Martin Hvidberg

Chronic Obstructive Pulmonary Disease and Long-Term Exposure to Traffic-related Air Pollution: A Cohort Study

RATIONALE Short-term exposure to air pollution has been associated with exacerbation of chronic obstructive pulmonary disease (COPD), whereas the role of long-term exposures on the development of COPD is not yet fully understood. OBJECTIVES We assessed the effect of exposure to traffic-related air pollution over 35 years on the incidence of COPD in a prospective cohort study. METHODS We followed 57,053 participants in the Danish Diet, Cancer, and Health cohort in the Hospital Discharge Register for their first hospital admission for COPD between 1993 and 2006. We estimated the annual mean levels of nitrogen dioxide (NO₂) and nitrogen oxides (NO(x)) at all residential addresses of the cohort participants since 1971 to an event or 2006 and used indicators of traffic near the residential address at recruitment. We assessed the association between exposure to air pollution and COPD incidence by Cox regression analyses for the full cohort, and for participants with and without comorbid conditions, including asthma, diabetes, or cardiovascular disease. MEASUREMENTS AND MAIN RESULTS A first hospital admission for COPD was recorded for 1,786 (3.4%) of 52,799 eligible subjects between recruitment (1993-1997) and 2006. COPD incidence was associated with the 35-year mean NO₂ level (hazard ratio, 1.08; 95% confidence interval, 1.02-1.14, per interquartile range of 5.8 μg/m³), with stronger associations in subjects with diabetes (1.29; 1.05-1.50) and asthma (1.19; 1.03-1.38). CONCLUSIONS Long-term exposure to traffic-related air pollution may contribute to the development of COPD with possibly enhanced susceptibility in people with diabetes and asthma.

Diabetes incidence and long-term exposure to air pollution: a cohort study.

OBJECTIVE Animal and cross-sectional epidemiological studies suggest a link between air pollution and diabetes, whereas the limited prospective data show mixed results. We studied the association between long-term exposure to traffic-related air pollution and incidence of diabetes. RESEARCH DESIGN AND METHODS We followed 57,053 participants of the Danish Diet, Cancer, and Health cohort in the Danish National Diabetes Register between baseline (1993–1997) and 27 June 2006. We estimated the mean levels of nitrogen dioxide (NO2) at the residential addresses of the cohort participants since 1971 and modeled the association between NO2 and diabetes incidence with a Cox regression model, separately for two definitions of diabetes: all cases and a more strict definition where unconfirmed cases were excluded. RESULTS Over a mean follow-up of 9.7 years of 51,818 eligible subjects, there were 4,040 (7.8%) incident diabetes cases in total and 2,877 (5.5%) with confirmed diagnoses. Air pollution was not associated with all diabetes cases (hazard ratio 1.00 [95% CI 0.97–1.04] per interquartile range of 4.9 μg/m3 mean NO2 levels since 1971), but a borderline statistically significant association was detected with confirmed cases of diabetes (1.04 [1.00–1.08]). Among confirmed diabetes cases, effects were significantly enhanced in nonsmokers (1.12 [1.05–1.20]) and physically active people (1.10 [1.03–1.16]). CONCLUSIONS Long-term exposure to traffic-related air pollution may contribute to the development of diabetes, especially in individuals with a healthy lifestyle, nonsmokers, and physically active individuals.

Road traffic noise and stroke: a prospective cohort study

AIMS Epidemiological studies suggest that long-term exposure to road traffic noise increases the risk of cardiovascular disorders. The aim of this study was to investigate the relation between exposure to road traffic noise and risk for stroke, which has not been studied before. METHODS AND RESULTS In a population-based cohort of 57,053 people, we identified 1881 cases of first-ever stroke in a national hospital register between 1993-1997 and 2006. Exposure to road traffic noise and air pollution during the same period was estimated for all cohort members from residential address history. Associations between exposure to road traffic noise and stroke incidence were analysed in a Cox regression model with stratification for gender and calendar-year and adjustment for air pollution and other potential confounders. We found an incidence rate ratio (IRR) of 1.14 for stroke [95% confidence interval (CI): 1.03-1.25] per 10 dB higher level of road traffic noise (L(den)). There was a statistically significant interaction with age (P < 0.001), with a strong association between road traffic noise and stroke among cases over 64.5 years (IRR: 1.27; 95% CI: 1.13-1.43) and no association for those under 64.5 years (IRR: 1.02; 95% CI: 0.91-1.14). CONCLUSION Exposure to residential road traffic noise was associated with a higher risk for stroke among people older than 64.5 years of age.

