Use of candles and risk of cardiovascular and respiratory events in a Danish cohort study.

Burning candles at home emit small particles and gases that pollute indoor air. Exposure to fine particles in outdoor air has been convincingly linked to cardiovascular and respiratory events, while the associations with fine and ultrafine particles from candle burning remain unexplored. We examined the association between the use of candles and incident cardiovascular and respiratory events. We collected data on 6757 participants of the Copenhagen Aging and Midlife Biobank cohort recruited in 2009 and followed them up for the first hospital contact for incident cardiovascular and respiratory events until 2018. We investigated an association between the self-reported frequency of candle use in wintertime and cardiovascular and respiratory events, using Cox regression models adjusting for potential confounders. During follow-up, 1462 and 834 were admitted for cardiovascular and respiratory events, respectively. We found null associations between candle use and a hospital contact due to cardiovascular and respiratory events, with hazard ratios (HRs) and 95% confidence intervals (CI) of 0.97 (95% CI: 0.84, 1.11) and 0.98 (95% CI: 0.81, 1.18), respectively, among those using candles >4 times/week compared with <1 time/week. For cause-specific cardiovascular diseases, HRs were 1.10 (95% CI: 0.85, 1.43) for ischemic heart disease and 1.18 (95% CI: 0.77, 1.81) for myocardial infarction. For chronic obstructive pulmonary disease, HR was 1.26 (95% CI: 0.81, 1.97). We found no statistically significant associations between candle use and the risk of cardiovascular and respiratory events. Studies with improved exposure assessments are warranted.

Breast cancer rate after oophorectomy: A Prospective Danish Cohort Study.

The association between oophorectomy and risk of breast cancer in the general population is uncertain. The aim of our study was to determine the breast cancer rate in women from the general population after oophorectomy (performed before/after menopause), and whether this varies by use of hormone replacement therapy (HRT), hysterectomy, body mass index (BMI) and shift work. The study included 24 409 female nurses (aged ≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from cohort entry until date of breast cancer, death, emigration or end of follow-up at 31 December 2018, whichever came first. Poisson regression with log-transformed person-years as the offset examined the association between oophorectomy and breast cancer (all ages and stratified by menopausal status at time of oophorectomy). The potential modifying effect of HRT use, hysterectomy, BMI and shift work on the associations was estimated. During 502 463 person-years of follow-up, 1975 (8.1%) nurses were diagnosed with breast cancer. Bilateral oophorectomy was associated with a reduced breast cancer rate compared to nurses with preserved ovaries, adjusted rate ratio (95% confidence interval): 0.79 (0.64; 0.99). Similar associations (magnitude and direction) were detected for unilateral oophorectomy and when stratifying according to menopausal status at time of oophorectomy, but without statistical significance. Unilateral and bilateral oophorectomy is associated with a reduced breast cancer rate in women from the general population. This association is not modified by use of HRT, hysterectomy, BMI or shift work.

Long-term exposure to low-level air pollution and incidence of asthma: the ELAPSE project.

BACKGROUND: Long-term exposure to ambient air pollution has been linked to childhood-onset asthma, although evidence is still insufficient. Within the multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we examined the associations of long-term exposures to particulate matter with a diameter <2.5 µm (PM2.5), nitrogen dioxide (NO2) and black carbon (BC) with asthma incidence in adults. METHODS: We pooled data from three cohorts in Denmark and Sweden with information on asthma hospital diagnoses. The average concentrations of air pollutants in 2010 were modelled by hybrid land-use regression models at participants' baseline residential addresses. Associations of air pollution exposures with asthma incidence were explored with Cox proportional hazard models, adjusting for potential confounders. RESULTS: Of 98 326 participants, 1965 developed asthma during a mean follow-up of 16.6 years. We observed associations in fully adjusted models with hazard ratios of 1.22 (95% CI 1.04-1.43) per 5 µg·m-3 for PM2.5, 1.17 (95% CI 1.10-1.25) per 10 µg·m-3 for NO2 and 1.15 (95% CI 1.08-1.23) per 0.5×10-5 m-1 for BC. Hazard ratios were larger in cohort subsets with exposure levels below the European Union and US limit values and possibly World Health Organization guidelines for PM2.5 and NO2. NO2 and BC estimates remained unchanged in two-pollutant models with PM2.5, whereas PM2.5 estimates were attenuated to unity. The concentration-response curves showed no evidence of a threshold. CONCLUSIONS: Long-term exposure to air pollution, especially from fossil fuel combustion sources such as motorised traffic, was associated with adult-onset asthma, even at levels below the current limit values.

