Exp Immunol 1996;109(3 Suppl):6S8S. 

 115. Kern DG. Outbreak of the reactive airways 

dysfunction syndrome after a spill of glacial acetic 

acid. Am Rev Respir Dis 1991;144(5):1058-64. 

 116. Piirila PL, Nordman H, Korhonen OS et al. A thirteenyear follow-up of respiratory effects of acute exposure 

to sulfur dioxide. Scand J Work Environ Health 

1996;22(3):191-6. 

 117. Malo JL, Cartier A, Cote J et al. Influence of inhaled 

steroids on recovery from occupational asthma after 

cessation of exposure: an 18-month double-blind 

crossover study. Am J Respir Crit Care Med 

1996;153(3):953-60. 

 118. Malo JL, Perrin B, L'Archeveque J et al. Effect on an 

inhaled beta-2 adrenergic agent on late asthmatic 

reactions due to occupational agents. Rev Mal Resp 

1994;11:479-84. 

 119. Mueller-Wening D, Neuhauss M. Protective effect of 

respiratory devices in farmers with occupational 

asthma. Eur Respir J 1998;12 (3):569-72. 

 120. Paggiaro PL, Bacci E, Talini D et al. Atropin does not 

inhibit late asthmatic responses induced by Toluene 

diisocyanate in sensitized subjects. Am Rev Respir 

Dis 1987;136(5):1237-41. 

 121. Armentia A, Martin-Santos JM, Quintero A et al. 

Baker's asthma: prevalence and evaluation of 

immunotherapy with wheat flour extract. Ann Allergy 

1990;65(4):265-72. 

 122. Fabbri LM, Di Giacomo GR, Dal Vecchio L et al. 

Prednisone, indomethacin and airway responsiveness 

in toluene diisocyanate sensitized subjects. Bull Eur 

Physiopathol Respir 1985;21:421-26. 

 123. Vandenplas O, Delwiche JP, Depelchin S et al. Latex 

gloves with a lower protein content reduce bronchial 

reactions in subjects with occupational asthma caused 

by latex. Am J Respir Crit Care Med 1995;151 (3 Pt 

1):887-91. 

 124. Crescioli S, De Marzo N, Boschetto P et al. 

Theophylline inhibits late asthmatic reactions induced 

by toluene diisocyanate in sensitized subjects. Eur J 

Pharmacol - Environ Toxicol Pharmacol Sect 

1992;1(1):45-50. 
76

 125. De Marzo N, Fabbri LM, Crescioli S et al. Dosedependent inhibitory effect of inhaled 

beclomethasone on late asthmatic reactions and 

increased responsiveness to methacholine induced 

by toluene diisocyanate in sensitised subjects. 

Pulm Pharmacol 1988;1(1):15-20. 

 126. Mapp CE, Boschetto P, Dal Vecchio L et al. 

Protective effect of antiasthma drugs on late 

asthmatic reactions and increased airway 

responsiveness induced ty toluene diisocyanate in 

sensitized subjects. Am Rev Respir Dis 

1987;136(6):1403-7. 

 127. Moscato G, Gherson G, Biscaldi G et al. 

Protective effect of nifedipine upon specific 

bronchial responses to isocyanates. G Ital Med 

Lav 1985;5(6):247-50. 

 128. Maestrelli P, De Marzo N, Saetta M et al. Effects 

of inhaled beclomethasone on airway 

responsiveness in occupational asthma. Placebocontrolled study of subjects sensitized to toluene 

diisocyanate. Am Rev Respir Dis 

1993;148(2):407-12. 

 129. Woitowitz HJ, Woitowitz RH. Clinical 

experiences with a new sympathicomimetic 

substance in the provoked attack in occupational 

asthma. Respir 1972;29(5):549-55. 

 130. Paggiaro PL, Bacci E, Paoletti P et al. 

Bronchoalveolar lavage and morphology of the 

airways after cessation of exposure in asthmatic 

subjects sensitized to toluene diisocyanate. Chest 

1990;98(3):536-42. 

 131. Burge PS. Occupational asthma in electronic 

workers caused by colophony fumes: follow-up of 

affected workers. Thorax 1982;37:348-53. 

 132. Malo JL, Cartier A, Ghezzo H et al. Patterns of 

improvement in spirometry, bronchial 

hyperresponsiveness, and specific IgE antibody 

levels after cessation of exposure in occupational 

asthma caused by snow-crab processing. Am Rev 

Respir Dis 1988;138(4):807-12. 

 133. Mapp CE, Corona PC, De Marzo N et al. 

Persistent asthma due to isocyanates. A follow-up 

study of subjects with occupational asthma due to 

toluene diisocyanate (TDI). Am Rev Respir Dis 

1988;137(6):1326-9. 

 134. Allard C, Cartier A, Ghezzo H et al. Occupational 

asthma due to various agents: absence of clinical 

and functional improvement at an interval of four 

or more years after cessation of exposure. Chest 

1989;96(5):1046-9. 

 135. Perfetti L, Cartier A, Ghezzo H et al. Follow-up of 

occupational asthma after removal from or diminution 

of exposure to the responsible agent: relevance of the 

length of the interval from cessation of exposure. 

Chest 1998;114(2):398-403. 

 136. Lemiere C, Cartier A, Dolovich J et al. Outcome of 

specific bronchial responsiveness to occupational 

agents after removal from exposure. Am J Respir Crit 

Care Med 1996;154(2 Pt 1):329-33. 

 137. Pisati G, Baruffini A, Zedda S. Toluene diisocyanate 

induced asthma: Outcome according to persistence or 

cessation of exposure. Br J Ind Med 1993;50(1):60-4. 

 138. Vandenplas O, Jamart J, Delwiche JP et al. 

Occupational asthma caused by natural rubber latex: 

outcome according to cessation or reduction of 

exposure. J Allergy Clin Immunol 2002;109(1):125-

30. 

 139. Rosenberg N, Garnier R, Rousselin X et al. Clinical 

and socio-professional fate of isocyanate-induced 

asthma. Clin Allergy 1987;17(1):55-61. 

 140. Sulotto F, Romano C, Piolatto G et al. [Effects of 

long-term use of inhaled steroids (beclomethasone 

dipropionate) in patients with occupational asthma no 

longer exposed]. Med Lav 1989;80(6):498-505. 

 141. Lozewicz S, Assoufi BK, Hawkins R et al. Outcome 

of asthma induced by isocyanates. Br J Dis Chest 

1987;81(1):14-22. 

 142. Banks DE, Rando RJ, Barkman HW Jr. Persistence of 

toluene diisocyanate-induced asthma despite 

negligible workplace exposures. Chest 

1990;97(1):121-5. 

 143. Lemiere C, Cartier A, Malo JL et al. Persistent 

specific bronchial reactivity to occupational agents in 

workers with normal nonspecific bronchial reactivity. 

Am J Resp Crit Care Med 2000;162(3 Pt 1):976-80. 

 144. Paggiaro PL, Loi AM, Rossi O et al. Follow-up study 

of patients with respiratory disease due to toluene 

diisocyanate. Clin Allergy 1984;14(5):463-9. 

 145. Marabini A, Siracusa A, Stopponi R et al. Outcome of 

occupational asthma in patients with continuous 

exposure - a 3-year longitudinal study during 

pharmacologic treatment. Chest 2003;124(6):2372-6. 

 146. Malo JL, Ghezzo H, L'Archeveque J et al. Late 

asthmatic reactions to occupational sensitizing agents: 

frequency of changes in nonspecific bronchial 

responsiveness and of response to inhaled beta-2 

adrenergic agent. J Allergy Clin Immunol 

1990;85:834-42. 
77

 147. Maghni K, Lemiere C, Ghezzo H et al. Airway 

inflammation after cessation of exposure to agents 

causing occupational asthma. Am J Respir Crit 

Care Med 2004;169(3):367-72. 

 148. Saetta M, Maestrelli P, Turato G et al. Airway 

wall remodeling after cessation of exposure to 

isocyanates in sensitized asthmatic subjects. Am J 

Respir Crit Care Med 1995;151(2 Pt 1):489-94. 

 149. O'Donnell TV, Welford B, Coleman ED. Potroom 

asthma: New Zealand experience and follow-up. 

Am J Ind Med 1989;15(1):43-9. 

 150. Simonsson BG, Sjoberg A, Rolf C et al. Acute 

and long-term airway hyperreactivity in 

aluminum-salt exposed workers with nocturnal 

asthma. Eur J Respir Dis 1985;66(2):105-18. 

 151. Park HS, Yu HJ, Jung KS. Occupational asthma 

caused by chromium. Clin Exp Allergy 

1994;24(7):676-81. 

 152. Taivainen A, Tukiainen O, Terho O et al. 

Powered dust respirator helmets in the prevention 

of occupational asthma among farmers. Scand J 

Work Environ Health 1998;24(6):503-7. 

 153. Paggiaro PL, Vagaggini B, Dente FL et al. 

Bronchial hyperresponsiveness and toluene 

diisocyanate. Long-term change in sensitized 

asthmatic subjects. Chest 1993;103(4):1123-8. 

 154. Gorski P, Kolacinska B, Wittczak T. Analysis of 

the clinical state of patients with occupational 

asthma following cessation of exposure to 

allergens. Occup Med 1999;49(5):285-9. 

 155. Park HS, Nahm DH. Prognostic factors for 

toluene diisocyanate-induced occupational asthma 

after removal from exposure. Clin Exper Allergy 

1997;27(10):1145-50. 

 156. Merget R, Reineke M, Rueckmann A et al. 

Nonspecific and specific bronchial responsiveness 

in occupational asthma caused by platinum salts 

after allergen avoidance. Am J Respir Crit Care 

Med 1994;150(4):1146-9. 

 157. Chan-Yeung M, MacLean L, Paggiaro P. Followup study of 232 patients with occupational asthma 

caused by western red cedar (thuja-plicata). J 

Allergy Clin Immunol 1987;79(5):792-6. 

 158. Barker RD, Harris JM, Welch JA et al. 

Occupational asthma caused by 

tetrachlorophthalic anhydride: a 12-year followup. J Allergy Clin Immunol 1998;101(6 Pt 

1):717-9. 

 159. Sen D, Wiley K, Williams JG. Occupational asthma in 

fruit salad processing. Clin Exp Allergy 

1998;28(3):363-7. 

 160. Virtanen T, Zeiler T, Rautiainen J et al. Immune 

reactivity of cow-asthmatic dairy farmers to the major 

allergen of cow (BDA20) and to other cow-derived 

proteins. The use of purified BDA20 increases the 

performance of diagnostic tests in respiratory cow 

allergy. Clin Exp Allergy 1996;26(2):188-96. 

 161. Chan-Yeung M, LeRiche J, MacLean L et al. 

Comparison of cellular and protein changes in 

bronchial lavage fluid of symptomatic and 

asymptomatic patients with red cedar asthma on 

follow-up examination. Clin Allergy 1988; 18(4):359-

66. 

 162. Chan-Yeung M, Obata H, Dittrick M et al. Airway 

inflammation, exhaled nitric oxide, and severity of 

asthma in patients with western red cedar asthma. Am 

J Respir Crit Care Med 159[5 Pt 1], 1434-8. 1999. 

 163. Harries MG, Burge PS, Samson M et al. Isocyanate 

asthma - respiratory symptoms due to 1,5-naphthylene 

diisocyanate. Thorax 1979;34(6):762-6. 

 164. Gassert TH, Hu H, Kelsey KT et al. Long-term health 

and employment outcomes of occupational asthma and 

their determinants. J Occup Environ Med 

1998;40(5):481-91. 

 165. Munoz X, Cruz MJ, Orriols R et al. Occupational 

asthma due to persulfate salts: diagnosis and followup. Chest 2003;123(6):2124-9. 

 166. Moscato G, Dellabianca A, Perfetti L et al. 

Occupational asthma: A longitudinal study on the 

clinical and socioeconomic outcome after diagnosis. 

Chest 1999;115(1):249-56. 

 167. Bernstein DI, Karnani R, Biagini RE et al. Clinical 

and occupational outcomes in health care workers 

with natural rubber latex allergy. Ann Allergy Asthma 

Immunol 2003;90(2):209-13. 

 168. Chan-Yeung M. Fate of occupational asthma. A 

follow-up study of patients with occupational asthma 

due to western red cedar (Thuja-Plicata). Am Rev 

Respir Dis 1977;116(6):1023-30. 

 169. Orriols R, Drobnic ME, Munoz X et al. [Occupational 

asthma due to isocyanates: a study of 21 patients]. 

Med Clin (Barc) 1999;113(17):659-62. 

 170. Merget R, Schulte A, Gebler A et al. Outcome of 

occupational asthma due to platinum salts after 

transferral to low-exposure areas. Int Arch Occup 

Environ Health 1999;72(1):33-9. 
78

 171. Park HS, Lee SK, Kim HY et al. Specific 

immunoglobulin E and immunoglobulin G 

antibodies to toluene diisocyanate-human serum 

albumin conjugate: Useful markers for predicting 

long-term prognosis in toluene diisocyanateinduced asthma. Clin Exp Allergy 

2002;32(4):551-5. 

 172. Meyer WC. [Prognosis of occupational bronchial 

asthma after change of occupation and 

elimination of antigen (author's transl)]. MMW 

Munch Med Wochenschr 1977;119(11):363-6. 

 173. Venables KM, Topping MD, Nunn AJ et al. 

Immunologic and functional consequences of 

chemical (tetrachlorophthalic anhydride)-induced 

asthma after four years of avoidance of exposure. 

J Allergy Clin Immunol 1987;80(2):212-8. 

 174. Grammer L C, Shaughnessy MA. Study of 

employees with anhydride-induced respiratory 

disease after removal from exposure. J Occup 

Environ Med 1996;38(8):771-4. 

 175. Grammer LC, Shaughnessy MA, Kenamore BD. 

Clinical and immunologic outcome of 42 

individuals with trimellitic anhydride-induced 

immunologic lung disease after transfer to low 

exposure. Allergy Asthma Proc 2000;21(6):355-9. 

 176. Smith TA, Patton J. Health surveillance in 

milling, baking and other food manufacturing 

operations - five years' experience. Occup Med 

(Oxf) 1999;49(3):147-53. 

 177. Slovak AJ, Orr RG, Teasdale EL. Efficacy of the 

helmet respirator in occupational asthma due to 

laboratory animal allergy. Am Ind Hygiene Assoc 

J 1985; 46(8):411-5. 

 178. Laoprasert N, Swanson MC, Jones RT et al. 

Inhalation challenge testing of latex-sensitive 

health care workers and the effectiveness of 

laminar flow HEPA-filtered helmets in reducing 

rhinoconjunctival and asthmatic reactions. J 

Allergy Clin Immunol 1998;102(6 Pt 1):998-

1004. 

 179. Malo JL, Boulet LP, Dewitte JD et al. Quality of 

life of subjects with occupational asthma. J 

Allergy Clin Immunol 1993;91(6):1121-7. 

 180. Carletti AM, Talini D, Carrara M et al. [Specific 

bronchial provocation tests with flour in the 

diagnosis of occupational bronchial asthma]. Med 

Lav 1997;88(5):406-15. 

 181. Cirla AM, Inzoli S, Aresini G et al. [Evaluation of 

the diagnostic criteria in occupational asthma 

caused by isocyanates]. Med Lav 1975;66(1):5-

23. 

 182. Cortona G, Beretta F, Traina G et al. [Preliminary 

investigation in a pharmaceutical industry: bromelininduced pathology (author's transl)]. Med Lav 

1980;1:70-5. 

 183. Mapp CE, Moro G, Fabbri L et al. [Toluene 

diisocyanate-induced asthma: specific and nonspecific bronchial challenge tests (author's transl)]. 

Med Lav 1979;70(3):203-14. 

 184. Mole R, Balletta A. [The significance of acetylcholine 

test in occupational allergic asthma (author's transl)]. 

Lav Um 1977;29(6):188-95. 

 185. Paggiaro PL, Pardi F, Amram D et al. [Validity of a 

specific bronchial provocation test with proteolytic 

enzymes in occupational bronchial asthma caused by 

enzymatic detergents]. G Ital Med Lav 1984;6(5-

6):201-4. 

 186. Paggiaro PL, Loi AM, Campinoti G et al. 

Ipereccitabilita bronchiale specifica e aspecifica 

nell'asma bronchiale da 

isocianati. 1984. Folia Immunol Clin 31:297-303 

 187. Sander I, Degens P, Goldscheid N et al. Divergente 

Prickhauttestergebnisse mit verschiedenen Weizenund Roggenmehlextrakten [German]. AtemwLungenkrkh 2001;27:333-4. 

 188. Schwarting HH. [Diagnostic significance of the 

radioallergosorbent test (RAST) in occupational, 

flour-related asthma. A comparison with previously 

used methods in allergy diagnosis]. Z Hautkr 

1979;54(7):306-8. 

 189. Wurzinger G, Gillich E, Kroneis C. Bakers/millersasthma - Different behaviour in inhalative provocation 

[German]. Atemw-Lungenkrkh 23[Suppl 1], S30-7. 

1997. 

 190. Balland S, Grosclaude M, Jarsaillon E et al. Realistic 

challenge and bronchial hyperreactivity in 

occupational asthma. [French]. J Toxicol Clin Exp 

1989;9(1 BIS):15-23. 

 191. Biot N, Grosclaude M, Meyer JL et al. [Contribution 

of biological tests in the evaluation of professional 

asthma (author's transl)]. [French]. Poumon Coeur 

1980;36(4):257-61. 

 192. Colas M, Grosclaude M, Balland S et al. Value of 

realistic exposure tests in the diagnosis of 

occupational asthma due to exotic woods [French]. 

Rev Pneumol Clin 1985;41(1):39-46. 

 193. Grosclaude M, Kofman J, Perrin-Fayolle M. 

Respiratory functional tests in professional asthma. 

Value of realistic tests. Poumon Coeur 

1980;36(4):249-54. 
79

 194. Duan YY, Et AL. Occupational toluene 

diisocyanate (TDI) asthma inhalation challenge 

test and TDI-HSA skin test and detection of 

specific IgE. Chinese J Tubercul Respir Dis 

1989;12(3):149-52. 

 195. Baur X, Fruhmann G. Papain-induced asthma: 

diagnosis by skin test, RAST and bronchial 

provocation test. Clin Allergy 1979;9(1):75-81. 

 196. Burge PS. Non-specific bronchial hyper-reactivity 

in workers exposed to toluene di-isocyanate, 

diphenyl methane di-isocyanate and colophony. 

Eur J Respir Dis 1982;Suppl 123:91-6. 

 197. Burge PS, Harries MG, Lam WK et al. 

Occupational asthma due to formaldehyde. 

Thorax 1985;40:255-60. 

 198. Coutts IL, Lozewicz S, Dally MB et al. 

Respiratory symptoms related to work in a factory 

manufacturing cimetidine tablets. BMJ (Clin Res 

Ed) 1984;288(6428):1418. 

 199. Davison AG, Britton MG, Forrester JA et al. 

Asthma in merchant seamen and laboratory 

workers caused by allergy to castor beans: 

analysis of allergens. Clin Allergy 1983;13:553-

61. 

 200. Gannon PF, Newton DT, Belcher J et al. 

Development of OASYS-2: a system for the 

analysis of serial measurement of peak expiratory 

flow in workers with suspected occupational 

asthma. Thorax 1996;51(5):484-9. 

 201. Graneek BJ, Durham SR, Newman Taylor AJ. 

Late asthmatic reactions and changes in histamine 

responsiveness provoked by occupational agents 

Bulletin. Eur Physiopathol Respir 

1987;23(6):577-81. 

 202. Harries MG, Burge PS, O'Brien IM. Occupational 

type bronchial provocation tests. Testing with 

soluble antigens by inhalation. Br J Ind Med 

1980;37(3):248-52. 

 203. Howe W, Venables KM, Topping MD et al. 

Tetrachlorophthalic anhydride asthma: evidence 

for specific IgE antibody. J Allergy Clin Immunol 

1983;71(1 Pt 1):5-11. 

 204. Lozewicz S. Occupational asthma due to 

methylcrylate and cyanoacrylates. Thorax 

 1985;40(11):836-9. 

 205. O'Brien IM, Harries MG, Burge PS et al. Toluene 

di-isocyanate-induced asthma. I. Reactions to 

TDI, MDI, HDI and histamine. Clin Allergy 

1979;9:1-6. 

 206. O'Brien IM, Newman-Taylor AJ, Burge PS et al. 

Toluene di-isocyanate-induced asthma. II. Inhalation 

challenge tests and bronchial reactivity studies. Clin 

Allergy 1979;9(1):7-15. 

 207. Slovak AJ. Occupational asthma caused by a plastics 

blowing agent AZO dicarbonamide. Thorax 

1981;36(12):906-9. 

 208. Symington IS, Kerr JW, McLean DA. Type I allergy 

in mushroom soup processors. Clin Allergy 

1981;11:43-7. 

 209. Tee RD, Cullinan P, Welch J et al. Specific IgE to 

isocyanates: A useful diagnostic role in occupational 

asthma. J Allergy Clin Immunol 1998;101(5):709-15. 

 210. Bernstein DI, Cartier A, Cote J et al. Diisocyanate 

antigen-stimulated monocyte chemoattractant protein1 synthesis has greater test efficiency than specific 

antibodies for identification of diisocyanate 

asthma.[see comment]. Am J Respir Crit Care Med 

2002;166(4):445-50. 

 211. Block G, Tse KS, Kijek K et al. Baker's asthma. 

Clinical and immunological studies. Clin Allergy 

1983;13(4):359-70. 

 212. Cartier A, Malo JL, Ghezzo H et al. IgE sensitization 

in snow crab-processing workers. J Allergy Clin 

Immunol 1986;78(2):344-8. 

 213. Cartier A, Malo J L, Dolovich J. Occupational asthma 

in nurses handling psyllium. Clin Allergy 

1987;17(1):1-6. 

 214. Cartier A, Grammer L, Malo J L et al. Specific serum 

antibodies against isocyanates: association with 

occupational asthma. J Allergy Clin Immunol 1989; 

84(4 Pt 1):507-14. 

 215. Ferguson K, Gallie A, Ahmad D et al. Asthma in 

isocyanate workers: How often is it related to 

occupation? J Occup Health Safety - Austr New Zeal 

1996;12(1):31-40. 

 216. Lam S, Wong R, Chan-Yeung M. Nonspecific 

bronchial reactivity in occupational asthma. J Allergy 

Clin Immunol 1979;63:28-34. 

 217. Malo JL, Ghezzo H, L'Archeveque J et al. Is the 

clinical history a satisfactory means of diagnosing 

occupational asthma? Am Rev Respir Dis 

1991;143:528-32. 

 218. Paggiaro PL, Chan-Yeung M. Pattern of specific 

airway response in asthma due to western red cedar 

(Thuja plicata): relationship with length of exposure 

and lung function measurements. Clin Allergy 

1987;17:333-9. 
80

 219. Tse KS, Chan H, Chan-Yeung M . 

Specific IgE antibodies in workers with 

occupational asthma due to western red cedar. 

Clin Allergy 1982;3:249-58. 

 220. De Zotti R, Gubian F, Negro C. [Changes in 

blood eosinophils and nonspecific bronchial 

reactivity after exposure tests to wheat flour and 

TDI]. Med Lav 1996;87(2):152-61. 

 221. Dellabianca A , Omodeo P, Colli MC et al. 

Bronchial responsiveness to ultrasonic "fog" in 

occupational asthma due to low molecular weight 

chemicals. Ann Allergy Asthma Immunol 

1996;77(5):378-84. 

 222. Dente PL, Rossi O, Talini D et al. Bronchial 

hyperresponsiveness and respiratory symptoms in 

toluene di-isocyanate (TDI) induced asthma. Bull 

Eur Physiopathol Respir 1986;22(Suppl 8):A739. 

 223. Mapp CE, Dal Vecchio L, Boschetto P et al. 

Toluene diisocyanate-induced asthma without 

airway hyperresponsiveness. Eur J Respir Dis 

 1986;68(2):89-95. 

 224. Moscato G, Dellabianca A, Corsico A et al. 

Bronchial responsiveness to ultrasonic fog in 

occupational asthma due to diisocyanate. Chest 

1993;104(4):1127-32. 

 225. Paggiaro PL, Cantalupi R, Filieri M et al. 

Bronchial asthma due to inhaled wood dust 

(Tanganyika aningre). Clin Allergy 

1981;11(6):605-10. 

 226. Paggiaro PL, Innocenti A, Bacci E et al. Specific 

bronchial reactivity to toluene diisocyanate: 

relationship with baseline clinical findings. 

Thorax 1986;41:279-82. 

 227. Pezzini A, Riviera A, Paggiaro PL et al. Specific 

IgE antibodies in twenty-eight workers with 

diisocyanate-induced bronchial asthma. Clin 

Allergy 1984;14(5):453-61. 

 228. Ricciardi L, Fedele R, Saitta S et al. Occupational 

asthma due to exposure to iroko wood dust. Ann 

Allergy Asthma Immunol 2003;91(4):393-7. 

 229. Merget R, Heger M, Globisch A et al. 

Quantitative bronchial challenge tests with wheat 

flour dust administered by Spinhaler: Comparison 

with aqueous wheat flour extract inhalation. J 

Allergy Clin Immunol 1997;100(2):199-207. 

 230. Merget R, Dierkes A, Ruckmann A et al. Absence 

of relationship between degree of nonspecific and 

specific bronchial responsiveness in occupational 

asthma due to platinum salts. [German]. Pneumol 

1997;51(4):345-350. 

 231. Schwaiblmair M, Vogelmeier C, Fruhmann G. 

Occupational asthma in hairdressers: results of 

inhalation tests with bleaching powder. Int Arch 

Occup Environ Health 1997;70(6):419-23. 

 232. Vogelmeier C, Baur X, Fruhmann G. Isocyanateinduced asthma: results of inhalation tests with TDI, 

MDI and methacholine. Int Arch Occup Environ 

Health 1991;63(1):9-13. 

 233. Kim H, Kim YD, Choi J. Serioimmunological 

characteristics of Korean workers exposed to toluene 

diisocyanate. Environ Res 1997;75(1):1-6. 

 234. Kim YK, Son JW, Kim HY et al. New occupational 

allergen in citrus farmers: citrus red mite (Panonychus 

citri). Ann Allergy Asthma Immunol 1999;82(2):223-

8. 

 235. Park HS, Kim YJ, Lee MK et al. Occupational asthma 

and IgE antibodies to reactive dyes. Yonsei Med J 

1989;30(3):298-304. 

 236. Park HS, Lee MK, Kim BO et al. Clinical and 

immunologic evaluations of reactive dye-exposed 

workers. J Allergy Clin Immunol 1991;87(3):639-49. 

 237. Park HS, Kim HY, Nahm DH et al. Specific IgG, but 

not specific IgE, antibodies to toluene diisocyanatehuman serum albumin conjugate are associated with 

toluene diisocyanate bronchoprovocation test results. J 

Allergy Clin Immunol 1999; 104(4 Pt 1):847-51. 

 238. Park HS, Kim HY, Suh YJ et al. Alpha amylase is a 

major allergenic component in occupational asthma 

patients caused by porcine pancreatic extract. J 

Asthma 2002;39(6):511-6. 

 239. Hinojosa M, Losada E, Moneo I et al. Occupational 

asthma caused by African maple (Obeche) and Ramin: 

evidence of cross reactivity between these two woods. 

Clin Allergy 1986;16(2):145-53. 

 240. Quirce S, Cuevas M, Diez-Gomez ML et al. 

Respiratory allergy to Aspergillus-derived enzymes in 

bakers' asthma. J Allergy Clin Immunol 1992;90(6 

I):970-8. 

 241. Quirce S, Hinojosa M, Maranon F et al. Identification 

of obeche wood (Triplochiton scleroxylon) allergens 

associated with occupational asthma. J Allergy Clin 

Immunol 2000;106(2):400-1. 

 242. Tabar AI, Alvarez-Puebla MJ, Gomez B et al. 

Diversity of asparagus allergy: clinical and 

immunological features. Clin Exp Allergy 

2004;34(1):131-6. 
81

 243. Avery SB, Stetson DM, Pan PM et al. 

Immunological investigation of individuals with 

toluene diisocyanate asthma. Clin Exp Immunol 

1969;4(5):585-96. 

 244. Butcher BT, O'Neil CE, Reed MA et al. 

Radioallergosorbent testing of toluene 

diisocyanate reactive individuals using ptolyl 

isocyanate antigen. J Allergy Clin Immunol 

1980;66(3):213-6. 

 245. Karol MH, Tollerud DJ, Campbell TP et al. 

Predictive value of airways hyperresponsiveness 

and circulating IgE for identifying types of 

responses to toluene diisocyanate inhalation 

challenge. Am J Respir Crit Care Med 

1994;149(3 Pt 1). 

 246. Moller DR, Gallagher JS, Bernstein DI et al. 

Detection of immunoglobulin E-mediated 

respiratory sensitization in workers exposed to 

hexahydrophthalic anhydride. J Allergy Clin 

Immunol 1985;75(6):663-72. 

 247. Moller DR, Brooks SM, McKay RT et al. Chronic 

asthma due to toluene diisocyanate. Chest 

1986;90(4):494-9. 

 248. Zeiss CR, Patterson R, Pruzansky JJ et al. 

Trimellitic anhydride-induced airway syndromes: 

clinical and immunologic studies. J Allergy Clin 

Immunol 1977; 60(2):96-103. 

 249. Keskinen H, Tupasela O, Tiikkainen U et al. 

Experiences of specific IgE in asthma due to 

diisocyanates. Clin Allergy 1988;18(6):597-604. 

 250. Nordman H, Keskinen H, Tuppurainen M. 

Formaldehyde asthma. Rare or overlooked. J 

Allergy Clin Immunol 1985;75(1 Pt 1):91-9. 

 251. Rasanen L, Kuusisto P, Penttila M et al. 

Comparison of immunologic tests in the diagnosis 

of occupational asthma and rhinitis. Allergy 

1994;49(5):342-7. 

 252. Vanhanen M, Tuomi T, Tupasela O et al. 

Cellulase allergy and challenge tests with 

cellulase using immunologic assessment. Scand J 

Work Environ Health 2000;26(3):250-6. 

 253. Zeiler T, Taivainen A, Mantyjarvi R et al. 

Threshold levels of purified natural Bos d 2 for 

inducing bronchial airway response in asthmatic 

patients. Clin Exp Allergy 2002;32(10):1454-60. 

 254. Choudat D, Fabries JF, Martin JC et al. 

Quantification of the dose of inhaled flour: 

relation with nonspecific bronchial and 

immunological reactivities. Eur Respir J 

1999;14(2):328-34. 

 255. Kopferschmitt-Kubler MC, Frossard N, Rohde G et al. 

Increase in non-specific bronchial 

hyperresponsiveness without specific response to 

isocyanate in isocyanate-induced asthma: a pilot 

study. Respir Med 1998;92(9):1093-8. 

 256. Nielsen J, Welinder H, Schütz A et al. Specific serum 

antibodies against phthalic anhydride in 

occupationally exposed subjects. J Allergy Clin 

Immunol 1988; 82:126-33. 

 257. Prichard MG, Ryan G, Musk AW. Wheat flour 

sensitisation and airways disease in urban bakers. Br J 

Ind Med 1984;41(4):450-4. 

 258. Kongerud J, Soyseth V, Burge PS. Serial 

measurements of peak expiratory flow and 

responsiveness to methacholine in the diagnosis of 

aluminium potroom asthma. Thorax 1992;47:292-7. 

 259. Shirakawa T, Kusaka Y, Fujimura N et al. The 

existence of specific antibodies to cobalt in hard metal 

asthma. Clin Allergy 1988;18:451-60. 

 260. De Zotti R, Gubian F. Asthma and rhinitis in wooding 

workers. Allergy Asthma Proc 1996;17(4):199-203. 

 261. Koskela H, Taivainen A, Tukiainen H et al. Inhalation 

challenge with bovine dander allergens: who needs it? 

Chest 2003;124(1):383-91. 

 262. Krakowiak A, Ruta U, Gorski P et al. Nasal lavage 

fluid examination and rhinomanometry in the 

diagnostics of occupational airway allergy to 

laboratory animals. Int J Occup Med Environ Health 

2003;16(2):125-32. 

 263. Schuermans D, Verbanck S, Vincken W. Role of 

histamine bronchial hyperresponsiveness (BHR) in the 

diagnosis of occupational asthma (OA) to latex. Eur 

Respir Soc 2003. 

 264. Vandenplas O. Prevalence of occupational asthma due 

to latex among hospital personnel. Am J Respir Crit 

Care Med 1995;151(1):54-60. 

 265. Burge PS, Harries MG, O'Brien et al. Bronchial 

provocation studies in workers exposed to the fumes 

of electronic soldering fluxes. Clin Allergy 

1980;10:137-49. 

 266. Larbanois A, Delwiche JP, Jamart J et al. Comparison 

of FEV1 and specific airway conductance in assessing 

airway response to occupational agents. Allergy 

2003;58(12):1256-60. 
82

 267. Merget R, Stollfuss J, Wiewrodt R et al. 

Diagnostic tests in enzyme allergy. J Allergy Clin 

Immunol 1993;92(2):264-77. 

 268. Palczynski C, Walusiak J, Krakowiak A et al. 

Nasal lavage fluid examination in diagnostics of 

occupational allergy to chloramine. Int J Occup 

Med Environ Health 2003;16(3):231-40. 

 269. Venables KM, Dally MB, Burge PS et al. 

Occupational asthma in a steel coating plant. Br J 

Ind Med 1985;42(8):517-524. 

 270. Malo J L, Ghezzo H. Recovery of methacholine 

responsiveness after end of exposure in 

occupational asthma. Am J Respir Crit Care Med 

2004;169(12):1304-7. 

 271. Jyo T, Kodomari Y, Kodomari N et al. 

Therapeutic effect and titers of the specific IgE 

and IgG antibodies in patients with sea squirt 

allergy Hoya asthma under a long-term 

hyposensitization with three sea squirt antigens. J 

Allergy Clin Immunol 1989;83(2 Pt 1):386-93. 

 272. Perfetti L, Hebert J, Lapalme Y et al. Changes in IgEmediated allergy to ubiquitous inhalants after removal 

from or diminution of exposure to the agent causing 

occupational asthma. Clin Exp Allergy 1998;28(1):66-

73. 

 273. Boulet LP, Roberts RS, Dolovich J et al. Prediction of 

late asthmatic responses to inhaled allergen. Clin 

Allergy 1984;14:379-95. 

 274. O’ Byrne PM, Dolovich J, Hargreave FE. Late 

asthmatic responses. Am Rev Respir Dis 

1987;136:740-51. 

 275. Stenton SC, Avery AJ, Walters EH et al. Statistical 

approaches to the identification of late asthmatic 

reactions. Eur Resp J 1994;7:806-12. 

 276. Lemiere C. The use of sputum eosinophils in the 

evaluation of occupational asthma. Curr Opin 

Allergy Clin Immunol 2004;4:81-5. 

 277. Abramson MJ, Puy RM, Weiner JM. Allergen 

immunotherapy for asthma (Cochrane Review). In: 

The Cochrane Library, Issue 2, 2004. Chichester, UK: 

John Wiley & Sons, Ltd.). 
83

Excluded Studies 

Four hundred and sixty-one studies were excluded from the review. Reasons for exclusion 

include: study design (n=164), inappropriate topic (n=124), population (n=63), inadequate data 

(n=58), and no treatment or tests (n=13). The reports of 38 studies were unobtainable at the 

time of this writing and one was realized upon completion of the final report. 

Study Design 

 1. Abramson MJ, Saunders NA, Hensley MJ. 

Analysis of bronchial reactivity in 

epidemiological studies. Thorax 1990;45(12):924-

9. 

 2. Acero S, Alvarez MJ, Garcia BE et al. 

Occupational asthma from natural rubber latex. 

Specific inhalation challenge test and evolution. J 

Investig Allergol Clin Immunol 2003;13(3):155-

61. 

 3. Acero S, Tabar AI, Alvarez MJ et al. 

Occupational asthma and food allergy due to 

carmine. Allergy 1998;53:897-901. 

 4. Agalliu I, Eisen EA, Hauser R et al. Truncating 

the dose range for methacholine challenge tests: 

three occupational studies. J Occup Environ Med 

2003;45(8):841-7. 

 5. Alberts WM. Getting the most from the "gold 

standard". Chest 2003;123(4):987-9. 

 6. Alberts WM, Brooks SM. Occupational Asthma - 

Serious Consequences for Workers and 

Employers. Postgrad Med 1995;97(6):93-104. 

 7. Anconetani JP, Badorrey MI, Monso E et al. 

Occupational asthma caused by persulphates: 

limited usefulness of the measurement of peak 

expiratory flow at work place. Med Clin 

2001;116(9):355-6. 

 8. Anees W. Use of pulmonary function tests in the 

diagnosis of occupational asthma. Ann Allergy 

Asthma Immunol 2003;90(5 Suppl 2):47-51. 

 9. Anonymous. [Normalization of the 

"occupational" specific bronchoreactive tests in 

occupational medicine, Study group of the Italian 

Society of Occupational Medicine and Industrial 

Hygiene] [Italian]. G Ital Med Lav 

1983;5(3):117-21. 

 10. Anonymous. Sputum cell profile: No help in 

occupational asthma (Echo). Occup Environ Med 

2002;59(8):561. 

 11. Bain EI. Perils in the air: Avoiding occupational 

asthma triggers in the workplace. AJN 

2000;100(6):88. 

 12. Banks DE, Barkman HW Jr, Butcher BT et al. 

Absence of hyperresponsiveness to methacholine in 

a worker with methylene diphenyl diisocyanate 

(MDI)-induced asthma. Chest 1986;89(3):389-93. 

 13. Banks DE, Tarlo SM, Masri F et al. 

Bronchoprovocation tests in the diagnosis of 

isocyanate-induced asthma. Chest 

1996;109(5):1370-9. 

 14. Bardana EJ Jr. Meatwrappers' asthma: clinical and 

pathogenetic observations. Book chapter 2 1980;14-

32. 

 15. Bardana EJ Jr. Reactive airways dysfunction 

syndrome (RADS): Guidelines for diagnosis and 

treatment and insight into likely prognosis. Ann 

Allergy Asthma Immunol 1999;83:583-6. 

 16. Barnhart S. Evaluation of impairment and disability 

in occupational lung disease. Occup Med 

1987;2(2):227-41. 

 17. Bascom R, Ford E. Don't just 'do spirometry'--

closing the loop in workplace spirometry programs. 

Occup Med 1992;7(2):347-63. 

 18. Beeson MJ, Dewdney JM, Edwards RG et al. 

Prevalence and diagnosis of laboratory animal 

allergy. Clin Allergy 1983;13:433-42. 

 19. Bernstein DI, Jolly A. Current diagnostic methods 

for diisocyanate induced occupational asthma. Am J 

Ind Med 1999;36(4):459-68. 
84

 20. Brhel P. Principles of diagnosis of occupational 

character of bronchial asthma. Prac Lek 

1997;49(2):93-7. 

 21. Bright P, Burge PS. The diagnosis of occupational 

asthma from serial measurements of lung function 

at and away from work. Thorax 1996;51(8):857-

3. 

 22. Bright P, Burge PS. Occupational lung disease. 

The diagnosis of occupational asthma from serial 

measurements of lung function at and away from 

work. Thorax 1996;51(8):857-3. 

 23. Bright P, Newton DT, Gannon PF et al. OASYS3: improved analysis of serial peak expiratory 

flow in suspected occupational asthma. Monaldi 

Arch Chest Dis 2001;56(3):281-8. 

 24. Brooks SM, Edwards JJ Jr, Apol A et al. An 

epidemiologic study of workers exposed to 

western red cedar and other wood dusts. Chest 

1981;80(Suppl):30S-2S. 

 25. Brooks SM, Weiss MA, Bernstein IL. Reactive 

Airways Dysfunction Syndrome (RADS) 

Persistent asthma syndrome after high level 

irritant exposures. Chest 1985;88(3):376-84. 

 26. Burge PS. Chapter 9: Physiologic assessment of 

occupational asthma. 171-88. 

 27. Burge PS. Occupational asthma due to soft 

soldering fluxes containing colophony (rosin, pine 

resin). Eur J Respir Dis 1982;123(Suppl):65-77. 

 28. Burge PS. Single and serial measurements of lung 

function in the diagnosis of occupational asthma. 

Eur J Respir Dis 1982;63(Supplement 123):47-59. 

 29. Burge PS, Edge G, O'Brien IM et al. 

Occupational asthma in a research centre breeding 

locusts. Clin Allergy 1980;10(4):355-63. 

 30. Burge PS, Pantin CF, Newton DT et al. 

Development of an expert system for the 

interpretation of serial peak expiratory flow 

measurements in the diagnosis of occupational 

asthma. Occup Environ Med 1999;56(11):758-64. 

 31. Bush RK. Assessment and treatment of laboratory 

animal allergy. ILARJ 2001;42(1):55-64. 

 32. Butcher B, Salvaggio JE, O' Neil CE et al. 

Toluene diisocyanate pulmonary disease: 

Immunopharmacologic and mecholyl challenge 

studies. J Allergy Clin Immunol 1977;59(3):223-

7. 

 33. Butcher BT. Inhalation challenge testing with 

toluene diisocyanate. J Allergy Clin Immunol 

1979;64(6 pt 2):655-7. 

 34. Butcher BT. Isocyanate induced asthma. Eur J 

Respir Dis 1982;123(Suppl):78-81. 

 35. Butcher BT, Bernstein IL, Schwartz HJ. Guidelines 

for the clinical evaluation of occupational asthma 

due to small molecular weight chemicals. Report of 

the Subcommittee on the Clinical Evaluation of 

Occupational Asthma due to Small Molecular 

Weight Chemicals. J Allergy Clin Immunol 

1989;84(5 Pt 2):834-8. 

 36. Butcher BT, Karr RM, O'Neil CE et al. Inhalation 

challenge and pharmacologic studies of toluene 

diisocyanate (TDI)-sensitive workers. J Allergy 

Clin Immunol 1979;64(2):146-52. 

 37. Canadian Thoracic Society Ad Hoc Committee on 

Occupational Asthma of the Standards Committee. 

Occupational asthma: Recommendations for 

diagnosis, management, and assessment of 

impairment. CMAJ 1989;140:1029-32. 

 38. Cartier A. Definition and Diagnosis of Occupational 

Asthma. Eur Respir J 1994;7(1):153-60. 

 39. Cartier A. Investigation of occupational asthma. 

Can Respir J 1998;5(Suppl A):71A-6A. 

 40. Cartier A, Bernstein IL, Burge PS et al. Guidelines 

for bronchoprovocation on the investigation of 

occupational asthma. Report of the Subcommittee 

on Bronchoprovocation for Occupational Asthma. J 

Allergy Clin Immunol 1989;84(5 Pt 2):823-9. 

 41. Cartier A, L'Archeveque J, Malo JL. Exposure to a 

sensitizing occupational agent can cause a longlasting increase in bronchial responsiveness to 

histamine in the absence of significant changes in 

airway calibre. J Allergy Clin Immunol 

1986;78:1185-9. 

 42. Cartier A, Malo JL. Chapter 12: Occupational 

challenge tests. 211-33. 

 43. Cartier A, Pineau L, Malo JL. Monitoring of 

maximum expiratory peak flow rates and histamine 

inhalation tests in the investigation of occupational 

asthma. Clin Allergy 1984;14:193-6. 

 44. Chan-Yeung M. Assessment of asthma in the 

workplace. ACCP Consensus Statement. Chest 

1995;108:1084-117. 

 45. Chan-Yeung M. Evaluation of 

impairment/disability in patients with occupational 

asthma. Am Rev Respir Dis 1987;135(4):950-1. 
85

 46. Chan-Yeung M. Immunological and 

nonimmunologic mechanism in asthma due to 

Western red cedar (Thuja plicata). J Allergy Clin 

Immunol 1982;70(32):32-7. 

 47. Chan-Yeung M, Ashley MJ, Corey P et al. A 

respiratory survey of cedar mill workers: 

Prevalence of symptoms and pulmonary function 

abnormalities. J Occup Med 1978;20(5):323-7. 

 48. Chan-Yeung M, Barton GM, McLean L et al. 

Bronchial reactions to western red cedar (Thuja 

plicata). CMAJ 1971;105(1):56-8. 

 49. Clark NM, Evans D, Mellins RB. Patient use of 

peak flow monitoring. Am Rev Respir Dis 

1992;145:722-5. 

 50. Clini E, Vitaca CM, Scalvini S et al. 

Methacholine inhaled challenge: study of 

correlation among different indices expressing the 

result. Monaldi Arch Chest Dis 1996;51(3):194-8. 

 51. Cloutier Y, Lagier F, Cartier A et al. Validation of 

an exposure system to particles for the diagnosis 

of occupational asthma. Chest 1992;102(2):402-7. 

 52. Coeli Mendonca EM, Algranti E, Cruz da Silva 

RC. Occupational asthma - Objective diagnosis 

by peak flow rate records [Portuguese]. G 

Pneumol 1990;16(4):181-6. 

 53. Conner PR. Experience with early detection of 

toluene diisocyanate-associated occupational 

asthma. Appl Occup Environ Hyg 

2002;17(12):856-62. 

 54. Curran AD, Fishwick D. Occupational asthma: 

Research, change and the 30% target. Ann Occup 

Hyg 2003;47(6):433-6. 

 55. De Zotti R, Muran A, Zambon F. Two cases of 

paraoccupational asthma due to toluene 

diisocyanate (TDI). Occup Environ Med 

2000;57(12):837-9. 

 56. Desjardins A, Malo JL, L'Archeveque J et al. 

Occupational IgE-mediated sensitization and 

asthma caused by clam and shrimp. J Allergy 

Clin Immunol 1995;96(5 Pt 1):608-17. 

 57. Dodge R. Sensitivity of methacholine testing in 

occupational asthma. Chest 1986;89(3):324-5. 

 58. Drexler H, Weber A, Letzel S et al. Detection and 

clinical relevance of a type I allergy with 

occupational exposure to hexahydrophthalic 

anhydride and methyltetrahydrophthalic 

anhydride. Int Arch Occup Environ Health 

1994;65(5):279-83. 

 59. Eiser NM, Kerrebijn KF, Quanjer PH. Guidelines 

for standardization of bronchial challenges with 

(nonspecific) bronchoconstricting agents. Bull Eur 

Physiopathol Respir 1983;19:495-515. 

 60. Fabbri LM. Inhalational challenge reactions to 

isocyanates [3]. J Allergy Clin Immunol 

1991;87(2):600. 

 61. Fabbri LM, Danieli D, Crescioli S et al. Fatal 

asthma in a subject sensitized to toluene 

diisocyanate. Am Rev Respir Dis 1988;137:1494-8. 

 62. Fabbri LM, Saetta M, Picotti G et al. Late asthmatic 

reactions, airway inflammation and chronic asthma 

in toluene-diisocyanate-sensitized subjects. 

Respiration 1991;58(Suppl 1):18-21. 

 63. Fitzgerald ST, Hill M, Santamari B et al. Diagnosis 

and management of asthma: occupational health 

nurses' awareness and use of national consensus 

practice guidelines. AAOHN Journal 

1996;44(2):78-83. 

 64. Fitzgerald ST, Huss K, Huss RW. The diagnosis 

and management of asthma: an update. AAOHN 

Journal 1996;44(2):94-104. 

 65. Friedman-Jimenez G, Beckett WS, Szeinuk J et al. 

Clinical evaluation, management, and prevention of 

work-related asthma. Am J Ind Med 2000;37:121-

41. 

 66. Fruhmann G. [Occupational asthma. New findings 

on work related obstructive respiratory diseases 

(author's transl)] German. MMW Munch Med 

Wochenschr 1981;123(8):299-303. 

 67. Fung F, Tappen D, Wood G. Alternaria-associated 

asthma. Appl Occup Environ Hyg 2000;15(12):924-

7. 

 68. Gadon ME, Melius JM, McDonald GJ et al. Newonset asthma after exposure to the steam system 

additive 2-diethylaminoethanol. A descriptive 

study. J Occup Med 1994;36(6):623-6. 

 69. Gannon PFG, Burge PS. Serial peak expiratory flow 

measurement in the diagnosis of occupational 

asthma. Eur Respir J 1997;10(Suppl 24):57s-63s. 

 70. Gerblich AA, Horowitz J, Chester EH et al. A 

proposed standardized method for 

bronchoprovocation tests in toluene diisocyanateinduced asthma. J Allergy Clin Immunol 

1979;64(6 pt 2):658-61. 

 71. Gonsior E. [Significance of the inhalation 

provocation test for the diagnosis of occupational 
86

 allergic bronchial asthma] [German]. Hefte zur 

Unfallheilkunde 1975;(121):536-40. 

 72. Gorski P, Krajewska E. The usefulness of 

functional test of the respiratory system for the 

diagnosis of occupational bronchial asthma. 

Czechoslovakian. Medycyna-Pracy 

1990;41(6):435-8. 

 73. Grammer LC, Patterson R. Immunologic 

evaluation of occupational asthma. In: Bernstein 

IL, Chan-Yeung M, Malo J-L, Bernstein DI, 

editors. Asthma in the Workplace. New York: 

Marcel Dekker Inc;1993:125-43. 

 74. Guidotti TL for The Occupational and 

Environmental Health Committee of the 

American Lung Association of San Diego and 

Imperial Counties. Taking the occupational 

history. Ann Int Med 1983;99:641-51. 

 75. Harber P, Rappaport S. Clinical decision analysis 

in occupational medicine. Choosing the optimal 

FEV1 criterion for diagnosing occupational 

asthma. J Occup Med 1985;27(9):651-8. 

 76. Heaney LG, McCrea P, Buick B et al. Brewer's 

asthma due to malt contamination. Occup Med 

1997;47(7):397-400. 

 77. Hendrick DJ. Diagnostic tests for occupational 

asthma. Am J Respir Crit Care Med 

2002;166(4):436-7. 

 78. Hendrick DJ. Management of occupational 

asthma. Eur Respir J 1994;7:961-8. 

 79. Hendrick DJ, Rando RJ, Lane DJ et al. 

Formaldehyde asthma: Challenge exposure levels 

and fate after 5 years. J Occup Med 

1982;24(11):893-7. 

 80. Jarvis JQ. Occupational Asthma - Diagnosis and 

prognosis. Sem Respir Med 1993;14(3):234-9. 

 81. Karol MH. Respiratory effects of inhaled 

isocyanates. Crit Rev Toxicol 1986;16(4):349-79. 