Lung Cancer Incidence and Long-Term Exposure to Air Pollution from Traffic

Background Previous studies have shown associations between air pollution and risk for lung cancer. Objective We investigated whether traffic and the concentration of nitrogen oxides (NOx) at the residence are associated with risk for lung cancer. Methods We identified 592 lung cancer cases in the Danish Cancer Registry among 52,970 members of the Diet, Cancer and Health cohort and traced residential addresses from 1 January 1971 in the Central Population Registry. We calculated the NOx concentration at each address by dispersion models and calculated the time-weighted average concentration for all addresses for each person. We used Cox models to estimate incidence rate ratios (IRRs) after adjustment for smoking (status, duration, and intensity), environmental tobacco smoke, length of school attendance, occupation, and dietary intake of fruit. Results For the highest compared with the lowest quartile of NOx concentration at the residence, we found an IRR for lung cancer of 1.30 [95% confidence interval (CI), 1.05–1.61], and the IRR for lung cancer in association with living within 50 m of a major road (> 10,000 vehicles/day) was 1.21 (95% CI, 0.95–1.55). The results showed tendencies of stronger associations among nonsmokers, among those with a relatively low fruit intake, and among those with a longer school attendance; only length of school attendance modified the effect significantly. Conclusions This study supports that risk for lung cancer is associated with different markers of air pollution from traffic near the residence.

Air pollution from traffic and cancer incidence: a Danish cohort study

BackgroundVehicle engine exhaust includes ultrafine particles with a large surface area and containing absorbed polycyclic aromatic hydrocarbons, transition metals and other substances. Ultrafine particles and soluble chemicals can be transported from the airways to other organs, such as the liver, kidneys, and brain. Our aim was to investigate whether air pollution from traffic is associated with risk for other cancers than lung cancer.MethodsWe followed up 54,304 participants in the Danish Diet Cancer and Health cohort for 20 selected cancers in the Danish Cancer Registry, from enrolment in 1993-1997 until 2006, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used modeled concentration of nitrogen oxides (NOx) and amount of traffic at the residence as indicators of traffic-related air pollution and used Cox models to estimate incidence rate ratios (IRRs) after adjustment for potential confounders.ResultsNOx at the residence was significantly associated with risks for cervical cancer (IRR, 2.45; 95% confidence interval [CI], 1.01;5.93, per 100 μg/m3 NOx) and brain cancer (IRR, 2.28; 95% CI, 1.25;4.19, per 100 μg/m3 NOx).ConclusionsThis hypothesis-generating study indicates that traffic-related air pollution might increase the risks for cervical and brain cancer, which should be tested in future studies.

Long-term exposure to traffic-related air pollution associated with blood pressure and self-reported hypertension in a Danish cohort.