Long-term exposure to fine particle elemental components and lung cancer incidence in the ELAPSE pooled cohort.

BACKGROUND: An association between long-term exposure to fine particulate matter (PM2.5) and lung cancer has been established in previous studies. PM2.5 is a complex mixture of chemical components from various sources and little is known about whether certain components contribute specifically to the associated lung cancer risk. The present study builds on recent findings from the "Effects of Low-level Air Pollution: A Study in Europe" (ELAPSE) collaboration and addresses the potential association between specific elemental components of PM2.5 and lung cancer incidence. METHODS: We pooled seven cohorts from across Europe and assigned exposure estimates for eight components of PM2.5 representing non-tail pipe emissions (copper (Cu), iron (Fe), and zinc (Zn)), long-range transport (sulfur (S)), oil burning/industry emissions (nickel (Ni), vanadium (V)), crustal material (silicon (Si)), and biomass burning (potassium (K)) to cohort participants' baseline residential address based on 100 m by 100 m grids from newly developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). RESULTS: The pooled study population comprised 306,550 individuals with 3916 incident lung cancer events during 5,541,672 person-years of follow-up. We observed a positive association between exposure to all eight components and lung cancer incidence, with adjusted HRs of 1.10 (95% CI 1.05, 1.16) per 50 ng/m3 PM2.5 K, 1.09 (95% CI 1.02, 1.15) per 1 ng/m3 PM2.5 Ni, 1.22 (95% CI 1.11, 1.35) per 200 ng/m3 PM2.5 S, and 1.07 (95% CI 1.02, 1.12) per 200 ng/m3 PM2.5 V. Effect estimates were largely unaffected by adjustment for nitrogen dioxide (NO2). After adjustment for PM2.5 mass, effect estimates of K, Ni, S, and V were slightly attenuated, whereas effect estimates of Cu, Si, Fe, and Zn became null or negative. CONCLUSIONS: Our results point towards an increased risk of lung cancer in connection with sources of combustion particles from oil and biomass burning and secondary inorganic aerosols rather than non-exhaust traffic emissions. Specific limit values or guidelines targeting these specific PM2.5 components may prove helpful in future lung cancer prevention strategies.

Night work and incidence of Parkinson's disease in the Danish Nurse Cohort.

OBJECTIVES: Evidence on the association between night work and Parkinson's disease (PD) is sparse and conflicting, calling for more definitive studies. METHODS: We included 20 138 female nurses from the Danish Nurse Cohort without PD who at baseline in 1993 and/or 1999 reported their most common current work schedule (day, evening, night, and rotating (a combination of at least two of these)), including information on lifetime cumulative duration (years) of each shift in a 2009 follow-up survey. We obtained information on PD hospital contacts and PD medication until November 2018 via linkage to the Danish National Patient (inpatient from 1977 and outpatient contacts from 1995 onwards) and Prescription Registers starting in 1995. We defined the incidence of PD as the first-ever hospital contact due to PD, or the first-ever redeemed levodopa prescription, whichever came first. We used Cox regression models to calculate HRs and 95% CIs, adjusting for age, smoking status, coffee consumption and use of hormone replacement therapy. RESULTS: We found no significant difference in PD risk among nurses who reported working evening (HR=0.86; 95% CI=0.55 to 1.34), night (HR=1.26; 95% CI=0.79 to 2.02) or rotating shifts (HR=0.83; 95% CI=0.56 to 1.21) at cohort baseline in 1993 or 1999, when compared with permanent day workers. Similarly, persistency of shift work (working the same work schedule for 6+ years) or duration of shift work was not associated with PD risk. CONCLUSIONS: Overall, there was little evidence for an association between various shift work schedules including night work and PD in this cohort of middle-aged female nurses.

Shift work and incidence of dementia: A Danish Nurse Cohort study.

INTRODUCTION: A few studies suggest that working night and rotating shifts increase the risk of dementia. We examined the association between shift work and the incidence of dementia in a cohort of female Danish nurses. METHODS: We linked Danish Nurse Cohort participants, who reported work schedules (day, evening, night, rotating shifts) in 1993 and/or 1999 and their duration in 2009, to Danish registers to obtain information on dementia hospitalizations and prescription medication until November 2018. RESULTS: Among 6048 nurses who reported work schedules in 1993 and 1999, nurses working night shifts ≥6 years had higher dementia incidence (hazard ratio: 2.43, 95% confidence interval: 1.39 to 4.23) than those working day shifts ≥6 years. Among 8059 nurses who reported shift work duration, nurses working night shifts ≥6 years had higher dementia incidence than those working night shifts <1 year (1.47, 1.06 to 2.06). DISCUSSION: Persistent night shift work may increase the risk of dementia.