 82. Karr RM. Bronchoprovocation studies in coffee 

worker's asthma. J Allergy Clin Immunol 

1979;64(6 pt 2):650-4. 

 83. Kimmel SR. Use of the peak flow meter in office 

practice. AFP 1986;34(6):107-11. 

 84. Koper I, Ruff T, Heise D et al. The estimation of 

unspecific and specific provocation by means of 

forced expiratory volume and specific 

conductance in bakers [German]. Atemwegs- und 

Lungenkrankheiten 1990;16(7):265-6. 

 85. Kopferschmitt-Kubler MC, Ameille J, Popin E et al. 

Occupational asthma in France: A 1-yr report of the 

Observatoire National de Asthmes Professionnels 

project. Eur Respir J 2002;19:84-9. 

 86. Kopferschmitt-Kubler MC, Dietemann A, Mahr L 

et al. Significant changes in non-specific 

hyperresponsiveness after negative isocyanate 

bronchial challenge tests in exposed symptomatic 

workers. A504. 

 87. Kurtz KM, Hamilton RG, Adkinson Jr NF. Role 

and application of provocation in the diagnosis of 

occupational latex allergy. Ann Allergy Asthma 

Immunol 1999;83:634-9. 

 88. Kuschner WG, Chitkara RK, Sarinas PSA. 

Occupational asthma: Practical points for diagnosis 

and management. West J Med 1998;169(6):342-50. 

 89. Lemiere C. Persistence of bronchial reactivity to 

occupational agents after removal from exposure 

and identification of associated factors. Ann 

Allergy, Asthma, Immunol 2003;90(Suppl):52-5. 

 90. Lemiere C, Efthimiadis A, Hargreave FE. 

Occupational esosinophilic bronchitis without 

asthma: an unknown occupational airway disease. J 

Allergy Clin Immunol 1997;100:852-3. 

 91. Lemiere C, Malo JL, Boulet M. Reactive airways 

dysfunction syndrome due to chlorine: sequential 

bronchial biopsies and functional assessment. Eur 

Respir J 1997;10:241-4. 

 92. Leroyer C, Perfetti L, Cartier A et al. Can reactive 

airways dysfunction syndrome (RADS) transform 

into occupational asthma due to "sensitization" to 

isocyanates? Thorax 1998;53:152-3. 

 93. Leroyer C, Perfetti L, Trudeau C et al. Comparison 

of serial monitoring of peak expiratory flow and 

FEV1 in the diagnosis of occupational asthma. Am 

J Respir Crit Care Med 1998;158(3):827-32. 

 94. Lewis J, Morgan WKC. Tea asthma: Response to 

specific and non-specific challenges. Br J Ind Med 

1989;46:350-1. 

 95. Lieutier-Colas F, Kopferschmitt MC, Pauli G et al. 

Do bronchial provocation tests correspond to reality 

in asthma patients? [French]. Rev Fr Allergol 

Immunol Clin 2003;43(5):310-3. 

 96. Longbottom JL. Occupational allergy due to animal 

allergens. Clin Immunol Allergy 1984;4(1):19-24. 

 97. Lopez-Rubio A, Rodriguez J, Crespo JF et al. 

Occupational asthma caused by exposure to 
87

 asparagus: Detection of allergens by 

immunoblotting. Allergy 1998;53(12):1216-20. 

 98. Maestrelli P, Saetta M, Mapp C et al. Diagnostic 

basis of occupational asthma. J Investig Allergol 

Clin Immunol 1997;7(5):316-7. 

 99. Malo JL. The case for confirming occupational 

asthma: Why, how much, how far? J Allergy Clin 

Immunol 1993;91(5):967-70. 

 100. Malo JL, Cartier A. Occupational Reactions in the 

Seafood Industry. Clin Rev Allergy 

1993;11(2):223-40. 

 101. Malo JL, Cartier A, Lemiere C et al. Exaggerated 

bronchoconstriction due to inhalation challenges 

with occupational agents. Eur Respir J 

2004;23:300-3. 

 102. Marek W, Marczynski B, Ammon J et al. Blood 

gas changes in comparison to mechanical 

breathing parameters after workplace-related 

provocations with diisocyanates [German]. 

Atemw Lungenkrankh 1994;20(8):454-6 

 103. Marks GB, Salome CM, Woolcock AJ. Asthma 

and allergy associated with occupational exposure 

to ispaghula and senna products in a 

pharmaceutical work force. Am Rev Respir Dis 

1991;144(5):1065-9. 

 104. Merget R, Schultze-Werninghaus G, Bode F et al. 

Quantitative skin prick and bronchial provocation 

tests with platinum salt. Br J Ind Med 

1991;48:830-7. 

 105. Mihalas LS. An approach to the diagnosis of 

occupational asthma. Ann Allergy Asthma 

Immunol 1999;83:577-82. 

 106. Miller MR. Potential problems in peak expiratory 

flow data used to diagnose occupational asthma. 

Occup Med 1996;46(3):239-41. 

 107. Moller DR, Mckay RT, Bernstein IL et al. 

Persistent airways disease caused by toluene 

diisocyanate. Am Rev Respir Dis 

1986;134(1):175-6. 

 108. Moscato G. Features and severity of occupational 

asthma upon diagnosis: an Italian multicentric 

case review. Allergy 2002;57:236-42. 

 109. Moscato G, Galdi E, Perfetti L. Early detection of 

occupational asthma and reactive airways 

dysfunction syndrome. Monaldi Arch Chest Dis 

2000;55(5):66-9. 

 110. Moscato G, Godnic-Cvar J, Maestrelli P et al. 

Statement on self-monitoring of peak expiratory 

flow in the investigation of occupational asthma. 

Allergy 1995;50(9):711-7. 

 111. Moscato G, Malo JL, Bernstein D. Series 

"Controversies in occupational asthma: Diagnosing 

occupational asthma: How, how much, how far? 

Eur Respir J 2003;21:879-85. 

 112. Musk AW, Peach S, Ryan G. Occupational asthma 

in a mineral analysis laboratory. Br J Ind Med 

1988;45:381-6. 

 113. Newman LS. Occupational asthma - diagnosis, 

management, and prevention. Clin Chest Med 

1995;16(4):621-36. 

 114. O'donnell TV. Chemical poisoning and 

occupational asthma: Diagnosis and/or acceptance 

for current compensation. N Z Med J 

1998;111(1074):372-3. 

 115. Paggario PL, Bacci E, Dente FL et al. Prognosis of 

occupational asthma induced by isocyanates. Bull 

Eur Physiopathol Respir 1988;23:565-9. 

 116. Palma-Carlos AG, Palma-Carlos ML. [Relation 

between bronchial sensitivity to provocation tests 

and reaction to later-histamine in asthma] [French]. 

Rev Fr Allergol 1970;10(4):313-25. 

 117. Papenfuss F, Baur X, Kraus G. Allergy to silk 

[German]. Arbeitsmed Sozialmed Umweltmed 

2000;35(7):316-8. 

 118. Park HS, Cho SH, Hong CS et al. Isocyanateinduced occupational asthma in far-east Asia: 

pathogenesis to prognosis. Clin Exp Allergy 

2002;32:198-204. 

 119. Park HS, Cho YS, Park JN et al. Significant 

changes of bronchial responsiveness to 

methacholine after early asthmatic reaction to 

toluene diisocyanate tdi in a tdi-sensitive asthmatic 

worker. J Korean Med Sci 1990;5(4):185-8. 

 120. Picon SJ, Carmona JGB, Del Mar Garces Sotillos 

M. Occupational asthma caused by vetch (Vicia 

sativa). J Allergy Clin Immunol 1991;88(1):135. 

 121. Piirila P, Kanerva L, Alanko K et al. Occupational 

IgE-mediated asthma, rhinoconjunctivitis, and 

contact urticaria caused by Easter lily (Lilium 

longiflorum) and tulip. Allergy 1999;54:273-7. 

 122. Piirila PL, Nordman H, Keskinen HM et al. Longterm follow-up of hexamethylene diisocyanate-, 

biphenylmethane diisocyanate-, and toluene 
88

 diisocyanate-induced asthma. Am J Respir Crit 

Care Med 2000;162(2):516-22. 

 123. Polio JC, Dalphin JC, Simon-Rigaud ML et al. 

The diagnostic value of provocation tests with 

mouldy hay in occupational respiratory disease in 

dairy farmers [French]. Rev Med Interne 

1991;12(Suppl 3):S52. 

 124. Pouchelle C, Dewitte JD, Leroyer C et al. Limit 

of peak-flow in occupational asthma: Concerning 

a case of asthma to formaldehyde [French]. Arch 

Mal Prof 1989;50(8):838-9. 

 125. Quinn TJ, Donham KJ, Merchant JA et al. Peak 

flow as a measure of airway dysfunction in swine 

confinement operators. Chest 1995;107(5):1303-

8. 

 126. Rabajin JT, Cowl CT. A guide to the diagnosis 

and treatment of occupational asthma. Mayo 

Clinic Proceedings 2001;76(6):633-40. 

 127. Redlich CA, Cain H, Wisnewski AV. The 

immunology and prevention of isocyanate 

asthma: A model for low molecular weight 

asthma. Sem Respir Crit Care Med 

1999;20(6):591-9. 

 128. Reed CE. Clinical management when the 

environment can be changed. Chest 1990;98(5 

Suppl):216S-9S. 

 129. Reif VE. [What contribution is made by the 

individual methods of pulmonary function testing 

to the clinical judgment in the evaluation of 

occupational diseases] [German]. Zentralblatt 

Arbeitsmedizin Arbeitsschutz Erogon 

1967;17(8):240-3. 

 130. Renzetti AD Jr, Bleecker ER, Epler GB et al. For 

the American Thoracic Society. Evaluation of 

impairment/disability secondary to respiratory 

disorders. Am Rev Respir Dis 1986;133(6):1205-

9. 

 131. Rischitelli DG. A workers' compensation primer. 

Ann Allergy Asthma Immunol 1999;83:614-7. 

 132. Rosenthal RR. Workshop proceedings on 

bronchoprovocation techniques for the evaluation 

of asthma. J Allergy Clin Immunol 1979;64(6 

Part 2):561-692. 

 133. Saia B, Marcer G, Mastrangelo G. [Specific 

bronchial provocation tests in the diagnosis of 

occupational lung diseases of allergic origin 

(author's transl)] [Italian]. Med Lav 

1980;71(1):48-61. 

 134. Sarlo K. Control of occupational asthma and allergy 

in the detergent industry. Ann Allergy Asthma 

Immunol 2003;90(Suppl):32-4. 

 135. Savonius B, Keskinen H, Tuppurainen M et al. 

Occupational asthma caused by ethanolamines. 

Allergy 1994;49:877-81. 

 136. Schenker MB. Occupational asthma: Eight 

questions physicians often ask. Consultant 1991 

Apr:74-7. 

 137. Schmidt-Nowara WW, Murphy RLH, Atkinson JD. 

Lung function after acute toluene di-isocyanate 

inhalation. Chest 1973;63(6):1039-40. 

 138. Schultze-Werninghaus G, Rust M. Bronchial 

asthma and allergic alveolitis due to occupational 

allergens [German]. Allergolo J 1988;11(11):437-

45. 

 139. Schwartz HJ. Effect of chronic chromolyn sodium 

therapy in a beautician with occupational asthma. J 

Occup Med 1989;31(2):112-4. 

 140. SHP News. Company had a duty to dismiss 

employee suffering from occupational asthma. The 

Safety & Health Practitioner 2002 Dec:3. 

 141. Smith AB, Bernstein DI, Aw TC et al. Occupational 

asthma from inhaled egg protein [erratum appears 

in Am J Med 1988;13(4):527]. Am J Ind Med 

1987;12(2):205-18. 

 142. Smith AB, Brooks SM, Blanchard J et al. Absence 

of airway hyper reactivity to methacholine in a 

worker sensitized to toluene di iso cyanate. J Occup 

Med 1980;22(5):327-31. 

 143. Soderlund N, Rees D, Wasserfall C et al. A survey 

of a small group of workers exposed to toluene diisocyanate. S Afr Med J 1993;83(2):100-3. 

 144. Tabar AI, Alvarez MJ, Acero S et al. Reactive 

Airways Dysfunction Syndrome: Two Case 

Reports. J Investig Allergol Clin Immunol 

1998;8(2):119-22. 

 145. Tabar-Purroy AI, Alvarez-Puebla MJ, Acero-Sainz 

S et al. Carmine (E-120)-Induced Occupational 

Asthma Revisited. J Allergy Clin Immunol 

2003;111(2):415-9. 

 146. Tan R, Spector SL. Diagnostic testing in 

occupational asthma. Ann Allergy Asthma Immunol 

1999;83 (6 Pt 2):587-92. 

 147. Tan RA, Spector SL. Provocation studies in the 

diagnosis of occupational asthma. Immunol Allergy 

Clin North Am 2003;23(2):251-66. 
89

 148. Tarlo SM. Recent advances in occupational 

asthma. Curr Opin Pulm Med 2000;6:145-50. 

 149. Tarlo SM, Boulet LP, Cartier A et al. Canadian 

Thoracic Society guidelines for occupational 

asthma. Can Respir J 1998;5(4):289-300. 

 150. Tarlo SM, Liss G. Highlights of the Canadian 

Thoracic Society guidelines for occupational 

asthma. Can Fam Physician 1999;45:1541-4. 

 151. Tarlo SM, Liss GM. Can medical surveillance 

measures improve the outcome of occupational 

asthma? J Allergy Clin Immunol 

2001;107(4):583-5. 

 152. Tarlo SM, Liss GM. Diisocyanate-induced 

asthma: Diagnosis, prognosis, and effects of 

medical surveillance measures. Appl Occup 

Environ Hyg 2002;17(12):902-8. 

 153. Tee RD, Gordon DJ, Lacey J et al. Occupational 

allergy to the common house fly (Musca 

domestica): Use of immunologic response to 

identify atmospheric allergen. J Allergy Clin 

Immunol 1985;76:826-31. 

 154. Turato G, Saetta M. Why does airway obstruction 

persist in asthma due to low-molecular-weight 

agents? A pathologist's view. Occup Med 

2000;15(2):445-53. 

 155. Vandenplas O, Malo JL. Inhalation challenges 

with agents causing occupational asthma. Eur 

Respir J 1997;10(11):2612-29. 

 156. Vandenplas O, Toren K, Blanc PD. Health and 

socioeconomic impact of work-related asthma. 

Eur Respir J 2003;22(4):689-97. 

 157. Vanderslice R , Bibeault L. Asthma and the 

environment: A physician's guide to resources, 

research and data. Med Health 1999;82(7):255-9. 

 158. Voelker R. Latex-induced asthma among health 

care workers. JAMA 1995;273(10): 764. 

 159. Waldburger R, Hofmann M, Ruegger M et al. Peak 

Flow profile and expert evidence: The significance 

of self-measured peak flow in expert evidence on 

pulmonary function. Schweiz Med Wochenschr 

1992;122(29):1070-8. 

 160. Wallenstein G, Rebohle E, Bergmann I. 

Experiences with the provocative inhalation test in 

occupationally induced allergic diseases of the 

respiratory tract. Allergie u Immunol 1979;25:140-

5. 

 161. Wass U, Belin L, Eriksson NE. Immunological 

specificity of chloramine-T-induced IgE antibodies 

in serum from a sensitized worker. Clin Exp 

Allergy 1989;19:463-71. 

 162. Weiss ST. A framework for assessing impairment 

from asthma. Chest 1990;98(5):225S-31S. 

 163. Weissman DN, Lewis DM. Is specific antibody 

determination diagnostic for asthma attributable to 

low-molecular-weight agents? Occup Med 

2000;15(2):385-97. 

 164. Wittczak T, Walusiak J, Krakowiak A et al. 

Occupational asthma and interstitial cobalt-induced 

changes in a dental technician: A case report 

[Zlozona postac kobaltozy (zmiany srodmiazszowe 

i astma oskrzelowa) u technika dentystycznego: 

Opis przypadku klinicznego] Czechoslovakian. 

Medycyna-Pracy 2003;54(2):159-64. 

Inappropriate Topic 

 1. Abramson MJ, Hensley MJ, Saunders NA et al. 

Evaluation of a new asthma questionnaire. J 

Asthma 1991;28(2):129-39. 

 2. Adams WG. Long-term effects on the health of 

men engaged in the manufacture of toluene 

diisocyanate. Br J Ind Med 1975;32:72-8. 

 3. Alanko K. Farmer's lung--an acute or chronic 

disease? Scand J Respir Dis 

1970;72(Supple):120-6. 

 

 4. Alberts WM. Using inhalation challenge tests to 

evaluate occupational asthma. J Respir Dis 

1999;20(7):464-5. 

 5. Alberts WM, Ramsdell JW. Bronchial provocation 

testing in occupational asthma. Respir Ther 

1983;13(2):41-2. 

 6. Allmers H, Chen Z, Barbinova L et al. Challenge 

from methacholine, natural rubber latex, or 4,4'-

diphenylmethane diisocyanate in workers with 

suspected sensitization affects exhaled nitric oxide 

[change in exhaled NO levels after allergen 
90

challenges]. Int Arch Occup Environ Health 

2000;73(3):181-6. 

 7. American Thoracic Society. Guidelines for the 

evaluation of impairment/disability in patients 

with asthma. Am Rev Respir Dis 1993;147:1056-

61. 

 8. Andersen P, Schonheyder H. Antibodies to hen 

and duck antigens in poultry workers. Clin 

Allergy 1984;14:421-8. 

 9. Anees W, Huggin SV, Burge S. Peak expiratory 

flow records for the diagnosis of occupational 

asthma: the effect of data quantity on diagnostic 

sensitivity and specificity. Eur Respir Society 

2001. 

 10. Anees W, Huggin SV, Pavord ID et al. 

Occupational asthma due to low molecular weight 

agents: eosinophilic and non-eosinophilic 

variants. Thorax 2002;57(3):231-36. 

 11. Anees W, Sibblies S, Spencer S et al. Fev1 

decline in workers with occupational asthma in 

response to continued workplace exposure. 

American Thoracic Society 2002. 

 12. Anibarro B, Fontela JL, De La Hoz F. 

Occupational asthma induced by garlic dust. J 

Allergy Clin Immunol 1997;100(6 Pt 1):734-8. 

 13. Aul DJ, Bhaumik A, Kennedy AL et al. Specific 

IgG response to monomeric and polymeric 

diphenylmethane diisocyanate conjugates in 

subjects with respiratory reactions to isocyanates. 

J Allergy Clin Immunol 1999;103(5 Pt 1):749-55. 

 14. Baldwin DR, Gannon P, Bright P et al. 

Interpretation of occupational peak flow records: 

level of agreement between expert clinicians and 

Oasys-2. Thorax 2002;57(10):860-4. 

 15. Bardy JD, Malo JL, Seguin P et al. Occupational 

asthma and IgE sensitization in a pharmaceutical 

company processing psyllium. Am Rev Respir 

Dis 1987;135(5):1033-8. 

 16. Barker RD, van Tongeren MJ, Harris JM et al. 

Risk factors for bronchial hyperresponsiveness in 

workers exposed to acid anhydrides. Eur Respir J 

2000;15:710-5. 

 17. Baur X. Nasal challenge tests with flour extracts 

[German]. Allergologie 1993;16(12):507-9. 

 18. Baur X, Chen Z, Flagge A et al. EAST and CAP 

specificity for the evaluation of IgE and IgG 

antibodies to diisocyanate-HSA conjugates. Int 

Arch Allergy Immunol 1996;110(4):332-8. 

 19. Belin L, Wass U, Audunsson G et al. Amines: 

Possible causative agents in the development of 

bronchial hyperreactivity in workers manufacturing 

polyurethanes from isocyanates. Br J Ind Med 

1983;40(3):251-7. 

 20. Beritic-Stahuljak D, Valic F, Cigula M et al. 

Aerosol analysis, respiratory function and skin 

sensitivity testing in workers exposed to soft and 

hardwood dust. Arhiv Za Higijenu Rada i 

Toksikologiju 1988;39(4):387-403. 

 21. Bernstein DI, Korbee L, Stauder T et al. The low 

prevalence of occupational asthma and antibodydependent sensitization to diphenylmethane 

diisocyanate in a plant engineered for minimal 

exposure to diisocyanates. J Allergy Clin Immunol 

1993;92:387-96. 

 22. Berren SL, Edwards JH. Antibodies to bird serum 

proteins in confectionery workers exposed to egg 

spray. Clin Allergy 1987;17:405-8. 

 23. Berube D, Cartier A, L'Archeveque J et al. 

Comparison of peak expiratory flow rate and FEV1 

in assessing bronchomotor tone after challenges 

with occupational sensitizers. Chest 

1991;99(4):831-6. 

 24. Bohadana AB, Massin N, Teculescu D et al. 

Tracheal wheezes during methacholine airway 

challenge (MAC) in workers exposed to 

occupational hazards. Respir Med 1994;88(8):581-

7. 

 25. Boschetto P, Fabbri LM, Zocca E et al. Prednisone 

inhibits late asthmatic reactions and airway 

inflammation induced by toluene diisocyanate in 

sensitized subjects. J Allergy Clin Immunol 

1987;80:261-7. 

 26. Brooks SM, Baker DB, Gann PH et al. Cold air 

challenge and platinum skin reactivity in platinum 

refinery workers. Bronchial reactivity precedes skin 

prick response. Chest 1990;97(6):1401-7. 

 27. Brooks SM, McCluskey JD. When to suspect 

reactive airways dysfunction syndrome: preexisting 

asthma rules out the diagnosis of RADS. J Respir 

Dis 2002;23(10):506-14. 

 28. Chai H, Farr RS, Froehlich LA et al. 

Standardization of bronchial inhalation challenge 

procedures. J Allergy Clin Immunol 

1975;56(4):323-7. 

 29. Choudat D, Villette C, Tabka F et al. Dose-response 

to flour in occupational asthma [French]. Arch Mal 

Prof 1998;59(6):417-8. 
91

 30. Cipolla C, Lugo G, Sassi C et al. A new risk of 

occupational disease: allergic asthma and 

rhinoconjunctivitis in persons working with 

beneficial arthropods. Int Arch Occup Environ 

Health 1996;68(2):133-5. 

 31. Cloutier Y, Lagier F, Lemieux R et al. New 

methodology for specific inhalation challenges 

with occupational agents in powder form. Eur 

Respir J 1989;2(8):769-77. 

 32. Conrad E, Lo W, deBoisblanc B et al. Reactive 

airways dysfunction syndrome after exposure to 

dinitrogen tetroxide. South Med J 

1998;91(4):338-42. 

 33. Cross D, Nelson HS. The role of the peak flow 

meter in the diagnosis and management of 

asthma. J Allergy Clin Immunol 1991;87(1):120-

8. 

 34. Cullen MR, Redlich CA, Beckett WS et al. 

Feasibility study of respiratory questionnaire and 

peak flow recordings in autobody shop workers 

exposed to isocyanate-containing spray paint: 

observations and limitations. Occup Med 

1996;46:197-204. 

 35. Curran AD. Flow cytometry in the exploration of 

the physiopathology of occupational lung disease. 

Occup Environ Med 1999;56:742-6. 

 36. Dykewicz MS, Fineman S. Executive summary of 

Joint Task Force Practice Parameters on 

Diagnosis and Management of Rhinitis. Ann 

Allergy Asthma Immunol 1998;81(Part II):463-8. 

 37. Dykewicz MS, Fineman S, Skoner DP et al. 

Diagnosis and management of rhinitis: Complete 

guidelines of the Joint Task Force on Practice 

Parameters in Allergy, Asthma and Immunology. 

Ann Allergy Asthma Immunol 1998;81:478-518. 

 38. Edwards JH, McConnochie K, Trotman DM et al. 

Allergy to inhaled egg material. Clin Allergy 

1983;13(5):427-32. 

 39. Eisen EA, Wegman DH, Louis TA. Effects of 

selection in a prospective study of forced 

expiratory volume in Vermont granite workers. 

Am Rev Respir Dis 1983;128:587-91. 

 40. Enarson DA, Vedal S, Schulzer M et al. Asthma, 

asthmalike symptoms, chronic bronchitis, and the 

degree of bronchial hyperresponsiveness in 

epidemiologic surveys. Am Rev Respir Dis 

1987;136(3):613-7. 

 41. Fabries JF, Choudat D, Wrobel R et al. 

Computerized equipment for the delivery of 

inhaled doses of solid particles in specific bronchial 

challenge. J Aerosol Med 2000;13(1):1-10. 

 42. Finnegan MJ, Little S, Gordon DJ et al. The effect 

of smoking on the development of allergic disease 

and specific immunological responses in a factory 

workforce exposed to humidifier contaminants. Br J 

Ind Med 1991;48(1):30-3. 

 43. Fourgaut G, Popin E, Kopferschmitt MC et al. 

Baker's asthma: Clinical study of 27 cases and the 

need for a decisional algorithm [French]. Rev Fr 

Allergol Immunol Clin 2002;42:633-9. 

 44. Franklin PJ, Goldenberg WS, Ducatman AM et al. 

Too hot to handle: An unusual exposure of HDI in 

specialty painters. Am J Ind Med 2000;37(4):431-7. 

 45. Gautrin D, Boulet LP, Boutet M et al. Is reactive 

airways dysfunction syndrome a variant of 

occupational asthma? J Allergy Clin Immunol 

1994;93:12-22. 

 46. Gautrin D, Ghezzo H, Infante-Rivard C et al. 

Natural history of sensitization, symptoms and 

occupational diseases in apprentices exposed to 

laboratory animals. Eur Respir J 2001;17(5):904-8. 

 47. Godnic-Cvar J , Plavec D, Jovanovic J. Moving 

average - An objective assessment of peak 

expiratory flow rate monitoring records in 

diagnosing occupational asthma. AtemwLungenkrkh Jahrgang 1994;20(Suppl 1):S67-S9. 

 48. Godnic-Cvar J, Plavec D, Somogyi-Zalud E et al. 

Non-specific nasal and bronchial reactivity are not 

correlated in non- asthmatic subjects occupationally 

exposed to irritants and in healthy subjects. Am J 

Ind Med 1999;35(4):426-31. 

 49. Goldstein MF, Veza BA, Dunsky EH et al. 

Comparisons of peak diurnal expiratory flow 

variation, postbronchodilator Fev1 responses, and 

methacholine inhalation challenges in the 

evaluation of suspected asthma. Chest 

2001;119(4):1001-10. 

 50. Gordon SB, Curran AD, Murphy J et al. Screening 

questionnaires for bakers' asthma--are they worth 

the effort? Occup Med 1997;47(6):361-6. 

 51. Gorski P. Nasal provocation test in diagnosis of 

occupational allergy. Int Rev Allergol Clin 

Immunol 2002;8(2):81-6. 

 52. Grammer L, Shaughnessy M, Kenamore B. Utility 

of antibody in identifying individuals who have or 

will develop anhydride-induced respiratory disease. 

Chest 1998;114(4):1199-202. 
92

 53. Grammer LC, Shaughnessy M, Hogan M B et al. 

Value of antibody level in diagnosing anhydrideinduced immunologic respiratory disease. J Lab 

Clin Med 1995;125(5):650-3. 

 54. Grammer LC, Shaughnessy MA, Lowenthal M et 

al. Risk factors for immunologically mediated 

disease in workers with respiratory symptoms 

when exposed to hexahydrophthalic anhydride. J 

Lab Clin Med 1996;127(5):443-7. 

 55. Hadjiliadis D , Khan K, Tarlo SM. Skin test 

responses to latex in an allergy and asthma clinic. 

J Allergy Clin Immunol 1995;96(3):431-2. 

 56. Hankinson JL. Beyond the peak flow meter: 

Newer technologies for determining and 

documenting changes in lung function in the 

workplace. Occup Med 2000;15(2):411-9. 

 57. Harber P, Scanlon PD, do Pico G et al. Role of 

chest physicians in detection and treatment of 

occupational and environmental respiratory 

disease: a practice survey. Chest 1995;107:1156-

61. 

 58. Hargreave FE, Ryan G, Thomson C et al. 

Bronchial responsiveness to histamine or 

methacholine in asthma: measurement and 

clinical significance. Eur J Respir Dis 

1982;121(Suppl):79-88. 

 59. Hendrick DJ. Epidemiological measurement of 

bronchial responsiveness in polyurethane 

workers. Bull Eur Physiopathol Respir 

1987;23(6):555-9. 

 60. Hendrick DJ, Fabbri LM, Hughes JM et al. 

Modification of the methacholine inhalation test 

and its epidemiologic use in polyurethane 

workers. Am Rev Respir Dis 1986;133:600-4. 

 61. Henneberger PK, Stanbury MJ, Trimbath LS et al. 

The use of portable peak flowmeters in the 

surveillance of occupational asthma. Chest 

1991;100(6):1515-21. 

 62. Hollander A, Heederik D, Brunekreef B. Workrelated changes in peak expiratory flow among 

laboratory animal workers. Eur Respir J 

1998;11:929-36. 

 63. Huy T, De Schipper K, Chan-Yeung M et al. 

Grain dust and lung function: Dose-response 

relationships. Am Rev Respir Dis 1991;144:1314-

21. 

 64. Innocenti A, Cirla AM, Pisati G et al. Crossreaction between aromatic isocyanates (TDI and 

 MDI): a specific bronchial provocation test study. 

Clin Allergy 1988;18(4):323-9. 

 65. Iversen M, Pedersen B, Dahl R. Relationship 

between respiratory symptoms and bronchial 

hyperreactivity in pig farmers. Am J Ind Med 

1990;17(1):64-5. 

 66. Jedrychowski W, Jagielsk E, Ksiezyk M. 

[Correlation between FEV 0 75 and FEV 1 0 in the 

populations at 2 different places of employment] 

[Polish]. Przeglad 1971;27(4):314-6. 

 67. Juniper EF, Frith P, Dunnett C et al. Reproducibility 

and comparison of responses to inhaled histamine 

and methacholine. Thorax 1978;33:705-10. 

 68. Karol MH, AlarieY. Antigens which detect IgE 

antibodies in workers sensitive to toluene 

diisocyanate. Clin Allergy 1980;10:101-9. 

 69. Kopferschmitt-Kubler MC, Pauli G. [Specific 

provocation tests] French. Rev Pneumol Clin 

1991;47(4):171-6. 

 70. Kowalska S, Krakowiak A, Sulkowski W et al. 

Nasal lavage, rhinomanometry and rhinoscopy in 

diagnosing occupational airway allergy. 

Otolaryngologia Polska 2001;3:279-86. 

 71. Kurtz JM, Hamilton RG, Schaefer JA et al. A 

hooded exposure chamber method for 

semiquantitative latex aeroallergen challenge. J 

Allergy Clin Immunol 2001;107:178-4. 

 72. Kus J, Krakowka P. The effectiveness of nasal 

provocation tests for the diagnosis of atopic 

bronchial asthma. Allergol Immunopathol 

1983;11(4):233-41. 

 73. Kus L, Milanowski J, Fafrowicz B. [Significance of 

exposure tests in diagnosis of occupational asthma] 

[Polish]. Pneumonol Pol 1990;58(7-8):370-3. 

 74. Lee HS. Serial peak expiratory flow rate 

monitoring: A useful tool in epidemiological studies 

on occupational asthma. Ann Acad Med Singapore 

1994;23(5):725-30. 

 75. Liss GM, Bernstein D, Genesove L et al. 

Assessment of risk factors for IgE-mediated 

sensitization to tetrachlopophthalic anhydride. J 

Allergy Clin Immunol 1993;92:237-47. 

 76. Malo JL, Cartier A, Ghezzo H et al. Compliance 

with peak expiratory flow readings affects the 

within- and between-reader reproducibility of 

interpretation of graphs in subjects investigated for 

occupational asthma. J Allergy Clin Immunol 

1996;98(6 Pt 1):1132-4. 
93

 77. Malo JL, Ghezzo H, Elie R. Occupational asthma 

caused by isocyanates: Patterns of asthmatic 

reactions to increasing day-to-day doses. Am J 

Respir Crit Care Med 1999;159:1879-83. 

 78. Malo JL, L'Archeveque J, Trudeau C et al. Should 

we monitor peak expiratory flow rates or record 

symptoms with a simple diary in the management 

of asthma? J Allergy Clin Immunol 

1993;91(3):702-9. 

 79. Malo JL, Pineau L, Cartier A et al. Reference 

values of the provocative concentrations of 

methacholine that cause 6% and 20% changes in 

forced expiratory volume in 1 second in a normal 

population. Am Rev Respir Dis 1983;128:8-11. 

 80. Malo JL, Trudeau C, Ghezzo H et al. Do subjects 

investigated for occupational asthma through 

serial peak expiratory flow measurements falsify 

their results. J Allergy Clin Immunol 

1995;96(5):601-7. 

 81. Mapp C, Dal Vecchio L, Boschetto P et al. 

Toluene dissocyanate-induced asthma without 

airway hyperresponsiveness. Eur Respir J 

1986;68:89-95. 

 82. Marin-Blazquez MF, Abad IG, Puente PH et al. 

[Occupational asthma] [Spanish]. Atención 

Primaria 1995;15(1):33-5. 

 83. Mastrangelo G, Bombana S, Priante E et al. 

Repeated case-control studies as a method of 

surveillance for asthma in occupations. J Occup 

Environ Med 1997;39(1):51-7. 

 84. Merget R, Caspari C, Dierkes-Globisch A et al. 

Effectiveness of a medical surveillance program 

for the prevention of occupational asthma caused 

by platinum salts: A nested case-control study. J 

Allergy Clin Immunol 2001;107(4):707-12. 

 85. Merget R, Caspari C, Korb-Bangang A et al. 

Spontaneous variability of the bronchial histamine 

reactivity in chemical industry workers 

[German]. Atemwegs- und Lungenkrankheiten 

1994;20(8):441-2. 

 86. Monkare S, Haahtela T, Vilkka V et al. A double 

blind-trial comparing the clinical efficacy of 

DSCG and placebo in prophylaxis of farmer's 

lung.:473. 

 87. Moscato G, Danna P, Dorigo N et al. Effect of 

nifedipine on hyperreactive bronchial responses to 

methacholine. Ann Allergy 1986;56:145-9. 

 88. Navratil M, Lebedova J. Unfavourable reactions 

after inhalations tests in the evaluation of 

occupational character of bronchial asthma. Cheche. 

Prac Lek 1985;37(4):130-2. 

 89. Nemery B, Van Leemputten R, Goemaere E et al. 

Lung-function measurements over 21 days 

shiftwork in steelworkers from a strandcasting 

department. Br J Ind Med 1985;42(9):601-11. 

 90. Nguyen B, Weytjens K, Cloutier Y et al. 

Determinants of the bronchial response to high 

molecular weight occupational agents in a dry 

aerosol form. Eur Respir J 1998;12:885-8. 

 91. Norrish AE, Beasley R, Hodgkinson EJ et al. A 

study of New Zealand wood workers - exposure to 

wood dust, respiratory symptoms, and suspected 

cases of occupational asthma. N Z Med J 

1992;105(934):185-7. 

 92. Oliver LC. Occupational and environmental asthma: 

Legal and ethical aspects of patient management. 

Chest 1990;98(5[Supp]):220S-224S. 

 93. Ortega HG, Weissman DN, Carter DL et al. Use of 

specific inhalation challenge in the evaluation of 

workers at risk for occupational asthma: A survey 

of pulmonary, allergy, and occupational medicine 

residency training programs in the United States 

and Canada. Chest 2002;121(4):1323-28. 

 94. Ostapkovich VE, Pankova VB. [Diagnosis of preasthmatic conditions in workers in chemical plants] 

[Russian]. Vestn Otorinolaringol 1980;(6):64-7. 

 95. Panzani R, Johansson SGO. Results of skin test and 

RAST in allergy to a clinically potent allergen 

(castor bean). Clin Allergy 1986;16:259-66. 

 96. Perdrix A, Gauthier-David F, Romazini S et al. 

Asthme professionnel Intéręt de la débitmétrie de 

longue durée pour l'approche diagnostique 

individuelle [Occupational asthma Interest of a 

longitudinal peak flow trend for an individual 

diagnosis] [French]. Arch Mal Prof 

1992;53(2):103-9. 

 97. Perfetti L, Brame B, Ferrari M et al. Occupational 

asthma (OA) with sensitization to diphenylmethane 

diisocyanate (MDI) presenting at the onset like a 

reactive airways dysfunction syndrome (RADS). 

Am J Ind Med 2003;44:325-8. 

 98. Phillips VL, Goodrich M, Sullivan TJ. Health care 

worker disability due to latex allergy and asthma: A 

cost analysis. Am J Public Health 1999;89(7):1024-

8. 

 99. Pickering CA. Inhalation tests with chemical 

allergens: complex salts of platinum. Proc R Soc 

Med 1972;65(3):272-4. 
94

 100. Piipari R, Keskinen H, Nordman H. Experiences 

of exhaled nitric oxide measurements in 

diagnostics of occupational asthma. Eur Respir 

Society 2001. 

 101. Portengen L, Hollander A, Doekes G et al. Lung 

function decline in laboratory animal workers: 

The role of sensitisation and exposure. Occup 

Environ Med 2003;60(11):870-5. 

 102. Promisloff RA, Lenchner GS, Phan A et al. 

Reactive airway dysfunction syndrome in three 

police officers following a roadside chemical 

spill. Chest 1990;98:928-9. 

 103. Quirce S, Contreras G, Dybuncio A et al. Peak 

expiratory flow monitoring is not a reliable 

method for establishing the diagnosis of 

occupational asthma. Am J Respir Crit Care Med 

1995;152(3):1100-2. 

 104. Revsbech P, Andersen G. Diurnal variation in 

peak expiratory flow rate among grain elevator 

workers. Br J Ind Med 1989;46(8):566-9. 

 105. Ryan G, Dolovich MGB, Roberts RS et al. 

Standardization of inhalation provocation tests: 

Two techniques of aerosol generation and 

inhalation compared. Am Rev Respir Dis 

1981;123:195-9. 

 106. Saak A, Lenaerts-Langanke H, Stresemann E. 

Specific IgE, IgG and IgG4 antibodies in allergic 

asthma due to isocyanate as compared to test 

persons and employees of different occupational 

groups exposed to isocyanate [German]. Zbl 

Arbeitsmed 1996;46(9):326-37. 

 107. Sarlo K, Clark ED, Ryan CA et al. ELISA for 

human IgE antibody to subtilisin A (Alcalase): 

Correlation with RAST and skin test results with 

occupationally exposed individuals. J Allergy 

Clin Immunol 1990;86:393-99. 

 108. Schiller-Fruhwirth I. RADS - Occupational 

irritant-induced asthma - BK 41 [German]. 

Atemw-Lungenkrkh Jahrgang 2002;28(6):311-3. 

 109. Schultebraucks R, Frank W, Loddenkemper R. 

Investigation of gastransfer in non-specific 

bronchial challenge [German]. Pneumologie 

1990;44(1):362-3. 

 110. Shapiro SM, Hendler JM, Ogirala RG et al. An 

evaluation of the accuracy of Assess and MiniWright peak flowmeters. Chest 1991;99:358-62. 

 111. Sheffer A, Taggart V. The National Asthma 

Education Program: Expert panel report 

 guidelines for the diagnosis and management of 

asthma. Med Care 1993;31(3):MS20-28 Suppl. 

 112. Tarlo SM, Easty A, Eubanks K et al. Outcomes of a 

natural rubber latex control program in an Ontario 

teaching hospital. J Allergy Clin Immunol 

2001;108:628-33. 

 113. Townley RG, Bewtra AK, Nair NM et al. 

Methacholine inhalation challenge studies. J 

Allergy Clin Immunol 1979;64(6, pt 2):569-74. 

 114. Vandenplas O, Cartier A, Ghezzo H et al. Response 

to isocyanates: Effect of concentration, duration of 

exposure and dose. Am Rev Respir Dis 

1993;147:1290-3. 

 115. Vandenplas O , Delwiche JP, Jamart J et al. 

Increase in non-specific bronchial 

hyperresponsiveness as an early marker of bronchial 

response to occupational agents during inhalation 

challenges. Thorax 1996;51:472-8. 

 116. Vandenplas O , Malo JL, Cartier A et al. Closedcircuit methodology for inhalation challenge tests 

with isocyanates. Am Rev Respir Dis 

1992;145(3):582-7. 

 117. Vedal S, Chan-Yeung M, Enarson D et al. 

Symptoms and pulmonary function in western red 

cedar workers related to duration of employment 

and dust exposure. Arch Environ Health 

1986;41(3):179-83. 

 118. Venables KM, Burge PS, Davison AG et al. Peak 

flow rate records in surveys: Reproducibility of 

observers' reports. Thorax 1984;39:828-32. 

 119. Wass U, Belin L. Immunologic specificity of 

isocyanate-induced IgE antibodies in serum from 10 

sensitized workers. J Allergy Clin Immunol 

1989;83:126-35. 

 120. Wass U, Nilssn R, Nordinder R et al. An optimized 

assay of specific IgE antibodies to reactive dyes and 

studies of immunologic responses in exposed 

workers. J Allergy Clin Immunol 1990;85:642-8. 

 121. Wergeland E, Lund E, Waage JE. Respiratory 

dysfunction after potroom asthma. Am J Ind Med 

1987;11(6):627-36. 

 122. Weytjens K, Malo JL, Cartier A et al. Comparison 

of peak expiratory flows and FEV1 in assessing 

immediate asthmatic reactions due to occupational 

agents. Allergy 1999;54(6):621-5. 
95

 123. Winck JC, Delgado L, Vanzeller M et al. 

Monitoring of Peak Expiratory Flow Rates in 

Cork Workers' Occupational Asthma. J Asthma 

2001;38(4):357-62. 

 124. Zock JP, Brederode D, Heederik D. Between- and 

within-observer agreement for expert judgment of 

peak flow graphs from a working population. J 

Occup Environ Med 1998;40(11):969-72. 

Population 

 1. Alexandersson R, Hedenstierna G. Pulmonary 

function in wood workers exposed to formaldehyde: 

A prospective study. Arch Environ Health 

1989;44(1):5-11. 

 2. Amaducci S, Arossa W, Mastrangelo G et al. 

[Survey on the sensitivity and reproducibility of 

forced expiration indices used in epidemiological 

investigations of obstructive lung disease carried out 

at local occupational health centres (author's transl)] 

[Italian]. Med Lav 1979;70(4):266-75. 

 3. Ameille J, Villoingt L. [Valeur pronostique de 

l'hyperréactivité bronchique chez des peintres 

automobiles exposés aux isocyanates] Prognostic 

value of bronchial hyperresponsiveness in car 

painters exposed to isocyanates [French]. Arch Mal 

Prof 1994;55(5):317-21. 

 4. Baldo BA, Krilis S, Wrigley CW. Hypersensitivity 

to inhaled flour allergens. Ann Allergy 1980;35:45-

56. 

 5. Baur X, Czuppo A. Diagnostic validation of specific 

IgE antibody concentrations, skin prick testing, and 

challenge tests in chemical workers with symptoms 

of sensitivity to different anhydrides. J Allergy Clin 

Immunol 1995;96:489-94. 

 6. Baur X, Konig G, Bencze K et al. Clinical 

symptoms and results of skin test, RAST and 

bronchial provocation test in thirty-three papain 

workers: evidence for strong immunogenic potency 

and clinically relevant 'proteolytic effects of 

airborne papain’. Clin Allergy 1982;12(1):9-17. 

 7. Belin LGA, Norman PS. Diagnostic tests in the skin 

and serum of workers sensitized to Bacillus subtilis 

enzymes. Clin Allergy 1977;7:55-68. 

 8. Berlin CM. Challenges in conducting pediatric drug 

trials. J Allergy Clin Immunol 2000;106:S125-27. 

 9. Bernstein DI, Patterson R, Zeiss CR. Clinical and 

immunologic evaluation of trimellitic anhydride-and 

phthalic anhydride-exposed workers using a 

questionnaire with comparative analysis of enzymelinked immunosorbent and radioimmunoassay 

studies. J Allergy Clin Immunol 1982;69(3):311-8. 

10. Bernstein DI, Zeiss CR, Wolkonsky P et al. The 

relationship of total serum IgE and blocking antibody 

in trimellitic anhydride--induced occupational asthma. 

J Allergy Clin Immunol 1983;72(6):714-9. 

11. Bohadana AB, Peslin R, Megherbi SE et al. Doseresponse slope of forced oscillation and forced 

expiratory parameters in bronchial challenge testing. 

Eur Respir J 1999 ;13(2):295-300. 

12. Brisman J, Lillienberg L, Belin L et al. Sensitisation to 

occupational allergens in bakers' asthma and rhinitis: a 

case-referent study. Int Arch Occup Environ Health 

2003;76:167-70. 

13. Burge PS, Finnegan M, Horsefield N et al. 

Occupational asthma in a factory with a contaminated 

humidifier. Thorax 1985;40:248-54. 

14. Chatham M, Bleecker ER, Norman P et al. A 

screening test for airways reactivity: an abbreviated 

methacholine inhalation challenge. Chest 

1982;82(1):15-8. 

15. Cockcroft DW, Berscheid BA. Measurement of 

responsiveness to inhaled histamine: comparison of 

FEV1 and SGaw. Ann Allergy 1983;51:374-7. 

16. Cockcroft DW, Murdock KY, Kirby J et al. Prediction 

of airway responsiveness to allergen from skin 

sensitivity to allergen and airway responsiveness to 

histamine. Am Rev Respir Dis 1987;135:264-7. 

17. de Jong NW, Vermeulen AM, Gerth van Wijk R et al. 

Occupational allergy caused by flowers. Allergy 

1998;53(2):204-9. 

18. Dolovich J, Little DC. Correlates of skin test reactions 

to bacillus-subtilis enzyme preparations. J Allergy 

Clin Immunol 1972;49(1):43-53. 

19. El-Zein M, Malo JL, Infante-Rivard C et al. Incidence 

of probable occupational asthma and changes in 

airway calibre and responsiveness in apprentice 

welders. Eur Respir J 2003;22:513-8. 

20. Gobba F, Ghittori S, Imbriani M et al. Evaluation of 

half-mask respirator protection in styrene-exposed 

workers. Int Arch Occup Environ Health 2000;73:56-

60. 
96

21. Gorski P, Bilewicz P, Krakowiak A. [Objective 

evaluation of respiratory ventilation at work by 

measuring peak expiratory flow rate (PEFR)] 

[Polish]. Medycyna Pracy 1992;43:1-5. 

22. Gorski P, Krakowiak A, Pazdrak K et al. Nasal 

challenge test in the diagnosis of allergic respiratory 

diseases in subjects occupationally exposed to a high 

molecular allergen (flour). Occup Med 

1998;48(2):91-7. 

23. Hadjiliadis D, Banks DE, Tarlo SM. The 

relationship between latex skin prick test responses 

and clinical allergic responses. J Allergy Clin 

Immunol 1996;97(6):1202-6. 

24. Hilvering C, de Vries K, Orie NG. [Farmer's 

lung;respiratory function, allergological and 

serological tests including inhalation tests] [Dutch]. 

Ned Tijdschr Geneeskd 1966;110(29):1297-307. 

25. Huggin SV, Anees W, Blainey D et al. Grain 

workers: relationship between serial peak expiratory 

flow measurements, symptoms and lung function. 

Eur Respir Society 2002. 

26. Ivanova IS. [Allergic skin tests in cotton spinners] 

[Russian]. Gig Tr Prof Zabol 1966;10(5):48. 

27. Karol MH. Concentration-dependent immunologic 

response to toluene diisocyanates (TDI) following 

inhalation exposure. Toxicol Appl Pharmacol 

1983;68:229-41. 

28. Karol MH, Sandberg T, Riley EJ et al. Longitudinal 

study of tolyl-reactive IgE antibodies in workers 

hypersensitive to TDI. J Occup Med 

1979;21(5):354-8. 

29. Karr RM, Lehrer SB, Butcher BT et al. Coffee 

worker's asthma: a clinical appraisal using the 

radioallergosorbent test. J Allergy Clin Immunol 

1978;62(3):143-8. 

30. Kennedy SM, Burrows B, Vedal S et al. 

Methacholine responsiveness among working 

populations: Relationship to smoking and airway 

calibre. Am Rev Respir Dis 1990;142:1377-83. 

31. Kline JN, Jagielo PJ, Watt JL et al. Bronchial 

hyperactivity is associated with enhanced grain dustinduced airflow obstruction. J Appl Physiol 

2000;89:1172-8. 

32. Kongerud J, Rambjor O. The influence of helmet 

respirator on peak flow rate in aluminium potroom. 

Am Ind Hyg Assoc J 1991;52(6):243-8. 

33. Kongerud J, Soyseth V. Methacholine 

responsiveness, respiratory symptoms and 

pulmonary function in aluminium potroom workers. 

Eur Respir J 1991;4(2):159-66. 

34. Kongerud J, Vale JR, Aalen OO. Questionnaire 

reliability and validity for aluminium potroom 

workers. Scand J Work Environ Health 1989;15:364-

70. 

35. Leynadier F, Herman D, Vervloet D et al. Specific 

immunotherapy with a standardized latex extract 

versus placebo in allergic healthcare workers. J 

Allergy Clin Immunol 2000;106:585-90. 

36. Liss GM, Bernstein DI, Moller DR et al. Pulmonary 

and immunologic evaluation of foundery workers 

exposed to methylene diphenyldiisocyanate (MDI). J 

Allergy Clin Immunol 1988;82:55-61. 

37. Losada Cosmes E. Occupational asthma caused by 

enzyme sensitization: Results of a clinical 

questionnaire and of the skin tests [Spanish]. Revista 

Espanola de Alergologia e Inmunologia Clinica 

1991;6(Suppl 3):2-12. 

38. McGarth KG, Roach D, Zeiss CR et al. Four-year 

evaluation of workers exposed to trimellitic anhydride. 

J Occup Med 1984;26(9):671-5. 

39. Meijer E, Grobbee DE, Heederik D. Detection of 

workers sensitised to high molecular weight allergens: 

a diagnostic study in laboratory animal workers. 

Occup Environ Med 2002;59:189-95. 

40. Murray AB, Hardwick DF, Pirie GE et al. Assessing 

the severity of asthma with Wright peak-flow meter. 

Lancet 1977;1:708. 

41. Musk AW, Venables KM, Crook B et al. Respiratory 

symptoms, lung function, and sensitisation to flour in 

a British bakery. Br J Ind Med 1989;46:636-42. 

