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Cardiovascular disease and long-term occupational exposure to ultrafine particles: A cohort study of airport workers
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Cardiovascular disease and long-term occupational exposure to ultrafine particles: A cohort study of airport workers Karina Lauenborg Møllera,∗, Charlotte Brauerb, Sigurd Mikkelsenb, Jens Peter Bondeb, Steffen Loftc, Karin Helweg-Larsena, Lau Caspar Thygesena a
National Institute of Public Health, University of Southern Denmark, Denmark Department of Occupational and Environmental Medicine, Bispebjerg University Hospital, Copenhagen, Denmark c Section of Environmental Health, Department of Public Health, University of Copenhagen, Denmark b
ARTICLE INFO
ABSTRACT
Keywords: Ultrafine particles Occupational exposure Cardiovascular disease Airport Epidemiology
Aim: To investigate if ischemic heart disease (IHD) and cerebrovascular disease is associated with long-term occupational exposure to ultrafine particles (UFP) outdoors at an airport. Methods and results: This is a register-based follow-up study based on a cohort comprising an exposed group of 6515 men employed in unskilled work at Copenhagen Airport and a reference group of 61,617 men in unskilled work in other firms in greater Copenhagen during 1990–2012. The exposure was assessed from information on proportion of time spent on the airport apron for each calendar year (apron-years) and the primary exposure measure was cumulated apron-years. The cohort was merged to the National Patient Register that includes data on all contacts to public and private hospitals in Denmark and the Register of Causes of Death. Risk estimates were provided by Poisson regression and adjusted for age, calendar year and educational level. We found no associations between cumulative apron-years and IHD (IRR, 1.00; 95%CI, 0.97–1.03) or cerebrovascular disease (IRR, 1.00; 0.98–1.02) when adjusted for confounders. Conclusion: In this large cohort study, we found no association between outdoor occupational exposure to UFP and IHD and cerebrovascular disease.
1. Introduction Air pollution comprises a mixture of gases (i.e. O3, CO, SO2 and NOx), and of particulate matter (PM) that vary in size, from a couple of nanometers to ten microns (Newby et al., 2015; Delfino et al., 2005). In the past years air pollution, especially PM and mainly traffic related pollution has been recognized as independent risk factors for cardiovascular diseases (CVD) (Newby et al., 2015; Du et al., 2016; Weichenthal, 2012; Andersen et al., 2010; Brook et al., 2010). However, only little attention has been given to occupational exposures that may be orders of magnitude higher than environmental exposure (Sjogren et al., 2013; Ibfelt et al., 2010). There are reasons to believe that UFP may be important in the morbidity and mortality of CVD (Delfino et al., 2005). Due to the size, UFP have high alveolar deposition, a large surface area with adhered toxins and can possibly penetrate into blood vessels, which may initiate oxidative stress and inflammation with subsequent atherosclerotic progression and thrombus formation (Newby et al., 2015; Du et al., 2016). Previous studies have shown that in urban environments, motor
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vehicles emissions especially from diesel engines and other combustion processes are the main source of UFP (Delfino et al., 2005; DominguezRodriguez et al., 2011). Also aircraft engines have high emissions of UFP (Hu et al., 2009). In 2010, the Danish Centre for Environment and Energy investigated air pollution on the apron at Copenhagen Airport and found that the level of gasses was below the level measured in the centre of Copenhagen and below the EU-limit values for air quality (ACI EUROPE Environmental Strategy Committee, 2012). However, the level of UFP was two to three times higher than the levels measured in the centre of Copenhagen. At the Airport, about 90% of the measured particles were ultrafine particles (UFP) less than 100 nm (Ellermann et al., 2012). There exist no EU-limit values for particle numbers (ACI EUROPE Environmental Strategy Committee, 2012). At airports ground personnel performs tasks such as aircraft fuel tanking, security, aircraft parking and towing and baggage handling near and around the aircraft often using diesel powered equipment (Ellermann et al., 2012; Cavallo et al., 2006). It is therefore reasonable to believe that airport employees are working in an environment with
Corresponding author. National Institute of Public Health, Øster Farimagsgade 5, Denmark. E-mail address: [email protected] (K.L. Møller).
https://doi.org/10.1016/j.ijheh.2019.08.010 Received 4 June 2019; Received in revised form 22 August 2019; Accepted 26 August 2019 1438-4639/ © 2019 Published by Elsevier GmbH.
Please cite this article as: Karina Lauenborg Møller, et al., International Journal of Hygiene and Environmental Health, https://doi.org/10.1016/j.ijheh.2019.08.010
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high exposure to UFP (Ellermann et al., 2012). Occupational exposure differs from environmental exposures with respect to frequency, duration, and concentration levels and the workforce is in average younger and more healthy than the general population of adults which may influence the risk of CVD (Fang et al., 2010). Some research suggest an association between occupational exposure to PM2.5 (diameter < 2.5 μm) and PM10 (diameter < 10 μm) and CVD (Wiebert et al., 2012) (Sjogren et al., 2013), but no studies on long-term occupational exposure to UFP have been conducted, probably because of the absence of routinely monitoring of UFP in most locations (HEI Review Panel on Ultrafine Particles, 2013). Fang et al., concluded in a systematic literature review that some evidence for an association between PM exposure and the morbidity and mortality of IHD exist (Fang et al., 2010). Moreover, some studies have examined occupational exposure to vehicle exhaust and mortality from IHD (Finkelstein et al., 2004; Laden et al., 2007; Toren et al., 2007) and cerebrovascular diseases (Toren et al., 2007). Because of vehicle exhaust from diesel powered handling equipment this exposure profile may be comparable with the exposure profile at the airport (Ellermann et al., 2012). To our knowledge, no previous study has investigated associations between occupational exposure to UFP at an airport and CVD. The aim of the present study, thus, was to assess the incidence of IHD and cerebrovascular disease in a well-defined cohort with a complete and long follow-up based on hospital discharge diagnoses related to previous UFP-exposure, based on a combination of job title history, personal measurements of particle exposure and expert assessments.
benchmarks and worker representatives with insightful knowledge of the working procedures at the airport assessed the average apron times for the remaining occupational groups. Based on this each occupational groups were attributed an exposure estimate expressed in percent of time worked on the apron, which is described in details elsewhere (Møller et al., 2017). This resulted in 10 occupational exposure groups with different average apron times (Møller et al., 2017). For each person the percentage of time spent on apron was calculated for each year according to entry and exit dates for work (based on job history) in specific occupational groups. e.g. baggage handling for 150 days, and cargo work for 90 days in a calendar year gives (150*0.76 + 90*0.25)/365 = 0.37 apron-years of UFP exposure for that year. Apron-years were cumulated during follow-up resulting in time-dependent apron-years (Møller et al., 2017). 2.3. Outcome The primary outcome was first hospital contact or death due to IHD and cerebrovascular disease. The Danish National Patient Register (NPR) (Lynge et al., 2011), established in 1977, contains data on all hospital admissions in Denmark including administrative information and medical data, e.g. discharge diagnoses (Lynge et al., 2011). From the Danish Register of Causes of Death (Helweg-Larsen, 2011), we obtained information about deaths for persons in the cohort with no former hospital contact due to IHD or cerebrovascular disease. The Danish Register of Causes of Death was electronically established in 1970 and contains information on date of death and the underlying cause of death (Helweg-Larsen, 2011). It is mandatory, by Danish law, for all hospitals to report to the registers (Lynge et al., 2011; HelwegLarsen, 2011). In 1994, Denmark adapted the International Classification System version 10 (ICD-10). Before diagnosis were coded according to ICD-8 (Lynge et al., 2011). By the linkage of the chort to the two registers, we identified all incident cases with a primary or secondary diagnosis of IHD or cerebrovascular disease, or a underlying cause of death due to IHD (ICD-8: 410–414, ICD-10: I20-I25) or cerebrovascular disease (ICD-8: 430–438, ICD-10: I60-I69).