Long-term exposure to road traffic noise and incidence of breast cancer: a cohort study.

BACKGROUND: Exposure to road traffic noise was associated with increased risk of estrogen receptor (ER)-negative (ER-) breast cancer in a previous cohort study, but not with overall or ER-positive (ER+) breast cancer, or breast cancer prognosis. We examined the association between long-term exposure to road traffic noise and incidence of breast cancer, overall and by ER and progesterone receptor (PR) status. METHODS: We used the data from a nationwide Danish Nurse Cohort on 22,466 female nurses (age > 44 years) who at recruitment in 1993 or 1999 reported information on breast cancer risk factors. We obtained data on the incidence of breast cancer from the Danish Cancer Registry, and on breast cancer subtypes by ER and PR status from the Danish Breast Cancer Cooperative Group, up to 31 December 2012. Road traffic noise levels at the nurses' residences were estimated by the Nord2000 method between 1970 and 2013 as annual means of a weighted 24 h average (Lden) at the most exposed facade. We used time-varying Cox regression to analyze the associations between the 24-year, 10-year, and 1-year mean of Lden and breast cancer, separately for total breast cancer and by ER and PR status. RESULTS: Of the 22,466 women, 1193 developed breast cancer in total during 353,775 person-years of follow up, of whom 611 had complete information on ER and PR status. For each 10 dB increase in 24-year mean noise levels at their residence, we found a statistically significant 10% (hazard ratio and 95% confidence interval 1.10; 1.00-1.20) increase in total breast cancer incidence and a 17% (1.17; 1.02-1.33) increase in analyses based on 611 breast cancer cases with complete ER and PR information. We found positive, statistically significant association between noise levels and ER+ (1.23; 1.06-1.43, N = 494) but not ER- (0.93; 0.70-1.25, N = 117) breast cancers, and a stronger association between noise levels and PR+ (1.21; 1.02-1.42, N = 393) than between noise levels and PR- (1.10; 0.89-1.37, N = 218) breast cancers. Association between noise and ER+ breast cancer was statistically significantly stronger in nurses working night shifts (3.36; 1.48-7.63) than in those not working at night (1.21; 1.02-1.43) (p value for interaction = 0.05). CONCLUSION: Long-term exposure to road traffic noise may increase risk of ER+ breast cancer.

Active smoking and risk of breast cancer in a Danish nurse cohort study.

BACKGROUND: No scientific consensus has been reached on whether active tobacco smoking causes breast cancer. We examine the association between active smoking and breast cancer risk in Denmark, which has some of the highest smoking and breast cancer rates in women worldwide. METHODS: We used the data from a nationwide Danish Nurse Cohort on 21,867 female nurses (age > 44 years) who at recruitment in 1993 or 1999 reported information on smoking status, onset, duration, and intensity, as well as breast cancer risk factors. We obtained data on incidence of breast cancer from Danish Cancer Registry until 2013, and used Cox regression models to analyze the association between smoking and breast cancer. RESULTS: Of 21,831 women (mean age 53.2 years) 1162 developed breast cancer during 15.7 years of follow-up. 33.7% of nurses were current and 30.0% former smokers at cohort baseline. Compared to never smokers, we found increased risk of breast cancer of 18% in ever (hazard ratio and 95% confidence interval: 1.18; 1.04-1.34) and 27% in current (1.27; 1.11-1.46) smokers. We detected a dose-response relationship with smoking intensity with the highest breast cancer risk in women smoking >15 g/day (1.31; 1.11-1.56) or >20 pack-years (1.32; 1.12-1.55). Parous women who smoked heavily (>10 pack-years) before first childbirth had the highest risk of breast cancer (1.58; 1.20-2.10). Association between smoking and breast cancer was not modified by menopausal status, obesity, alcohol or hormone therapy use, and seemed to be limited to the estrogen receptor positive breast cancer subtype. CONCLUSIONS: Active smoking increases risk of breast cancer, with smoking before first birth being the most relevant exposure window.

Determinants of frequent attendance in Danish general practice: a cohort-based cross-sectional study.