42. Obase Y, Shimoda T, Mitsuta K et al. Two patients 

with occupational asthma who returned to work with 

dust respirators. Occup Environ Med 2000;57:62-4. 

43. Ofner B, Marelja J. [Bronchial hyperreactivity to 

methacholine in workers in an aluminium electrolysis 

potroom] [Croatian]. Arhiv Za Higijenu Rada i 

Toksikologiju 1986;37(3):301-9. 

44. Ortega HG, Daroowalla F, Petsonk EL et al. 

Respiratory symptoms among crab processing workers 

in Alaska: epidemiological and environmental 

assessment. Am J Ind Med 2001;39:598-607. 

45. Pavlovic M, Spasojevic M, Tasic Z et al. Bronchial 

hyperactivity in bakers and its relation to atopy and 

skin reactivity. Science of the Total Environment 

2001;270:71-5. 
97

46. Pham QT, Mur JM, Massin N et al. Longitudinal 

five year study of respiratory symptoms and 

pulmonary function in truck factory painters 

[Évolution clinique et fonctionnelle respiratoire sur 

une période de cinq ans chez les peintres d'une usine 

de véhicules industriels] French. Arch Mal Prof 

1989;50(5):421-5. 

47. Pien LC, Zeiss CR, Leach CL et al. Antibody 

response to trimellityl hemoglobin in trimellitic 

anhydride-induced lung injury. J Allergy Clin 

Immunol 1988;82:1098-103. 

48. Pisati G, Bernabeo F, Cirla AM. Utilizzo di un test 

di broncostimolazione specifica verso cobalto nella 

diagnosi dell'asma da metalli duri [A bronchial 

challenge test specific for cobalt in the diagnosis of 

asthma due to hard metals]. [Italian] Medicina del 

Lavoro 1986;77(5):538-46. 

49. Pollini G, Biscaldi G, Malamani T et al. Value of 

efficacy of salbutamol aerosol administration by 

intermittent positive pressure breathing in patients 

affected by small airway obstruction. G Ital Med 

Lav 1982;4:107-8. 

50. Raulf-Heimsoth M, Wirtz C, Papenfuss F et al. 

Nasal lavage mediator profile and cellular 

composition of nasal brushing material during latex 

challenge tests. Clin Exp Allergy 2000;30:110-21. 

51. Ryan G, Cookson WO, Musk AW. Allergy and 

nonallergic bronchial reactivity as determinants of 

work-related respiratory symptoms in seasonal grain 

handlers. Chest 1985;87(5):215S. 

52. Saric M, Marelja J. Bronchial hyperreactivity in 

potroom workers and prognosis after stopping 

exposure. Br J Ind Med 191;48:653-5. 

53. Schlunssen V, Schaumburg I, Heederik D et al. 

Indices of asthma among atopic and non-atopic 

woodworkers. Occup Environ Med 2004;61:504-11. 

 

54. Sunyer J, Anto JM, Rodrigo MJ et al. Case-control 

study of serum immunoglobulin-E antibodies reactive 

with soybean in epidemic asthma. Lancet 

1989;1(8631):179-82. 

55. Talini D, Benvenuti A, Carrara M et al. Diagnosis of 

flour-induced occupational asthma in a cross-sectional 

study. Respir Med 2002;96(4):236-43. 

56. Tse KS, Johnson A, Chan H et al. A study of serum 

antibody activity in workers with occupational 

exposure to diphenylmethane diisocyanate. Allergy 

1985;40:314-20. 

57. Vedal S, Chan-Yeung M, Enarson D et al. Plicatic 

acid-specific IgE and nonspecific bronchial 

hyperresponsiveness in western red-cedar workers. J 

Allergy Clin Immunol 1986;78:1103-9. 

58. Vrcelj J. Comparative value of allergen tests and 

immunoglobulin for diagnosing allergic diseases. 

Medicinski Podmladak 1969;21(3-4):21-30. 

59. Walls AF, Longbottom JL. Comparison of rat fur, 

urine, saliva, and other rat allergen extracts by skin 

testing, RAST, and RAST inhibition. J Allergy Clin 

Immunol 1985;75:242-51. 

60. Wieslander G, Norback D, Janson C et al. Validation 

of a self-administered questionnaire on asthmatic 

symptoms and atopy in house painters. J Occup Health 

1997;39(4):331-8. 

61. Zaikov SV, Pukhlik BM, Zaikova AA et al. [The 

diagnosis of allergy to industrial chemical compounds 

using a method of immunothermistometry] [Russian]. 

Likarska Sprava 1996;(3-4):148-50. 

62. Zeiss CR, Leach CL, Smith LJ et al. A serial 

immunologic and histopathologic study of lung injury 

induced by trimellitic anhydride. Am Rev Respir Dis 

1988;137:191-6. 

63. Zetterstrom O. Challenge and exposure test reactions 

to enzyme detergents in subjects sensitized to 

subtilisin. Clin Allergy 1977;7:355-63. 

Inadequate Data 

 1. Adisesh LA, Kharitonov SA, Yates DH et al. 

Exhaled and nasal nitric oxide is increased in 

laboratory animal allergy. Clin Exp Allergy 

1998;28(7):876-80. 

 2. Anees W, Huggin SV, Burge PS. Changes in 

induced sputum in workers with occupational 

asthma one year after initial assessment. Am J Crit 

Care Med 2002;165:8:a524 

 3. Banks DE, Sastre J, Butcher BT et al. Role of 

inhalation challenge testing in the diagnosis of 

isocyanate-induced asthma. Chest 1989;95(2):414-23. 
98

 4. Baur X, Barbinova L. Correlation between bronchial 

hyperreativity and exhaled nitric oxide concentration 

[German]. Atemwegs- und Lungenkrankheiten 

2000;26(8):401-4. 

 5. Baur X, Marczynski B, Barbinova L et al. 

Arbeitspatzbezogene expositionsteste mit dem 

diisocyanat MDI. Atemw Lungenkrkh , 

2001;27(7):346-8. 

 6. Bherer L, Cushman R, Courteau JP et al. Survey of 

construction workers repeatedly exposed to chlorine 

over a three to six month period in a pulpmill: II. 

Follow up of affected workers by questionnaire, 

spirometry, and assessment of bronchial 

responsiveness 18 to 24 months after exposure 

ended. Occup Environ Med 51(4), 225-8. 1994. 

 7. Borchert J. [Observations on the development of 

allergic asthma and allergic rhinitis in bakers] 

[German]. Acta Allergologica 1972;27(3):195-211. 

 8. Boulet LP, Boutet M, Laviolette M et al. Airway 

inflammation after removal from the causal agent in 

occupational asthma due to high and low molecular 

weight agents. Eur Respir J 1994;7:1567-75. 

 9. Bruckner HC, Avery SB, Stetson DM et al. Clinical 

and immunologic appraisal of workers exposed to 

diisocyanates. Arch Environ Health 968;16:619-25. 

10. Burge PS, Edge G, Hawkins R et al. Occupational 

asthma in a factory making flux-cored solder 

containing colophony. Thorax 1981;36:828-34. 

11. Cadrin D, Fedeli U, Gemigani C et al. Follow-up of 

occupational asthma induced by wheat flour. G Ital 

Med Lav 2003;25:207. 

12. Cannon J, Cullinan P, Newman Taylor AJ. 

Consequences of occupational asthma (effect on 

income and employment). BMJ 1995;311:602-3. 

13. Choudat D, Fabries JF, Martin JC et al. Bronchial 

challenge with flour: early response is dependent on 

the dose of activated allergen inhaled. Eur Respir J 

2002;20(2):409-16. 

14. Cocco G, D'Amato G, Liccardi G et al. [The 

bronchial provocation test (BPT) in the diagnosis of 

occupational asthma caused by chemical substances] 

[Italian]. Archivio Monaldi Per la Tisiologia e Le 

Malattie dell'Apparato Respiratorio 1978;33(1-

2):31-8. 

15. Cullinan P, Harris JM, Newman Taylor AJ et al. An 

outbreak of asthma in a modern detergent factory. 

Lancet 2000;356:1899-900. 

 

16. Danks JM, Cromwell O, Buckingham JA et al. 

Toluene-diisocyanate induced asthma: evaluation of 

antibodies in the serum of affected workers against a 

tolyl mono-isocyanate protein conjugate. Clin Allergy 

1981;11(2):161-8. 

17. De Zotti R, Bovenzi M, Negro C et al. Specific 

inhalation challenge with wheat flour in workers with 

suspected baker's asthma. Int Arch Occup Environ 

Health 1999;72(5):335-7. 

18. Di Franco A, Vagaggini B, Bacci E et al. Leukocyte 

counts in hypertonic saline-induced sputum in subjects 

with occupational asthma. Respir Med 

1998;92(3):550-7. 

19. Di Gioacchino M, Cavallucci E, Di Stefano F et al. 

Influence of total IgE and seasonal increase of 

eosinophil cationic protein on bronchial 

hyperreactivity in asthmatic grass-sensitized farmers. 

Allergy 2000;55:1030-4. 

20. Douglas JDM, McSharry C, Blaikie L et al. 

Occupational asthma caused byautomated salmon 

processing. Lancet 1995;346:737-40. 

21. Dueva LA, Grishina TI, Ozhiganova VN. [Specific 

immunological tests with industrial chemical allergens 

in occupational bronchial asthma] [Russian]. Gig Tr 

Prof Zabol 1981;(8):20-3. 

22. Durda M, Skublewski A, Zimecka-Rakowska E et al. 

Results of inhalation tests with the allergen of Erwinia 

herbicola in subjects with occupational exposure to 

organic dust [Czech]. Studia Pneumologica et 

Phtiseologica Cechoslovaca 1989;49(7):419-22. 

23. Fuortes LJ, Kiken S, Makowsky J. An outbreak of 

naphthalene diisocyanate-induced asthma in a plastics 

(factory). Arch Environ Health 1995;50(5):337-40. 

24. Gandevia B, Milne J. Occupational asthma and rhinitis 

due to Western red cedar (Thuja plicata), with special 

reference to bronchial reactivity. Br J Ind Med 

1970;27(3):235-44. 

25. Green RH, Brightling CE, Woltmann G et al. The use 

of induced sputum in the diagnosis of occupational 

asthma. ATS meeting 2001. 

26. Huber H, Allmers H, Ammon J et al. Vergleich von 

methacholintest, arbeismedizinischer asthmaanamnese und spezifischer provokation bei patienten 

mit verdacht auf berufsasthma. Atemw Lungenkrkh 

1996;22(6):314-7. 

27. Kentner M, Hartung M, Thurauf J et al. Zur wertigkeit 

immunologischer und inhalativ-provokativer 

testverfahren in der diagnostik beruflich bedingter 

mehlstauballergien des respirationstraktes [The value 
99

of immunological and inhalation challenge tests in 

the diagnosis of occupational flour allergies of the 

respiratory system]. Prax Klin Pneumol 36(4), 183-

9. 1982. 

28. Larbanois A, Jamart J, Delwiche JP et al. 

Socioeconomic outcome of subjects experiencing 

asthma symptoms at work. Eur Respir J 

2002;19:1107-13. 

29. Lemiere C, Chaboilliez S, Trudeau C et al. 

Characterization of airway inflammation after 

repeated exposures to occupational agents. J Allergy 

Clin Immunol 2000;106(6):1163-70. 

30. Lemiere C, Pizzichini MM, Balkissoon R et al. 

Diagnosing occupational asthma: use of induced 

sputum. Eur Respir J 1999;13(3):482-8. 

31. Lin FJ, Chan-Yeung M. New method for an 

occupational dust challenge test. Occup Environ 

Med 1995;52(1):54-6. 

32. Losada E, Hinojosa M, Quirce S et al. Occupational 

asthma caused by alpha-amylase inhalation: clinical 

and immunologic findings and bronchial response 

patterns. J Allergy Clin Immunol 1992;89:118-25. 

33. Malo JL, Dewitte JD, Cartier A et al. [The Quebec 

system of indemnification for occupational asthma. 

Description, efficacy, and costs]. Rev Mal Respir 

1993;10(4);313-23. 

34. Marabini A, Brugnami G, Curradi F et al. [The 

response to a specific bronchial provocation test and 

the evolution of occupational asthma. A longitudinal 

study in subjects with toluene diisocyanate-induced 

asthma] Italian. Med Lav 1994;85(2):134-41. 

35. Merget R, Caspari C, Kulzer R et al. Effective 

secondary prevention in occupational asthma: 

Results of a prospective study of subjects exposed to 

platinum salts in the manufacture of catalysts over a 

4-year period. Allergische und chemisch-toxische 

Atemw Lungenkrkh 1995;21(8):418. 

36. Merget R, Schultze-Werninghaus G, Muthorst T et 

al. Asthma due to the complex salts of platinum- a 

cross-sectional survey of workers in a platinum 

refinery. Clin Allergy 1988;18:569-80. 

37. Nakladalova M, Fialova J. Reexposure 

bronchoprovocation tests on the working place of 

the patient- proposal of procedure. Alergie 

2000;Suppl 1:38-9. 

38. Padoan M, Pozzato V, Simoni M et al. Long-term 

follow-up of toluene diisocyanate-induced asthma. 

Eur Respir J 2003;21:637-40. 

39. Padoan M, Pozzato V, Zedda L et al. A follow-up 

study of patients with occupational asthma due to 

diisocyanates. Eur Respir J 2003;21(4):637. 

40. Palczynski C, Walusiak J, Ruta U et al. Nasal 

provocation test in the diagnosis of natural rubber 

latex allergy. Allergy 2000;55:34-41. 

41. Palczynski C, Walusiak J, Ruta U et al. Occupational 

asthma and rhinitis due to glutaraldehyde: changes in 

nasal lavage fluid after specific inhalatory challenge 

test. Allergy 2001;56(12):1186-91. 

42. Petrozzino M, Carletti A, Macchioni P et al. 

Increasing duration of exposure and dose during 

challenge test can change the airway response to 

toluendiisocyanates (TDI) in hyperreactive workers. 

Eur Respir J Suppl 1995;Suppl 8:19220S. 

43. Pham QT, Meyer-Bisch C, Mur JM et al. Etude de 

l'evolution clinique et fontionnelle respiratoire sur 5 

ans, d'ouvriers exposes a de faibles teneurs de 

diisocyanate de diphenylmethane. Arch Mal Prof 

1986;47:311-20. 

44. Piipari R, Piirila P, Keskinen H et al. Exhaled nitric 

oxide in specific challenge tests to assess occupational 

asthma. Eur Respir J 2002;20(6):1532-7. 

45. Schwarting HH. [Significance of skin testing in 

allergic occupational asthma] [German]. Hefte zur 

Unfallheilkunde 1975;(121):533-6. 

46. Shirai T, Reshad K, Yoshitomi CK et al. Green teainduced asthma: Skin sensitivity and airway 

responsiveness to epigallocatechin gallate and airway 

responsiveness to methacholine. ATS conference 

Poster 2003. 

47. Sikora R, Harris KE, Kenamore B et al. 

Immunoglobulin E antibody against environmental 

allergens in subjects with trimellitic anhydrideinduced asthma. J Occup Environ Med 

1999;41(3):190-4. 

48. Tarlo SM, Banks D, Liss G et al. Outcome 

determinants for isocyanate induced occupational 

asthma among compensation claimants. Occup 

Environ Med 1997;54:756-61. 

49. Tarlo SM, Liss G, Corey P et al. A workers' 

compensation claim population for occupational 

asthma: comparison of subgroups. Chest 

1995;107(3):634-41. 

50. Topping MD, Forster HW, Ide CW et al. Respiratory 

allergy and specific immunoglobin E and 

immunoglobin G antibodies to reactive dyes used in 

the wool industry. J Occup Med 1989;31(10):857-62. 
100

51. Ucgun I, Ozdemir N, Metintas M et al. Prevalence 

of occupational asthma among automobile and 

furniture painters in the center of Eskisehir 

(Turkey): the effects of atopy and smoking habits on 

occupational asthma. Allergy 1998;53(11):1096-

100. 

52. Ulrik CS, Backer V, Skov PG. Usefulness of 

repeated measurements of bronchial 

hyperresponsiveness for the diagnosis of 

occupational asthma. J Asthma 1994;31(1):35-42. 

53. Valentino M, Pizzichini MA, Monaco F et al. Latexinduced asthma in four healthcare workers in a 

regional hospital. Occup Med 1994;44:161-4. 

54. Venables KM, Davison AG, Newman-Taylor AJ. 

Consequences of occupational asthma. Respiratory 

Medicine 1989;83:437-40. 

55. Wheeler S, Rosenstock SW, Barnhart S. A case series 

of 71 patients referred to a hospital-based occupational 

and environmental medicine clinic for occupational 

asthma. West J Med 1998;168:98-104. 

56. White WG, Morris MJ, Sugden E et al. Isocyanateinduced asthma in a car factory. Lancet 

1980;1(8171):756-60. 

57. Wirtz C, Allmers H, Papenfuss F et al. Nitric oxide in 

expired air - A suitable parameter for the assessment 

of occupation-related inhalation challenge tests? 

[German]. Atemwegs- und Lungenkrankheiten 

1997;23(8):436-7. 

58. Woitowitz HJ, Woitowitz RH. [Occupational allergic 

bronchial asthma. Reliability of inhalation tests] 

[German]. Praxis der Pneumologie Vereinigt Mit der 

Tuberkulosearzt 1971;25(4):185-93. 
101

No Treatment or Tests 

 1. Balland S, Grosclaude M, Jarsaillon E et al. 

[Challenge provocation tests and non-specific 

bronchial hyperactivity in occupational asthma] 

French. J Toxicol Clin Exp 1989;9(1 Suppl Pt 2):15-

23. 

 2. Banauch GI, Alleyne D, Sanchez R et al. Persistent 

hyperreactivity and reactive airway dysfunction in 

firefighters at the World Trade Center. Am J Respir 

Crit Care Med 2003;168(1):54-62. 

 3. Baur X, Dewair M, Fruhmann G. Detection of 

immunologically sensitized isocyanate workers by 

RAST and intracutaneous skin tests. J Allergy Clin 

Immunol 1984;73(5 pt 1):610-8. 

 4. Bernstein DI, Smith AB, Moller DR et al. Clinical 

and immunologic studies among egg-processing 

workers with occupational asthma. J Allergy Clin 

Immunol 1987;80(6):791-7. 

 5. Budanova LF, Makarova VN. [Occupational 

bronchial asthma] Russian. Med Tr Prom Ekol 

1998;11:1-4. 

 6. Cipolla C, Belisario A, Auletti G et al. Studio della 

iperreattivita bronchiale alla metacolina in un 

grouppo di panificatori sensibilizzati alle polveri di 

farina di frumento [Bronchial hyperreactivity to 

methacholine in a group of bakers sensitized to 

wheat flour]. Med Lav 2002;93(1):20-5. 

 7. Fabbri LM, Chiesura-Corona P, Dal Vecchio L et al. 

Prednisone inhibits late asthmatic reactions and the 

associated increase in airway responsiveness induced 

by toluene diisocyanate in sensitized subjects. Am Rev 

Respir Dis 1985;132:1010-4. 

 8. Irsigler GB, Visser PJ, Spangenberg PAL. Asthma and 

chemical bronchitis in Vanadium plant workers. Am J 

Ind Med 1999;35:366-74. 

 9. Kurosawa M, Kobayashi S, Yanagihara Y et al. 

Antigen-induced histamine release from peripheral 

leukocytes of "Konnyaku asthmatic patients". Ann 

Allergy 1990;64(3):319-21. 

10. Prezant DJ, Weiden M, Banauch GI et al. Cough and 

bronchial responsiveness in firefighters at the World 

Trade Center site. N Engl J Med 2002;347(11):806-

15. 

11. Smith AB, Bernstein DI, London MA et al. Evaluation 

of occupational asthma from airborne egg protein 

exposure in multiple settings. Chest 1990;98(2):398-

404. 

12. Thiel H, Zimmermann I, Rasche B et al. Allergenspecific histamine release from whole blood in floursensitive bakers. Respiration 1982;43(3):208-20. 

13. Zedda S, Cirla A, Aresini G et al. Occupational type 

test for the etiological diagnosis of asthma due to 

toluene di-isocyanate. Respiration 1976;33(1):14-21. 

Unobtainable 

 1. al Jarad N. Occupational asthma. J R Coll 

Physicians Lond 1999;33(6):537-40. 

 2. Baur X. Baker's asthma: causes and prevention. Int 

Arch Occup Environ Health 1999;72(5):292-6. 

 3. Baur X, Dorsch W, von Liebe V. [Comparative 

studies between RAST, skin test and inhalation 

provocation test in patients with baker's asthma and 

moniliales asthma] German. Z Hautkr 

1979;54(7):301-5. 

 4. Budanova LF, Makarova VN. [Occupational 

bronchial asthma] Russian. Med Tr Prom Ekol 

1998;11:1-4. 

 5. Burge PS. Prolonged and frequent recordings of peak 

expiratory flow rate in workers with suspected 

occupational asthma due to colophony and 

isocyanates. 1978. 

 6. Davies RJ. Respiratory Hypersensitivity to 

Diisocyanates. Clinics in Immunology and Allergy 

1984;4(1):103-123. 

 7. De Meer G, Heederik D, Postma DS. Bronchial 

responsiveness to adenosine 5'-monophosphate (AMP) 

and methacholine differ in their relationship with 

airway allergy and baseline FEV(1). Am J Respir Crit 

Care Med 2002;165(3):327-31. 

 8. Di Franco A, Giannini D, Kotopulos C et al. Effect of 

inhaled corticosteroids on induced sputum cell counts 
102

in subjects with occupational asthma and persistent 

exposure [abstract]. American Journal of 

Respiratory and Critical Care Medicine 2000;161(3 

Suppl):A761. 

 9. Dueva LA. [Micromodification of the complement 

fixation test with chemical allergens] Russian. Lab 

Delo 1979;7:440-1. 

10. Dueva LA. [Value of immunomodulators in 

complex treatment of occupational 

bronchopulmonary diseases] Russian. Med Tr Prom 

Ekol 2002;12:37-44. 

11. Fleming MJ. Agricultural Health Program. 

12. Hendrick DJ, Lane DJ. Formalin asthma in hospital 

staff. Br Med J 1975;1(5958):607-8. 

13. Hinojosa Macias M. Occupational asthma caused by 

wood. [Spanish]. Revista Espanola de Alergologia e 

Inmunologia Clinica 1991;6(Suppl 3):19-24. 

14. Jyo T, Kuwabara M, Kodomari Y et al. Effects of 

improvements in working conditions on 

occupational asthma. Japanese Journal of 

Allergology 1986;35(10):1003-10. 

15. Kido T, Yamada Y, Teranishi H et al. Toluene di iso 

cyanate asthma 1. clinico allergological tests. 

Japanese Journal of Allergology. 1983;32(2):111-

20. 

16. Kolacinska B, Gorski P. [Clinical state, bronchial 

reactivity and atopic symptoms in patients with 

occupational bronchial asthma 3-4 years after 

cessation of occupational exposure]. [Polish]. 

Medycyna 1996;47(4):347-52. 

17. Kotlinowska T, Obtulowicz K, Lapczuk T. 

Bronchial provocation test (BPT) and skin patch test 

in diagnosis of professional allergy. International 

Review of Allergology & Clinical Immunology 

1996:2(4):142-144. 

18. Lebedova J, Navratil M, Hykes P et al. The role of 

provocation bronchoconstriction test for the 

diagnosis of bronchial asthma in patients examined 

for suspected occupational bronchial asthma. 

Pracovni-Lekarstvi. 1987;39(10):440-2. 

19. Lind P. Biomarkers of aromatic isocyanates in 

exposed workers [dissertation]. Lund, Sweden: 

Lund University;1997. 

20. Mannix ET, Dresser KS, Aukley D et al. 

Cardiopulmonary exercise testing in the evaluation 

of patients with occupational asthma and reactive 

airways dysfunction syndrome. J Investig Med 

1998;46(5):236-42. 

21. May JJ. New York Center for Agricultural Medicine 

& Health Institution. 

22. Mazaeva L, Shmelev E, Aisanov Z. Comparative 

efficacy of different treatment regimens in mild 

asthmatic patients with hypersensitivity to rye and 

wheat. European Respiratory Society Annual 

Congress 2002. 2002;abstract P453. 

23. Merget R, Zachgo W, Schultze-Werninghaus G et al. 

[Quantitative skin test and inhalation provocation test 

in asthma using platinum salts] German. Pneumologie 

1990;44(Suppl 1):226-8. 

24. Moller DR, McKay RTK, Bernstein IL et al. Long 

term follow-up of workers with TDI asthma [abstract]. 

Am Rev Respir Dis 1984;129:A159. 

25. Nakamura S. [Investigation on the long-term 

prognosis of occupational asthma] Japanese. Arerugi 

1990;39(1):12-20. 

26. National Asthma Education Program. US Dept of 

Health and Human Services, National Heart, Lung and 

Blood Institute, National Institutes of Health. 

27. NIOSH. Criteria for a Recommended Standard. 

Occupational exposure to diisocyanates. US Dept of 

Health, Education and Welfare 1978;(PHS CDC 

publication No. 78-215). 

28. Paggiaro PL, Loi AM, Rossi O et al. Outcome of 

specific and nonspecific bronchial challenge tests in 

TDI bronchial asthma. Folia Allergol Immunol Clin 

1983;30(suppl 4):118-22. 

29. Palczynski C, Walusiak J, Wittczak T et al. Specific 

nasal challenge test in the diagnostics of occupational 

asthma and rhinitis due to glutaraldehyde. European 

Respiratory Society 1999. 

30. Park HS, Nahm DH. Isocyanate-induced occupational 

asthma: challenge and immunologic studies. Korean 

Med Sci 1996;11(4):314-8. 

31. Pepys J. Occupational Allergy Due to Platinum 

Complex Salts. Clinics in Immunology and Allergy 

1984;4(1):131-57. 

32. Pepys J, Hutchcroft BJ. Bronchial provocation tests in 

etiologic diagnosis and analysis of asthma. Am Rev 

Respir Dis 1975;112(6):829-59. 

33. Shida T, Mimaki K, Sasaki N et al. Studies on western 

red cedar asthma part 3 a research by inquiry in Oume 

city Tokyo and inhalation tests with nezucone into 

asthma. Japanese Journal of Allergology. 

1971;20:915-21. 
103

34. Soyseth V, Kongerud J, Boe J et al. Bronchial 

responsiveness and work-related asthma in 

aluminium potroom workers: effect of removal from 

exposure. Eur Respir J 1992;5(7):829-33. 

35. Tarlo SM. Occupational allergies and asthma. Can 

Fam Physician 1999;45:1516-22. 

36. Torres Da Costa J, Ferreira JA, Castro E et al. 

Occupational asthma in the cotton textile industry: 

Assessment by bronchial hyperreactivity and peak 

expiratory flow recording. Revista Portuguesa de 

Pneumologia 2002;8(2):115-29. 

37. van der Zee JS, de Jager KS, Kuipers BF et al. 

Outbreak of occupational allergic asthma in a 

Stephanotis floribunda nursery. J Allergy Clin 

Immunol 1999;103(5 Pt 1):950-2. 

38. Zuskin E, Kanceljak B, Mataija M et al. [Specific 

bronchial reactivity in unripe coffee processing 

workers] Croatian. Arh Hig Rada Toksikol 

1989;40(1):3-8. 
104

Addendum 

After the review was completed, the authors were made aware of the following study: 

 1. Sastre J, Fernandez-Nieto M, Rico P et al. Specific immunotherapy with a standardized latex extract in 

allergic workers: a double-blind, placebo-controlled study. J Allergy Clin Immunol 2003;111:985-94. 
105

Abbreviations 

ACCP: American College of Chest Physicians 

AC: Azodicarbonamide 

BHR: Bronchial hyper-responsiveness 

C: Current 

CAP: Developed by Pharmacia Diagnostics for measuring specific IgE 

cbu: Cumulative breath unit 

CCT: Controlled clinical trial 

CI: Confidence intervals 

CO-HSA: Conjugated human serum albumin 

cpm: Counts per minute 

CS: Corticosteroids 

DCP: Diagnostics products corp. 

EAST: Enzyme allergosorbent test 

ECG: Electrocardiogram 

ECP: Eosinophilic cationic protein 

ECSC: European coal and steel community 

ED: Emergency department 

ELISA: Enzyme-linked immuno sorbent assay 

EIB: Exercise-induced bronchoconstriction 

eNO: Exhaled nitric oxide 

Ex: Ex 

FEF: Forced expiratory flow 

FEV1: Forced expiratory volume in one second 

FU: Follow-up 

FVC: Forced vital capacity 

H: High 

HDI: Hexamethylene di-isocyanate 

HHPA: Hexahydrophthalic anhydride 

HMW: High molecular weight 

ICS: Inhaled corticosteroids 

IL-8: Interleukin-8 

IQR: Interquatrile range 

kPa: Kilopascal 

L: Low 

LABA: Long acting beta-agonists 

LKTRA: Leukotriene receptor antagonists 

LMW: Low molecular weight 

LR: Likelihood ratios 

M: Mixed 

MCP-1: Monocyte chemoattractant protein-1 

MDI: Diphenylmethane di-isocyanate 

MEF: Maximal expiratory flow 

MEF25: Maximal expiratory flow at 25% of vital capacity 
106

MEF50: Maximal expiratory flow at 50% of vital capacity 

MPO: Myeloperoxidase 

MSDS: Material safety data sheet 

N: Never 

NDI: Naphthalene di-isocyanate 

NRL: Natural rubber latex 

NSBP test: Non-specific bronchial provocation test 

NSBR: Non-specific bronchial reactivity 

OA: Occupational asthma 

OASYS-2: Occupational asthma systems 

OD: Optical density 

PaO2: Arterial oxygen partial pressure 

PC20: Provocative concentration causing a 20% drop in FEV1 

PD15: Provocative dose causing a 15% drop in FEV1

PD20: Provocative dose causing a 20% drop in FEV1 

PD50: Provocative dose causing a 50% drop in FEV1

PEF: Peak expiratory flow 

PEFR: Peak expiratory flow rate 

PFT: Pulmonary function test 

PPE: Personal protective equipment 

PRIST: Paper radioimmunosorbent test 

PTRIA: Polystyrene-tube radioimmunoassay 

PRU: Phadebas RAST units 

QOL: Quality of life 

RADS: Reactive airways dysfunction syndrome 

RAST: Radio allegro sorbent test 

RCT: Randomized controlled trial 

REIA: Reverse enzyme immunoassay 

RIA: Radioimmunoassay 

RIACT: Radioimmunoassay kit for measuring IgE 

RV: Residual volume 

USD: United States dollar 

SABA: Short acting beta-agonists 

SD: Standard deviation 

SDS: Sodium dodecyl sulphate 

SEM: Standard error of the mean 

sGaw: Specific airways conductance 

SIC: Specific inhalation challenge 

SOB: Shortness of breath 

SPBRIA: Solid-phase bead radioimmunoassay; 

SPT: Skin prick test 

sRAW: Specific airway resistance 

SWORD: Surveillance of work-related occupational respiratory disease 

TCPA: Tetrachlorophthalic anhydride 

TCPA-HSA: Tetrachlorophthalic anhydride human serum albumin 

TDI: Toluene di-isocyanates 
107

TDI-HSA: Toluene di-isocyanates human serum albumin 

TEP: Technical expert panel 

TLco: Single breath carbon monoxide 

TMA: Trimellitic anhydride 

WCB: Workers’ Compensation Board 

IU: International unit 

UniCAP: Fluoroenzymeimmunoassay kit developed by Pharmacia Diagnostics 

Vmax: Maximum flow
A-1

Appendix A: Exact Search Strings 

Diagnosis of Occupational Asthma Searches 

Table A-1: Agricola and Biological Abstracts 

Table A-2: Cinahl 

Table A-3: Embase 

Table A-4: Medline 

Table A-5: Web of Science 

Management of Occupational Asthma Searches 

Table A-6: Agricola and Biological Abstracts 

Table A-7: Cinahl 

Table A-8: Cochrane Airways Group 

Table A-9: Embase 

Table A-10: Medline 

Table A-11: Web of Science 

Occupational Asthma Searches 

Table A-12: Dissertation Abstracts 

Table A-13: Expanded Academia 

Table A-14: NASD 
A-2

Table A-1. Agricola and Biological Abstracts: Diagnosis of occupational asthma (1970 to September 

2003) 

Set # and Keyword Search 

1. (asthma or wheez* or respiratory sound* or airway obstruction* or airway* 

2. (respiratory or pneumonitis or alveol* or bronchial or airway* or lung*) silo filler* disease or bird 

fancier* lung or pneumoconiosis or baker* or skin prick* or respiratory function test* or 

bronchial provocation test* or work caus* or work aggravat* or concurrent or job or employ* or 

occupation* 

3. 1 or 2 

4. (occupational disease* or agricultural worker* disease* or farmer* lung or 

5. (animal* or fowl or farmer* or pheasant* or bird* or pigeon* or hen or 

6. occupation* asthma* 

7. 4 or 5 

8. 3 and 7 

9. 6 or 8 and (hypersensitiv* or hyperreactiv* or hyper reactiv* or allerg* or breath test* or 

spirometry or spirometr* or bronchospirometry or physical bronchial responsive* or nsbr or 

nsbh or bronchospas* or bronchoconstric* or chloride or immunologic test* or immunosorbent 

technique* or skin test* or dysfunction* or airway obstruct* or reactive airway* or lung disease* 

or epoxy resin* or latex or red cedar* or occupation* air pollutant* or exam* or medical history 

taking or questionnaire*) expiratory flow rate* or pef or pefr or forced expiratory volume or fev1 

or expiratory flow-volume curve* or maximal midexpiratory flow rate* or peak forced expiratory 

flow rate* or maximal expiratory flow rate* or maximal grain* or industry or worker* or worksite* 

or work site* or work relat* or handler*) (hens) and (fancier* or worker* or breeder* or keeper* 

or raiser* or hyperreactiv* or bronchial spasm* or bronch* spas* or bronchial disease* or 

hyperresponsiv* or non specific bronchial responsive* or non-specific inhalation expos* or 

occupational expos* or di-isocynate* or isocynate* or insufficien*) methacholine or pulmonary 

or inhal* or antigen* or allergen* or hypertonic monitor* or measur* or provocation) non specific 

bronchial hyperresponsiv* or nonspecific bronchial obstructive lung disease* or respiratory 

tract disease or bronchial occupational airway*) or environment* or workplace or employment 

or environmental expos* or isocapnic or hyperosmolar) and (challenge* or test or tests or 

testing or rhonchi or twitchy airway*) 

10. (induced sputum* or inhalation challeng* or peak flow* or methacholine 

11. (bronchial or carbachol or serial or cold air or histamine* or 

12. 10 or 11 

13. 9 and 12 
A-3

Table A-2. Cinahl: Diagnosis of occupational asthma (1982 to February Week 1 2004) 

Set # and Keyword Search 

1. asthma/ or asthma$.tw. 

2. wheez$.tw. 

3. respiratory sounds/ 

4. airway obstruction/ 

5. (airway$ adj3 (dysfunction$ or obstruct$)).tw. 

6. reactive airway$.tw. 

7. lung diseases/ 

8. lung diseases, obstructive/ 

9. respiratory tract diseases/ 

10. bronchial hyperreactivity/ 

11. bronchial spasm/ or (bronch$ adj5 spas$).tw. 

12. bronchial diseases/ 

13. (non specific bronchial hyperresponsiv$ or nonspecific bronchial hyperresponsiv$).tw. 

14. (non specific bronchial responsiv$ or nonspecific bronchial responsiv$).tw. 

15. (nsbr or nsbh).tw. 

16. (bronchospas$ or bronchoconstric$ or rhonchi).tw. 

17. twitchy airway$.tw. 

18. (respiratory or pneumonitis or alveol$ or bronchial or airway$ or lung$) adj3 (hypersensitiv$ or 

hyperreactiv$ or hyper reactiv$ or allerg$ or insufficien$)).mp. 

19. or/1-18 

20. occupational diseases/ 

21. pneumoconiosis/ 

22. ((animal$ or fowl or farmer$ or pheasant$ or bird$ or pigeon$ or hen or hens) adj3 (fancier$ or 

worker$ or breeder$ or keeper$ or raiser$ or handler$)).mp. 

23. (baker$ or grain$).tw. 

24. exp industry/ 

25. (worker$ or worksite$ or work site$ or work relat$ or work caus$ or work aggravat$ or 

concurrent or job or employ$ or occupation$ or environment$).tw. 

26. (workplace or employment).mp. 

27. environmental exposure/ 

28. occupational exposure/ 

29. (environmental exposur$ or inhalation exposur$ or occupational exposur$).mp. 

30. (di-isocynate$ or isocynate$).tw. 

31. (epoxy resin$ or latex or red cedar$).mp. 

32. air pollutants, occupational/ 

33. occupational airway$.mp. 

34. (occupation$ adj5 asthma$).mp. 

35. or/20-33 

37. 19 and 35 

38. 37 or 34 

39. induced sputum$.tw. 

40. inhalation challeng$.tw. 

41. ((bronchial or carbachol or serial or cold air or histamine$ or methacholine or pulmonary or 

inhal$ or antigen$ or allergen$ or hypertonic or isocapnic or hyperosmolar) adj3 (challenge$ or 

test or tests or testing or monitor$ or measur$ or provocation)).tw. 

42. peak flow$.tw. 

43. methacholine chloride/du 

44. immunologic tests/ or exp immunosorbent techniques/ 

45. exp skin tests/ or skin prick$.mp. 

46. respiratory function tests/ 

47. bronchial provocation tests/ 

48. forced expiratory flow rates/ 

49. maximal expiratory flow rate/ 

50. maximal expiratory flow-volume curves/ 

51. peak expiratory flow rate/ 

52. (pef or pefr).tw. 

53. forced expiratory volume.mp. or fev1.tw. 

54. breath tests/ 

55. spirometry/ or spirometr$.tw. 

56. physical examination/ 
A-4

Table A-2. Cinahl: Diagnosis of occupational asthma (1982 to February Week 1 2004) 

(continued)

Set # and Keyword Search 

57. medical history taking/ 

58. questionnaires/ 

59. diagnostic techniques, respiratory system/ 

60. or/39-59 

61. diagnostic accuracy.tw. 

62. exp diagnosis/ 

63. diagnos$.tw. 

64. "sensitivity and specificity"/ 

65. (sensitivity or specificity).tw. 

66. (predictive adj4 value$).tw. 

67. diagnostic errors/ 

68. false negative reactions/ 

69. false positive reactions/ 

70. (false negativ$ or false positiv$).tw. 

71. observer variation$.mp. 

72. ((roc or receiver operating) adj curve$).tw. 

73. roc curve/ 

74. (likelihood adj4 ratio$).tw. 

75. likelihood function/ 

76. (di or du or et or ae or ci).fs. 

77. or/61-76 

78. and/38,60,77 

79. limit 78 to (newborn infant <birth to 1 month>or infant <1 to 23 months>or preschool child <2 

to 5 years>or child <6 to 12 years>or adolescence <13 to 18 years>) 

80. 78 not 79 

81. limit 80 to (case study or review) 

82. 80 not 81
A-5

Table A-3. Embase: Diagnosis of occupational asthma (1988 to January Week 0 2004) 

Set # and Keyword Search 

1. asthma/ 

2. asthma$.tw. 

3. Wheezing/ 

4. wheez$.tw. 

5. abnormal respiratory sound/ 

6. breathing disorder/ 

7. Airway Obstruction/ 

8. respiratory tract disease/ or bronchus disease/ or lung disease/ or respiratory distress/ 

or respiratory function disorder/ or respiratory tract inflammation/ 

9. reactive airway$.tw. 

10. ((airway$ or lung$) adj3 (dysfunction$ or obstruct$)).tw. 

11. Bronchus Hyperreactivity/ 

12. Bronchospasm/ 

13. (bronch$ adj3 (disease$ or spas$)).tw. 

14. (non-specific bronchial hyperresponsiv$ or nonspecific bronchial hyperresponsiv$).tw. 

15. (non-specific bronchial responsiv$ or nonspecific bronchial responsiv$).tw. 

16. (nsbr or nsbh).tw. 

17. (bronchospas$ or bronchoconstrict$ or rhonchi).tw. 

18. twitchy airway$.tw. 

19. ((respiratory or pneumonitis or alveol$ or bronchial or airway$ or lung$) adj3 

(hypersensitiv$ or hyperreactiv$ or hyper reactiv$ or allerg$ or insufficien$)).mp. 

20. Lung Insufficiency/ 

21. or/1-20 

22. occupational disease/ or occupational allergy/ or occupational lung disease/ 

23. bird breeder lung/ 

24. allergic pneumonitis/ 

25. Pneumoconiosis/ 

26. ((animal$ or fowl or farmer$ or pheasant$ or bird$ or pigeon$ or hen or hens) adj3 

(fancier$ or worker$ or breeder$ or keeper$ or raiser$ or handler$)).mp. 

27. farmer$ lung.tw. 

28. ((agricultur$ or silo filler$) adj3 disease$).tw. 

29. (baker$ or grain$).tw. 

30. (worker$ or worksite$ or work site$ or work relate$ or work cause$ or work aggravat$ 

or concurrent or job or employ$ or occupation$ or environment$).mp. 

31. work/ or work environment/ 

32. exp worker/ 

33. environmental exposure/ 

34. exposure/ 

35. occupational exposure/ 

36. (environment$ exposur$ or inhalation exposur$ or occupation$ exposur$).tw. 

37. Isocyanate/ 

38. (di-isocynate$ or isocyanate$).mp. 

39. (Epoxy Resin or latex or "red cedar").mp. 

40. air pollutant/ 

41. occupational airway$.tw. 

42. (occupation$ adj5 asthma$).mp. 

43. exp Occupational Asthma/ 

44. 42 or 43 

45. or/22-41 

46. 21 and 45 

47. 46 or 44 

48. sputum analysis/ 

49. induced sputum$.tw. 

50. provocation test/ 
A-6

Table A-3. Embase: Diagnosis of occupational asthma (1988 to January Week 0 2004) 

(continued)

Set # and Keyword Search 

51. inhalation challenge$.tw. 

52. ((bronchial or carbachol or serial or cold air or histamine$ or methacholine or 

pulmonary or inhal$ or antigen$ or allergen$ or hypertonic or isocapnic or 

hyperosmolar) adj3 (challenge$ or test or tests or testing or monitor$ or measur$ or 

provocation)).tw. 

53. METHACHOLINE CHLORIDE/ 

54. enzyme linked immunosorbent assay/ 

55. ((bronchial or carbachol or serial or cold air or histamine$ or methacholine or 

pulmonary or inhal$ or antigen$ or allergen$ or hypertonic or isocapnic or 

hyperosmolar or immunologic$) adj3 (challenge$ or test or tests or testing or monitor$ 

or measur$ or provocation)).tw. 

56. skin test/ 

57. prick test/ 

58. exp lung function test/ 

59. inhalation test/ 

60. forced expiratory flow/ 

61. forced expiratory volume/ 

62. maximal expiratory flow$.tw. 

63. (maximal expiratory flow$ or maximal midexpiratory flow$).tw. 

64. peak expiratory flow/ 

65. (pef or pefr).tw. 

66. peak flow.tw. 

67. (forced expiratory volume or fev1).tw. 

68. breath analysis/ 

69. breath test$.tw. 

70. spirometr$.tw. 

71. bronchospirography/ 

72. bronchospirometry.tw. 

73. physical examination/ 

74. anamnesis/ 

75. questionnaire/ 

76. exp respiratory tract examination/ 

77. or/48-76 

78. diagnostic accuracy/ 

79. exp diagnosis/ 

80. diagnos$.tw. 

81. "sensitivity and specificity"/ 

82. (sensitivity or specificity).tw. 

83. (predictive adj4 value$).tw. 

84. diagnostic error/ 

85. (false negativ$ or false positiv$).tw. 

86. observer variation$.mp. 

87. roc curve/ 

88. receiver operating characteristic/ 

89. (likelihood adj4 ratio$).tw. 

90. statistical model/ 

91. (di or du or et or ae or ci).fs. 

92. or/78-91 

93. and/47,77,92 

94. limit 93 to (embryo <first trimester>or infant <to one year>or child <unspecified 

age>or preschool child <1 to 6 years>or school child <7 to 12 years> or adolescent 

<13 to 17 years>) 

95. 93 not 94 

96. limit 95 to (report or review) 

97. 95 not 96 

98. exp case report/ 

99. 97 not 98
A-7

Table A-4. Medline: Diagnosis of occupational asthma (1966 to January Week 3 2004) 

Set # and Keyword Search 

1. asthma/ or asthma$.tw. 

2. wheez$.tw. 

3. respiratory sounds/ 

4. airway obstruction/ 

5. (airway$ adj3 (dysfunction$ or obstruct$)).tw. 

6. reactive airway$.tw. 

7. lung diseases/ 

8. lung diseases, obstructive/ 

9. respiratory tract diseases/ 

10. bronchial hyperreactivity/ 

11. bronchial spasm/ or (bronch$ adj5 spas$).tw. 

12. bronchial diseases/ 

13. (non specific bronchial hyperresponsiv$ or nonspecific bronchial 

hyperresponsiv$).tw. 

14. (non specific bronchial responsiv$ or nonspecific bronchial responsiv$).tw. 

15. (nsbr or nsbh).tw. 

16. (bronchospas$ or bronchoconstric$ or rhonchi).tw. 

17. twitchy airway$.tw. 

18. ((respiratory or pneumonitis or alveol$ or bronchial or airway$ or lung$) adj3 

(hypersensitiv$ or hyperreactiv$ or hyper reactiv$ or allerg$ or insufficien$)).mp. 

19. or/1-18 

20. occupational diseases/ 

21. agricultural workers' diseases/ 

22. farmer's lung/ 

23. silo filler's disease/ 

24. bird fancier's lung/ 

25. pneumoconiosis/ 

26. ((animal$ or fowl or farmer$ or pheasant$ or bird$ or pigeon$ or hen or hens) adj3 

(fancier$ or worker$ or breeder$ or keeper$ or raiser$ or handler$)).mp. 

27. (baker$ or grain$).tw. 

28. exp industry/ 

29. (worker$ or worksite$ or work site$ or work relat$ or work caus$ or work aggravat$ 

or concurrent or job or employ$ or occupation$ or environment$).tw. 

30. (workplace or employment).mp. 

31. environmental exposure/ 

32. inhalation exposure/ 

33. occupational exposure/ 

34. (environmental exposur$ or inhalation exposur$ or occupational exposur$).mp. 

35. (di-isocynate$ or isocynate$).tw. 

36. (epoxy resin$ or latex or red cedar$).mp. 

37. air pollutants, occupational/ 

38. occupational airway$.mp. 

39. (occupation$ adj5 asthma$).mp. 

40. or/20-39 

41. 19 and 40 

42. 39 or 41 

43. induced sputum$.tw. 

44. inhalation challeng$.tw. 

45. ((bronchial or carbachol or serial or cold air or histamine$ or methacholine or 

pulmonary or inhal$ or antigen$ or allergen$ or hypertonic or isocapnic or 

hyperosmolar) adj3 (challenge$ or test or tests or testing or monitor$ or measur$ or 

provocation)).tw. 

46. peak flow$.tw. 

47. methacholine chloride/du 

48. immunologic tests/ or exp immunosorbent techniques/ 

49. exp skin tests/ or skin prick$.mp. 

50. respiratory function tests/ 
A-8

Table A-4. Medline: Diagnosis of occupational asthma (1966 to January Week 3 2004) 

(continued) 

Set # and Keyword Search 

51. bronchial provocation tests/ 

52. forced expiratory flow rates/ 

53. maximal expiratory flow rate/ 

54. maximal expiratory flow-volume curves/ 

55. maximal midexpiratory flow rate/ 

56. peak expiratory flow rate/ 

57. (pef or pefr).tw. 

58. forced expiratory volume.mp. or fev1.tw. 

59. breath tests/ 

60. spirometry/ or spirometr$.tw. 

61. bronchospirometry/ 

62. physical examination/ 

63. medical history taking/ 

64. questionnaires/ 

65. diagnostic techniques, respiratory system/ 

66. or/43-65 

67. diagnostic accuracy.tw. 

68. exp diagnosis/ 

69. diagnos$.tw. 

70. "sensitivity and specificity"/ 

71. (sensitivity or specificity).tw. 

72. (predictive adj4 value$).tw. 

73. diagnostic errors/ 

74. false negative reactions/ 

75. false positive reactions/ 

76. (false negativ$ or false positiv$).tw. 

77. observer variation$.mp. 

78. ((roc or receiver operating) adj curve$).tw. 

79. roc curve/ 

80. (likelihood adj4 ratio$).tw. 

81. likelihood function/ 

82. (di or du or et or ae or ci).fs. 

83. or/67-82 

84. and/42,66,83 

85. limit 84 to (all infant <birth to 23 months> or all child <0 to 18 years> or newborn 

infant <birth to 1 month> or infant <1 to 23 months> or preschool child <2 to 5 years> 

or child <6 to 12 years> or adolescent <13 to 18 years>) 

86. 84 not 85 

87. limit 86 to (case reports or review or review, academic or review literature or review, 

tutorial) 

88. 86 not 87
A-9

Table A-5. Web of Science: Diagnosis of occupational asthma (1966 to January Week 3 2004) 

Set # and Keyword Search 

1. Burge PS, O'Brien IM, Harries MG. Peak flow rate records in the diagnosis of occupational asthma due 

to isocyanates. Thorax 1979;34:317-323. 

2. Cote J, Kennedy S, Chan-Yeung M. Sensitivity and specificity of pc20 and peak expiratory flow rate in 

cedar asthma. J Allergy Clin Immunol 1990;85:592-598. 

