Abstract
Background:
The objective was to update the 2011 Cochrane systematic review on the effectiveness of workplace interventions for the treatment of occupational asthma.
Methods:
A systematic review was conducted with the selection of articles and reports through 2019. The quality of extracted data was evaluated, and meta-analyses were conducted using techniques recommended by the Cochrane Handbook for Systematic Reviews of Interventions.
Results:
Data were extracted from 26 nonrandomized controlled before-and-after studies. The mean number of participants per study was 62 and the mean follow-up time was 4.5 years. Compared with continued exposure, removal from exposure had an increased likelihood of improved symptoms and change in spirometry. Reduction of exposure also had more favorable results for symptom improvement than continued exposure, but no difference for change in spirometry. Comparing exposure removal to reduction revealed an advantage for removal with both symptom improvement and change in spirometry for the larger group of patients exposed to low-molecular-weight agents. Also, the risk of unemployment was greater for exposure removal versus reduction.
Conclusions:
Exposure removal and reduction had better outcomes than continued exposure. Removal from exposure was more likely to improve symptoms and spirometry than reduction among patients exposed to low-molecular-weight agents. The potential benefits associated with exposure removal versus reduction need to be weighed against the potential for unemployment that is more likely with removal from exposure. The findings are based on data graded as very low quality, and additional studies are needed to generate higher quality data.
Keywords: asthma management, exposure reduction, exposure removal, interventions at work, work-related asthma
1 ∣. INTRODUCTION
Work-related asthma includes (i) occupational asthma (OA), which is caused by workplace exposures, and (ii) work-exacerbated asthma, in which workplace exposures worsen existing or concurrent asthma. A recent literature review concluded that 16% of adult-onset asthma is attributable to occupation,1 although this is likely an underestimate. Both sensitizers and irritants are known to cause OA. Sensitizer-induced asthma is characterized by an immunologic-mediated sensitization to a workplace agent and can result from exposure to either high-molecular-weight (HMW) agents (e.g., animal or vegetable proteins) or low-molecular-weight (LMW) agents (e.g., diisocyanates, plicatic acid from western red cedar).2 Irritant-induced OA has typically been characterized by onset shortly after high-level exposure to respiratory irritants (e.g., chlorine gases),3 although it might also result from chronic low- to moderate-level irritant exposures.4 Over 300 workplace agents are known to cause OA and can occur in a variety of occupations and industries.5 OA can have a profound adverse impact on a patient's quality of life, employment status, and income.6,7
A 2011 Cochrane systematic review evaluated the effectiveness of workplace interventions on the outcome of OA.8 When compared with continued exposure, both removal from exposure and reduction of exposure increased the likelihood of subsequently reporting an absence of symptoms, but only removal was associated with improvement in the forced expiratory volume in 1 s as the percentage of a predicted or reference value (FEV1%). When compared with reduction of exposure, removal from exposure increased the likelihood of an absence of symptoms but not of improvement in FEV1%. Unfortunately, unemployment was also more likely after removal from exposure compared with exposure reduction.
Several studies of workplace interventions for OA were published after the 2011 review. With a comprehensive approach of including recently published studies,9-12 along with those studies already identified in the 2011 Cochrane review, we produced an updated systematic review of evidence on the effectiveness of workplace interventions for the treatment of OA.13
2 ∣. MATERIALS AND METHODS
We searched relevant publications in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE (Ovid), NIOSHTIC-2, and CISILO (CCOHS) up to July 31, 2019. We looked for but did not find any randomized controlled trials or interrupted time-series of workplace interventions. However, we identified nonrandomized controlled before-and-after studies. We included studies evaluating workplace interventions that eliminated or reduced OA patients' exposure at work and excluded studies that investigated the effects of medication only or medical monitoring/surveillance. The primary health outcomes of interest were changes in asthma symptoms, FEV1%, and nonspecific bronchial hyperreactivity (NSBH) from baseline to follow-up. Two authors worked independently to assess study eligibility and risk of bias, and extract data.
