Occupational asthma in Ontario, Canada (2000-2022): A retrospective, clinic-based study evaluating sex differences

Clinical ImplicationsThe findings of our clinic-based study substantiate historical sex difference trends in occupational asthma distribution and exposures and suggest increased disease severity and a trend to a longer time to diagnosis in men compared with women. The findings of our clinic-based study substantiate historical sex difference trends in occupational asthma distribution and exposures and suggest increased disease severity and a trend to a longer time to diagnosis in men compared with women. Asthma is a chronic inflammatory respiratory disease that affects 8% of Canadian adults.1Statistics Canada. Table 13-10-0096-08 Asthma, by age group. 2022. Accessed June 1, 2023. https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=1310009608Google Scholar New-onset asthma precipitated by workplace exposures, termed occupational asthma, is estimated to account for about 16% of cases of adult-onset asthma.2Tarlo S.M. Lemiere C. Occupational asthma.N Engl J Med. 2014; 370: 640-649Crossref PubMed Scopus (283) Google Scholar Studies in occupational asthma have highlighted sex differences in prevalence. A Finnish study of adult-onset asthma cases calculated an occupational-attributable fraction of 29% for men and 17% for women.3Karjalainen A. Kurppa K. Martikainen R. Klaukka T. Karjalainen J. Work is related to a substantial portion of adult-onset asthma incidence in the Finnish population.Am J Respir Crit Care Med. 2001; 164: 565-568Crossref PubMed Google Scholar In Sweden, these rates were estimated to be 17.3% and 5.1% for men and women, respectively.4Torén K. Ekerljung L. Kim J.L. Hillström J. Wennergren G. Rönmark E. et al.Adult-onset asthma in west Sweden--incidence, sex differences and impact of occupational exposures.Respir Med. 2011; 105: 1622-1628Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar Several specific industries and occupations carry an elevated risk for developing occupational asthma and also differ by sex distribution. These have included mining, manufacturing, and construction (male-predominant) and health care and retail trade (female-predominant).2Tarlo S.M. Lemiere C. Occupational asthma.N Engl J Med. 2014; 370: 640-649Crossref PubMed Scopus (283) Google Scholar,3Karjalainen A. Kurppa K. Martikainen R. Klaukka T. Karjalainen J. Work is related to a substantial portion of adult-onset asthma incidence in the Finnish population.Am J Respir Crit Care Med. 2001; 164: 565-568Crossref PubMed Google Scholar Common causative agents of occupational asthma include animal and plant allergens, molds, grains, diisocyanates, wood dusts, acid anhydrides, acrylic monomers, and metals.2Tarlo S.M. Lemiere C. Occupational asthma.N Engl J Med. 2014; 370: 640-649Crossref PubMed Scopus (283) Google Scholar Women are more likely to report exposure to cleaning materials, indoor air pollutants, and mold, whereas men report greater exposure to pyrolysis products, diisocyanates, metals, and flour.5White G.E. Seaman C. Filios M.S. Mazurek J.M. Flattery J. Harrison R.J. et al.Gender differences in work-related asthma: surveillance data from California, Massachusetts, Michigan, and New Jersey, 1993-2008.J Asthma. 2014; 51: 691-702Crossref PubMed Scopus (33) Google Scholar,6Raulf M. Brüning T. Jensen-Jarolim E. van Kampen V. Gender-related aspects in occupational allergies—secondary publication and update.World Allergy Organ J. 2017; 10: 44Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar A 2020 consensus statement published by the European Academy of Allergy and Clinical Immunology outlined key issues on gender and occupational allergy and identified research on this topic as an unmet need.7Moscato G. Apfelbacher C. Brockow K. Eberle C. Genuneit J. Mortz C.G. et al.Gender and occupational allergy: report from the task force of the EAACI Environmental and Occupational Allergy Interest Group.Allergy. 