Per Nafstad

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE)

BACKGROUND Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. METHODS This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses. FINDINGS The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 μg/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 μg/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 μg/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day). INTERPRETATION Particulate matter air pollution contributes to lung cancer incidence in Europe. FUNDING European Communitys Seventh Framework Programme.

Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project

BACKGROUND Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. METHODS We used data from 22 European cohort studies, which created a total study population of 367,251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and between 10 μm and 2.5 μm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. FINDINGS The total study population consisted of 367,251 participants who contributed 5,118,039 person-years at risk (average follow-up 13.9 years), of whom 29,076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 μg/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I(2) p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 μg/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 μg/m(3) (1.07, 1.01-1.13). INTERPRETATION Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value. FUNDING European Communitys Seventh Framework Program (FP7/2007-2011).

In utero exposure to cigarette smoking influences lung function at birth

To avoid the possible confounding effects of postnatal exposure to tobacco smoke, we investigated possible effects of uterine tobacco smoke (UTS) exposure upon infant lung function shortly after birth. Infants with no major disease, in one maternity ward in Oslo, Norway, participating in a cohort study established in 1992/1993, were included in the present study (n=803). Exposure information, assessed as maternal active and passive smoking during pregnancy and other personal and environmental factors, was obtained by questionnaire. Tidal flow-volume (TFV) loops (n=802) and compliance (Crs) and resistance (Rrs) of the respiratory system (n=663) were measured at a mean age of 2.7 days. In girls, the TFV ratio (time to reach peak expiratory flow to total expiratory time (tPEF/tE)), and Crs were significantly lower with active as well as passive maternal smoking compared to nonexposure to UTS. Respiratory rate and Rrs were not significantly influenced by UTS exposure. However, in linear regression analysis adjusted for confounding factors (including respiratory rate), tPEF/tE and Crs, but not Rrs, were related to maternal active but not passive daily smoking. One daily cigarette corresponded to a change in tPEF/tE of -0.0021 (95% confidence interval (95% CI) -0.0040 to -0.0002) and a change in Crs of -0.026 mL x cmH2O (95% CI -0.045 to -0.007 mL x cmH2O). The decrease was 0.023 and 0.29, respectively, in infants of an average smoker. Maternal smoking during pregnancy adversely affected tidal flow-volume ratios in healthy newborn babies, as well as the compliance of the respiratory system in girls, independently of the reduced body size also resulting from maternal smoking.

Ambient air pollution and low birthweight: a European cohort study (ESCAPE)

BACKGROUND Ambient air pollution has been associated with restricted fetal growth, which is linked with adverse respiratory health in childhood. We assessed the effect of maternal exposure to low concentrations of ambient air pollution on birthweight. METHODS We pooled data from 14 population-based mother-child cohort studies in 12 European countries. Overall, the study population included 74 178 women who had singleton deliveries between Feb 11, 1994, and June 2, 2011, and for whom information about infant birthweight, gestational age, and sex was available. The primary outcome of interest was low birthweight at term (weight <2500 g at birth after 37 weeks of gestation). Mean concentrations of particulate matter with an aerodynamic diameter of less than 2·5 μm (PM2·5), less than 10 μm (PM10), and between 2·5 μm and 10 μm during pregnancy were estimated at maternal home addresses with temporally adjusted land-use regression models, as was PM2·5 absorbance and concentrations of nitrogen dioxide (NO2) and nitrogen oxides. We also investigated traffic density on the nearest road and total traffic load. We calculated pooled effect estimates with random-effects models. FINDINGS A 5 μg/m(3) increase in concentration of PM2·5 during pregnancy was associated with an increased risk of low birthweight at term (adjusted odds ratio [OR] 1·18, 95% CI 1·06-1·33). An increased risk was also recorded for pregnancy concentrations lower than the present European Union annual PM2·5 limit of 25 μg/m(3) (OR for 5 μg/m(3) increase in participants exposed to concentrations of less than 20 μg/m(3) 1·41, 95% CI 1·20-1·65). PM10 (OR for 10 μg/m(3) increase 1·16, 95% CI 1·00-1·35), NO2 (OR for 10 μg/m(3) increase 1·09, 1·00-1·19), and traffic density on nearest street (OR for increase of 5000 vehicles per day 1·06, 1·01-1·11) were also associated with increased risk of low birthweight at term. The population attributable risk estimated for a reduction in PM2·5 concentration to 10 μg/m(3) during pregnancy corresponded to a decrease of 22% (95% CI 8-33%) in cases of low birthweight at term. INTERPRETATION Exposure to ambient air pollutants and traffic during pregnancy is associated with restricted fetal growth. A substantial proportion of cases of low birthweight at term could be prevented in Europe if urban air pollution was reduced. FUNDING The European Union.