2. Material and method 2.1. Study population and design This study was based on the Copenhagen Airport Cohort, described in details elsewhere (Møller et al., 2017). Briefly, Copenhagen Airport Cohort includes 69,175 men in unskilled jobs either employed at Copenhagen Airport or in other unskilled jobs in the greater Copenhagen area. Only men were included, as Copenhagen Airport employs few women in outdoor jobs. From company employment registers and union membership registers, we obtained a complete occupational history for each person concerning both present and former employment. The exposed group consisted of men who had ever been employed in outdoor jobs on the apron (the area at the airport where aircrafts are parked, unloaded and loaded) at Copenhagen Airport. The reference group consisted of men working indoors at Copenhagen Airport and of men working in unskilled jobs in the greater Copenhagen area.
2.4. Confounding To assess potential confounders we constructed a directed acyclic graph (DAG) (Greenland et al., 1999). Age, calendar year, educational level and smoking were assessed as confounding variables and as the minimal sufficient adjustment set (Greenland et al., 1999). Age (5-years age group), calendar year and educational groups (elementary school, high school, vocational education and higher education) were included in the analysis as categorical variables and were available for the whole cohort. Data on lifestyle were collected from a survey conducted in 2012. The questionnaires were delivered to all baggage handlers and security service personal employed at Copenhagen Airport at April 1, 2012 and to a stratified random sample of the remaining groups meeting the following criteria; had permanent residence in Denmark, age between 25 and 75 and those who were not under research protection (an option in the Danish civil registration). The questionnaires were sent to 5475 men of the cohort whereof 3749 responded (68.5%). From the survey we included information on potential confounding factors including smoking habits, alcohol intake, physical activity and body mass index (BMI). We used these variable as a descriptive background measure to compare the exposed and the referents. The average air pollution at residence were based on calculated distances from residence to the nearest road with annual daily traffic (ADT) of 10,000 vehicles or more. We retrieved the ADT value for the identified road segment and used the presence of a major road (≥10,000 vehicles/day) within 50 m as a proxy for exposure to air pollution at residence (Møller et al., 2017).
2.2. Exposure In a previous study, we measured the UFP number concentration (n/ cm3) by personal monitoring during a workday in combination with time spent on the apron during these measurements using GPS technology (Moller et al., 2014). Measurements were made on 30 employees from the five largest occupational groups at the airport (baggage handlers, catering drivers, cleaning staff, airside security staff and landside security staff (working indoors)). Baggage handlers were exposed to significantly larger average concentrations (geometric mean, GM: 37 × 103 UFP/cm3 compared to employees mainly working indoors (GM: 5 × 103 UFP/cm3) (Moller et al., 2014). Furthermore, catering drivers, cleaning staff and airside security were exposed to concentrations around the same range (GM: 12 × 103 UFP/cm3 to 20 × 103 UFP/cm3). On the apron the measured concentrations were much higher compared to concentrations measured at other locations (Moller et al., 2014). The proportion of daily working hours spent on the apron may therefore serve as a proxy for exposure to UFP. The measured apron time for the five occupational groups were used as 2
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2.5. Statistical analysis
Table 1 Baseline characteristics for the Copenhagen Airport Cohort by the exposed and the reference group.
We followed the cohort from start of employment, 1st January 1990 or immigration after employment, whichever came last, and until first diagnosis or death of IHD or cerebrovascular disease, emigration, other cause of death or end of follow-up (31 December 2012), whichever came first. We excluded persons with a diagnosis of IHD or cerebrovascular disease before 1990 and persons who only had employment after a diagnosis of IHD or cerebrovascular disease. After these exclusions, 68,132 men were eligible for study of IHD and 68,834 men for cerebrovascular disease. In the analyses we included the exposure variable in three different models: 1. the exposed group compared to the reference group; 2. apron-years as a categorical variable (non-exposed, 0.1–2.9 years, 3.0–6.9 years and ≥7 years), based on the quantile distribution (Q1 = 0.8, median = 2.7 and Q3 = 6.7); 3. Apron-years as a continuous linear variable adjusted for the binary variable (exposed/reference group) to evaluate the influence of cumulative apron-years among the exposed group. Proportions, frequencies, medians and quartiles were calculated to describe baseline characteristics for the exposed and the reference group. To analyze the association between exposure and the outcomes we used Poisson regression with log-transformation of person years at risk. 5% significance levels were used. Data were analyzed both unadjusted and adjusted for age, educational level and calendar year. To investigate any effect of more recent exposure on IHD and cerebrovascular disease we did additional analysis and repeated the analysis restricting the exposure time-window to one year. All analyses were performed with SAS 9.3 and 9.4.
Data from registers Variables N Age, median (Q1-Q3) Danish country of origin, n (%) Educational level, n (%) Elementary school High school Vocational education Higher education Marital status, n (%) Married Unmarried Divorced Widow Average pollution at residence Major road within 50 m of residence, n (%)* Data from Survey N Smoking, n (%) No Former Current Units of alcohol per week, n (%) 0 1–21 > 21 BMI, n (%) < 18.5 18.5–25 25.1–30 > 30 Leisure-time physical activity hours/week, n (%) Sedentary Low Medium High
3. Results The cohort studying IHD comprised 6515 in the exposed group and 61,617 in the reference group and provided 983,754 person years at risk (Table 1). The baseline characteristics of the reference- and the exposed group used for analyzing IHD and cerebrovascular disease were almost similar thus data for cerebrovascular disease are not shown. At baseline the median age for the reference group and the exposed group was 31 and 28 years, respectively (Table 1). A larger proportion of the reference group had lower educational levels (56.8% completed elementary school in the reference group compared to 47.1% in the exposed group). In addition, a larger proportion of the reference group was current smokers 32% compared to 27% of the exposed group. Regarding marital status, average pollution at residence the reference group and the exposed group was almost similar. Regarding alcohol, BMI and leisure time of physical activity small differences between the groups were observed (Table 1). In the binary analysis we found a higher incidence of IHD among the reference groups, with a crude incidence rate ratio (IRR) of 1.96 (95% CI; 1.71–2.24) and adjusted IRR = 1.24; 1.08–1.42 compared to the exposed group (Table 2). Regarding cerebrovascular disease we found no significant differences between the groups when adjusted for confounders (Table 3). In the analyses of internal comparison among exposed we found no significant associations between the outcomes and the continuous linear exposure of cumulated apron-years (Tables 2 and 3). In the additional analysis the results only changed slightly and all results were insignificant when adjusted for confounders (Table 4).