2020; 75: 2753-2763Crossref PubMed Scopus (16) Google Scholar The purpose of our study was to assess sex differences in occupational and clinical characteristics of patients with occupational asthma. We conducted a retrospective study analyzing data from patients with sensitizer-induced occupational asthma seen at occupational disease specialty clinics at 2 tertiary care hospitals in Toronto, Canada, between 2000 and 2022. Patient chart data were obtained using an extraction form (available from the authors on request). The data included results of respiratory investigations and allergy tests performed during patients’ assessments. We identified patients who were diagnosed with work-related asthma and further stratified this group into those with sensitizer-induced occupational asthma and those with work-exacerbated asthma (the latter referring to asthma not specifically caused by workplace exposure(s) but considered to be worsened by them). Our report is confined to the subset of patients with occupational asthma. Our research questions were to elucidate sex differences in time to onset and diagnosis of occupational asthma and severity of occupational asthma, the latter measured by spirometry and methacholine challenge testing. Data analyses were conducted using 2-sided independent samples t tests, median tests, and χ2 tests with Bonferroni post hoc analyses where applicable (SPSS Statistics 27, IBM Corporation, Armonk, NY). The study protocol and chart extraction were approved by research ethics boards. From 2000 through 2022, among a total of 447 patients with chart review, 401 patients were determined to have work-related asthma, of whom 255 were diagnosed with occupational asthma (96 females [38%] and 159 males [62%]). Demographic and occupational characteristics are illustrated in Table I and Table E1 (in this article’s Online Repository at www.jaci-inpractice.org). There were significantly fewer males who were never cigarette smokers than females (47% vs 65%; P = .02). Males were more likely than females to be employed in the automotive industry (22% vs 4%; P = .01), with similar trends in the construction and forestry and wood industries (5% vs 0%; P = .78 for both; data not shown). Females were overrepresented in health care (15% vs 1%; P < .001). Males tended to report diisocyanates more often as culprit asthmagens (26% vs 11%; P = .18), and females cleaning products (13% vs 3%; P = .08), molds and yeasts (9% vs 2%; P = .44), and medications (6% vs 1%; P = .94; data not shown). Male patients were more likely to have had their employment terminated because of their occupational symptoms (24% vs 3%; P = .02).Table IDemographic and occupational characteristics for patients with occupational asthma (frequency with relative percentage, unless otherwise noted)∗The percentage of the response is expressed relative to the number of valid respondents for that specific characteristic.†Bonferroni correction for multiple pairwise comparisons for smoking, industry category, and suspected exposure category. P values included for subrows were initially significant at P < .05 level before correction.CharacteristicFemales (N = 96)Males (N = 159)Overall (N = 255)P valueDemographic Age (y), mean ± SD (N = 96 + 158)47 ± 1048 ± 1148 ± 11.29 Time period of first assessment (N = 95 + 158), n (%).372000-200416 (17)36 (23)52 (21)2005-200911 (12)26 (16)37 (15)2010-201422 (23)25 (16)47 (19)2015-201942 (44)67 (42)109 (43)2020-20214 (4)4 (3)8 (3) Cigarette smoking (N = 96 + 159), n (%).018Current7 (7)24 (15)31 (12).19Previous27 (28)60 (38)87 (34).35Never62 (65)75 (47)137 (54).021 Cigarette pack years, median ± IQR (N = 56 + 98)2 ± 79 ± 195 ± 20.0038Occupational Industry category (N = 71 + 124), n (%)<.001Manufacturing17 (24)37 (30)54 (28)>.99Automotive3 (4)27 (22)30 (15).014Food9 (13)18 (15)27 (14)>.99Service13 (18)7 (6)20 (10).065Chemical8 (11)6 (5)14 (7)>.99Health care11 (15)1 (1)12 (6)<.001Other10 (14)28 (23)38 (19)>.99 Suspected exposure category (N = 80 + 142), n (%)<.001Isocyanates9 (11)37 (26)46 (21).18Flour8 (10)19 (13)27 (12)Metals2 (3)13 (9)15 (7)Plastics, plasticizers, resins, and foams5 (6)9 (6)14 (6)Cleaning products10 (13)4 (3)14 (6).08Other dusts3 (4)10 (7)13 (6)Chemical fumes2 (3)10 (7)12 (5)Woods and wood dusts1 (1)9 (6)10 (5)Molds and yeasts7 (9)3 (2)10 (5).44 Suspected exposure to high- molecular-weight agent (N = 96 + 158), n (%)19 (20)29 (18)48 (19).78 Workplace event precipitating symptoms (N = 49 + 101), n (%)9 (18)10 (10)19 (13).14 Actively working at time of clinic assessment (N = 51 + 101), n (%)41 (80)75 (74)116 (76).40Working with same employer at time of assessment (N = 42 + 80)41 (98)68 (85)109 (89).032Working in same work area at time of assessment (N = 43 + 79)31 (72)53 (67)84 (69).57Ongoing exposure to suspected agent at time of assessment (N = 48 + 93)30 (63)58 (62)88 (62).99Work modification requested (N = 28 + 48)21 (75)34 (71)55 (72).70Employment terminated because of condition (N = 29 + 54)1 (3)13 (24)14 (17).017WSIB‡Ontario Workplace Safety and Insurance Board. claim submitted (N = 51 + 101)37 (73)76 (75)113 (74).72IQR, Interquartile range; WSIB, Workplace Safety and Insurance Board.Bold indicates statistical significance (P < .05).