BACKGROUND: Previous studies addressing determinants of frequent attendance have mainly focused on socio-demographic, psychosocial and medical factors, and few had data on lifestyle and gender-specific factors. This study aims to describe determinants of general practice frequent attendance in Danish adult population, by examining lifestyle, socio-demographic, medical and gender-specific factors. METHOD: For 54,849 participants of the Danish Diet, Cancer and Health cohort (50-65 year old) we obtained data on visits to general practitioner (GP) from the Danish National Health Service Register at cohort baseline (1993-97), when information on medical conditions and lifestyle, socio-demographic and gender-specific factors was collected by questionnaire. Logistic regression was used to identify determinants of frequent attendance, defined as top 10% GP users at the year of recruitment into the cohort (baseline) in the period between 1993 and 1997. RESULTS: Frequent attenders accounted for 40% of all face-to-face GP consultations with a mean 12 visits/year. Women were more likely to be frequent attenders, in crude (Odds ratio: 1.95; 95% Confidence Interval: 1.85-2.06) and fully adjusted (1.26; 1.09-1.47) model. In a fully adjusted model, strongest determinants of frequent attendance were pre-existing medical conditions, with hypertension (2.58; 2.42-2.75), diabetes (2.24; 1.94-2.59), and mental illness (2.29; 2.09-2.52) more than doubling the odds of being FA. High education (0.63; 0.57-0.69, >4 years higher education vs. no vocational training) and employment (0.61; 0.57-0.65) were inversely associated with frequent attendance. Finally, obesity (1.54; 1.14-2.08), smoking (1.21; 1.12-1.30, current vs. never), physical activity (0.84; 0.80-89), alcohol consumption (0.83; 0.78-0.87 above vs. below recommended level), and hormone therapy in women (1.52; 1.42-1.63) were all significant determinants of frequent attendance. CONCLUSIONS: In addition to pre-existing medical conditions, gender, socio-demographic and gender-specific factors, lifestyle (obesity, smoking, exercise and alcohol use) is also an independent determinant of frequent attendance at general practitioner.

Determinants related to gender differences in general practice utilization: Danish Diet, Cancer and Health Cohort.

OBJECTIVE: This study aims to describe the determinants related to gender differences in the GP utilization in Danish population aged 50-65 years. DESIGN: Cohort-based cross-sectional study. SETTING: Danish general practice. SUBJECTS: Totally, 54,849 participants of the Danish Diet, Cancer and Health cohort (50-65 years). MAIN OUTCOME MEASURES: The sum of cohort members' face-to-face consultations with general practitioner (GP) at the cohort baseline year (1993-1997). We obtained data on GP visits from the Danish National Health Service Register at the cohort baseline (1993-1997), when information on lifestyle (smoking, body mass index (BMI), alcohol use, physical activity), medical conditions (somatic and mental), employment, education, gravidity, and hormone therapy (HT) use was collected by questionnaire. RESULTS: Women had on average 4.1 and men 2.8 consultations per year. In a crude model, women had 47% higher rate of GP visits than men (incidence rate ratio: 1.47; 95% Confidence Interval: 1.45-1.50), which remained unchanged after adjustment for lifestyle, socio-demographic and medical factors, but attenuated to 18% (1.18; 1.13-1.24) after adjustment for female factors (gravidity and post-menopausal HT. In a fully adjusted model, subjects with hypertension (1.63; 1.59-1.67), mental illness (1.63; 1.61-1.66), diabetes (1.56; 1.47-1.65), angina pectoris (1.28; 1.21-1.34), and unemployed persons (1.19; 1.18-1.21) had highest rates of GP visits. CONCLUSIONS: Gravidity and HT use explain a large proportion, but not all of the gender difference in GP utilization. Medical conditions (somatic and mental) and unemployment are the main determinants of GP utilization in men and women, while lifestyle has minor effect. Key points Female gender remained a dominant determinant of GP utilization, after adjustment for lifestyle, socio-demography, medical and gender specific factors, with females consulting their GP 18% more often than males. Female reproductive factors (use of postmenopausal hormone therapy and gravidity) explained a large proportion of the gender variation in use of GP. Strongest determinants for GP use among Danish adults aged 50-65 years were the presence of medical conditions (somatic and mental) and unemployment, while lifestyle factors (e.g., body mass index, alcohol consumption and smoking) had minor effect.

Inflammatory markers and lung function in relation to indoor and ambient air pollution.