3. Perrin B, Lagier F, L'Archeveque J, Cartier A, Boulet LP, Cote J, Malo JL. Occupational asthma: validity 

of monitoring of peak expiratory flow rates and non-allergic bronchial responsiveness as compared to 

specific inhalation challenge. Eur Respir J. 1992;5:40-8.
A-10

Table A-6. Agricola and Biological Abstracts: Management of occupational asthma (1970 to 

September 2003) 

Set # and Keyword Search 

1. (asthma or wheez* or respiratory sound* or airway obstruction* or airway* 

dysfunction* or airway obstruct* or reactive airway* or lung disease* or obstructive 

lung disease* or respiratory tract disease or bronchial hyperreactiv* or bronchial 

spasm* or bronch* spas* or bronchial disease* or non specific bronchial 

hyperresponsiv* or nonspecific bronchial hyperresponsiv* or non specific bronchial 

responsive* or non-specific bronchial responsive* or nsbr or nsbh or bronchospas* or 

bronchoconstric* or rhonchi or twitchy airway*) 

2. (respiratory or pneumonitis or alveol* or bronchial or airway* or lung*) and 

(hypersensitiv* or hyperreactiv* or hyper reactiv* or allerg* or insufficien*) 

3. 1 or 2 

4. (occupational disease* or agricultural worker* disease* or farmer* lung or silo filler* 

disease or bird fancier* lung or pneumoconiosis or baker* or grain* or industry or 

worker* or worksite* or work site* or work relat* or work caus* or work aggravat* or 

concurrent or job or employ* or occupation* or environment* or workplace or 

employment or environmental expos* or inhalation expos* or occupational expos* or 

di-isocynate* or isocynate* or epoxy resin* or latex or red cedar* or occupation* air 

pollutant* or occupational airway*) 

5. (animal* or fowl or farmer* or pheasant* or bird* or pigeon* or hen or hens) and 

(fancier* or worker* or breeder* or keeper* or raiser* or handler*) 

6. occupation* asthma* 

7. 4 or 5 

8. 3 and 7 

9. 6 or 8 

10. (work or job or occupation* or profession* or employe*) and (remov* or modif* or 

adjust* or transfer* or alter* or leave or terminat* or cease or cessation or return*) 

11. change and (employe* or work* or occupation* or work* or process* or procedur*) 

12. (prevent* or reduc* or eliminat* or minimiz* or minimis* or minimal* or control*) and 

(expos* or agent* or irritant* or sensitizer*) 13 (change or retrain* or alter*) and 

(employe* or work* or occupation* or work* or process* or procedur*) 

14. 10 or 11 or 12 or 13 

15. 9 and 14
A-11

Table A-7. Cinahl: Management of occupational asthma (1982 to February Week 1 2004) 

Set # and Keyword Search 

1. asthma/ or asthma$.tw. 

2. wheez$.tw. 

3. respiratory sounds/ 

4. airway obstruction/ 

5. (airway$ adj3 (dysfunction$ or obstruct$)).tw. 

6. reactive airway$.tw. 

7. lung diseases/ 

8. lung diseases, obstructive/ 

9. respiratory tract diseases/ 

10. bronchial hyperreactivity/ 

11. bronchial spasm/ or (bronch$ adj5 spas$).tw. 

12. bronchial diseases/ 

13. (non specific bronchial hyperresponsiv$ or nonspecific bronchial 

hyperresponsiv$).tw. 

14. (non specific bronchial responsiv$ or nonspecific bronchial responsiv$).tw. 

15. (nsbr or nsbh).tw. 

16. (bronchospas$ or bronchoconstric$ or rhonchi).tw. 

17. twitchy airway$.tw. 

18. ((respiratory or pneumonitis or alveol$ or bronchial or airway$ or lung$) adj3 

(hypersensitiv$ or hyperreactiv$ or hyper reactiv$ or allerg$ or insufficien$)).mp. 

19. or/1-18 

20. occupational diseases/ 

21. pneumoconiosis/ 

22. ((animal$ or fowl or farmer$ or pheasant$ or bird$ or pigeon$ or hen or hens) adj3 

(fancier$ or worker$ or breeder$ or keeper$ or raiser$ or handler$)).mp. 

23. (baker$ or grain$).tw. 

24. exp industry/ 

25. (worker$ or worksite$ or work site$ or work relat$ or work caus$ or work aggravat$ or 

concurrent or job or employ$ or occupation$ or environment$).tw. 

26. (workplace or employment).mp. 

27. environmental exposure/ 

28. occupational exposure/ 

29. (environmental exposur$ or inhalation exposur$ or occupational exposur$).mp. 

30. (di-isocynate$ or isocynate$).tw. 

31. (epoxy resin$ or latex or red cedar$).mp. 

32. air pollutants, occupational/ 

33. occupational airway$.mp. 

34. (occupation$ adj5 asthma$).mp. 

35. or/20-33 

37. 19 and 35 

38. 37 or 34 

39. ((work or job or occupation$ or profession$ or employe$) adj5 (remov$ or modif$ or 

adjust$ or transfer$ or alter$ or leave or terminat$ or cease or cessation or 

return$)).tw. 

40. (change adj5 (employe$ or work$ or occupation$ or work$ or process$ or 

procedur$)).tw. 

41. ((prevent$ or reduc$ or eliminat$ or minimiz$ or minimis$ or minimal$ or control$) 

adj5 (expos$ or agent$ or irritant$ or sensitizer$)).tw. 

42. ((change or retrain$ or alter$) adj5 (employe$ or work$ or occupation$ or work$ or 

process$ or procedur$)).tw. 

43. or/39-42 

44. 38 and 43
A-12

Table A-8. Cochrane Airways Group: Management of occupational asthma (March 2004) 

Set # and Keyword Search 

1. Searched using the following free text terms: occupation* or work* or baker* or mining 

or miner* or asbestos* or silicosis or wheat or flour* or farmer* or latex*
A-13

Table A-9. Embase: Management of occupational asthma (1988 to February Week 6 2004) 

Set # and Keyword Search 

1. asthma/ 

2. asthma$.tw. 

3. Wheezing/ 

4. wheez$.tw. 

5. abnormal respiratory sound/ 

6. breathing disorder/ 

7. Airway Obstruction/ 

8. respiratory tract disease/ or bronchus disease/ or lung disease/ or respiratory distress/ 

or respiratory function disorder/ or respiratory tract inflammation/ 

9. reactive airway$.tw. 

10. ((airway$ or lung$) adj3 (dysfunction$ or obstruct$)).tw. 

11. Bronchus Hyperreactivity/ 

12. Bronchospasm/ 

13. (bronch$ adj3 (disease$ or spas$)).tw. 

14. (non-specific bronchial hyperresponsiv$ or nonspecific bronchial 

hyperresponsiv$).tw. 

15. (non-specific bronchial responsiv$ or nonspecific bronchial responsiv$).tw. 

16. (nsbr or nsbh).tw. 

17. (bronchospas$ or bronchoconstrict$ or rhonchi).tw. 

18. twitchy airway$.tw. 

19. ((respiratory or pneumonitis or alveol$ or bronchial or airway$ or lung$) adj3 

(hypersensitiv$ or hyperreactiv$ or hyper reactiv$ or allerg$ or insufficien$)).mp. 

20. Lung Insufficiency/ 

21. or/1-20 

22. occupational disease/ or occupational allergy/ or occupational lung disease/ 

23. bird breeder lung/ 

24. allergic pneumonitis/ 

25. Pneumoconiosis/ 

26. ((animal$ or fowl or farmer$ or pheasant$ or bird$ or pigeon$ or hen or hens) adj3 

(fancier$ or worker$ or breeder$ or keeper$ or raiser$ or handler$)).mp. 

27. farmer$ lung.tw. 

28. ((agricultur$ or silo filler$) adj3 disease$).tw. 

29. (baker$ or grain$).tw. 

30. (worker$ or worksite$ or work site$ or work relate$ or work cause$ or work aggravat$ 

or concurrent or job or employ$ or occupation$ or environment$).mp. 

31. work/ or work environment/ 

32. exp worker/ 

33. environmental exposure/ 

34. exposure/ 

35. occupational exposure/ 

36. (environment$ exposur$ or inhalation exposur$ or occupation$ exposur$).tw. 

37. Isocyanate/ 

38. (di-isocynate$ or isocyanate$).mp. 

39. (Epoxy Resin or latex or "red cedar").mp. 

40. air pollutant/ 

41. occupational airway$.tw. 

42. (occupation$ adj5 asthma$).mp. 

43. exp Occupational Asthma/ 

44. 42 or 43 

45. or/22-41 

46. 21 and 45 

47. 46 or 44 

48. ((work or job or occupation$ or profession$ or employ$) adj5 (remov$ or modif$ or 

adjust$ or transfer$ or alter$ or leave or terminat$ or cease or cessation or 

return$)).tw. 

49. (change adj5 (employ$ or work$ or occupation$ or work$ or process$ or 

procedur$)).tw. 

50. ((prevent$ or reduc$ or eliminat$ or minimiz$ or minimis$ or minimal$ or control$) 

adj5 (expos$ or agent$ or irritant$ or sensitizer$)).tw. 
A-14

Table A-9. Embase: Management of occupational asthma (1988 to February Week 6 2004) 

(continued) 

Set # and Keyword Search 

51. ((change or retrain$ or alter$) adj5 (employ$ or work$ or occupation$ or process$ or 

procedur$)).tw. 

52. or/48-51 

53. 47 and 52 
A-15

Table A-10. Medline: Management of occupational asthma (1966 to January Week 4 2004) 

Set # and Keyword Search 

1. ASTHMA/ 

2. asthma$.tw. 

3. wheez$.tw. 

4. respiratory sounds/ 

5. airway obstruction/ 

6. (airway$ adj3 (dysfunction$ or obstruct$)).tw. 

7. reactive airway$.tw. 

8. Lung Diseases/ 

9. Lung Diseases, obstructive/ 

10. Respiratory Tract Diseases/ 

11. bronchial hyperreactivity/ 

12. bronchial spasm/ or (bronch$ adj5 spas$).tw. 

13. bronchial diseases/ 

14. (non-specific bronchial hyperresponsiv$ or nonspecific bronchial 

hyperresponsiv$).tw. 

15. (non-specific bronchial responsiv$ or nonspecific bronchial responsiv$).tw. 

16. (nsbr or nsbh).tw. 

17. bronchospas$ or bronchoconstrict$ or rhonchi).tw. 

18. twitchy airway$.tw. 

19. ((respiratory or pneumonitis or alveol$ or bronchial or airway$ or lung$) adj3 

(hypersensitiv$ or hyperreactiv$ or hyper reactiv$ or allerg$ or insufficien$)).mp. 

20. or/1-19 

21. occupational diseases/ 

22. agricultural workers' diseases/ 

23. farmer's lung/ 

24. silo filler's disease/ 

25. bird fancier's lung/ 

26. pneumoconiosis/ 

27. ((animal$ or fowl or farmer$ or pheasant$ or bird$ or pigeon$ or hen or hens) adj3 

(fancier$ or worker$ or breeder$ or keeper$ or raiser$ or handler$)).mp. 

28. (baker$ or grain$).tw. 

29. (worker$ or worksite$ or work site$ or work relate$ or work cause$ or work aggravat$ 

or concurrent or job or employ$ or occupation$ or environment$).tw. 

30. (workplace or employment).mp. 

31. environmental exposure/ 

32. inhalation exposure/ 

33. Occupational Exposure/ 

34. (environmental exposur$ or inhalation exposur$ or occupational exposur$).mp. 

35. (di-isocynate$ or isocynate$).tw. 

36. (epoxy resin$ or latex or "red cedar").mp. 

37. air pollutants, occupational/ 

38. occupational airway$.mp. 

39. (occupation$ adj5 asthma$).mp. 

40. or/21-38 

41. 20 and 40 

42. 39 or 41 

43. ((work or job or occupation$ or profession$ or employe$) adj5 (remov$ or modif$ or 

adjust$ or transfer$ or alter$ or leave or terminat$ or cease or cessation or 

return$)).tw. 

44. (change adj5 (employe$ or work$ or occupation$ or work$ or process$ or 

procedur$)).tw. 

45. ((prevent$ or reduc$ or eliminat$ or minimiz$ or minimis$ or minimal$ or control$) 

adj5 (expos$ or agent$ or irritant$ or sensitizer$)).tw. 

46. ((change or retrain$ or alter$) adj5 (employe$ or work$ or occupation$ or work$ or 

process$ or procedur$)).tw. 

47. or/43-46 

48. 42 and 47
A-16

Table A-11. Web of Science: Management of occupational asthma (1966 to January Week 4 2004) 

Set # and Keyword Search 

1. Pisati G, Baruffini A, Zedda S. Toluene diisocyante induced asthma: outcome according to persistence 

or cessation of exposure. Br J Ind Med 1993;50:60-64.

2. Cote J, Kennedy S, Chan-Yeung M. Outcome of patients with cedar asthma with continuous exposure. 

Am Rev Respir Dis 1990;141:373-6.
A-17

Table A-12. Dissertation Abstracts: Occupational asthma (searched February 2004) 

Set # and Keyword Search 

1. Searched using keyword: "occupational asthma"
A-18

Table A-13. Expanded Academic: Occupational asthma (1980 to February 2004) 

Set # and Keyword Search 

1. Searched using keyword: "occupational asthma"
A-19

Table A-14. NASD: Occupational asthma (searched January 2004) 

Set # and Keyword Search 

1. Searched using keywords: "occupational asthma", work related asthma, work caused 

asthma, occupation* disease, respiratory disease, specific inhalation challenge, peak 

flow, methacholine, forced expiratory volume, spirometry
B-1

Appendix B: Sample Data Forms 

Inclusion/Exclusion Criteria 

Form B-1: Inclusion form: Diagnosis of occupational asthma 

Form B-2: Inclusion form: Management of occupational asthma 

Quality Assessment 

Form B-3: Assessment of methodology for diagnostic studies: Diagnosis of occupational 

asthma 

Form B-4: Assessment of methodology for non-randomized controlled trials: 

Management of occupational asthma 

Form B-5: Assessment of methodology for randomized controlled trials: Management of 

occupational asthma 

Data Extraction 

Form B-6: Data extraction form: Diagnosis of occupational asthma 

Form B-7: Data extraction form: Management of occupational asthma 
B-2

Form B-1. Inclusion form: Diagnosis of occupational asthma 

Reviewer: Date: Reference Number: 

TOPIC, include if either: 

[ ] Examining the diagnostic utility of one test in workers with a previous diagnosis of 

work-related or occupational asthma [previous diagnosis of asthma counts as one of 

the reference standards] 

[ ] Comparing the diagnostic utility of two or more tests in workers with suspected 

occupational asthma 

[ ] Examining the role of specific inhalation challenge testing in the diagnosis of 

occupational asthma 

DESIGN, include if any of the following: 

[ ] Randomized clinical trial 

[ ] Controlled clinical trial 

[ ] Prospective cohort 

[ ] Retrospective cohort/case-series 

[ ] Cross-sectional 

PARTICPIANTS, include if: 

Workers with either: 

[ ] De novo occupationally induced asthma 

[ ] A previous diagnosis of asthma that is exacerbated at work (i.e. work related 

asthma). ‘Exacerbated at work’ refers to underlying asthma that is made worse by a 

workplace exposure. This includes an episode of bronchoconstriction triggered by 

cold air or exercise. 

REFERENCE STANDARD, include if there is at least one of the following: 

[ ] Specific inhalation challenge testing 

[ ] Supervised workplace challenge 

[ ] Serial peak flow or serial spirometry monitoring (some type of serial lung function) 

[ ] Serial measurement of non-specific airway reactivity, such as methacholine, 

histamine, or other challenges 

[ ] Immunological testing 

[ ] Clinical diagnosis of occupational asthma by an expert (occupational or pulmonary 

medicine specialist) and exposure to an “asthmagen” 

OTHER COMPARISON TEST, include if there is at least one of the following: 

[ ] Specific inhalation challenge testing 

[ ] Supervised workplace challenge 

[ ] Serial peak flow or serial spirometry monitoring (some type of serial lung function) 

[ ] Serial measurement of non-specific airway reactivity, such as methacholine, 

histamine, or other challenges 

[ ] Immunological testing 
B-3

[ ] Clinical diagnosis of occupational asthma by an expert (occupational or pulmonary 

medicine specialist) and exposure to an “asthmagen”

[ ] Sputum, metabonomics, etc 

[ ] Nitrous oxide 

[ ] Other: 

OUTCOMES, include if there is at least one of the following: 

[ ] Absolute numbers are presented to construct a 2 x 2 (comparing two diagnostic 

techniques) or 2 x 1 (assessing one diagnostic technique in patients with a previous 

diagnoses of occupational asthma) table 

[ ] Sensitivity, specificity, or likelihood ratios 

[ ] Cost of diagnosis 

[ ] Time to complete diagnosis 

[ ] Adverse effects 

FINAL DECISION: 

[ ] INCLUDE (meets all of the above inclusion criteria) 

[ ] EXCLUDE 

[ ] CAN’T TELL 

[ ] Further information is required 

[ ] Not English (state language): 

If disagreement between reviewers, final outcome: 

[ ] INCLUDED [ ] EXCLUDED 

Check box if study provides useful background information 
B-4

Form B-2. Inclusion form: Management of occupational asthma 

Reviewer: Date: Reference Number: 

TOPIC, include if either: 

[ ] Examining the treatment or management in workers with a previous diagnosis of 

occupational asthma 

DESIGN, include if any of the following: 

[ ] Randomized clinical trial 

[ ] Controlled clinical trial 

[ ] Prospective cohort 

[ ] Retrospective cohort/case-series 

[ ] Cross-sectional 

PARTICPIANTS, include if: 

Currently employed workers or previously employed workers with either: 

[ ] De novo occupationally induced asthma 

[ ] A previous diagnosis of asthma that is exacerbated at work. This includes an 

episode of bronchoconstriction triggered by cold air or exercise. 

[ ] Can’t tell, but participants have occupational asthma 

INTERVENTION, include if there is at least one of the following: 

[ ] Removal from the offending workplace 

[ ] Relocated to a position with decreased exposure to the “asthmagen” within the same 

workplace 

[ ] Provided personal protective equipment (e.g. masks, respirators) 

[ ] Engineering controls 

[ ] Pharmacological treatment (e.g. bronchodilators, inhaled corticosteroids) 

[ ] Other: 

OUTCOMES, include if there is at least one of the following: 

[ ] Pulmonary function 

[ ] Use of medication 

[ ] Healthcare utilization (e.g. admissions, ED visits, visits to primary care providers, 

referral to specialist) 

[ ] Frequency of exacerbations 

[ ] Quality of life 

[ ] Symptoms 

[ ] Economic consequences (to worker, employer, society) 

[ ] Adverse events 
B-5

FINAL DECISION: 

[ ] INCLUDE (meets all of the above inclusion criteria) 

[ ] EXCLUDE 

[ ] CAN’T TELL 

[ ] Further information is required 

[ ] Not English (state language): 

If disagreement between reviewers, final outcome: 

[ ] INCLUDED [ ] EXCLUDED 

Check box if study provides useful background information 
B-6

Form B-3. Assessment of methodology for diagnostic studies: 

Diagnosis of occupational asthma

Reviewer: Date: Reference Number: 

(Empirically validated items marked with an asterisk- Adapted from Lijmer et al.) 

1. Design * 

a. Case control 

b. Cohort 

c. Other – specify________________ 

2. Blinding of measurements (test vs. reference standard) * 

a. Both measurements blinded 

b. One measurement blinded- specify (test vs. reference)_______________ 

c. Other – specify________________ 

d. Neither measurements blinded 

e. Unclear 

3. Appropriate reference standard * 

a. Level of evidence reference standard:________________ 

b. Other – specify________________ 

4. Description of reference standard * 

a. Adequate (e.g. referral to standard SIC methodology, timing of lung 

function tests, referral to standard challenge dosages and methodology, 

how an OA specialist made the diagnosis; there is enough information to 

reproduce the test) 

b. Inadequate 

5. Description of test * 

Test I: _____________________ 

a. Adequate (i.e. referral to standard methodology; there is enough 

information to reproduce the test) 

b. Inadequate 

Test II: _____________________ 

a. Adequate (i.e. referral to standard methodology; there is enough 

information to reproduce the test) 

b. Inadequate 

Test III: _____________________ 

a. Adequate (i.e. referral to standard methodology; there is enough 

information to reproduce the test) 

b. Inadequate 

Test IV: _____________________ 

a. Adequate (i.e. referral to standard methodology; there is enough 

information to reproduce the test) 

b. Inadequate 
B-7

Test V: _____________________ 

a. Adequate (i.e. referral to standard methodology; there is enough 

information to reproduce the test) 

b. Inadequate 

6. Description of population * 

a. Adequate (i.e. patients described in terms of age, sex and presenting signs 

and symptoms) 

b. Inadequate 

7. Differential reference bias * (i.e. those who test negatively or strongly positive are 

given a less or more thorough reference test for verification of the negative test; 

those who test negative or strongly positive are given a less thorough reference 

standard) 

a. Yes 

b. No 

c. Unclear 

8. Partial verification bias (i.e. decision to perform the reference test is based upon 

the results of the test under examination; result of the test predicts patient moving 

on to the reference standard or vice versa) 

a. No – specify number ___________ (must be ≥90% for the risk of partial 

verification bias to be minimal) 

b. Yes 

c. Unclear 

9. Data collection 

a. Retrospective 

b. Prospective (may be selected retrospectively but data is collected 

prospectively) 

c. Unclear 

10. Patient selection 

a. Consecutive or random selection 

b. Other – specify __________________ 

c. Not reported 

11. Inter-rater reliability 

a. Reported 

b. Not reported 

12. Reporting of results 

a. Allows for re-creation of contingency tables 

b. Does not allow for recreation of contingency tables 
B-8

Form B-4. Assessment of methodology for non-randomized 

controlled trials: Management of occupational asthma 

Reporting 

1. Is the hypothesis/aim/objective of the study clearly described? This question 

refers to a clear statement of the objective, i.e. to measure the effectiveness of x in 

population y with respect to z, even if x, y and z are not clearly described (see 

questions 2, 3 and 4) 

Yes 1 

No 0 

2. Are the main outcomes to be measured clearly described in the Introduction or 

Methods section? If the main outcomes are first mentioned in the Results section, 

the question should be answered no. In case-control studies the case definition should 

be considered the outcome. 

Yes 1 

No 0 

3. Are the characteristics of the patients included in the study clearly described in 

the Introduction or Methods section? In cohort studies and trials, inclusion and or 

exclusion criteria should be given. In case-control studies, a case definition and the 

source for controls should be given. 

Yes 1 

No 0 

4. Are the interventions of interest clearly described in the Introduction or 

Methods section? Treatments and placebo (where relevant) that are to be compared 

should be clearly described. 

Yes 1 

No 0 
B-9

5. Are the distributions of principal confounders in each group of subjects to be 

compared clearly described? A list of principal confounders is provided. 

Yes 2 

Partially 1 

No 0 

6. Are the main findings of the study clearly described? Simple outcome data 

(including denominators and numerators) should be reported for all major findings so 

that the reader can check the major analyses and conclusions. This question does not 

cover statistical tests, which are considered below. 

Yes 1 

No 0 

7. Does the study provide estimates of the random variability in the data for the 

main outcomes? In non-normally distributed data the inter-quartile range of results 

should be reported. In normally distributed data the standard error, standard deviation 

or confidence intervals should be reported. If the distribution of the data is not 

described, it must be assumed that the estimates used were appropriate and the 

question should be answered yes. 

Yes 1 

No 0 

8. Have all important adverse events that may be a consequence of the intervention 

been reported? This should be answered yes if the study demonstrates that there 

was a comprehensive attempt to measure adverse events. (A list of possible adverse 

events is provided). 

Yes 1 

No 0 
B-10

9. Have the characteristics of patients lost to follow-up been described? This should 

be answered yes where there were no losses to follow-up or where losses to follow-up 

were so small that findings would be unaffected by their inclusion. This should be 

answered no where a study does no report the number of patients lost to follow-up. 

Yes 1 

No 0 

10. Have 95% CIs and/or actual probability values been reported (e.g. 0.035 rather 

than <0.05) for the main outcomes except where the probability value is less than 

0.001? (both CI and p value, either CI or p value, neither) 

Yes 1 

No 0 

External validity 

11. Were the subjects asked to participate in the study representative of the entire 

population from which they were recruited? The study must identify the source 

population for patients and describe how the patients were selected. Patients would 

be representative if they comprised the entire source population, an unselected sample 

of consecutive patients, or a random sample. Random sampling is only feasible 

where a list of all members of the relevant population exists. Where a study does not 

report the proportion of the source population from which the patients are derived, the 

question should be answered as unable to determine. 

Yes 1 

No 0 

Unable to determine 0 

12. Were those subjects who were prepared to participate representative of the 

entire population from which they were recruited? The proportion of those asked 

who agreed should be stated. Validation that the sample was representative would 

include demonstrating that the distribution of the main confounding factors was the 

same in the study sample and the source population. 

Yes 1 

No 0 

Unable to determine 0 
B-11

13. Were the staff, places, and facilities where the patients were treated, 

representative of the treatment the majority of patients receive? For the study to 

be answered yes the study should demonstrate that the intervention was representative 

of that in use in the source population. The question should be answered no if, for 

example, the intervention was undertaken in a specialist centre unrepresentative of the 

hospitals most of the source population would attend. 

Yes 1 

No 0 

Unable to determine 0 

Internal validity – bias 

14. Was an attempt made to blind study subjects to the intervention they have 

received? For studies where the patients would have no way of knowing which 

intervention they received, this should be answered yes. 

Yes 1 

No 0 

Unable to determine 0 

15. Was an attempt made to blind those measuring the main outcomes of the 

intervention?

Yes 1 

No 0 

Unable to determine 0 

16. If any of the results of the study were based on “data dredging”, was this made 

clear? Any analyses that had not been planned at the outset of the study should be 

clearly indicated. If no retrospective unplanned subgroup analyses were reported, 

then answer yes. 

Yes 1 

No 0 

Unable to determine 0 
B-12

17. In trials and cohort studies, do the analyses adjust for different lengths of followup of patients, or in case-control studies, is the time period between the 

intervention and outcome the same for cases and controls? Where follow-up was 

the same for all study patients that answer should be yes. If different lengths of 

follow-up were adjusted for by, for example, survival analysis the answer should be 

yes. Studies where differences in follow-up are ignored should be answered no. 

Yes 1 

No 0 

Unable to determine 0 

18. Were the statistical tests used to assess the main outcomes appropriate? The 

statistical techniques used must be appropriate to the data. For example nonparametric methods should be used for small sample sizes. Where little statistical 

analysis has been undertaken but where there is no evidence of bias, the question 

should be answered yes. If the distribution of the data (normal or not) is not 

described it must be assumed that the estimates used were appropriate and the 

question should be answered yes. 

Yes 1 

No 0 

Unable to determine 0 

19. Was compliance with the interventions reliable? Where there was non compliance 

with the allocated treatment or where there was contamination of one group, the 

question should be answered no. For studies where the effect of any misclassification 

was likely to bias any association to the null, the question should be answered yes. 

Yes 1 

No 0 

Unable to determine 0 

20. Were the main outcome measures used accurate (valid and reliable)? For studies 

where the outcome measured are clearly described, the question should be answered 

yes. For studies which refer to other work or that demonstrates the outcome measures 

are accurate, the question should be answered as yes. 

Yes 1 

No 0 

Unable to determine 0 
B-13

Internal validity – confounding (selection bias) 

21. Were the patients in different intervention groups (trials and cohort studies) or 

were the cases and controls (case-control studies) recruited from the same 

population? For example, patients for all comparison groups should be selected 

from the same hospital. The question should be answered unable to determine for 

cohort and case-control studies where there is no information concerning the source 

of patients included in the study. 

Yes 1 

No 0 

Unable to determine 0 

22. Were study subjects in different intervention groups (trials and cohort studies) 

or were the cases and controls (case-control studies) recruited over the same 

period of time? For a study which does not specify the time period over which 

patients were recruited, the question should be answered as unable to determine. 

Yes 1 

No 0 

Unable to determine 0 

23. Were the subjects randomized to intervention groups? Studies which state that 

subjects were randomized should be answered yes except where method of 

randomization would not ensure random allocation. For example alternate allocation 

would score no because it is predictable. 

Yes 1 

No 0 

Unable to determine 0 

24. Was the randomized intervention assignment concealed from both patients and 

health care staff until recruitment was complete and irrevocable? All nonrandomized studies should be answered no. If assignment was concealed from 

patients but not from staff, it should be answered no. 

Yes 1 

No 0 

Unable to determine 0 
B-14

25. Was there adequate adjustment for confounding in the analyses from which the 

main findings were drawn? This question should be answered no for trials if: the 

main conclusions of the study were based on analyses of treatment rather than 

intention to treat; the distribution of known confounders in the different treatment 

groups was not described; or the distribution of known confounders different between 

the treatment groups but was not taken into account in the analyses. In nonrandomized studies if the effect of the main confounders was not investigated or 

confounding was demonstrated but no adjustment was made in the final analyses the 

question should be answered as no. 

Yes 1 

No 0 

Unable to determine 0 

26. Were losses to patients to follow-up take into account? (yes, no, unable to 

determine) If the numbers of patients lost to follow-up are not reported, the question 

should be answered as unable to determine. If the proportion lost to follow-up was 

too small to affect the main findings, the question should be answered yes. 

Yes 1 

No 0 

Unable to determine 0 

Power 

27. Was a power calculation reported for the primary outcome? 

Yes 1 

No 0 

Unable to determine 0 

28. Did the study have sufficient power to detect a clinically important effect where 

the probability value for a difference being due to chance in less than 5%?

Yes 1 

No 0 

Unable to determine 0 
B-15

Form B-5. Assessment of methodology for randomized 

controlled trials: Management of occupational asthma 

JADAD SCORE: circle the appropriate response and total for the final Jadad score 

Randomization: 

1. Was the study described as being randomized? 1 = Yes 0 = No 

2. Was the method of randomization appropriate? 1 = Yes 0 = No 

3. Was the method of randomization inadequate? -1 = Yes 0 = No 

Double Blindedness: 

4. Was the study described as double-blind? 1 = Yes 0 = No 

5. Was the method of double-blinding appropriate? 1 = Yes 0 = No 

6. Was the method of double-blinding inadequate? -1 = Yes 0 = No 

Withdrawals: 

7. Was there an adequate description of withdrawals? 1 = Yes 0 = No 

 Total Score: 

CONCEALMENT OF ALLOCATION: was the method used to conceal the 

randomization list 

[ ] adequate 

[ ] inadequate 

[ ] unclear 
B-16

Form B-6. Data extraction form: Diagnosis of occupational 

asthma 

ID__________ Reviewer_________ Checker_________ Date_________ 

Study Characteristics 

First author: 

Title: (short) 

Journal citation: 

Year published: Language: Country where conducted: 

Funding: 

 Private industry  Government  Internal  Foundation  Other  NR 

Probable Cause(s) of OA 

 Isocyanates  Flour  Cedar/wood dust  Latex  Fish/shellfish  Chemical 

 Disinfectant  Pharmaceutical  Animal/bird  LMWS  HMWS  Metal dust 

 Potroom  Other_______________  Mixed causes  Unidentified agent 

 NR 

Subject Source 

 Clinic(s)  Workplace  Mixed 

 Other _____________________________ 

Recruitment 

 Random  Consecutive  All eligible 

 Other__________________  NR 

Time frame _____________________  NR 

Description of Subjects (e.g. referred for _ ___) Occupation(s) (list if 4 or less) 

 > 4 identified 

Reference Standard 

 SIC with ______________________________ 

 Other _________________________________ 

 NR 

Comparison Test(s): 

 Supervised work challenge  Sputum, metabonics, etc. 

 Serial PEF or FEV1  NO 

 NSBPT (histamine or methacholine)  Clinical Dx by expert 

 Pulmonary Function Test (single e.g. Reversibility) 

 Immunological testing  Total IgE 

  Specific IgE 

 SPT (specific and/or for atopy) 

 Eosinophils 

 Other _________________________________ 
B-17

Patient Flow 

1. Initial number selected/screened/eligible: n=___________________ 

2. Total agreed to participate: n= _______________________ 

3. Exclusions:  Yes n=_____  No  Unclear  NR 

 Reasons: 

4. Withdrawals / dropouts / refusals:  Yes n=_____  No  Unclear  NR 

 Reasons: 

5. Number who completed the study: n=___________ 

6. Was there a comparison group or control subgroup within cohort  Yes n=____  No 

Methods 

Anti-asthma medications stopped pre-testing:  Yes (attempted)  No  NR 

Baseline Characteristics 

Please indicate the statistic, (%, SD, SEM, range, AND the units) (insert a ‘ - ‘ if no data available) 

 Group A: __________ 

N ___ 

Group B: _____________ 

N ___ 

ALL ________ 

N ___ 

Males/females (%)

 

Age: 

Mean; SD 

Race: 

(White % ) 

Mean duration work 

related symptoms (yr) 

Mean duration 

workplace exposure (yr) 

Latency (yr) 

Atopic (%) 

 

 

Smokers: (%) 

Current smokers 

Ex-smokers 

Never smoked 

Hx asthma (%) 

Pulmonary function

(single measure - specify)

 

Other -Specify 

Other -Specify 

Current medications documented  Yes  No 
B-18

Other outcomes reported  Yes  No

 Group A: __________ 

N ___ 

Group B: _____________ 

N ___ 

ALL ________ 

N ___ 

Costs 

mean; sd

 

Time to complete Dx 

mean; sd

Adverse events 

Other - specify 

Other - specify 

Test Characteristics 

1. SIC Method followed ______________________________  referenced  described in text 

a. Inclusion criteria 

_________________________________________________________________ 

 NR

b. Exclusion criteria 

_________________________________________________________________ 

 NR

c. +ve test or significant change: 

_________________________________________________________________

  NR 

2. NSBPT Method followed ___________________________  referenced  described in text 

  Methacholine  Histamine  Both 

  Single  Serial (i.e. >1 challenge) 

a. Inclusion criteria 

_________________________________________________________________ 

 NR

b. Exclusion criteria 

_________________________________________________________________ 

 NR

c. +ve test or significant change: 

_________________________________________________________________

Serial measure: 

____________________________________________________________ 

 NR 
B-19

3. Single Pulmonary Function Measure 

 (specify)_____________________________________________ 

  Reversibility reported  Yes No 

a. Inclusion criteria 

_________________________________________________________________ 

 NR

b. Exclusion criteria 

_________________________________________________________________ 

 NR

c. +ve test or significant change: 

_________________________________________________________________

 NR 

4. Serial Pulmonary Function 

 Duration: ______________@ work___________@ away from work; 

 recorded__________ times/day 

 Measure taken:  FEV1  PEF 

a. Inclusion criteria 

_________________________________________________________________ 

 NR

b. Exclusion criteria 

_________________________________________________________________ 

 NR

c. +ve test or significant change: 

_________________________________________________________________

 NR 

5. Other: ________________________ 

 Method ____________________________  Referenced  Described in text 

a. Inclusion criteria 

_________________________________________________________________ 

b. Exclusion criteria 

_________________________________________________________________ 

c. +ve test or significant change: 

_________________________________________________________________

 NR 
B-20

6. Clinical Diagnosis of OA (as defined in article) 

____________________________________________ 

  NR 

7. Immunological Testing 

a. Skin prick test: Method followed ____________________ Referenced  Described in text 

 Reason  Atopy (common allergens)  Specific  Both 

 

+ve test: ___________________________________________________________ NR 

b. Total IgE  Yes  No +ve test or significant change:_____________________  NR 

 Method:  RAST  ELISA  Other, Specify___________________ 

c. Specific IgE  yes  no +ve test or significant change: ____________________  NR 

 Method:  RAST  ELISA  Other, Specify___________________ 

d. Other:__________________+ve test or significant change:_____________________  NR 

 Method:  RAST  ELISA  Other, Specify___________________ 

e. Other:__________________+ve test or significant change:_____________________  NR 

 Method:  RAST  ELISA  Other, Specify___________________ 

Results Reported 

Test results (put highest level of evidence test at the top, comparison test on the left side)

1. ___________________ compared to __________________ 

 2 x 2 table  Reported  Calculated 

 OA not OA 

 +ve 

 -ve 

Sensitivity:_____________________ Specificity:_____________________ 
B-21

2. ___________________ compared to __________________ 

 2 x 2 table  Reported  Calculated 

 OA not OA 

 +ve 

 -ve 

Sensitivity:_____________________ Specificity:_____________________ 

3. ___________________ compared to __________________ 

 2 x 2 table  Reported  Calculated 

 OA not OA 

 +ve 

 -ve 

Sensitivity:_____________________ Specificity:_____________________ 

4.___________________ compared to __________________ 

 2 x 2 table  Reported  Calculated 

 OA not OA 

 +ve 

 -ve 

Sensitivity:_____________________ Specificity:_____________________ 

 
B-22

5. ___________________ compared to __________________ 

 2 x 2 table  Reported  Calculated 

 OA not OA 

 +ve 

 -ve 

Sensitivity:_____________________ Specificity:_____________________ 

 

6. ___________________ compared to __________________ 

 2 x 2 table  Reported  Calculated 

 OA not OA 

 +ve 

 -ve 

Sensitivity:_____________________ Specificity:_____________________ 
B-23

Form B-7. Data extraction form: Management of occupational 

asthma 

ID__________ Reviewer_________ Checker_________ Date_________ 

Study Characteristics 

First author: 

Title: (short) 

Journal citation: 

Year of 

publication: 

Language: Country where conducted: 

Funding: 

 Private industry □ Government □ Internal □ Foundation □ Other  NR 

Probable Cause(s) of OA 

 Isocyanates  Flour  Cedar/wood dust  Latex  Fish/shellfish  Chemical 

 Disinfectant  Pharmaceutical  Animal/bird  LMWS  HMWS  Metal dust 

 Potroom  Other_______________  Mixed causes  Unidentified agent  NR 

Subject Source 

 Clinic(s)  Workplace  Mixed 

 Other 

__________________________ 

 NR 

Recruitment 

 Random  Consecutive  All eligible  WCB  NR 

 Other _____________________________________________ 

Time frame _____________________  NR 

Description of Subjects 

(e.g. referred for _ ___) Occupation(s) (list if 4 or less) 

 > 4 identified 

OA Diagnosis Confirmed by: 

 SIC  Supervised work 

challenge 

 SPF  SPT (specific) 

 NSBPT 

 CD by expert  Questionnaire 

 Immunological testing 

 Wk-Hx 

 NR 

Time Since Dx 

FU 1: _______________ Min ________ Max ______ 

FU 2: _______________ Min ________ Max ______ 

FU 2: _______________ Min ________ Max ______ 
B-24

Follow-up Test(s): 

 SIC  Sputum cell counts  Sputum cytokines  Spirometry (PF) 

 Serial PEF  SPT (atopy / specific)  Nitrous oxide 

 NSBPT  CD by expert  Immunological testing (total IgE, specific IgE, IgG,) 

 Bronchodilator response  Serum Eosinophils  Neutrophils  Disease related costs 

 Questionnaire  Interview 

 Other 

_________________________________________________________________________________ 

Patient Flow 

1. Initial number eligible (i.e. confirmed Dx of OA): n=___________________  Not known 

2. Total agreed to participate: n= _______________________ 

3. Exclusions:  Yes n=_____  No  Unclear  NR 

 Reasons: 

4. Withdrawals / dropouts / refusals:  Yes n=_____  No  Unclear  NR 

 Reasons: 

5. Number who completed the study / follow-up: n=___________ 

6. Was there a comparison group or control subgroup within cohort  Yes n=____  No 

 Describe: 

Intervention:  Removal from offending workplace n=_______ 

 Advised to avoid exposure n=_________ 

 Remained at same workplace: 

 Moved to reduced exposure n=________ 

 Moved to no exposure n= ______ 

 Used protective equipment n=________ 

type: ________________________________________ 

 Used medications n=_____ 

type: ________________________________________ 

 Remained fully exposed n=_____ 

Methods 

Data Collection:  Questionnaire  Interview  Clinical review  Retrospective chart review 

Medications (anti-asthma) stopped pre-testing:  Yes (attempted)  No  NR 
B-25

Baseline Characteristics at Diagnosis: Please indicate the statistic, e.g. %, mean, SD, range AND the units (which gets filled in will depend on how reported) 

 Group A 

___________ 

n= 

Group B 

_________ 

n= 

Group C 

___________ 

n= 

Group D 

___________ 

n= 

Group E 

___________ 

n= 

Males % 

Age: 

Mean; SD 

Race: 

White % 

Hx asthma: % 

Atopic: % 

 

 

Smokers: % 

CS 

ExS 

NS 

 

Duration of exposure (y) 

Duration of symptoms 

(y)

 

Latency (y)

 

Medications (yes %) 

ICS % 

OCS % 

BD % 

BD + steroids % 

Others % 

Asthma/symptom 

severity

 

 

 

Notes: 
B-26

Other Baseline Data at Diagnosis: (specify measure plus metric) 

 Group A 

___________ 

n= 

Group B 

_________ 

n= 

Group C 

___________ 

n= 

Group D 

___________ 

n= 

Group E 

___________ 

n= 

 

 

 

 

 

 

Follow-Up Results: 

 Group A 

___________ 

n= 

Group B 

___________ 

n= 

Group C 

___________ 

n= 

Group D 

___________ 

n= 

Group D 

___________ 

n= 

Smokers: n (%) CS

ExS 

NS 

 

 

 

 

 
B-27

Test Characteristics and Results 

Test ________________________________ 

Method followed ____________________________________________ 

 Referenced  Described in text 

+ve test or significant change: 

_______________________________________________________________ NR 

FU time______________

Group A 

___________ 

n= 

Group B 

___________ 

n= 

Group C 

___________ 

n= 

Group D 

___________ 

n= 

Group D 

___________ 

n= 

 

 

 

Notes: 

Test ________________________________ 

Method followed _____________________________________________ 

 Referenced  Described in text 

+ve test or significant change: 

_______________________________________________________________ NR 

FU time______________ Group A 

___________ 

n= 

Group B 

___________ 

n= 

Group C 

___________ 

n= 

Group D 

___________ 

n= 

Group D 

___________ 

n= 

 

 

 
B-28

Test ________________________________ 

Method followed ____________________________________________ 

 Referenced  Described in text 

+ve test or significant change: 

_______________________________________________________________ NR 

FU time______________

Group A 

___________ 

n= 

Group B 

___________ 

n= 

Group C 

___________ 

n= 

Group D 

___________ 

n= 

Group D 

___________ 

n= 

 

 

 

Test ________________________________ 

Method followed ____________________________________________ 

 Referenced  Described in text 

+ve test or significant change: 

_______________________________________________________________ NR 

FU time______________

Group A 

___________ 

n= 

Group B 

___________ 

n= 

Group C 

___________ 

n= 

Group D 

___________ 

n= 

Group D 

___________ 

n= 

 

 

 
C-1

Appendix C: Levels of Evidence 

Levels of Evidence: Diagnosis of Occupational Asthma 

Table C-1: Levels of evidence: Occupational asthma with latency of allergic or presumed 

immunological mechanism 

Table C-2: Levels of evidence: Occupational asthma without latency 

Table C-3: Levels of evidence: Work-aggravated asthma 
C-2

Table C-1. Levels of evidence: Occupational asthma with latency of allergic or presumed 

immunological mechanism

Test Level 

Specific inhalation challenge test OR supervised workplace inhalation challenge Level Ia 

Lung function test* and methacholine challenge test^, and immunological 

testing** 

Level Ib 

Combination of lung function tests* and methacholine challenge test^ Level II 

Combination of methacholine challenge^ testing and immunological testing** Level IIIa 

Combination of lung function tests* and immunological testing** Level IIIb 

Combination of lung function testing* or serial methacholine challenge testing 

and cessation of symptoms following removal from the workplace 

Level IV 

^^Clinical diagnosis of occupational or work-related asthma by a physician 

specializing in Occupational Medicine or Pulmonary Medicine and exposure to 

an “asthmagen” 

Level V 

*Lung function tests include FEV1 and PEF and must be done serially at work and away from work; 

^Methacholine testing must be done at and away from work; 

**Immunological testing refers to skin prick tests or specific IgE; 

^^We propose that, regardless of the final hierarchy, that ‘physician diagnosis’ be the lowest 

acceptable reference standard for the purposes of comparisons made in this review. The physician’s 

diagnosis may have been reached using a variety of historical information, examination and tests, 

and this will differ from study to study. It is recognized that a physician diagnosis in the absence of 

any objective testing would not usually be considered sufficient acceptable evidence in an individual 

clinical case of suspected occupational asthma.
C-3

Table C-2. Levels of Evidence: Occupational asthma without latency 

Test Level 

Combination of: 

No preceding symptoms 

*Symptoms after single specific exposure incident 

*Exposure to irritant gas/smoke/fume/vapour in high concentrations 

*Symptom onset <24hours after exposure 

*Symptoms persist >3months after onset 

Symptoms similar to asthma with cough wheeze and dyspnoea predominant 

*PFTs show airflow obstruction with significant bronchial response (180mL/12%) 

*Non-specific airway responsiveness present 

Other pulmonary disease excluded 

Level I 

One of above * criteria not documented or not present Level II 

Two of above * criteria not documented or not present Level III 

Three of above * criteria not documented or not present Level IV 

^Clinical diagnosis of occupational or work-related asthma by a physician 

specializing in Occupational Medicine or Pulmonary Medicine 

Level V 

^ We propose that, regardless of the final hierarchy, that ‘physician diagnosis’ be the lowest 

acceptable reference standard for the purposes of comparisons made in this review. The 

physician’s diagnosis may have been reached using a variety of historical information, 

examination and tests, and this will differ from study to study. It is recognized that a physician 

diagnosis in the absence of any objective testing would not usually be considered sufficient 

acceptable evidence in an individual clinical case of suspected occupational asthma. 
C-4

Table C-3. Levels of Evidence: Work-aggravated asthma 

*Lung function tests include FEV1 and PEF

 ** We propose that, regardless of the final hierarchy, that ‘physician diagnosis’ be the lowest acceptable 

reference standard for the purposes of comparisons made in this review. The physician’s diagnosis may 

have been reached using a variety of historical information, examination and tests, and this will differ from 

study to study. It is recognized that a physician diagnosis in the absence of any objective testing would not 

usually be considered sufficient acceptable evidence in an individual clinical case of suspected occupational 

asthma.

Test Level 

Previous history of asthma. Documented work related changes in lung function* 

with documented exposure to a relevant precipitating or ‘triggering’ agent, but 

not a recognised asthmagen, at work 

Level Ia 

Previous history of asthma. Documented work related changes in lung function* 

with documented exposure to a relevant precipitating or ‘triggering’ agent at 

work. Exposure also to an asthmagen(s) at work, but negative specific 

inhalation challenge to asthmagen(s) 

Level Ib 

Previous history of asthma. History of worsening symptoms related to periods at 

work with improvements when away from work, and exposure to a relevant 

precipitating or ‘triggering’ agent, but not a recognised asthmagen, at work 

Level II 

No previous or concurrent history of asthma. History of worsening symptoms 

related to periods at work with improvements when away from work, and 

exposure to a relevant precipitating or ‘triggering’ agent, but not a recognised 

asthmagen, at work 

Level III 

Clinical diagnosis of work aggravated asthma by a physician specializing in 

Occupational Medicine or Pulmonary Medicine** 

Level IV 
D-1

Appendix D: Multiple Publications 

Occupational Asthma Cohorts 

Table D-1: Diagnosis cohorts 

Table D-2: Management cohorts 

Table D-3: Trial cohort 
D-2

During the study screening and data extraction processes, several articles were 

identified where different outcomes were reported for what appeared to be the same 

clinical cohort. We did not want to exclude any relevant results, but also did not want to 

over-represent results when the same outcome had been reported for a cohort in different 

publications. A main (usually most recent) publication for these cohorts was identified 

based on a careful review of the paper for references to prior publications, contact with 

the authors when possible, and cross-referencing descriptions of patient demographics. 

These references are described below for the diagnosis and management systematic 

reviews respectively. 

Table D-1. Diagnosis cohorts 

Linked 

References 

(* indicates 

the primary 

publication) 

Rational 

Cartier, 

1986*1

; 

Cartier, 

19842

Cartier et al. (1986) describe results from IgE testing of snow crab processors diagnosed 

with OA. The authors refer to Cartier et al. (1984) in the description of subjects included in 

the present analysis. 

Cote, 

1993*3

; 

Cote, 19904

Cote et al. (1992) investigated the utility of serial PEFR in 25 subjects investigated for OA 

caused by red cedar. In 1990, the same authors report results on 23 subjects; study design, 

subject, and methods sections are very similar to the later publication. We assumed the 

1992 paper extends the results of the 1990 publication. 

Howe, 

1983*5

; 

Venables, 

19906

Howe et al. (1983) report results from seven patients investigated for OA caused by TCPA. 

Venables et al. (2003) refer to Howe et al. (1983) stating that it “presented only the tests with 

highest TCPA concentrations”; this paper presented results using “data from all the tests”. 

Liss, 1991*7; 

Tarlo, 19918 Liss and Tarlo (1991) report on an investigation of serial PEFR measurements in a cohort of 

50 subjects referred to a clinic in Toronto, Canada. The authors refer to Tarlo and Broder 

(1991) in their methods section with respect to how patients were identified and diagnosed. 

Malo, 

1991*9

; 

Perrin, 

199210

Malo et al. (1991) describe diagnostic findings from a cohort of 162 patients with OA caused 

by various agents. Perrin et al. (1992) appear to report on a subset of 61 patients with serial 

PEFR measurements. 

Moscato, 

1993*11; 

Moscato, 

199112

Moscato et al. (1993) report results from an assessment of two NSBPT substances for 

diagnosing OA caused by TDI. The authors refer to Moscato et al. (1991) in their 

description of the methacholine NSBPT. Moscato et al. (1993) appears to report on a 

subset of patients, originally identified in the 1991 paper, who underwent both tests. 

Paggiaro, 

1987*13; 

Lam, 198314

Paggiaro and Chan-Yeung (1987) report on a cohort of 332 subjects investigated for OA 

caused by exposure to red cedar noting that it includes “206 previously reported subjects”. 

Lam et al. (1983) is the publication for those 206 subjects. 

Abbreviations: NSBPT = non-specific bronchial provocation test; OA = occupational asthma; PEFR = peak 

expiratory flow rate; TCPA = tetrachlorophthalic anhydride; TDI = toluene di-isocyanates 
D-3

Table D-2. Management cohorts 

Linked 

References 

(* indicates 

the primary 

publication) 

Rational 

Grammer, 

2000*15; 

Grammer, 

199316

Grammer et al. (2000) describe a cohort of 29 OA patients; 22 who had been transferred to low 

exposure and seven who had been completely removed. The authors state that the purpose of the 

study was to “extend our previous observations”, referring to their 1993 paper. 

