PAUL K. HENNEBERGER, SCD, CHRISTOPHER D. HOFFMAN, MS, DAVID J. MAGID, MD, ELLA E. LYONS, MS

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Original Articles Work-related Exacerbation of Asthma PAUL K. HENNEBERGER, SCD, CHRISTOPHER D. HOFFMAN, MS, DAVID J. MAGID, MD, ELLA E. LYONS, MS Adults with asthma who had been enrolled in an HMO for at least a year were requested to complete a questionnaire about their health status. Approximately 25% of the 1,461 participants responded positively to Does your current work environment make your asthma worse? and were classified as having workplace exacerbation of asthma. Those with workplace exacerbation were more likely to have never attended college, be current or former smokers, have a history of other respiratory diseases, have missed work or usual activities at least one day in the past four weeks, and report their asthma was moderate, severe, or very severe. Percentages with workplace exacerbation of asthma were highest for mining and construction (36%), wholesale and retail trade (33%), and public administration (33%), and lowest for educational services (22%), finance, insurance, and real estate (22%), and non-medical and non-educational services (18%). Future studies are needed for objective validation of self-reported workplace exacerbation, and to follow subjects prospectively to clarify the temporal sequence of workplace exacerbation and asthma severity, and how other respiratory conditions and smoking might contribute to work-related worsening of asthma. Key words: asthma; workplace exacerbation; industry. INT J OCC UP ENVIR O N H EALTH 2 002;8: 291 29 6 Work-related asthma (WRA) is the most common non asbestos-related lung disease seen in occupational health clinics in the United States. 1,2 Findings from several studies conducted in the United States indicate that from 3% to 26% of incident cases of asthma among adults are attributable to workplace exposures. These estimates Received from the Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia (PKH, CDH); the Colorado Permanente Clinical Research Unit, Denver, Colorado (DJM, EEL); and the University of Colorado Health Sciences Center, Denver, Colorado (DJM). Address correspondence and reprint requests to: Paul Henneberger, Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, U.S.A.; telephone: (304)285-6161; fax: (304)285-5820; e-mail: <pkh0@cdc.gov>. come from a variety of sources, including national disability data, 3 a community-based sample of individuals with asthma, 4 hospital discharge data, 5 and patients with asthma in a health maintenance organization. 6 Workplace exacerbation of existing asthma is potentially as common as work-initiated asthma, and with both kinds of cases repeated asthma attacks associated with environmental exposures can lead to chronic pulmonary impairment. 7 From a community sample of adults in Australia, 20% of individuals with asthma reported that their symptoms were exacerbated by workplace conditions. 8 In a study conducted in Norway, participants were classified as having work-related asthma if they reported ever having respiratory symptoms associated with work that abated on weekends or holidays. 9 A full third (33%) of the men and 18% of the women with asthma fulfilled the work-related criterion. Available data on workplace exacerbation of asthma in the United States are limited. From the surveillance of work-related asthma conducted by four states as part of the NIOSH-sponsored SENSOR program, 19.1% of the cases registered during 1993 1995 were classified as work-aggravated asthma rather than new-onset asthma. 10 From a case series of patients referred for occupational asthma to an occupational and environmental medicine clinic in the United States, 27% were judged to have exacerbation of pre-existing asthma. 11 Additional research is needed to estimate what proportion of adults with asthma experience worsening of their condition in association with work. In the current study, adults with asthma who were enrolled in a health maintenance organization (HMO) completed a standardized questionnaire that gathered information about a variety of topics, including demographic features, the person s health status, health care for asthma, and indicators of the severity of asthma. Responses to a question about worsening of asthma in association with work were the focus of the following analyses. The research questions addressed in this study were: 1. What proportion of adults with asthma report that their current work environment makes their asthma worse? 291