Exposed
Reference
6515 28 (24–35) 5482 (86.2)
61,617 31.0 (24–43) 50,483 (83.9)
3068 (47.1) 889 (13.7) 2452 (37.6) 105 (1.6)
34,978 (56.8) 8800 (14.3) 16,531 (26.8) 1308 (2.1)
1740 (26.7) 4399 (67.5) 368 (5.7) 8 (0.1)
19,043 (30.9) 36,348 (59.0) 5564 (9.0) 662 (1.1)
595 (10.3) Exposed
5555 (11.2) Reference
2250
1471
865 (38.7) 766 (34.3) 602 (27.0)
489 (33.4) 504 (34.5) 470 (32.1)
575 (25.9) 1549 (69.7) 100 (4.5)
357 (24.5) 995 (68.2) 106 (7.3)
2 (0.1) 785 (35.3) 1087 (48.5) 366 (16.2)
8 (0.5) 512 (35.5) 658 (45.6) 266 (18.4)
239 (10.7) 782 (35.1) 866 (38.8) (15.3)
184 (12.7) 534 (36.9) 540 (37.3) 341,190 (13.1)
**Major road > 10,000 vehicles/day.
reference group having higher risk than the exposed. In dose-response analyses, we found no significant associations between the cumulated apron-years and the outcomes. No previous study has investigated an association between CVD and occupational exposure to UFP at an airport. A few studies have analyzed mortality from IHD and cerebrovascular diseases and former occupational exposure to vehicle exhaust (Finkelstein et al., 2004; Laden et al., 2007), an exposure profile that may be comparable to the airport due to vehicle powered handling equipment on the apron. In a large cohort study (N = 54,319 men), Laden et al. found an increased mortality rate of IHD (SMR = 1.49; 1.40–1.59) among drivers exposed to vehicle exhaust in the trucking industry and among dockworkers compared to the general U.S. population (Laden et al., 2007). Similarly, Finkelstein et al. observed in a cohort study an increased IHD mortality among heavy construction workers exposed to exhaust from dieselpowered equipment compared to workers in other trades (Finkelstein et al., 2004). The results obtained in the study by Hart et al. suggested an increased risk of mortality due to IHD with increasing years of work, however this was not statistically significant (Hart et al., 2013). Furthermore, Toren et al. found that construction workers exposed to occupational diesel exhaust had an significant increased risk of IHD mortality (IRR = 1.18; 1.13–1.24) but an insignificant association between the mortality of occupational exposure to particulate air pollution cerebrovascular diseases and (IRR = 1.09; 0.99–1.20), compared to unexposed male construction workers (Toren et al., 2007). Generally a weakness in cohort studies with long follow-up is the ability to control for potential confounders related to life style factors (Fang et al., 2010).
4. Discussion The results are based on a large cohort with comprehensive exposure assessment and a well-defined outcome, IHD and cerebrovascular disease, identified by a complete register-based follow-up. We found no sign of increased risk of IHD and cerebrovascular disease associated with exposure to UFP at Copenhagen Airport with the 3
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Table 2 Association between exposure to ultrafine particles and ischemic heart disease, Copenhagen Airport Cohort, 1990–2012. Model 1
2
3
Exposed No Yes p-value Apron-years, categorical Non exposed 0.1–2.9 years 3.0–6.9 years ≥7.0 years p-valueb Apron-years, continuous c Exposed No Yes Cont. linear (per 1 years) p-value
Disease
Person-years
IR
IRR (unadj)
IRR (adj)a
4804 221
902,355.0 81,398.9
532.4 271.5
1.96 (1.71–2.24) 1.00 (ref) < 0.0001
1.24 (1.08–1.42) 1.00 (ref) 0.002
4804 80 53 88
902,355.0 42,635.5 19,589.9 19,173.6
532.4 187.6 270.5 459.0
2.84 (2.27–3.54) 1.00 (ref) 1.44 (1.02–2.04) 2.45 (1.81–3.31) < 0.0001
1.30 1.00 1.03 1.08 0.02
2.81 (2.32–3.40) 1.00 (ref) 1.07 (1.05–1.09) < 0.0001
1.25 (1.02–1.52) 1.00 (ref) 1.00 (0.98–1.02) 0.80
(1.04–1.63) (ref) (0.73–1.46) (0.83–1.52)
Abbreviations: IR, incidence rate per 100,000 person-years; IRR, incidence rate ratio. a Adjusted for age, educational level, calendar year. b The p-value included all four categories. c Also adjusted for exposed (yes/no).
Only the study by Toren et al. controlled for smoking status, but information on smoking status were only available at baseline (Toren et al., 2007). The studies on relationships between occupational exposures to PM and cardiovascular disease are few. One cross-sectional study out of two have reported positive associations, whereas three case-control studies showed some positive association with different occupational PM exposures as summarized in a systematic review (Fang et al., 2010). Similarly, the review also summarized that heart rate variability as marker of short-term autonomic nervous system effects and potential indicator of risk CVD has been associated with occupational exposure to traffic-related particles (Fang et al., 2010). One cohort study has reported on a positive association between occupational exposure to PM and myocardial infarction, especially with size below one μm (Wiebert et al., 2012). The lack of risk associated with UFP exposure in our study might be explained by the fact that the UFP number concentrations at Copenhagen Airport are dominated by emission from jet engines and not from vehicles and diesel exhaust (Ellermann et al., 2012). Unfortunately, the hazards of jet engine emission particles, ideally in comparison with diesel exhaust particles, appear not to have been investigated to further address this issue.
The healthy worker effect is a phenomenon where employees have a lower morbidity and mortality compared to the general population, as healthier individuals to a higher degree gain employment or remain employed (Thygesen et al., 2011; Steenland and Stayner, 1991). In the present study design we carefully restricted the reference population only including men in unskilled positions, thereby minimizing the influence of health worker effect in our study (Thygesen et al., 2011). 4.1. Strengths and limitations A major strength of the present study is the long and complete register-based follow-up made possible by the comprehensive Danish national registers. Thus, we could draw data on contacts to hospitals and deaths by disease specific cause, and include mortality and migration. Furthermore, we established an average quantitative estimate of UFP exposure for the different occupational groups, which we attributed to each person for each calendar year and used as benchmark to estimate the percentage amount of stay on the apron among the remaining groups. By this figure, we increased the precision of estimated exposed apron-years and lowered the risk of misclassification. The study has some limitations. In the construction of the cohort, we used several data sources of different quality to establish employee job
Table 3 Association between exposure to ultrafine particles and cerebrovascular disease, Copenhagen Airport Cohort, 1990–2012. Model 1
2
3
Exposed No Yes p-value Apron-years, categorical Non exposed 0.1–2.9 years 3.0–6.9 years ≥7.0 years p-valueb Apron-years, continuous c Exposed No Yes Cont. linear (per 1 year) p-value
Disease
Person-years
IR
IRR (unadj)
IRR (adj)a
2832 111
924,909.9 82,530.5
306.2 134.5
2.28 (1.88–2.75) 1.00 (ref) < 0.0001
1.17 (0.96–1.42) 1.00 (ref) 0.10
2832 33 33 45
924,909.9 43,030.0 19,853.1 19,647.4
306.2 76.7 166.2 229.0
3.99 (2.83–5.63) 1.00 (ref) 2.17 (1.34–3.51) 2.99 (1.91–4.68) < 0.0001
1.46 1.00 1.56 1.30 0.11
3.52 (2.68–4.64) 1.00 (ref) 1.08 (1.05–1.11) < 0.0001
1.22 (0.92–1.61) 1.00 (ref) 1.00 (0.97–1.03) 0.98
Abbreviations: IR, incidence rate per 100,000 person-years; IRR, incidence rate ratio. a Adjusted for age, educational level, calendar year. b The p-value included all four categories. c Also adjusted for exposed (yes/no). 4
(1.04–2.07) (ref) (0.96–2.52) (0.83–2.05)
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Table 4 Supplementary analyses with 1-year time-window. Association between exposure to ultrafine particles and ischemic heart disease/cerebrovascular disease, Copenhagen Airport Cohort, 1990–2012.