We combined the extracted health results from eligible studies in meta-analyses and calculated statistics using techniques recommended by the Cochrane Handbook for Systematic Reviews of Interventions.14 Most results from the meta-analyses were reported as a risk ratio (RR), mean difference (MD), or a standardized mean difference (SMD), each with a 95% confidence interval (95% CI). We contacted authors if their publications lacked required statistical information or did not clearly describe the calculations in their studies. We used the I2 statistic to test statistical heterogeneity in the meta-analyses, interpreting values of I2 > 50% to indicate substantial heterogeneity. We used funnel plots to evaluate publication bias when at least five studies were available for this analysis and checked whether papers had overlapping study samples. We evaluated the quality of evidence for the different outcomes using the GRADE approach.15
3 ∣. RESULTS
We included 26 observational, nonrandomized controlled before-and-after-studies with 1695 participants that reported on 36 comparisons used in the meta-analyses. Only three of the 26 studies were designed as intervention studies. For different comparisons, we identified 18 studies of removal from exposure versus continued exposure; 7 reduction of exposure versus continued; and 10 removal from exposure versus reduction. The types of agents investigated were HMW in 5 studies, LMW in 15 studies, both HMW and LMW in 5 studies, and pot room gases in 1 study. Sample sizes ranged from nine to 232 participants with a median of 41 and a mean of 62. The follow-up times for the 26 studies had a mean of 4.5 years, median of 3.2 years, and range 5 weeks to 12 years. Median durations were 5.6 years for exposure before symptoms (reported by 10 studies) and 3.8 years for symptoms before diagnosis (reported by 13 studies). The diagnosis of OA was based on a specific inhalation challenge with the suspected workplace agent in 20 studies.
The relative effects of workplace interventions on health outcomes are presented in Table 1. When compared with continued exposure, removal from exposure had a greater likelihood of the absence of symptoms (RR, 4.80; 95% CI, 1.67 to 13.86), improvement of symptoms (RR, 2.47; 95% CI, 1.26 to 4.84), better change in FEV1% (MD, 4.23 percentage points; 95% CI, 1.14 to 7.31), and improved NSBH (SMD, 0.43; 95% CI, 0.03 to 0.82; Table 1). The comparison of reduction of exposure to continued exposure revealed a greater likelihood of absence of symptoms (RR, 2.65; 95% CI, 1.24 to 5.68) and no difference for change in FEV1%. No data were available to analyze symptom improvement and change in NSBH. Based on all available studies, the comparison of removal from exposure to the reduction of exposure showed no statistically significant differences for symptoms or FEV1%, and a lack of data for NSBH (Table 1). However, the subset of studies on exposure to LMW agents showed more favorable results for exposure removal versus reduction for the absence of symptoms (RR, 9.31; 95% CI, 1.56 to 55.73), improvement of symptoms (RR, 1.61; 95% CI, 1.02 to 2.53), and change in FEV1% (MD, 5.79 percentage points; 95% CI, 0.02 to 11.56; Table 1).
TABLE 1.
Relative effects of workplace interventions for occupational asthma on the absence of asthma symptoms, improvement of asthma symptoms, change in FEV1%, and change in NSBH, for three different comparisonsa
| Comparisons |
||||||
|---|---|---|---|---|---|---|
| Removal from exposure versus continued exposure |
Reduction of exposure versus continued exposure |
Removal from exposure versus reduction of exposure |
||||
| Outcome | Relative effect (95% CI) | Number of participants (studies) |
Relative effect (95% CI) | Number of participants (studies) |
Relative effect (95% CI) | Number of participants (studies) |
| Absence of asthma symptoms | RR, 4.80 (1.67 to 13.86) | 641 (9 observational studies) | RR, 2.65 (1.24 to 5.68) | 334 (7 observational studies) | RR, 6.05 (0.86 to 42.34) | 359 (6 observational studies) |
| Improvement of asthma symptoms | RR, 2.47 (1.26 to 4.84) | 435 (9 observational studies) | b | b | RR, 1.11 (0.84 to 1.47) | 140 (5 observational studies) |
| Change in FEV1% predicted: FU minus baseline values | MD, 4.23 percentage points (1.14 to 7.31) | 898 (10 observational studies) | MD, 2.76 percentage points (−1.53 to 7.04) | 224 (4 observational studies) | MD, 2.58 percentage points (−3.02 to 8.17) | 388 (7 observational studies) |
| Change in NSBH: FU minus baseline values | SMD, 0.43 (0.03 to 0.82) | 387 (6 observational studies) | b | b | b | b |
Abbreviations: CI, confidence interval; FEV1%, forced expiratory volume in one second as the percentage of a predicted or expected value; FU, follow-up; MD, mean difference; NSBH, nonspecific bronchial hyperreactivity; RR, risk ratio; SMD, standardized mean difference.