∗ The percentage of the response is expressed relative to the number of valid respondents for that specific characteristic.† Bonferroni correction for multiple pairwise comparisons for smoking, industry category, and suspected exposure category. P values included for subrows were initially significant at P < .05 level before correction.‡ Ontario Workplace Safety and Insurance Board. Open table in a new tab IQR, Interquartile range; WSIB, Workplace Safety and Insurance Board. Bold indicates statistical significance (P < .05). Clinical characteristics and results of respiratory and allergy investigations are presented in Table II and Table E1. Males tended to report a longer latency period between occupational exposure and development of asthmatic symptoms (36 months vs 18 months; P = .11), as well as a longer time to diagnosis (24 months vs 14 months; P = .08) (Table II). Mean FEV1 percent-predicted and forced vital capacity (FVC) percent-predicted were 76% and 89% in males, whereas these values were 84% and 94%, respectively, in females (P = .001 and P = .02) (Table E1). The FEV1/FVC ratio was also lower in males compared with females (68% vs 75%; P < .001) (Table E1). When subanalyses were done for patients who were never-smokers, the sex difference in the FEV1/FVC ratio remained significant, and a greater proportion of males had FEV1/FVC ratios consistent with airflow limitation compared with females (42% vs 20%; P = .008) (Table II). There were no significant differences in peak expiratory flow work variability, severity of airway hyperresponsiveness as determined by PC20 values, and improvement in airway hyperresponsiveness while off-work (Table II). Positivity to allergy skin tests to environmental inhalants and individual suspected culprit allergens was similar (Table E1).Table IIClinical characteristics and respiratory investigations for patients with occupational asthma (frequency with relative percentage, unless otherwise stated)∗The percentage of the response is expressed relative to the number of valid respondents for that specific characteristic.CharacteristicFemales (N = 96)Males (N = 159)Overall (N = 255)P valueClinical features Preexisting asthma diagnosis (N = 93 + 152), n (%)15 (16)17 (11)32 (13).27 Symptomatic preexisting asthma before work symptoms (N = 82 + 133), n (%)12 (15)11 (8)23 (11).14 Use of medication for preexisting asthma (N = 82 + 140), n (%)9 (11)15 (11)24 (11).95 ICS use (N = 95 + 151), n (%)66 (70)116 (77)182 (74).20 Duration of exposure before asthma onset (mo), median ± IQR (N = 86 + 137)17.5 ± 10636 ± 11424 ± 105.11 Total duration of symptoms at time of assessment (mo), median ± IQR (N = 91 + 143)14 ± 3924 ± 6221 ± 51.081Investigations Spirometric characteristics, only never-smoker cases†Reference values, adjusted for sex, age, and height, were used.‡Spirometric characteristics of complete occupational asthma group available in Table E2.FEV1 (N = 59+71), mean ± SD2.41 ± 0.632.93 ± 0.952.70 ± 0.86<.001FEV1 percent-predicted (N = 59 + 71), mean ± SD83.36 ± 17.5876.70 ± 21.0879.72 ± 19.78.056FVC (N = 59 + 71), mean ± SD3.18 ± 0.744.23 ± 1.113.76 ± 1.09<.001FVC percent-predicted (N = 59 + 71), mean ± SD92.34 ± 16.8088.45 ± 19.0690.22 ± 18.11.22FEV1/FVC (N = 59 + 71), mean ± SD75.90 ± 9.1868.75 ± 9.9571.99 ± 10.21<.001FEV1/FVC percent-predicted (N = 31 + 50), mean ± SD90.06 ± 9.9687.64 ± 10.6488.57 ± 10.39.31Airflow obstruction (FEV1/FVC <0.70) (N = 59 + 71), n (%)12 (20)30 (42)42 (32).0078Significant bronchodilator response§Based on American Thoracic Society and Global Initiative for Asthma criteria of a postbronchodilator FEV1 and/or FVC increase of ≥12% and at least 200 mL. (N = 21 + 35), n (%)6 (29)16 (46)22 (39).20 PEFs recorded (N = 96 + 159), n (%)44 (46)81 (51)125 (49).43 PEF work variabilityPEF variability of at least 20% in a day