Lin, 1996*17; 

Chan-Yeung, 

198718; ChanYeung, 

198219; ChanYeung, 

197720; Lam, 

198721; ChanYeung, 

198822; 

Cote, 

1990b23; 

Marabini, 

199324; 

Chan-Yeung, 

199925

Lin et al. (1996) describes the largest cohort of subjects followed at a clinic in Vancouver, Canada 

after diagnosis with OA caused by exposure to western red cedar. Outcomes are assessed based 

on each patient’s symptoms and exposure status at follow-up. Chan-Yeung et al. (1987), ChanYeung et al. (1982) and Chan-Yeung et al. (1977) are previous reports of smaller cohorts of 

similarly described subjects. Lam et al. (1987) describes a subset of patients who underwent 

bronchial lavage before and at various intervals after SIC. Chan-Yeung et al. (1988) considered 

similar outcomes in a group of subjects who had been removed from exposure for at least 1 year. 

Cote at al. (1990) report clinical outcomes of a subset of patients who continued exposure and 

categorized them as stable or deteriorated. Socioeconomic and clinical outcomes were reported 

by Marabini et al. in 1993. Chan-Yeung et al. (1999) describes airway inflammation and exhaled 

nitric oxide in a subset of patients followed for at least one year; patients were classified according 

to exposure and medication status. 

Malo, 1988*26; 

Hudson, 

198527 

Malo et al. (1988) describe a cohort of 31 subjects with OA from working in a snow crab processing 

facility and report results from three follow-up visits at approximately 1, 2.5, and 5 years. Hudson et 

al. (1985) report on two cohorts, one of which is a group of 31 workers with OA caused by snow 

crab with 12 months of follow-up. Results from this paper were similar to the first follow-up visit in 

Malo et al. (1988). 

Malo 1993*28

Dewitte 

199429

Malo et al. (1993) included 134 Quebec workers diagnosed with OA who are removed from 

exposure and receiving compensation. Outcomes included quality of life and pulmonary function, 

bronchial responsiveness, and asthma severity. Dewitte et al. (1994) describes 134 workers with 

OA that were diagnosed at the same clinic during the same time period; economic consequences of 

OA are evaluated. Also, the baseline characteristics of the patients in the two studies are similar. 

Merget, 

1999*30; 

Merget, 

199431

Merget et al. (1999) reports results from a cohort of 74 patients with OA due to platinum salts who 

are grouped by exposure status at follow-up. This publication refers to Merget et al. (1994) and 

states “the present study was designed to describe a larger cohort of workers”. 

Park, 

2002a*32; 

Park, 199733

Park et al. (2002) report follow-up results from 41 patients with OA caused by TDI who had been 

removed from exposure who were categorized as not improved, improved, and in remission. In 

Park et al. (1997), 35 patients were categorized using the same definitions. Park et al. (2002) refers 

to Park et al. (1997), but does not state that the results are an extension of previous work. 

Perfetti, 

1998a*34; 

Perfetti, 

1998b35

Perfetti et al. (1998a) reports results of 99 patients with OA who had been removed from exposure 

and followed for various lengths of times; outcomes are assessed comparing those followed for less 

than 5 years and those followed for more than 5 years. Perfetti et al. (1998b) from the same clinical 

group, describes the same study design; however, outcomes are compared based on molecular 

weight of the suspected asthmagen. 

Saetta, 

1995*36; 

Saetta, 199237

Saetta et al. (1995) describe a cohort of 10 subjects with OA caused by isocyanates. The authors 

state that this publication is an extension of their previous work (Saetta 1992). 

Abbreviations: OA = occupational asthma; TDI = toluene di-isocyanates
D-4

Table D-3. Trial cohort 

Linked 

References 

(* indicates 

the primary 

publication) 

Rational 

Armentia, 

1990*38; 

Armentia, 

199239

Armentia et al. have two publications describing an immunothearpy trial of 30 asthmatic bakers. 

Armentia et al. (1990) describes skin prick tests, NSBPT, and serum specific IgE results before and 

after treatment. Armentia et al. (1992) evaluates immune complexes in these patients. 

Abbreviations: NSBPT = non-specific bronchial provocation test 

References

 1. Cartier A, Malo JL, Ghezzo H et al. IgE 

sensitization in snow crab-processing workers. J 

Allergy Clin Immunol 1986;78(2):344-48. 

 2. Cartier A, Malo JL, Forest F et al. Occupational 

Asthma in Snow Crab-Processing Workers. J 

Allergy Clin Immunol 1984;74(3):261-69. 

 3. Cote J, Kennedy S, Chan-Yeung M. Quantitative 

versus qualitative analysis of peak expiratory flow 

in occupational asthma. Thorax 1993;48(1):48-50. 

 4. Cote J, Kennedy S, Chan-Yeung M. Sensitivity and 

specificity of PC20 and peak expiratory flow rate in 

cedar asthma. J Allergy Clin Immunol 

1990;85(3):592-98. 

 5. Howe W, Venables KM, Topping MD et al. 

Tetrachlorophthalic anhydride asthma: evidence for 

specific IgE antibody. J Allergy Clin Immunol 

1983;71(1 Pt 1):5-11. 

 6. Venables KM, Newman-Taylor AJ. Exposureresponse relationships in asthma caused by 

tetrachlorophthalic anhydride. J Allergy Clin 

Immunol 1990;85(1 Pt 1):55-8. 

 7. Liss GM, Tarlo SM. Peak expiratory flow rates in 

possible occupational asthma. Chest 

1991;100(1):63-9. 

 8. Tarlo SM, Broder I. Outcome of assessments for 

occupational asthma. Chest 1991;100:329-35. 

 9. Malo JL, Ghezzo H, L'Archeveque J et al. Is the 

clinical history a satisfactory means of diagnosing 

occupational asthma? Am Rev Respir Dis 

1991;143:528-32. 

 10. Perrin B, Lagier F, L'Archeveque J et al. 

Occupational asthma: validity of monitoring of peak 

expiratory flow rates and non-allergic bronchial 

responsiveness as compared to specific inhalation 

challenge. Eur Respir J 1992;5:40-8. 

 11. Moscato G, Dellabianca A, Corsico A et al. 

Bronchial responsiveness to ultrasonic fog in 

occupational asthma due to diisocyanate. Chest 

1993;104(4):1127-32. 

 12. Moscato G, Dellabianca A, Vinci G et al. Toluene 

diisocyanate-induced asthma: clinical findings and 

bronchial responsiveness studies in 113 exposed 

subjects with work-related respiratory symptoms. J 

Occup Med 1991;33(6):720-25. 

 13. Paggiaro P, Chan-Yeung M. Pattern of specific 

airway response in asthma due to western red cedar 

(Thuja plicata): relationship with length of exposure 

and lung function measurements. Clin Allergy 

1987;17:333-39. 

 14. Lam S, Tan F, Chan H et al. Relationship between 

types of asthmatic reaction, nonspecific bronchial 

reactivity and specific IgE antibodies in patients 

with red cedar asthma. J Allergy Clin Immunol 

1983;72(2):134-39. 

 15. Grammer LC, Shaughnessy MA, Kenamore BD. 

Clinical and immunologic outcome of 42 

individuals with trimellitic anhydride-induced 

immunologic lung disease after transfer to low 

exposure. Allergy Asthma Proc 2000;21(6):355-35. 

 16. Grammer LC, Harris KE, Yarnold PR. A clinical 

and immunologic study of workers with trimelliticanhydride-induced immunologic lung disease after 

transfer to low expsoure jobs. Am Rev Respir Dis 

1993;148:54-57. 

 17. Lin FJ, Dimichward H, Chan-Yeung M. 

Longitudinal decline in lung function in patients 

with occupational asthma due to western red cedar. 

Occup Environ Med 1996;53(11):753-6. 

 18. Chan-Yeung M, MacLean L, Paggiaro P. Follow-up 

study of 232 patients with occupational asthma 

caused by western red cedar (thuja-plicata). J 

Allergy Clin Immunol 1987;79(5):792-96. 
D-5

 19. Chan-Yeung M , Lam S, Koener S. Clinical features 

and natural history of occupational asthma due to 

western red cedar (Thuja plicata). Am J Med 

1982;72(3):411-15. 

 20. Chan-Yeung M. Fate of occupational asthma. A 

follow-up study of patients with occupational 

asthma due to western red cedar (Thuja-Plicata). 

Am Rev Respir Dis 1977;116(6):1023-30. 

 21. Lam S, LeRiche J, Phillips D et al. Cellular and 

protein changes in bronchial lavage fluid after late 

asthmatic reaction in patients with red cedar asthma. 

J Allergy Clin Immunol 1987;80(1):44-50. 

 22. Chan-Yeung M, LeRiche J, MacLean L et al. 

Comparison of cellular and protein changes in 

bronchial lavage fluid of symptomatic and 

asymptomatic patients with red cedar asthma on 

follow-up examination. Clin Allergy 

1988;18(4):359-66. 

 23. Cote J, Kennedy S, Chan-Yeung M. Outcome of 

patients with cedar asthma with continuous 

exposure. Am Rev Respir Dis 1990;141:373-76. 

 24. Marabini A, Dimich-Ward H, Kwan SY et al. 

Clinical and socioeconomic features of subjects 

with red cedar asthma: a follow-up study. Chest 

1993;104:821-24. 

 25. Chan-Yeung M , Obata H, Dittrick M et al. Airway 

inflammation, exhaled nitric oxide, and severity of 

asthma in patients with western red cedar asthma. 

Am J Respir Crit Care Med 1999;159(5 Pt 1):1434-

38. 

 26. Malo JL, Cartier A, Ghezzo H et al. Patterns of 

improvement in spirometry, bronchial 

hyperresponsiveness, and specific IgE antibody 

levels after cessation of exposure in occupational 

asthma caused by snow-crab processing. Am Rev 

Respir Dis 1988;138(4):807-12. 

 27. Hudson P, Cartier A, Pineau L et al. Follow-up of 

occupational asthma caused by crab and various 

agents. J Allergy Clin Immunol 1985;76(5):682-28. 

 28. Malo JL, Boulet LP, Dewitte JD et al. Quality of 

life of subjects with occupational asthma. J Allergy 

Clin Immunol 1993;91:1121-27. 

 29. Dewitte JD, Chan-Yeung M, Malo JL. Medicolegal 

and compensation aspects of occupational asthma. 

Eur Respir J 1994;7:969-80. 

 30. Merget R, Schulte A, Gebler A et al. Outcome of 

occupational asthma due to platinum salts after 

transferral to low-exposure areas. Intl Arch Occup 

Environ Health 1999;72(1):33-9. 

 31. Merget R, Reineke M, Rueckmann A et al. 

Nonspecific and specific bronchial responsiveness 

in occupational asthma caused by platinum salts 

after allergen avoidance. Am J Respir Crit Care 

Med 1994;150(4):1146-49. 

 32. Park HS, Lee SK, Kim HY et al. Specific 

immunoglobulin E and immunoglobulin G 

antibodies to toluene diisocyanate-human serum 

albumin conjugate: Useful markers for predicting 

long-term prognosis in toluene diisocyanateinduced asthma. Clin Exper Allergy 

2002;32(4):551-55. 

 33. Park HS, Nahm DH. Prognostic factors for toluene 

diisocyanate-induced occupational asthma after 

removal from exposure. Clin Exper Allergy 

1997;27(10):1145-50. 

 34. Perfetti L, Cartier A, Ghezzo H et al. Follow-up of 

occupational asthma after removal from or 

diminution of exposure to the responsible agent: 

relevance of the length of the interval from 

cessation of exposure. Chest 1998;114(2):389-403. 

 35. Perfetti L, Hebert J, Lapalme Y et al. Changes in 

IgE-mediated allergy to ubiquitous inhalants after 

removal from or diminution of exposure to the 

agent causing occupational asthma. Clin Exp 

Allergy 1998;28(1):66-73. 

 36. Saetta M, Maestrelli P, Turato G et al. Airway wall 

remodeling after cessation of exposure to 

isocyanates in sensitized asthmatic subjects. Am J 

Respir Crit Care Med 1995;151(2 Pt 1):489-94. 

 37. Saetta M, Maestrelli P, Di Stefano A et al. Effect of 

cessation of exposure to toluene diisocyanate (TDI) 

on bronchial mucosa of subjects with TDI-induced 

asthma. Am Rev Respir Dis 1992;145(1):169-74. 

 38. Armentia A, Arranz M, Martin JM et al. Baker's 

asthma: prevelance and evaluation of 

immunotherapy with wheat flour extract. Ann 

Allergy 1990;65(4):265-72. 

 39. Armentia A, Martin-Santos JM, Quintero A et al. 

Evaluation of immune complexes after 

immunotherapy with wheat flour in bakers' asthma. 

Ann Allergy 1992;69(5):441-44. 
D-6
E-1

Appendix E: Evidence Tables 

Diagnosis of Occupational Asthma 

Table E-1: Description of included studies (Diagnosis review) 

Table E-2: Demographic characteristics of included patients (Diagnosis review) 

Table E-3: Description of diagnostic tests (Diagnosis review) 

Table E-4: Methodological quality of included studies (Diagnosis review) 

Management of Occupational Asthma: Cohorts 

Table E-5: Description of included studies (Management cohorts review) 

Table E-6: Demographic characteristics of included patients (Management cohorts 

review) 

Table E-7: Description of interventions and outcomes (Management cohorts review) 

Management of Occupational Asthma: Trials 

Table E-8: Description of included studies (Management trials review) 

Table E-9: Demographic characteristics of included patients (Management trials review) 

Table E-10: Description of interventions and outcomes (Management trials review) 

Management of Occupational Asthma: Methodological 

Quality

Table E-11: Methodological quality of included studies (Management cohorts review) 

Table E-12: Methodological quality of included studies (Management trials review) 

References 

Reference listing: Diagnosis 

Reference listing: Cohort 

Reference listing: Trials 
E-2

Table E-1. Description of included studies (Diagnosis review) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Alvarez, 2001 

Spain English Yes Eosinophils, 

single NSBPT, skin prick, serum specific IgE 

Flour: oilseed rape (H) 

Farmers with respiratory symrelated to fodder manipulatio

Alvarez, 1996 

Spain English Yes Single NSBPT, 

skin prick, serum specific IgE 

Cereals (H) Bakers, millers, and farmers 

diagnosed with OA over a fivperiod 

Anees, 2004 

United Kingdom 

English No Serial PFT 

(PEFR) 

Mixed (M) Consecutive workers of mixe

occupation with definite OA 

Avery, 1969 

United States 

English No Lymphocyte 

blast cell transformation, TDI-HSA 

Isocyanates (L) Workers exposed toTDI; som

severe symptoms at low expothers with less symptoms ahigher exposures 

Balland, 1989 

France French Yes Single NSBPT, 

serum specific IgE, serum total IgE 

Mixed (M) Workers presenting with sym

of suspected work-related asand rhinitis 

Baur, 1998 

Germany English Yes Clinical 

diagnosis, single NSBPT 

Mixed (M) Healthcare workers, bakers, 

isocyanate workers, and hairdressers who consulted because of suspected OA 

Baur, 1979 

United Kingdom 

English Yes Skin prick, 

serum specific IgE 

Papain (H) Meat or pharmaceutical plan

workers exposed to airborne papain 

Behr, 1990 

Germany German Yes Clinical 

diagnosis, single NSBPT 

Isocyanates (L) Workers exposed to isocyan

with workplace related respisymptoms 

Bernstein, 2002 

Canada English Yes Di-isocyanate 

antigen stimulation of MCP-1, single NSBPT, serum specific IgE 

Isocyanates (L) Di-isocyanate exposed work

with history of OA, referred ftesting 
E-3

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Biot, 1980 

France French Yes Basophils 

granules liberation, single NSBPT, serum total IgE 

Mixed (M) Workers complaining of aller

manifestations in practicing tprofession 

Block, 1983 

Canada English Yes Single NSBPT, 

skin prick, serum specific IgE 

Flour: wheat and rye (H) 

Bakers with respiratory sympidentified from workplace sureferred to study 

Burge, 1985 

United Kingdom 

English Yes Single NSBPT Formaldehyde (L) Workers of mixed occupation 

referred for investigation of symptoms suggestive of OA 

Burge, 1982b 

United Kingdom 

English Yes Single NSBPT Isocyanates (L) Workers with respiratory sym

when exposed to TDI, MDI, colophony 

Burge, 1980 

United Kingdom 

English Yes Single NSBPT Colophony (L) Electronics workers referred 

investigation of respiratory symptoms 

Burge, 1979a 

United Kingdom 

English Yes Clinical 

diagnosis, serial PFT (PEFR) 

Colophony (L) Electronics factory workers w

had had a bronchial provocatest by exposure to solder-flufumes in the hospital and haa record of their PEFR at hoat work for at least two wks 

Burge, 1979b 

United Kingdom 

English Yes Clinical 

diagnosis, serial PFT (PEFR) 

Isocyanates (L) Workers from factories printi

laminating flexible packaging had been admitted for SIC akept at least two wks of PEFrecords 

Burge, 1978 

United Kingdom 

English Yes Eosinophils, 

single PFT, skin prick 

Colophony (L) Electronics industry workers 

exposed to colophony who developed asthma or evidenperipheral airway reaction 

Butcher, 1980 

United States 

English Yes Serum specific 

IgE, serum total IgE 

Isocyanates (L) Workers previously shown to 

adverse bronchial reactions with TDI 
E-4

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Carletti, 1997 

Italy Italian Yes Clinical 

diagnosis, single NSBPT, single PFT, skin prick 

Flour (H) Millers and bakers with susp

OA 

Cartier, 1989 

Canada English Yes Serial NSBPT, 

single NSBPT, skin prick, serum specific IgE, serum specific IgG 

Isocyanates (L) Subjects of various occupati

who were being investigated possible OA caused by isocywho underwent SIC 

Cartier, 1987 

Canada English Yes Single NSBPT, 

skin prick, serum specific IgE 

Psyllium (H) Nurses with history of asthm

symptoms after exposure to psyllium 

Cartier, 1986 

Canada English Yes Skin prick, 

serum specific IgE 

Snow crab (H) Snow crab workers previous

diagnosed with OA 

Choudat, 1999 

France English Yes Single NSBPT, 

serum specific IgE 

Flour: wheat (H) Bakers and pastry makers re

for assessment of OA causeflour 

Cirla, 1975 

Italy Italian Yes Single NSBPT, 

skin prick 

Isocyanates (L) Furniture manufacturing wor

with symptoms of asthma at 

Colas, 1985 

France French Yes Carbon dioxide 

diffusion, eosinophils, single NSBPT, single PFT, skin prick, serum total IgE 

Wood dust: exotic (L) 

Workers who had been hospitalized for OA due to exwoods 

Cortona, 1980 

Italy Italian No Skin prick Enzymes: 

bromolin (H) 

Workers from a pharmacuetindustry handling bromelin 

Cote, 1993 

Canada English Yes Serial PFT 

(PEFR) 

Wood dust: cedar (L) 

Consecutive sawmill workers referred by family physician work related increases in dyand cough 
E-5

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Coutts, 1984 

United Kingdom 

English Yes Single NSBPT, 

skin prick 

Chemical: cimetidine (L) 

Syptomatic workers manuctucimetidine tablets 

Curran, 1996 

United Kingdom 

English No Serum specific 

IgE, serum total IgE 

Chemical: glutaraldehyde (L) 

Health professionals exposeglutaraldehyde, some had bediagnosed with OA by respirphysician, some had respirasymptoms without diagnosis 

Davison, 1983 

United Kingdom 

English Yes Skin prick, 

serum specific IgE 

Castor beans (H) Merchant seamen and labor

workers who developed allesymptoms following exposurcastor beans 

DeZotti, 1996a 

Italy English Yes Eosinophils, 

single NSBPT, single PFT, skin prick 

Wood dust: exotic (L) 

Furniture manufacturers and processors complaining of respiratory symptoms at wor

DeZotti, 1996b 

Italy Italian Yes Eosinophils, 

single NSBPT, single PFT, skin prick, serum specific IgE 

Mixed (M) Workers with OA due to isoc

or wheat exposure 

Dellabianca, 1996 

Italy English Yes Single NSBPT, 

single NSBPT 

Mixed (M) Consecutive subjects of mix

occupation referred to clinic probable OA due to low moleweight chemicals- both SIC reactors and non-reactors 

Dente, 1986 

Italy English Yes Single NSBPT Isocyanates (L) Workers with occupational 

exposure to TDI 

DiFranco, 1998 

Italy English Yes Eosinophils, 

single NSBPT 

Mixed (M) Workers with OA induced by 

high molecular weight compseen in a clinic over a two yr 

DiStefano, 1999 

United Kingdom 

English No Single NSBPT, 

skin prick 

Chemical: glutaraldehyde (L) 

Health care workers with symsuggestive of OA due to expto glutaraldehyde 
E-6

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Duan, 1989 

China Chinese Yes Clinical 

diagnosis, serial NSBPT, serial PFT, single PFT, skin prick, serum specific IgE 

Isocyanates (L) Symptomatic TDI factory wo

compared to non-symptomaworkers and ordinary asthma workers 

Ferguson, 1996 

Canada English Yes Single NSBPT, 

single PFT, serum specific IgE 

Isocyanates (L) Auto manufacturers and spra

painters with chest symptomcompatible with asthma and exposure to isocyanates 

Gannon, 1996 

United Kingdom 

English No Serial PFT 

(PEFR) 

Mixed (M) Records from workers from 

different industries attending occupational lung disease clwith suspected OA, and from cross sectional survey of respiratory symptoms in possorting workers 

Girard, 2004 

Canada English Yes Eosinophils, 

serial NSBPT, serial PFT, skin prick 

Mixed (M) Subjects referred to OA refe

centres for possible OA 

Graneek, 1987 

United Kingdom 

English Yes Single NSBPT Mixed (M) Workers from various indust

who were admitted to hospitinvestigation of OA 

Grosclaude, 1980 

France French Yes Single NSBPT, 

skin prick, serum total IgE 

Mixed (M) Workers of mixed occupation 

OA due to various causes 

Harries, 1980 

United Kingdom 

English Yes Eosinophils, 

skin prick 

Mixed (M) Workers of various occupatio

a history of respiratory illnesworsening at work 

Hinojosa, 1986 

Spain English Yes Skin prick, 

serum specific IgE, serum total IgE 

Wood dust: African maple and ramin (L) 

Workers exposed to African dust who were admitted for safter being away from work fleast two wks 
E-7

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Howe, 1983 

United Kingdom 

English Yes Skin prick, 

serum specific IgE 

Chemical: TCPA (L) 

Factory workers with respirasymptoms referred by factormanagement 

Huggins, 2003 

United Kingdom 

English No Serial PFT 

(PEFR) 

Enzymes: detergent (H) 

Factory workers with work-rerespiratory symptoms and poserum specific IgE or skin prtests to one of the enzymes biological detergents 

Jager, 1993 

Germany German Yes Single NSBPT, 

skin prick, serum specific IgE, supervised work challenge, serum total IgE 

Latex (H) Health care workers with an 

immediate allergic-type reaclatex gloves 

Karol, 1994 

United States 

English Yes Clinical 

diagnosis, single NSBPT, serum specific IgE, serum specific IgG, serum total IgE 

Isocyanates (L) Workers with a history of 

sensitization to isocyanates, referred for evaluation of respiratory symptoms 

Kern, 1991 

United States 

English No Single NSBPT Chemical: glacial 

acetic acid (L) 

Hospital laboratory and radioworkers exposed to a one timof 100% acetic acid for two ahalf hrs 

Keskinen, 1988 

Finland English Yes Skin prick, 

serum specific IgE 

Isocyanates (L) Workers of mixed occupatio

verified asthma due to diisocyanates based on symptand SIC 

Kim, 1999 

Korea English Yes Single NSBPT, 

single PFT, skin prick, serum specific IgE, serum total IgE 

Citrus red mite (H) Citrus fruit farmers with resp

symptoms 
E-8

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Kim, 1997 

Korea English No Single PFT, 

serum specific IgE, serum specific IgG 

Isocyanates (L) Workers who had been expo

TDI in workshops manufactufurniture or musical instrumerepairing motor vehicles 

Kongerud, 1992 

Norway English No Clinical 

diagnosis, eosinophils, serial NSBPT, single NSBPT, symptom score, serum total IgE 

Potroom (L) Potroom workers with a histo

suggestive of OA after standardized interview and methacholine challenge PC2

g/L 

KopferschmittKubler, 1998 

France English Yes Serial PFT 

(FEV1), single 

NSBPT 

Isocyanates (L) Workers with clinical history 

isocyanate-induced asthma reversibility and no positive reaction to low doses of TDI 

Koskela, 2003 

Australia and Finland 

English Yes Exhaled nitric 

oxide, single NSBPT, skin prick, serum specific IgE, serum total IgE 

Animal/bird: cow dander (H) 

Dairy farmers who were refethe laboratory because of a suspicion of OA due to bovinallergens 

Krakowiak, 2003 

Poland English Yes Clinical 

diagnosis, eosinophils, single NSBPT, skin prick, serum specific IgE 

Animal/bird: lab animals (H) 

Laboratory animal workers rto an occupational disease casthma and allergic rhinitis 

Lam, 1979 

Canada English Yes Single NSBPT, 

skin prick 

Wood dust: cedar (L) 

Subjects with OA that were twhile symptomatic or after re

from exposure 

LaPaglia, 1986 

Italy Italian Yes Clinical 

diagnosis, skin prick 

Mixed (M) Subjects with a work-associa

respiratory disease 
E-9

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Larbanois, 2003 

Belgium English Yes Serial PFT 

(sGaw), single NSBPT 

Mixed (M) Consecutive subjects of vari

occupations who were invesfor OA and underwent SIC 

Lemiere, 2001 

Canada English Yes Eosinophils, 

single NSBPT, skin prick 

Mixed (M) Workers of various occupatio

referred to clinic for possible and subjects who had a diagof asthma (concentration of methacholine inducing a 20% FEV1 of less than 8mg/mL a

could produce sputum) 

Liss, 1991 

Canada English Yes Serial PFT 

(PEFR), single NSBPT, single PFT, skin prick 

Mixed (M) Consecutive workers with m

occupations referred for assessment of possible OA 

Lozewicz, 1985 

United Kingdom 

English Yes Single NSBPT, 

skin prick 

Chemical: acrylates (L) 

Subjects with asthma assocwith exposure to cyanoacryla

Malo, 1993a 

Canada English Yes Serial PFT 

(PEFR) 

Mixed (M) Workers of mixed occupation 

referred for investigation of possible OA 

Malo, 1991 

Canada English Yes Questionnaire, 

serial NSBPT, serial PFT (PEFR), single NSBPT, skin prick 

Mixed (M) Workers of mixed occupation 

referred because of possible 

Malo, 1990 

Canada English Yes Single NSBPT, 

skin prick 

Mixed (M) Records of subjects with late 

asthmatic reactions and isolaimmediate reactions to SIC 

Malo, 1988a 

Canada English Yes Eosinophils, 

questionnaire, serial PFT (PEFR), single NSBPT, skin prick 

Spiromycin (L) All workers in a pharmaceut

company, intermittently expospiromycin, investigated to determine frequency of OA 

Mapp, 1986 

Italy English Yes Single NSBPT, 

skin prick 

Isocyanates (L) Subjects with sensitivity to T
E-10

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Mapp, 1979 

Italy Italian Yes Single NSBPT, 

skin prick 

Isocyanates (L) Employees who worked in p

varnish and plastics manufawith chronic respiratory symat work 

Merget, 1997 

Germany English Yes Single NSBPT, 

skin prick, serum specific IgE, serum total IgE 

Flour: wheat (H) Highly selected bakers refer

clinic for assessment of OA 

Merget, 1996 

Germany English Yes Single NSBPT, 

skin prick, serum total IgE 

Chemical: platinum salts (L) 

Platinum refinery and catalysproduction workers who werconsidered to have OA due platinum salts 

Merget, 1993 

Germany English Yes Single NSBPT, 

skin prick, serum specific IgE, serum total IgE 

Enzymes (H) Enzyme manufacturing plan

workers referred to the pulmdepartment with work related symptoms 

Mole, 1977 

Italy Italian No Single NSBPT, 

skin patch test 

Mixed (M) Workers of many occupation

suspected OA 

Moller, 1986 

United States 

English Yes Clinical 

diagnosis, single NSBPT, single PFT 

Isocyanates (L) Workers of various occupatio

referred for possible TDI astbased on consistent clinical occupational history 

Moller, 1985 

United States 

English No Eosinophils, 

questionnaire, serial PFT (FEV1), serum 

specific IgE 

Chemical: hexahydrophthalic anhydride (L) 

Workers in a plant manufactbushings for electrical transfwho reported symptoms of a

Moscato, 1993 

Italy English Yes Single 

NSBPTs, single PFT, skin prick 

Isocyanates (L) Workers in furniture and plas

industries, auto body repair workers, and carpenters refefor probable OA due to TDI 
E-11

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Munoz, 2004 

Spain English Yes Serial PFT 

(PEFR), single NSBPT, skin prick, serum total IgE 

Chemical: persulfate (L) 

Hairdressers and cosmetic iworkers exposed to hair bleadiagnosed with OA 

Nielsen, 1988 

Sweden English No Single NSBPT, 

skin prick, serum specific IgE, serum specific IgG, serum total IgE 

Chemical: phthalic anhydride (L) 

Workers from factories produpolyester resins reporting assymptoms during exposure 

Nordman, 1985 

Finland English Yes Eosinophils, 

serial PFT (PEFR), single NSBPT, single PFT, serum total IgE 

Formaldehyde (L) Workers with various occupa

investigated because of suspformaldehyde-induced asthm

O'Brien, 1979a 

United Kingdom 

English Yes Single NSBPT Isocyanates (L) Subjects referred for investig

of possible work related respsymptoms 

O'Brien, 1979b 

United Kingdom 

English Yes Exercise test, 

single NSBPT, skin prick 

Isocyanates (L) Workers occupationally expo

TDI referred for investigation possible work related asthmsymptoms 

Obata, 1999 

Canada English Yes Eosinophils, 

exhaled nitric oxide, single NSBPT, skin prick 

Wood dust: cedar (L) 

Sawmill workers or carpentereferred to respiratory clinic symptoms of cough, wheeze chest tightness after working red cedar for at least six mos 

Obtulowicz, 1998 

Poland English Yes Eosinophils, 

skin prick, serum total IgE 

Mixed (M) Steel and tobacco factory wo

with bronchial asthma suspebe of occupational origin 

Paggiaro, 1987b 

Canada English Yes Single NSBPT, 

skin prick, serum specific IgE 

Wood dust: cedar (L) 

Workers with OA due to wesred cedar 
E-12

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Paggiaro, 1986 

Italy English Yes Single NSBPT, 

skin prick 

Isocyanates (L) Furniture industry workers w

induced by TDI 

Paggiaro, 1984b 

Italy Italian Yes Single NSBPT, 

skin prick, serum specific IgE, serum total IgE 

Enzymes: proteolytic (H) 

Workers in a factory producidetergents with symptoms o

Paggiaro, 1984c 

Italy Italian Yes Clinical 

diagnosis, single NSBPT 

Isocyanates (L) Workers from a furniture ind

exposed to isocyanates 

Paggiaro, 1981 

Italy English Yes Single NSBPT, 

skin prick, serum specific IgE 

Wood dust: tanganyika aningre (L) 

Woodworkers exposed to tanganyika aningre with symof dyspnea, cough, and whe

Palczynski, 2003 

Poland English Yes Eosinophils, 

single NSBPT, skin prick, serum specific IgE, serum total IgE 

Chloramine (L) Healthcare workers with a h

of respiratory symptoms relachloramine T 

Park, 2002b 

Korea English Yes Immunoblotting, 

single NSBPT, skin prick, serum specific IgE 

Alpha amylase (H) Nurses with asthma symptom

when exposed to porcine pancreatic extracts at work 

Park, 2001 

Korea English Yes Skin prick, 

serum specific IgE 

Reactive dyes (L) Workers with OA from reacti

dyes (SIC positive) who visitclinic in last ten yrs, asymptoworkers in a reactive dye facand unexposed subjects with negative SIC to reactive dye

Park, 1999 

Korea English Yes Single NSBPT, 

single PFT, skin prick, serum specific IgE 

Isocyanates (L) Workers with TDI induced as

as well as SIC negative workand control subjects with alleasthma 
E-13

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Park, 1998 

Korea English Yes Eosinophils, 

immunoblotting, single NSBPT, skin prick, serum specific IgE 

Grain dust (H) Animal feed industry workers 

exposed to grain dust 

Park, 1994 

Korea English Yes Serial PFT 

(PEFR), single NSBPT, skin patch test, skin prick 

Chemical: chromium (L) 

Metal plating factory, cemenmanufacturers and construcworkers complaining of work related symptoms 

Park, 1991 

Korea English Yes Single NSBPT, 

skin prick, serum specific IgE, serum total IgE 

Reactive dyes (L) Symptomatic textile dye indu

workers with bronchial hyperreactivity 

Park, 1989 

Korea English Yes Single NSBPT, 

single PFT, skin prick, serum specific IgE 

Reactive dyes (L) Dye process workers who 

complained of asthmatic symfollowing various lengths of exposure to reactive dyes 

Perrin, 1990 

Canada English Yes Serial NSBPT, 

serial PFT (PEFR) 

Mixed (M) Subjects referred for OA to v

agents 

Pezzini, 1984 

Italy English Yes Single NSBPT, 

skin prick, serum specific IgE 

Isocyanates (L) Polyurethane foam shoe fac

and furniture plant workers wdiagnosis of isocyanate-induOA based on symptoms and 

Prichard, 1984 

Australia English No Single NSBPT, 

skin prick 

Flour: wheat (H) Bakers and bakery workers 

fulfilled the definition of work related asthma 

Quirce,  2000 

Spain English No Skin prick, 

serum specific IgE 

Wood dust: obeche (L) 

Woodworkers with symptomasthma after exposure to obwood dust 
E-14

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Quirce, 1992 

Spain English Yes Single NSBPT, 

skin prick, serum specific IgE 

Alpha amylase (H) Bakers evaluated in clinic be

of respiratory symptoms due exposure to flours and enzymwork 

Rasanen, 1994 

Finland English Yes Basophil 

histamine release, skin prick, serum specific IgE, serum total IgE 

Mixed (M) Workers of mixed occupation 

challenge-proven occupationrhinitis or asthma and workeseasonal rhinitis or other respiratory symptoms 

Redlich, 1996 

United States 

English Yes Bronchial 

alveolar lavage, eosinophils, single NSBPT 

Isocyanates (L) Currently exposed workers w

isocyanate asthma 

Ricciardi, 2003 

Italy English Yes Eosinophils, 

serial PFT (PEFR), single NSBPT, skin prick, serum specific IgE, serum total IgE 

Wood dust: iroko (L) 

Wood workers who reported asthma symptoms 

Sander, 2001 

Germany German Yes Skin prick Flour: wheat and 

rye (H) 

Bakers with asthma symptom

Sastre, 2003 

Spain English Yes Single NSBPT, 

serum specific IgE 

Isocyanates (L) Workers with a suspected cl

history of di-isocyanate-induasthma 

Schuermans, 2003 

Belgium English Yes Single NSBPT Latex (H) Workers of unreported occu

referred to centre for suspeclatex OA 

Schwaiblmair, 1997 

Germany English Yes Single NSBPT, 

single PFT, skin prick 

Bleaching powder (L) 

Hairdressers who had regulacontact with various hair proand a clinical history of job rerhinitic/asthma symptoms 
E-15

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Schwarting, 1979 

Germany German Yes Clinical 

diagnosis, skin prick, serum specific IgE 

Flour (H) Bakers who were exposed to 

dust for at least eight hrs pe

Shirai, 2003 

Japan English Yes Clinical 

diagnosis, single NSBPT, skin prick 

Green tea (L) Green tea factory workers w

clinical history suggestive of asthma referred to Internal Medicine and associated ho

Shirakawa, 1988 

Japan English Yes Antibodies (COHSA), 

eosinophils, single NSBPT, skin prick, serum specific IgE 

Chemical: cobalt (L) 

Hard metal plant workers whclinical criteria for OA 

Slovak, 1981 

United Kingdom 

English No Serial PFT 

(PEFR), skin prick 

Chemical: AZO dicarbonamide (L) 

Personnel with positive histowheezing or chest tightness cough) related to exposure tazodicarbonamide dust on screening at a manufacturing 

Symington, 1981 

United Kingdom 

English Yes Skin prick Mushroom dust 

(H) 

Food manufacturing workers presenting with work related symptoms to dried mushroom 

Tabar, 2004 

Spain English Yes Immunoblotting, 

skin patch test, skin prick, serum specific IgE, serum total IgE 

Asparagus (H) Workers with various occupa

diagnosed with asparagus ain the past five yrs 

Taivainen, 1994 

Finland Finnish Yes Clinical 

diagnosis, skin prick, serum specific IgE 

Animal/bird: cow dander (H) 

Farmers refered to a clinic foinvestigation of OA 
E-16

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Tee, 1998 

United Kingdom 

English No Skin prick, 

serum specific IgE 

Isocyanates (L) All workers exposed to isocy

who were referred for investof OA from whom blood was available for measurement oserum specific IgE and in whfirm diagnosis was reached 

Tse, 1982 

Canada English Yes Serum specific 

IgE 

Wood dust: cedar (L) 

Workers suspected to have cedar asthma who were refethe clinic to undergo antigenbronchoprovocation test to hthe diagnosis confirmed 

Vandenplas, 2001 

Belgium English Yes Clinical 

diagnosis, serial NSBPT, single NSBPT, skin prick 

Latex (H) Consecutive workers who w

referred for the investigation possible OA and who were exposed at work to airborne allergens from natural rubbegloves 

Vandenplas, 1995b 

Belgium English Yes Single NSBPT, 

skin prick 

Latex (H) Hospital employees (nurses

technologists, cleaning staff) exposed to latex 

Vanhanen, 2000 

Finland English Yes Single NSBPT, 

skin prick, serum specific IgE 

Cellulase (H) Workers with suspected OA 

rhinitis due to cellulase who referred to a clinic 

Virtanen, 1996 

Finland English No Serum specific 

IgE, serum specific IgG 

Animal/bird: cow dander (H) 

Randomly selected dairy fardiagnosed with cow asthma were workers of the pulmonaclinic 

Vogelmeier, 1991 

Germany English Yes Single NSBPT, 

skin prick, serum specific IgE 

Isocyanates (L) Workers who had occupation

contact with TDI and/or MDI strong clinical history or workrelated asthma and normal volunteers; subjects with astand no isocyanate exposure 
E-17

Table E-1. Description of included studies (Diagnosis review) (continued) Author, Year 

Location Language of 

Publication 

SIC used as Reference Standard 

Comparison Tests 

Suspected Agent (molecular weight) 

Description of Included Wo

Wurzinger, 1997 

Austria German Yes Single NSBPT, 

skin prick, serum specific IgE, serum total IgE 

Flour (H) Cooks, bakers, farmers, and 

confectioners with suspected 

Zeiler, 2002 

Finland English Yes Single NSBPT, 

skin prick, serum specific IgE, serum specific IgG 

Animal/bird: cow dander (H) 

Consecutive dairy farmers reto pulmonary clinic for confirof the bovine origin of their O

Zeiss, 1977 

United States 

English No Skin prick, 

serum specific IgE, serum specific IgG 

Chemical: trimellitic anhydride (L) 

Chemical plant workers with asthma and/or rhinitis symptdue to TMA exposure 

Abbreviations: AC = azodicarbonamide; CO-HSA = conjugated human serum; FEV1 = forced expiratory volume in one second; H = higMCP-1 = monocyte chemoattractant protein-1; MDI = diphenylmethane di-isocyanate; mos = months; NR = not reported; NSBPT = non-

provocation; OA = occupational asthma; PC20 = provocative concentration causing a 20% drop in FEV1; PEFR = peak expiratory flow rat

function test; sGaw = specific airways conductance; SIC = specific inhalational challenge; TCPA = tetrachlorophthalic anhydride; TDI-HS

isocyanates human serum albumin; TMA = trimellitic anhydride; wks = weeks; yr = year; yrs = years 
E-18

Table E-2. Demographic characteristics of included patients (Diagnosis review) 

Male Age Atopic Smoking 

Status 

History of Asthma 

%predicted FEV1 (unless otherwise stated) 

Years of Exposure

Years oSympto

Author, Year

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (S

Alvarez, 2001 

3 66.7 40.3 

(13.6) 

0 C: 0 

Ex: 0 N: 100 

- 94.7 

(1.5) 

- 1.7 

(0.6) 

Alvarez, 1996 

21 95.2 38.3 

(15.7) 

42.9 C: 14.3 - - - 5.5 

(7.7) 

Anees, 2004 

141 73.8 46 

(10.2) 

45.4 C: 17.7 

Ex: 33.3 N: 48.9 

- - - - 

Avery, 1969 

18 - - - - - - - - 

Balland, 1989 

75 61.3 - 24 - 52 - - - 

Baur, 1998 

229 66.4 35.1 

(11.4) 

- - - - 8.6 

(8.4) 

- 

Baur, 1979 

7 - - - - - - 4.8 

(2.8) 

- 

Behr, 1990 

70 - - - - - - - - 

Bernstein, 2002 

54 96.3 39.9 - - - - 11.2 

(11.1) 

- 

Biot, 1980 

12 - 41.6 

(11.4) 

- - - - - - 

Block, 1983 

7 100 50 

(13.6) 

85.7 C: 42.9 

Ex: 42.9 N: 14.3 

- 101.7 

(28.8) 

28.4 (16) 

- 

Burge, 1985 

15 93.3 45.7 

(11.1) 

46.7 C: 26.7 

Ex: 40 N: 33.3 

0 - - - 

Burge, 1982b 

136 - - - - - - - - 

Burge, 1980 

49 - - - - - - - - 

Burge, 1979a 

29 - - - - - - - - 
E-19

Table E-2. Demographic characteristics of included patients (Diagnosis review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

%predicted FEV1 (unless otherwise stated) 

Years of Exposure

Years oSympto

Author, Year

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (S

Burge, 1979b 

23 - - - - - - - - 

Burge, 1978 

21 14.3 45.2 

(12.5) 

42.9 C: 23.8 

Ex: 14.3 N: 66.7 

23.8 88.3 

(16.5) 

- - 

Butcher, 1980 

26 - - - - - - - - 

Carletti, 1997 

37 100 41 

(12) 

37.8 C: 48.6 - - - - 

Cartier, 1989 

62 93.5 - 40.3 C: 27.4 

Ex: 37.1 N: 35.5 

- 94 

(22) 

8.8 (8.5) 

- 

Cartier, 1987 

5 20 38.8 

(9.9) 

100 - 20 90 

(16.3) 

12.6 (4.3) 

0.7 (0.3) 

Cartier, 1986 

54 - - - - - - - - 

Choudat, 1999 

21 95.2 29.6 

(5.7) 

- - - 97 

(12.3) 

11.6 (6.4) 

- 

Cirla, 1975 

33 - - - - - 77 

(7.8) 

- - 

Colas, 1985 

10 100 47 30 - 10 - 21.6 3.4 

Cortona, 1980 

76 - 35 - - - - - - 

Cote, 1993 

25 100 - - - - - - - 

Coutts, 1984 

4 100 38 

(13) 

- - - - - - 

Curran, 1996 

20 10 46.7 

(11.4) 

- - - - - - 

Davison, 1983 

3 100 29 

(2.7) 

100 C: 66.7 

Ex: 0 N: 33.3 

0 PEF: 193.3 

(135.8) 

- - 
E-20

Table E-2. Demographic characteristics of included patients (Diagnosis review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

%predicted FEV1 (unless otherwise stated) 

Years of Exposure

Years oSympto

Author, Year

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (S

DeZotti, 1996a 

4 75 47.3 

(12.3) 

50 N: 100 - - - - 

DeZotti, 1996b 

54 61.1 30.6 

(9.6) 

25.9 C: 24.1 44.4 - 8.7 

(9.6) 

- 

Dellabianca, 1996 

40 47.5 35.6 

(11.1) 

20 C: 20 

Ex: 40 N: 42.5 

- - - 2.35 

(10.6) 

Dente, 1986 

42 - - - - - - - - 

DiFranco, 1998 

24 75 45.3 

(9.6) 

25 C: 0 

Ex: 54.2 N: 45.8 

- - - 7.33 

(4.5) 

DiStefano, 1999 

24 12.5 38.6 

(8.8) 

37.5 C: 29.2 

Ex: 16.7 N: 54.2 

12.5 75.8 

(14.6) 

- - 

Duan, 1989 

18 33.3 - - - 100 - 9.5 

(4.8) 

- 

Ferguson, 1996 

90 63.3 34.3 

(10.2) 

- C: 46.7 

Ex: 35.6 N: 16.7 

- - 5.7 

(5.9) 

1.92 (3.3) 

Gannon, 1996 

127 - - - - - - - - 

Girard, 2004 

52 57.7 40.4 

(11.5) 

69.2 C: 23.1 

Ex: 44.2 N: 26.9 

- - 7.2 

(8.1) 

10.65 (11.4) 

Graneek, 1987 

9 - - - - - - - - 

Grosclaude, 1980 

30 73.3 38.7 10 - - - 10 1.9 

Harries, 1980 

37 45.9 37.5 

(9.8) 

59.5 - - - - - 
E-21

Table E-2. Demographic characteristics of included patients (Diagnosis review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

%predicted FEV1 (unless otherwise stated) 

Years of Exposure

Years oSympto

Author, Year

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (S

Hinojosa, 1986 

4 100 40 

(6.2) 

25 C: 25 

Ex: 25 N: 50 

- - 8.8 

(3.3) 

4.8 (2.6) 

Howe, 1983 

7 0 41.1 

(5) 

14.3 C: 100 

Ex: 0 N: 0 

0 - - - 

Huggins, 2003 

52 - - - - - - - - 

Jager, 1993 

14 14.3 34.7 

(8.1) 

42.9 - 71.4 - - - 

Karol, 1994 

63 73 30.6 - - - - 10.1 

(9) 

3.08 (3.9) 

Kern, 1991 

51 19.6 37.9 

(10.3) 

23.5 C: 41.2 

Ex: 13.7 N: 45.1 

5.9 - - - 

Keskinen, 1988 

35 80 37 

(10.5) 

31.4 C: 34.3 

Ex: 0 N: 65.7 

- - - - 

Kim, 1999 

16 56.3 48.6 

(10.4) 

37.5 C: 6.3 - - 20 

(5) 

- 

Kim, 1997 

81 50.6 41.8 

(8.1) 

- - - - - - 

Kongerud, 1992 

14 92.9 38.1 

(9.7) 

28.6 C: 50 

Ex: 14.3 N: 35.7 

- 94.9 

(9.9) 

- - 

Kopferschmitt-Kubler, 1998 

11 90.9 36.1 

(7.3) 

54.5 C: 18.2 

Ex: 54.5 N: 27.3 

9.1 FEV1: 3.4 

(0.5) 

- - 

Koskela, 2003 

37 35.1 42.8 

(8.3) 

- C: 13.5 - - - - 

Krakowiak, 2003 

25 - 41.9 

(11.6) 

72 C: 20 

Ex: 12 N: 68 

16 FEV1: 3.9 

(0.4) 

13 (7) 

- 
E-22

Table E-2. Demographic characteristics of included patients (Diagnosis review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

%predicted FEV1 (unless otherwise stated) 

Years of Exposure

Years oSympto

Author, Year

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (S

Lam, 1979 

86 - 41.4 

(10.5) 

23.3 C: 7 

Ex: 18.6 N: 74.4 

- - - - 

LaPaglia, 1986 

309 - 55.6 

(10.1) 

- - 5.2 - 32.8 

(10.5) 

- 

Larbanois, 2003 

174 62.6 38.4 

(10) 

58 N: 59.8 - - - 3.41 

(4.5) 

Lemiere, 2001 

31 90.3 42.1 

(13) 

71 C: 58.1 

Ex: 0 N: 41.9 

- - - 3.35 

(4.9) 

Liss, 1991 

50 72 44 56 - - - 12 3.5 

Lozewicz, 1985 

7 42.9 43 

(11) 

42.9 C: 14.3 - - - - 

Malo, 1993a 

74 91.9 - - C: 13.5 

Ex: 41.9 N: 44.6 

- 91 

(18) 

9.4 (8.1) 

- 

Malo, 1991 

162 77.2 39.6 

(11.8) 

54.3 C: 30.2 

Ex: 40.7 N: 27.2 

- 92.7 

(16.4) 

6.5 (8.8) 

1.9 (2.7) 

Malo, 1990 

164 76.2 38.8 

(12.2) 

57.3 C: 27.4 

Ex: 34.8 N: 37.8 

- - 8.8 

(8.4) 

3.15 (3.4) 

Malo, 1988a 

51 49 37 

(10) 

39.2 N: 49 7.8 - 10 

(8) 

- 

Mapp, 1986 

6 66.7 31.7 

(13) 

33.3 C: 16.7 

Ex: 33.3 N: 50 

- 104 

(20.6) 

11.6 (10) 

2.11 (2.3) 

Mapp, 1979 

15 86.7 36.8 

(12.2) 

- C: 6.7 

Ex: 13.3 N: 80 

- FEV1: 3.6 

(0.7) 

7 - 

Merget, 1997 

34 76.5 26 

(10.5) 

- - - - 7.7 

(8.4) 

- 
E-23

Table E-2. Demographic characteristics of included patients (Diagnosis review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

%predicted FEV1 (unless otherwise stated) 

Years of Exposure

Years oSympto

Author, Year

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (S

Merget, 1996 

57 94.7 37 

(10) 

49.1 C: 54.4 

Ex: 17.5 N: 10.5 

0 98 

(14) 

- 5.25 

(5.3) 

Merget, 1993 

42 - - 38.1 C: 35.7 

Ex: 42.9 N: 21.4 

- - 9.5 

(8.5) 

- 

Mole, 1977 

40 100 34.6 

(6) 

- C: 37.5 - - - - 

Moller, 1986 

12 83.3 41.1 

(14.6) 

16.7 C: 25 

Ex: 25 N: 50 

16.7 - 2.1 

(3) 

- 

Moller, 1985 

7 - - 28.6 - 28.6 - - - 

Moscato, 1993 

75 85.3 40.1 

(10.5) 

41.3 C: 29.3 

Ex: 26.7 N: 42.7 

- - 19.5 

(31.8) 

4.2 (5.4) 

Munoz, 2004 

8 0 37 

(7.3) 

37.5 C: 37.5 - FEV1: 2.9 

(0.7) 

11 (5.5) 

- 

Nielsen, 1988 

5 - - - - - - 13.8 

(9.7) 

- 

Nordman, 1985 

12 25 - 16.7 - - FEV1: 2.8 

(0.7) 

- - 

O'Brien, 1979a 

24 100 - - - - - - - 

O'Brien, 1979b 

63 - 43 

(8.8) 

