Introduction

Occupational asthma (OA) is characterized by

airway inflammation (partially or completely

reversible), bronchoconstriction, and airway

hyper-responsiveness in response to workplace

airway asthmagens. More than 250 asthmagens

have been implicated and identified as causative

agents in the development of OA and new causes

are identified each year. In developed countries,

OA is among the most prevalent occupational

lung diseases.1 A review of 43 attributable risk

estimates from 19 counties found the

attributable risk of OA to be approximately 9

percent (interquartile range [IQR] 5 to 19

percent).2

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.1 When a

worker has OA with latency, specific inhalation

testing with the causal agent will usually be

positive and often an immunological response is

achieved with specific skin prick tests (SPT)

and/or IgE testing, particularly for high

molecular weight (HMW) asthmagens. Many of

the immunological responses associated with OA

from low molecular weight (LMW) compounds

have yet to be fully characterized. OA can also

exist without a latency period and often occurs

after exposure to irritant gases, fumes, or

chemicals.3 If the irritant occurs in a large,

concentrated exposure, the worker can develop

reactive airways dysfunction syndrome (RADS).

Because there is no recognizable sensitization, the

battery of diagnostic tests does not include

specific inhalational challenge (SIC) or specific

immunological tests. OA without latency is

believed to represent only 5 to 15 percent of all

OA cases.4-6

While a SIC test is considered to be the

reference standard test, a definitive diagnostic test

for OA does not exist. False negatives can occur

when a worker with OA is challenged with the

incorrect asthmagen.1 Also, SIC is not widely

available and testing is generally confined to

academic centers in large metropolitan areas.7

There are several alternative techniques, used

in isolation or in combination, which can be

used to diagnose OA. Alternative diagnostic tests

include: history and questionnaire, non-specific

bronchial provocation (NSBP) challenge, serial

lung function testing, specific immunological

testing, exhaled nitrous oxide, and sputum

induction. There are also several different

approaches to managing OA. First, workers can

be treated pharmacologically in a similar manner

to patients with non-occupational asthma.

Second, the worker’s environment can be altered

to reduce exposures to an “acceptable” level by

making engineering changes to the workplace, by

making administrative changes to work patterns,

or by using personal protective equipment

(PPE). Alternatively, the worker can be relocated

to a different job or area of the workplace, or it

may be possible to eliminate the agent or

substitute a non-hazardous agent for the

causative agent in use. Often, the final option is

to remove the worker entirely from workplace;

however, workers may not wish to be removed

Evidence Report/Technology Assessment

Number 129

Diagnosis and Management of 

Work-Related Asthma

Summary

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

Agency for Healthcare Research and Quality

Advancing Excellence in Health Care • www.ahrq.gov

Agency for Healthcare Research and Quality Evidence-Based

Practice
2

for a variety of financial or social reasons. Removal from

exposure can have important economic implications for

workers, industry, health care providers, and society.8

Moreover, it has been reported that symptoms and impaired

lung function persist, even after extended periods away from

the causative agent9 and this can result in permanent

unemployment.

Objectives and Key Questions

The objectives of the University of Alberta Evidence-based

Practice Center (EPC) were to systematically gather the

existing evidence to determine which diagnostic techniques are

effective at determining a case of OA and to evaluate the

optimal treatment for such workers. The report was requested

by the American College of Chest Physicians (ACCP). 

Researchers attempted to answer the following questions:

1. What is the best diagnostic approach for a patient with

suspected OA? 

2. In what situations would SIC testing provide additional

useful diagnostic information?

3. Which treatment is most effective for OA?

4. Must patients with OA be removed from the workplace

environment to control symptoms and/or disease

progression?

Methods

Literature Search

Appropriate search terms were adapted to search the

following electronic resources: MEDLINE®, EMBASE®,

Dissertation Abstracts®, Expanded Academic®, National

Agricultural and Safety Database®, CINHAL®, Biological

Abstracts®, Agricola®, Cochrane Airways Review Group

registry, 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.10-15 The search

was not limited by language or publication status and is

considered current until February 2004.

