Ursula Krämer

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).

Age of entry to day nursery and allergy in later childhood

BACKGROUND Infections in early childhood may prevent allergies in later life. If this hypothesis is true, early exposure to childcare outside the home would protect against atopy by promotion of cross infections. We investigated whether children who attend a nursery at a young age have a lower rate of atopy and fewer allergies than children who attend from an older age. METHODS In a cross-sectional study carried out in 1992-93, we examined 2471 children in three age-groups (5-7, 8-10, and 11-14 years) from the towns of Bitterfeld, Hettstedt, and Zerbst in eastern Germany. The childrens parents answered a questionnaire about allergies and symptoms, attendance at day care, and related factors. Sensitisation was assessed by skin-prick tests and measurement of allergen-specific IgE antibodies in serum. FINDINGS In 669 children from small families (up to three people), the prevalence of atopy was higher among children who started to attend day nursery at an older age than in those who started to attend at a younger age (p<0.05). Compared with children who first attended at age 6-11 months, the adjusted odds ratios for a positive skin-prick test were 1.99 (95% CI 1.08-3.66) for children who attended at age 12-23 months and 2.72 (1.37-5.40) for those who attended at age 24 months and older. In 1761 children from large families (more than three people), age of entry to day nursery had no effect on atopy. INTERPRETATION Our findings accord with the hypothesis that early infection may protect against allergies in later life.

Atopic Diseases, Allergic Sensitization, and Exposure to Traffic-related Air Pollution in Children

RATIONALE In vitro studies, animal experiments, and human exposure studies have shown how ambient air pollution increases the risk of atopic diseases. However, results derived from observational studies are inconsistent. OBJECTIVES To assess the relationship between individual-based exposure to traffic-related air pollutants and allergic disease outcomes in a prospective birth cohort study during the first 6 years of life. METHODS We studied 2,860 children at the age of 4 years and 3,061 at the age of 6 years to investigate atopic diseases and allergic sensitization. Long-term exposure to particulate matter (PM(2.5)), PM(2.5) absorbance, and long-term exposure to nitrogen dioxide (NO(2)) was assessed at residential addresses using geographic information systems based regression models and air pollution measurements. The distance to the nearest main road was used as a surrogate for traffic-related air pollutants. MEASUREMENTS AND MAIN RESULTS Strong positive associations were found between the distance to the nearest main road and asthmatic bronchitis, hay fever, eczema, and sensitization. A distance-dependent relationship could be identified, with the highest odds ratios (ORs) for children living less than 50 m from busy streets. For PM(2.5) absorbance, statistically significant effects were found for asthmatic bronchitis (OR, 1.56; 95% confidence interval [CI], 1.03-2.37), hay fever (OR, 1.59; 95% CI, 1.11-2.27), and allergic sensitization to pollen (OR, 1.40; 95% CI, 1.20-1.64). NO(2) exposure was associated with eczema, whereas no association was found for allergic sensitization. CONCLUSIONS This study provides strong evidence for increased risk of atopic diseases and allergic sensitization when children are exposed to ambient particulate matter.

Chronic rhinosinusitis in Europe--an underestimated disease. A GA²LEN study.

To cite this article: Hastan D, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, Bousquet PJ, Brozek G, Bruno A, Dahlén SE, Forsberg B, Gunnbjörnsdóttir M, Kasper L, Krämer U, Kowalski ML, Lange B, Lundbäck B, Salagean E, Todo‐Bom A, Tomassen P, Toskala E, van Drunen CM, Bousquet J, Zuberbier T, Jarvis D, Burney P. Chronic rhinosinusitis in Europe – an underestimated disease. A GA2LEN study. Allergy 2011; 66: 1216–1223.