Background: Short-term exposure to air pollution has been associated with changes in blood pressure (BP) and emergency department visits for hypertension, but little is known about the effects of long-term exposure to traffic-related air pollution on BP and hypertension. Objectives: We studied whether long-term exposure to air pollution is associated with BP and hypertension. Methods: In 1993–1997, 57,053 participants 50–64 years of age were enrolled in a population-based cohort study. Systolic and diastolic BP (SBP and DBP, respectively) were measured at enrollment. Self-reported incident hypertension during a mean follow-up of 5.3 years was assessed by questionnaire. We used a validated dispersion model to estimate residential long-term nitrogen oxides (NOx), a marker of traffic-related air pollution, for the 1- and 5-year periods prior to enrollment and before a diagnosis of hypertension. We conducted a cross-sectional analysis of associations between air pollution and BP at enrollment with linear regression, adjusting for traffic noise, measured short-term NOx, temperature, relative humidity, and potential lifestyle confounders (n = 44,436). We analyzed incident hypertension with Cox regression, adjusting for traffic noise and potential confounders. Results: A doubling of NOx exposure during 1- and 5-year periods preceding enrollment was associated with 0.53-mmHg decreases [95% confidence interval (CI): –0.88, –0.19 mmHg] and 0.50-mmHg decreases (95% CI: –0.84, –0.16 mmHg) in SBP, respectively. Long-term exposure also was associated with a lower prevalence of baseline self-reported hypertension (per doubling of 5-year mean NOx: odds ratio = 0.96; 95% CI: 0.91, 1.00), whereas long-term NOx exposure was not associated with incident self-reported hypertension during follow-up. Conclusions: Long-term exposure to traffic-related air pollution was associated with a slightly lower prevalence of BP at baseline, but was not associated with incident hypertension.

Increased micronuclei and bulky DNA adducts in cord blood after maternal exposures to traffic-related air pollution ☆

Exposure to traffic-related air pollution in urban environment is common and has been associated with adverse human health effects. In utero exposures that result in DNA damage may affect health later in life. Early effects of maternal and in utero exposures to traffic-related air pollution were assessed through the use of validated biomarkers in blood cells from mother-newborn pairs. A cross-sectional biomonitoring study with healthy pregnant women living in the Greater Copenhagen area, Denmark, was conducted. Bulky DNA adducts and micronuclei (MN) were measured in blood from 75 women and 69 umbilical cords, concurrently collected at the time of planned Caesarean section. Modeled residential traffic density, a proxy measure of traffic-related air pollution exposures, was validated by indoor levels of nitrogen dioxide and polycyclic aromatic hydrocarbons in 42 non-smoking homes. DNA adduct levels were similar and positively correlated in maternal and cord blood (1.40 vs. 1.37 n/10(8) nucleotides; r=0.99; p<0.01). Maternal MN frequencies were significantly associated with age (p<0.01), and higher than those of the newborns (7.0 vs. 3.2 MN per 1000 binucleated cells). Adduct levels were highest among mother-newborn pairs who lived near medium-traffic-density (>400-2500 vehicle km/24h; p<0.01) places. MN frequencies among newborns from women who lived at high-traffic-density homes (>2500 vehicle km/24h) were significantly increased (p=0.02). This trend remained after adjusting for potential confounders and effect modifiers. For the first time increased bulky DNA adducts and MN in cord blood after maternal exposures to traffic-related air pollution are found, demonstrating that these transplacental environmental exposures induce DNA damage in newborns. Given that increased DNA damage early in life indicate an increased risk for adverse health effects later in life, these findings justify intervention of pregnant women.

Exposure to road traffic and railway noise and associations with blood pressure and self-reported hypertension: a cohort study

BackgroundEpidemiological studies suggest that long-term exposure to transport noise increases the risk for cardiovascular disorders. The effect of transport noise on blood pressure and hypertension is uncertain.MethodsIn 1993-1997, 57,053 participants aged 50-64 year were enrolled in a population-based cohort study. At enrolment, systolic and diastolic blood pressure was measured. Incident hypertension during a mean follow-up of 5.3 years was assessed by questionnaire. Residential long-term road traffic noise (Lden) was estimated for 1- and 5-year periods preceding enrolment and preceding diagnosis of hypertension. Residential exposure to railway noise was estimated at enrolment. We conducted a cross-sectional analysis of associations between road traffic and railway noise and blood pressure at enrolment with linear regression, adjusting for long-term air pollution, meteorology and potential lifestyle confounders (N = 44,083). Incident self-reported hypertension was analyzed with Cox regression, adjusting for long-term air pollution and potential lifestyle confounders.ResultsWe found a 0.26 mm Hg higher systolic blood pressure (95% confidence intervals (CI): -0.11; 0.63) per 10 dB(A) increase in 1-year mean road traffic noise levels, with stronger associations in men (0.59 mm Hg (CI: 0.13; 1.05) per 10 dB(A)) and older participants (0.65 mm Hg (0.08; 1.22) per 10 dB(A)). Road traffic noise was not associated with diastolic blood pressure or hypertension. Exposure to railway noise above 60 dB was associated with 8% higher risk for hypertension (95% CI: -2%; 19%, P = 0.11).ConclusionsWhile exposure to road traffic noise was associated with systolic blood pressure in subgroups, we were not able to identify associations with hypertension.