Prominent authors were contacted regarding any missing

studies and the reference lists of all included articles were

reviewed. Relevant conference proceedings were hand

searched for the years 2001–2003.

Study Selection

Each title, and when available, abstract was independently

screened by two reviewers. The references identified as

“potentially relevant” and “unclear” were then screened by an

occupational medicine specialist with an interest in

occupational asthma and an asthma researcher; the full text of

those articles were retrieved.

Using pre-determined inclusion criteria, two reviewers

independently assessed the full text of the articles.

Disagreement among reviewers was resolved by discussion and

consulting a third party as needed. 

We excluded studies that assessed screening for workplace

respiratory symptoms. In cases where multiple publications

involving the same or a portion of the same workers were

identified, the most recent article or the largest cohort was

selected and any additional, unique information from previous

publications was incorporated. 

Quality Assessment

Assessment of the methodological quality was completed

independently by two reviewers. The methodological quality

of a diagnostic study was assessed using a quality tool based on

Lijmer’s empirical research examining biases in diagnostic

studies.16 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”.17 Also, the funding source was

recorded for each study. Controlled clinical trials were assessed

using the validated Jadad scale and the Cochrane method.18

Allocation concealment was assessed as “adequate,”

“inadequate,” or “unclear.”19

Data Extraction

Data were extracted by one reviewer using standardized

forms and checked for completeness and accuracy by a second

reviewer. For the diagnosis questions, data regarding the study

population characteristics, diagnostic tests, and results (e.g.,

sensitivity, specificity, likelihood ratios, etc.) were collected.

For each diagnostic test, the methodology, timing,

inclusion/exclusion criteria, medication use, and definition of a

positive test result were extracted. Additional outcomes

included cost of diagnosis, time to complete diagnosis, and

presence of adverse events. For the management questions,

details concerning worker characteristics, interventions, tests

used to measure outcomes, and outcomes were recorded.

Interventions were described by change in exposure (continual,

decreased, or removal from exposure), or the type, dosage,

route, and timing of pharmaceutical treatment. Outcomes

extracted included lung function, symptoms and medication

scores, economic status, and adverse events. The length of

followup was also recorded.

Data Analysis

For the diagnosis review, standard 2 x 2 tables (or 2 x 1 if

only reference standard positive or reference standard negative
subjects were included) for each comparison test or

combination of tests were generated. We pooled data from 2 x

1 tables separately from studies that presented data from which

a 2 x 2 table could be generated. All results are presented with

95% confidence intervals (CI).

For studies pertaining to the management of OA, extreme

heterogeneity prevented the use of meta-analytic techniques.

Nonetheless, with some re-organization of the data we were

able to sufficiently homogenize the information provided to

include it within a descriptive summary.

For continuous outcomes, a mean was used as the measure

of central tendency. In cases where the mean was not

reported, the following substitutions were used: median and

midpoint of the range or IQR. Similarly, standard deviation

(SD) was used as the measure of variation and imputed if it

was not available. When possible, a mean and SD were

calculated from individual patient data. Data were grouped

according to exposure status in followup as continued

exposure, reduced exposure, or ceased exposure. 

Results

Description of Diagnostic Studies

One hundred twenty-four unique cohorts were included in

the diagnosis review. SIC was the most commonly cited

reference standard; it was performed in 105 of the studies and

most frequently, with di-isocyanates. The alternative reference

standard was clinical diagnosis. Over half of the studies (67)

included workers exposed to LMW agents. Not all studies

had workers with a uniform exposure and/or type of OA: 24

studies included workers from several different occupations

with various probable causes of OA. The most commonly

reported diagnostic test was a single NSBP test. Only one

study examined workers with RADS.

Workers were relatively infrequently selected consecutively

or randomly and 37 studies failed to report the selection

method; the remaining studies used alternative methods, such

as choosing some workers in a factory or some clinic patients.

All but 14 studies collected data prospectively; data collection

was unclear in six studies. However, only three studies

reported that both the reference standard and comparison test

results were assessed blindly. The reference standard was

adequately described in approximately 70 percent of the

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 also

present in 31 studies and it was unclear if it occurred in 18

studies. Partial verification bias did not occur in the remaining

75 studies. 