Environmental exposure to polychlorinated biphenyls and quality of the home environment: effects on psychodevelopment in early childhood

BACKGROUND There is uncertainty whether environmental levels of exposure to polychlorinated biphenyls (PCBs) adversely affect mental and motor development in early childhood. We aimed to establish whether such an effect is of only prenatal or additional postnatal origin, and if a favourable home environment can counteract this effect. METHODS Between 1993 and 1995 we recruited 171 healthy mother-infant pairs and prospectively measured psychodevelopment in newborn infants aged 7, 18, 30, and 42 months. We estimated prenatal and perinatal PCB exposure of newborn babies in cord blood and maternal milk. At 42 months we measured postnatal PCB concentrations in serum. At 18 months the quality of the home environment was assessed using the Home Observation for Measurement of the Environment scale. Mental and psychomotor development of the children were assessed using the Bayley Scales of Infant Development until 30 months and the Kaufman Assessment Battery for Children at 42 months. FINDINGS Negative associations between milk PCB and mental/motor development were reported at all ages, becoming significant from 30 months onwards. Over 30 months, for a PCB increase from 173 (5th percentile) to 679 ng/g lipids in milk (95th percentile) there was a decrease of 8.3 points (95% CI -16.5 to 0.0) in the Bayley Scales of Infant Development mental scores, and a 9.1 point decrease (95% CI -17.2 to -1.02) in the Bayley Scales of Infant Development motor scores. There was also a negative effect of postnatal PCB exposure via breastfeeding at 42 months. Home environment had a positive effect from 30 months onwards (Bayley Scales of Infant Development mental score increase of 9.4 points [95% CI 2.2-16.7]). INTERPRETATION Prenatal PCB exposure at current European background levels inhibits, and a favourable home environment supports, mental and motor development until 42 months of age. PCB exposure also has an effect postnatally.

Traffic-related air pollution is associated with atopy in children living in urban areas

Traffic emissions are a major source of air pollution in Western industrialized countries. To investigate the association between traffic-related air pollution and parameters of atopy, we studied 317 children 9 years of age living near major roads in two urban areas and one suburban area of a city in West Germany. Atopic sensitization was analyzed by skin-prick testing and determination of allergen-specific serum immunoglobulin E. Parents recorded allergic symptoms in a symptom diary, and physicians assessed allergic diseases. Personal NO2 exposure and NO2 concentrations in front of each childs home were measured. Outdoor NO2 was a good predictor for traffic exposure but a poor predictor for NO2 exposure at the personal level. Atopy was found to be related to outdoor NO2 (odds ratio for the association between symptoms of allergic rhinitis and outdoor NO2 = 1.81; 95% confidence interval = 1.02-3.21) but not to personal NO2 (odds ratio for the association between symptoms of allergic rhinitis and personal NO2 = 0.99; 95% confidence interval = 0.55-1.79). When the analysis was restricted to urban areas, we found that hay fever, symptoms of allergic rhinitis, wheezing, sensitization against pollen, house dust mites or cats, and milk or eggs were associated with outdoor NO2. The results indicate that traffic-related air pollution leads to increased prevalence of atopic sensitizations, allergic symptoms, and diseases.

Long-term air pollution exposure and living close to busy roads are associated with COPD in women

BackgroundLung function and exacerbations of chronic obstructive pulmonary disease (COPD) have been associated with short-term exposure to air pollution. However, the effect of long-term exposure to particulate matter from industry and traffic on COPD as defined by lung function has not been evaluated so far. Our study was designed to investigate the influence of long-term exposure to air pollution on respiratory symptoms and pulmonary function in 55-year-old women. We especially focused on COPD as defined by GOLD criteria and additionally compared the effects of air pollution on respiratory symptoms by questionnaire data and by lung function measurements.MethodsIn consecutive cross sectional studies conducted between 1985–1994, we investigated 4757 women living in the Rhine-Ruhr Basin of Germany. NO2 and PM10 exposure was assessed by measurements done in an 8 km grid, and traffic exposure by distance from the residential address to the nearest major road using Geographic Information System data. Lung function was determined and COPD was defined by using the GOLD criteria. Chronic respiratory symptoms and possible confounders were defined by questionnaire data. Linear and logistic regressions, including random effects were used to account for confounding and clustering on city level.ResultsThe prevalence of COPD (GOLD stages 1–4) was 4.5%. COPD and pulmonary function were strongest affected by PM10 and traffic related exposure. A 7 μg/m3 increase in five year means of PM10 (interquartile range) was associated with a 5.1% (95% CI 2.5%–7.7%) decrease in FEV1, a 3.7% (95% CI 1.8%–5.5%) decrease in FVC and an odds ratio (OR) of 1.33 (95% CI 1.03–1.72) for COPD. Women living less than 100 m from a busy road also had a significantly decreased lung function and COPD was 1.79 times more likely (95% CI 1.06–3.02) than for those living farther away. Chronic symptoms as based on questionnaire information showed effects in the same direction, but less pronounced.ConclusionChronic exposure to PM10, NO2 and living near a major road might increase the risk of developing COPD and can have a detrimental effect on lung function.

