Occupational Asthma and Work- Exacerbated Asthma* Factors Associated With Time to Diagnostic Steps

Original Research ASTHMA Occupational Asthma and Work- Exacerbated Asthma* Factors Associated With Time to Diagnostic Steps Marlene S. Santos, MD; Hyejung Jung, MSc; Javad Peyrovi, MD; Wendy Lou, PhD; Gary M. Liss, MD; and Susan M. Tarlo, MBBS, FCCP Background: Little is known regarding the factors associated with the times for patients first physician visit, the first physician suspicion of work-related asthma (WRA), and final diagnosis after the onset of WRA symptoms. This study examined individual and work-related factors that are associated with longer times to these diagnostic milestones among groups with occupational asthma (OA) and work-exacerbated asthma (WEA). Method: Suspected WRA cases were identified from an occupational lung disease clinic and claimants to the Ontario Workplace Safety and Insurance Board (100 patients each). Questionnaire administration and chart review were undertaken. Results: Eighty participants were classified as having sensitizer-induced OA and 87 as having WEA. For the OA group, the risk factors for delay included male sex, being unmarried, low education, and lack of awareness of association of symptoms with work. Other factors included older age, being the sole income earner, and lack of knowledge of the Workplace Hazardous Materials Information System program. For WEA, lower household income, lower education, absence of a health-and-safety program at work, absence of a union, and lack of awareness of OA and of agents at work that could affect asthma significantly increased the time to diagnostic milestones. Conclusions: Different factors affect the diagnostic milestones for OA and WEA. Findings suggest a need for educational programs for workers who are at risk of OA and WEA and a need for further primary care physician education on WRA. (CHEST 2007; 131:1768 1775) Key words: asthma; diagnosis; occupational asthma; socioeconomic factors; work-exacerbated asthma; workplace; workrelated asthma Abbreviations: MSDS material safety data sheet; OA occupational asthma; OR odds ratio; WEA work-exacerbated asthma; WHMIS Workplace Hazardous Materials Information System; WRA work-related asthma; WSIB Workplace Safety and Insurance Board Approximately 13% of the Canadian adult population has been reported to have asthma, and, based on the answers to a questionnaire, 36% of *From the Gage Occupational and Environmental Health Unit (Drs. Santos, Liss, and Tarlo), Toronto, ON, Canada; University of Toronto (Ms. Jung and Dr. Lou), Toronto, ON, Canada; and Toronto Western Hospital (Dr. Peyrovi), Toronto, ON, Canada. Presented in part at the 2005 American Thoracic Society Meeting, San Diego, May 2005. Funded by a research grant provided by the Research Advisory Council of the Workplace Safety and Insurance Board (Ontario). Dr. Tarlo has provided consultation to the Ontario Workplace Safety and Insurance Board (WSIB) and has assessed Ontario WSIB claimants at the request of the Ontario WSIB. The WSIB Research Advisory Council is an independent committee awarding research funds for the Ontario WSIB; this is not thought by the author to be those with adult-onset asthma had possible or probable occupational asthma. 1 Asthma caused by exposure to an agent specific to a workplace and not to a conflict of interest. Drs. Santos, Peyrovi, Lou, and Liss, and Ms. Jung have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Manuscript received October 10, 2006; revision accepted February 12, 2007. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Susan M. Tarlo, MBBS, FCCP, Gage Occupational and Environmental Health Unit, University of Toronto, 223 College St, Toronto, ON, Canada M5T 1R4; e-mail susan.tarlo@utoronto.ca DOI: 10.1378/chest.06-2487 1768 Original Research