Folic acid supplements in pregnancy and early childhood respiratory health

Background: Folate supplementation is recommended for pregnant women to reduce the risk of congenital malformations. Maternal intake of folate supplements during pregnancy might also influence childhood immune phenotypes via epigenetic mechanisms. Objective: To investigate the relationship between folate supplements in pregnancy and risk of lower respiratory tract infections and wheeze in children up to 18 months of age. Methods: In the Norwegian Mother and Child Cohort Study, questionnaire data collected at several time points during pregnancy and after birth on 32 077 children born between 2000 and 2005 were used to assess the effects of folate supplements during pregnancy on respiratory outcomes up to 18 months of age, while accounting for other supplements in pregnancy and supplementation in infancy. Results: Folate supplements in the first trimester were associated with increased risk of wheeze and respiratory tract infections up to 18 months of age. Adjusting for exposure later in pregnancy and in infancy, the relative risk for wheeze for children exposed to folic acid supplements in the first trimester was 1.06 (95% CI 1.03 to 1.10), the relative risk for lower respiratory tract infections was 1.09 (95% CI 1.02 to 1.15) and the relative risk for hospitalisations for lower respiratory tract infections was 1.24 (95% CI 1.09 to 1.41). Conclusions: Folic acid supplements in pregnancy were associated with a slightly increased risk of wheeze and lower respiratory tract infections up to 18 months of age. The results suggest that methyl donors in the maternal diet during pregnancy may influence respiratory health in children consistent with epigenetic mechanisms.

Exposure to pets and atopy-related diseases in the first 4 years of life

Background: It is still unclear how early‐life exposure to pets is related to childrens risk of developing atopy‐related diseases. We estimated associations between early‐life exposure to pets and atopy‐related diseases at 0‐4 years of life in a cohort of Norwegian children.

Relation between occurrence of type 1 diabetes and asthma

A negative association has been observed between type 1 diabetes and atopic diseases in individuals, a finding that supports the Th1/Th2 paradigm. By using published data on disease occurrence in different countries, we show a strong positive association between the occurrence of type 1 diabetes and symptoms of asthma at the population level in Europe and elsewhere. Our finding suggests that there may be common factors influencing susceptibility to the two disorders at the country level. Our observation must be accommodated in explanations of the epidemiology of type 1 diabetes or atopic diseases.

An electron microscope study on the termination of the perforant path fibres in the hippocampus and the fascia dentata.

SummaryMorphology and distribution of the perforant path fibres in the hippocampus and the fascia dentata of the rat have been studied in the electron microscope. Investigations were carried out on normal tissue as well as on tissue degenerating after entorhinal damage. The perforant path fibres were relatively thin and the terminals small. Two terminal fields were found to be of quantitative importance, one in the middle third of stratum moleculare of the fascia dentata, the other in stratum lacunosum moleculare of regio inferior of the hippocampus. Some of the observations have been expressed in numerical terms.

Interior surface materials in the home and the development of bronchial obstruction in young children in Oslo, Norway.

OBJECTIVES This study assessed the role of polyvinyl chloride (PVC) plastics and textile materials in the home in the development of bronchial obstruction during the first 2 years of life. METHODS The study was a matched pair case-control study based on a cohort of 3754 newborns in Oslo in 1992 and 1993 who were followed up for 2 years. The case group consisted of 251 children with bronchial obstruction; the control group was matched one-to-one for date of birth. RESULTS In conditional logistic regression analysis, the risk of bronchial obstruction was related to the presence of PVC flooring (adjusted odds ratio [OR] = 1.89; 95% confidence interval [CI] = 1.14, 3.14) and textile wall materials (adjusted OR = 1.58; 95% CI = 0.98, 2.54). The reference category was wood or parquet flooring and painted walls and ceiling. Further analysis revealed an exposure-response relationship between the assessed amount of PVC and other plasticizer-containing surface materials and the risk of bronchial obstruction. CONCLUSIONS This study provides new evidence of the role of PVC and textile wall materials in the development of bronchial obstruction in young children.

Day Care Centers and Respiratory Health

Objective. To estimate the effects of the type of day care on respiratory health in preschool children. Methods. A population-based cross-sectional study of Oslo children born in 1992 was conducted at the end of 1996. A self-administered questionnaire inquired about day care arrangements, childrens health, environmental conditions, and family characteristics (n = 3853; response rate, 79%). Results. In logistic regression controlling for confounding, children in day care centers had more often nightly cough (adjusted odds ratio, 1.89; 95% confidence interval, 1.34–2.67), and blocked or runny nose without common cold (1.55; 1.07–1.61) during the past 12 months compared with children in home care. Poisson regression analysis showed an increased risk of the common cold (incidence rate ratio, 1.21; 1.12–1.30) and otitis media (1.48; 1.22–1.80), and the attributable proportion was 17.4% (95% confidence interval, 10.7–23.1) for the common cold and 32.4% (18.0–44.4) for otitis media. Early starting age in the day care center increased the risk of developing recurrent otitis media. Also the lifetime risk of doctor-diagnosed asthma was higher in children who started day care center attendance during the first 2 years of life. Conclusions. Attendance to day care centers increases the risk of upper respiratory symptoms and infections in 3- to 5-year-old children. The starting age seems to be an important determinant of recurrent otitis media as well as asthma. The effect of day care center attendance on asthma is limited to age up to 2 years. This effect is most likely mediated via early respiratory tract infections that are substantially more common in children in day care centers compared with children in home care.