2. Among adults with asthma, do those with workrelated worsening differ with respect to demographic features, health and health-care features, and selfreported severity? 3. Which industries have the highest proportions with work-related worsening of asthma? METHODS The participants in the study were adults with asthma who were members or enrollees of the Kaiser Foundation Health Plan of Colorado (KPCO). Potential participants were those members of KPCO who had been continuously enrolled in a health care plan during August 1, 1996, through July 31, 1997, had been between the ages of 18 and 44 as of July 31, 1997, and had asthma. A member was considered to have asthma if he or she either had received at least four dispensings of one or more asthma medications or had had an inpatient stay with a discharge diagnosis of asthma during the year of continuous enrollment. A questionnaire was mailed to all eligible members of the KPCO. A second questionnaire was mailed to non-respondents. Those who did not respond to either the first or the second mailed questionnaire were then contacted by telephone and completed the questionnaire via telephone interview upon choosing to enter the study. Telephone interviewers were blinded to the policy holder s industry of current work. Individuals contacted were asked whether a doctor had ever told them they had asthma and whether they had taken medications for asthma within the preceding year. Only those who answered yes to these two questions were asked to complete the part of the questionnaire that inquired about features of their illness and the quality of treatment. Participants who gave a positive response to the question: Does your current work environment make your asthma worse? were classified as having workplace exacerbation of asthma. As the work-related aspect of asthma was not a primary focus of the survey as originally planned, information about industry of current work was available for primary policy holders only. For this reason, the prevalence of workplace exacerbation was examined by industry of current work for only a subset of the participants. There were 970 participants who were the primary policy holders for care at the HMO and, therefore, for whom current industry could be determined. Those with industry indicated as unknown or missing (n = 15) or non-classifiable (n = 169) were excluded, leaving a total of 786 people, or 54% of the 1,461 study participants. Neither current occupation (in contrast to current industry) nor lifetime work history was available. High-risk and low-risk industries were identified a priori based on published studies of asthma from the United States and other industrialized nations. 12 21 Based on these sources, three high-risk industry groups were identified: agriculture, fishery, and forestry ; mining and construction; and manufacturing. Two lowrisk industry groups were also identified: non- medical and non-educational services, referred to as all other services ; and finance, insurance, and real estate. The industry group of public administration includes firefighters and police officers, and has been observed to have the highest rate of inhalation injuries among several industry groups. 22 As a result, public administration was also considered one of the high-risk categories for exacerbation of asthma. Testing of statistical significance between those with and without workplace exacerbation of symptoms was accomplished using the chi-square and Fisher s exact tests for categorical variables and the Student s t-test and Wilcoxon rank-sum test for continuous variables. P 0.05 was considered statistically significant. Statistical analyses were performed using the SAS statistical package for Windows. 23 When examining the relationship between workplace exacerbation of asthma and employment in a high-risk industry, we considered several variables as potential effect modifiers/confounders: gender, race (non-white vs white), annual family income ( $50,000 vs < $50,000), education (some college education vs no college), age (> 37 vs 37), and cigarette smoking (ever vs never). We tested for homogeneity of odds ratios between high-risk industries and all other industries in order to identify effect modification, with p 0.05 as a cutoff. Potential confounding was investigated by comparing the Mantel Haenszel odds ratio adjusted for the effect of the potential confounder with the crude odds ratio. Prevalence ratios were determined using the PHREG procedure in SAS with the BRESLOW procedure to handle ties. 24 Both forward and backward stepwise procedures were used to fit models. If a covariate had a p value 0.20, it was excluded from the model. Any covariate with 0.10 < p < 0.20 was further tested by removing it from the model. If removal resulted in at least a 15% change in the prevalence ratio for the exposure of interest, the covariate was retained in the model. The final models from the forward and backward stepwise procedures were compared and the model containing the most covariates was reported. RESULTS Overall, 1,589 adults with asthma (78%) agreed to participate in the study, approximately 60% by mail and 40% by telephone. Participants were excluded if they did not indicate whether or not they had work-related worsening of symptoms (n = 40), were missing gender or age (n = 61), or were beyond the specified age range (n = 27). These exclusions left 1,461 adults with asthma who completed the survey, of whom 367 (25.1%) reported workplace exacerbation of asthma symptoms. Approximately two thirds of the participants were 292 Henneberger et al. INT J OCCUP ENVIRON HEALTH