stimuli outside the work environment, is termed occupational asthma (OA), 2,3 more strictly distinguishing it from coincidental/concurrent asthma that is aggravated or exacerbated at work, referred to as work-exacerbated asthma (WEA) or work-aggravated asthma. Work-related asthma (WRA) is a term including both OA and WEA. WEA is relatively common, accounting for approximately 50% of accepted WRA compensation claims in Ontario. 4 WEA claims are associated with a relatively short period of time missed from work, 5 and, unlike patients with OA, patients with WEA can often return to their usual workplace with adjustments to reduce exposures to likely airway irritants and/or with optimized asthma medication. A minority of OA cases is due to a large exposure to a respiratory irritant. The clearest example of this was the initial description of reactive airways dysfunction syndrome, 6 but broader criteria for irritantinduced asthma have also been used. 7 More commonly ( 90% in a compensation claim population 4 ), OA is caused by sensitization to a specific work chemical or allergen. 4 The outcome of sensitizerinduced OA improves with early diagnosis and removal from further exposure to the suspected sensitizers. 8 11 Delayed diagnosis, more severe asthma at diagnosis, and prolonged exposure to the workplace agent after the onset of symptoms are associated with persisting asthma and morbidity, including hospitalizations. 12 In Ontario, the average time to the medical diagnosis of OA among workers with compensated Workplace Safety and Insurance Board (WSIB) claims was 2 to 3 years after the onset of symptoms. 4 A pilot study 13 has suggested a link between the average time to medical diagnosis and delays associated with worker/patient-related factors, workplace factors, physician/health-care factors, and compensation factors. To our knowledge, no other studies to date have addressed this in patients with WRA. Therefore, we aimed to identify individual and workplace factors relating to the longer time to diagnosis of OA and WEA. Materials and Methods The Research Ethics Board, the University Health Network, and the University of Toronto provided study approval. Patients with suspected WRA from a occupational lung disease clinic of a teaching hospital, with clinical visits from 2002 to 2004, and additional Ontario WSIB claimants from the same time period completed a questionnaire, which was slightly modified from that used in our pilot study. 13 The questionnaire included age, education level, self-perception of work conditions, and physician factors related to diagnosis. It was administered during the study period by a research assistant to those attending the clinic, just before a clinic visit, and by telephone for the additional WSIB claimants. File extraction included dates and outcomes of physician visits, diagnostic investigations, and exposure agents. Definitions The term sensitizer-induced OA refers to asthma that started during the patient s working life, with symptoms improving on weekends or holidays off work, pulmonary function evidence of asthma (ie, at least 12% postbronchodilator improvement in FEV 1, or a provocative concentration of methacholine causing a 20% fall in FEV 1 8 mg/ml), and exposure to a known or presumed work sensitizer. Subcategories included the following: definite OA, including at least one positive work-related test result, work-related changes on serial peak flow readings, at least a threefold improvement in the provocative concentration of methacholine causing a 20% fall in FEV 1 during a period away from work vs during a work period, a positive skin test response to a relevant sensitizer or positive specific challenge response to a workplace sensitizer, and the absence of conflicting findings; probable OA, including a positive work-related test result but also negative response to another test (eg, positive serial peak flow findings but no significant improvement in methacholine response); and possible OA, a negative result for one objective work-related test, but other tests were not performed or had not been performed by the time of the review. The term WEA refers to physician-diagnosed asthma, in which symptoms are worse at work, and in which there is workplace exposure to respiratory irritants such as dusts, smoke, fumes, or sprays. Excluded