Matthias Ketzel

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.

Size distribution and total number concentration of ultrafine and accumulation mode particles and hospital admissions in children and the elderly in Copenhagen, Denmark

Objectives: To study the association between short-term exposure to ultrafine particles and morbidity in Copenhagen, Denmark. Methods: We studied the association between urban background levels of the total number concentration of particles (NCtot, 6–700 nm in diameter) measured at a single site (15 May 2001 to 31 December 2004) and hospital admissions due to cardiovascular (CVD) and respiratory disease (RD) in the elderly (age ⩾65 years), and due to asthma in children (age 5–18 years). We examined these associations in the presence of PM10, PM2.5 (particulate matter <10 and 2.5 µm in diameter, respectively) and ambient gasses. We utilised data on size distribution to calculate NCtot for four modes with median diameters 12, 23, 57 and 212 nm, and NC100 (number concentration of particles <100 nm in diameter) and examined their associations with health outcomes. We used a time series Poisson generalised additive model adjusted for overdispersion, season, day of the week, public holidays, school holidays, influenza, pollen and meteorology, with up to 5 days’ lagged exposure. Results and conclusions: The adverse health effects of particulate matter on CVD and RD hospital admissions in the elderly were mainly mediated by PM10 and accumulation mode particles with lack of effects for NC100. For paediatric asthma, accumulation mode particles, NC100 and nitrogen oxides (mainly from traffic related sources) were relevant, whereas PM10 appeared to have little effect. Our results suggest that particle volume/mass from long-range transported air pollution is relevant for CVD and RD admissions in the elderly, and possibly particle numbers from traffic sources for paediatric asthma.

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.

Association between short-term exposure to ultrafine particles and hospital admissions for stroke in Copenhagen, Denmark

AIMS The relevance of ultrafine particles (UFPs, particles <0.1 microm diameter), the smallest fraction of ambient particulate matter, on stroke morbidity has not been documented. We studied the effects of short-term changes in exposure to these particles on stroke, separately for ischaemic and haemorrhagic strokes, mild and severe strokes, and ischaemic strokes with (likely embolic) and without (likely thrombotic) atrial fibrillation (AF). METHODS AND RESULTS We used a time-stratified case-crossover design to study the association between short-term exposure to UFPs, particulate matter <10 microm in diameter (PM(10)), nitrogen oxides (NO(x)) and carbon monoxide (CO) (measured at single background station) and hospital admissions for stroke in Copenhagen (2003-2006). Of 7485 stroke admissions, 6798 were ischaemic and 687 haemorrhagic, 3485 mild, and 2248 severe. Of the ischaemic stroke cases, 1204 had AF and 5273 did not. We found significant positive association with exposure to UFPs, NO(x) and CO, and ischaemic strokes, and UFPs and NO(x) and mild strokes, 4 days before admission. The strongest associations were with UFPs. Exposure to UFPs lead to a 21% increase in hospital admissions (per interquartile range of 5-day averages; 95% confidence interval 4-41%) for mild ischaemic stroke of without AF (likely thrombotic origin). CONCLUSION Our results indicate possible effects of traffic-related air pollution, mainly UFPs, on hospital admissions for ischaemic stroke, especially for mild ischaemic stroke of likely thrombotic origin (without AF). These are novel findings regarding the relevance of UFPs and the heterogeneous effect of air pollution on the severity and origin of stroke, and need confirmation by other data.

Ambient Air Pollution Triggers Wheezing Symptoms in Infants

Background: There is limited evidence for the role of air pollution in the development and triggering of wheezing symptoms in young children. A study was undertaken to examine the effect of exposure to air pollution on wheezing symptoms in children under the age of 3 years with genetic susceptibility to asthma. Methods: Daily recordings of symptoms were obtained for 205 children participating in the birth cohort study Copenhagen Prospective Study on Asthma in Children and living in Copenhagen for the first 3 years of life. Daily air pollution levels for particulate matter <10 μm in diameter (PM10) and the concentrations of ultrafine particles, nitrogen dioxide (NO2), nitrogen oxide (NOx) and carbon monoxide (CO) were available from a central background monitoring station in Copenhagen. The association between incident wheezing symptoms and air pollution on the concurrent and previous 4 days was estimated by a logistic regression model (generalised estimating equation) controlling for temperature, season, gender, age, exposure to smoking and paternal history of asthma. Results: Significant positive associations were found between concentrations of PM10, NO2, NOx, CO and wheezing symptoms in infants (aged 0–1 year) with a delay of 3–4 days. Only the traffic-related gases (NO2, NOx) showed significant effects throughout the 3 years of life, albeit attenuating after the age of 1 year. Conclusions: Air pollution related to traffic is significantly associated with triggering of wheezing symptoms in the first 3 years of life.

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.

Traffic air pollution and mortality from cardiovascular disease and all causes: a Danish cohort study

BackgroundTraffic air pollution has been linked to cardiovascular mortality, which might be due to co-exposure to road traffic noise. Further, personal and lifestyle characteristics might modify any association.MethodsWe followed up 52 061 participants in a Danish cohort for mortality in the nationwide Register of Causes of Death, from enrollment in 1993–1997 through 2009, and traced their residential addresses from 1971 onwards in the Central Population Registry. We used dispersion-modelled concentration of nitrogen dioxide (NO2) since 1971 as indicator of traffic air pollution and used Cox regression models to estimate mortality rate ratios (MRRs) with adjustment for potential confounders.ResultsMean levels of NO2 at the residence since 1971 were significantly associated with mortality from cardiovascular disease (MRR, 1.26; 95% confidence interval [CI], 1.06–1.51, per doubling of NO2 concentration) and all causes (MRR, 1.13; 95% CI, 1.04–1.23, per doubling of NO2 concentration) after adjustment for potential confounders. For participants who ate < 200 g of fruit and vegetables per day, the MRR was 1.45 (95% CI, 1.13–1.87) for mortality from cardiovascular disease and 1.25 (95% CI, 1.11–1.42) for mortality from all causes.ConclusionsTraffic air pollution is associated with mortality from cardiovascular diseases and all causes, after adjustment for traffic noise. The association was strongest for people with a low fruit and vegetable intake.

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.