Urban residential greenness and adiposity: A cohort study in Stockholm County.

BACKGROUND: Increasing evidence suggests that exposure to residential greenness is associated with positive health outcomes among urban populations. However, few studies have considered effects on adiposity development in a longitudinal setting. OBJECTIVES: This study aimed to explore the association between long-term exposure to urban residential greenness and markers of adiposity. METHODS: A cohort of 5126 adults from five municipalities in Stockholm County was examined clinically at baseline (1992-1998) and follow-up (2002-2006) after on average nine years. Time-weighted average exposure to urban greenness was estimated by Normalized Difference Vegetation Index (NDVI) within 100 m, 250 m, and 500 m buffers around the residential addresses of each participant. Multiple linear and Poisson regression models were used to estimate associations between greenness and change in weight and waist circumference as well as risk of overweight, obesity and central obesity. Co-exposures to air pollution, traffic noise and distance to water were also examined. RESULTS: In women, higher levels of residential greenness were associated with a reduced increase in waist circumference during follow-up (ß = -0.11 cm/year, 95% CI -0.14; -0.08 per one interquartile range increase in NDVI) and decreased risk for central obesity (IRR = 0.88: 95% CI 0.79; 0.99) in the 500 m buffer. No associations were observed for men or with regard to weight development or the risk of developing overweight or obesity. Exposure to low NDVI levels in combination with high NOx from road traffic and transportation noise as well as long distance to water rendered statistically significant increases in waist circumference in both sexes. CONCLUSION: Higher long-term exposure to greenness was associated with a reduced increase in waist circumference and lower risk of central adiposity in women but not in men. In both sexes, low NDVI exposure in combination with other environmental risk factors appeared particularly harmful.

Dietary total antioxidant capacity in early school age and subsequent allergic disease.

BACKGROUND: Dietary antioxidant intake has been hypothesized to influence the development of allergic diseases; however, few prospective studies have investigated this association. OBJECTIVE: Our aim was to study the association between total antioxidant capacity (TAC) of the diet at age 8 years and the subsequent development of asthma, rhinitis and sensitization to inhalant allergens between 8 and 16 years, and to assess potential effect modification by known risk factors. METHODS: A total of 2359 children from the Swedish birth cohort BAMSE were included. Dietary TAC at age 8 years was estimated by combining information on the child's diet the past 12 months from a food frequency questionnaire with a database of common foods analysed with the oxygen radical absorbance capacity method. Classification of asthma and rhinitis was based on questionnaires, and serum IgE antibodies were measured at 8 and 16 years. RESULTS: A statistically significant inverse association was observed between TAC of the diet and incident sensitization to inhalant allergens (adjusted odds ratio: 0.73, 95% confidence interval: 0.55-0.97 for the third compared to the first tertile, P-value for trend = 0.031). Effect modification by traffic-related air pollution exposure was observed, with a stronger association between dietary TAC and sensitization among children with low traffic-related air pollution exposure (P-value for interaction = 0.029). There was no evidence for effect modification by GSTP1 or TNF genotypes, although these results should be interpreted with caution. No clear associations were observed between TAC and development of rhinitis or asthma, although a significant inverse association was observed for allergic asthma (ORadj 0.57, 95% CI 0.34-0.94). CONCLUSIONS AND CLINICAL RELEVANCE: Higher TAC of the diet in early school age may decrease the risk of developing sensitization to inhalant allergens from childhood to adolescence. These findings indicate that implementing an antioxidant-rich diet in childhood may contribute to the prevention of allergic disease.

Mold and dampness exposure and allergic outcomes from birth to adolescence: data from the BAMSE cohort.

BACKGROUND: Exposure to moldy or damp indoor environments is associated with allergic disease in young children, but it is unclear whether the effects persist to adolescence. Our objective was to assess whether exposure to mold or dampness during infancy increases the risk of asthma, rhinitis, or IgE sensitization in children followed from birth to 16 years of age. METHODS: We collected questionnaire derived reports of mold or dampness indicators and allergic outcomes from 3798 children in a Swedish birth cohort (BAMSE). Sensitization was assessed from blood samples in 3293 children. Longitudinal associations between prevalent asthma, rhinitis, and IgE sensitization and mold or dampness indicators were assessed using generalized estimating equations. RESULTS: Exposure to any mold or dampness indicator was associated with asthma up to 16 years of age (OR 1.31; 95% CI 1.08-1.59), while exposure to mold odor (OR 1.29; 95% CI 1.03-1.62) and visible mold (OR 1.28; 95% CI 1.04-1.58) were associated with rhinitis. Increased risks were observed for nonallergic asthma (OR 1.80; 95% CI 1.27-2.55) and rhinitis (OR 1.41; 95% CI 1.03-1.93). No association was observed between mold or dampness indicators and IgE sensitization. Exposure to any mold or dampness indicator was associated with persistent asthma (OR 1.73; 95% CI 1.20-2.50), but not with early-transient or late-onset asthma. CONCLUSION: Exposure to mold or dampness during infancy increased the risk of asthma and rhinitis up to 16 years of age, particularly for nonallergic disease. Early exposure to mold or dampness appeared particularly associated with persistent asthma through adolescence.

Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma.

Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma.

Residential greenness is differentially associated with childhood allergic rhinitis and aeroallergen sensitization in seven birth cohorts.

BACKGROUND: The prevalence of allergic rhinitis is high, but the role of environmental factors remains unclear. We examined cohort-specific and combined associations of residential greenness with allergic rhinitis and aeroallergen sensitization based on individual data from Swedish (BAMSE), Australian (MACS), Dutch (PIAMA), Canadian (CAPPS and SAGE), and German (GINIplus and LISAplus) birth cohorts (n = 13 016). METHODS: Allergic rhinitis (doctor diagnosis/symptoms) and aeroallergen sensitization were assessed in children aged 6-8 years in six cohorts and 10-12 years in five cohorts. Residential greenness was defined as the mean Normalized Difference Vegetation Index (NDVI) in a 500-m buffer around the home address at the time of health assessment. Cohort-specific associations per 0.2 unit increase in NDVI were assessed using logistic regression models and combined in a random-effects meta-analysis. RESULTS: Greenness in a 500-m buffer was positively associated with allergic rhinitis at 6-8 years in BAMSE (odds ratio = 1.42, 95% confidence interval [1.13, 1.79]) and GINI/LISA South (1.69 [1.19, 2.41]) but inversely associated in GINI/LISA North (0.61 [0.36, 1.01]) and PIAMA (0.67 [0.47, 0.95]). Effect estimates in CAPPS and SAGE were also conflicting but not significant (0.63 [0.32, 1.24] and 1.31 [0.81, 2.12], respectively). All meta-analyses were nonsignificant. Results were similar for aeroallergen sensitization at 6-8 years and both outcomes at 10-12 years. Stratification by NO2 concentrations, population density, an urban vs rural marker, and moving did not reveal consistent trends within subgroups. CONCLUSION: Although residential greenness appears to be associated with childhood allergic rhinitis and aeroallergen sensitization, the effect direction varies by location.

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.

Parental smoking and development of allergic sensitization from birth to adolescence.

BACKGROUND: The relation between secondhand tobacco smoke (SHS) exposure and the development of allergic sensitization in children is unclear. The aim of this study was to determine whether maternal smoking during pregnancy and postnatal SHS exposure contributes to the development of allergic sensitization in children and adolescents up to 16 years of age. METHODS: We included 3316 children from a birth cohort followed up for 16 years. SHS exposure and symptoms of allergic disease were assessed using repeated parental questionnaires. Serum immunoglobulin E against eight common inhalant and six food allergens was assessed at ages 4, 8, and 16 years with ImmunoCAP. The association between SHS exposure and sensitization was explored using logistic regression and generalized estimating equations. RESULTS: Exposure to SHS in infancy without prior exposure in utero was associated with an excess risk of food sensitization at age 4 years (OR 1.47, 95% CI 1.08-2.00), with comparable ORs at ages 8 and 16 years. In longitudinal analyses, an overall association was indicated between SHS in infancy and food sensitization up to age 16 years (OR 1.24, 95% CI 0.98-1.56). Maternal smoking during pregnancy was unrelated to sensitization up to 16 years of age. When sensitization was combined with concurrent symptoms of allergic disease, SHS in infancy was associated with an overall elevated risk of eczema with sensitization (OR 1.62, 95% CI 1.20-2.18). CONCLUSIONS: SHS exposure in infancy appears to increase the risk of sensitization to food allergens up to age 16 years, as well as eczema in combination with sensitization.

Exposure to grass pollen--but not birch pollen--affects lung function in Swedish children.