from analyses were the following: unrelated asthma (ie, two or more work-related test results were negative); and irritant-induced asthma (based on criteria reported by Brooks et al 6 or modified 5,7 ). Statistical Analysis The outcomes of the analyses (ie, diagnostic milestones) were the time from the onset of work-attributed asthma symptoms to the time of (1) the first physician visit (for OA and WEA), (2) the first physician suspicion of WRA (for OA and WEA), and (3) the final diagnosis (for OA). Personal and workplace variables were examined as possible predictors of outcomes. Data analysis was performed using a statistical software package (SAS, version 9; SAS Institute; Cary, NC). Comparisons between OA and WEA groups for the demographic characteristics, individual and workplace factors, and diagnostic tests were assessed using the t test and the 2 test, or, when appropriate, the Wilcoxon test and the Fisher exact test. In univariate analyses, relationships between each response variable and each explanatory variable were examined with the 2 test for binary variables and with logistic regression analysis for continuous variables. Associations of outcomes with covariates were investigated controlling for age and gender. Since the distributions of the time period durations were skewed, we dichotomized them at the median and considered which predictors were associated with a longer duration (greater than median) [additional details are provided in supplemental material on the Web]. Analyses were repeated with subgroups of those patients with probable or definite OA and in WEA subjects who had been assessed by a specialist (results not shown due to similar trends). Results From 200 participants, 100 were recruited from among 102 consecutive eligible patients in the occuwww.chestjournal.org CHEST / 131 / 6/ JUNE, 2007 1769

pational lung disease clinic, and 100 others from consecutive Ontario WSIB asthma claimants. Eighty participants (40%; 60 clinic patients and 20 WSIB claimants) were classified as having sensitizer-induced OA, as follows: definite sensitizer-induced OA, 23 participants; probable sensitizer-induced OA, 26 participants; and possible sensitizer-induced OA, 31 participants, The most common agents to which sensitizer-induced OA was attributed were diisocyanates (38% of OA cases). The 87 participants (44%) in the WEA group comprised 14 clinic patients and 73 WSIB claimants. Participants with irritant-induced asthma (n 4) and no WRA (n 29) were excluded from the analyses. As shown in Table 1, those with OA, vs WEA, were more likely to be men (p 0.0002) and to have a primary language other than French or English (p 0.001). There was a greater likelihood of having never smoked in those patients with WEA. More OA patients had used Workplace Hazardous Materials Information System (WHMIS) material safety data sheets (MSDSs) and had reported a workplace screening program (31%), as expected with an occupational sensitizer, but a minority of patients had reported undergoing spirometry and responding to screening questionnaires in the workplace. Only 54% of WEA patients had received an assessment from a specialist (ie, pulmonary physician, allergist, or occupational medicine physician) for work-related symptoms at some time compared to all patients with OA (Table 2). The type of physician who was first consulted among 185 patients in the entire group who responded to the question on duration from symptom onset to first physician visit was a family doctor (64%), a company doctor (6%), and a physician in an emergency department or a walk-in clinic (30%). The self-reported median time to the initial physician visit for the patients with WRA symptoms was significantly shorter in patients with WEA ( 1 month) vs those with OA (3 months; p 0.0001). Most patients saw a doctor only when symptoms became worse or unbearable (Table 2); a minority of patients were referred by workplace screening. Only a third of patients with OA had prior knowledge of exposure to a work agent that could cause asthma, but most of these patients said it