Long-Term Exposure to AIR Pollution and COVID-19 Mortality and Morbidity in DENmark: Who Is Most Susceptible? (AIRCODEN).

INTRODUCTION: Early ecological studies have suggested a link between air pollution and Coronavirus Diseases 2019 (COVID-19); however, the evidence from individual-level prospective cohort studies is still sparse. Here, we have examined, in a general population, whether long-term exposure to air pollution is associated with the risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developing severe COVID-19, resulting in hospitalization or death and who is most susceptible. We also examined whether long-term exposure to air pollution is associated with hospitalization or death due to COVID-19 in those who have tested positive for SARS-CoV-2. METHODS: We included all Danish residents 30 years or older who resided in Denmark on March 1, 2020. and followed them in the National COVID-19 Surveillance System until first positive test (incidence), COVID-19 hospitalization, or death until April 26, 2021. We estimated mean levels of nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter <2.5 µm (PM2.5), black carbon (BC), and ozone (O3) at cohort participants' residence in 2019 by the Danish Eulerian Hemispheric Model/Urban Background Model. We used Cox proportional hazard models to estimate the associations of air pollutants with COVID-19 incidence, hospitalization, and mortality adjusting for age, sex, and socioeconomic status (SES) at the individual and area levels. We examined effect modification by age, sex, SES (education, income, wealth, employment), and comorbidities with cardiovascular disease, respiratory disease, acute lower respiratory infections, diabetes, lung cancer, and dementia. We used logistic regression to examine association of air pollutants with COVID-19-related hospitalization or death among SARS-CoV-2 positive patients, adjusting for age, sex, individual- and area-level SES. RESULTS: Of 3,721,810 people, 138,742 were infected, 11,270 hospitalized, and 2,557 died from COVID-19 during 14 months of follow-up. We detected strong positive associations with COVID-19 incidence, with hazard ratio (HR) and 95% confidence interval (CI) of 1.10 (CI: 1.05-1.14) per 0.5-µg/m3 increase in PM2.5 and 1.18 (CI: 1.14-1.23) per 3.6-µg/m3 increase in NO2. For COVID-19 hospitalizations and for COVID-19 deaths, corresponding HRs and 95% CIs were 1.09 (CI: 1.01-1.17) and 1.19 (CI: 1.12-1.27), respectively for PM2.5, and 1.23 (CI: 1.04-1.44) and 1.18 (CI: 1.03-1.34), respectively for NO2. We also found strong positive and statistically significant associations with BC and negative associations with O3. Associations were strongest in those aged 65 years old or older, participants with the lowest SES, and patients with chronic cardiovascular, respiratory, metabolic, lung cancer, and neurodegenerative disease. Among 138,742 individuals who have tested positive for SARS-Cov-2, we detected positive association with COVID-19 hospitalizations (N = 11,270) with odds ratio and 95% CI of 1.04 (CI: 1.01- 1.08) per 0.5-µg/m3 increase in PM2.5 and 1.06 (CI: 1.01-1.12) per 3.6-µg/m3 increase in NO2, but no association with PM with an aerodynamic diameter <10 µm (PM10), BC, or O3, and no association between any of the pollutants and COVID-19 mortality (N = 2,557). CONCLUSIONS: This large nationwide study provides strong new evidence in support of association between long-term exposure to air pollution and COVID-19.

Ultrafine particle exposure for bicycle commutes in rush and non-rush hour traffic: A repeated measures study in Copenhagen, Denmark.

Ultrafine particles (UFP), harmful to human health, are emitted at high levels from motorized traffic. Bicycle commuting is increasingly encouraged to reduce traffic emissions and increase physical activity, but higher breathing rates increase inhaled UFP concentrations while in traffic. We assessed exposure to UFP while cycling along a fixed 8.5 km inner-city route in Copenhagen, on weekdays over six weeks (from September to October 2020), during morning and afternoon rush-hour, as well as morning non-rush-hour, traffic time periods starting from 07:45, 15:45, and 09:45 h, respectively. Continuous measurements were made (each second) of particle number concentration (PNC) and location. PNC levels were summarized and compared across time periods. We used generalized additive models to adjust for meteorological factors, weekdays and trends. A total of 61 laps were completed, during 28 days (∼20 per time period). Overall mean PNC was 18,149 pt/cm3 (range 256-999,560 pt/cm3) with no significant difference between morning rush-hour (18003 pt/cm3), afternoon rush-hour (17560 pt/cm3) and late morning commute (17560 pt/cm3) [p = 0.85]. There was substantial spatial variation of UFP exposure along the route with highest PNC levels measured at traffic intersections (∼38,000-42000 pt/cm3), multiple lane roads (∼38,000-40000 pt/cm3) and construction sites (∼44,000-51000 pt/cm3), while lowest levels were measured at smaller streets, areas with open built environment (∼12,000 pt/cm3), as well as at a bus-only zone (∼15,000 pt/cm3). UFP exposure in inner-city Copenhagen did not differ substantially when bicycling in either rush-hour or non-rush-hour, or morning or afternoon, traffic time periods. UFP exposure varied substantially spatially, with highest concentrations around intersections, multiple lane roads, and construction sites. This suggests that exposure to UFP is not necessarily reduced by avoiding rush-hours, but by avoiding sources of pollution along the bicycling route.