36.5 C: 22.2 

Ex: 23.8 N: 36.5 

- - - - 

Obata, 1999 

17 100 35.3 

(10.6) 

70.6 C: 0 

Ex: 5.9 N: 94.1 

- - 6.2 

(9.2) 

2.1 (2.7) 

Obtulowicz, 1998 

49 59.2 48.5 

(8.3) 

36.7 C: 46.9 - - - - 
E-24

Table E-2. Demographic characteristics of included patients (Diagnosis review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

%predicted FEV1 (unless otherwise stated) 

Years of Exposure

Years oSympto

Author, Year

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (S

Paggiaro, 1987b 

332 - 25.5 

(12) 

36.1 N: 67.8 - - - - 

Paggiaro, 1986 

114 75.4 46.2 

(11.8) 

20.2 C: 19.3 

Ex: 22.8 N: 57 

- - - 3.69 

(3.5) 

Paggiaro, 1984b 

6 33.3 37.2 

(11.7) 

50 C: 50 

Ex: 0 N: 50 

- 95.5 

(20.2) 

11.8 (4.4) 

5.7 (1.3) 

Paggiaro, 1984c 

- - - - - - - - - 

Paggiaro, 1981 

3 100 49.3 

(13.4) 

33.3 C: 100 

Ex: 0 N: 0 

- 93.3 

(14) 

3.3 (3.9) 

3.1 (4.1) 

Palczynski, 2003 

6 16.7 43.7 

(7.9) 

16.7 C: 0 - - - - 

Park, 2002b 

4 - 24.8 

(1.3) 

75 C: 0 

Ex: 0 N: 100 

- - - - 

Park, 2001 

136 89 40.8 

(8.7) 

38.2 - - - 9.2 

(5.2) 

- 

Park, 1999 

63 73 38.5 

(10.6) 

52.4 - - - 5.7 

(5.6) 

- 

Park, 1998 

15 100 - 93.3 - - - - - 

Park, 1994 

4 100 42 

(13) 

75 C: 0 

Ex: 100 N: 0 

- - - - 

Park, 1991 

13 - - - - - - - - 

Park, 1989 

9 100 35.6 

(6) 

33.3 C: 44.4 

Ex: 55.6 N: 0 

- FEV1: 3.5 

(0.6) 

1.5 (0.5) 

- 
E-25

Table E-2. Demographic characteristics of included patients (Diagnosis review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

%predicted FEV1 (unless otherwise stated) 

Years of Exposure

Years oSympto

Author, Year

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (S

Perrin, 1990 

23 - - - - - - - - 

Pezzini, 1984 

28 64.3 - 25 - - - 12.2 

(8.5) 

- 

Prichard, 1984 

20 100 32 - C: 45 

Ex: 15 N: 40 

- FEV1: 4 - - 

Quirce, 2000 

5 80 49.2 

(9.5) 

60 C: 0 

Ex: 20 N: 80 

- - 23.8 

(12.8) 

11.7 (5.9) 

Quirce, 1992 

5 80 40.8 

(17.2) 

80 C: 60 

Ex: 0 N: 40 

- 90 

(8.2) 

22.2 (15.8) 

7.4 (5.6) 

Rasanen, 1994 

28 39.3 37.6 

(9) 

- - - - - - 

Redlich, 1996 

3 - - - - - - - - 

Ricciardi, 2003 

9 77.8 47.3 

(10.6) 

11.1 C: 11.1 

Ex: 0 N: 88.9 

- FEV1: 4.4 

(0) 

- - 

Sander, 2001 

7 - - - - - - - - 

Sastre, 2003 

22 81.8 38.6 

(10.6) 

36.4 C: 4.5 

Ex: 9.1 N: 81.8 

- - 13.7 

(9.1) 

3.7 (3.1) 

Schuermans, 2003 

39 - - - - - - - - 

Schwaiblmair, 1997 

55 0 30.8 

(14.1) 

14.5 C: 34.5 - FEV1: 3 

(0.7) 

15.1 (14.8) 

4.8 (5.2) 

Schwarting, 1979 

- - - - - - - - - 
E-26

Table E-2. Demographic characteristics of included patients (Diagnosis review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

%predicted FEV1 (unless otherwise stated) 

Years of Exposure

Years oSympto

Author, Year

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (S

Shirai, 2003 

21 42.9 44 

(14.5) 

52.4 C: 14.3 

Ex: 33.3 N: 52.4 

- - - 3.17 

(4.3) 

Shirakawa, 1988 

12 - 48.3 

(5.4) 

66.7 C: 41.7 - - - - 

Slovak, 1981 

28 100 41 

(8.5) 

46.4 C: 42.9 

Ex: 32.1 N: 25 

0 - - - 

Symington, 1981 

8 37.5 - 25 - - - 8.1 

(4) 

- 

Tabar, 2004 

10 20 38.3 

(10.2) 

60 - - - - - 

Taivainen, 1994 

100 47 44 

(10.8) 

- C: 4 

Ex: 28 N: 68 

97 - - - 

Tee, 1998 

101 93.1 - - - - - - - 

Tse, 1982 

28 - - - - - - - - 

Vandenplas, 2001 

45 4.4 33.6 

(6.1) 

68.9 N: 73.3 20 - - 3.01 

(2.8) 

Vandenplas, 1995b 

13 0 33 

(4) 

53.8 C: 15.4 

Ex: 23.1 N: 61.5 

- 97.4 

(9.7) 

- 4 

(3) 

Vanhanen, 2000 

11 36.4 36.5 

(7.2) 

63.6 C: 27.3 - 93.5 

(8.2) 

- - 

Virtanen, 1996 

11 63.6 46 

(7.3) 

- - - - - - 

Vogelmeier, 1991 

19 94.7 49.4 

(2.5) 

- - - - 6 

(5.8) 

- 
E-27

Table E-2. Demographic characteristics of included patients (Diagnosis review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

%predicted FEV1 (unless otherwise stated) 

Years of Exposure

Years oSympto

Author, Year

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (S

Wurzinger, 1997 

5 40 39.6 

(19.3) 

- - - - - - 

Zeiler, 2002 

9 66.7 40 

(10) 

66.7 C: 0 

Ex: 44.4 N: 55.6 

- - - - 

Zeiss, 1977 

4 - 40.3 

(13.4) 

25 - - - 2 

(2.7) 

- 

Abbreviations: C = current; Ex = ex; FEV1 = forced expiratory volume in one second; N = never; PEF = peak expiratory flow; SD = stan
E-28

Table E-3. Description of diagnostic tests (Diagnosis review) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Alvarez, 2001 

SIC: oilseed rape flour 

≧20% decline in FEV1 Referenced 

(Chatham et al., 1982) 

Eosinophils: sputum Single NSBPT: methacholine Skin prick: atopy and specific 

Not reported Not reported Wheal diameter ≧3 mm 

 Serum specific IgE >0.35 KU/L Alvarez, 1996 

SIC: cereals (wheat, alpha amylase, soyabean, l.destructor) 

≧20% decline in FEV1 Described in 

text 

Single NSBPT: methacholine Skin prick: atopy 

PD20 FEV1 ≦250 cbu 

Wheal diameter ≧3 mm 

with no reaction to negative control 

 Serum specific IgE CAP score ≧class 1 Anees, 2004 

Other: clinical diagnosis 

SIC and/or serum specific IgE and/or serial NSBPT 

Not reported Serial PFT (PEFR): 

monitored at least 3 times/day for at least 5 work (4-6 days) and rest (2-3 days) periods 

OASYS-2 score >2.5 

Avery, 1969 

Other: clinical diagnosis 

Not reported Not reported Other: TDI-HSA Not reported 

Balland, 1989 

SIC: suspected agent 

≧100% increase in specific 

airway resistance 

Not reported Single NSBPT: 

methacholine 

≧2 fold increase in 

airway resistance between 0-1500 gamma of methacholine 

 Serum specific IgE Not reported  Serum total IgE Not reported Baur, 1998 

SIC: suspected agent 

≧40% decline in sGaw Referenced 

(Jaeger et al., 1992; Marek et al., 1994; Schwaiblmair et al.1991) 

Clinical diagnosis Case history: reversible 

airway narrowing in the sense of SOB and wheezing causally related to exposure in the working environment 

 Single NSBPT: 

methacholine 

PD40 sGaw <0.3 mg 
E-29

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Baur, 1979 

SIC: papain Not reported Not reported Skin prick: atopy 

and specific 

Not reported 

 Serum specific IgE Not reported Behr, 1990 

SIC: isocyanates ≧100% increase in sRaw 

from baseline and absolute values ≧2.0 kPa/s 

Described in text 

Clinical diagnosis Single NSBPT: methacholine 

Not reported 

≧100% increase in 

sRaw from baseline and absolute values ≧2.0 

kPa/s 

Bernstein, 2002 

SIC: isocyanates ≧20% decline in FEV1 Referenced 

(Ryan et al., 1981; Stark et al., 1993) 

Other: di-isocyanate antigen stimulation of MCP-1 

Maximal antigen stimulation of MCP-1 

≧mean + 2SD of control 

subjects 

 Single NSBPT: 

methacholine 

PC20 FEV1 ≦8 mg/ml 

 Serum specific IgE OD at 405 ≧0.1 Biot, 1980 

SIC: suspected agent 

Not reported Described in 

text 

Other: basophils granules liberation 

Not reported 

 Single NSBPT: 

acetylcholine 

Not reported 

 Serum total IgE Not reported Block, 1983 

SIC: wheat and/or rye flour 

≧20% decline in FEV1 Referenced 

(Lam et al., 1979) 

Single NSBPT: methacholine Skin prick: atopy and specific 

PC20 FEV1: no cutoff 

reported Wheal diameter ≧2 mm 

 Serum specific IgE Not reported Burge, 1985 

SIC: formaldehyde 

Not reported Described in 

text 

Single NSBPT: histamine 

PC20 FEV1 ≦32 mg/ml 

Burge, 1982b 

SIC: suspected agent 

Not reported Described in 

text 

Single NSBPT: histamine 

PD20 FEV1 <32 mg/mL 

Burge, 1980 

SIC: colophony, abietic acid, methyl ester, glycerol ester, amine hydrocholride 

≧15% decline in FEV1 Described in 

text 

Single NSBPT: histamine 

PC20 FEV1 ≦16 mg/ml 
E-30

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Burge, 1979a 

SIC: solder-flux fumes 

≧15% decline in FEV1 Referenced 

(Burge et al., 1978) 

Clinical diagnosis History and effects of 

subsequent exposure at work 

 Serial PFT (PEFR): 

monitored every hour while away for at least 2 wks at work and at least 2 wks away 

Comparison of recordings taken at work compared to those taken away from work 

Burge, 1979b 

SIC: isocyanates ≧15% decline in FEV1 Referenced 

(O'Brien et al., 1979) 

Clinical diagnosis Final assessment based 

on subsequent course of asthma on reexposure at work 

 Serial PFT (PEFR): 

monitored every hour or 2 hrs for at least 2 wks at work and 2 wks away 

≧25% of cases 

demonstrated specific daily pattern with a weekly pattern 

Burge, 1978 

SIC: colophony >15% decline in FEV1 Not reported Eosinophils: blood 

Single PFT: FEV1, 

FVC 

Not reported Not reported 

 Skin prick: atopy Mean wheal diameter 

>2 mm with negative control 

Butcher, 1980 

SIC: TDI Not reported Not reported Serum specific IgE 2 definitions: ratio >2; 

test cpm >control mean + 3SD 

 Serum total IgE Not reported 
E-31

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Carletti, 1997 

SIC: wheat flour >20% decline in FEV1 Described in 

text 

Clinical diagnosis Symptoms of cough, 

expectoration,wheezing, dyspnea, difficulties breathing associated with exposure to wheat powder/flour 

 Single NSBPT: 

methacholine 

PD20 FEV1 <1 mg 

 Single PFT: FVC, 

FEV(25-75) 

Not reported 

 Skin prick: atopy 

and specific 

Mean wheal diameter 

≧5 mm for atopy and ≧3 mm for specific 

Cartier, 1989 

SIC: isocyanates ≧3 consecutive values with 

≧20% decline in FEV1 and 

fluctuations not exceeding 10% on the control 

Referenced (Pepys and Hutchcroft, 1975) 

Serial NSBPT: histamine or methacholine Single NSBPT: histamine or methacholine 

≧3.2 fold change in PC20

FEV1 before and after 

SIC PC20 FEV1 ≦16 mg/ml 

 Skin prick: atopy 

and specific 

Wheal diameter ≧3 mm 

without dermographism and with wheal diameter 

≧3 mm to histamine 

control 

 Serum specific IgE OD reading ≧two times 

the OD of the mean of the negative controls 

 Serum specific IgG OD reading ≧two times 

the OD of the mean of the negative controls 

Cartier, 1987 

SIC: psyllium ≧20% decline in FEV1 Referenced 

(Pepys and Hutchcroft, 1975) 

Single NSBPT: histamine Skin prick: atopy and specific 

PC20 FEV1 <8 mg/ml 

Not reported 

 Serum specific IgE Not reported 
E-32

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Cartier, 1986 

SIC: snowcrab extract 

Not reported Not reported Skin prick: specific1 Wheal diameter >2 mm 

larger than control 

 Serum specific IgE1 2 cutoff values: >2; >4.5  Eosinophils: blood2 >500 cells/cc  Serial NSBPT: 

histamine2

≧3.2 fold change in PC20

FEV1 upon return to 

work 

 Single NSBPT: 

histamine2

PC20 FEV1 ≦16 mg/ml 

Choudat, 1999 

SIC: wheat flour ≧20% decline in FEV1 Referenced 

(Cloutier et al., 1989) 

Single NSBPT: methacholine Serum specific IgE 

PD20 FEV1: no cutoff 

Not reported 

Cirla, 1975 

SIC: TDI Not reported Described in 

text 

Single NSBPT: acetylcholine 

Not reported 

 Skin prick: atopy 

and specific 

Not reported 

Colas, 1985 

SIC: wood dust (exotic) 

≧100% increase in specific 

airway resistance 

Described in text 

Eosinophils: blood Other: carbon dioxide diffusion 

Not reported Not reported 

 Single NSBPT: 

carbachol 

≧100% increase in 

airways resistance (threshold dose) 

 Single PFT: FEV1, 

FVC 

Presence of "trouble ventilatoire obstructif" (airway obstruction) 

 Skin prick: atopy 

and specific 

Not reported 

 Serum total IgE Not reported 
E-33

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Cortona, 1980 

Other: clinical diagnosis 

Included results from ECSC questionnaire and lung function testing 

Described in text 

Skin prick: atopy and Specific 

Not reported 

Cote, 1993 

SIC: plicatic acid ≧15% decline in FEV1 Referenced 

(Chan-Yeung et al., 1973) 

Serial PFT (PEFR): monitored 6 times/day for 3 wks at work and 2 wks away3

2 of 3 physicians agreed that PEF graphs showed work related change in 2 of 3 work wks 

 Other: 

questionnaire3 Not reported 

 Serial NSBPT: 

methacholine4

>2 fold decrease in PC20 FEV1 after 3 work 

wks compared to after 2 holiday wks 

Coutts, 1984 

SIC: cimetidine powder 

Not reported Not reported Single NSBPT: 

histamine 

Not reported 

 Skin prick: atopy 

and specific 

Not reported 

Curran, 1996 

Other: clinical diagnosis 

Not reported Not reported Serum specific IgE >0.88 net RAST % 

binding with serum total IgE equal to or less than 150 kU/L 

 Serum total IgE <150 kU/L Davison, 1983 

SIC: castor beans Not reported Referenced 

(Davies et al., 1974) 

Skin prick: atopy Serum specific IgE 

Not reported % binding >2 times the control 

DeZotti, 1996a 

SIC: wood dust (exotic) 

≧15% decline in FEV1 Described in 

text 

Eosinophils: blood Single NSBPT: methacholine 

Not reported PD20 FEV1: no cutoff 

 Single PFT: FEV1, 

FVC 

Not reported 

 Skin prick: atopy Wheal diameter >3 mm 
E-34

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response DeZotti, 1996b 

SIC: suspected agent 

≧15% decline in FEV1 Described in 

text 

Eosinophils: blood Single NSBPT: methacholine 

Not reported PD20 FEV1: no cutoff 

 Single PFT: FEV1 Not reported  Skin prick: atopy Wheal diameter ≧3 mm  Serum specific IgE Not reported Dellabianca, 1996 

SIC: suspected agent 

≧15% decline in FEV1 Not reported Single NSBPT: 

methacholine 

PD20 FEV1 ≦1560 μg 

Dente, 1986 

SIC: TDI Not reported Described in 

text 

Single NSBPT: methacholine 

PD15 FEV1 <1.0 mg 

DiFranco, 1998 

SIC: suspected agent 

Not reported Not reported Eosinophils: sputum 

Single NSBPT: methacholine 

>1% PD20 FEV1 <1 mg 

DiStefano, 1999 

Other: clinical diagnosis 

Included SIC and/or serial PFT 

Described in text 

Single NSBPT: histamine 

Not reported 

 Skin prick: atopy Wheal diameter >3 mm Duan, 1989 

SIC: TDI ≧15% decline in FEV1

(lasted 15 minutes) 

Described in text 

Clinical diagnosis Asthma symptoms at 

work, better or no symptoms away from work 

 Serial NSBPT: 

methacholine 

2 times (Chinese translation) 

 Serial PFT: PEFR Not reported  Single PFT: FEV1

(including reversibility) 

FEV1 decrease 15-20% 

 Skin prick: specific Not reported  Serum specific IgE Not reported Ferguson, 1996 

SIC: isocyanates ≧15% decline in FEV1

(persistent) 

Described in text 

Single NSBPT: histamine 

Not reported 

 Single PFT: FEV1, 

FVC (including reversibility) 

Reversibility: ≧15% 

increase in FEV1

 Serum specific IgE Not reported 
E-35

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Gannon, 1996 

Other: clinical diagnosis 

Included SIC and/or bronchial hyperreactivity and/or serum specific IgE (RAST) and/or asymptomatic 

Not reported Serial PFT (PEFR): 

monitored every 2 hrs for 2 wks at work and 2 wks away 

OASYS-2 score ≧2.51 

Girard, 2004 

SIC: suspected agent 

Not reported Referenced 

(Cartier, 1997) 

Eosinophils: sputum 3 cutoffs used: >1%, 

2%, or 6.4% 

 Serial NSBPT: 

methacholine 

≧3.2 fold change in PC20

FEV1 between at work 

and away 

 Serial PFT: PEFR 2 definitions: OASYS-2 

score ≧2.51; clinical 

opinion 

 Skin prick: atopy Not reported Graneek, 1987 

SIC: suspected agent 

>15% decline in FEV1 Referenced 

(Pepys and Hutchcroft, 1975) 

Single NSBPT: histamine 

PC20 FEV1 ≦16 mg/ml 

Grosclaude, 1980 

SIC: suspected agent 

≧50% increase in airway 

resistance 

Described in text 

Single NSBPT: acetylcholine 

Dose provoking augmentation of 50% of airway resistance ≦1000 

μg 

 Skin prick: atopy 

and specific 

Not reported 

 Serum total IgE Not reported Harries, 1980 

SIC: suspected agent 

≧15% decline in FEV1 Described in 

text 

Eosinophils: blood Skin prick: atopy 

Not reported Wheal diameter >3 mm to at least 1 allergen with negative reaction to control 

Hinojosa, 1986 

SIC: wood dust (African maple and ramin) 

≧20% decline in FEV1 Described in 

text 

Skin prick: atopy and specific Serum specific IgE 

Not reported Not reported 

 Serum total IgE Not reported 
E-36

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Howe, 1993 

SIC: lactose powder, TCPA powder, epoxy resin powder, blue pigment powder 

≧15% decline in FEV1 Described in 

text 

Skin prick: atopy and specific5

Serum specific IgE5

Single NSBPT: histamine6

Wheal diameter >2 mm larger than control Not reported Not reported 

Huggins, 2003 

Other: clinical diagnosis 

Included symptoms and/or serum specific IgE and/or SPT 

Not reported Serial PFT (PEFR): 

monitored every 2 hrs for 4 wks 

Various definitions: expert interpretation; OASYS-2 score ≧2.75; 

rest-work PEF ≧16 

L/min; daily variation at work >daily variation away 

Jager, 1993 

SIC: latex 100% increase in sRaw to 

at least 5 cm H2O/L/s 

Described in text 

Other: supervised work challenge 

Not reported 

 Single NSBPT: 

methacholine 

Not reported 

 Skin prick: atopy 

and specific 

Not reported 

 Serum specific IgE Not reported  Serum total IgE Not reported Karol, 1994 

SIC: TDI ≧20% decline in FEV1 Referenced 

(Mapp et al., 1988) 

Clinical diagnosis Single NSBPT: methacholine 

Clinical and workplace history PD20 FEV1 <1.4 mg 

 Serum specific IgE >mean + 2SD of control 

subjects 

 Serum specific IgG Not reported  Serum total IgE >114 IU/ml Kern, 1991 

Other: clinical diagnosis 

Based on criteria for diagnosis of RADS 

Referenced (Harkonen et al., 1983) 

Single NSBPT: methacholine 

PD20 FEV1: no cutoff 
E-37

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Keskinen, 1988 

SIC: isocyanates ≧20% decline in PEF or 15-

19% if other supporting findings 

Referenced (NewmanTaylor and Davies, 1981) 

Skin prick: atopy Reaction >1/2 reaction 

to histamine to at least 1 allergen with negative reaction to dilutant 

 Serum specific IgE Ratio values ≧2 with 

absorbance reading 

≧1/2 of the D-reference 

point 

Kim, 1999 

SIC: citrus red mite 

Not reported Described in 

text 

Single NSBPT: methacholine 

PC20 FEV1 <16 mg/ml 

 Single PFT: FEV1 Reversibility: ≧15% 

increase in FEV1

 Skin prick: atopy 

and specific 

Allergen:histamine wheal diameter ratio >1 

 Serum specific IgE Absorbance value 

>0.24 

 Serum total IgE ≧160 IU/ml Kim, 1997 

Other: clinical diagnosis 

Included symptoms and serial PFT 

Described in text 

Single PFT: FEV1, 

FVC 

Not reported 

 Serum specific IgE Counts per minute of 

reference disk was >2 times control disk 

 Serum specific IgG OD ratio >mean +/- 3SD 

for negative control 

Kongerud, 1992 

Other: serial PFT >15% variation in diurnal 

PEF 

Referenced (Burge, 1982) 

Clinical diagnosis Criteria proposed by 

Burge (1982) 

 Eosinophils: blood Not reported  Other: symptom 

score 

Not reported 

 Serial NSBPT: 

methacholine 

>2 fold change in PC20

FEV1 between work and 

away periods 

 Single NSBPT: 

methacholine 

PC20 FEV1 <8 mg/ml 

 Serum total IgE Not reported 
E-38

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response KopferschmittKubler, 1998 

SIC: TDI ≧20% decline in FEV1 Described in 

text 

Serial PFT (FEV1): 

monitored at least 3 times/day on a 1 month diary card 

Not reported 

 Single NSBPT: 

methacholine 

PD20 FEV1 <3200 μg 

Koskela, 2003 

SIC: bovine dander 

>15% decline in FEV1 Not reported Exhaled nitric oxide >46 ppm 

 Single NSBPT: 

histamine or mannitol 

Histamine: PC20 FEV1

<8mg/mL / mannitol: >15% decrease in FEV1

 Skin prick: specific Wheal diameter ≧3 mm  Serum specific IgE >5 IU/L  Serum total IgE Not reported Krakowiak, 2003 

SIC: rodent flour/dust 

>20% decline in FEV1 Described in 

text 

Clinical diagnosis Included medical 

history, physical examination and spirometry 

 Eosinophils: nasal 

lavage 

Not reported 

 Single NSBPT: 

histamine 

PC20 FEV1: no cutoff 

 Skin prick: atopy 

and specific 

Wheal 4mm >control; flare 5mm >control 

 Serum specific IgE Not reported Lam, 1979 

SIC: red cedar, aerosol inhalation or exposure to work environment 

Not reported Referenced 

(Chan-Yeung et al., 1973) 

Single NSBPT: methacholine 

PC20 FEV1 ≦16 mg/ml 

 Skin prick: atopy ≧2 positive reactions 
E-39

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response LaPaglia, 1986 

SIC: wheat, straw, hay, wood, animal allergens 

≧15% decline in FEV1 Described in 

text 

Clinical diagnosis Significant reduction in 

FEV1, shortness of 

breath, wheezing episodes 

 Skin prick: atopy 

and specific 

Not reported 

Larbanois, 2003 

SIC: suspected agent 

≧20% decline in FEV1 Referenced 

(Vandenplas and Malo, 1997) 

Serial PFT (sGaw): before and after SIC Single NSBPT: histamine 

2 cutoff values: >35 decrease; >50% decrease PC20 FEV1 <16 mg/ml 

Lemiere, 2001 

SIC: suspected agent 

≧20% decline in FEV1 Referenced 

(Cartier, 1994) 

Eosinophils: sputum ≧0.26x106 cells/ml 

 Single NSBPT: 

methacholine 

PC20 FEV1 <8 mg/ml 

 Skin prick: atopy 

and specific 

Wheal diameter ≧3 mm 

to at least 1 allergen with positive reaction to histamine and negative reaction to diluent 

Liss, 1991 

SIC: suspected agent 

Not reported Referenced 

(Pepys and Hutchcroft, 1975) 

Serial PFT (PEFR): monitored 4 times/day for at least 2 wks at work and 2 wks away7

≧20% diurnal variation 

on at least 2 days with lowest value on a work day 

 Single NSBPT: 

methacholine7

PC20 FEV1 ≦8 mg/ml 

 Single PFT: FEV1

(including reversibility)7

Reversibility: ≧15% 

increase in FEV1

 Skin prick: atopy 

and specific7

Wheal diameter >2 mm larger than control 

 Serial NSBPT: 

methacholine8

≧4 fold shift in PC20

FEV1 between after a day at work and after 10 to 14 days off work 
E-40

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Lozewicz, 1985 

SIC: cyanoacrylate based susbstances 

Not reported Not reported Single NSBPT: 

histamine Skin prick: atopy 

PC10 FEV1 ≦32 mg 

Not reported 

Malo, 1993a 

SIC: suspected agent 

Not reported Not reported Serial PFT (PEFR): 

monitored every 2 hrs for 2 wks at work and 2 wks away 

Not reported 

Malo, 1991 

SIC: red cedar, flour, psyllium, guar gum 

>20% decline in FEV1 Referenced 

(Pepys and Hutchcroft, 1975) 

Other: Questionnaire Serial NSBPT: histamine or methacholine 

Not reported 

≧3.2 fold change in PC20

FEV1 between work and 

away 

 Serial PFT (PEFR): 

monitored every 2 hrs or at least 4 times/day 

Interpreted by experienced physicians 

 Single NSBPT: 

histamine or methacholine 

PC20 FEV1 ≦16 mg/ml 

 Skin prick: atopy Wheal diameter ≧3 mm 

to at least 1 allergen with positive reaction to histamine and negative reaction to diluent 

Malo, 1990 

SIC: suspected agent 

Immediate: ≧15% decline 

in FEV1; late: ≧12% decline 

in FEV1

Referenced (Pepys and Hutchcroft, 1975) 

Single NSBPT: histamine or methacholine Skin prick: atopy 

PC20 FEV1 <16 mg/ml 

Immediate reaction within 10-15 minutes 
E-41

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Malo, 1988a 

SIC: spiromycin ≧20% decline in FEV1 Referenced 

(Pepys and Hutchcroft, 1975) 

Eosinophils: blood Not reported 

 Other: 

questionnaire 

Not reported 

 Serial PFT (PEFR): 

monitored 4 times/day and when they had chest symptoms for 2 wks including weekends 

>20% variation 

 Single NSBPT: 

methacholine 

PD20 FEV1 ≦16 mg/ml 

 Skin prick: atopy Not reported Mapp, 1986 

SIC: TDI Not reported Described in 

text 

Single NSBPT: methacholine 

PD20 FEV1 ≦0.7 mg 

 Skin prick: atopy Not reported Mapp, 1979 

SIC: isocyanates >15% decline in FEV1, 

change in Vmax >20% and change in sGaw >25% 

Referenced (Fantuzzi et al., 1973) 

Single NSBPT: carbachol 

>15% decline if FEV1: 

no cutoff, change in Vmax >20% and change in sGaw >25%/ND 

 Skin prick: atopy Not reported Merget, 1997 

SIC: wheat flour ≧50% decline in sGaw after 

inhalation of 100 mg/ml flour extract, seven cumulative capsules or less 

Not reported Single NSBPT: 

methacholine Skin prick: atopy and specific 

PD50 sGaw ≦1 mg 

Wheal diameter ≧3 mm 

larger than saline control 

 Serum specific IgE RAST ≧0.35 Phadebus 

RAST units/ml 

 Serum total IgE Not reported 
E-42

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Merget, 1996 

SIC: platinum salts 

≧50% decline in sGaw with 

platinum salt concentration 

≦0.01 mol/L 

Referenced (Merget et al., 1991) 

Single NSBPT: methacholine 

PD50 sGaw ≦8 mg/ml 

 Skin prick: atopy 

and specific 

Atopy: wheal diameter 

≧4 mm / Specific: wheal 

diameter ≧2 mm 

 Serum total IgE Not reported Merget, 1993 

SIC: enzymes ≧50% decline in sGaw with 

enzyme concentration 

≦10mg/ml 

Described in text 

Single NSBPT: methacholine Skin prick: atopy and specific 

PD50 sGaw with dose 

<mg Wheal diameter 

≧histamine control 

 Serum specific IgE ≧0.35 PRU  Serum total IgE Not reported Mole, 1977 

Other: clinical diagnosis 

Included pulmonary function tests, ECG, chest x-ray, and skin prick tests 

Described in text 

Other: skin patch test 

Not reported 

 Single NSBPT: 

acetylcholine 

>10% decrease in FEV1 

Moller, 1986 

SIC: TDI ≧20% decline in FEV1 Described in 

text 

Clinical diagnosis Clinical and 

occupational history 

 Single NSBPT: 

methacholine 

PD20 FEV1: no cutoff 

 Single PFT: FEV1, 

FVC, PEFR 

Not reported 

Moller, 1985 

Other: physician diagnosis 

Based on shortness of breath, wheezing or coughing exacerbated at work and/or at night, improvement 

Described in text 

Eosinophils: not reported Other: questionnaire Serial PFT (FEV1): 

pre- and post- shift 

Not reported Not reported >20% decline in FEV1

post-shift compared to pre-shift 

 Serum specific IgE ≧1 ng/ml 
E-43

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Moscato, 1993 

SIC: TDI ≧15% decline in FEV1 Described in 

text 

Single NSBPT: methacholine 

PD15 FEV1 <0.85 mg 

 Single PFT: FEV1, 

FVC 

Not reported 

 Skin prick: atopy Wheal diameter >5 mm Munoz, 2004 

SIC: potassium persulfate 

>20% decline in FEV1more than placebo challenge 

Referenced (Pepys and Hutchcroft, 1975) 

Serial PFT (PEFR): monitored every 4 hrs for 2 wks at work and 2 wks away 

Qualitative assessment revealed evident changes between periods 

 Single NSBPT: 

methacholine 

PC20 FEV1 <8 mg/ml 

 Skin prick: atopy 

and specific 

Average of largest and smallest wheal diameter >3mm and more than reaction to histamine control 

 Serum total IgE >150 IU Nielsen, 1988 

Other: clinical diagnosis 

Included symptoms during employment and unequivocal and plausible relation to irritant exposure 

Described in text 

Single NSBPT: methacholine Skin prick: atopy and specific 

Not reported Wheal area >1/2 of histamine reaction 

 Serum specific IgE Ratio >2.2  Serum specific IgG Not reported  Serum total IgE Not reported 
E-44

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Nordman, 1985 

SIC: formaldehyde 

Immediate: ≧15% decline 

in PEF; late: ≧20% decline 

in PEF 

Referenced (Pepys et al., 1972; NewmanTaylor and Davies, 1981) 

Eosinophils: not reported Serial PFT (PEFR): monitored every 3 hrs for at least 24 hrs before SIC 

Not reported Not reported 

 Single NSBPT: 

histamine or methacholine 

Histamine: ≧15% drop 

in PEF / methacholine: Not reported 

 Single PFT: FEV1, 

FVC (including reversibility) 

Reversibility: ≧15% 

increase and 150 ml in FEV1

 Serum total IgE Not reported O'Brien, 1979a 

SIC: isocyanates ≧15% decline in FEV1 Described in 

text 

Single NSBPT: histamine 

≧20% decline in FEV1≦32 mg/ml 

O'Brien, 1979b 

SIC: TDI ≧15% decline in FEV1 Described in 

text 

Other: exercise test >9% fall in FEV1 or 

PEFR 

 Single NSBPT: 

histamine 

PC20 FEV1 ≦32 mg/ml 

 Skin prick: atopy Not reported Obata, 1999 

SIC: plicatic acid >20% decline in FEV1 or 

PEF 

Referenced (Chan-Yueng et al., 1982) 

Eosinophils: sputum Exhaled nitric oxide Single NSBPT: methacholine 

Not reported Not reported PC20 FEV1 ≦8 mg/ml 

 Skin prick: atopy Wheal diameter ≧3 mm 

larger than negative control 

Obtulowicz, 1998 

SIC: suspected agent 

>20% decline in FEV1 and MEF 25-75% 

Described in text 

Eosinophils: blood Skin prick: atopy and specific 

Not reported Not reported 

 Serum total IgE Not reported 
E-45

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Paggiaro, 1987b 

SIC: plicatic acid >20% decline in FEV1 Referenced 

(Lam et al., 1983) 

Single NSBPT: methacholine 

PC20 FEV1: no cutoff 

reported 

 Skin prick: atopy 

and specific 

Wheal diameter ≧3 mm 

 Serum specific IgE Ratio >2.0 Paggiaro, 1986 

SIC: TDI ≧15% decline in FEV1 Described in 

text 

Single NSBPT: methacholine 

PD20 FEV1 ≦2 mg 

 Skin prick: atopy Wheal diameter >5 mm Paggiaro, 1984b 

SIC: enzymes >15% decline in FEV1 Described in 

text 

Single NSBPT: bethanechol 

>15% decline in FEV1: 

no cutoff reported 

 Skin prick: atopy 

and specific 

Wheal diameter ≧5 mm 

 Serum specific IgE Not reported  Serum total IgE Not reported Paggiaro, 1984c 

SIC: isocyanates ≧15% decline in FEV1 Referenced 

(Zedda et al., 1976) 

Clinical diagnosis Presence of dyspnea, 

wheezing from exposure to TDI or MDI and a positive response to SIC 

 Single NSBPT: 

bethanechol 

PD15 FEV1 ≦8 

Paggiaro, 1981 

SIC: wood dust (tanganyika aningre) 

Not reported Referenced 

(Pickering et al., 1972) 

Single NSBPT: acetylcholine or bethanechol 

Not reported 

 Skin prick: atopy 

and specific 

Not reported 

 Serum specific IgE Not reported Palczynski, 2003 

SIC: chloramine Not reported Not reported Eosinophils: nasal 

lavage 

Not reported 

 Single NSBPT: 

histamine 

Not reported 

 Skin prick: atopy 

and specific 

Wheal diameter >3 mm larger than negative control 

 Serum specific IgE >35 KU/L  Serum total IgE >35 KU/L 
E-46

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Park, 2002b 

SIC: porcine pancreatic extract 

≧20% decline in FEV1 Referenced 

(Park and Nahm, 1997) 

Other: immunoblotting Single NSBPT: methacholine 

Not reported Not reported 

 Skin prick: specific Not reported  Serum specific IgE >mean + 2SD of 

unexposed controls 

Park, 2001 

SIC: reactive dyes ≧20% decline in FEV1 Not reported Skin prick: atopy 

and specific 

Wheal diameter >2 mm larger than negative control and erythema reaction >21 mm 

 Serum specific IgE OD at 410 >0.013 Park, 1999 

SIC: TDI Not reported Referenced 

(Park et al., 1999) 

Single NSBPT: methacholine Single PFT: not reported 

PC20 FEV1: no cutoff 

reported Not reported 

 Skin prick: atopy Not reported  Serum specific IgE >mean + 2SD of control 

subjects 

Park, 1998 

SIC: grain dust ≧20% decline in FEV1 Referenced 

(Park and Nahm, 1997) 

Eosinophils: blood Other: Immunoblotting 

Not reported Not reported 

 Single NSBPT: 

methacholine 

PD20 FEV1 ≦25 mg/ml 

 Skin prick: atopy 

and specific 

Allergen:histamine area ratio between 0.1 and 1 and erythema >21 mm 

 Serum specific IgE ≧0.064 
E-47

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Park, 1994 

SIC: chromium salts 

≧20% decline in FEV1 Described in 

text 

Other: skin patch test 

Not reported 

 Serial PFT (PEFR): 

monitored every 2 hrs for 2 days at work 

Not reported 

 Single NSBPT: 

methacholine 

PC20 FEV1 ≦25 mg/ml 

 Skin prick: atopy 

and specific 

Not reported 

Park, 1991 

SIC: reactive dyes ≧20% decline in FEV1 Referenced 

(Park et al., 1989) 

Single NSBPT: methacholine Skin prick: atopy and specific 

PC20 FEV1 ≦5 mg/ml 

Allergen: histamine area ratio between 0.1 and 1 and erythema >21 mm 

 Serum specific IgE binding ≧2%  Serum total IgE >160 IU/ml Park, 1989 

SIC: reactive dyes ≧20% decline in FEV1 Referenced 

(Chai et al., 1975) 

Single NSBPT: methacholine Single PFT: FEV1

PC20 FEV1: no cutoff 

reported Not reported 

 Skin prick: atopy 

and specific 

Not reported 

 Serum specific IgE RAST binding >2% Perrin, 1990 

SIC: suspected agent 

Not reported Not reported Serial NSBPT: 

histamine or methacholine 

≧2 fold increase in PC20FEV1 between at work 

and away 

 Serial PFT (PEFR): 

monitored every 2 hrs for 2 wks or less at work and 2 wks away 

Various definitions: number of days with 

≧20% variation in PEFR ≧20%; lower maximum 

PEFR values at work; lower minimum PEFR values at work; lower mean PEFR values at work 
E-48

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Pezzini, 1984 

SIC: isocyanates ≧20% fall in FEV1 or 35% 

drop in FEF(25-75) 

Referenced (Zedda et al., 1976) 

Single NSBPT: bethanechol Skin prick: atopy Serum specific IgE 

PD20 FEV1: no cutoff 

≧2 positive reactions 

 NBR level >0.9 Prichard, 1984 

Other: clinical diagnosis 

Included symptoms and physician diagnosed asthma since began working in industry 

Described in text 

Single NSBPT: methacholine Skin prick: atopy and specific 

PD20 FEV1 <30 μg 

Wheal ≧3 mm more 

than negative control 

Quirce, 2000 

Other: clinical diagnosis 

Included SIC or serial PFT SIC: 

Referenced (Hinojosa et al., 1984) 

Skin prick: specific Serum specific IgE 

Not reported 

≧4 times more serum 

specific IgE than mean titer of control sera 

Quirce, 1992 

SIC: alphaamylase from aspergillus oryzae and cellulase from a. niger 

≧20% decline in FEV1 Described in 

text 

Single NSBPT: methacholine Skin prick: atopy and specific Serum specific IgE 

Not reported Wheal diameter ≧3 mm 

Not reported 

Rasanen, 1994 

SIC: suspected agent 

≧15% decline in FEV1 and 

PEFR 

Not reported Other: basophil 

histamine release 

≧8% 

 Skin prick: atopy 

and specific 

Wheal diameter ≧1/2 

the size of the reaction to histamine standard 

 Serum specific IgE ≧0.7 kU/L  Serum total IgE Not reported Redlich, 1996 

SIC: isocyanates Not reported Not reported Eosinophils: blood 

Other: bronchial alveolar lavage 

Not reported Not reported 

 Single NSBPT: 

methacholine 

Not reported 
E-49

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Ricciardi, 2003 

SIC: wood dust (iroko) 

≧25% decline in FEV1 Referenced 

(Frolund, 1996) 

Eosinophils: blood Serial PFT (PEFR): monitored every two hrs for 1 wk at work and 1 wk away 

Not reported Not reported 

 Single NSBPT: 

methacholine 

≧20% decline in FEV1: 

no cutoff 

 Skin prick: atopy 

and specific 

Wheal diameter >7 mm 

 Serum specific IgE Not reported  Serum total IgE Not reported Sander, 2001 

SIC: wheat and rye 

Not reported Not reported Skin prick: specific ≧1/2 of histamine wheal 

Sastre, 2003 

SIC: isocyanates ≧20% decline in FEV1 Not reported Single NSBPT: 

methacholine 

PC20 FEV1 <16 mg/ml 

Schuermans, 2003 

SIC: latex Not reported Not reported Single NSBPT: 

histamine 

PC20 FEV1 <0.5 mg/ml 

Schwaiblmair, 1997 

SIC: bleaching powder 

≧100% increase in specific 

airway resistance and reached at least 2.0 kPa/s 

Described in text 

Single NSBPT: methacholine 

≧100% increase in 

specific airway resistance and reached 2.0 kPa 

 Single PFT: FVC, 

MEF50, FEV1, RV, 

TLco, Raw Pa02

Not reported 

 Skin prick: atopy 

and specific 

Wheal diameter >3 mm larger than negative control 

Schwarting, 1979 

SIC: flour Not reported Not reported Clinical diagnosis Included medical 

history, skin prick test, bronchial provocation test, nasal provocation, conjuctivities, and serum specific IgE 

 Skin prick: specific Not reported  Serum specific IgE Not reported 
E-50

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Shirai, 2003 

SIC: epigallocatechin gallate (EGCg) 

≧20% decline in FEV1 Referenced 

(Shirai et al., 1997) 

Clinical diagnosis Single NSBPT: methacholine 

Clinical history, postive SIC, positive SPT PC20 FEV1 <10 mg/ml 

 Skin prick: specific Wheal diameter >7 mm Shirakawa, 1988 

SIC: cobalt chloride 

Not reported Referenced 

(Chai et al., 1975) 

Eosinophils: blood Other: antibodies (CO-HSA) 

>200/mm3

Not reported 

 Single NSBPT: 

methacholine 

Not reported 

 Skin prick: specific Wheal diameter >9 mm 

at <0.1% 

 Serum specific IgE >673 cpm (upper 

normal limit) 

Slovak, 1981 

Other: clinical diagnosis 

Based history of repeated episodes of wheezing or chest tightness (with or without cough) related to 

Described in text 

Serial PFT (PEFR): monitored every 2 hrs while awake for 3 mos 

Not reported 

 Skin prick: atopy 

and specific 

Wheal diameter >3 mm 

Symington, 1981 

SIC: mushroom dust 

Not reported Described in 

text 

Skin prick: atopy and specific 

Wheal diameter ≧3 mm 

Tabar, 2004 

SIC: asparagus ≧20% decline in FEV1 Described in 

text 

Other: immunoblotting 

Not reported 

 Skin prick: atopy 

and specific 

Wheal area ≧7 mm2 

 Serum specific IgE Not reported  Serum total IgE Not reported Taivainen, 1994 

SIC: cow dander Immediate: ≧15% change 

in PEFR; late: ≧20% 

change in PEFR 

Described in text 

Clinical diagnosis Skin prick: specific 

Described in text Two cutoff values: wheal diameter ≧3 mm or >than positive control 

 Serum specific IgE Two cutoff values: ≧0.35 

kU/L or ≧0.70 kU/L 
E-51

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Tee, 1998 

Other: clinical diagnosis 

Included SIC and/or clinical history and/or serial PFT and/or NSBPT 

SIC: Referenced (NewmanTaylor and Davies, 1981) 

Skin prick: atopy Serum specific IgE 

Wheal diameter >3 mm Two cutoff values: ratio 

≧2; ratio ≧3 

Tse, 1982 

SIC: plicatic acid Not reported Referenced 

(Chan-Yeung et al., 1973) 

Serum specific IgE >mean + 2SD of control 

subjects 

Vandenplas, 2001 

SIC: latex ≧20% decline in FEV1 Referenced 

(Vandenplas et al., 1995) 

Clinical diagnosis Questionnaire and 

clinical history with OA considered likely or highly likely on the basis of consensus assessment by 4 observers 

 Serial NSBPT: 

histamine 

>3 fold change in PC20

FEV1 before and after 

SIC 

 Single NSBPT: 

histamine 

PC20 FEV1 <16 mg/ml 

 Skin prick: atopy 

and specific 

≧1 positive reaction 

Vandenplas, 1995b 

SIC: latex ≧20% decline in FEV1 Described in 

text 

Single NSBPT: histamine 

PC20 FEV1 <16 mg/ml 

 Skin prick: atopy 

and specific 

Wheal ≧3mm greater 

than control 

Vanhanen, 2000 

SIC: cellulase (econase ECP) 

≧15% decline in FEV1 Not reported Single NSBPT: 

histamine 

PD15 FEV1 ≦1.6 mg 

 Skin prick: atopy 

and specific 

Not reported 

 Serum specific IgE >35 KU/L 
E-52

Table E-3. Description of diagnostic tests (Diagnosis review) (continued) Author, Highest Reference Standard Comparison Tests Year Test Positive Response Methodology Test Positive Response Virtanen, 1996 

Other: clinical diagnosis 

Included SIC and/or SPT and/or serum specific IgE 

Serum specific IgE: described in text 

Serum specific IgE Serum specific IgG 

Not reported Not reported 

Vogelmeier, 1991 

SIC: TDI ≧50% decline in sGaw from 

the zero value 

Referenced (Dharmarajan and Rando, 1979; O'Brien et al. 1979) 

Single NSBPT: methacholine Skin prick: specific Serum specific IgE 

≧50% decline in specific 

airway conductance Not reported Not reported 

Wurzinger, 1997 

SIC: flour Not reported Described in 

text 

Single NSBPT: histamine 

Not reported 

 Skin prick: atopy 

and specific 

Not reported 

 Serum specific IgE Not reported  Serum total IgE Not reported Zeiler, 2002 

SIC: Bos d2 and standard bovine dander allergen 

≧15% decline in FEV1 or 

PEF 

Described in text 

Single NSBPT: histamine 

PD15 FEV1 <1.6 mg 

 Skin prick: specific Wheal diameter ≧3 mm  Serum specific IgE Not reported  Serum specific IgG Not reported Zeiss, 1977 

Other: clinical diagnosis 

Included history, physical, and skin tests when indicated 

Described in text 

Skin prick: atopy and specific Serum specific IgE Serum specific IgG 

Not reported Not reported Not reported 

Abbreviations: CAP = developed by Pharmacia Diagnostics for measuring specific IgE; cbu = cumulative breath unit; CO-HSA = conju

albumin; cpm = counts per minute; DPC = diagnostics products corp.; EAST = enzyme allergosorbent test; ECG = electrocardiogram; E

protein; ECSC = European coal and steel community; ELISA = enzyme-linked immuno sorbent assay; FEF = forced expiratory flow; FEV

volume in one second; FVC = forced vital capacity; kPa = kilopascal; MCP-1= monocyte chemoattractant protein-1; MEF = maximal exp

months; NSBPT = non-specific bronchial provocation; OASYS-2 = occupational asthma system; OD = optical density; PC20 = provocativ

20% drop in FEV1; PaO2 = arterial oxygen partial pressure; PD15 = provocative dose causing a 15% drop in FEV1; PD50 = provocative do

FEV1; PD20 = provocative dose causing a 20% drop in FEV1; PEF = peak expiratory flow; PEFR = peak expiratory flow rate; PFT = pulm

= paper radioimmunosorbent test; PRU = phadebas RAST units; PTRIA = polystyrene-tube radioimmunoassay; RADS = reactive airway

RAST = radio allegro sorbent test; REIA = reverse enzyme immunoassay; RIA = radioimmunoassay; RIACT = radioimmunoassay kit for 

residual volume; SD = standard deviation; SDS = sodium dodecyl sulphate; sGaw = specific airway conductance; SIC = specific inhalati

shortness of breath; SPBRIA = solid-phase bead radioimmunoassay; sRaw = specific airway resistance; TCPA = tetrachlorophthalic anh

isocyanates; TDI-HSA = toluene di-isocyanates human serum albumin; TLco = single breath carbon monoxide; IU = international units; 

fluoroenzymeimmunoassay kit developed by Pharmacia Diagnostics; Vmax = maximum flow; wk = week; wks = weeks 
E-53

Table E-4. Methodological quality of included studies (Diagnosis review) Author, Year 

Data Collection 

Patient Recruitment 

Blinding Adequate 

Description of Reference Standard 

Avoidance of Differential Bias 

Avoidance of Partial Verification Bias 

Fun

Alvarez, 2001 

Prospective Other Partial Yes No No Not 

Alvarez, 1996 

Prospective Other Unclear Yes Yes Yes Oth

Anees, 2004 

Retrospective Consecutive or 

random selection 

Unclear Yes No No Fou

Avery, 1969 

Prospective Other Unclear No No Unclear Gov

Balland, 1989 

Prospective Not reported Unclear No Unclear Yes Not 

Baur, 1998 

Prospective Other Unclear Yes No No Not 

Baur, 1979 

Prospective Not reported Unclear No Yes Yes Fou

Behr, 1990 

Prospective Not reported Unclear Yes Unclear Unclear Not 

Bernstein, 2002 

Prospective Other Partial Yes No No Gov

Biot, 1980 

Prospective Not reported Unclear No No No Not 

Block, 1983 

Prospective Other Unclear Yes Yes Yes Gov

Burge, 1985 

Prospective Not reported Unclear No No No Not 

Burge, 1982 

Prospective Other Unclear No No No Not 

Burge, 1980 

Prospective Other Unclear Yes No No Not 

Burge, 1979a 

Prospective Other Partial Yes No No Not 

Burge, 1979b 

Retrospective Other Partial Yes No No Not 

Burge, 1978 

Prospective Other Unclear Yes Unclear Unclear Not 
E-54

Table E-4. Methodological quality of included studies (Diagnosis review) (continued) Author, Year 