Ischemic heart disease
Cerebrovascular disease
a
Disease
Person-years
IR
IRR (unadj)
IRR (adj)a
Exposed No Yes p-value
4898 127
934,681.8 49,072.1
524.0 258.8
2.02 (1.70–2.41) 1.00 (ref) < 0.0001
1.22 (1.02–1.45) 1.00 (ref) 0.03
Exposed No Yes p-value
2884 59
957,802.5 49,637.87
301.1 118.9
2.53 (1.96–3.28) 1.00 (ref) < 0.0001
1.19 (0.91–1.54) 1.00 (ref) 0.20
Adjusted for age, educational level, calendar year.
histories. However, in the large majority we found good agreement between the different data sources. Hence, we estimate that this bias is small (Moller et al., 2014). It is well documented that misclassification of exposure levels is an essential weakness when using averages (Pekkanen and Kulmala, 2004). Finally, UFP number concentrations and places with high levels as well as individual job functions in the Airport might well have changed over time. These misclassifications are probably non-differential as exposure was assessed independently of the outcomes and thus may have biased the results towards no association. Furthermore, the reference and exposed groups differed with respect to several cardiovascular risk factors, including educational level, physical activity, BMI and smoking history. Indeed, adjustment for the available confounders substantially attenuated the increased risk in the reference group compared to the UFP exposed group and it is possible that the remaining difference in risk was due to residual confounding or inadequate control for smoking status. However, in the analysis where internal comparison group were used the results did not change. Also the test for non-linearity among exposed employees showed in-significant results. In future research it could be interesting to consider methods addressing this study impossibility to control for important confounders. Finally, we did not find an association between occupational exposure to UFP at Copenhagen Airport and the risk of IHD or cerebrovascular diseases, but we cannot reject that such a risk exist. In relation to the relatively young median age in the exposed group and in the reference group, it may be interesting to follow-up the study in 10 or 20 years, including a longer observation time. In addition, this is the first study investigate this association at an airport and more research is needed.
Conflicts of interest None declared. Author responsibility information KLM wrote the first draft of the paper. CB, SM, JPB, SL, KHL, LCT and KM contributed to the design, analyzing, critical discussion of data and revision of the manuscript. All authors have approved the final version of the manuscript. References ACI EUROPE Environmental Strategy Committee, 2012. Ultrafine Particles at Airports. Discussion and Assessment of Ultrafine Particles (UFP) in Aviation and at Airports in. Andersen, Z.J., Olsen, T.S., Andersen, K.K., Loft, S., Ketzel, M., Raaschou-Nielsen, O., 2010. Association between short-term exposure to ultrafine particles and hospital admissions for stroke in Copenhagen, Denmark. Eur. Heart J. 31 (16), 2034–2040. Brook, R.D., Rajagopalan, S., Pope 3rd, C.A., Brook, J.R., Bhatnagar, A., Diez-Roux, A.V., Holguin, F., Hong, Y., Luepker, R.V., Mittleman, M.A., Peters, A., Siscovick, D., Smith Jr., S.C., Whitsel, L., Kaufman, J.D., 2010. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 121 (21), 2331–2378. Cavallo, D., Ursini, C.L., Carelli, G., Iavicoli, I., Ciervo, A., Perniconi, B., Rondinone, B., Gismondi, M., Iavicoli, S., 2006. Occupational exposure in airport personnel: characterization and evaluation of genotoxic and oxidative effects. Toxicology 223 (1–2), 26–35. Delfino, R.J., Sioutas, C., Malik, S., 2005. Potential role of ultrafine particles in associations between airborne particle mass and cardiovascular health. Environ. Health Perspect. 113 (8), 934–946. Dominguez-Rodriguez, A., Abreu-Afonso, J., Rodriguez, S., Juarez-Prera, R.A., ArroyoUcar, E., Jimenez-Sosa, A., Gonzalez, Y., Abreu-Gonzalez, P., Avanzas, P., 2011. Comparative study of ambient air particles in patients hospitalized for heart failure and acute coronary syndrome. Rev. Española Cardiol. 64 (8), 661–666. Du, Y., Xu, X., Chu, M., Guo, Y., Wang, J., 2016. Air particulate matter and cardiovascular disease: the epidemiological, biomedical and clinical evidence. J. Thorac. Dis. 8 (1), E8–e19. Ellermann, T., Massling, A., Løfstrøm, P., Winther, M., Nøjgaard, J., Ketzel, M., 2012. Assesment of the Air Quality at the Apron of Copenhagen Airport Kastrup in Relation to the Working Environment. Fang, S.C., Cassidy, A., Christiani, D.C., 2010. A systematic review of occupational exposure to particulate matter and cardiovascular disease. Int. J. Environ. Res. Public Health 7 (4), 1773–1806. Finkelstein, M.M., Verma, D.K., Sahai, D., Stefov, E., 2004. Ischemic heart disease mortality among heavy equipment operators. Am. J. Ind. Med. 46 (1), 16–22. Greenland, S., Pearl, J., Robins, J.M., 1999. Causal diagrams for epidemiologic research. Epidemiology 10 (1), 37–48. Hart, J.E., Garshick, E., Smith, T.J., Davis, M.E., Laden, F., 2013. Ischaemic heart disease mortality and years of work in trucking industry workers. Occup. Environ. Med. 70 (8), 523–528. HEI Review Panel on Ultrafine Particles, 2013. Understanding the Health Effects of Ambient Ultrafine Particles. In: HEI Perspectives 3. Health Effects Institute, Boston, MA. Helweg-Larsen, K., 2011. The Danish register of causes of death. Scand. J. Public Health 39 (7 Suppl. l), 26–29. Hu, S., Fruin, S., Kozawa, K., Mara, S., Winer, A.M., Paulson, S.E., 2009. Aircraft emission impacts in a neighborhood adjacent to a general aviation airport in southern California. Environ. Sci. Technol. 43 (21), 8039–8045. Ibfelt, E., Bonde, J.P., Hansen, J., 2010. Exposure to metal welding fume particles and risk for cardiovascular disease in Denmark: a prospective cohort study. Occup. Environ.
5. Conclusion In this first large cohort study we found no associations between occupational exposure to UFP at Copenhagen Airport and IHD and cerebrovascular disease. Funding This study was financially supported by the Danish Working Environment Research Fund (Grant Number 22-2011-09). Ethical approval This project did not require approval by a research ethics committee as this, by Danish law, is only mandatory for projects using biological materials (Journal number: H-3-2012-027). 5
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K.L. Møller, et al. Med. 67 (11), 772–777. Laden, F., Hart, J.E., Smith, T.J., Davis, M.E., Garshick, E., 2007. Cause-specific mortality in the unionized U.S. trucking industry. Environ. Health Perspect. 115 (8), 1192–1196. Lynge, E., Sandegaard, J.L., Rebolj, M., 2011. The Danish national patient register. Scand. J. Public Health 39 (7 Suppl. l), 30–33. Moller, K.L., Thygesen, L.C., Schipperijn, J., Loft, S., Bonde, J.P., Mikkelsen, S., Brauer, C., 2014. Occupational exposure to ultrafine particles among airport employees-combining personal monitoring and global positioning system. PLoS One 9 (9), 22 e106671. Møller, K.L., Brauer, C., Mikkelsen, S., Loft, S., Simonsen, E.B., Koblauch, H., Bern, S.H., Alkjær, T., Hertel, O., Becker, T., Larsen, K.H., Bonde, J.P., Thygesen, L.C., 2017 May 6. Copenhagen Airport Cohort: air pollution, manual baggage handling and health. BMJ Open 7 (5), e012651. Newby, D.E., Mannucci, P.M., Tell, G.S., Baccarelli, A.A., Brook, R.D., Donaldson, K., Forastiere, F., Franchini, M., Franco, O.H., Graham, I., Hoek, G., Hoffmann, B., Hoylaerts, M.F., Kunzli, N., Mills, N., Pekkanen, J., Peters, A., Piepoli, M.F., Rajagopalan, S., Storey, R.F., 2015. Expert position paper on air pollution and cardiovascular disease. Eur. Heart J. 36 (2), 83–93b.