Description of Management Studies

There were 67 publications referring to 52 cohorts. Two

studies examined workers with RADS; in one study, the

workers were exposed to sulfur dioxide in a pyrite mine

explosion and, in the second, pipefitters were exposed to

chlorine over three months. 

The most common identified asthmagens in these studies

were chemicals. The median sample size of the included

studies was 26 workers (range 3–1011). Length of followup

was variable within and between studies.

The most common intervention was removal from the

workplace. Fourteen cohorts report results for subjects who

continued exposure, and reduced exposure was assessed in 18

studies. Eight studies examined the effectiveness of PPE, while

only two studies compared the use of medication. The most

commonly reported outcomes were NSBP test and pulmonary

function.

Thirteen trials were included. The most common

asthmagen studied was isocyanates. Two trials assessed

methods to reduce the level of asthmagen exposure, including

the use of a respirator or hypoallergenic latex gloves. The

remaining studies examined the efficacy of beclomethasone

(with removal from exposure in two trials), indomethacin,

atropine, nifedipine, verapamil, cromolyn, fenoterol,

prednisone, and immunotherapy. All but one of the

pharmacological trials was placebo controlled. The length of

study intervention and followup varied; three studies followed

patients for at least 6 months and the remaining studies were

shorter. Response to SIC was a commonly assessed outcome

and was measured in nine trials.

Among the cohort studies, the mean Downs and Black

score of the 52 included studies was 16.4 (SD 4.0) from a total

possible score of 29. Approximately half (27/52) of the studies

provided some individual patient data. When reported,

funding was most commonly provided by a government

agency; 31 of the studies failed to disclose their funding

source. Of the 13 clinical trials, the median Jadad score was 2

(IQR 2–3). Concealment of allocation was adequately

reported in two of the trials, and inadequately in four trials;

the remainder were unclear. Six trials did not report their

source of funding and two trials were supported solely by

government grants.

Diagnosis Results

Sixty-one studies compared the sensitivity and specificity

(n=39), sensitivity alone (n=21) or specificity alone (n=1) of

single NSBP test to SIC. Twenty-four of these studies

reported both sensitivity and specificity among patients

exposed to LMW agents. The pooled estimates for sensitivity

was 66.7 percent (95% CI: 58.4 to 74.0 percent) and for

3
4

specificity was 63.9 percent (95% CI: 56.1 to 71.0 percent).

Among the 10 studies examining HMW asthmagens, 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). Five studies reported sensitivity and

specificity results for various suspected agents of differing

molecular weights. 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). 

Forty-seven studies reported comparisons of specific SPT to

SIC. Five studies reported both sensitivity and specificity of

SPT of LMW agents and the pooled sensitivity was 72.9

percent (95% CI: 59.7 to 83.0 percent) while the pooled

specificity was 86.2 percent (95% CI: 77.4 to 91.9 percent).

Of the 16 studies that reported both sensitivity and specificity

for patients exposed to HMW agents the pooled sensitivity

was 80.6 percent (95% CI: 69.8 to 88.1 percent) while the

pooled specificity was 59.6 percent (95% CI: 41.7 to 75.3

percent). Among the five studies that included patients

exposed to various agents, the pooled estimates for sensitivity

was 63.0 percent (95% CI: 41.5 to 80.3 percent) and the

pooled estimate of specificity was 59.2 percent (95% CI: 45.4

to 71.7 percent).

Forty studies reported sensitivity and 19 reported specificity

for serum specific IgE compared to SIC. Eleven studies

reported both sensitivity and specificity for LMW agents; the

pooled sensitivity was 31.2 percent (95% CI: 22.9 to 40.8

percent) and the pooled specificity was 88.9 percent (95% CI:

84.7 to 92.1 percent). Sensitivity was higher for the HMW

agents studied; the pooled estimate of sensitivity was 73.3

percent (95% CI: 63.9 to 81.0 percent) and the pooled

estimate of specificity was 79.0 percent (95% CI: 50.5 to 93.3

percent). Two studies examining a variety of agents reported

both sensitivity and specificity. The pooled estimate of

sensitivity was 85.1 percent (95% CI: 40.3 to 98.0 percent)

and the pooled estimate or specificity was 61.2 percent (95%

CI: 7.0 to 97.1 percent).