Contents of table based on the three tables in the Summary of Findings section of the 2019 Cochrane review “Workplace interventions for treatment of occupational asthma.”13 We rated the quality of the evidence as very low for all outcomes in this table. See original document for details.
No studies reported or enabled the calculation of the outcome for this comparison.
Based on data from two studies, the risk of unemployment after removal from exposure was increased compared with the reduction of exposure, with RR, 14.28 (95% CI, 2.06 to 99.16). Also, four studies reported a decrease in income varying from 20% to 50% after removal from exposure.
4 ∣. DISCUSSION
All studies in the current systematic review were observational and had a high risk of bias along with unexplained heterogeneity in study results. Therefore, we graded the quality of this evidence as “very low” for all outcomes.
We concluded that both removal from exposure and reduction of exposure for OA patients may improve asthma symptoms compared with continued exposure. While not observed for reduction of exposure, studies of removal from exposure indicated improved lung function compared with continued exposure. The direct comparison of removal from exposure to the reduction of exposure revealed that removal may improve symptoms and lung function among OA patients exposed to LMW agents, but this was not apparent among the relatively small group of reported cases exposed to HMW agents or both HMW and LMW agents. Due to the smaller sample size and overall lower graded quality of evidence, we do not recommend any change to clinical practice advice to remove exposure in HMW OA based on our findings. Unfortunately, removal from exposure may also increase the risk of unemployment compared with reduction of exposure. Considering these findings, care providers should carefully balance the potential clinical benefits of removal from exposure or reduction of exposure with potentially detrimental effects of unemployment while addressing management options.
Additional high-quality studies are needed to evaluate the effectiveness of workplace interventions for OA. Randomizing OA patients to removal from exposure, reduction of exposure, and continued exposure would likely be rejected by most ethics committees and treating physicians. Alternatively, improvements in methods for before and after studies are possible if not always easy. For example, there are opportunities to improve the methods for gathering information about respiratory symptoms. Summary estimates for improvement of symptoms (Table 1) were based on 9 articles for removal versus continued exposure and 5 articles for removal versus reduction of exposure, which together accounted for 11 unique articles. Three investigations used questions based on a validated questionnaire, three used questionnaires of unclear origin, and five used interviews with no mention of the questions used. Subsequent studies could produce more reliable results by using validated and standardized questions about respiratory symptoms. Examples of additional improvements include prospective enrollment of newly diagnosed OA cases for longitudinal follow-up, following all participants at the same intervals since diagnosis, and collecting more details about socioeconomic impact.
While the current review addressed the treatment of OA, it is important to note that primary prevention is possible. Recommendations from the European Respiratory Society Task Force on the Management of Work-Related Asthma identified exposure elimination as the preferred approach to primary prevention of OA, with exposure reduction as the next best option.16
ACKNOWLEDGMENTS
The authors thank the Cochrane organization for innumerable acts of support during the preparation of the 2019 systematic review. The only funding the study received was from the National Institute for Occupational Safety and Health, Morgantown, WV, The University of Texas Health Science Center at Houston, Houston, TX, University of Arkansas for Medical Sciences, Little Rock, AR, Coronel Institute of Occupational Health, Amsterdam, The Netherlands, University of Alberta, Edmonton, Alberta, Canada, University of Toronto, Toronto, Ontario, Canada, and University of Bologna, Bologna, Italy that supported the salaries of the authors.
Footnotes
CONFLICTS OF INTEREST
The authors declare that there are no conflicts of interest.
DISCLAIMER
The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.
DISCLOSURE BY AJIM EDITOR OF RECORD
John D. Meyer declares that he has no conflict of interest in the review and publication decision regarding this article.
DATA AVAILABILITY STATEMENT
Data used in this brief summary of a systematic review are available from published articles that are referenced in the current article or the parent document.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data used in this brief summary of a systematic review are available from published articles that are referenced in the current article or the parent document.