TABLE 1. Demographic Features of Adults with Asthma by Workplace Exacerbation Status Workplace Exacerbation of Asthma Yes No (n = 367) (n = 1,094) p Value* Gender Female 65% 68% 0.47 Male 35% 32% Age,mean (SD) 36.0 years 34.9 years 0.02 (7.31) (8.11) Race White 75% 81% 0.02 Non-white 25% 19% Education No college 33% 20% <0.01 Some college 67% 80% Annual Income < $50,000 61% 55% 0.05 $50,000 39% 45% Cigarette smoking <0.01 Current 16% 12% Former 31% 25% Never 53% 63% *p value based on chi square, c o n t i n u i t y - c o r rected chi square,or two-tail Fisher s exact test for categorical variables, and Student s t-test for age. female, and this proportion did not vary much by workplace exacerbation status (Table 1). Those with workplace exacerbation were older (mean age 36.0 vs 34.9 years), more likely to be non-white (25% vs 19%), less likely to have attended college (67% vs 80%), and less likely to have an annual family income of at least $50,000 (39% vs 45%) (Table 1). Also, the participants with work-related symptoms had a greater proportion of ever-smokers. Participants were asked whether they had ever been told by a health care professional that they had certain conditions, with 29% reporting chronic sinusitis and 85% reporting allergies or hay fever. These percentages did not vary substantially by workplace-exacerbation status (Table 2). However, the participants who reported workplace exacerbation were more likely to have had chronic bronchitis (29% vs 16%, p < 0.01) and emphysema or chronic obstructive pulmonary disease (COPD) (2.4% vs 0.9%, p = 0.05). The proportions of participants with a regular source of health care for asthma and with an asthma specialist for that care were very similar regardless of workplace-exacerbation status (Table 2). The two groups did not differ with respect to hospitalization for asthma, but those with workplace exacerbation were more likely to have had treatment for an acute asthma attack. Use of asthma medications, in particular inhaled beta agonists, inhaled steroids, and a burst of oral steroids, did not vary between the two groups of participants (Table 2). However, those with workplace exacerbation of asthma had a higher median number of days with symptoms in the preceding 2 weeks (14 vs 11, p < 0.01). Those with workplace exacerbation were more likely to judge their asthma as moderate, severe, or very severe ( Table 3). When asked to compare their current asthma TABLE 2. Health and Health Care Features of Adults with Asthma by Workplace Exacerbation Status Workplace Exacerbation of Asthma Yes No Other conditions Chronic sinusitis 30% 28% Allergies or hay fever 88% 85% Chronic bronchitis 29% 16% Emphysema or COPD 2.4% 0.9% Regular health care for asthma Received health care for asthma in preceding 12 months 75% 73% Had regular source of care 88% 87% Source of care is asthma specialist 31% 30% Unplanned health care for asthma 1 treatment for asthma attack in preceding year 44% 36% Overnight hospitalization for asthma in preceding year 5.5% 4.4% Medications for asthma Use inhaled beta agonists 98% 99% With mod/severe asthma* use inhaled steroids 83% 82% Burst of oral steroids in past year 37% 39% Days with asthma symptoms in preceding two weeks Median 14 days 11 days With > overall median of 11 days with symptoms 53% 43% *200 work-exacerbated cases and 508 other cases reported that their asthma was moderate,severe,or very severe. p < 0.05 by continuity-corrected chi square. p < 0.01 by continuity-corrected chi square. p < 0.01 by Wilcoxon rank-sum test. VOL 8/NO 4,OCT/DEC 2002 Work-related Exacerbation of Asthma 293

TABLE 3. Self-reported Asthma Severity and Work/Activities Missed, by Workplace Exacerbation Status Workplace Exacerbation of Asthma Yes No (%) (%) Self-reported current condition of asthma* Very mild 7 14 Mild 27 30 Moderate 51 44 Severe 11 10 Very severe 4 2 Self-reported asthma condition compared with one year ago* Much better 15 21 Somewhat better 21 16 Same 46 51 Somewhat worse 15 10 Much worse 3 2 Missed work or usual activities Missed work/usual activities 1 day in preceding 4 weeks 19 12 *p < 0.01 by chi square. p < 0.01 by continuity-corrected chi square. TABLE 4. Prevalence of Workplace Exacerbation of Asthma by Industry Categor y Workplace Industry Categor y Exacerbation p Value* Mining and construction 4/11 = 36.4% 0.24 Wholesale and retail trade 20/60 = 33.3% 0.04 Public administration 53/162 = 32.7% <0.01 Transportation,communications, electricity, gas, sanitary services 33/105 = 31.4% 0.03 Manufacturing 21/73 = 28.8% 0.15 Medical services 31/120 = 25.8% 0.25 Educational services 19/85 = 22.4% 0.70 Finance,Insurance, real estate 16/74 = 21.6% Ref All other services 17/96 = 17.7% Ref TOTAL 214/786 = 27.2% *p value based on continuity-corrected chi square or Fisher s exact test.each category was compared with the combination of finance, insurance, real estate and all other services, which together had a pr evalence of 33/170 = 19.4%. Low-risk industries identified from literature review. condition with what it had been like a year earlier, the individuals with workplace exacerbation were more likely