that occurs relatively more frequently at work (taking into account the number of working days vs off-work days); based on the occupational disease physician’s interpretation of PEF data. (N = 44 + 84), n (%)25 (57)49 (58)74 (58).75 Categorized PC20 while working in provoking environmentPEF variability of at least 20% in a day that occurs relatively more frequently at work (taking into account the number of working days vs off-work days); based on the occupational disease physician’s interpretation of PEF data. (N = 67 + 98), n (%).56Normal9 (13)10 (10)19 (12)Borderline18 (27)20 (20)38 (23)Mild14 (21)28 (29)42 (26)Moderate to severe26 (39)40 (41)66 (40) Categorized PC20 while away from work for at least 1 wk¶Based on the American Thoracic Society Guidelines for Methacholine and Exercise Challenge Testing (1999). (N = 44 + 80), n (%).054Normal11 (25)38 (48)49 (40)Borderline16 (36)15 (19)31 (25)Mild10 (23)18 (23)28 (23)Moderate to severe7 (16)9 (11)16 (13) Improvement in PC20 away from work#Categorization based on the American College of Chest Physicians Consensus Statement on Diagnosis and Management of Work-Related Asthma (2008). (N = 30 + 55), n (%).26None1 (3)7 (13)8 (9)Indeterminate5 (17)12 (22)17 (20)Probable7 (23)6 (11)13 (15)Definite17 (57)30 (55)47 (55)ICS, Inhaled corticosteroid; PC20, provocative concentration of methacholine resulting in a 20% decrease in FEV1; PEF, peak expiratory flow.Bold indicates statistical significance (P < .05).∗ The percentage of the response is expressed relative to the number of valid respondents for that specific characteristic.† Reference values, adjusted for sex, age, and height, were used.‡ Spirometric characteristics of complete occupational asthma group available in Table E2.§ Based on American Thoracic Society and Global Initiative for Asthma criteria of a postbronchodilator FEV1 and/or FVC increase of ≥12% and at least 200 mL.|| PEF variability of at least 20% in a day that occurs relatively more frequently at work (taking into account the number of working days vs off-work days); based on the occupational disease physician’s interpretation of PEF data.¶ Based on the American Thoracic Society Guidelines for Methacholine and Exercise Challenge Testing (1999).# Categorization based on the American College of Chest Physicians Consensus Statement on Diagnosis and Management of Work-Related Asthma (2008). Open table in a new tab ICS, Inhaled corticosteroid; PC20, provocative concentration of methacholine resulting in a 20% decrease in FEV1; PEF, peak expiratory flow. Bold indicates statistical significance (P < .05). Given the suggested sex differences in occupational industry and time of diagnosis, we subsequently conducted post hoc analyses for using industries forestry and and and time to diagnosis as Table in this article’s Online Repository at www.jaci-inpractice.org). There were no significant differences in latency to development of asthmatic time to diagnosis, and spirometry between males in industries and those in the FEV1/FVC compared using values from the time of diagnosis, was lower in males with a time to diagnosis greater than months those diagnosed at than to months from onset vs P = .02). In our we data from 255 patients diagnosed with occupational asthma between 2000 and We a greater proportion of females in health care and males in the automotive We report a for longer to onset and to diagnosis for men compared with women. sex, age, and FEV1 and FVC values were significantly lower in males compared with with a greater in FEV1/FVC in were no sex differences in methacholine challenge We that occupational industries and diagnosis have to findings of increased disease severity in males compared with hoc analyses using industries and time to diagnosis as in never-smoker patients suggested the latter to be a because males who a time to diagnosis of greater than months had a lower FEV1/FVC ratio on compared with those with A study identified a median time to diagnosis of for patients with occupational gender was with a longer time to an be related to of and/or M.S. J. S.M. Occupational asthma and work-exacerbated asthma: with time to Full Text Full Text PDF PubMed Scopus Google Scholar in our study include group in occupations and exposures that variability in and rates of occupational for specific testing. of asthma and were also not in these Our findings substantiate historical sex difference trends in occupational asthma distribution and exposures and suggest longer time to diagnosis and increased disease severity in men compared with women. research be work-related that in occupational asthma severity between men and women. Table characteristics and respiratory and allergy investigations for patients with occupational asthma (frequency with relative percentage, unless otherwise noted)∗The percentage of the response is expressed relative to the number of valid respondents for that specific characteristic.