influenced their decision to see a doctor. Most patients with OA reported that coworkers had similar symptoms, and about a third of these patents were influenced by this. A similar proportion reported being influenced by a workplace health-and-safety program. More patients with WEA than with OA recognized symptoms as being work-related (p 0.02), whereas more patients with OA than with WEA feared a diagnosis would lead to job change (p 0.0001). More WEA patients had gone to an emergency department or a walk-in clinic initially, whereas most Table 1 Demographic Characteristics of Those With OA and WEA* Demographics and Other Characteristics OA Group (n 80) WEA Group (n 87) OR (95% CI) p Value Clinic patient 60 (75) 14 (16) 0.06 (0.03 0.14) 0.0001 Age, yr 46.1 10.5 43.7 10.4 1.02 (0.99 1.05) 0.15 Male gender 47 (59) 26 (30) 0.30 (0.16 0.57) 0.0002 Unmarried 20 (25) 28 (34) 1.53 (0.77 3.02) 0.22 Income level $30,000/yr 17 (22) 18 (21) 0.96 (0.46 2.04) 0.92 Sole source of family income 29 (36) 34 (40) 0.87 (0.46 1.63) 0.66 Primary language English or French 62 (81) 84 (97) 0.15 (0.04 0.53) 0.001 Secondary education and above 71 (90) 82 (94) 0.54 (0.17 1.73) 0.29 Smoking status Ever smoked 44 (55) 34 (39) 1.91 (1.03 3.53) 0.04 Current smoker 11 (24) 10 (29) 0.78 (0.28 2.12) 0.62 Health and safety program 69 (86) 79 (91) 0.64 (0.24 1.67) 0.35 Health and safety training 48 (61) 52 (65) 0.83 (0.44 1.59) 0.58 Union 46 (58) 72 (83) 0.29 (0.14 0.59) 0.0005 Know what WHMIS/MSDS are 72 (90) 78 (90) 1.04 (0.38 2.84) 0.94 WHMIS/MSDS available 60 (83) 72 (92) 0.42 (0.15 1.18) 0.09 If yes, ever used them 51 (71) 42 (54) 2.08 (1.06 4.09) 0.03 Workplace screening 24 (31) 10 (11) 3.42 (1.51 7.74) 0.003 Included questionnaire 15 (63) 3 (43) 2.22 (0.40 12.29) 0.41 Included PFTs 19 (79) 9 (90) 0.42 (0.04 4.16) 0.64 Diisocyanates at work 30 (38) 1 (1) 0.02 (0.003 0.15) 0.0001 *Values are given as No. (% of those answering the question) or mean SD, unless otherwise indicated. PFT pulmonary function test; CI confidence interval. Prediagnosis (in Canadian dollars). 1770 Original Research

Table 2 Individual and Workplace Factors Influencing First Physician Visit and First Physician Suspicion of WRA Among OA and WEA Patients* Variables OA Group (n 80) WEA Group (n 87) OR (95% CI) p Value Symptoms got worse or unbearable 74 (93) 81 (93) 0.91 (0.28 2.96) 0.88 Workplace screening program 24 (31) 10 (11) 3.42 (0.16 3.27) 0.002 Referred through program 7 (29) 4 (36) 0.72 (0.51 7.64) 0.71 Aware of exposure to an agent at work 26 (33) 51 (59) 0.33 (0.18 0.62) 0.0005 Influenced by this 23 (88) 39 (75) 2.56 (0.66 9.93) 0.17 Health and safety program at work influenced visit 24 (36) 14 (19) 2.49 (1.16 5.36) 0.02 Coworkers with similar symptoms 58 (73) 49 (56) 2.04 (1.07 3.91) 0.03 Influenced visit 20 (35) 15 (30) 1.26 (0.56 2.85) 0.58 Knowledge of OA before diagnosis 12 (15) 31 (36) 0.32 (0.15 0.69) 0.003 Influenced visit 10 (77) 27 (84) 0.62 (0.12 3.07) 0.67 Afraid of job change 64 (80) 42 (48) 4.29 (2.15 8.55) 0.0001 Thought symptoms were work-related 52 (66) 71 (82) 0.43 (0.21 0.89) 0.02 Physician asked about work association 48 (60) 52 (62) 0.92 (0.49 1.73) 0.80 Physician first suspected work relation 47 (59) 62 (71) 0.57 (0.30 1.09) 0.09 Physician told by worker of worsening at work 71 (89) 78 (90) 0.91 (0.34 2.42) 0.85 Physician referred immediately 42 (53) 22 (26) 3.11 (1.62 6.00) 0.0006 First physician seen 0.002 Company doctor 6 (8) 1 (1) Family doctor 56 (73) 46 (56) ED/walk-in clinic 15 (19) 35 (43) Most specialized physician seen 0.0001 Pulmonary physician 75 (96) 35 (44) Allergist 1 (1) 5 (6) Occupational physician 2 (3) 3 (4) Family physician 0 (0) 29 (37) ED physician 0 (0) 7 (9) *Values are given as the No. (% of those answering the question). ED emergency department. See Table 1 for abbreviation not used in the text. OA patients initially saw their family doctor. OA patients were more likely to have had an immediate referral to a specialist when WRA was suspected; almost all OA patients had seen a respiratory physician (Table 2). The reported median