Allergic response to pollen is increasing worldwide, leading to high medical and social costs. However, the effect of pollen exposure on lung function has rarely been investigated. Over 1800 children in the Swedish birth cohort BAMSE were lung-function- and IgE-tested at the age of 8 and 16 years old. Daily concentrations for 9 pollen types together with measurements for ozone, NO2 , PM10 , PM2.5 were estimated for the index day as well as up to 6 days before the testing. Exposure to grass pollen during the preceding day was associated with a reduced forced expiratory volume in 8-yr-olds; -32.4 ml; 95% CI: -50.6 to -14.2, for an increase in three pollen counts/m³. Associations appeared stronger in children sensitized to pollen allergens. As the grass species flower late in the pollen season, the allergy care routines might be weakened during this period. Therefore, allergy information may need to be updated to increase awareness among grass pollen-sensitized individuals.

Antioxidant intake and allergic disease in children.

BACKGROUND: Antioxidant intake may reduce the risk of allergic disease by protecting against oxidative tissue damage. Major sources of antioxidants in the Western world are fruits, vegetables (vitamin C, ß-carotene, α-tocopherol), meat and milk (selenium, magnesium, zinc). Children may exclude or eat less of some fruits and vegetables due to cross-reactivity between pollen and these foods, complicating assessment of causal relationships. OBJECTIVE: To investigate the association between dietary antioxidant intake and allergic disease, taking potential reverse causation into account. METHODS: Data on 2442 8-year-old children from the Swedish birth cohort study BAMSE were analysed. Children with completed parental questionnaires on exposures and health, including a food-frequency questionnaire and who provided a blood sample were included. Associations between antioxidant intake during the past year and current allergic disease were analysed using logistic regression. RESULTS: An inverse association was observed between intake of ß-carotene and rhinitis (OR(adj), highest vs. lowest quartile, 0.67, 95% CI 0.49-0.93). Magnesium intake was inversely related to asthma (OR(adj), 0.65, 95% CI 0.42-1.00) and atopic sensitisation (OR(adj), 0.78, 95% CI 0.61-1.00). Following exclusion of children who avoided certain fruits, vegetables or milk due to allergic symptoms (n = 285), the inverse association remained between magnesium intake and asthma (OR(adj), 0.58, 95% CI 0.35-0.98), whereas all other associations became non-significant. CONCLUSION AND CLINICAL RELEVANCE: Diet modifications due to allergy may affect the antioxidant intake and needs to be considered when investigating the relationship between diet and allergic disease. Magnesium intake seems to have a protective effect on childhood asthma.

Environmental bacteria and childhood asthma.

BACKGROUND: We have previously found an inverse association of bacterial diversity with childhood asthma. It remains unclear whether certain bacteria account for the protective effect. METHODS: The high variability of the bacterial 16S rRNA gene allows assessing diversity and specificity of bacterial communities by single-strand configuration polymorphism (SSCP). DNA was extracted from mattress dust samples of 489 school-age children from rural and suburban regions in Germany. A fragment of the bacteria-specific 16S rRNA gene was amplified by PCR, digested to single-strand DNA, and subjected to electrophoresis. The resulting band patterns reflect the underlying DNA sequences. The individual bands were tested for associations with asthma, hay fever, and atopy in quantitative and qualitative multivariable analyses. Significantly associated bands were isolated and sequenced. The sequences were compared to a database, and distinct bacteria were identified. RESULTS: Seven of 76 independent bands were found to be inversely associated with asthma, atopic sensitization, and hay fever with odds ratios ranging from 0.17 to 0.73. The bands contained the sequences of Acinetobacter sp., Lactobacillus spp., Neisseria spp., Staphylococcus sciuri, Jeotgalicoccus sp., Corynebacterium spp., and others. CONCLUSIONS: In a diverse microbial environment, certain bacteria may account for the protective effect on the development of asthma and atopy.

Pathophysiology of asthma: lessons from genetic research with particular focus on severe asthma.

There is good evidence that both inherited and environmental factors influence the risk of developing asthma. Only recently, large well-designed studies have been undertaken with the power to identify the genetic causes for asthma, and methods developed in parallel with the Human Genome Project, such as gene expression and epigenetic studies, have made large-scale analyses of functional genetics possible. In this review, we discuss the recent findings from genetic and genomic research studies of asthma, particularly severe asthma, and highlight specific genes for which there are multiple lines of evidence for involvement in asthma pathogenesis. Bio-ontologic enrichment analyses of the most recently identified asthma-related genes point to attributes such as 'molecular and signal transducer activity' and 'immune system processes', which indicates the importance of immunoregulation and inflammatory response in the pathogenesis of asthma. Finally, we discuss how genetic and environmental factors jointly influence asthma susceptibility and summarize how the results may increase understanding of the pathophysiology of asthma-related diseases.

