Evidence Report/Technology Assessment: Number 129
This information is for reference purposes only. It was current when produced and may now be outdated. Archive material is no longer maintained, and some links may not work. Persons with disabilities having difficulty accessing this information should contact us at: https://info.ahrq.gov. Let us know the nature of the problem, the Web address of what you want, and your contact information.
Please go to www.ahrq.gov for current information.
Under its Evidence-based Practice Program, the
Agency for Healthcare Research and Quality (AHRQ) is developing scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools. Contractor institutions review all relevant scientific literature on assigned clinical care topics and produce evidence reports and technology assessments, conduct research on methodologies and the effectiveness of their implementation, and participate in technical assistance activities.
Select for PDF File (110 KB). Plugin Software Help.
Introduction / Objectives and Key Questions / Methods / Results / Discussion / Conclusions / Future Research / Availability of Full Report / References
Beach J, Rowe BH, Blitz S, Crumley E, Hooton N, Russell K, Spooner C, Klassen T.
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
OA can be broadly classified into two
categories: OA with latency and OA without
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
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
- History and questionnaire.
- Non-specific bronchial provocation (NSBP) challenge.
- Serial lung function testing.
- Specific immunological testing.
- Exhaled nitrous oxide.
- 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 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
Return to Contents
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:
- What is the best diagnostic approach for a patient with suspected OA?
- In what situations would SIC testing provide additional useful diagnostic information?
- Which treatment is most effective for OA?
- Must patients with OA be removed from the workplace environment to control symptoms and/or disease progression?
Return to Contents
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. 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.
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.
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 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.
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-percent 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.
Return to Contents
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
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
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 3-1,011). 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
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
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 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).
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 hyper-responsiveness.
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
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).
- 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
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
Return to Contents
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.
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.
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
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
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.
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
Improvement in non-specific bronchial hyper-responsiveness
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
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 anti-inflammatories,
calcium channel blockers, cromolyn, or
placebo demonstrate limited or no benefit in the acute
treatment of OA.
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
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
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.
Return to Contents
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 management
- 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.
- 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 non-specific 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 short-term (<6 months) therapy for OA; however, limited high-quality research has been performed on patients with OA.
Return to Contents
- 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.
Return to Contents
Availability of 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 Evidence-based
Practice Center, under Contract No. 290-02-0023. Printed copies may be obtained free of charge from the AHRQ Publications Clearinghouse by calling 800-358-9295. Requesters should ask for Evidence Report/Technology Assessment No. 129, Diagnosis and Management of Work-Related Asthma.
The Evidence Report is also online on the National Library of Medicine Bookshelf, or can also be downloaded as a PDF File (1.2 MB). Plugin Software Help.
Return to Contents
1. Chan-Yeung M, Malo JL. Occupational asthma. N Engl J Med
2. Blanc PD, Toren K. How much adult asthma can be attributed to
occupational factors? Am J Med 1999;107:580-7.
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. Banks DE, Wang ML. Occupational asthma: "the big picture".
Occup Med 2000;15(2):335-58.
5. 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.
6. Tarlo SM, Broder I. Irritant-induced occupational asthma. Chest 1989;96(2):297-300.
7. 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.
8. Leigh JP, Romano PS, Schenker MB, et al. Costs of Occupational
COPD and Asthma. Chest 2002;121:264-72.
9. Chan-Yeung M. Occupational asthma. Chest 1990; 98:148S-161S.
10. Burge PS, O'Brien IM, Harries MG. Peak flow rate records in the
diagnosis of occupational asthma due to isocyanates. Thorax 1979;
11. Cote J, Kennedy S, Chan-Yeung M. Sensitivity and specificity of
PC20 and peak expiratory flow rate in cedar asthma. J Allergy Clin
12. 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.
13. Pisati G, Baruffini A, Zedda S. Toluene diisocyanate induced asthma:
Outcome according to persistence or cessation of exposure. Br J Ind
14. Cote J, Kennedy S, Chan-Yeung M. Outcome of patients with cedar
asthma with continuous exposure. Am Rev Respir Dis 1990;141:373-76.
15. Merget R, Schulte A, Gebler A, et al. Outcome of occupational
asthma due to platinum salts after transferal to low-exposure areas.
Intl Arch Occup Environ Health 1999;72(1):33-9.
16. Lijmer JG, Mol BW, Heisterkamp S, et al. Empirical evidence of
design-related bias in studies of diagnostic tests. JAMA
17. Downs SH, Black N. The feasibility of creating a checklist for the
assessment of the methodological quality both of randomised and
non-randomised studies of health care interventions. J Epidemiol
Community Health 1998;52(6):377-84.
18. 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.
19. 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.
20. Stenton SC, Avery AJ, Walters EH, et al. Statistical approaches to the
identification of late asthmatic reactions. Eur Resp J 1994;7:806-12.
21. Boulet LP, Roberts RS, Dolovich J, et al. Prediction of late asthmatic
responses to inhaled allergen. Clin Allergy 1984;14:379-95.
22. 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.).
Return to Contents
AHRQ Publication Number 06-E003-1
Current as of October 2005