time to the first suspicion of WRA by a physician was 1 year for WEA patients and 2 years for OA patients. Both groups reported income loss postdiagnosis, which was more marked among OA patients (p 0.045). As expected, objective tests were more common in OA patients. All patients had a medical history consistent with WRA (by definition). Objective support for asthma was evident in chart review for all OA patients but only for 32% of WEA patients (p 0.0001). Test results for the work relationship were present in most OA patients (76%) but only for 11% of WEA patients. The most common tests performed in OA patients were serial peak expiratory flow recordings at work and off work (58%), repeat methacholine challenges during work and off-work periods (49%), and skin tests using a work agent (29%). Only two patients had specific chamber challenges. Factors associated with a longer than median time to the first physician visit after the onset of workrelated symptoms were examined separately among OA and WEA patients (Table 3). Men with WEA were more likely to have a longer than median time to first visit than women (p 0.03). WEA patients were more likely to have a longer time to the first physician visit (adjusted for age and gender) if they feared having to change jobs (p 0.04), lacked awareness of agents at work that could affect their asthma (p 0.04), had no prior knowledge of work and asthma (p 0.002), had no workplace healthand-safety program, health-and-safety training, or union (p 0.003, 0.009, and 0.02, respectively), and had a personal annual income of $30,000 (in Canadian dollars) [p 0.047]. OA subjects were more likely to have a longer time to first physician visit (adjusted for age and gender) if they failed to recognize that symptoms were related to work (p 0.03), were unmarried, (p 0.04), had lived longer in Canada (p 0.001), and had no more than a primary school education (p 0.34). Factors associated with a longer than median time to suspicion of WRA by the physician (as reported by the patient) for OA patients (adjusting for age and gender) [Table 4] were being the sole income earner (p 0.05), not having knowledge of WHMIS www.chestjournal.org CHEST / 131 / 6/ JUNE, 2007 1771

Table 3 Bivariate Analysis of Factors Associated With a Longer Than Median Time to First Physician Visit After Onset of Work-Related Symptoms* Variables OA Group (n 71 ) WEA Group (n 85 ) No. (% ) OR (95% CI) No. (% ) OR (95% CI) Time to first physician visit, mo 8 (12.4) 3 5.7 (21.2) 1 Clinic patient 26 (48) 2.71 (0.79 9.35) 8 (67) 0.25 (0.07 1.00) Male 25 (61) 0.40 (0.15 1.08) 13 (50) 0.35 (0.13 0.92) Age, yr 46.5 (10) 1.03 (0.98 1.07) 44.6 (12) 1.01 (0.96 1.06) Time in Canada, yr 43 (12) 1.08 (1.03 1.14) 43 (12.5) 0.97 (0.90 1.06) Afraid of job loss 20 (44) 0.43 (0.15 1.23) 14 (44) 2.24 (0.85 5.94) Afraid of job change 30 (52) 0.82 (0.23 2.96) 18 (44) 2.76 (1.05 7.27) Afraid to lose work time 23 (43) 0.26 (0.07 0.94) 23 (21) 1.39 (0.38 5.06) Took advice of a friend/family 12 (48) 0.74 (0.26 2.11) 12 (50) 2.70 (0.98 7.44) Workplace screening program 7 (41) 0.62 (0.20 1.98) 2 (20) 0.28 (0.05 1.57) available Aware exposed to an agent 10 (42) 0.57 (0.20 1.64) 13 (26) 0.29 (0.09 0.93) Presence of health and safety 28 (49) 0.88 (0.23 3.30) 20 (27) 0.02 (0.001 0.25) program Prior knowledge of OA 3 (27) 0.25 (0.05 1.20) 3 (10) 0.12 (0.03 0.45) Symptoms thought work-related 19 (42) 0.27 (0.09 0.86) 21 (30) 0.43 (0.13 1.42) Highest education greater than 31 (50) 0.45 (0.08 2.64) 3 (60) 0.51 (0.07 3.63) primary Personal income $30,000/yr# 26 (48) 0.39 (0.09 1.62) 19 (29) 0.31 (0.10 0.99) Sole income earner 13 (59) 1.54 (0.54 4.41) 8 (24) 0.46 (0.17 1.29) First language English or French 34 (60) 26.97 (3.57 203.87) 27 (33) 0.35 (0.02 6.59) Unmarried 12 (71) 0.28 (0.08 0.96) 7 (26) 1.50 (0.53 4.25) Presence of health and safety 30 (50) 0.90 (0.22 3.79) 25 (33) 0.68 (0.14 3.32) committee Health and safety training 21 (48) 0.69 (0.25 1.92) 11 (22) 0.23 (0.08 0.69) Presence of a union 18 (47) 0.77 (0.29 2.05) 19 (27) 0.23 (0.07 0.77) Know what WHMIS/MSDS