When possible, results were combined in union for the

most frequently reported comparison tests. That is, all tests in

combination had to be positive for the combined result to be

considered positive; if any result was negative, the combination

was considered negative. Four studies examined a single

NSBP test and specific SPT in combination among HMW

agents. The pooled estimate of sensitivity was 60.6 percent

(95% CI: 21.0 to 89.9 percent) while the estimate of

specificity was 82.5 percent (95% CI: 54.0 to 95.0 percent).

Only one study investigated this combination of tests in LMW

OA; the sensitivity was 100 percent (95% CI: 74.1 to 100

percent) and specificity was 80 percent (95% CI: 49.0 to 94.3

percent). Three studies of HMW agents yielded results for the

combination of a single NSBP test, specific SPT, and serum

specific IgE. The pooled estimate of sensitivity was 65.2

percent (95% CI: 6.7 to 98.0 percent) and for specificity was

74.3 percent (95% CI: 45.0 to 91.0 percent).

Management Results

We considered baseline (or diagnosis) lung function to

ascertain whether there were differences in severity among

subjects whose intervention may have included removal,

reduced, or continued exposure to the workplace asthmagen.

All but two studies reported an average baseline percent

predicted FEV1 above 80 percent, indicating reasonable lung

function at the time of study entry, irrespective of their

followup exposure status.

Less than half of the studies examining patients who were

removed or reduced their exposure showed improved lung

function over time as indicated by a positive difference

between mean followup and mean baseline percent predicted

FEV1. Only one study of patients who remained exposed had

a positive change in mean percent predicted FEV1.

The ratio of non-specific airway hyper-responsiveness at

followup compared with baseline concentration was calculated

to assess change in hyper-responsiveness over time. All but

one study of individuals who were removed had decreased

hyper-responsiveness at followup. Less than half of the studies

examining exposed patients displayed improved hyperresponsiveness. There were insufficient data to draw

conclusions about change in hyper-responsiveness among

patients with reduced exposure.

Medication needs were used as a proxy measure for disease

severity and continued asthma symptoms. Among patients

removed from exposure, the percentage of patients using

medication at followup ranged from 17 to 100 percent and

there was no indication that fewer patients were using

medication as time from work removal increased. Only five

studies reported medication use among patients who remained

exposed or had reduced exposure; no clear pattern emerged.

Symptoms were measured by: mean symptom scores,

categorical symptom scores, number of subjects who were

asymptomatic or recovered, or were symptomatic, or had

specific symptoms. Of the studies that reported results on

removed patients, the majority demonstrated symptom

improvement from time of removal for most of the patients.

This was assessed by an improvement in symptom score or the

majority of patients reported improved symptoms, or were

considered asymptomatic. In nine studies describing

symptoms among subjects whose exposure had been reduced

by a workplace intervention or PPE, the same pattern

emerged. Few studies reported that the bulk of patients were

completely asymptomatic. Only two studies reported

improved symptoms among those who remained exposed.
Seven studies examined socioeconomic outcomes among

workers with OA. Four studies assessed change in financial

situation after OA diagnosis and consistently found that

removed workers suffered a loss in income. Two studies

assessed the rate of worker’s compensation claims and

associated acceptance. In one study, a national Workers’

Compensation Board more frequently approved claims among

workers who were removed from the workplace than those

who reduced their exposure. A different study concluded that

the acceptance rate was similar, regardless of exposure status.

Two studies measured quality of life (QOL) and, in one, the

results showed QOL did not significantly differ among those

removed versus those who reduced their exposure. The second

study concluded that workers with OA who had been removed

from exposure and were receiving compensation had reduced

QOL compared to workers with non-occupational asthma.