Pekkanen, J., Kulmala, M., 2004. Exposure assessment of ultrafine particles in epidemiologic time-series studies. Scand. J. Work Environ. Health 30 (Suppl. 2), 9–18. Sjogren, B., Lonn, M., Fremling, K., Feychting, M., Nise, G., Kauppinen, T., Plato, N., Wiebert, P., Gustavsson, P., 2013. Occupational exposure to particles and incidence of stroke. Scand. J. Work Environ. Health 39 (3), 295–301. Steenland, K., Stayner, L., 1991. The importance of employment status in occupational cohort mortality studies. Epidemiology 2 (6), 418–423. Thygesen, L.C., Hvidtfeldt, U.A., Mikkelsen, S., Bronnum-Hansen, H., 2011. Quantification of the healthy worker effect: a nationwide cohort study among electricians in Denmark. BMC Public Health 11, 571. Toren, K., Bergdahl, I.A., Nilsson, T., Jarvholm, B., 2007. Occupational exposure to particulate air pollution and mortality due to ischaemic heart disease and cerebrovascular disease. Occup. Environ. Med. 64 (8), 515–519. Weichenthal, S., 2012. Selected physiological effects of ultrafine particles in acute cardiovascular morbidity. Environ. Res. 115, 26–36. Wiebert, P., Lonn, M., Fremling, K., Feychting, M., Sjogren, B., Nise, G., Kauppinen, T., Plato, N., Gustavsson, P., 2012. Occupational exposure to particles and incidence of acute myocardial infarction and other ischaemic heart disease. Occup. Environ. Med. 69 (9), 651–657.
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International Journal of Hygiene and Environmental Health journal homepage: www.elsevier.com/locate/ijheh
Cardiovascular disease and long-term occupational exposure to ultrafine particles: A cohort study of airport workers Karina Lauenborg Møllera,∗, Charlotte Brauerb, Sigurd Mikkelsenb, Jens Peter Bondeb, Steffen Loftc, Karin Helweg-Larsena, Lau Caspar Thygesena a
National Institute of Public Health, University of Southern Denmark, Denmark Department of Occupational and Environmental Medicine, Bispebjerg University Hospital, Copenhagen, Denmark c Section of Environmental Health, Department of Public Health, University of Copenhagen, Denmark b
ARTICLE INFO
ABSTRACT
Keywords: Ultrafine particles Occupational exposure Cardiovascular disease Airport Epidemiology
Aim: To investigate if ischemic heart disease (IHD) and cerebrovascular disease is associated with long-term occupational exposure to ultrafine particles (UFP) outdoors at an airport. Methods and results: This is a register-based follow-up study based on a cohort comprising an exposed group of 6515 men employed in unskilled work at Copenhagen Airport and a reference group of 61,617 men in unskilled work in other firms in greater Copenhagen during 1990–2012. The exposure was assessed from information on proportion of time spent on the airport apron for each calendar year (apron-years) and the primary exposure measure was cumulated apron-years. The cohort was merged to the National Patient Register that includes data on all contacts to public and private hospitals in Denmark and the Register of Causes of Death. Risk estimates were provided by Poisson regression and adjusted for age, calendar year and educational level. We found no associations between cumulative apron-years and IHD (IRR, 1.00; 95%CI, 0.97–1.03) or cerebrovascular disease (IRR, 1.00; 0.98–1.02) when adjusted for confounders. Conclusion: In this large cohort study, we found no association between outdoor occupational exposure to UFP and IHD and cerebrovascular disease.
1. Introduction Air pollution comprises a mixture of gases (i.e. O3, CO, SO2 and NOx), and of particulate matter (PM) that vary in size, from a couple of nanometers to ten microns (Newby et al., 2015; Delfino et al., 2005). In the past years air pollution, especially PM and mainly traffic related pollution has been recognized as independent risk factors for cardiovascular diseases (CVD) (Newby et al., 2015; Du et al., 2016; Weichenthal, 2012; Andersen et al., 2010; Brook et al., 2010). However, only little attention has been given to occupational exposures that may be orders of magnitude higher than environmental exposure (Sjogren et al., 2013; Ibfelt et al., 2010). There are reasons to believe that UFP may be important in the morbidity and mortality of CVD (Delfino et al., 2005). Due to the size, UFP have high alveolar deposition, a large surface area with adhered toxins and can possibly penetrate into blood vessels, which may initiate oxidative stress and inflammation with subsequent atherosclerotic progression and thrombus formation (Newby et al., 2015; Du et al., 2016). Previous studies have shown that in urban environments, motor
∗
vehicles emissions especially from diesel engines and other combustion processes are the main source of UFP (Delfino et al., 2005; DominguezRodriguez et al., 2011). Also aircraft engines have high emissions of UFP (Hu et al., 2009). In 2010, the Danish Centre for Environment and Energy investigated air pollution on the apron at Copenhagen Airport and found that the level of gasses was below the level measured in the centre of Copenhagen and below the EU-limit values for air quality (ACI EUROPE Environmental Strategy Committee, 2012). However, the level of UFP was two to three times higher than the levels measured in the centre of Copenhagen. At the Airport, about 90% of the measured particles were ultrafine particles (UFP) less than 100 nm (Ellermann et al., 2012). There exist no EU-limit values for particle numbers (ACI EUROPE Environmental Strategy Committee, 2012). At airports ground personnel performs tasks such as aircraft fuel tanking, security, aircraft parking and towing and baggage handling near and around the aircraft often using diesel powered equipment (Ellermann et al., 2012; Cavallo et al., 2006). It is therefore reasonable to believe that airport employees are working in an environment with
Corresponding author. National Institute of Public Health, Øster Farimagsgade 5, Denmark. E-mail address: [email protected] (K.L. Møller).
https://doi.org/10.1016/j.ijheh.2019.08.010 Received 4 June 2019; Received in revised form 22 August 2019; Accepted 26 August 2019 1438-4639/ © 2019 Published by Elsevier GmbH.
Please cite this article as: Karina Lauenborg Møller, et al., International Journal of Hygiene and Environmental Health, https://doi.org/10.1016/j.ijheh.2019.08.010
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high exposure to UFP (Ellermann et al., 2012). Occupational exposure differs from environmental exposures with respect to frequency, duration, and concentration levels and the workforce is in average younger and more healthy than the general population of adults which may influence the risk of CVD (Fang et al., 2010). Some research suggest an association between occupational exposure to PM2.5 (diameter < 2.5 μm) and PM10 (diameter < 10 μm) and CVD (Wiebert et al., 2012) (Sjogren et al., 2013), but no studies on long-term occupational exposure to UFP have been conducted, probably because of the absence of routinely monitoring of UFP in most locations (HEI Review Panel on Ultrafine Particles, 2013). Fang et al., concluded in a systematic literature review that some evidence for an association between PM exposure and the morbidity and mortality of IHD exist (Fang et al., 2010). Moreover, some studies have examined occupational exposure to vehicle exhaust and mortality from IHD (Finkelstein et al., 2004; Laden et al., 2007; Toren et al., 2007) and cerebrovascular diseases (Toren et al., 2007). Because of vehicle exhaust from diesel powered handling equipment this exposure profile may be comparable with the exposure profile at the airport (Ellermann et al., 2012). To our knowledge, no previous study has investigated associations between occupational exposure to UFP at an airport and CVD. The aim of the present study, thus, was to assess the incidence of IHD and cerebrovascular disease in a well-defined cohort with a complete and long follow-up based on hospital discharge diagnoses related to previous UFP-exposure, based on a combination of job title history, personal measurements of particle exposure and expert assessments.