Asthma in adults and its association with chronic rhinosinusitis: the GA2LEN survey in Europe

To cite this article: Jarvis D, Newson R, Lotvall J, Hastan D, Tomassen P, Keil T, Gjomarkaj M, Forsberg B, Gunnbjornsdottir M, Minov J, Brozek G, Dahlen SE, Toskala E, Kowalski ML, Olze H, Howarth P, Krämer U, Baelum J, Loureiro C, Kasper L, Bousquet PJ, Bousquet J, Bachert C, Fokkens W, Burney P. Asthma in adults and its association with chronic rhinosinusitis: The GA2LEN survey in Europe. Allergy 2012; 67: 91–98.

Genome-Wide Scan on Total Serum IgE Levels Identifies FCER1A as Novel Susceptibility Locus

High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait. In a genome-wide association study (GWAS), we tested 353,569 SNPs for association with serum IgE levels in 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed in four independent population-based study samples (total n = 9,769 individuals). Functional variants in the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) on chromosome 1q23 (rs2251746 and rs2427837) were strongly associated with total IgE levels in all cohorts with P values of 1.85×10−20 and 7.08×10−19 in a combined analysis, and in a post-hoc analysis showed additional associations with allergic sensitization (P = 7.78×10−4 and P = 1.95×10−3). The “top” SNP significantly influenced the cell surface expression of FCER1A on basophils, and genome-wide expression profiles indicated an interesting novel regulatory mechanism of FCER1A expression via GATA-2. Polymorphisms within the RAD50 gene on chromosome 5q31 were consistently associated with IgE levels (P values 6.28×10−7−4.46×10−8) and increased the risk for atopic eczema and asthma. Furthermore, STAT6 was confirmed as susceptibility locus modulating IgE levels. In this first GWAS on total IgE FCER1A was identified and replicated as new susceptibility locus at which common genetic variation influences serum IgE levels. In addition, variants within the RAD50 gene might represent additional factors within cytokine gene cluster on chromosome 5q31, emphasizing the need for further investigations in this intriguing region. Our data furthermore confirm association of STAT6 variation with serum IgE levels.

Preventive effect of hydrolyzed infant formulas persists until age 6 years: Long-term results from the German Infant Nutritional Intervention Study (GINI)

BACKGROUND The long-term effect of nutritional intervention with hydrolyzed infant formulas on allergy development has not been sufficiently evaluated. OBJECTIVE We performed a follow-up of the German Infant Nutritional Intervention study until 6 years of life to investigate the long-term allergy-preventive effect of 3 hydrolyzed infant formulas compared with cows milk formula (CMF) in a randomized, double-blind trial. METHODS Between 1995 and 1998, 2252 newborns with atopic heredity were randomly assigned at birth to receive one of 4 blinded formulas: partially or extensively hydrolyzed whey formula, extensively hydrolyzed casein formula, or CMF as milk substitute for the first 4 months when breast-feeding was insufficient. The cohort was followed from birth until 6 years of age with yearly questionnaires. Outcomes were physician-diagnosed allergic diseases (atopic dermatitis, food allergy, allergic urticaria, asthma, and hay fever/allergic rhinitis). Log-binomial regression modeled with generalized estimation equations was used for the statistical analysis. RESULTS In the intent-to-treat analysis the relative risk of a physicians diagnosis of allergic manifestation (AM) compared with CMF was 0.82 (95% CI, 0.70-0.96) for partially hydrolyzed whey formula, 0.90 (95% CI, 0.78-1.04) for extensively hydrolyzed whey formula, and 0.80 (95% CI, 0.69-0.93) for extensively hydrolyzed casein formula. The corresponding figures for atopic eczema were 0.79 (95% CI, 0.64-0.97), 0.92 (95% CI, 0.76-1.11), and 0.71 (95% CI, 0.58-0.88), respectively. In the per-protocol analysis all effects were stronger and significant. No significant effect on other AMs was found. CONCLUSION The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age.