Thirteen clinical trials were identified: nine trials examined

the effectiveness of pharmaceutical interventions (two of which

treated patients who were also removed from exposure), two

assessed workplace interventions, and the final study

investigated immunotherapy. The following results were

observed among the pharmaceutical trials: prednisone is more

efficacious than indomethacin; inhaled beclomethasone is

superior to placebo (including among patients removed from

workplace exposure); and lung function did not change when

using high-dose beclomethasone, but lung function was

impaired when low-dose beclomethasone and placebo were

used. Compared to placebo, salbutamol resulted in greater

improvement in FEV1. One study reported the results of four

crossover trials where outcomes were measured after SIC,

beclomethasone decreased airway responsiveness and improved

FEV1, and theophylline reduced the severity of asthma

exacerbations but did not decrease airway responsiveness;

verapamil, cromolyn, and placebo decreased FEV1 and

increased airway responsiveness. Another study comparing

theophylline to placebo also concluded that theophylline had

no effect on airway hyper-responsiveness, but did significantly

reduce the severity of late asthmatic reactions. Finally,

atropine was shown to have minimal effect on reducing

asthmatic reactions after SIC, fenoterol significantly

normalized airway resistance and improved expiratory thoracic

gas volume, and nifedipine was shown to prevent immediate

asthmatic reactions after SIC in three separate studies.

Compared to placebo, wheat flour immunotherapy resulted

in a significant decrease in serum specific IgE, less skin prick

sensitivity, non-specific bronchial reactivity, and subjective

clinical improvement. 

Two trials examined the effect of reducing exposure among

workers with OA. In a crossover trial examining the efficacy

of respiratory PPE, airway resistance and specific airway

resistance were significantly improved when SIC was

performed while wearing the respiratory PPE. The second

study compared healthcare workers’ asthmatic reactions to

various latex gloves. Among the eight healthcare workers,

hypoallergenic gloves reduced the risk of latex asthma

exacerbations. 

Discussion

Diagnosis

Prior to determining the accuracy of diagnostic tests, a

reference standard must be available for comparison. The

usual reference test for OA is SIC; however, it is of limited

availability7 and this test remains, to an extent, 

unstandardized .20-21 It appears that there are no better

alternatives in OA diagnosis at this time.

This review did not specifically examine the utility of

symptom questionnaires in screening for OA. There appears

little doubt about the utility of these approaches in screening

patients for further evaluation and testing. In this review, all

patients received referral to a clinic and/or symptom screening

prior to further evaluation for diagnosis of OA.

Overall, it appears that a positive test result of a single

comparison diagnostic test can assist clinicians in diagnosing

OA in populations where the suspicion of OA is already

reasonably high, but it cannot completely confirm the

diagnosis. However, even within such selected populations, a

single negative test result cannot exclude OA. For example,

the data showed that a single NSBP test gave a reasonable

sensitivity but somewhat lower specificity in predicting the

outcome of SIC, usually from studies among workers

identified in specialty clinics or workplace surveys where the

pre-test probability of disease was high. Immunological testing

also appears to be of use. Skin prick testing showed a higher

sensitivity than serum IgE in comparison with SIC, whereas

the converse was true for specificity. A clinical diagnosis (often

comprised of many diagnostic tests) resulted in high

sensitivities for HMW, LMW, and mixed asthmagens;

however, the lower specificity suggested a negative clinical

diagnosis was not sufficient to exclude OA. In addition, there

were differences in how these tests performed in HMW and

LMW agents.

Given the paucity of data available, further research is

required to determine if any combination of tests may be a

suitable alternative to SIC. The highest specificities arose from

a combination of a single NSBP test and SPT, or a single

NSBP test and specific IgE among HMW asthmagens. Given

a high pre-test probability of disease, a positive combined test

would largely confirm OA (post-test likelihood of ~80

percent). However, negative combined testing would not

provide sufficient certainty that OA was absent. It should be

noted that the data obtained precluded an evaluation of a

sequential testing scheme as proposed by others.1

5
It is important, in interpreting these data, to recognize that

these results are produced from a highly selected population

that was pre-screened, usually by referral to a specialist clinic, a

questionnaire, or a workplace study. However, in a clinical

setting where patients are being investigated for OA, patients

presumably would have undergone similar screening.