are 35 (55) 5.92 (0.87 40.09) 25 (33) 0.65 (0.13 3.25) Distance from specialist 60 km 10 (59) 1.47 (0.47 4.66) 8 (62) 3.85 (0.99 14.95) *See Table 1 for abbreviation not used in the text. Number of subjects responding to this outcome variable. Percentage of those answering the question. Values are given as the mean (SD) median. Time units of 1 were assigned a value of 0 in the analyses, p 0.0001. p 0.05. Values are given as the mean (SD). OR indicates effect per unit. #In Canadian dollars. MSDSs (p 0.06), and older age (p 0.009). For WEA patients, associated factors were as follows: physician not asking about a work association with asthma (p 0.006); lack of knowledge of work and asthma by the worker (p 0.007); travel distance of 60 km to reach a specialist (p 0.08); more dependents (p 0.04); and longer period working (p 0.06). The median time to a final diagnosis of OA after the onset of work-related symptoms was 4 years (Table 5). A longer than median time to a final diagnosis was associated with age (p 0.06). After adjusting for age and gender, a shorter than median time to diagnosis was associated with an awareness of exposure to a work agent causing asthma (p 0.05). Surprisingly, a greater likelihood of a longer time to diagnosis was found in those patients who reported the presence of a workplace screening program (p 0.05). Subgroups of patients with more definite diagnoses (meeting the criteria for definite or probable OA and those with WEA who had been assessed by a specialist) showed trends similar to those of the larger groups (results not shown). Age and gender were important covariates in relationship to the time to the initial visit to a doctor. (Variables with a p value of 0.10 in the multivariate model and potential confounders are demonstrated in the online data supplement; Table E1.) In the final model for OA, age (p 0.04), gender (p 0.01), and personal income (p 0.01) remained associated with the time to the initial visit to a doctor. Years having lived in Canada was highly associated with the outcome (p 0.01; odds ratio [OR], 1.12 [ie, the odds of having a longer time to initial visit to a doctor, greater than median of 3 months, increased approximately 12% with each additional year spent living in Canada]). A workplace screening program had bor- 1772 Original Research

Table 4 Bivariate Analysis of Factors Associated With a Longer Than Median Time to First Physician Suspicion of WRA* Variables OA Group (n 79 ) WEA Group (n 35 ) No. (% ) OR (95% CI) No. (% ) OR (95% CI) Time to first physician suspicion, yr 3.8 (4.3) 2 3.7 (7.3) 1 Clinic patient 33 (56) 0.37 (0.12 1.16) 10 (77) 0.02 (0.001 0.28) Age, yr 49.5 (8.7) 1.07 (1.02 1.12) 48.7 (7.5) 1.08 (0.99 1.17) MD asked about work association 27 (56) 2.33 (0.86 6.31) 3 (14) 0.06 (0.01 0.45) Prior knowledge of OA 3 (25) 0.46 (0.11 2.02) 1 (11) 0.02 (0.001 0.34) Highest education greater than 32 (46) 0.64 (0.10 4.00) 11 (33) 0.28 (0.01 13.44) primary Sole income earner 19 (66) 2.69 (0.99 7.31) 3 (20) 0.09 (0.01 0.70) Unmarried 11 (55) 0.72 (0.24 2.15) 2 (20) 5.23 (0.74 36.72) Know what WHMIS/MSDS are 32 (45) 0.12 (0.01 1.13) 11 (35) 0.34 (0.02 7.43) Distance from specialist 60 km 10 (56) 1.96 (0.63 6.04) 5 (63) 8.58 (0.78 94.91) Dependents at symptom onset, No. 1.1 (1.2) 0.84 (0.58 1.24) 1.6 (1.2) 2.84 (1.05 7.65) Work-yr 17.2 (9.2) 1.03 (0.98 1.08) 18.3 (10.6) 1.09 (1.00 1.19) *See Table 1 for abbreviation not used in the text. Number of subjects responding to this outcome variable. Percentage of those answering the question. Values are given as the mean (SD) median. Time units of 1 were assigned a value of 0 in the analyses, p 0.07. p 0.05. Values are given as the mean (SD). OR indicates effect per unit. derline significance (p 0.08). For WEA patients, gender (p 0.04), prior knowledge of WRA (p 0.01), and the presence of a union at the workplace (p 0.05) were significant. Discussion Potential interventions to reduce the time to the diagnosis of WRA include changing regulatory or enforcement policies, better access to compensation, employer education, education