to report either somewhat worse or much worse. Also, they were more likely to have missed work or usual activities in the preceding four weeks (Table 3). The prevalence of workplace exacerbation by industry of current work is presented in Table 4. The highrisk industry groups were determined in advance to be: agriculture, fishery, and forestry; mining and construction; manufacturing; and public administration. None of the participants in the current study were working in agriculture, fishery, and forestry, and mining and construction accounted for only 11. The findings for the 246 study participants in the high-risk group largely reflect the experience of workers in public administration (n = 162, 66% of 246) and manufacturing (n = 73, 30% of 246). The prevalence of work-related exacerbation for the high-risk group was 78/246 = 32%, versus 136/540=25% (p = 0.07) for all other participants and 33/170=19% (p = 0.007) for the low-risk group, composed of all other services and finance, insurance, and real estate. Several of the industry groups that had high prevalences were not suspected a priori to have increased risks. For example, the categories wholesale and retail trade had the second highest prevalence, at 33%, and transportation etc. had the fourth highest prevalence at 31%. Prevalence ratios were obtained for workplace exacerbation of asthma by several different treatment types, severity indices, and competing illnesses (Table 5). Cigarette smoking (ever vs never) and education (some college vs no college) were found to have consistent prevalence ratios in the models, with values of approximately 1.2 for smoking and 0.6 for education. After controlling for smoking and education, workplace exacerbation was associated with ever having had chronic bronchitis, emphysema, or COPD (prevalence ratio = 1.5, 95% CI 1.1, 1.9), a self-report of more severe asthma (prevalence ratio = 1.3, 95% CI 1.0, 1.8), and having missed work or usual activities at least one day in the preceding four weeks (prevalence ratio = 1.4, 95% CI 1.0, 2.0) (Table 5). Prevalence ratios for workplace exacerbation of asthma were also determined by high-risk industries compared with all other industries controlling for selfperceived asthma severity, education, and competing illnesses (Table 6). There was a slightly, although not statistically significantly elevated, prevalence ratio for those in the high-risk industries (prevalence ratio = 1.2, 95% CI 0.9, 1.6). Education (prevalence ratio = 0.6, 95% CI 0.4, 0.8) and competing illnesses (prevalence ratio = 1.5, 95% CI 1.1, 2.0) were the strongest predictors of workplace exacerbation of asthma from the model. Separate models were also run for high-risk industries controlling for: education alone; education and self-perceived asthma severity; education and competing illnesses; and no other variables (data not shown). These models all had consistent prevalence ratios for high-risk industries between 1.2 and 1.3. DISCUSSION The perception of work-related worsening of asthma was common in this study, being reported by one of every four adults with asthma. Several factors were associated with workplace exacerbation of asthma, includ- 294 Henneberger et al. INT J OCCUP ENVIRON HEALTH

TABLE 5. Prevalence Ratios from Regression Models for Workplace Exacerbation of Asthma Covariates* Prevalence Ratio (95% CI) p Value Ever had chronic bronchitis, emphysema,or COPD 1.5 (1.1,1.9) 0.01 Treated for acute asthma attack in preceding year 1.1 (0.9,1.5) 0.39 Hospitalized for asthma in preceding year 1.0 (0.5,1.9) 0.96 Burst of oral steroids in preceding year 1.1 (0.9,1.2) 0.48 > median of 12 days in preceding 14 with asthma symptoms 1.1 (0.9,1.5) 0.34 Asthma status moderate,severe,or very severe 1.3 (1.0,1.8) 0.04 Missed work or usual activities 1 day in preceding 4 weeks 1.4 (1.0,2.0) 0.06 *Each model included covariates to control for smoking and education.there were a consistent positive effect in each model for smoking (ever vs never) and a consistent negative effect for education (some college vs no college). TABLE 6. Results of Modeling Workplace Exacerbation of Asthma among High-risk Industries Compared with All Other Industries, Controlling for Self-perceived Asthma Severity, Education, and Competing Illnesses Covariates* Prevalence Ratio (95% CI) p Value High-risk industries 1.2 (0.9,1.6) 0.14 Asthma status moderate,severe,or very severe 1.3 (1.0,1.7) 0.09 Some college 0.6 (0.4,0.8) <0.01 Ever had chronic bronchitis, emphysema,or COPD 1.5 (1.1,2.0) <0.01 ing a lower socioeconomic status (based on education and income), being non-white, current or former cigarette smoking, and a history of having chronic bronchitis, emphysema, or COPD. People with workplace exacerbation reported more severe asthma and more days with asthma symptoms, and at the same time did not report more intense asthma care, with the exception of more frequent treatments for asthma attacks. Keeping in mind that the work-exacerbated study participants had a lower socioeconomic status and were more likely to be non-white, they might have received insufficient treatment when presenting with more severe asthma. An elevated prevalence of workplace exacerbation was not limited to the industries chosen a priori to be at high risk. The a priori judgment about high-risk industries was based on a review of findings from other studies that focused on either new-onset asthma or a combination of new-onset and work-exacerbated asthma. 