Development and comorbidity of eczema, asthma and rhinitis to age 12: data from the BAMSE birth cohort.

BACKGROUND: Allergy-related diseases are a public health issue, but knowledge on development and comorbidity among children is scarce. The aim was to study the development of eczema, asthma and rhinitis in relation to sex and parental allergy, in a population-based cohort, during childhood. METHODS: At 1, 2, 4, 8 and 12 years, parental questionnaires were used to obtain data on allergy-related diseases. Complete data for all five follow-up occasions were available from 2916 children. Odds ratios for the risk of any allergy-related disease in relation to heredity and sex were calculated using generalized estimating equations. RESULTS: At 12 years, 58% of the children had had eczema, asthma and/or rhinitis at some time. Disease turnover was high for all three diseases throughout the study. Comorbidity increased with age, and at 12 years, 7.5% of all the children were affected by at least two allergy-related diseases. Parental allergy was associated with increased comorbidity and more persistent disease and increased the risk of having any allergy-related disease (adjusted OR 1.76; 95% CI 1.57-1.97) up to 12 years. Male sex was associated with an increased risk throughout childhood. Boys and girls did not differ in disease persistence, and for comorbidity, the differences were minor. CONCLUSIONS: Allergy-related diseases may affect a majority of children. Eczema, asthma and rhinitis develop dynamically throughout childhood, and allergic comorbidity is common. These findings indicate that allergy-related diseases should be neither seen nor studied as isolated entities.

Lifestyle factors and sensitization in children - the ALADDIN birth cohort.

BACKGROUND: Several cross-sectional studies indicate that an anthroposophic lifestyle reduces the risk of allergy in children. We initiated the Assessment of Lifestyle and Allergic Disease During Infancy (ALADDIN) birth cohort to elucidate the role of specific factors supposed to mediate this effect. The aims of this study are to describe the ALADDIN cohort and to report patterns of exposure and allergic sensitization during the first years of life. METHODS: The ALADDIN study is a prospective birth cohort study of 330 children from families with an anthroposophic, partly anthroposophic, or nonanthroposophic lifestyle. The children and their parents were following an extensive data collection scheme, including repeated questionnaires and biological samples. Blood samples were collected from the parents and from the child at birth as well as at 6, 12, and 24 months of age. RESULTS: Several lifestyle factors differed between the groups, such as diet, medication, and place of delivery. Children of families with an anthroposophic lifestyle had a markedly decreased risk of sensitization during the first 2 years of life compared with children of nonanthroposophic families with adjusted OR 0.25 (95% CI 0.10-0.64) and P-value 0.004. A similar situation held true for children from families with a partly anthroposophic lifestyle, adjusted OR 0.31 (95% CI 0.15-0.54), and P-value 0.002. CONCLUSIONS: The anthroposophic lifestyle comprises several factors of interest for allergy development and is here shown to be associated with reduced risk of IgE sensitization already in infancy. Identifying the factors responsible for this association would be of significant clinical importance.

Interaction between early maternal smoking and variants in TNF and GSTP1 in childhood wheezing.

BACKGROUND: Children exposed to tobacco smoke early in life have a higher risk of wheeze. Individual susceptibility may depend on genetic factors. OBJECTIVE: We studied whether variations in single nucleotide polymorphisms (SNPs) in the TNF, glutathione S transferase P1 (GSTP1) and beta2-adrenoreceptor (ADRB2) genes modify the effect of early maternal smoking on the development of childhood asthma, wheeze and allergic sensitization. METHODS: In the Swedish prospective birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) (n=4089), data collection included questionnaires to measure tobacco smoke exposure and clinical outcomes up to age 4 and medical examinations with blood sampling for specific IgE measurements and genotyping. We defined early maternal smoking as daily smoking by the mother during pregnancy and/or postnatally. We investigated five TNF, six GSTP1 and three ADRB2 SNPs in 982 selected wheezers and non-wheezers. RESULTS: An interaction with early maternal smoking was found for three TNF SNPs (-857C/T, Intron 1, Intron 3) with respect to early wheeze (up to 2 years of age). For example, the odds ratio (OR) for developing early wheeze related to early maternal smoking was 2.4 [95% confidence interval (CI) 1.6-3.7] in children with a wild-type CC homozygote genotype of the TNF-857 SNP, while no tobacco-related risk was seen in children carrying the rare T allele. A clear dose response was observed in children with the CC genotype, with an OR of 1.3 (95% CI 1.1-1.5) per each additional pack per week smoked by the mother during pregnancy. A suggestive interaction with early maternal smoking was also seen for three GSTP1 SNPs (Intron 5, Intron 6 and Ile105Val) with respect to transient wheeze, but not for ADRB2 and wheeze phenotypes. No effect modifications were observed for allergic sensitization. CONCLUSION: Our results suggest that the risk of early childhood wheeze associated with early maternal smoking may be modified by TNF and GSTP1 polymorphisms.