of primary treating physicians, and education of pulmonary specialists on the diagnosis and management of WRA. This study extends previous findings 13 by assessing larger groups, including both OA and WEA patients, from populations in clinics and persons who had filed workers compensation claims. Personal and work factors were associated with longer diagnostic milestones. Among those patients with OA, men and those with lower education reported a longer time to first physician visit, perhaps due to greater concerns about the socioeconomic impact. A shorter time to physician assessment and diagnosis was associated with worker knowledge of agents at work that could affect their asthma and the presence of a healthand-safety program, suggesting a benefit from these factors for earlier recognition of WRA. Table 5 Bivariate Analysis of Factors Associated With a Longer Than Median Time to Final Diagnosis of OA From Onset of WRA Symptoms* Variables OA Group (n 77 ) No. (% ) OR (95% CI) Time to final diagnosis, yr 5.0 (4.9) 4 Clinic patient 33 (58) 0.33 (0.11 1.02) Age, yr 48.3 (9.4) 1.04 (1.00 1.09) Took advice of friend/family 10 (34) 0.41 (0.15 1.11) Workplace screening program 16 (67) 2.88 (1.00 8.27) Aware exposed to an agent 8 (31) 0.35 (0.12 0.99) Physician visits before suspecting OA, No. 4.6 (8.6) 1.25 (1.02 1.54) *See Table 1 for abbreviation not used in the text. Number of subjects responding to this outcome variable. Percentage of those answering the question. Values are given as the mean (SD) median. Time units of 1 were assigned a value of 0 in the analyses. Values are given as the mean (SD). OR indicates the effect per unit. p 0.05. www.chestjournal.org CHEST / 131 / 6/ JUNE, 2007 1773

There are several limitations to the interpretation of these data. First, the questionnaire was administered after the diagnosis was reached and is potentially subject to recall bias. As expected, there was a significant difference between the median time to diagnosis of OA and that for WEA (ie, those patients with preexisting asthma should already have had medical follow-up and should have been seen by a physician sooner due to a worsening of their condition), so the potential for inaccurate recollection may be greater among patients in the OA group. The onset of OA may be gradual, and the exact onset date may be difficult to determine. However, the results were assessed separately for each group, and the groups were not directly compared for outcome determinants. OA and WEA groups differed by the source of identification for this study. Those patients with OA were more likely to have a greater amount of information available in their files and to have undergone investigations to confirm the diagnosis, usually requiring specialist referral and reflecting the relative predominance of OA patients from the hospital clinic. In contrast, WEA patients were likely to have received their diagnosis from a primary care physician based on symptoms, 4 and their short time to first physician visit was consistent with an acute exacerbation. 5 Although WEA subjects were most often identified through the Ontario WSIB and OA was most often diagnosed in a hospital-based clinic, OA patients also had WSIB claims. All subjects were clearly informed that the research study would not influence their compensation claim, minimizing the likelihood that responses varied with identification source. The proportions of OA/WEA, although similar to that previously found by us among WSIBaccepted asthma claims, 4 did not necessarily reflect the proportion of WEA among current WSIB-accepted claims since we aimed to enroll similar numbers of patients from the clinic and the WSIB. There could be recall bias in the reporting of workplace factors such as surveillance programs and safety training. However, within each group of OA or WEA patients, there would not be expected to be systematic differences in bias for such reporting. As expected, screening programs at work and diisocyanate exposures were reported more often by the OA group (Ontario has mandated medical surveillance