†Bonferroni correction for multiple pairwise comparisons for assessment skin agent and specific agent P values included for subrows were initially significant at P < .05 level before correction.CharacteristicFemales (N = 96)Males (N = 159)Overall (N = 255)P valueDemographic (N = 96 + 159), n (N = + n Workplace Safety and Insurance features (N = + n Spirometric values, adjusted for sex, age, and height, were (N = + mean ± ± ± ± percent-predicted (N = + mean ± ± ± ± (N = + mean ± ± ± ± percent-predicted (N = + mean ± ± ± ± (N = + mean ± ± ± ± percent-predicted (N = 49 + mean ± ± ± ± obstruction (FEV1/FVC <0.70) (N = + n bronchodilator on American Thoracic Society and Global Initiative for Asthma criteria of a postbronchodilator FEV1 and/or FVC increase of greater than to and at least 200 mL. (N = + 80), n skin results to environmental inhalants (N = + n skin skin tests performed for suspected agent respondents were to multiple the were (N = + n and and wood specific specific tests done for suspected agent respondents were to multiple (N = 2 + n plasticizers, resins, and Workplace Safety and Insurance Board.Bold indicates statistical significance (P < .05).∗ The percentage of the response is expressed relative to the number of valid respondents for that specific characteristic.† Bonferroni correction for multiple pairwise comparisons for assessment skin agent and specific agent P values included for subrows were initially significant at P < .05 level before correction.‡ Ontario Workplace Safety and Insurance Reference values, adjusted for sex, age, and height, were Based on American Thoracic Society and Global Initiative for Asthma criteria of a postbronchodilator FEV1 and/or FVC increase of greater than to and at least 200 respondents were to multiple the were Open table in a new tab Table and characteristics for never-smoker patients occupational asthma, with industries included forestry and and and time of diagnosis as (frequency with relative percentage, unless otherwise industries as (N = (N = (N = valueDemographic Age (y), mean ± SD (N = + ± ± ± features Duration of exposure before asthma onset (mo), median ± IQR (N = 21 + ± ± ± Total duration of symptoms at time of assessment (mo), median ± IQR (N = + ± ± ± Spirometric values, adjusted for age and height, were (N = + mean ± ± ± ± percent-predicted (N = + mean ± ± ± ± (N = + mean ± ± ± ± percent-predicted (N = + mean ± ± ± ± (N = + mean ± ± ± ± percent-predicted (N = 18 + mean ± ± ± ± obstruction (FEV1/FVC <0.70) (N = + n (%)12 bronchodilator on American Thoracic Society and Global Initiative for Asthma criteria of a postbronchodilator FEV1 and/or FVC increase of ≥12% and at least 200 mL. (N = 14 + n (%)6 of diagnosis as (N = (N = (N = valueDemographic Age (y), mean ± SD (N = 31 + ± ± ± Spirometric values, adjusted for age and height, were (N = 30 + mean ± ± ± ± percent-predicted (N = 30 + mean ± ± ± ± (N = 30 + mean ± ± ± percent-predicted (N = 30 + mean ± ± ± ± (N = 30 + mean ± ± ± ± percent-predicted (N = + mean ± ± ± ± obstruction (FEV1/FVC <0.70) (N = 30 + n (%)15 bronchodilator on American Thoracic Society and Global Initiative for Asthma criteria of a postbronchodilator FEV1 and/or FVC increase of ≥12% and at least 200 mL. (N = 18 + n indicates statistical significance (P < .05).∗ industries included forestry and and Reference values, adjusted for age and height, were used.‡ Based on American Thoracic Society and Global Initiative for Asthma criteria of a postbronchodilator FEV1 and/or FVC increase of ≥12% and at least 200 mL. Open table in a new tab WSIB, Workplace Safety and Insurance Board. Bold indicates statistical significance (P < .05). Bold indicates statistical significance (P < .05).

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