12 21 It might be that the risk of work-related exacerbation of existing asthma is much more widespread than the risk of work-related new-onset asthma. Another possibility is that more sensitive people with asthma select into jobs with fewer exposures, so that the distributions of susceptible individuals are not equal across industries. There are several limitations of the study. One of these limitations is the cross-sectional design. It seems reasonable both that those with more severe asthma are more likely to be impacted by workplace exposures and that exacerbation of asthma due to workplace exposures could contribute to severity. We can not discern from this study how much a report of exacerbation reflects the individual s baseline asthma status (i.e., pre-workplace-exacerbation status) versus worsening after the work-related exacerbation. In a study of adults with asthma that included a follow-up component, both baseline severity and workplace exposures were observed to be associated with partial or complete work disability. 25 Future studies that incorporate a longitudinal phase can contribute to elaborating the temporal relationship between severity of asthma and workplace exacerbation, as well as how other exposures such as cigarette smoking and other respiratory conditions such as chronic bronchitis might contribute to work- related worsening of asthma. The work-related aspect of asthma was not a primary focus of the survey as originally planned, and information about current industry was limited to 54% of the participants who completed the questionnaire. Without more comprehensive work histories, there is no way to examine employment at time of asthma onset for all participants or to fully evaluate the contribution of length of employment in high-risk jobs. In future studies, a more complete work history and specific questions about leaving a job due to work-related respirat o ry problems would help to determine whether selection out of a high-risk job had ever occurred. Another limitation of the study is the lack of information about exposures. Exposures are assumed to have been the same for all people who reported working in the same industry. It is likely that each industry has a broad range of types and levels of exposures. This potential misclassification of exposures could partially explain why higher prevalences of work-related exacerbation were not limited to those industries determined a priori to be at high risk. Workplace exacerbation was based on self-report rather than a more objective standard. It might be possible to validate self-reports by using hand-held portable spirometers to collect serial measurements of peak expiratory flow rate (PEFR) or forced expiratory VOL 8/NO 4,OCT/DEC 2002 Work-related Exacerbation of Asthma 295

volume in one second (FEV 1 ) on both work days and days away from work. Studies conducted in Canada suggest that a symptom diary might be as good as serial PEFR measurements for revealing acute exacerbations of asthma. 26,27 The diagnosis of work-related asthma based on history alone will yield some false positives. For example, Malo and colleagues found that of 104 patients who were rated by a physician at an initial clinical assessment as likely or very likely to have occupational asthma, 63% subsequently had that diagnosis c o n f i r m e d. 28 Baur and colleagues, in Germany, observed that only 32 of 106 study participants with claims of work-related asthmatic symptoms had the diagnosis of asthma confirmed by specific inhalation challenge. 29 The authors proposed that many of these might have been suffering cough and upper airway symptoms rather than symptoms such as shortness of breath and wheezing, which are more indicative of asthma. It is possible that some of those who tested negative on the specific inhalation challenge were tested with the wrong substance. Also, the workers studied by Baur et al. were all applying for worker s compensation and might have been overzealous in claiming workrelated symptoms in order to realize personal financial gain. Adults with asthma solicited for the current survey would not have had the same motivation to claim work-related health problems, partly because it is relatively difficult to obtain worker s compensation for asthma in most states in the United States. Future studies should include a longitudinal component to elaborate the temporal sequence of workplace exacerbation and asthma severity, and how other respiratory conditions and cigarette smoking might contribute to work-related worsening of asthma. The survey instrument should include a more comprehensive work history and questions about leaving or changing work due to asthma. 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