Data Collection 

Patient Recruitment 

Blinding Adequate 

Description of Reference Standard 

Avoidance of Differential Bias 

Avoidance of Partial Verification Bias 

Fun

Butcher, 1980 

Retrospective Not reported Unclear No No No Gov

fou

Carletti, 1997 

Prospective Not reported Unclear Yes Unclear Unclear Not 

Cartier, 1989 

Prospective Other Partial Yes Yes No Fou

gov

Cartier, 1987 

Retrospective Not reported Unclear Yes No No Not 

Cartier, 1984 

Prospective Other Unclear Yes Unclear Yes Gov

Choudat, 1999 

Prospective Other Unclear Yes No No Oth

Cirla, 1975 

Prospective Other Unclear Yes Unclear Unclear Not 

Colas, 1985 

Prospective Not reported Unclear Yes No No Not 

Cortona, 1980 

Prospective Not reported Partial No No Yes Not 

Cote, 1990 

Prospective Consecutive or 

random selection 

Partial Yes No No Gov

Coutts, 1984 

Prospective Other Unclear No No Unclear Not 

Curran, 1996 

Prospective Other Unclear No No No Not 

Davison, 1983 

Prospective Other Unclear Yes Unclear Yes Not 

Dellabianca, 1996 

Prospective Consecutive or 

random selection 

Unclear Yes No No Not 

Dente, 1986 

Prospective Not reported Unclear No No No Not 

De Zotti, 1996a 

Prospective Other Unclear Yes No No Not 

De Zotti, 1996b 

Prospective Not reported Unclear Yes No Unclear Not 
E-55

Table E-4. Methodological quality of included studies (Diagnosis review) (continued) Author, Year 

Data Collection 

Patient Recruitment 

Blinding Adequate 

Description of Reference Standard 

Avoidance of Differential Bias 

Avoidance of Partial Verification Bias 

Fun

DiFranco, 1998 

Prospective Other Partial No Yes Yes Gov

Duan, 1989 

Prospective Not reported Inadequate Yes Unclear Unclear Not 

Ferguson, 1996 

Prospective Other Unclear Yes No No Not 

Gannon, 1996 

Prospective Other Unclear No Yes Yes Gov

Girard, 2004 

Prospective Other Partial Yes No No Gov

Graneek, 1988 

Unclear Other Partial Yes Yes No Not 

Grosclaude, 1980 

Prospective Not reported Unclear Yes No No Not 

Harries, 1980 

Prospective Other Unclear Yes No No Not 

Hinojosa, 1986 

Prospective Not reported Unclear Yes No No Not 

Howe, 1983 

Prospective Other Unclear Yes Yes No Oth

Huggins, 2003 

Prospective Consecutive or 

random selection 

Partial No Unclear Yes Not 

Jager, 1993 

Unclear Other Unclear Yes No Yes Not 

Karol, 1994 

Prospective Other Unclear Yes No No Gov

Kern, 1991 

Prospective Other Unclear Yes No No Gov

Keskinen, 1988 

Retrospective Consecutive or 

random selection 

Unclear Yes No No Not 

Kim, 1999 

Prospective Other Unclear No No Yes Not 

Kim, 1997 

Prospective Other Unclear Yes Yes Yes Gov
E-56

Table E-4. Methodological quality of included studies (Diagnosis review) (continued) Author, Year 

Data Collection 

Patient Recruitment 

Blinding Adequate 

Description of Reference Standard 

Avoidance of Differential Bias 

Avoidance of Partial Verification Bias 

Fun

KopferschmittKubler, 1998 Prospective Other Unclear Yes No No Not Kongerud, 1992 

Prospective Other Partial No No Unclear Not 

Koskela, 2003 

Prospective Consecutive or 

random selection 

Unclear Yes Yes No Inte

Krakowiak, 2003 

Prospective Other Partial Yes No No Not 

Lam, 1979 

Prospective Other Unclear Yes Unclear Unclear Fou

La Paglia, 1986 

Unclear Not reported Unclear No Yes Unclear Not 

Larbanois, 2003 

Unclear Consecutive or 

random selection 

Unclear Yes No No Gov

Lemiere, 1999 

Prospective Other Full Yes No No Fou

Liss, 1991 

Retrospective Other Full Yes Yes No Not 

Lozewicz, 1985 

Prospective Other Partial No No Yes Not 

Malo, 1993 

Retrospective Other Partial No No No Not 

Malo, 1991 

Prospective Consecutive or 

random selection 

Full Yes No Yes Not 

Malo, 1990 

Retrospective Other Unclear Yes Yes No Not 

Malo, 1988 

Prospective Consecutive or 

random selection 

Unclear Yes Yes Yes Not 

Mapp, 1986 

Prospective Not reported Unclear Yes No No Gov

Mapp, 1979 

Prospective Not reported Unclear Yes No Yes Not 

Merget, 1997 

Prospective Other Unclear Yes No No Not 
E-57

Table E-4. Methodological quality of included studies (Diagnosis review) (continued) Author, Year 

Data Collection 

Patient Recruitment 

Blinding Adequate 

Description of Reference Standard 

Avoidance of Differential Bias 

Avoidance of Partial Verification Bias 

Fun

Merget, 1996 

Prospective Other Unclear Yes No No Oth

Merget, 1993 

Prospective Consecutive or 

random selection 

Unclear Yes No No Not 

Mole, 1977 

Prospective Not reported Unclear Yes No Yes Not 

Moller, 1986 

Prospective Other Unclear Yes Yes No Not 

Moller, 1985 

Prospective Other Unclear No No No Gov

Moscato, 1991 

Retrospective Other Unclear Yes No No Not 

Munoz, 2004 

Prospective Other Unclear Yes No No Not 

Nielsen, 1988 

Prospective Not reported Partial Yes No No Fou

Nordman, 1985 

Retrospective Consecutive or 

random selection 

Unclear Yes Unclear Unclear Not 

Obata, 1999 

Prospective Consecutive or 

random selection 

Partial Yes No No Fou

O'Brien, 1979b 

Prospective Not reported Unclear Yes No Unclear Priv

O'Brien, 1979a 

Prospective Other Unclear Yes Yes No Priv

Obutulowicz, 1998 

Prospective Other Unclear No No No Not 

Paggiaro, 1987 

Retrospective Other Unclear Yes No Yes Not 

Paggiaro, 1986 

Prospective Other Unclear Yes Unclear No Not 

Paggiaro, 1984c 

Prospective Not reported Unclear Yes Unclear Unclear Not 

Paggiaro, 1984b 

Prospective Not reported Unclear Yes No Yes Not 
E-58

Table E-4. Methodological quality of included studies (Diagnosis review) (continued) Author, Year 

Data Collection 

Patient Recruitment 

Blinding Adequate 

Description of Reference Standard 

Avoidance of Differential Bias 

Avoidance of Partial Verification Bias 

Fun

Paggiaro, 1981 

Prospective Not reported Inadequate Yes No No Not 

Palczynski, 2003 

Prospective Other Partial No No No Gov

Park, 2002 

Prospective Other Unclear Yes No No Priv

Park, 2001 

Prospective Other Partial Yes Yes No Inte

Park, 1999 

Prospective Other Unclear Yes No No Oth

Park, 1998 

Prospective Other Unclear Yes Yes Yes Inte

Park, 1994 

Prospective Not reported Unclear Yes No No Not 

Park, 1991 

Prospective Other Unclear Yes Yes Yes Not 

Park, 1989 

Prospective Not reported Unclear Yes No No Inte

Perrin, 1990 

Prospective Not reported Unclear No No No Not 

Pezzini, 1984 

Prospective Not reported Unclear Yes Unclear Unclear Gov

Prichard, 1984 

Prospective Other Unclear No No No Oth

Quirce, 2000 

Prospective Other Unclear No Unclear Unclear Not 

Quirce, 1992 

Retrospective Other Unclear Yes No No Fou

Rasanen, 1994 

Prospective Not reported Unclear Yes No Yes Not 

Redlich, 1996 

Prospective Not reported Unclear No No No Inte

Ricciardi, 2003 

Prospective Other Unclear Yes Yes Yes Not 
E-59

Table E-4. Methodological quality of included studies (Diagnosis review) (continued) Author, Year 

Data Collection 

Patient Recruitment 

Blinding Adequate 

Description of Reference Standard 

Avoidance of Differential Bias 

Avoidance of Partial Verification Bias 

Fun

Sander, 2001 

Prospective Not reported Unclear Inadequate Unclear Unclear Not 

Sastre, 2003 

Prospective Not reported Unclear Yes Yes No Not 

Schuermans, 2003 

Prospective Not reported Unclear No Unclear Unclear Not 

Schwaiblmair, 1997 

Prospective Other Unclear Yes No Yes Not 

Schwarting, 1979 

Unclear Other Unclear No No Yes Not 

Shirai, 2003 

Prospective Other Unclear Yes No No Not 

Shirakawa, 1988 

Prospective Other Unclear No No No Not 

Slovak, 1981 

Prospective Other Unclear No No No Not 

Stefano, 1999 

Prospective Other Unclear Yes Unclear Yes Not 

Symington, 1981 

Prospective Other Unclear No Yes No Not 

Tabar, 2004 

Retrospective Other Unclear Yes Yes No Not 

Taivainen, 1994 

Prospective Consecutive or 

random selection 

Unclear Yes No Yes Not 

Tee, 1998 

Retrospective Other Partial Yes No No Not 

Tse, 1982 

Prospective Not reported Unclear No Yes Yes Gov

Vandenplas, 2001 

Prospective Consecutive or 

random selection 

Partial Yes No No Priv

Vandenplas, 1995 

Prospective Other Unclear Yes Yes Yes Oth

Vanhanen, 2000 

Prospective Not reported Inadequate Yes No No Not 
E-60

Table E-4. Methodological quality of included studies (Diagnosis review) (continued) Author, Year 

Data Collection 

Patient Recruitment 

Blinding Adequate 

Description of Reference Standard 

Avoidance of Differential Bias 

Avoidance of Partial Verification Bias 

Fun

Virtanen, 1996 

Prospective Consecutive or 

random selection 

Unclear Yes Yes No Fou

Vogelmeier, 1991 

Prospective Not reported Unclear Yes No No Oth

Wurzinger, 1997 

Unclear Not reported Unclear Yes No Yes Not 

Zeiler, 2002 

Prospective Consecutive or 

random selection 

Unclear Yes No No Inte

Zeiss, 1977 

Prospective Other Inadequate Yes No No Gov
E-61

Table E-5. Description of included studies (Management cohorts review) Author, Year 

Location Language of 

Publication 

Intervention Categories 

Suspected Agent (molecular weight) 

Subject Source 

Description of Include

Allard, 1989 

Canada English Removed Mixed (M) Clinic Workers with OA due to 

exposed >5 yrs 

Ameille, 1997 

France English Exposed, protection, 

reduced, removed 

Mixed (M) Clinic Workers diagnosed with 

between 1989-93, followlater 

Banks, 1990 

United States 

English Reduced Isocyanates (L) Workplace Polyurethane foam work

follow-up 1982-86 

Barker, 1998 

United Kingdom 

English Removed Chemical: TCPA (L) Clinic Female electronic facto

OA due to TCPA, follow

Bernstein, 2003 

United States 

English Exposed, protection, 

reduced, removed 

Latex (H) Other Volunteer health care w

Burge, 1982a 

United Kingdom 

English Reduced, removed Colophony (L) Clinic Electronics workers with 

fumes 

Gannon, 1993 

United Kingdom 

English Exposed, removed Mixed (M) Clinic Workers with OA due to 

at least 1 yr ago 

Gassert, 1998 

United States 

English Removed Mixed (M) Clinic Workers with OA 

Gorski, 1999 

Poland English Removed Flour (H) Clinic Workers with bakers as

follow-up approximately 

Grammer, 2000 

United States 

English Reduced, removed Chemical: trimellitic 

anhydride (L) 

Workplace Workers at TMA manufa

moved to low exposure 

Grammer, 1996 

United States 

English Removed Chemical: anhydride 

(L) 

Other Workers that prepare e

induced respiratory diseapproximately 1 yr 

Harries, 1979 

United Kingdom 

English Reduced, removed Isocyanates (L) Workplace Workers in rubber manu

isocyanate-induced asthapproximately 3 yrs 

Jyo, 1989 

Japan English Medications Sea squid (H) - Oyster shuckers with as

Laoprasert, 1998 

United States 

English Protection Latex (H) Clinic Female health care wor

Lemiere, 2000 

Canada English Removed Isocyanates (L) Clinic Workers diagnosed with 

agents had normal NSBapproximately 5 yrs 

Lemiere, 1996 

Canada English Removed Mixed (M) Clinic Workers with OA due to 

longer exposed 
E-62

Table E-5. Description of included studies (Management cohorts review) (continued) Author, Year 

Location Language of 

Publication 

Intervention Categories 

Suspected Agent (molecular weight) 

Subject Source 

Description of Include

Lin, 1996 

Canada English Exposed, removed Wood dust: cedar (L) Clinic Male workers with OA d

cedar diagnosed betwee

Lozewicz, 1987 

United Kingdom 

English Reduced, removed Isocyanates (L) Clinic Various workers diagno

induced asthma betweeapproximately 4 yrs 

Maghni, 2004 

Canada English Removed Mixed (M) Clinic Workers with OA due to 

exposed 

Malo, 2004 

Canada English Removed Mixed (M) - Workers with OA with se

at diagnosis and after re

Malo, 1994a 

Canada English Removed Chemical: chlorine (L) Clinic Pipefitters and welders 

bronchial hyperresponsexposure to chlorine 

Malo, 1993b 

Canada English Removed Mixed (M) Clinic Workers, mostly expose

confirmed diagnosis of Ocompensation from WB

Mapp, 1988 

Italy English Exposed, removed Isocyanates (L) - Lumber workers with OA 

approximately 10 mos 

Malo, 1988b 

Canada English Removed Snow crab (H) - Snowcrab workers with 

follow-up between 12-64 

Marabini, 2003 

Italy English Exposed Mixed (M) Clinic Carpenters/bakers/farm

Merget, 1999 

Germany English Exposed, reduced, 

removed, 

Chemical: platinum salts (L) 

Workplace Metal refinery/catalyst p

due to platinum salts 

Meyer, 1977 

Germany German Removed Metal dust (L) Workplace Workers with metal dust 

workplace 

Moscato, 1999 

Italy English Exposed, reduced, 

removed, 

Mixed (M) Clinic Workers diagnosed with 

between 1992-95, follow

Munoz, 2003 

Spain English Protection, removed Chemical: persulfate 

(L) 

Clinic Cosmetic factory worke

due to persulfate salts 

O'Donnell, 1989 

New Zealand 

English Exposed Potroom (L) Workplace Smelter workers diagno

Orriols, 1999 

Spain Spanish Protection, removed Isocyanates (L) Clinic Workers with OA cause

Paggiaro, 1993 

Italy English Reduced, removed Isocyanates (L) Workplace Furniture manufacturing 

TDI 
E-63

Table E-5. Description of included studies (Management cohorts review) (continued) Author, Year 

Location Language of 

Publication 

Intervention Categories 

Suspected Agent (molecular weight) 

Subject Source 

Description of Include

Paggiaro, 1990 

Italy English Removed Isocyanates (L) - Workers with TDI asthm

Paggiaro, 1984a 

Italy English Exposed, removed Isocyanates (L) - Furniture manufacturing 

TDI 

Park, 2002a 

Korea English Removed Isocyanates (L) Clinic Workers with TDI asthm

yrs 

Park, 1994 

Korea English Removed Chemical: chromium 

(L) 

Clinic Workers in metalplating

with OA due to chromiu

Perfetti, 1998a 

Canada English Removed Mixed (M) Clinic Volunteer workers rando

charts diagnosed with O

Piirila, 1996 

Finland English Reduced, removed Chemical: sulfur 

dioxide (L) 

Workplace Miners accidentally exp

reviewed 13 yrs later 

Pisati, 1994 

Italy English Exposed, removed Chemical: cobalt (L) Clinic Workers with OA due to 

1982-90 

Pisati, 1993 

Italy English Reduced, removed Isocyanates (L) Clinic Workers exposed to pai

with TDI asthma betwee

Rosenberg, 1987 

France English Exposed, protection, 

reduced, removed 

Isocyanates (L) Clinic Car spray-painters/foam 

makers, etc. with isocya54 mos 

Ross, 1998 

United Kingdom 

English Removed Mixed (M) Other Charts of workers with O

project 

Saetta, 1995 

Italy English Removed Isocyanates (L) - Workers with OA due to 

Sen, 1998 

United Kingdom 

English Removed Enzymes: fruit (H) Workplace Factory workers prepari

enzymes 

Simonsson, 1985 

Sweden English Exposed, removed Metal: aluminum 

fluoride or sulfate (L) 

Clinic Workers from aluminum 

aluminum fluoride/sulph

Slovak, 1985 

United Kingdom 

English Protection Animal/bird: lab 

animals (H) 

Workplace Lab animal workers diag

exposed 

Smith, 1999 

United Kingdom 

English Exposed, reduced Flour (H) Other Workers across flour-us

Sulotto, 1989 

Italy Italian Removed, 

medications 

Mixed (M) Clinic Workers with clinically d

causes 

Taivainen, 1998 

Finland English Protection Animal/bird: cow 

dander and grain (H) 

Clinic Farmers with OA due to 
E-64

Table E-5. Description of included studies (Management cohorts review) (continued)Author, Year 

Location Language of 

Publication 

Intervention Categories 

Suspected Agent (molecular weight) 

Subject Source 

Description of Include

Vandenplas, 2002 

Belgium English Reduced, removed Latex (H) Clinic Health-care/non-health-

to latex 

Venables, 1987 

United Kingdom 

English Removed Chemical: TCPA (L) Workplace Female process worker

longer exposed, follow-u

Venables, 1985 

United Kingdom 

English Reduced Isocyanates (L) Workplace Various workers in a ste

due to coating vapours 

Abbreviations: H = high; HHPA = hexahydrophthalic anhydride; L = low; M = mixed; mos = months; NRL = natural rubber latex; NSBPT 

provocation; NSBR = non-specific bronchial reactivity; OA = occupational asthma; SWORD = surveillance of work-related occupational r

= tetrachlorophthalic anhydride; TDI = toluene di-isocyanates; TMA = trimellitic anhydride; WCB = workers’ compensation board; yr = ye
E-65

Table E-6. Demographic characteristics of included patients (Management cohorts review) 

Male Age Atopic Smoking 

Status 

History of Asthma 

% predicted FEV1 (unless 

otherwise stated) 

Years of Exposure 

Years of Symptoms 

Author, Year 

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (SD)

Allard, 1989 

28 92.9 46 

(11) 

60.7 C: 17.9 - 87 

(21.3) 

0.5 (0.8) 

0.3 (0.2) 

Ameille, 1997 

209 75.1 38 

(12) 

- - - 88 

(20) 

- 3.7 

(5.1) 

Banks, 1990 

6 - - - C: 33.3 

N: 66.7 

0 - - - 

Barker, 1998 

6 0 37 

(4.2) 

- - - FEV1: 2.1 

(0.2) 

- - 

Bernstein, 2003 

67 4.5 36.1 

(11.5) 

82.1 - - - - 4.5 

(4.8) 

Burge, 1982a 

45 20 49 

(6.8) 

- N: 48.9 - - - 2.5 

Gannon, 1993 

224 74.1 - - C: 12.1 

Ex: 21.9 N: 15.6 

- - - - 

Gassert, 1998 

55 29.1 41.1 

(9.8) 

- C: 9.1 

Ex: 32.7 N: 58.2 

25.5 - 10.7 

(6.9) 

- 

Gorski, 1999 

56 - 38 

(9) 

- C: 26.8 

Ex: 26.8 N: 46.4 

- - - - 

Grammer, 2000 

29 89.7 36.5 

(8.8) 

- C: 44.8 

Ex: 13.8 N: 41.4 

- - 1.1 

(5.2) 

- 

Grammer, 1996 

7 100 37 

(4.3) 

- C: 14.3 

Ex: 28.6 N: 57.1 

- - - - 

Harries, 1979 

3 100 41.3 

(3.7) 

66.7 C: 66.7 

Ex: 33.3 N: 0 

- FEV1: 3 

(0.4) 

8 (9.6) 

2.5 (3.1) 

Jyo, 1989 

- - - - - - - - - 
E-66

Table E-6. Demographic characteristics of included patients (Management cohorts review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

% predicted FEV1 (unless 

otherwise stated) 

Years of Exposure 

Years of Symptoms 

Author, Year 

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (SD)

Laoprasert, 1998 

11 0 35.5 

(6.2) 

63.6 C: 0 

N: 100 

- - - - 

Lemiere, 2000 

16 68.8 41.3 

(9.9) 

75 C: 31.3 

Ex: 50 N: 18.8 

- 99 

(14.4) 

10.7 (9.5) 

- 

Lemiere, 1996 

15 73.3 49.1 

(10.4) 

53.3 C: 0 

Ex: 40 N: 60 

- 96 

(12) 

18.1 (13.6) 

6 (5.6) 

Lin, 1996 

280 100 40.9 

(11.2) 

27.9 C: 4.6 

Ex: 28.2 N: 67.1 

- 86.1 

(16.7) 

6.1 (6.4) 

- 

Lozewicz, 1987 

56 83.9 46.1 

(9.8) 

35.7 C: 21.4 

Ex: 41.1 N: 26.8 

3.6 82.5 

(21.1) 

6.5 (7.4) 

2.7 (2.1) 

Maghni, 2004 

133 60.9 43 

(12) 

59.4 C: 18 

Ex: 39.8 N: 42.1 

- 84.1 

(20.3) 

12.1 (10.6) 

3.9 (4.7) 

Malo, 2004 

80 80 42.8 

(12.4) 

53.8 C: 20 

Ex: 37.5 N: 42.5 

- 90.2 

(16.5) 

11.5 (10.7) 

3.3 (4.2) 

Malo, 1994a 

20 100 48 

(10) 

50 C: 55 

Ex: 40 N: 5 

- 80.4 

(19.3) 

- - 

Malo, 1993b 

134 76.1 44 

(12) 

60.4 - - 91 

(20) 

- - 

Malo, 1988b 

31 9.7 37.1 

(12.2) 

29 C: 64.5 

Ex: 19.4 N: 16.1 

- - 1.1 

(0.5) 

0.6 (0.4) 

Mapp, 1988 

35 71.4 34.6 

(13.7) 

22.9 C: 8.6 

Ex: 28.6 N: 62.9 

0 - 13.5 

(11.3) 

3.7 
E-67

Table E-6. Demographic characteristics of included patients (Management cohorts review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

% predicted FEV1 (unless 

otherwise stated) 

Years of Exposure 

Years of Symptoms 

Author, Year 

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (SD)

Marabini, 2003 

10 90 49.9 

(7) 

30 C: 10 

Ex: 60 N: 30 

- 75.1 

(12.6) 

24.2 (14.3) 

- 

Merget, 1999 

83 - 38 

(10.4) 

45.8 C: 51.8 

Ex: 22.9 N: 25.3 

- - - - 

Meyer, 1977 

168 - - - - - - - - 

Moscato, 1999 

25 72 34 

(9.3) 

16 C: 28 

Ex: 24 N: 48 

- 103 

(6.8) 

5 (5) 

1.8 (1.2) 

Munoz, 2003 

8 0 35 

(10.3) 

37.5 C: 37.5 0 99.3 

(9.9) 

14.6 (8.7) 

- 

O'Donnell, 1989 

57 100 31 

(6.3) 

29.8 C: 50.9 - - - - 

Orriols, 1999 

21 81 36.4 

(10.9) 

23.8 C: 57.1 

Ex: 19 N: 23.8 

- 80.8 

(21) 

6.1 (6.9) 

- 

Paggiaro, 1993 

16 68.8 46.7 

(9.4) 

- C: 12.5 

Ex: 37.5 N: 50 

- 81.7 

(12.5) 

20.7 (8.9) 

3.8 (4.1) 

Paggiaro, 1990 

10 80 49.5 

(7.4) 

- C: 10 

Ex: 50 N: 40 

- 82.7 

(15.6) 

- 4.3 

(2.6) 

Paggiaro, 1984a 

27 59.3 50.2 

(9.1) 

- C: 29.6 

Ex: 0 N: 70.4 

- - 15.5 

(10) 

- 

Park, 2002a 

41 - - - - - - 22.4 

(5.5) 

- 

Park, 1994 

3 100 47.3 

(9.1) 

100 C: 0 

Ex: 100 N: 0 

- - - - 
E-68

Table E-6. Demographic characteristics of included patients (Management cohorts review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

% predicted FEV1 (unless 

otherwise stated) 

Years of Exposure 

Years of Symptoms 

Author, Year 

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (SD)

Perfetti, 1998a 

99 73.7 43 

(12) 

59.6 C: 15.2 

Ex: 39.4 N: 45.5 

- - 12.5 

(11.3) 

3.2 

Piirila, 1996 

7 100 26.9 

(5.1) 

- C: 57.1 

Ex: 0 N: 28.6 

- - - - 

Pisati, 1994 

9 - - - C: 11.1 

Ex: 11.1 N: 77.8 

- - - - 

Pisati, 1993 

60 - 37.3 

(11.6) 

13.3 C: 15 

Ex: 0 N: 85 

5 - 15.3 

(9.1) 

4.4 

Rosenberg, 1987 

31 87.1 35.9 

(16.6) 

29 C: 19.4 3.2 97 

(35.7) 

3 (6) 

1.4 (2.2) 

Ross, 1998 

1011 70.6 40.9 

(12.3) 

- C: 22.4 

Ex: 27.8 N: 40.8 

- - 4 

(8.1) 

- 

Saetta, 1995 

10 50 39.1 

(12.8) 

20 C: 0 

Ex: 0 N: 100 

- 98.6 

(15) 

17.5 (14.5) 

3.5 (3.7) 

Sen, 1998 

3 66.7 31.3 

(13.3) 

100 C: 33.3 

Ex: 0 N: 66.7 

66.7 - - 0.5 

(0.1) 

Simonsson, 1985 

19 100 24 

(4.5) 

10.5 C: 57.9 

Ex: 31.6 N: 10.5 

10.5 93 

(6) 

1.2 (1.3) 

- 

Slovak, 1985 

8 - - 100 - - - - - 

Smith, 1999 

- - - - - - - - - 

Sulotto, 1989 

10 50 39 

(7.3) 

- C: 70 - 101.6 

(9.5) 

9.5 (7) 

- 
E-69

Table E-6. Demographic characteristics of included patients (Management cohorts review) (continued) 

Male Age Atopic Smoking 

Status 

History of Asthma 

% predicted FEV1 (unless 

otherwise stated) 

Years of Exposure 

Years of Symptoms 

Author, Year 

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (SD)

Taivainen, 1998 

24 - - - - - - - - 

Vandenplas, 2002 

36 11.1 32 

(4.4) 

63.9 C: 5.6 

Ex: 5.6 N: 88.9 

30.6 - - 7.2 

Venables, 1987 

6 0 39 

(2.8) 

16.7 C: 100 0 - - - 

Venables, 1985 

21 100 41.2 28.6 C: 47.6 - 93 7.7 - 

Abbreviations: C = current; Ex = ex; FEV1 = forced expiratory volume in one second; N = never; OA = occupational asthma; SIC = spec
E-70

Table E-7. Description of interventions and outcomes (Management cohorts review) Author, Intervention(s) Outcome(s) Year Type of 

Intervention 

Description Number of 

Patients 

Test Description 

Allard, 1989 

Removed Ceased exposure for at 

least 6 mos 

28 NSBPT 

Pulmonary function Questionnaire 

Histamine: PC20 F

FEV1

Including symptomneed for medicatio

Ameille, 1997 

Exposed Protection 

No change Improved ventilation or used appropriate respirator 

20 46 

Questionnaire Including current w

situation 

 Reduced Different job in same 

workplace 

38 

 Removed Left workplace 85 Banks, 1990 

Reduced Moved to areas with 

negligable or no exposure 

6 NSBPT 

Pulmonary function 

Methacholine: PD2

FEV1 and FVC 

 Questionnaire Including symptomBarker, 1998 

Removed All subjects left the factory 

in 1980 

6 NSBPT 

Pulmonary function 

Histamine bronchiAverage daily ampminimum PEFR/mday period 

 Questionnaire Including symptom

smoking 

 Skin prick test 1% TCPA-HSA  Serum specific IgE RAST Bernstein, 2003 

Exposed Protection 

No intervention initiated Used NRL gloves 

1 19 

Skin prick test Latex 

 Reduced Transferred 1  Removed Left workplace 4 Burge, 1982a 

Reduced Moved within factory, no 

description of exposure status 

9 NSBPT Histamine reactivit

 Removed Changed workplace 22 Pulmonary function FEV1 and FVC  Questionnaire Including symptomGannon, 1993 

Exposed Removed 

Not described Removed from exposure 

34 78 

Questionnaire Including symptom

current financial si

Gassert, 1998 

Removed Removed from exposure 55 Questionnaire Including symptom

medication use 
E-71

Table E-7. Description of interventions and outcomes (Management cohorts review) 

(continued) 

Author, Intervention(s) Outcome(s) Year Type of 

Intervention 

Description Number of 

Patients 

Test Description 

Gorski, 1999 

Removed Changed jobs or stopped 

working 

56 NSBPT 

Pulmonary function 

Histamine: PC20 F

FEV1

 Questionnaire Including symptom Skin prick test Common allergens  Serum specific IgE RAST Grammer, 2000 

Reduced Transferred to lower 

exposure 

22 Pulmonary function Spirometry (not sp

 Removed Completely removed from 

exposure 

7 Questionnaire 

Serum specific IgE 

Including type and Described in text 

 Serum specific IgG Described in text Grammer, 1996 

Removed Removed from exposure 

for at least 1 yr 

11 Pulmonary function 

Questionnaire 

Spirometry (not spIncluding type and 

 Serum specific IgE Described in text  Serum specific IgG Described in text Harries, 1979 

Reduced Removed 

Changed tasks Moved to a safer location or left industry 

1 2 

Interview Pulmonary function 

Including medicatiFEV1 and FVC 

Jyo, 1989 

Medications Immunotherapy 47 Improvement after 

hyposensitization therapy 

Improvement after 

 Serum specific IgE RAST  Serum specific IgG RAST Laoprasert, 1998 

Protection Used NRL gloves and/or 

helmet filter 

11 SIC 

Symptoms 

Latex aeroallergen Not described 

Lemiere, 2000 

Removed Removed from exposure 16 Questionnaire Including symptom

and smoking habit

 SIC Suspected agent  Skin prick test Cereals, guar gum Serum specific IgE RAST Lemiere, 1996 

Removed No longer exposed after 

diagnosis 

15 Questionnaire 

SIC 

Including symptomSuspected agent 

 Skin prick test Common inhalants  Serum specific IgE RAST  Serum specific IgG Not described 
E-72

Table E-7. Description of interventions and outcomes (Management cohorts review) 

(continued) 

Author, Intervention(s) Outcome(s) Year Type of 

Intervention 

Description Number of 

Patients 

Test Description 

Lin, 1996 

Exposed Continued exposure 158 Pulmonary 

function17

FEV1

 Removed Left industry after 

diagnosis 

122 Exhaled nitric 

oxide25 Not reported 

 NSBPT25 Methacholine: PC2 Questionnaire25 Not described  Sputum cell counts25 Eosinophils, neutro

lymphocytes, and 

 Bronchial lavage22 Total cell count an

lymphocytes, neutepithelial cells, degprotein, and album

 Interview20 Including current w Skin prick test20 Common allergens  Serum specific IgG20 Radial immunodiff Reduced18 Changed jobs resulting in 

intermittant exposure 

42 Serum eosinophil 

count19 Serum eosinophil 

 Bronchial lavage21 Including protein, a

neutrophils 

Lozewicz, 1987 

Reduced Relocated to another area 

within the plant 

28 NSBPT 

Pulmonary function Questionnaire 

Histamine: 10% fa

FEV1 and FVC 

Including symptom

 Removed Left workplace 21 SIC TDI, MDI, HDI, ND Skin prick test Common allergens Maghni, 2004 

Removed No longer exposed 133 NSBPT 

Pulmonary function 

Methacholine: PC2

FEV1

 Questionnaire Including exposure 

medication needs 

 Sputum cell counts Eosinophils, neutr

eotaxin 

Malo, 2004 

Removed No longer exposed to 

causal agent 

80 NSBPT Methacholine: PC2
E-73

Table E-7. Description of interventions and outcomes (Management cohorts review) 

(continued) 

Author, Intervention(s) Outcome(s) Year Type of 

Intervention 

Description Number of 

Patients 

Test Description 

Malo, 1994a 

Removed Not exposed to chlorine 

during the 1 yr follow-up period 

20 Medications 

NSBPT 

Beta-2-agonist and none Methacholine: PC2

 Pulmonary function FEV1Malo, 1993b 

Removed Subjects had left work for 

at least 2 yrs prior to entering the study 

134 Quality of life 

questionnaire28

WCB claim data29

Asthma quality of Administrative WC

 NSBPT 28 Methacholine: PC2 Pulmonary function 29 FEV1 Questionnaire 29 Including symptomMalo, 1988b 

Removed Removed from exposure 

since the time of diagnosis 

31 NSBPT 

Pulmonary function 

Histamine or meth

FEV1 and FVC 

 Questionnaire Including sympom

and smoking habit

 Serum specific IgE RAST Mapp, 1988 

Exposed Removed 

Not described No longer exposed 

5 30 

NSBPT Pulmonary function 

Methacholine: PD2

FEV1

 SIC TDI, MDI, HDI, ND Symptoms Not described Marabini, 2003 

Exposed Attempted to reduce 

exposure (n=7) but none moved to no exposure 

10 NSBPT 

Pulmonary function 

Methacholine: PC2

FEV1 and FVC 

Merget, 1999 

Exposed Reduced 

Same workplace Transferred to jobs not directly exposed to irritant 

9 16 

NSBPT30

Pulmonary function30

Methacholine: PD5

FEV1

 Removed Transferred outside of 

workplace 

19 Questionnaire30 Including symptom

and employment s

 Skin prick test30 Platinum salts  SIC31 Platinum salts Meyer, 1977 

Removed Ceased exposure 168 NSBPT Acetycholine: impr
E-74

Table E-7. Description of interventions and outcomes (Management cohorts review) 

(continued) 

Author, Intervention(s) Outcome(s) Year Type of 

Intervention 

Description Number of 

Patients 

Test Description 

Moscato, 1999 

Exposed Performed the same task 

in the same workplace 

7 NSBPT Methacholine: PD2

 Reduced Changed task within 

workplace and reported intermittent or lower exposure 

5 Pulmonary function 

Questionnaire 

PEF for the duratioIncluding symptomfinancial condition

 Removed Left workplace 7 Munoz, 2003 

Protection Not described 3 NSBPT Methacholine: PC2

 Removed All subjects advised to 

avoid exosure 

5 Pulmonary function Serial PEF 4 times

work 

 SIC Potassium persulfa Skin prick test Potassium and amO'Donnell, 1989 

Exposed Moved within factory, no 

description of exposure 

57 NSBPT Methacholine: PC2

Orriols, 1999 

Protection Removed 

Not described Avoided casual exposure 

4 17 

Symptoms Persistent, worsen

Paggiaro, 1993 

Reduced Moved within factory with 

occasional exposure 

7 NSBPT Methacholine: PD2

 Removed Left industry 9 SIC TDI Paggiaro, 1990 

Removed Ceased exposure after 

diagnosis 

10 Bronchial lavage Total cell count an

lymphocytes, neut

 NSBPT Methacholine: PD1Paggiaro, 1984a 

Exposed Continued exposure 15 NSBPT 

Pulmonary function 

Bethanechol: 15% 

FEV1 and FVC 

 Removed Left workplace 12 SIC Not described  Skin prick test Common allergens Park, 2002a 

Removed Withdrawn from work to 

avoid further exposure 

41 Serum specific IgE32 ELISA 

Park, 1994 

Removed Advised to discontinue 

exposure 

3 NSBPT 

Serum specific IgG32

Methacholine: PC2

ELISA 

 NSBPT33 Methacholine: PC2
E-75

Table E-7. Description of interventions and outcomes (Management cohorts review) 

(continued) 

Author, Intervention(s) Outcome(s) Year Type of 

Intervention 

Description Number of 

Patients 

Test Description 

Perfetti, 1998a 

Removed34 Subjects removed from 

exposure >or equal to 5 yrs, and those removed from exposure for <5 yrs 

99 NSBPT34

Pulmonary function34Questionnaire34

Methacholine: PC2FEV1

Including current asteroids and expos

 Skin prick test34 Ubiquitous agents  Reduced35 Occasional or reduced 

levels of exposure (wearing a mask or respirator) 

8 Serum specific IgE35 EAST 

Piirila, 1996 

Reduced Same task after industrial 

accident (RADS) 

3 Bronchodilatory 

response 

Change in FEV1 5 

rimiterol hydrobrom

 Removed Retired after industrial 

accident (RADS) 

1 Exercise test 

NSBPT 

Change in PEF aftHistamine: percen

 Pulmonary function FEV1 and FVC Pisati, 1994 

Exposed Not described 1 NSBPT 

Pulmonary function 

Methacholine: PD1

FEV1 and FVC 

 Removed Moved to another industry 8 Questionnaire Including exposure 

medication needs 

 SIC Cobalt  Skin prick test Common inhalant 

cobalt sulphate 

Pisati, 1993 

Reduced Different task with 

reduced exposure and used protective respiratory device 

17 Interview 

NSBPT Pulmonary function 

Including working need for medicatioMethacholine: PD1

FEV1 and FVC 

 Removed Ceased exposure within 6 

mos of diagnosis 

43 Skin prick test Common inhalant 

Rosenberg, 1987 

Exposed Unchanged work 

conditions 

4 NSBPT 

Pulmonary function 

Acetycholine: perc

FEV1 and FVC 

 Protection 

Reduced 

Efficient masks, ventilation Changed task within workplace 

3 4 

Questionnaire Including work sta

requirement for mehabits 

 Removed Completely removed from 

exposure 

20 
E-76

Table E-7. Description of interventions and outcomes (Management cohorts review) 

(continued) 

Author, Intervention(s) Outcome(s) Year Type of 

Intervention 

Description Number of 

Patients 

Test Description 

Ross, 1998 

Removed Not described 1033 Questionnaire Including symptom

Saetta, 1995 

Removed Ceased exposure 10 Bronchoscopy36

NSBPT36

Fibroblast counts Methacholine: PD2

 SIC36 TDI  Bronchoscopy37 Basement membraSen, 1998 

Removed Left industry 3 Serum specific IgE 

Serum specific IgG 

RAST RAST 

Simonsson, 1985 

Exposed Not described 6 NSBPT 

Pulmonary function 

Methacholine: TD1

FEV1 and FVC 

 Removed Not described 13 SIC Aluminium salts Slovak, 1985 

Protection Helmet respirator and 

outer protective clothing 

10 Pulmonary function 

Skin prick test 

Serial PEF every 2 Lab animal allergy 

Smith, 1999 

Exposed Reduced 

Same workplace Different job in same workplace 

11 11 

Interview Including symptom

Sulotto, 1989 

Removed and medications 

Took beclomethasone for 3 to 12 mos after cessation of exposure 

10 NSBPT 

Pulmonary function 

Methacholine: PD2

FEV1, FVC, MEF50

Taivainen, 1998 

Protection Helmet respirator 26 Pulmonary function 

Symptoms 

Serial PEF: morninRecorded daily on 

Vandenplas, 2002 

Reduced Removed 

<20 pairs of latex gloves used per wk by coworkers Latex gloves never used 

20 16 

NSBPT Pulmonary function Questionnaire 

Histamine: PC20 F

FEV1

Including occupatihabits, symptoms, other allergic react

 SIC Latex gloves Venables, 1987 

Removed Not described 6 NSBPT 

Pulmonary function 

Histamine: PC20 F

FEV1

 Questionnaire Including current r

medication, and sm

 Skin prick test 1% TCPA-HSA  Serum specific IgE RAST 
E-77

Table E-7. Description of interventions and outcomes (Management cohorts review) 

(continued) 

Author, Intervention(s) Outcome(s) Year Type of 

Intervention 

Description Number of 

Patients 

Test Description 

Venables, 1985 

Reduced Industrial intervention to 

reduce TDI levels 

21 Pulmonary function 

Questionnaire 

Serial PEF: every Including symptom

Abbreviations: EAST = enzyme allergosorbent test; ELISA = enzyme-linked immuno sorbent assay; FEV1 = forced expiratory volume in 

forced vital capacity; HDI = hexamethylene di-isocyanate; hrs = hours; IL-8 = interleukin-8; MDI = diphenylmethane di-isocyanate; MEF2

flow at 25% of vital capacity; MEF50 = maximal expiratory flow at 50% of vital capacity; mos = months; MPO = myeloperoxidase; NDI = n

NSBPT = non-specific bronchial provocation; NRL = natural rubber latex; PC20 = provocative concentration causing a 20% drop in FEV1

causing a 15% drop in FEV1; PD50 = provocative dose causing a 50% drop in FEV1; PEF = peak expiratory flow; PEFR = peak expiratory 

reactive airways dysfunction syndrome; RAST = radio allegro sorbent test; SIC = specific inhalational challenge; TCPA-HSA = tetrachlor

human serum albumin; TD15 = threshold dose causing a 15% drop in FEV1; TDI = toluene di-isocyanates; WCB = workers’ compensatio= weeks; yr = year; yrs = years 
E-78

Table E-8. Description of included studies (Management trials review) Author, Year 

Location Language of 

Publication 

Intervention Categories 

Suspected Agent (molecular weight) 

Subject Source 

Description of Inc

Armentia, 1990 

Spain English Medications Flour (H) - Bakers and pastry c

symptoms due to w

Crescioli, 1992 

Italy English Medications Isocyanates (L) - Workers SIC positiv

DeMarzo, 1988 

Italy English Medications Isocyanates (L) - Workers sensitized 

Fabbri, 1985 

Italy English Medications Isocyanates (L) - Workers SIC positiv

Maestrelli, 1993 

Italy English Removed and 

medications 

Isocyanates (L) - Workers with OA d

Malo, 1996 

Canada English Removed and 

medications 

Mixed (M) - Workers with OA du

Malo, 1994b 

Canada French Medications Mixed (M) - Workers, mostly ex

referred to a clinic f

Mapp, 1987 

Italy English Medications Isocyanates (L) Clinic Workers with OA d

Moscato, 1985 

Italy English Medications Isocyanates (L) - Male workers with O

Mueller, 1998 

Germany English Protection Straw/grain (U) - Dairy/bull breeding 

OA 

Paggiaro, 1987a 

Italy English Medications Isocyanates (L) - Workers with OA d

Vandenplas, 1995a 

Belgium English Reduced Latex (H) - Healthcare workers 

asthma 

Woitowitz, 1972 

Germany English Medications Flour (H) - Workers with OA d

Abbreviations: H = high; L = low; OA = occupational asthma; SIC = specific inhalational challenge; TDI = toluene di-isocyanates; U = u
E-79

Table E-9. Demographic characteristics of included patients (Management trials review) 

Male Age Atopic Smoking 

Status 

History of Asthma 

% predicted FEV1 (unless 

otherwise stated) 

Years of Exposure 

Years of Symptoms 

Author, Year 

Number of Patients 

(%) mean (SD) (%) (%) (%) mean (SD) mean (SD) mean (SD)

Armentia, 1990 

30 - 34.5 

(12.2) 

- - - - 12.8 

(9.6) 

5 (4) 

Crescioli, 1992 

6 100 42.8 

(6.5) 

0 C: 0 

Ex: 0 N: 100 

- 104.5 

(10.4) 

- - 

DeMarzo, 1988 

9 88.9 34.7 

(10.4) 

0 - - 96.7 

(10.4) 

- - 

Fabbri, 1985 

5 60 39.6 

(17.3) 

0 C: 0 

Ex: 20 N: 80 

- 108 

(11.7) 

- - 

Maestrelli, 1993 

15 26.7 37.4 

(10) 

20 - - - 12.6 

(7.2) 

3.4 (-) 

Malo, 1996 

32 68.8 39.3 

(12.9) 

59.4 C: 21.9 

Ex: 9.4 N: 68.8 

- - 9.4 

(11) 

2.7 (-) 

Malo, 1994b 

22 63.6 46 

(10) 

59.1 C: 22.7 

Ex: 27.3 N: 50 

- 84 

(13) 

13 (12) 

3 (3) 

Mapp, 1987 

24 66.7 35.2 

(11.6) 

29.2 - - - - - 

Moscato, 1985 

5 100 29.4 

(9) 

- - - 92.2 

(13.8) 

- - 

Mueller, 1998 

26 69.2 38.6 

(11.8) 

23.1 C: 38.5 - FEV1: 3.5 

(1) 

34 (14.9) 

9.1 (6.8) 

Paggiaro, 1987a 

10 80 48 

(8.2) 

20 C: 20 

Ex: 30 N: 50 

- 82.2 

(16.2) 

- 5.5 

(4) 

Vandenplas, 1995a 

8 12.5 31 

(3.7) 

62.5 C: 0 

Ex: 12.5 N: 87.5 

- 98.6 

(10.2) 

- - 

Woitowitz, 1972 

18 100 31.4 

(10.2) 

- - - - - - 

Abbreviations: C = current; Ex = ex; FEV1 = forced expiratory volume in one second; N = never; OA = occupational asthma; SD = stand

specific inhalational challenge
E-80

Table E-10. Description of interventions and outcomes (Management trials review) Author, Intervention(s) Outcome(s) Year Type of 

Intervention 

Description Number of 

Patients 

Test Desc

Armentia, 1990 

Medications Hyposensitization 

(immunotherapy) and placebo 

26 Hypersensitivity after 20 mos of 

immunotherapy or placebo 

Immu

Whea

challe

serum 

Crescioli, 1992 

Medications Theophylline and placebo 6 2 SICs separated by 1 wk: 1 with 

drug / 1 without 

Chan

DeMarzo, 1988 

Medications High dose beclomethasone, 

low dose beclomethasone, placebo 

9 3 SICs separated by at least 1 wk: 

for each treatment phase 

Chan

Fabbri, 1985 

Medications Indomethacin and prednisone 5 2 SICs: pre-treatment and 3 days 

after treatment started 

Chan

Maestrelli, 1993 

Removed and medications 

Beclomethasone and placebo 15 Hypersensitivity after 5 mos of drug 

or placebo 

Maxim

PD20 

challelevel 

Malo, 1996 

Removed and medications 

Beclomethasone and placebo 32 Spirometry/hyper-reponsiveness 

after 12 mos with treatment 1 and 6 mos with treatment 2 

ChanPC20 

challesympt

Malo, 1994b 

Medications Salbutamol and placebo 25 Change in FEV1 after SIC Chan

adminor plaasthm

Mapp, 1987 

Medications Beclomethasone and placebo, 

thoephylline and placebo, varapamil and placebo, cromolyn and placebo 

6, 6, 6, 6 

2 SICs separated by at least 1 wk: 1 with drug / 1 without 

Chan

Moscato, 1985 

Medications Nifedipine and placebo 5 2 SICs separated by at least 1 wk: 

1 with drug / 1 without 

Chan

Mueller, 1998 

Protection Respirators with P2 filters 26 2 SIC's separated by 21 wks: 1 

without respirator / 1 with 

Chanand thand a

Paggiaro, 1987a 

Medications Atropine and placebo 18 2 SICs separated by at least 1 wk: 

1 with drug / 1 without 

Chanand thand a
E-81

Table E-10. Description of interventions and outcomes (Management trials review) (continued) Author, Intervention(s) Outcome(s) Year Type of 

Intervention 

Description Number of 

Patients 

Test Desc

Vandenplas, 1995a 

Reduced 4 types of gloves: Triflex®, 

low-powdered Triflex®, nonpowdered Nutex®, powdered Sensi-Touch® 

8 3 SICs with different gloves (all 

Triflex® then randomized to two of low-powdered Triflex®, nonpowdered Nutex®, or powdered Sensi-Touch®) 

Maxim

Woitowitz, 1972 

Medications Fenoterol and placebo 9 SIC after treatment with drug or 

placebo 

Airwa

Abbreviations: FEV1 = forced expiratory volume in one second; PC20 = provocative concentration causing a 20% drop in FEV1; PD20 = 

a 20% drop in FEV1; SIC = specific inhalational challenge; wk = week; wks = weeks
E-82

Table E-11. Methodological quality of included studies (Management cohorts review) Author, Year 

Downs and Black Quality Score 

Data Collection Provided Individual 

Patient Data 

Funding Source 

Allard, 1989 

16 Prospective No Not reported 

Ameille, 1997 

17 Prospective No Not reported 

Banks, 1990 

17 Prospective Yes Government 

Barker, 1998 

21 Prospective Yes Government 

Bernstein, 2003 

15 Prospective No Government 

Burge, 1982a 

16 Prospective No Not reported 

Gannon, 1993 

19 Prospective No Not reported 

Gassert, 1998 

21 Prospective No Government 

Gorski, 1999 

12 Prospective No Not reported 

Grammer, 2000 

15 Prospective No Internal and private 

Grammer, 1996 

17 Prospective Yes Internal 

Harries, 1979 

17 Prospective Yes Not reported 

Jyo, 1989 

9 Prospective Yes Government 

Laoprasert, 1998 

19 Prospective Yes Private and internal 

Lemiere, 2000 

20 Prospective Yes Foundation 

Lemiere, 1996 

22 Prospective Yes Private and other 

Lin, 1996 

22 Prospective No Not reported 

Lozewicz, 1987 

19 Prospective No Not reported 
E-83

Table E-11. Methodological quality of included studies (Management cohorts review) (continued) Author, Year 

Downs and Black Quality Score 

Data Collection Provided Individual 

Patient Data 

Funding Source 

Maghni, 2004 

21 Prospective No Not reported 

Malo, 2004 

17 Prospective No Not reported 

Malo, 1994 

18 Prospective Yes Government and 

other 

Malo, 1993 

14 Prospective No Not reported 

Malo, 1988 

18 Prospective Yes Not reported 

Mapp, 1988 

18 Prospective Yes Government and 

other 

Marabini, 2003 

18 Prospective No Other 

Merget, 1999 

20 Prospective No Not reported 

Meyer, 1977 

6 Prospective No Not reported 

Moscato, 1999 

22 Prospective No Government 

Munoz, 2003 

19 Prospective Yes Not reported 

O'Donnell, 1989 

13 Prospective No Not reported 

Orriols, 1999 

12 Prospective No Not reported 

Paggiaro, 1993 

16 Prospective Yes Government 

Paggiaro, 1990 

18 Prospective Yes Government 

Paggiaro, 1984 

15 Prospective Yes Not reported 

Park, 2002 

18 Prospective Yes Private 

Park, 1994 

12 Prospective Yes Not reported 
E-84

Table E-11. Methodological quality of included studies (Management cohorts review) (continued) Author, Year 

Downs and Black Quality Score 

Data Collection Provided Individual 

Patient Data 

Funding Source 

Perfetti, 1998 

19 Prospective Yes Foundation 

Piirila, 1996 

17 Prospective Yes Not reported 

Pisati, 1994 

14 Prospective Yes Not reported 

Pisati, 1993 

18 Prospective No Not reported 

Rosenberg, 1987 

10 Prospective Yes Not reported 

Ross, 1998 

22 Retrospective No Government 

Saetta, 1995 

17 Prospective Yes Government 

Sen, 1998 

13 Prospective Yes Not reported 

Simonsson, 1985 

13 Prospective Yes Not reported 

Slovak, 1985 

9 Prospective Yes Not reported 

Smith, 1998 

12 Prospective No Not reported 

Sulotto, 1989 

10 Prospective No Not reported 

Taivainen, 1998 

21 Prospective Yes Not reported 

Vandenplas, 2002 

22 Prospective No Other 

Venables, 1987 

20 Prospective Yes Not reported 

Venables, 1985 

10 Prospective No Not reported 
E-85

Table E-12. Methodological quality of included studies (Management trials review) Author, Year 

Randomization Randomization 

Method 

Double Blind Double Blind 

Method 

Explanation of Withdrawal or Follow-up 

Allocation Concealment 

Armentia, 1990 

No Unclear Yes Unclear Adequate Inadequate 

Crescioli, 1992 

Yes Unclear Yes Unclear Adequate Unclear 

DeMarzo, 1988 

Yes Unclear Yes Unclear Adequate Unclear 

Fabbri, 1985 

No Unclear No Unclear Adequate Inadequate 

Malo, 1996 

Yes Unclear Yes Unclear Adequate Adequate 

Malo, 1994 

No Unclear Yes Unclear Adequate Unclear 

Mapp, 1987 

Yes Unclear Yes Unclear Adequate Unclear 

Mastrelli, 1993 

Yes Unclear Yes Unclear Adequate Unclear 

Moscato, 1983 

Yes Unclear No Unclear Adequate Unclear 

Muller-Wening, 1998 

No Unclear No Unclear Adequate Inadequate 

Paggiaro, 1987 

No Unclear No Unclear Adequate Inadequate 

Vandenplas, 1995 

Yes Unclear No Unclear Adequate Unclear 

Woitowitz, 1972 

Yes Unclear Yes Unclear Adequate Adequate 
E-86

References 

Diagnosis 

 1. Alvarez MJ, Estrada JL, Gozalo F et al. 

Oilseed rape flour: another allergen causing 

occupational asthma among farmers. Allergy 

2001; 56(2):185-8. 