for diisocyanates). Only a minority of patients reported that screening included questionnaires and pulmonary function tests, perhaps reflecting diisocyanate exposure in small companies such as autobody repair shops with difficulty complying with medical surveillance. The short median time to first seeing a physician (1 month) for WEA demonstrates opportunities for physicians to intervene early in the course of WEA, to optimize asthma control, to provide education as to possible work relationships, and to reduce exposures at work to respiratory triggers. Even in OA patients, the 3-month median time to first physician visit suggests opportunities for primary care physicians to question patients about work relationships and to intervene relatively early. Although 53% of those patients with OA reported that their physician referred them for testing as soon as the diagnosis was suspected, further primary care physician education might enhance early referral for more rapid diagnostic testing, thus allowing earlier diagnosis and intervention to improve prognosis. There has been a self-identified need for improved physician knowledge of WRA in Ontario both among primary care physicians and pulmonary specialists. 14 Our findings suggest the need for additional studies to identify factors that may prevent the recognition of WRA. Although the diagnosis is likely to be missed in a significant subset of workers, our study included only those persons who had received a diagnosis of WRA. Factors associated with lack of diagnosis could only be examined in communitybased or worker-based studies. Also, our findings may not be generalizable to workers in countries or regions without universal health-care access or with different physician or compensation systems. ACKNOWLEDGMENT: The authors wish to thank Maya Obadia for assistance with extraction of file data. References 1 Johnson AR, Dimich-Ward HD, Manfreda J, et al. Occupational asthma in adults in six Canadian communities. Am J Respir Crit Care Med 2000; 162:2058 2062 2 Chan-Yeung M, Malo JL, Tarlo SM, et al. Proceedings of the first Jack Pepys Occupational Asthma Symposium. Am J Respir Crit Care Med 2003; 167:450 471 3 Bernstein I, Chan-Yeung M, Malo JL, et al. Asthma in the workplace. 2nd ed. New York, NY: Marcel Dekker, 1999; 1 2 4 Tarlo SM, Liss G, Corey P, et al. A workers compensation claim population for occupational asthma: comparison of subgroups. Chest 1995; 107:634 641 5 Chatkin JM, Tarlo SM, Liss G, et al. The outcome of asthma related to workplace irritant exposures: a comparison of irritant-induced asthma and irritant aggravation of asthma. Chest 1999; 116:1780 1785 6 Brooks SM, Weiss MA, Bernstein IL. Reactive airways dysfunction syndrome (RADS): persistent asthma syndrome after high level irritant exposures. Chest 1985; 88:376 384 7 Tarlo SM, Broder I. Irritant-induced occupational asthma. Chest 1989; 96:297 300 8 Lozewicz S, Assoufi BK, Hawkins R, et al. Outcome of asthma induced by isocyanates. Br J Dis Chest 1987; 81: 14 22 9 Gannon PF, Weir DC, Robertson AS, et al. Health, employment, and financial outcomes in workers with occupational asthma. Br J Ind Med 1993; 50:491 496 10 Lemiere C, Cartier A, Dolovich J, et al. Outcome of specific 1774 Original Research

bronchial responsiveness to occupational agents after removal from exposure. Am J Respir Crit Care Med 1996; 154:329 333 11 Gassert TH, Hu H, Kelsey KT, et al. Long-term health and employment outcomes of occupational asthma and their determinants. J Occup Environ Med 1998; 40:481 491 12 Liss GM, Tarlo SM, MacFarlane Y, et al. Hospitalization among workers compensated for occupational asthma. Am J Respir Crit Care Med 2000; 162:112 118 13 Poonai N, Tarlo SM, van Diepen S, et al. Barriers to diagnosis of occupational asthma in Ontario. Can J Public Health 2005; 96:230 233 14 Tabassum S, Tarlo S, Liss G, et al. Practice Patterns and Educational Assessment of Ontario Respirologists (RPs) for Occupational Lung Disease (OLD) [abstract]. Proc Am Thorac Soc 2005; 2:A443 www.chestjournal.org CHEST / 131 / 6/ JUNE, 2007 1775