Air pollution from traffic and risk for lung cancer in three Danish cohorts.

Background: Air pollution is suspected to cause lung cancer. The purpose was to investigate whether the concentration of nitrogen oxides (NOx) at the residence, used as an indicator of air pollution from traffic, is associated with risk for lung cancer. Methods: We identified 679 lung cancer cases in the Danish Cancer Registry from the members of three prospective cohorts and selected a comparison group of 3,481 persons from the same cohorts in a case-cohort design. Residential addresses from January 1, 1971, were traced in the Central Population Registry. The NOx concentration at each address was calculated by dispersion models, and the time-weighted average concentration for all addresses was calculated for each person. We used Cox models to estimate incidence rate ratios after adjustment for smoking (status, duration, and intensity), educational level, body mass index, and alcohol consumption. Results: The incidence rate ratios for lung cancer were 1.30 [95% confidence interval (95% CI), 1.07-1.57] and 1.45 (95% CI, 1.12-1.88) for NOx concentrations of 30 to 72 and >72 μg/m3, respectively, when compared with <30 μg/m3. This corresponds to a 37% (95% CI, 6-76%) increase in incidence rate ratio per 100 μg/m3 NOx. The results showed no significant heterogeneity in the incidence rate ratio for lung cancer between cohorts or between strata defined by gender, educational level, or smoking status. Conclusion: The study showed a modest association between air pollution from traffic and the risk for lung cancer. Impact: This study points at traffic as a source of carcinogenic air pollution and stresses the importance of strategies for reduction of population exposure to traffic-related air pollution. Cancer Epidemiol Biomarkers Prev; 19(5); 1284–91. ©2010 AACR.

Stroke and Long-Term Exposure to Outdoor Air Pollution From Nitrogen Dioxide: A Cohort Study

Background and Purpose— Years of exposure to tobacco smoke substantially increase the risk for stroke. Whether long-term exposure to outdoor air pollution can lead to stroke is not yet established. We examined the association between long-term exposure to traffic-related air pollution and incident and fatal stroke in a prospective cohort study. Methods— We followed 57 053 participants of the Danish Diet, Cancer and Health cohort in the Hospital Discharge Register for the first-ever hospital admission for stroke (incident stroke) between baseline (1993–1997) and 2006 and defined fatal strokes as death within 30 days of admission. We associated the estimated mean levels of nitrogen dioxide at residential addresses since 1971 to incident and fatal stroke by Cox regression analyses and examined the effects by stroke subtypes: ischemic, hemorrhagic, and nonspecified stroke. Results— Over a mean follow-up of 9.8 years of 52 215 eligible subjects, there were 1984 (3.8%) first-ever (incident) hospital admissions for stroke of whom 142 (7.2%) died within 30 days. We detected borderline significant associations between mean nitrogen dioxide levels at residence since 1971 and incident stroke (hazard ratio, 1.05; 95% CI, 0.99–1.11, per interquartile range increase) and stroke hospitalization followed by death within 30 days (1.22; 1.00–1.50). The associations were strongest for nonspecified and ischemic strokes, whereas no association was detected with hemorrhagic stroke. Conclusions— Long-term exposure to traffic-related air pollution may contribute to the development of ischemic but not hemorrhagic stroke, especially severe ischemic strokes leading to death within 30 days.