Ambient air pollution causes a range of adverse health effects, whereas effects of indoor sources of air pollution are not well described in high-income countries. We compared hazards of ambient air pollution and indoor sources with respect to important biomarkers of cardiorespiratory effects in terms of lung function and systemic inflammation in a middle-aged Danish cohort. Our cohort comprised 5199 men and women aged 49-63 years at the recruitment during April 2009 to March 2011, with information on exposure to second-hand smoke (SHS) and use of candles, wood stove, kerosene heater and gas cooker as well as relevant covariates. Ambient air pollution exposure was assessed as 2-year mean nitrogen dioxide (NO2) at the address (mean ± SD: 17.1 ± 9.9 µg/m3) and 4-day average levels of particulate matter with diameter <2.5 µm (PM2.5; mean ± SD: 12.5 ± 6.0 µg/m3) in urban background. Lung function was assessed as % predicted forced expiratory volume in the first second (FEV1) and inflammatory markers comprised interleukin-6 (IL-6), IL-10, IL-18, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hs-CRP). We used random-effect regression models controlling for potential confounders as well as models with further adjustment for self-reported health or for all other exposures. In models adjusted for confounders FEV1 was inversely associated with exposure to NO2, (-0,83% per 10 µg/m3; 95% CI: -1.26; -0.41%), SHS (-0.56% per 1 of 5 categories increment; 95% CI: -0.89; -0.23%), and gas cooker without hood (-0.89%; 95% CI: -1.62; -0.17%), whereas use of wood stove and candles showed positive associations, although these attenuated by mutual adjustment for all exposures or self-reported health. IL-6 showed positive associations with NO2 (6.30% increase in log-transformed values per 10 µg/m3; 95% CI: 3.54; 9.05%), PM2.5 (7.82% per 10 µg/m3; 95% CI: 3.35; 12.4%), SHS (4.38% per increase of 1 of 5 categories; 95% CI: 2.22; 6.54%) and use of kerosene (13.8%; 95% CI: 2.51; 25.1%), whereas the associations with use of wood stove and candles were inverse. PM2.5 and NO2 showed positive associations with IFN-γ and TNF-α, while PM2.5 further associated with IL-10 and IL-18. Hs-CRP was inversely associated with use of candles. These results suggest that the levels of exposure to ambient air pollution and SHS are more harmful than are the levels of exposure to indoor combustion sources from candles and wood stoves in a high-income setting.

Long-term exposure to road traffic noise and all-cause and cause-specific mortality: a Danish Nurse Cohort study.

BACKGROUND: Long-term road traffic noise exposure is linked to cardio-metabolic disease morbidity, whereas evidence on mortality remains limited. OBJECTIVES: We investigated association of long-term exposure to road traffic noise with all-cause and cause-specific mortality. METHODS: We linked 22,858 females from the Danish Nurse Cohort (DNC), recruited into the Danish Register of Causes of Death up to 2014. Road traffic noise levels since 1970 were modelled by Nord2000 as the annual mean of a weighted 24 h average (Lden). Cox regression models examined the associations between Lden (5-year and 23-year means) and all-cause and cause-specific mortalities, adjusting for lifestyle and exposure to PM2.5 (particulate matter with diameter < 2.5 µm) and NO2 (nitrogen dioxide). RESULTS: During follow-up (mean 17.4 years), 3902 nurses died: 1622 from cancer, 922 from CVDs (289 from stroke), 338 from respiratory diseases (186 from chronic obstructive pulmonary disease, 114 from lower respiratory tract infections [ALRIs]), 234 from dementia, 95 from psychiatric disorders, and 79 from diabetes. Hazard ratios (95% confidence intervals) for all-cause mortality from fully-adjusted models were 1.06 (1.01, 1.11) and 1.09 (1.03, 1.15) per 10 dB of 5-year and 23-year mean Lden, respectively, which attenuated slightly in our main model (fully-adjusted plus PM2.5: 1.04 [1.00, 1.10]; 1.08 [1.02, 1.13]). Main model estimates suggested the strongest associations between 5-year mean Lden and diabetes (1.14: 0.81, 1.61), ALRIs (1.13: 0.84, 1.54), dementia (1.12: 0.90, 1.38), and stroke (1.10: 0.91, 1.31), whereas associations with 23-year mean Lden were suggested for respiratory diseases (1.15: 0.95, 1.39), psychiatric disorders (1.11: 0.78, 1.59), and all cancers (1.08: 0.99, 1.17). DISCUSSION: Among the female nurses from the DNC, we observed that long-term exposure to road traffic noise led to premature mortality, independently of air pollution, and its adverse effects may extend well beyond those on the cardio-metabolic system to include respiratory diseases, cancer, neurodegenerative and psychiatric disorders.