benchmarks and worker representatives with insightful knowledge of the working procedures at the airport assessed the average apron times for the remaining occupational groups. Based on this each occupational groups were attributed an exposure estimate expressed in percent of time worked on the apron, which is described in details elsewhere (Møller et al., 2017). This resulted in 10 occupational exposure groups with different average apron times (Møller et al., 2017). For each person the percentage of time spent on apron was calculated for each year according to entry and exit dates for work (based on job history) in specific occupational groups. e.g. baggage handling for 150 days, and cargo work for 90 days in a calendar year gives (150*0.76 + 90*0.25)/365 = 0.37 apron-years of UFP exposure for that year. Apron-years were cumulated during follow-up resulting in time-dependent apron-years (Møller et al., 2017). 2.3. Outcome The primary outcome was first hospital contact or death due to IHD and cerebrovascular disease. The Danish National Patient Register (NPR) (Lynge et al., 2011), established in 1977, contains data on all hospital admissions in Denmark including administrative information and medical data, e.g. discharge diagnoses (Lynge et al., 2011). From the Danish Register of Causes of Death (Helweg-Larsen, 2011), we obtained information about deaths for persons in the cohort with no former hospital contact due to IHD or cerebrovascular disease. The Danish Register of Causes of Death was electronically established in 1970 and contains information on date of death and the underlying cause of death (Helweg-Larsen, 2011). It is mandatory, by Danish law, for all hospitals to report to the registers (Lynge et al., 2011; HelwegLarsen, 2011). In 1994, Denmark adapted the International Classification System version 10 (ICD-10). Before diagnosis were coded according to ICD-8 (Lynge et al., 2011). By the linkage of the chort to the two registers, we identified all incident cases with a primary or secondary diagnosis of IHD or cerebrovascular disease, or a underlying cause of death due to IHD (ICD-8: 410–414, ICD-10: I20-I25) or cerebrovascular disease (ICD-8: 430–438, ICD-10: I60-I69).
2. Material and method 2.1. Study population and design This study was based on the Copenhagen Airport Cohort, described in details elsewhere (Møller et al., 2017). Briefly, Copenhagen Airport Cohort includes 69,175 men in unskilled jobs either employed at Copenhagen Airport or in other unskilled jobs in the greater Copenhagen area. Only men were included, as Copenhagen Airport employs few women in outdoor jobs. From company employment registers and union membership registers, we obtained a complete occupational history for each person concerning both present and former employment. The exposed group consisted of men who had ever been employed in outdoor jobs on the apron (the area at the airport where aircrafts are parked, unloaded and loaded) at Copenhagen Airport. The reference group consisted of men working indoors at Copenhagen Airport and of men working in unskilled jobs in the greater Copenhagen area.
2.4. Confounding To assess potential confounders we constructed a directed acyclic graph (DAG) (Greenland et al., 1999). Age, calendar year, educational level and smoking were assessed as confounding variables and as the minimal sufficient adjustment set (Greenland et al., 1999). Age (5-years age group), calendar year and educational groups (elementary school, high school, vocational education and higher education) were included in the analysis as categorical variables and were available for the whole cohort. Data on lifestyle were collected from a survey conducted in 2012. The questionnaires were delivered to all baggage handlers and security service personal employed at Copenhagen Airport at April 1, 2012 and to a stratified random sample of the remaining groups meeting the following criteria; had permanent residence in Denmark, age between 25 and 75 and those who were not under research protection (an option in the Danish civil registration). The questionnaires were sent to 5475 men of the cohort whereof 3749 responded (68.5%). From the survey we included information on potential confounding factors including smoking habits, alcohol intake, physical activity and body mass index (BMI). We used these variable as a descriptive background measure to compare the exposed and the referents. The average air pollution at residence were based on calculated distances from residence to the nearest road with annual daily traffic (ADT) of 10,000 vehicles or more. We retrieved the ADT value for the identified road segment and used the presence of a major road (≥10,000 vehicles/day) within 50 m as a proxy for exposure to air pollution at residence (Møller et al., 2017).
2.2. Exposure In a previous study, we measured the UFP number concentration (n/ cm3) by personal monitoring during a workday in combination with time spent on the apron during these measurements using GPS technology (Moller et al., 2014). Measurements were made on 30 employees from the five largest occupational groups at the airport (baggage handlers, catering drivers, cleaning staff, airside security staff and landside security staff (working indoors)). Baggage handlers were exposed to significantly larger average concentrations (geometric mean, GM: 37 × 103 UFP/cm3 compared to employees mainly working indoors (GM: 5 × 103 UFP/cm3) (Moller et al., 2014). Furthermore, catering drivers, cleaning staff and airside security were exposed to concentrations around the same range (GM: 12 × 103 UFP/cm3 to 20 × 103 UFP/cm3). On the apron the measured concentrations were much higher compared to concentrations measured at other locations (Moller et al., 2014). The proportion of daily working hours spent on the apron may therefore serve as a proxy for exposure to UFP. The measured apron time for the five occupational groups were used as 2
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2.5. Statistical analysis
Table 1 Baseline characteristics for the Copenhagen Airport Cohort by the exposed and the reference group.
We followed the cohort from start of employment, 1st January 1990 or immigration after employment, whichever came last, and until first diagnosis or death of IHD or cerebrovascular disease, emigration, other cause of death or end of follow-up (31 December 2012), whichever came first. We excluded persons with a diagnosis of IHD or cerebrovascular disease before 1990 and persons who only had employment after a diagnosis of IHD or cerebrovascular disease. After these exclusions, 68,132 men were eligible for study of IHD and 68,834 men for cerebrovascular disease. In the analyses we included the exposure variable in three different models: 1. the exposed group compared to the reference group; 2. apron-years as a categorical variable (non-exposed, 0.1–2.9 years, 3.0–6.9 years and ≥7 years), based on the quantile distribution (Q1 = 0.8, median = 2.7 and Q3 = 6.7); 3. Apron-years as a continuous linear variable adjusted for the binary variable (exposed/reference group) to evaluate the influence of cumulative apron-years among the exposed group. Proportions, frequencies, medians and quartiles were calculated to describe baseline characteristics for the exposed and the reference group. To analyze the association between exposure and the outcomes we used Poisson regression with log-transformation of person years at risk. 5% significance levels were used. Data were analyzed both unadjusted and adjusted for age, educational level and calendar year. To investigate any effect of more recent exposure on IHD and cerebrovascular disease we did additional analysis and repeated the analysis restricting the exposure time-window to one year. All analyses were performed with SAS 9.3 and 9.4.
Data from registers Variables N Age, median (Q1-Q3) Danish country of origin, n (%) Educational level, n (%) Elementary school High school Vocational education Higher education Marital status, n (%) Married Unmarried Divorced Widow Average pollution at residence Major road within 50 m of residence, n (%)* Data from Survey N Smoking, n (%) No Former Current Units of alcohol per week, n (%) 0 1–21 > 21 BMI, n (%) < 18.5 18.5–25 25.1–30 > 30 Leisure-time physical activity hours/week, n (%) Sedentary Low Medium High
3. Results The cohort studying IHD comprised 6515 in the exposed group and 61,617 in the reference group and provided 983,754 person years at risk (Table 1). The baseline characteristics of the reference- and the exposed group used for analyzing IHD and cerebrovascular disease were almost similar thus data for cerebrovascular disease are not shown. At baseline the median age for the reference group and the exposed group was 31 and 28 years, respectively (Table 1). A larger proportion of the reference group had lower educational levels (56.8% completed elementary school in the reference group compared to 47.1% in the exposed group). In addition, a larger proportion of the reference group was current smokers 32% compared to 27% of the exposed group. Regarding marital status, average pollution at residence the reference group and the exposed group was almost similar. Regarding alcohol, BMI and leisure time of physical activity small differences between the groups were observed (Table 1). In the binary analysis we found a higher incidence of IHD among the reference groups, with a crude incidence rate ratio (IRR) of 1.96 (95% CI; 1.71–2.24) and adjusted IRR = 1.24; 1.08–1.42 compared to the exposed group (Table 2). Regarding cerebrovascular disease we found no significant differences between the groups when adjusted for confounders (Table 3). In the analyses of internal comparison among exposed we found no significant associations between the outcomes and the continuous linear exposure of cumulated apron-years (Tables 2 and 3). In the additional analysis the results only changed slightly and all results were insignificant when adjusted for confounders (Table 4).