Exposure to ultrafine particles while walking or bicycling during COVID-19 closures: A repeated measures study in Copenhagen, Denmark.

Ultrafine particles (UFP; particulate matter <0.1 µm diameter) emitted from motorized traffic may be highly detrimental to health. Active mobility (walking, bicycling) is increasingly encouraged as a way to reduce traffic congestion and increase physical activity levels. However, it has raised concerns of increased exposure to UFP, due to increased breathing rates in traffic microenvironments, immediately close to their source. The recent Coronavirus Disease 2019 (COVID-19) societal closures reduced commuting needs, allowing a natural experiment to estimate contributions from motorized traffic to UFP exposure while walking or bicycling. From late-March to mid-July 2020, UFP was repeatedly measured while walking or bicycling, capturing local COVID-19 closure ('Phase 0') and subsequent phased re-opening ('Phase 1', '2', '2.1' & '3'). A DiSCmini continuously measured particle number concentration (PNC) in the walker/bicyclist's breathing zone. PNC while walking or bicycling was compared across phased re-openings, and the effect of ambient temperature, wind speed and direction was determined using regression models. Approximately 40 repeated 20-minute walking and bicycling laps were made over 4 months during societal re-opening phases related to the COVID-19 pandemic (late-March to mid-July 2020) in Copenhagen. Highest median PNC exposure of both walking (13,170 pt/cm3, standard deviation (SD): 3560 pt/cm3) and bicycling (21,477 pt/cm3, SD: 8964) was seen during societal closures (Phase 0) and decreased to 5367 pt/cm3 (SD: 2949) and 8714 pt/cm3 (SD: 4309) in Phase 3 of re-opening. These reductions in PNC were mainly explained by meteorological conditions, with most of the deviation explained by wind speed (14-22%) and temperature (10-13%). Highest PNC was observed along major roads and intersections. In conclusion, we observed decreases in UFP exposure while walking and bicycling during societal re-opening phases related to the COVID-19 pandemic, due largely to meteorological factors (e.g., wind speed and temperature) and seasonal variations in UFP levels.

Particulate matter air pollution components and risk for lung cancer.

BACKGROUND: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. METHODS: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. RESULTS: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant. In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 1.25; 95% CI, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m(3)), PM10 S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10 K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S. CONCLUSIONS: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important.

Long-term exposure to traffic-related air pollution and diabetes-associated mortality: a cohort study.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether air pollution from traffic at a residence is associated with mortality related to type 1 or type 2 diabetes. METHODS: We followed up 52,061 participants in the Danish Diet, Cancer and Health cohort for diabetes-related mortality in the nationwide Register of Causes of Death, from baseline in 1993-1997 up to the end of 2009, and traced their residential addresses since 1971 in the Central Population Registry. We used dispersion-modelled concentration of nitrogen dioxide (NO2) since 1971 and amount of traffic at the baseline residence as indicators of traffic-related air pollution and used Cox regression models to estimate mortality-rate ratios (MRRs) with adjustment for potential confounders. RESULTS: Mean levels of NO2 at the residence since 1971 were significantly associated with mortality from diabetes. Exposure above 19.4 µg/m³ (upper quartile) was associated with a MRR of 2.15 (95% CI 1.21, 3.83) when compared with below 13.6 µg/m³ (lower quartile), corresponding to an MRR of 1.31 (95% CI 0.98, 1.76) per 10 µg/m³ NO2 after adjustment for potential confounders. CONCLUSIONS/INTERPRETATION: This study suggests that traffic-related air pollution is associated with mortality from diabetes. If confirmed, reduction in population exposure to traffic-related air pollution could be an additional strategy against the global public health burden of diabetes.

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 microm in diameter (PM(10)) and the concentrations of ultrafine particles, nitrogen dioxide (NO(2)), nitrogen oxide (NO(x)) 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 PM(10), NO(2), NO(x), CO and wheezing symptoms in infants (aged 0-1 year) with a delay of 3-4 days. Only the traffic-related gases (NO(2), NO(x)) 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.

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 (NC(tot), 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 >or=65 years), and due to asthma in children (age 5-18 years). We examined these associations in the presence of PM(10), PM(2.5) (particulate matter <10 and 2.5 microm in diameter, respectively) and ambient gasses. We utilised data on size distribution to calculate NC(tot) for four modes with median diameters 12, 23, 57 and 212 nm, and NC(100) (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 PM(10) and accumulation mode particles with lack of effects for NC(100). For paediatric asthma, accumulation mode particles, NC(100) and nitrogen oxides (mainly from traffic related sources) were relevant, whereas PM(10) 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.

Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy.

The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2.43-7.01) and RR 2.17 (95% CI: 1.42-3.30), respectively (P=0.063). For breast cancers with other prognostic characteristics, the risk was increased equally for the favourable and non favourable types. Current users of HRT experience a two- to four-fold increased risk of breast cancer with various prognostic characteristics, both the favourable and non favourable types. For receptor status, the risk with HRT was statistically significantly higher for hormone receptor-positive breast cancer compared to receptor-negative breast cancer.