Shift work and incidence of psychiatric disorders: The Danish Nurse Cohort study.

BACKGROUND: Research on health effects of shift work has especially focused on somatic diseases, such as breast cancer and cardiometabolic disease, while less attention has been given to the association between shift work and mental health. METHODS: We used information on 19 964 female nurses (≥44 years) from the Danish Nurse Cohort, who reported current work schedule (day, evening, night, or rotating) at recruitment (1993/1999). In 5102 nurses who participated in both cohort waves, we defined persistent night shift work as working night shift in 1993 and 1999. We used Cox regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for relevant confounders. Through linkage of cohort participants to national registers, we defined incidence of mood and neurotic disorders as first hospital contact or redeemed prescription until November 2018. RESULTS: We found association between night shift work with mood disorders (HR = 1.31; 95%CI = 1.17-1.47) and neurotic disorders (1.29; 1.17-1.42), compared to day work. Associations were enhanced in nurses with persistent night shift work (1.85; 1.43-2.39 and 1.62; 1.26-2.09 for mood and neurotic disorders, respectively) and in nurses with specialist confirmed mood (1.69; 1.24-2.29) and neurotic (1.72; 1.22-2.44) disorders. Nurses with preexisting psychiatric disorders and full-time work seemed most susceptible. CONCLUSIONS: Night shift work is associated with increased risk of major psychiatric disorders. The novel suggestive findings of vulnerable groups, including nurses with a history of psychiatric disorders and full-time workers, are based on a limited number of cases, and further research is needed to confirm the results.

Long-term low-level ambient air pollution exposure and risk of lung cancer - A pooled analysis of 7 European cohorts.

BACKGROUND/AIM: Ambient air pollution has been associated with lung cancer, but the shape of the exposure-response function - especially at low exposure levels - is not well described. The aim of this study was to address the relationship between long-term low-level air pollution exposure and lung cancer incidence. METHODS: The "Effects of Low-level Air Pollution: a Study in Europe" (ELAPSE) collaboration pools seven cohorts from across Europe. We developed hybrid models combining air pollution monitoring, land use data, satellite observations, and dispersion model estimates for nitrogen dioxide (NO2), fine particulate matter (PM2.5), black carbon (BC), and ozone (O3) to assign exposure to cohort participants' residential addresses in 100 m by 100 m grids. We applied stratified Cox proportional hazards models, adjusting for potential confounders (age, sex, calendar year, marital status, smoking, body mass index, employment status, and neighborhood-level socio-economic status). We fitted linear models, linear models in subsets, Shape-Constrained Health Impact Functions (SCHIF), and natural cubic spline models to assess the shape of the association between air pollution and lung cancer at concentrations below existing standards and guidelines. RESULTS: The analyses included 307,550 cohort participants. During a mean follow-up of 18.1 years, 3956 incident lung cancer cases occurred. Median (Q1, Q3) annual (2010) exposure levels of NO2, PM2.5, BC and O3 (warm season) were 24.2 µg/m3 (19.5, 29.7), 15.4 µg/m3 (12.8, 17.3), 1.6 10-5m-1 (1.3, 1.8), and 86.6 µg/m3 (78.5, 92.9), respectively. We observed a higher risk for lung cancer with higher exposure to PM2.5 (HR: 1.13, 95% CI: 1.05, 1.23 per 5 µg/m3). This association was robust to adjustment for other pollutants. The SCHIF, spline and subset analyses suggested a linear or supra-linear association with no evidence of a threshold. In subset analyses, risk estimates were clearly elevated for the subset of subjects with exposure below the EU limit value of 25 µg/m3. We did not observe associations between NO2, BC or O3 and lung cancer incidence. CONCLUSIONS: Long-term ambient PM2.5 exposure is associated with lung cancer incidence even at concentrations below current EU limit values and possibly WHO Air Quality Guidelines.

Long-term exposure to low levels of air pollution and mortality adjusting for road traffic noise: A Danish Nurse Cohort study.