Exposed
Reference
6515 28 (24–35) 5482 (86.2)
61,617 31.0 (24–43) 50,483 (83.9)
3068 (47.1) 889 (13.7) 2452 (37.6) 105 (1.6)
34,978 (56.8) 8800 (14.3) 16,531 (26.8) 1308 (2.1)
1740 (26.7) 4399 (67.5) 368 (5.7) 8 (0.1)
19,043 (30.9) 36,348 (59.0) 5564 (9.0) 662 (1.1)
595 (10.3) Exposed
5555 (11.2) Reference
2250
1471
865 (38.7) 766 (34.3) 602 (27.0)
489 (33.4) 504 (34.5) 470 (32.1)
575 (25.9) 1549 (69.7) 100 (4.5)
357 (24.5) 995 (68.2) 106 (7.3)
2 (0.1) 785 (35.3) 1087 (48.5) 366 (16.2)
8 (0.5) 512 (35.5) 658 (45.6) 266 (18.4)
239 (10.7) 782 (35.1) 866 (38.8) (15.3)
184 (12.7) 534 (36.9) 540 (37.3) 341,190 (13.1)
**Major road > 10,000 vehicles/day.
reference group having higher risk than the exposed. In dose-response analyses, we found no significant associations between the cumulated apron-years and the outcomes. No previous study has investigated an association between CVD and occupational exposure to UFP at an airport. A few studies have analyzed mortality from IHD and cerebrovascular diseases and former occupational exposure to vehicle exhaust (Finkelstein et al., 2004; Laden et al., 2007), an exposure profile that may be comparable to the airport due to vehicle powered handling equipment on the apron. In a large cohort study (N = 54,319 men), Laden et al. found an increased mortality rate of IHD (SMR = 1.49; 1.40–1.59) among drivers exposed to vehicle exhaust in the trucking industry and among dockworkers compared to the general U.S. population (Laden et al., 2007). Similarly, Finkelstein et al. observed in a cohort study an increased IHD mortality among heavy construction workers exposed to exhaust from dieselpowered equipment compared to workers in other trades (Finkelstein et al., 2004). The results obtained in the study by Hart et al. suggested an increased risk of mortality due to IHD with increasing years of work, however this was not statistically significant (Hart et al., 2013). Furthermore, Toren et al. found that construction workers exposed to occupational diesel exhaust had an significant increased risk of IHD mortality (IRR = 1.18; 1.13–1.24) but an insignificant association between the mortality of occupational exposure to particulate air pollution cerebrovascular diseases and (IRR = 1.09; 0.99–1.20), compared to unexposed male construction workers (Toren et al., 2007). Generally a weakness in cohort studies with long follow-up is the ability to control for potential confounders related to life style factors (Fang et al., 2010).
4. Discussion The results are based on a large cohort with comprehensive exposure assessment and a well-defined outcome, IHD and cerebrovascular disease, identified by a complete register-based follow-up. We found no sign of increased risk of IHD and cerebrovascular disease associated with exposure to UFP at Copenhagen Airport with the 3
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Table 2 Association between exposure to ultrafine particles and ischemic heart disease, Copenhagen Airport Cohort, 1990–2012. Model 1
2
3
Exposed No Yes p-value Apron-years, categorical Non exposed 0.1–2.9 years 3.0–6.9 years ≥7.0 years p-valueb Apron-years, continuous c Exposed No Yes Cont. linear (per 1 years) p-value
Disease
Person-years
IR
IRR (unadj)
IRR (adj)a
4804 221
902,355.0 81,398.9
532.4 271.5
1.96 (1.71–2.24) 1.00 (ref) < 0.0001
1.24 (1.08–1.42) 1.00 (ref) 0.002
4804 80 53 88
902,355.0 42,635.5 19,589.9 19,173.6
532.4 187.6 270.5 459.0
2.84 (2.27–3.54) 1.00 (ref) 1.44 (1.02–2.04) 2.45 (1.81–3.31) < 0.0001
1.30 1.00 1.03 1.08 0.02
2.81 (2.32–3.40) 1.00 (ref) 1.07 (1.05–1.09) < 0.0001
1.25 (1.02–1.52) 1.00 (ref) 1.00 (0.98–1.02) 0.80
(1.04–1.63) (ref) (0.73–1.46) (0.83–1.52)
Abbreviations: IR, incidence rate per 100,000 person-years; IRR, incidence rate ratio. a Adjusted for age, educational level, calendar year. b The p-value included all four categories. c Also adjusted for exposed (yes/no).
Only the study by Toren et al. controlled for smoking status, but information on smoking status were only available at baseline (Toren et al., 2007). The studies on relationships between occupational exposures to PM and cardiovascular disease are few. One cross-sectional study out of two have reported positive associations, whereas three case-control studies showed some positive association with different occupational PM exposures as summarized in a systematic review (Fang et al., 2010). Similarly, the review also summarized that heart rate variability as marker of short-term autonomic nervous system effects and potential indicator of risk CVD has been associated with occupational exposure to traffic-related particles (Fang et al., 2010). One cohort study has reported on a positive association between occupational exposure to PM and myocardial infarction, especially with size below one μm (Wiebert et al., 2012). The lack of risk associated with UFP exposure in our study might be explained by the fact that the UFP number concentrations at Copenhagen Airport are dominated by emission from jet engines and not from vehicles and diesel exhaust (Ellermann et al., 2012). Unfortunately, the hazards of jet engine emission particles, ideally in comparison with diesel exhaust particles, appear not to have been investigated to further address this issue.
The healthy worker effect is a phenomenon where employees have a lower morbidity and mortality compared to the general population, as healthier individuals to a higher degree gain employment or remain employed (Thygesen et al., 2011; Steenland and Stayner, 1991). In the present study design we carefully restricted the reference population only including men in unskilled positions, thereby minimizing the influence of health worker effect in our study (Thygesen et al., 2011). 4.1. Strengths and limitations A major strength of the present study is the long and complete register-based follow-up made possible by the comprehensive Danish national registers. Thus, we could draw data on contacts to hospitals and deaths by disease specific cause, and include mortality and migration. Furthermore, we established an average quantitative estimate of UFP exposure for the different occupational groups, which we attributed to each person for each calendar year and used as benchmark to estimate the percentage amount of stay on the apron among the remaining groups. By this figure, we increased the precision of estimated exposed apron-years and lowered the risk of misclassification. The study has some limitations. In the construction of the cohort, we used several data sources of different quality to establish employee job
Table 3 Association between exposure to ultrafine particles and cerebrovascular disease, Copenhagen Airport Cohort, 1990–2012. Model 1
2
3
Exposed No Yes p-value Apron-years, categorical Non exposed 0.1–2.9 years 3.0–6.9 years ≥7.0 years p-valueb Apron-years, continuous c Exposed No Yes Cont. linear (per 1 year) p-value
Disease
Person-years
IR
IRR (unadj)
IRR (adj)a
2832 111
924,909.9 82,530.5
306.2 134.5
2.28 (1.88–2.75) 1.00 (ref) < 0.0001
1.17 (0.96–1.42) 1.00 (ref) 0.10
2832 33 33 45
924,909.9 43,030.0 19,853.1 19,647.4
306.2 76.7 166.2 229.0
3.99 (2.83–5.63) 1.00 (ref) 2.17 (1.34–3.51) 2.99 (1.91–4.68) < 0.0001
1.46 1.00 1.56 1.30 0.11
3.52 (2.68–4.64) 1.00 (ref) 1.08 (1.05–1.11) < 0.0001
1.22 (0.92–1.61) 1.00 (ref) 1.00 (0.97–1.03) 0.98
Abbreviations: IR, incidence rate per 100,000 person-years; IRR, incidence rate ratio. a Adjusted for age, educational level, calendar year. b The p-value included all four categories. c Also adjusted for exposed (yes/no). 4
(1.04–2.07) (ref) (0.96–2.52) (0.83–2.05)
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Table 4 Supplementary analyses with 1-year time-window. Association between exposure to ultrafine particles and ischemic heart disease/cerebrovascular disease, Copenhagen Airport Cohort, 1990–2012.