 2. Alvarez MJ, Tabar AI, Quirce S et al. 

Diversity of allergens causing occupational 

asthma among cereal workers as demonstrated 

by exposure procedures. Clin Exp Allergy 

1996; 26(2):147-53. 

 3. Anees W, Gannon PF, Huggins V et al. Effect 

of Peak Expiratory Flow Data Quantity on 

Diagnostic Sensitivity and Specificity in 

Occupational Asthma. Eur Respir J 2004; 

23(5):370-4. 

 4. Avery SB, Stetson DM, Pan PM et al. 

Immunological investigation of individuals 

with toluene diisocyanate asthma. Clin Exp 

Immunol 1969; 4(5):585-96. 

 5. Balland S, Grosclaude M, Jarsaillon E et al. 

Realistic challenge and bronchial 

hyperreactivity in occupational asthma. 

[French]. J Toxicol Clin Exp 1989; 9(1 

BIS):15-23. 

 6. Baur X, Fruhmann G. Papain-induced asthma: 

diagnosis by skin test, RAST and bronchial 

provocation test. Clin Allergy 1979; 9(1):75-

81. 

 7. Baur X, Huber H, Degens PO et al. Relation 

between occupational asthma case history, 

bronchial methacholine challenge, and specific 

challenge test in patients with suspected 

occupational asthma. Am J Ind Med 1998; 

33(2):114-22. 

 8. Behr J, Baur X, Rommelt H et al. [Diagnosis 

of irritative-toxic isocyanate asthma with the 

isocyanate exposure test]. Pneumologie 1990; 

44 Suppl 1:229-31. 

 9. Bernstein DI, Cartier A, Cote J et al. 

Diisocyanate antigen-stimulated monocyte 

chemoattractant protein-1 synthesis has greater 

test efficiency than specific antibodies for 

identification of diisocyanate asthma.[see 

comment]. Am J Respir Crit Care Med 2002; 

166(4):445-50. 

 10. Biot N, Grosclaude M, Meyer JL et al. 

[Contribution of biological tests in the 

evaluation of professional asthma (author's 

transl)]. [French]. Poumon Coeur 1980; 

36(4):257-61. 

 11. Block G, Tse KS, Kijek K et al. Baker's 

asthma. Clinical and immunological studies. 

Clin Allergy 1983; 13(4):359-70. 

 12. Burge PS. Non-specific bronchial hyperreactivity in workers exposed to toluene diisocyanate, diphenyl methane di-isocyanate 

and colophony. Eur J Respir Dis 1982; Suppl 

123:91-6. 

 13. Burge PS, Harries MG, Lam WK et al. 

Occupational asthma due to formaldehyde. 

Thorax 1985; 40:255-60. 

 14. Burge PS, Harries MG, O'Brien et al. 

Bronchial provocation studies in workers 

exposed to the fumes of electronic soldering 

fluxes. Clin Allergy 1980; 10:137-49. 

 15. Burge PS, Harries MG, O'Brien IM et al. 

Respiratory disease in workers exposed to 

solder flux fumes containing colophony (pine 

resin). Clin Allergy 1978; 8(1):1-14. 

 16. Burge PS, O'Brien IM, Harries MG. Peak flow 

rate records in the diagnosis of occupational 

asthma due to colophony. Thorax 1979; 

34:308-16. 

 17. Burge PS, O'Brien IM, Harries MG. Peak flow 

rate records in the diagnosis of occupational 

asthma due to isocyanates. Thorax 1979; 

34(3):317-23. 

 18. Butcher BT, O'Neil CE, Reed MA et al. 

Radioallergosorbent testing of toluene 

diisocyanate reactive individuals using ptolyl 

isocyanate antigen. J Allergy Clin Immunol 

1980; 66(3):213-6. 

 19. Carletti AM, Talini D, Carrara M et al. 

[Specific bronchial provocation tests with flour 

in the diagnosis of occupational bronchial 

asthma]. Med Lav 1997; 88(5):406-15. 
E-87

 20. Cartier A, Grammer L, Malo J L et al. Specific 

serum antibodies against isocyanates: 

association with occupational asthma. J 

Allergy Clin Immunol 1989; 84(4 Pt 1):507-

14. 

 21. Cartier A, Malo J L, Dolovich J. Occupational 

asthma in nurses handling psyllium. Clin 

Allergy 1987; 17(1):1-6. 

 22. Cartier A, Malo JL, Ghezzo H et al. IgE 

sensitization in snow crab-processing workers. 

J Allergy Clin Immunol 1986; 78(2):344-8. 

 23. Choudat D, Fabries JF, Martin JC et al. 

Quantification of the dose of inhaled flour: 

relation with nonspecific bronchial and 

immunological reactivities. Eur Respir J 1999; 

14(2):328-34. 

 24. Cirla AM, Inzoli S, Aresini G et al. 

[Evaluation of the diagnostic criteria in 

occupational asthma caused by isocyanates]. 

Med Lav 1975; 66(1):5-23. 

 25. Colas M, Grosclaude M, Balland S et al. Value 

of realistic exposure tests in the diagnosis of 

occupational asthma due to exotic woods 

[French]. Rev Pneumol Clin 1985; 41(1):39-

46. 

 26. Cortona G, Beretta F, Traina G et al. 

[Preliminary investigation in a pharmaceutical 

industry: bromelin-induced pathology (author's 

transl)] Italian. Med Lav 1980; 1:70-5. 

 27. Cote J, Kennedy S, Chan-Yeung M. 

Quantitative versus qualitative analysis of peak 

expiratory flow in occupational asthma. 

Thorax 1993; 48(1):48-51. 

 28. Coutts IL, Lozewicz S, Dally MB et al. 

Respiratory symptoms related to work in a 

factory manufacturing cimetidine tablets. BMJ 

(Clin Res Ed) 1984; 288(6428):1418. 

 29. Curran AD, Burge PS, Wiley K. Clinical and 

immunologic evaluation of workers exposed to 

glutaraldehyde. Allergy 1996; 51(11):826-32. 

 30. Davison AG, Britton MG, Forrester JA et al. 

Asthma in merchant seamen and laboratory 

workers caused by allergy to castor beans: 

analysis of allergens. Clin Allergy 1983; 

13:553-61. 

 31. De Zotti R, Gubian F. Asthma and rhinitis in 

wooding workers. Allergy Asthma Proc 1996; 

17(4):199-203. 

 32. De Zotti R, Gubian F, Negro C. [Changes in 

blood eosinophils and nonspecific bronchial 

reactivity after exposure tests to wheat flour 

and TDI]. Med Lav 1996; 87(2):152-61. 

 33. Dellabianca A, Omodeo P, Colli MC et al. 

Bronchial responsiveness to ultrasonic "fog" in 

occupational asthma due to low molecular 

weight chemicals. Ann Allergy Asthma 

Immunol 1996; 77(5):378-84. 

 34. Dente PL, Rossi O, Talini D et al. Bronchial 

hyperresponsiveness and respiratory symptoms 

in toluene di-isocyanate (TDI) induced asthma. 

Bull Eur Physiopathol Respir 1986; 22(Suppl 

8): A739. 

 35. Di Franco A, Vagaggini B, Bacci E et al. 

Leukocyte counts in hypertonic saline-induced 

sputum in subjects with occupational asthma. 

Respir Med 1998; 92(3):550-7. 

 36. Di Stefano F, Siriruttanapruk S, McCoach J et 

al. Glutaraldehyde: an occupational hazard in 

the hospital setting. Allergy 1999; 

54(10):1105-9. 

 37. Duan YY, et al. Occupational toluene 

diisocyanate (TDI) asthma inhalation challenge 

test and TDI-HSA skin test and detection os 

specific IgE. Chinese J Tubercul Respir Dis 

1989; 12 (3):149-52. 

 38. Ferguson K, Gallie A, Ahmad D et al. Asthma 

in isocyanate workers: How often is it related 

to occupation? J Occup Health Safety - Austr 

New Zeal 1996; 12(1):31-40. 

 39. Gannon PF, Newton DT, Belcher J et al. 

Development of OASYS-2: a system for the 

analysis of serial measurement of peak 

expiratory flow in workers with suspected 

occupational asthma. Thorax. 1996; 51(5):484-

9. 

 40. Girard F, Chaboillez S, Cartier A et al. An 

Effective Strategy for Diagnosing 

Occupational Asthma: Use of Induced Sputum. 

Am J Respir Crit Care Med 2004; 170(8):845-

50. [Epub ahead of print]. 

 41. Graneek BJ, Durham SR, Newman Taylor AJ. 

Late asthmatic reactions and changes in 

histamine responsiveness provoked by 

occupational agents Bulletin. Eur 

Physiopathol Respir 1987; 23(6):577-81. 
E-88

 42. Grosclaude M, Kofman J, Perrin-Fayolle M. 

Respiratory functional tests in professional 

asthma. Value of realistic tests. Poumon Coeur 

1980; 36(4):249-54. 

 43. Harries MG, Burge PS, O'Brien IM. 

Occupational type bronchial provocation tests. 

Testing with soluble antigens by inhalation. Br 

J Ind Med 1980; 37(3):248-52. 

 44. Hinojosa M, Losada E, Moneo I et al. 

Occupational asthma caused by African maple 

(Obeche) and Ramin: evidence of cross 

reactivity between these two woods. Clin 

Allergy 1986; 16(2):145-53. 

 45. Howe W, Venables KM, Topping MD et al. 

Tetrachlorophthalic anhydride asthma: 

evidence for specific IgE antibody. J Allergy 

Clin Immunol 1983; 71(1 Pt 1):5-11. 

 46. Huggins V, Hole A, Burge PS et al. Peak 

expiratory flow responses analyzed with 

OASYS in workers exposed to detergent 

enzymes. Eur Respir Soc 2003. 

 47. Jager D, Engelke T, Rennert S et al. [Stepwise 

diagnosis of respiratory latex allergy]. 

Pneumologie 1993; 47(8):491-6. 

 48. Karol MH, Tollerud DJ, Campbell TP et al. 

Predictive value of airways 

hyperresponsiveness and circulating IgE for 

identifying types of responses to toluene 

diisocyanate inhalation challenge. Am J Respir 

Crit Care Med 1994; 149(3 Pt 1):611-5. 

 49. Kern DG. Outbreak of the reactive airways 

dysfunction syndrome after a spill of glacial 

acetic acid. Am Rev Respir Dis 1991; 

144(5):1058-64. 

 50. Keskinen H, Tupasela O, Tiikkainen U et al. 

Experiences of specific IgE in asthma due to 

diisocyanates. Clin Allergy 1988; 18(6):597-

604. 

 51. Kim H, Kim YD, Choi J. Serioimmunological 

characteristics of Korean workers exposed to 

toluene diisocyanate. Environ Res 1997; 

75(1):1-6. 

 52. Kim YK, Son JW, Kim HY et al. New 

occupational allergen in citrus farmers: citrus 

red mite (Panonychus citri). Ann Allergy 

Asthma Immunol 1999; 82(2):223-8. 

 53. Kongerud J, Soyseth V, Burge PS. Serial 

measurements of peak expiratory flow and 

responsiveness to methacholine in the 

diagnosis of aluminum potroom asthma. 

Thorax 1992; 47:292-7. 

 54. Kopferschmitt-Kubler MC, Frossard N, Rohde 

G et al. Increase in non-specific bronchial 

hyperresponsiveness without specific response 

to isocyanate in isocyanate-induced asthma: a 

pilot study. Respir Med 1998; 92(9):1093-8. 

 55. Koskela H, Taivainen A, Tukiainen H et al. 

Inhalation challenge with bovine dander 

allergens: who needs it? Chest 2003; 

124(1):383-91. 

 56. Krakowiak A, Ruta U, Gorski P et al. Nasal 

lavage fluid examination and rhinomanometry 

in the diagnostics of occupational airway 

allergy to laboratory animals. Int J Occup Med 

Environ Health 2003; 16(2):125-32. 

 57. La Paglia G, Ruvolo M, Scancarello D et al. 

[Usefulness of specific bronchial provocation 

tests in the diagnosis of compensable 

occupational allergic pneumopathies]. G Ital 

Med Lav 1986; 8(3-4):139-44. 

 58. Lam S, Wong R, Chan-Yeung M. Nonspecific 

bronchial reactivity in occupational asthma. J 

Allergy Clin Immunol 1979; 63:28-34. 

 59. Larbanois A, Delwiche JP, Jamart J et al. 

Comparison of FEV1 and specific airway 

conductance in assessing airway response to 

occupational agents. Allergy 2003; 

58(12):1256-60. 

 60. Lemiere C, Chaboillez S, Malo JL et al. 

Changes in sputum cell counts after exposure 

to occupational agents: what do they mean? J 

Allergy Clin Immunol 2001; 107(6):1063-8. 

 61. Liss GM, Tarlo SM. Peak expiratory flow rates 

in possible occupational asthma.[see 

comment]. Chest 1991; 100(1):63-9. 

 62. Lozewicz S. Occupational asthma due to 

methylcrylate and cyanoacrylates. Thorax 

 1985; 40(11):836-9. 

 63. Malo JL, Cartier A. Occupational asthma in 

workers of a pharmaceutical company 

processing spiramycin. Thorax 1988; 43:371-7. 

 64. Malo JL, Cote J, Cartier A et al. How many 

times per day should peak expiratory flow 

rates be assessed when investigating 

occupational asthma. Thorax 1993; 48:1211-7. 
E-89

 65. Malo JL, Ghezzo H, L'Archeveque J et al. Late 

asthmatic reactions to occupational sensitizing 

agents: frequency of changes in nonspecific 

bronchial responsiveness and of response to 

inhaled beta-2 adrenergic agent. J Allergy Clin 

Immunol 1990; 85:834-42. 

 66. Malo JL, Ghezzo H, L'Archeveque J et al. Is 

the clinical history a satisfactory means of 

diagnosing occupational asthma? Am Rev 

Respir Dis 1991; 143:528-32. 

 67. Mapp CE, Dal Vecchio L, Boschetto P et al. 

Toluene diisocyanate-induced asthma without 

airway hyperresponsiveness. Eur J Respir Dis 

 1986; 68(2):89-95. 

 68. Mapp CE, Moro G, Fabbri L et al. [Toluene 

diisocyanate-induced asthma: specific and nonspecific bronchial challenge tests (author's 

transl)]. Med Lav 1979; 70(3):203-14. 

 69. Merget R, Dierkes A, Ruckmann A et al. 

Absence of relationship between degree of 

nonspecific and specific bronchial 

responsiveness in occupational asthma due to 

platinum salts. [German]. Pneumol 1996; 

51(4):345-50. 

 70. Merget R, Heger M, Globisch A et al. 

Quantitative bronchial challenge tests with 

wheat flour dust administered by Spinhaler: 

Comparison with aqueous wheat flour extract 

inhalation. J Allergy Clin Immunol 1997; 

100(2):199-207. 

 71. Merget R, Stollfuss J, Wiewrodt R et al. 

Diagnostic tests in enzyme allergy. J Allergy 

Clin Immunol 1993; 92(2):264-77. 

 72. Mole R, Balletta A. [The significance of 

acetylcholine test in occupational allergic 

asthma (author's transl)]. Lav Um 1977; 

29(6):188-95. 

 73. Moller DR, Brooks SM, McKay RT et al. 

Chronic asthma due to toluene diisocyanate. 

Chest 1986; 90(4):494-9. 

 74. Moller DR, Gallagher JS, Bernstein DI et al. 

Detection of immunoglobulin E-mediated 

respiratory sensitization in workers exposed to 

hexahydrophthalic anhydride. J Allergy Clin 

Immunol 1985; 75(6):663-72. 

 75. Moscato G, Dellabianca A, Corsico A et al. 

Bronchial responsiveness to ultrasonic fog in 

occupational asthma due to diisocyanate. Chest 

1993; 104(4):1127-32. 

 76. Munoz X. Validation of specific inhalation 

challenge for the diagnosis of occupational 

asthma due to persulphate salts. Occup 

Environ Med 2004; 61(10):861-6. 

 77. Nielsen J, Welinder H, Schütz A et al. Specific 

serum antibodies against phthalic anhydride in 

occupationally exposed subjects. J Allergy 

Clin Immunol 1988; 82:126-33. 

 78. Nordman H, Keskinen H, Tuppurainen M. 

Formaldehyde asthma. Rare or overlooked. J 

Allergy Clin Immunol 1985; 75(1 Pt 1):91-9. 

 79. O'Brien IM, Harries MG, Burge PS et al. 

Toluene di-isocyanate-induced asthma. I. 

Reactions to TDI, MDI, HDI and histamine. 

Clin Allergy 1979; 9:1-6. 

 80. O'Brien IM, Newman-Taylor AJ, Burge PS et 

al. Toluene di-isocyanate-induced asthma. II. 

Inhalation challenge tests and bronchial 

reactivity studies. Clin Allergy 1979; 9(1):7-

15. 

 81. Obata H, Dittrick M, Chan H et al. Sputum 

eosinophils and exhaled nitric oxide during late 

asthmatic reactions in patients with western red 

cedar asthma. Eur Respir J 1999; 13(3):489-95. 

 82. Obtulowicz K, Laczkowska T, Kolarzyk E et 

al. Obstruction of the small airways in the 

spirometric diagnosis of occupational 

bronchial asthma. J Investig Allergol Clinl 

Immunol 1998; 8(5):300-3. 

 83. Paggiaro PL, Cantalupi R, Filieri M et al. 

Bronchial asthma due to inhaled wood dust 

(Tanganyika aningre). Clin Allergy 1981; 

11(6):605-10. 

 84. Paggiaro PL, Chan-Yeung M. Pattern of 

specific airway response in asthma due to 

western red cedar (Thuja plicata): relationship 

with length of exposure and lung function 

measurements. Clin Allergy 1987; 17:333-9. 

 85. Paggiaro PL, Innocenti A, Bacci E et al. 

Specific bronchial reactivity to toluene 

diisocyanate: relationship with baseline clinical 

findings. Thorax 1986; 41:279-82. 

 86. Paggiaro PL, Loi AM, Campinoti G et al. 

Ipereccitabilita bronchiale specifica e 

aspecifica nell'asma bronchiale da isocianati. 

1984. 
E-90

 87. Paggiaro PL, Pardi F, Amram D et al. [Validity 

of a specific bronchial provocation test with 

proteolytic enzymes in occupational bronchial 

asthma caused by enzymatic detergents]. G Ital 

Med Lav 1984; 6(5-6):201-4. 

 88. Palczynski C, Walusiak J, Krakowiak A et al. 

Nasal lavage fluid examination in diagnostics 

of occupational allergy to chloramine. Int J 

Occup Med Environ Health 2003; 16(3):231-

40. 

 89. Park HS, Kim HY, Nahm DH et al. Specific 

IgG, but not specific IgE, antibodies to toluene 

diisocyanate-human serum albumin conjugate 

are associated with toluene diisocyanate 

bronchoprovocation test results. J Allergy Clin 

Immunol 1999; 104(4 Pt 1):847-51. 

 90. Park HS, Kim HY, Suh YJ et al. Alpha 

amylase is a major allergenic component in 

occupational asthma patients caused by 

porcine pancreatic extract. J Asthma 2002; 

39(6):511-6. 

 91. Park HS, Kim YJ, Lee MK et al. Occupational 

asthma and IgE antibodies to reactive dyes. 

Yonsei Med J 1989; 30(3):298-304. 

 92. Park HS, Lee MK, Kim BO et al. Clinical and 

immunologic evaluations of reactive dyeexposed workers. J Allergy Clin Immunol 

1991; 87(3):639-49. 

 93. Park HS, Nahm DH, Suh CH et al. 

Occupational asthma and IgE sensitization to 

grain dust. J Korean Med Sci 1998; 13(3):275-

80. 

 94. Park HS, Yu HJ, Jung KS. Occupational 

asthma caused by chromium. Clin Exp Allergy 

1994; 24(7):676-81. 

 95. Park JW, Kim CW, Kim KS et al. Role of skin 

prick test and serological measurement of 

specific IgE in the diagnosis of occupational 

asthma resulting from exposure to vinyl 

sulphoreactive dyes. Occup Environ Med 

2001; 58:417. 

 96. Perrin B, Malo JL, L'Archeveque J et al. 

Comparison of peak expiratory flow rates and 

bronchial responsiveness with specific 

inhalation challenges in occupational asthma 

(abstract). Am Rev Respir Dis 1990; 141. 

 97. Pezzini A, Riviera A, Paggiaro PL et al. 

Specific IgE antibodies in twenty-eight 

workers with diisocyanate-induced bronchial 

asthma. Clin Allergy 1984; 14(5):453-61. 

 98. Prichard MG, Ryan G, Musk AW. Wheat flour 

sensitisation and airways disease in urban 

bakers. Br J Ind Med 1984; 41(4):450-4. 

 99. Quirce S, Cuevas M, Diez-Gomez ML et al. 

Respiratory allergy to Aspergillus-derived 

enzymes in bakers' asthma. J Allergy Clin 

Immunol 1992; 90(6 I):970-8. 

 100. Quirce S, Hinojosa M, Maranon F et al. 

Identification of obeche wood (Triplochiton 

scleroxylon) allergens associated with 

occupational asthma. J Allergy Clin Immunol 

2000; 106(2):400-1. 

 101. Rasanen L, Kuusisto P, Penttila M et al. 

Comparison of immunologic tests in the 

diagnosis of occupational asthma and rhinitis. 

Allergy. 1994; 49(5):342-7. 

 102. Redlich CA, Homer RJ, Smith BR et al. 

Immunologic responses to isocyanates in 

sensitized asthmatic subjects. Clin Exp 

Immunol 1996; 109(3 Suppl):6S-8S. 

 103. Ricciardi L, Fedele R, Saitta S et al. 

Occupational asthma due to exposure to iroko 

wood dust. Ann Allergy Asthma Immunol 

2003; 91(4):393-7. 

 104. Sander I, Degens P, Goldscheid N et al. 

Divergente Prickhauttestergebnisse mit 

verschiedenen Weizen- und 

Roggenmehlextrakten [German]. AtemwLungenkrkh 2001; 27:333-4. 

 105. Sastre J, Fernandez-Nieto M, Novalbos A et al. 

Need for monitoring nonspecific bronchial 

hyperresponsiveness before and after 

isocyanate inhalation challenge.[see comment]. 

Chest. 2003; 123(4):1276-9. 

 106. Schuermans D, Verbanck S, Vincken W. Role 

of histamine bronchial hyperresponsiveness 

(BHR) in the diagnosis of occupational asthma 

(OA) to latex. Eur Respir Soc 2003. 

 107. Schwaiblmair M, Vogelmeier C, Fruhmann G. 

Occupational asthma in hairdressers: results of 

inhalation tests with bleaching powder. Int 

Arch Occup Environ Health 1997; 70(6):419-

23. 

 108. Schwarting HH. [Diagnostic significance of 

the radioallergosorbent test (RAST) in 

occupational, flour-related asthma. A 

comparison with previously used methods in 

allergy diagnosis]. Z Hautkr 1979; 54(7):306-

8. 
E-91

 109. Shirai T, Reshad K, Yoshitomi A et al. Green 

tea-induced asthma: relationship between 

immunological reactivity, specific and nonspecific bronchial responsiveness. Clin Exp 

Allergy 2003; 33(9):1252-5. 

 110. Shirakawa T, Kusaka Y, Fujimura N et al. The 

existence of specific antibodies to cobalt in 

hard metal asthma. Clin Allergy 1988; 18:451-

60. 

 111. Slovak AJ. Occupational asthma caused by a 

plastics blowing agent AZO dicarbonamide. 

Thorax 1981; 36(12):906-9. 

 112. Symington IS, Kerr JW, McLean DA. Type I 

allergy in mushroom soup processors. Clin 

Allergy 1981; 11:43-7. 

 113. Tabar AI, Alvarez-Puebla MJ, Gomez B et al. 

Diversity of asparagus allergy: clinical and 

immunological features. Clin Exp Allergy 

2004; 34(1):131-6. 

 114. Taivainen A, Iivonen E, Kokkarinen J et al. 

[The diagnosis of asthma caused by cow hair 

epithelium]. Duodecim 1994; 110( 21):1999-

2003. 

 115. Tee RD, Cullinan P, Welch J et al. Specific 

IgE to isocyanates: A useful diagnostic role in 

occupational asthma. J Allergy Clin Immunol 

1998; 101(5):709-15. 

 116. Tse KS, Chan H, Chan-Yeung M. Specific IgE 

antibodies in workers with occupational 

asthma due to western red cedar. Clin Allergy 

1982; 3:249-58. 

 117. Vandenplas O. Prevalence of occupational 

asthma due to latex among hospital personnel. 

Am J Respir Crit Care Med 1995; 151(1):54-

60. 

 118. Vandenplas O, Van Cangh FB, Brumagne A et 

al. Occupational asthma in symptomatic 

workers exposed to natural rubber latex: 

evaluation of diagnostic procedures. J Allergy 

Clin Immunol 2001; 107(3):542-7. 

 119. Vanhanen M, Tuomi T, Tupasela O et al. 

Cellulase allergy and challenge tests with 

cellulase using immunologic assessment. 

Scand J Work Environ Health 2000; 

26(3):250-6. 

 120. Virtanen T, Zeiler T, Rautiainen J et al. 

Immune reactivity of cow-asthmatic dairy 

farmers to the major allergen of cow (BDA20) 

and to other cow-derived proteins. The use of 

purified BDA20 increases the performance of 

diagnostic tests in respiratory cow allergy. Clin 

Exp Allergy 1996; 26(2):188-96. 

 121. Vogelmeier C, Baur X, Fruhmann G. 

Isocyanate-induced asthma: results of 

inhalation tests with TDI, MDI and 

methacholine. Int Arch Occup Environ Health 

1991; 63(1):9-13. 

 122. Wurzinger G, Gillich E, Kroneis C. 

Bakers/millers-asthma - Different behaviour in 

inhalative provocation [German]. AtemwLungenkrkh 23[Suppl 1], S30-7. 1997. 

 123. Zeiler T, Taivainen A, Mantyjarvi R et al. 

Threshold levels of purified natural Bos d 2 for 

inducing bronchial airway response in 

asthmatic patients. Clin Exp Allergy 2002; 

32(10):1454-60. 

 124. Zeiss CR, Patterson R, Pruzansky JJ et al. 

Trimellitic anhydride-induced airway 

syndromes: clinical and immunologic studies. J 

Allergy Clin Immunol 1977; 60(2):96-103. 
E-92

Cohorts 

 1. Allard C, Cartier A, Ghezzo H et al. 

Occupational asthma due to various agents: 

absence of clinical and functional improvement at 

an interval of four or more years after cessation 

of exposure. Chest 1989; 96(5):1046-9. 

 2. Ameille J, Pairon JC, Bayeux MC et al. 

Consequences of occupational asthma on 

employment and financial status: a follow-up 

study. Eur Respir J 1997; 10(1):55-8. 

 3. Banks DE, Rando RJ, Barkman HW Jr. 

Persistence of toluene diisocyanate-induced 

asthma despite negligible workplace exposures. 

Chest 1990; 97(1):121-5. 

 4. Barker RD, Harris JM, Welch JA et al. 

Occupational asthma caused by 

tetrachlorophthalic anhydride: a 12-year followup. J Allergy Clin Immunol 1998; 101(6 Pt 

1):717-9. 

 5. Bernstein DI, Karnani R, Biagini RE et al. 

Clinical and occupational outcomes in health care 

workers with natural rubber latex allergy. Ann 

Allergy Asthma Immunol 2003; 90(2):209-13. 

 6. Burge PS. Occupational asthma in electronic 

workers caused by colophony fumes: follow-up 

of affected workers. Thorax 1982; 37:348-53. 

 7. Gannon PF, Weir DC, Robertson AS et al. 

Health, employment, and financial outcomes in 

workers with occupational asthma. Br J Ind Med 

1993; 50(6):491-6. 

 8. Gassert TH, Hu H, Kelsey KT et al. Long-term 

health and employment outcomes of occupational 

asthma and their determinants. J Occup Environ 

Med 1998; 40(5):481-91. 

 9. Gorski P, Kolacinska B, Wittczak T. Analysis of 

the clinical state of patients with occupational 

asthma following cessation of exposure to 

allergens. Occup Med 1999; 49(5):285-9. 

10. Grammer L C, Shaughnessy MA. Study of 

employees with anhydride-induced respiratory 

disease after removal from exposure. J Occup 

Environ Med 1996; 38(8):771-4. 

11. Grammer LC, Shaughnessy MA, Kenamore BD. 

Clinical and immunologic outcome of 42 

individuals with trimellitic anhydride-induced 

immunologic lung disease after transfer to low 

exposure. Allergy Asthma Proc 2000; 21(6):355-

9. 

12. Harries MG, Burge PS, Samson M et al. 

Isocyanate asthma-respiratory symptoms due to 

1,5-naphthylene diisocyanate. Thorax 1979; 

34(6):762-6. 

13. Jyo T, Kodomari Y, Kodomari N et al. 

Therapeutic effect and titers of the specific IgE 

and IgG antibodies in patients with sea squirt 

allergy Hoya asthma under a long-term 

hyposensitization with three sea squirt antigens. J 

Allergy Clin Immunol 1989; 83(2 Pt 1):386-93. 

14. Laoprasert N, Swanson MC, Jones RT et al. 

Inhalation challenge testing of latex-sensitive 

health care workers and the effectiveness of 

laminar flow HEPA-filtered helmets in reducing 

rhinoconjunctival and asthmatic reactions. J 

Allergy Clin Immunol 1998; 102(6 Pt 1):998-

1004. 

15. Lemiere C, Cartier A, Dolovich J et al. Outcome 

of specific bronchial responsiveness to 

occupational agents after removal from exposure. 

Am J Respir Crit Care Med 1996; 154(2 Pt 

1):329-33. 

16. Lemiere C, Cartier A, Malo JL et al. Persistent 

specific bronchial reactivity to occupational 

agents in workers with normal nonspecific 

bronchial reactivity. Am J Resp Crit Care Med 

2000; 162(3 Pt 1):976-80. 

17. Lin FJ, Dimichward H, Chan-Yeung M . 

Longitudinal decline in lung function in patients 

with occupational asthma due to western red 

cedar. Occup Environ Med 1996; 53(11):753-6. 

18. Lozewicz S, Assoufi BK, Hawkins R et al. 

Outcome of asthma induced by isocyanates. Br J 

Dis Chest 1987; 81(1):14-22. 

19. Maghni K, Lemiere C, Ghezzo H et al. Airway 

inflammation after cessation of exposure to 

agents causing occupational asthma. Am J Respir 

Crit Care Med 2004; 169(3):367-72. 

20. Malo J L, Ghezzo H. Recovery of methacholine 

responsiveness after end of exposure in 

occupational asthma. Am J Respir Crit Care Med 

2004; 169(12):1304-7. 

21. Malo JL, Boulet LP, Dewitte JD et al. Quality of 

life of subjects with occupational asthma. J 

Allergy Clin Immunol 1993; 91(6):1121-7. 

 
E-93

22. Malo JL, Cartier A, Boulet LP et al. Bronchial 

hyperresponsiveness can improve while 

spirometry plateaus two to three years after 

repeated exposure to chlorine causing respiratory 

symptoms. Am J Respir Crit Care Med 1994; 

150(4):1142-5. 

23. Malo JL, Cartier A, Ghezzo H et al. Patterns of 

improvement in spirometry, bronchial 

hyperresponsiveness, and specific IgE antibody 

levels after cessation of exposure in occupational 

asthma caused by snow-crab processing. Am Rev 

Respir Dis 1988; 138(4):807-12. 

24. Mapp CE, Corona PC, De Marzo N et al. 

Persistent asthma due to isocyanates. A follow-up 

study of subjects with occupational asthma due to 

toluene diisocyanate (TDI). Am Rev Respir Dis 

1988; 137(6):1326-9. 

25. Marabini A, Siracusa A, Stopponi R et al. 

Outcome of occupational asthma in patients with 

continuous exposure - a 3-year longitudinal study 

during pharmacologic treatment. Chest 2003; 

124(6):2372-6. 

26. Merget R, Schulte A, Gebler A et al. Outcome of 

occupational asthma due to platinum salts after 

transferral to low-exposure areas. Int Arch Occup 

Environ Health 1999; 72(1):33-9. 

27. Meyer WC. [Prognosis of occupational bronchial 

asthma after change of occupation and 

elimination of antigen (author's transl)]. MMW 

Munch Med Wochenschr 1977; 119(11):363-6. 

28. Moscato G, Dellabianca A, Perfetti L et al. 

Occupational asthma: A longitudinal study on the 

clinical and socioeconomic outcome after 

diagnosis. Chest 1999; 115(1):249-56. 

29. Munoz X, Cruz MJ, Orriols R et al. Occupational 

asthma due to persulfate salts: diagnosis and 

follow-up. Chest 2003; 123( 6):2124-9. 

30. O'Donnell TV, Welford B, Coleman ED. 

Potroom asthma: New Zealand experience and 

follow-up. Am J Ind Med 1989; 15(1):43-9. 

31. Orriols R, Drobnic ME, Munoz X et al. 

[Occupational asthma due to isocyanates: a study 

of 21 patients]. Med Clin (Barc) 1999; 

113(17):659-62. 

32. Paggiaro PL, Bacci E, Paoletti P et al. 

Bronchoalveolar lavage and morphology of the 

airways after cessation of exposure in asthmatic 

subjects sensitized to toluene diisocyanate. Chest 

1990; 98(3):536-42. 

33. Paggiaro PL, Loi AM, Rossi O et al. Follow-up 

study of patients with respiratory disease due to 

toluene diisocyanate. Clin Allergy 1984; 

14(5):463-9. 

34. Paggiaro PL, Vagaggini B, Dente FL et al. 

Bronchial hyperresponsiveness and toluene 

diisocyanate. Long-term change in sensitized 

asthmatic subjects. Chest 1993; 103(4):1123-8. 

35. Park HS, Lee SK, Kim HY et al. Specific 

immunoglobulin E and immunoglobulin G 

antibodies to toluene diisocyanate-human serum 

albumin conjugate: Useful markers for predicting 

long-term prognosis in toluene diisocyanateinduced asthma. Clin Exp Allergy 2002; 

32(4):551-5. 

36. Park HS, Yu HJ, Jung KS. Occupational asthma 

caused by chromium. Clin Exp Allergy 1994; 

24(7):676-81. 

37. Perfetti L, Cartier A, Ghezzo H et al. Follow-up 

of occupational asthma after removal from or 

diminution of exposure to the responsible agent: 

relevance of the length of the interval from 

cessation of exposure. Chest 1998; 114(2):398-

403. 

38. Piirila PL, Nordman H, Korhonen OS et al. A 

thirteen-year follow-up of respiratory effects of 

acute exposure to sulfur dioxide. Scand J Work 

Environ Health 1996; 22(3):191-6. 

39. Pisati G, Baruffini A, Zedda S. Toluene 

diisocyanate induced asthma: Outcome according 

to persistence or cessation of exposure. Br J Ind 

Med 1993; 50(1):60-4. 

40. Pisati G, Zedda S. Outcome of occupational 

asthma due to cobalt hypersensitivity. Sci Total 

Environ 1994; 150(1-3):167-71. 

41. Rosenberg N, Garnier R, Rousselin X et al. 

Clinical and socio-professional fate of 

isocyanate-induced asthma. Clin Allergy 1987; 

17(1):55-61. 

42. Ross DJ, Mcdonald JC. Health and employment 

after a diagnosis of occupational asthma: a 

descriptive study. Occup Med (Oxf) 1998; 

48(4):219-25. 

43. Saetta M, Maestrelli P, Turato G et al. Airway 

wall remodeling after cessation of exposure to 

isocyanates in sensitized asthmatic subjects. Am 

J Respir Crit Care Med 1995; 151(2 Pt 1):489-94. 

 
E-94

44. Sen D, Wiley K, Williams JG. Occupational 

asthma in fruit salad processing. Clin Exp 

Allergy 1998; 28(3):363-7. 

45. Simonsson BG, Sjoberg A, Rolf C et al. Acute 

and long-term airway hyperreactivity in 

aluminum-salt exposed workers with nocturnal 

asthma. Eur J Respir Dis 1985; 66(2):105-18. 

46. Slovak AJ, Orr RG, Teasdale EL. Efficacy of the 

helmet respirator in occupational asthma due to 

laboratory animal allergy. Am Ind Hygiene 

Assoc J 1985; 46(8):411-5. 

47. Smith TA, Patton J. Health surveillance in 

milling, baking and other food manufacturing 

operations - five years' experience. Occup Med 

(Oxf) 1999; 49(3):147-53. 

 

48. Sulotto F, Romano C, Piolatto G et al. [Effects of 

long-term use of inhaled steroids 

(beclomethasone dipropionate) in patients with 

occupational asthma no longer exposed]. Med 

Lav 1989; 80(6):498-505. 

49. Taivainen A, Tukiainen O, Terho O et al. 

Powered dust respirator helmets in the prevention 

of occupational asthma among farmers. Scand J 

Work Environ Health 1998; 24(6):503-7. 

50. Vandenplas O, Jamart J, Delwiche JP et al. 

Occupational asthma caused by natural rubber 

latex: outcome according to cessation or 

reduction of exposure. J Allergy Clin Immunol 

2002; 109(1):125-30. 

51. Venables KM, Dally MB, Burge PS et al. 

Occupational asthma in a steel coating plant. Br J 

Ind Med 1985; 42(8):517-24. 

52. Venables KM, Topping MD, Nunn AJ et al. 

Immunologic and functional consequences of 

chemical (tetrachlorophthalic anhydride)-induced 

asthma after four years of avoidance of exposure. 

J Allergy Clin Immunol 1987; 80(2):212-8. 
E-95

Trials 

 1. Armentia A, Martin-Santos JM, Quintero A et al. 

Baker's asthma: prevalence and evaluation of 

immunotherapy with wheat flour extract. Ann 

Allergy 1990; 65(4):265-72. 

 2. Crescioli S, De Marzo N, Boschetto P et al. 

Theophylline inhibits late asthmatic reactions 

induced by toluene diisocyanate in sensitized 

subjects. Eur J Pharmacol - Environ Toxicol 

Pharmacol Sect 1992; 1(1):45-50. 

 3. De Marzo N, Fabbri LM, Crescioli S et al. Dosedependent inhibitory effect of inhaled 

beclomethasone on late asthmatic reactions and 

increased responsiveness to methacholine 

induced by toluene diisocyanate in sensitised 

subjects. Pulm Pharmacol 1988; 1(1):15-20. 

 4. Fabbri LM, Di Giacomo GR, Dal Vecchio L et al. 

Prednisone, indomethacin and airway 

responsiveness in toluene diisocyanate sensitized 

subjects. Bull Eur Physiopathol Respir 1985; 

21:421-6. 

 5. Maestrelli P, De Marzo N, Saetta M et al. Effects 

of inhaled beclomethasone on airway 

responsiveness in occupational asthma. Placebocontrolled study of subjects sensitized to toluene 

diisocyanate. Am Rev Respir Dis 1993; 148 

(2):407-12. 

 6. Malo JL, Cartier A, Cote J et al. Influence of 

inhaled steroids on recovery from occupational 

asthma after cessation of exposure: an 18-month 

double-blind crossover study. Am J Respir Crit 

Care Med 1996; 153(3):953-60. 

 7. Malo JL, Perrin B, L'Archeveque J et al. Effect 

on an inhaled beta-2 adrenergic agent on late 

asthamtic reactions due to occupational agents. 

Rev Mal Resp 1994; 11:479-84. 

 8. Mapp CE, Boschetto P, Dal Vecchio L et al. 

Protective effect of antiasthma drugs on late 

asthmatic reactions and increased airway 

responsiveness induced by toluene diisocyanate 

in sensitized subjects. Am Rev Respir Dis 1987; 

136(6):1403-7. 

 9. Moscato G, Gherson G, Biscaldi G et al. 

Protective effect of nifedipine upon specific 

bronchial responses to isocyanates. G Ital Med 

Lav 1985; 5(6):247-50. 

10. Mueller-Wening D, Neuhauss M. Protective 

effect of respiratory devices in farmers with 

occupational asthma. Eur Respir J 1998; 12 

(3):569-72. 

11. Paggiaro PL, Bacci E, Talini D et al. Atropin 

does not inhibit late asthmatic responses induced 

by Toluene diisocyanate in sensitized subjects. 

Am Rev Respir Dis 1987; 136(5):1237-41. 

12. Vandenplas O, Delwiche JP, Depelchin S et al. 

Latex gloves with a lower protein content reduce 

bronchial reactions in subjects with occupational 

asthma caused by latex. Am J Respir Crit Care 

Med 1995; 151 (3 Pt 1):887-91. 

13. Woitowitz HJ, Woitowitz RH. Clinical 

experiences with a new sympathicomimetic 

substance in the provoked attack in occupational 

asthma. Respir 1972; 29(5):549-55. 
F-1

Appendix F: Technical Expert Panel, List of Peer 

Reviewers, and Translators 
F-2

Technical Expert Panel 

Margaret Coopey 

 Agency for Healthcare Research and Quality, Washington, United States 

Richard Jones 

 University of Alberta, Edmonton, Canada 

Catherine Lemiere 

 University of Montreal, Montreal, Canada 

David Muir 

 McMaster University, Hamilton, Canada 

Susan Tarlo 

 University of Toronto, Toronto, Canada 

Dilini Vethanayagam 

 University of Alberta, Edmonton, Canada 

Peer Reviewers 

Ronald Balkissoon 

University of Colorado School of Medicine, United States 

Sherwood Burge 

 Birmingham Heartlands Hospital, United Kingdom 

Prasant Adhikari 

 Workers’ Compensation Board of Manitoba, Canada 

Mark Cullen 

 Yale University School of Medicine, United States 

Paul Cullinan 

 Royal Brompton Hospital, United Kingdom 

Clive Deutscher 

 Workers’ Compensation Board of Alberta, Canada 

David Hendrick 

 University of Newcastle Upon Tyne, United Kingdom 
F-3

Jean Luc Malo 

 University of Montreal Medical School, Canada 

Philliipa Poole 

 University of Auckland, New Zealand 

Carrie Redlich 

 Yale University School of Medicine, United States 

Olivier Vandenplas 

 Université Catholique de Louvain, Belgium 

Translators 

Rudy Bella 

 Lefarge, Edmonton, Canada 

Maurice Blitz 

 Capital Health, Edmonton, Canada 

Anatoly Dobrousin 

 Capital Health, Edmonton, Canada 

Bing Gao 

 Capital Health, Edmonton, Canada 

Walter Kipp 

 University of Alberta, Edmonton, Canada 

Zhi Li 

 University of Alberta, Edmonton, Canada 

Arto Ohinmaa 

 University of Alberta, Edmonton, Canada 

Maria Ospina 

 University of Alberta, Edmonton, Canada 

Rob Polakowski 

University of Alberta, Edmonton, Canada 

Galina Portmoi 

University of Alberta, Edmonton, Canada 
F-4

Jacques Rizkallah 

 University of Alberta, Edmonton, Canada 

Paul Sperka 

 University of Alberta, Edmonton, Canada 
G-1

Appendix G: Quality Analysis of the Diagnostic 

Occupational Asthma Studies 
G-2

Quality Analysis 

For the diagnosis review, the quality of the included studies was low. More formal 

analyses of the overall quality was attempted to determine the impact study quality on the 

results. This was evaluated by visual assessment of the distribution of results according 

to the validated criteria described in the Methods section of the report. 

The figures below illustrate the distribution of efficiency (total proportion of correctly 

identified patients) according the six relevant diagnostic test methodological criteria 

outlined in the Methods section for single NSBP test compared to SIC for the 39 studies 

which gave results for both disease positive and disease negative patients. The seventh 

validated criterion involves the use of a valid reference standard, and our research team 

considered SIC to be a valid reference standard for these OA studies. Single NSBP test 

was selected for evaluation from all other options because it was the most frequently 

reported comparison test. 

Our conclusion that the quality of the studies did not impact the results in the review 

is based on our observation that the distribution of efficiency did not markedly differ 

depending on any specific quality maker. We also considered sensitivity and specificity 

alone and reached the same conclusion. 
G-3

Figure G-1. Distribution of efficiency of tests comparing NSBP 

test to SIC by diagnostic study quality criteria

33

6

Design

Cohort

Other

6

33

Blinding

Full/Partial

None/Unclear

10

29

Description of reference test

Adequate

Inadequate

8

31

Description of comparison test

Adequate

Inadequate

10

29

Description of population

Adequate

Inadequate

27

6

6

Differential reference bias

No

Yes

Unclear

Number of

studies

0 20 40 60 80 100

Efficiency (%)
H-1

Appendix H: Sensitivity and Specificity of 

Comparison Tests that Used SIC as a Reference 

Standard

Table H-1: High molecular weight asthmagens 

Table H-2: Low molecular weight asthmagens 

Table H-3: Mixed/unknown asthmagens
H-2

Table H-1. High molecular weight asthmagens

Comparison Test 

Number of 

Studies 

Pooled Sensitivity 

(95% CI) 

Pooled Specificity 

(95% CI) 

NSBP test 10 79.3 (67.7, 87.6) 51.3 (35.2, 67.2) 

Specific skin prick test 16 80.6 (69.8, 88.1) 59.6 (41.7, 75.3) 

Specific IgE 9 73.3 (63.9, 81.0) 79.0 (50.5, 93.3) 

NSBP test combined with 

 Specific skin prick test 4 60.6 (21.0, 89.9) 82.5 (54.0, 95.0) 

 Specific IgE 2 35.6 (1.2, 96.1) 84.6 (48.2, 97.0) 

 Specific skin prick test and specific IgE 3 65.2 (6.7, 98.0) 74.3 (45.0, 91.0) 

 Specific skin prick test or specific IgE 3 60.4 (11.8, 94.5) 81.5 (47.8, 95.5) 

Serial NSBP test 1 100 (34.2, 100) 100 (20.7, 100) 

Clinical diagnosis 2 93.7 (69.3, 99.0) 32.3 (7.5, 73.8) 

Table H-2. Low molecular weight asthmagens 

Comparison Test 

Number of 

Studies 

Pooled Sensitivity 

(95% CI) 

Pooled Specificity 

(95% CI) 

NSBP test 24 66.7 (58.4, 74.0) 63.9 (56.1, 71.0) 

Specific skin prick test 5 72.9 (59.7, 83.0) 86.2 (77.4, 91.9) 

Specific IgE 11 31.2 (22.9, 40.8) 88.9 (84.7, 92.1) 

NSBP test combined with 

 Specific skin prick test 1 100 (74.1, 100) 80.0 (49.0, 94.3) 

 Specific IgE 1 0 (0, 49.0) 100 (61.0, 100) 

Serial NSBP test 2 67.5 (42.6, 85.3) 65.6 (41.1, 84.0) 

Serial PFT (usually PEFR) 1 86.7 (59.5, 96.6) 90.0 (53.3, 98.6) 

Clinical diagnosis 5 93.6 (85.0, 97.5) 68.9 (54.7, 80.3) 

Table H-3. Mixed/Unknown Asthmagens 

Comparison Test 

Number of 

Studies 

Pooled Sensitivity 

(95% CI) 

Pooled Specificity 

(95% CI) 

NSBP test 5 83.7 (66.8, 92.9) 48.4 (25.9, 71.6) 

Specific skin prick test 5 63.0 (41.5, 80.3) 59.2 (45.4, 71.7) 

Specific IgE 2 85.1 (40.3, 98.0) 61.2 (7.0, 97.1) 

Serial NSBP test 3 50.0 (35.5, 64.5) 66.8 (53.3, 78.0) 

Serial PFT (usually PEFR) 5 63.6 (43.4, 79.9) 77.2 (66.5, 85.2) 

Clinical diagnosis 2 95.1 (86.8, 98.3) 47.7 (26.7, 69.7) 

Eosinophil counts 3 54.9 (23.7, 82.7) 72.3 (54.1, 85.3) 

Abbreviations: CI = confidence interval; NSBP = non-specific bronchial provocation; PFT = pulmonary 

function test; PEFR = peak expiratory flow rate