Consequently, it seems reasonable to apply the pooled

estimates of sensitivity and specificity derived from these

analyses to those groups.

Management

Most reports indicate patients with OA have mild-moderate

airflow limitation (>80 percent predicted FEV1) at the initial

assessment. We initially compared 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). From these comparisons, it

does not appear that a selection bias occurred with respect to

subsequent work exposure based on baseline severity of illness

(measured by FEV1 status).

Workers who remain exposed (either partially or fully)

experience continued deterioration in FEV1 compared to

baseline and this also appears to deteriorate over the time of

exposure. In contrast, most of the groups who are removed

from exposure appear to generally report improvement

compared to baseline lung function. Despite removal,

improvement appears to be neither dramatic nor progressive

with time.

Improvement in non-specific bronchial hyperresponsiveness among the group who are completely removed

from exposure did appear to be more impressive and

progressive with time than FEV1 results alone. Almost all of

the groups who were removed from their workplace appear to

improve compared to NSBP test results at diagnosis. Groups

who remain exposed experience continued deterioration in

NSBP test results compared to baseline and over time. This

suggests that continued exposure is required for non-specific

bronchial hyper-responsiveness to continue to decline.

Due to small study numbers, conclusions about medication

and symptoms are difficult to draw. Overall, workers with

OA, irrespective of subsequent exposure, often require asthma

medications long after their initial diagnosis. Symptoms

appear to persist and possibly worsen among workers who

continue their exposure. There is mixed evidence that removal

improves symptoms. Among workers who reduce their

exposure, symptoms abate in some workers; however, the

overall effect seems to be persistence of symptoms.

According to the studies cited, the economic consequences

of developing OA are impressive. Among the workers

included in the studies, those who left the workplace suffered

economic repercussions of reduced income and/or

unemployment. Workers who reduce their exposure or stay

employed at the same workplace still appeared to lose some

income over time, and their costs of medication increased.

One small clinical trial suggested spirometric,

immunological, and symptomatic improvement when workers

experiencing OA were treated with immunotherapy. A

comprehensive Cochrane Review confirmed this therapeutic

approach might be useful for asthma in general.22 While this

therapy may be as effective as inhaled corticosteroids, it is

complicated by its long duration, limited availability, and not

all immunotherapy compounds have been identified.

The evidence examining the effect of reducing exposure in

the workplace is limited to two clinical trials. Evidence

suggests that protective devices can reduce bronchial

obstruction; however, they failed to provide complete

protection and they require workers to be compliant with their

use. In the special situation of latex allergy-induced OA, the

use of non-latex gloves appeared to be a successful method of

improving OA.

Finally, conclusions regarding OA medication are difficult to

draw, as the trials suffered from limited duration of treatment

and dissimilar comparisons; however, the effectiveness trends

appear to be similar for OA and chronic asthma. In general,

there was evidence that anti-inflammatory agents, such as

systemic and inhaled corticosteroids, are effective in the

treatment of OA. Theophylline reduced the severity of asthma

exacerbations after SIC; however, airway responsiveness did

not decrease. Other agents such as non-steroidal antiinflammatories, calcium channel blockers, cromolyn, or

placebo demonstrate limited or no benefit in the acute

treatment of OA.

Potential Limitations

There is a possibility of publication bias in this systematic

review. By missing unpublished unimpressive diagnostic or

negative therapy studies, we may be over-estimating the

diagnostic properties of OA tests and/or the effect of OA

treatment, respectively. However, a comprehensive search was

conducted, authors were contacted, and grey literature was

extensively searched. Despite these efforts, we recognize that

more unpublished studies may exist.