BACKGROUND: The association between air pollution and mortality is well established, yet some uncertainties remain: there are few studies that account for road traffic noise exposure or that consider in detail the shape of the exposure-response function for cause-specific mortality outcomes, especially at low-levels of exposure. OBJECTIVES: We examined the association between long-term exposure to particulate matter [(PM) with a diameter of <2.5 µm (PM2.5), <10 µm (PM10)], and nitrogen dioxide (NO2) and total and cause-specific mortality, accounting for road traffic noise. METHODS: We used data on 24,541 females (age > 44 years) from the Danish Nurse Cohort, who were recruited in 1993 or 1999, and linked to the Danish Causes of Death Register for follow-up on date of death and its cause, until the end of 2013. Annual mean concentrations of PM2.5, PM10, and NO2 at the participants' residences since 1990 were estimated using the Danish DEHM/UBM/AirGIS dispersion model, and annual mean road traffic noise levels (Lden) were estimated using the Nord2000 model. We examined associations between the three-year running mean of PM2.5, PM10, and NO2 with total and cause-specific mortality by using time-varying Cox Regression models, adjusting for individual characteristics and residential road traffic noise. RESULTS: During the study period, 3,708 nurses died: 843 from cardiovascular disease (CVD), 310 from respiratory disease (RD), and 64 from diabetes. In the fully adjusted models, including road traffic noise, we detected associations of three-year running mean of PM2.5 with total (hazard ratio; 95% confidence interval: 1.06; 1.01-1.11), CVD (1.14; 1.03-1.26), and diabetes mortality (1.41; 1.05-1.90), per interquartile range of 4.39 µg/m3. In a subset of the cohort exposed to PM2.5 < 20 µg/m3, we found even stronger association with total (1.19; 1.11-1.27), CVD (1.27; 1.01-1.46), RD (1.27; 1.00-1.60), and diabetes mortality (1.44; 0.83-2.48). We found similar associations with PM10 and none with NO2. All associations were robust to adjustment for road traffic noise. DISCUSSION: Long-term exposure to low-levels of PM2.5 and PM10 is associated with total mortality, and mortality from CVD, RD, and diabetes. Associations were even stronger at the PM2.5 levels below EU limit values and were independent of road traffic noise.

Long-Term Exposure to Road Traffic Noise and Incidence of Diabetes in the Danish Nurse Cohort.

BACKGROUND: Evidence on the association between road traffic noise and diabetes risk is sparse and inconsistent with respect to how confounding by air pollution was treated. OBJECTIVES: In this study, we aimed to examine whether long-term exposure to road traffic noise over 25 years is associated with incidence of diabetes, independent of air pollution. METHODS: A total of 28,731 female nurses from the Danish Nurse cohort ([Formula: see text] at recruitment in 1993 or 1999) were linked to the Danish National Diabetes Register with information on incidence of diabetes from 1995 until 2013. The annual mean weighted levels of 24-h average road traffic noise ([Formula: see text]) at nurses' residences from 1970 until 2013 were estimated with the Nord2000 method and annual mean levels of particulate matter (PM) with diameter [Formula: see text] and [Formula: see text] ([Formula: see text] and [Formula: see text]), nitrogen dioxide ([Formula: see text]), and nitrogen oxide ([Formula: see text]) with the Danish AirGIS modeling system. Cox proportional hazards regression models were used to examine the association between residential [Formula: see text] in four different exposure windows (1-, 5-, 10-, and 25-years) and the incidence of diabetes, adjusted for lifestyle factors and air pollutants. RESULTS: Of 23,762 nurses free of diabetes at the cohort baseline, 1,158 developed diabetes during a mean follow-up of 15.2 years. We found weak positive associations between 5-y mean exposure to [Formula: see text] (per [Formula: see text] increase) and diabetes incidence in a crude model [hazard ratio (HR): 1.07; 95% confidence interval (CI): 0.99, 1.12], which attenuated in a model adjusted for lifestyle factors (HR:1.04; 95% CI: 0.97, 1.12), and reached unity after additional adjustment for [Formula: see text] (HR: 0.99; 0.91, 1.08). In analyses by level of urbanization, we found a positive association between noise and diabetes in urban areas (HR:1.27; 95% CI: 0.98, 1.63) that was unchanged after adjusting for [Formula: see text] (HR: 1.25; 95% CI: 0.97, 1.62), but we found no apparent association in provincial (HR: 1.02; 95% CI: 0.88, 1.18) or rural areas (HR: 0.97; 95% CI: 0.87, 1.08). CONCLUSION: In the nationwide cohort of Danish nurses 44 years of age and older, we found no association between long-term exposure to road traffic noise and diabetes incidence after adjustment for [Formula: see text] but found suggestive evidence of an association limited to urban areas. https://doi.org/10.1289/EHP4389.