Associations of long- and short-term air pollution exposure with markers of inflammation and coagulation in a population sample.

BACKGROUND: Exposure to elevated levels of ambient air pollutants can lead to adverse cardiovascular effects. Potential mechanisms include systemic inflammation and perturbation of the coagulation balance. OBJECTIVES: To investigate long- and short-term effects of air pollution exposure on serum levels of inflammatory (IL-6, TNF-alpha and CRP) and coagulation (fibrinogen and PAI-1) markers relevant for cardiovascular pathology. METHODS: The study group consisted of a population sample of 1028 men and 508 women aged 45-70 years from Stockholm. Long-term air pollution exposure was assessed using spatial modelling of traffic-related NO(2) and heating-related SO(2) emissions at each subject's residential addresses over retrospective periods of 1, 5 and 30 years. Short-term exposure was assessed as averages of rooftop measurements over 12-120 h before blood sampling. RESULTS: Long-term exposures to both traffic-NO(2) and heating-SO(2) emissions showed consistent associations with IL-6 levels. 30-year average traffic-NO(2) exposure was associated with a 64.5% (95% CI 6.7% to 153.8%) increase in serum IL-6 per 28.8 microg/m(3) (corresponding to the difference between the 5th and 95th percentile exposure value), and 30-year exposure to heating-SO(2) with a 67.6% (95% CI 7.1% to 162.2%) increase per 39.4 microg/m(3) (5th-95th percentile value difference). The association appeared stronger in non-smokers, physically active people and hypertensive subjects. We observed positive non-significant associations of inflammatory markers with NO(2) and PM(10) during 24 h before blood sampling. Short-term exposure to O(3) was associated with increased, and SO(2) with decreased, fibrinogen levels. CONCLUSIONS: Our results suggest that exposure to moderate levels of air pollution may influence serum levels of inflammatory markers.

The protective effect of farm animal exposure on childhood allergy is modified by NPSR1 polymorphisms.

BACKGROUND: Little is known about the asthma candidate gene neuropeptide S receptor 1 (NPSR1) in relation to environmental exposures, but recent evidences suggest its role as an effect modifier. OBJECTIVES: To explore the interaction between NPSR1 polymorphisms and environmental exposures related to farming lifestyle and to study the in vitro effects of lipopolysaccharide (LPS) stimulation on NPSR1 expression levels. METHODS: We studied 3113 children from PARSIFAL, a European cross-sectional study on environmental/lifestyle factors and childhood allergy, partly focused on children brought up on a farm. Information on exposures and outcomes was primarily obtained from parental questionnaires. Seven tagging polymorphisms were analysed in a conserved haplotype block of NPSR1. Multivariate logistic regression was used to evaluate a multiplicative model of interaction. NPSR1 protein and messenger RNA (mRNA) levels in monocytes were measured after LPS stimulation by fluorescence activated cell sorting (FACS) and quantitative real-time polymerase chain reaction (PCR). RESULTS: A strong interaction was seen between current regular contact to farm animals and several NPSR1 polymorphisms, particularly rs323922 and rs324377 (p<0.005), with respect to allergic symptoms. Considering the timing of initiation of such current regular farm animal contact, significant interactions with these and two additional polymorphisms (SNP546333, rs740347) were revealed. In response to LPS, NPSR1-A protein levels in monocytes were upregulated (p = 0.002), as were NPSR1-A mRNA levels (p = 0.02). CONCLUSIONS: The effect of farm animal contact on the development of allergic symptoms in children is modified by NPSR1 genetic background.

Gene expression measurements in the context of epidemiological studies.