Ischemic heart disease
Cerebrovascular disease
a
Disease
Person-years
IR
IRR (unadj)
IRR (adj)a
Exposed No Yes p-value
4898 127
934,681.8 49,072.1
524.0 258.8
2.02 (1.70–2.41) 1.00 (ref) < 0.0001
1.22 (1.02–1.45) 1.00 (ref) 0.03
Exposed No Yes p-value
2884 59
957,802.5 49,637.87
301.1 118.9
2.53 (1.96–3.28) 1.00 (ref) < 0.0001
1.19 (0.91–1.54) 1.00 (ref) 0.20
Adjusted for age, educational level, calendar year.
histories. However, in the large majority we found good agreement between the different data sources. Hence, we estimate that this bias is small (Moller et al., 2014). It is well documented that misclassification of exposure levels is an essential weakness when using averages (Pekkanen and Kulmala, 2004). Finally, UFP number concentrations and places with high levels as well as individual job functions in the Airport might well have changed over time. These misclassifications are probably non-differential as exposure was assessed independently of the outcomes and thus may have biased the results towards no association. Furthermore, the reference and exposed groups differed with respect to several cardiovascular risk factors, including educational level, physical activity, BMI and smoking history. Indeed, adjustment for the available confounders substantially attenuated the increased risk in the reference group compared to the UFP exposed group and it is possible that the remaining difference in risk was due to residual confounding or inadequate control for smoking status. However, in the analysis where internal comparison group were used the results did not change. Also the test for non-linearity among exposed employees showed in-significant results. In future research it could be interesting to consider methods addressing this study impossibility to control for important confounders. Finally, we did not find an association between occupational exposure to UFP at Copenhagen Airport and the risk of IHD or cerebrovascular diseases, but we cannot reject that such a risk exist. In relation to the relatively young median age in the exposed group and in the reference group, it may be interesting to follow-up the study in 10 or 20 years, including a longer observation time. In addition, this is the first study investigate this association at an airport and more research is needed.
Conflicts of interest None declared. Author responsibility information KLM wrote the first draft of the paper. CB, SM, JPB, SL, KHL, LCT and KM contributed to the design, analyzing, critical discussion of data and revision of the manuscript. All authors have approved the final version of the manuscript. References ACI EUROPE Environmental Strategy Committee, 2012. Ultrafine Particles at Airports. Discussion and Assessment of Ultrafine Particles (UFP) in Aviation and at Airports in. Andersen, Z.J., Olsen, T.S., Andersen, K.K., Loft, S., Ketzel, M., Raaschou-Nielsen, O., 2010. Association between short-term exposure to ultrafine particles and hospital admissions for stroke in Copenhagen, Denmark. Eur. Heart J. 31 (16), 2034–2040. Brook, R.D., Rajagopalan, S., Pope 3rd, C.A., Brook, J.R., Bhatnagar, A., Diez-Roux, A.V., Holguin, F., Hong, Y., Luepker, R.V., Mittleman, M.A., Peters, A., Siscovick, D., Smith Jr., S.C., Whitsel, L., Kaufman, J.D., 2010. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 121 (21), 2331–2378. Cavallo, D., Ursini, C.L., Carelli, G., Iavicoli, I., Ciervo, A., Perniconi, B., Rondinone, B., Gismondi, M., Iavicoli, S., 2006. Occupational exposure in airport personnel: characterization and evaluation of genotoxic and oxidative effects. Toxicology 223 (1–2), 26–35. Delfino, R.J., Sioutas, C., Malik, S., 2005. Potential role of ultrafine particles in associations between airborne particle mass and cardiovascular health. Environ. Health Perspect. 113 (8), 934–946. Dominguez-Rodriguez, A., Abreu-Afonso, J., Rodriguez, S., Juarez-Prera, R.A., ArroyoUcar, E., Jimenez-Sosa, A., Gonzalez, Y., Abreu-Gonzalez, P., Avanzas, P., 2011. Comparative study of ambient air particles in patients hospitalized for heart failure and acute coronary syndrome. Rev. Española Cardiol. 64 (8), 661–666. Du, Y., Xu, X., Chu, M., Guo, Y., Wang, J., 2016. Air particulate matter and cardiovascular disease: the epidemiological, biomedical and clinical evidence. J. Thorac. Dis. 8 (1), E8–e19. Ellermann, T., Massling, A., Løfstrøm, P., Winther, M., Nøjgaard, J., Ketzel, M., 2012. Assesment of the Air Quality at the Apron of Copenhagen Airport Kastrup in Relation to the Working Environment. Fang, S.C., Cassidy, A., Christiani, D.C., 2010. A systematic review of occupational exposure to particulate matter and cardiovascular disease. Int. J. Environ. Res. Public Health 7 (4), 1773–1806. Finkelstein, M.M., Verma, D.K., Sahai, D., Stefov, E., 2004. Ischemic heart disease mortality among heavy equipment operators. Am. J. Ind. Med. 46 (1), 16–22. Greenland, S., Pearl, J., Robins, J.M., 1999. Causal diagrams for epidemiologic research. Epidemiology 10 (1), 37–48. Hart, J.E., Garshick, E., Smith, T.J., Davis, M.E., Laden, F., 2013. Ischaemic heart disease mortality and years of work in trucking industry workers. Occup. Environ. Med. 70 (8), 523–528. HEI Review Panel on Ultrafine Particles, 2013. Understanding the Health Effects of Ambient Ultrafine Particles. In: HEI Perspectives 3. Health Effects Institute, Boston, MA. Helweg-Larsen, K., 2011. The Danish register of causes of death. Scand. J. Public Health 39 (7 Suppl. l), 26–29. Hu, S., Fruin, S., Kozawa, K., Mara, S., Winer, A.M., Paulson, S.E., 2009. Aircraft emission impacts in a neighborhood adjacent to a general aviation airport in southern California. Environ. Sci. Technol. 43 (21), 8039–8045. Ibfelt, E., Bonde, J.P., Hansen, J., 2010. Exposure to metal welding fume particles and risk for cardiovascular disease in Denmark: a prospective cohort study. Occup. Environ.
5. Conclusion In this first large cohort study we found no associations between occupational exposure to UFP at Copenhagen Airport and IHD and cerebrovascular disease. Funding This study was financially supported by the Danish Working Environment Research Fund (Grant Number 22-2011-09). Ethical approval This project did not require approval by a research ethics committee as this, by Danish law, is only mandatory for projects using biological materials (Journal number: H-3-2012-027). 5
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