Shift work and overall and cause-specific mortality in the Danish nurse cohort.

Objectives Evidence of an effect of shift work on all-cause and cause-specific mortality is inconsistent. This study aims to examine whether shift work is associated with increased all-cause and cause-specific mortality. Methods We linked 28 731 female nurses (age ≥44 years), recruited in 1993 or 1999 from the Danish nurse cohort where they reported information on shift work (night, evening, rotating, or day), to the Danish Register of Causes of Death to identify deaths up to 2013. We used Cox regression models with age as the underlying scale to examine the associations between night, evening, and rotating shift work (compared to day shift work) and all-cause and cause-specific mortality in models adjusted for potentially confounding variables. Results Of 18 015 nurses included in this study, 1616 died during the study time period from the following causes: cardiovascular disease (N=217), cancer (N= 945), diabetes (N=20), Alzheimer's disease or dementia (N=33), and psychiatric diseases (N=67). We found that working night [hazard ratio (HR) 1.26, 95% confidence interval 95% CI) 1.05-1.51] or evening (HR 1.29, 95% CI 1.11-1.49) shifts was associated with a significant increase in all-cause mortality when compared to working day shift. We found a significant association of night shift work with cardiovascular disease (HR 1.71, 95% CI 1.09-2.69) and diabetes (HR 12.0, 95% CI 3.17-45.2, based on 8 cases) and none with overall cancer mortality (HR 1.05, 95% CI 0.81-1.35) or mortality from psychiatric diseases (HR 1.17, 95% CI 0.47-2.92). Finally, we found strong association between evening (HR 4.28, 95% CI 1.62-11.3) and rotating (HR 5.39, 95% CI 2.35-12.3) shift work and mortality from Alzheimer's disease and dementia (based on 8 and 14 deaths among evening and rotating shift workers, respectively). Conclusions Women working night and evening shifts have increased all-cause, cardiovascular, diabetes, and Alzheimer's and dementia mortality.

Long-term exposure to ambient air pollution and incidence of brain tumours: The Danish Nurse Cohort.

BACKGROUND: Air pollution has been considered a potent environmental risk factor for neuropathology through neuroinflammation and oxidative stress, which might also cause brain tumour formation. However, epidemiological evidence on the association between air pollution and brain tumours in humans is sparse, with no data on exposure to particles. In this study we aim to examine associations between long-term exposure to ambient air pollution and risk for development of brain tumours. METHODS: We used the Danish Nurse Cohort with 28,731 female nurses (age≥44years) recruited in 1993 or 1999 when self-reported information on lifestyle was collected. We obtained data on the incidence of brain tumours until 2013 from the Danish Cancer Register, and estimated annual mean concentrations of particulate matter with diameter<2.5µm (PM2.5), particulate matter with diameter<10µm (PM10), nitrogen oxides (NOx) and nitrogen dioxide (NO2) at the residence since 1990 using an atmospheric integrated chemistry-transport models system, and examined the association between the 3-year running mean of pollutants and brain tumour incidence using time-varying Cox regression, separately for total brain tumours, and for tumour subtypes by location (brain or meninges), and by malignancy (malignant or benign), and estimated hazard ratios and 95% confidence intervals per increase in interquartile range of exposure. RESULTS: Of 25,143 tumour-free nurses at recruitment, 121 developed brain cancer during 15.7 years of follow-up. We found a weak positive association between total brain tumours and PM2.5 (1.06; 0.80-1.40 per 3.37µg/m(3)), NO2 (1.09; 0.91-1.29) per 7.5µg/m(3), and NOx (1.02; 0.93-1.12 per 10.22µg/m(3)), and none with PM10 (0.93; 0.70-1.23 per 3.31µg/m(3)). Associations with PM2.5 and NO2 were stronger for tumours located in meninges than in brain, and for benign than for malignant tumours. Finally, association of total brain tumours with PM2.5 was modified by BMI, and was statistically significantly enhanced in obese women (2.03; 1.35-3.05). CONCLUSION: We found weak evidence for association between risk of brain tumours and long-term exposure to air pollution in women older than 44 years. However, we present novel results that obese women may be susceptible, as well as a positive tendency towards elevated risk for meninges and benign tumours, which require further investigation.