While SIC is considered the reference standard for

diagnosing OA, some studies did not report this result for all

patients. Some studies used a clinical “consensus” diagnosis to

determine the presence of OA, which may have included SIC;

it was usually not clear which patients had undergone SIC and

why. Other studies only presented data from patients who

were SIC positive. These situations could introduce two forms

of bias: differential reference standard bias and partial

verification bias.16

6
A further limitation was that not all studies presented data

in a useful form to evaluate the diagnostic accuracy of a

comparison test. It was 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, individual

patient data were available; however, the absence of an

established cut-off value to define a “positive” test excluded

these results. Consequently, fewer studies than identified

could be pooled in some of the comparisons.

Finally, 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. In an effort to reduce heterogeneity, the results

are presented by HMW and LMW and subgrouped by the

specific asthmagen. 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 recommend that the reader carefully

examine and interpret the diagnostic results presented in this

report.

One limitation of the management review is that the

methodological quality of the included studies was relatively

weak. The interventions were generally divided into removal,

reduced exposure, or continued exposure; however, the

definition of these approaches differed and allocation was not

randomized. Also, the outcome assessments were often not

comparable and tended to focus on physiological test results

(e.g., pulmonary function tests, NSBP test, SIC, etc.) rather

than quality of life. There was variability in length of followup

within and between studies, making pooling problematic.

Conclusions

There is a lack of high-quality research to guide clinicians in

the diagnosis and management of OA. Until better evidence

exists, the findings from this systematic review may be

unsatisfying to some. Based on the evidence, the following

conclusions can be made about the diagnosis and namagement

of OA:

Diagnosis

• Despite limited availability, SIC appears to be the main

reference standard for the diagnosis of OA.

• In isolation, none of the diagnostic tests yielded a high

combination of sensitivity and specificity that could

replace SIC.

• In the absence of SIC, NSBP testing and SPT (although

of limited availability) are the best available alternative

tests in population with a relatively high pre-test

probability of OA, yet their sensitivity and specificity

alone are insufficiently discriminative to confirm or

exclude OA.

• Adding SPT or specific IgE can enhance the specificity of

NSBP testing and increase the likelihood that workers

who test negative to both tests do not have OA. Many

other combination tests have not been evaluated in

sufficient detail to provide recommendations.

Management

• Within published research data the baseline FEV1 does

not predict subsequent exposure status.

• Workers who remain exposed will experience decreased

FEV1 over time, increased non-specific bronchial hyperresponsiveness, and continue to require medications.

• Most workers with OA who cease exposure will

experience improved FEV1 over time and less nonspecific bronchial hyper-responsiveness; however, many

workers will continue to have symptoms and require

treatment.

• The evidence regarding outcomes for workers who

reduce, rather than cease, their exposure is insufficient to

draw firm conclusions.

• Anti-inflammatory agents appear to be effective shortterm (<6 months) therapy for OA; however, limited highquality research has been performed on patients with OA.

Future Research

• Clear comparisons between reference standards

(preferably SIC) and alternative test approaches and

report results using standardized diagnostic test methods.

• Conduct prospective, long-term outcome studies to

understand the outcomes (physiological, social,

economic, and quality of life) of OA using standardized

reporting.

• Conduct longer term studies to determine optimal

medication regimens and disease management for various

OA populations, combined or not with continuous,

reduced, or absent exposure.

Availability of the Full Report

The full evidence report from which this summary was

taken was prepared for the Agency for Healthcare Research

and Quality (AHRQ) by the University of Alberta Evidencebased Practice Center, under Contract No. 290-02-0023. It is

expected to be available in November 2005. At that time,

printed copies may be obtained free of charge from the AHRQ

Publications Clearinghouse by calling 800-358-9295.

7
8

Requesters should ask for Evidence Report/Technology

Assessment No. 129, Diagnosis and Management of WorkRelated Asthma. In addition, Internet users will be able to

access the report and this summary online through AHRQ’s

Web site at www.ahrq.gov.

Suggested Citation

Beach J, Rowe BH, Blitz S, Crumley E, Hooton N, Russell

K, Spooner C, Klassen T. Summary, 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-

E003-1. Rockville, MD: Agency for Healthcare Research and

Quality. October 2005.

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