BACKGROUND: Gene expression measurements became an attractive tool to assess biological responses in epidemiological studies. However, collection of blood samples poses various technical problems. We used gene expression data from two epidemiological studies to evaluate differences between sampling methods, comparability of two methods for measuring RNA levels and stability of RNA samples over time. METHODS: For the PARSIFAL study, PBLC of 1155 children were collected using EDTA tubes in two countries. In the PASTURE study, tubes containing RNA-stabilizing solutions (PAXgene) Blood RNA Tubes; PreAnalytiX) were used to collect cord blood leucocytes of 982 children in five countries. Real-time PCR (conventional single tube assay and high-throughput low density arrays) was used to quantify expression of various innate immunity genes. In 77 PARSIFAL samples, gene expression was measured repeatedly during prolonged storage. RESULTS: In PARSIFAL (EDTA tubes) the median RNA yield after extraction significantly differed between the two centres (70 and 34 ng/microl). Collecting blood into an RNA-stabilizing solution markedly reduced differences in RNA yield in PASTURE (range of medians 91-107 ng/microl). The agreement [Spearman rank correlation (r)] between repeated measurements of gene expression decreased with increasing storage time [e.g., for CD14: r (first/second measurement) = 0.35; r (first/third measurement) = 0.03]. RNA levels measured with either the conventional method or low-density arrays were comparable (r > 0.9). CONCLUSION: Collecting blood samples into tubes containing an RNA-stabilizing solution increases RNA yield and reduces its variability. Long-term storage of samples may lead to RNA degradation, requiring special attention in longitudinal studies.

Symptoms to pollen and fruits early in life and allergic disease at 4 years of age.

BACKGROUND: The predictive value of reported early symptoms to pollen or fruits on later allergic disease is unclear. Our aim is to evaluate if symptoms to pollen and/or to fruits early in life are associated with allergic disease and sensitization to pollen at 4 years. METHODS: The study included 3619 children from the Barn (Children), Allergy, Milieu, Stockholm, Epidemiology project (BAMSE) birth cohort. Reported symptoms of wheeze, sneeze or rash to birch, grass or weed, symptoms (vomiting, diarrhea, rash, facial edema, sneeze, or wheeze) to fruits including tree-nuts at 1 or 2 years of age, and definitions of asthma, rhinitis and eczema at 4 years were derived from questionnaire data. Sensitization to pollen allergens was defined as allergen-specific IgE-antibodies to any pollen (birch/timothy/mugwort) > or =0.35 kU(A)/l. RESULTS: At 1 or 2 years of age, 6% of the children were reported to have pollen-related symptoms, 6% had symptoms to fruits, and 1.4% to both pollen and fruits. Children with symptoms to both pollen and fruits at 1 or 2 years of age had an increased risk for sensitization to any pollen allergen at age 4 (OR(adj) = 4.4, 95% CI = 2.1-9.2). This group of children also had a substantially elevated risk for developing any allergic disease (asthma, rhinitis, or eczema) at 4 years irrespective of sensitization to pollen (OR(adj) = 8.6, 95% CI = 4.5-16.4). CONCLUSIONS: The prevalence of reported symptoms to pollen and fruits is very low in early childhood. However, children with early symptoms to both pollen and fruits appear to have a markedly elevated risk for allergic disease.

Sensitization to inhalant allergens between 4 and 8 years of age is a dynamic process: results from the BAMSE birth cohort.

BACKGROUND: There is limited knowledge of the development of IgE-antibody levels over time in childhood, with respect to persistency and co-sensitization to specific inhalant allergens. METHODS: Data from 2033 children participating in the BAMSE birth cohort was used. Background factors and clinical parameters were obtained and IgE antibody (ab) levels to eight common airborne allergens were measured (>or=0.35 kU(A)/L) when the children were 4 and 8 years of age. RESULTS: Between 4 and 8 years the proportion of children sensitized to any of the inhalant allergens tested increased from 15% to 25%. At 4 years IgE-ab to birch and cat dominated, whereas at the age of 8, there was a considerable increase in the proportion of sensitization to timothy and dog. Except for mites and moulds, IgE-ab levels to all aeroallergens increased significantly between 4 and 8 years among those already sensitized at 4. Transient sensitization to inhalant allergen was uncommon. Furthermore, sensitization to birch pollen at 4 years increased the risk for becoming sensitized to timothy, cat and dog later in life. Such an association was not observed among those sensitized primarily to animal dander. CONCLUSIONS: There is a prominent process of sensitization at pre-school age to inhalant allergens, and in Northern Europe sensitization to birch pollen early in life seems to be important for this process. Such a process has a probable impact on the development of allergic disease in the growing child.