The indoor environment and childhood allergic diseases : the importance of allergens and microbial components

Indoor environmental agents are believed to contribute to allergic disease development. Based upon the prospective cohort "The Environment and Childhood Asthma Study", this thesis explores associations between allergens and microbial substances in the homes and the development of allergic disease in children. Increased levels of cat allergen at 2 years were found to be associated with increased risk of asthma, but not allergic sensitization, at 10 years. On the other hand, the levels of dog allergen, endotoxin (bacteria), and ß(1,3)-glucans (moulds) showed no association with allergic disease. At the age of 10 years, girls had higher levels of cat and dog allergens in mattress dust compared to boys, which could not be explained by more pet keeping. House dust mite allergens were only detected in 12% of the samples, and were associated with symptoms of rhinitis in girls only. Families of children with rhinitis more often avoided pets whereas asthma did not reduce the likelihood of having a pet at home. Factors like parental smoking, single parenthood and having daughters were also found to be important for the families’ choice in regard to pet keeping

Exposure to environmental phenols and parabens, and relation to body mass index, eczema and respiratory outcomes in the Norwegian RHINESSA study

Background Many phenols and parabens are applied in cosmetics, pharmaceuticals and food, to prevent growth of bacteria and fungi. Whether these chemicals affect inflammatory diseases like allergies and overweight is largely unexplored. We aimed to assess the associations of use of personal care products with urine biomarkers levels of phenols and paraben exposure, and whether urine levels (reflecting body burden of this chemical exposures) are associated with eczema, rhinitis, asthma, specific IgE and body mass index. Methods Demographics, clinical variables, and self-report of personal care products use along with urine samples were collected concurrently from 496 adults (48% females, median age: 28 years) and 90 adolescents (10–17 years of age) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan (TCS), triclocarban (TCC), parabens and benzophenone-3, bisphenols and dichlorophenols (DCP) were quantified by mass spectrometry. Results Detection of the urine biomarkers varied according to chemical type and demographics. TCC was detected in 5% of adults and in 45% of adolescents, while propyl (PPB) and methyl (MPB) parabens were detected in 95% of adults and in 94% (PPB) and 99% (MPB) of adolescents. Women had higher median urine concentrations of phenolic chemicals and reported a higher frequency of use of personal care products than men. Urine concentration of MPB increased in a dose-dependent manner with increased frequency of use of several cosmetic products. Overall, urinary biomarker levels of parabens were lower in those with current eczema. The biomarker concentrations of bisphenol S was higher in participants with positive specific IgE and females with current asthma, but did not differ by eczema or rhinitis status. MPB, ethylparaben (EPB), 2,4-DCP and TCS were inversely related to BMI in adults; interaction by gender were not significant. Conclusions Reported frequency of use of personal care products correlated very well with urine biomarker levels of paraben and phenols. Several chemicals were inversley related to BMI, and lower levels of parabens was observed for participants with current eczema. There is a need for further studies of health effects of chemicals from personal care products, in particular in longitudinally designed studies.publishedVersio

Association of oral bacteria with oral hygiene habits and self-reported gingival bleeding

Aim To describe associations of gingival bacterial composition and diversity with self-reported gingival bleeding and oral hygiene habits in a Norwegian regional-based population. Materials and Methods We examined the microbiome composition of the gingival fluid (16S amplicon sequencing) in 484 adult participants (47% females; median age 28 years) in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) study in Bergen, Norway. We explored bacterial diversity and abundance differences by the community periodontal index score, self-reported frequency of gingival bleeding, and oral hygiene habits. Results Gingival bacterial diversity increased with increasing frequency of self-reported gingival bleeding, with higher Shannon diversity index for “always” β = 0.51 and “often” β = 0.75 (p < .001) compared to “never” gingival bleeding. Frequent gingival bleeding was associated with higher abundance of several bacteria such as Porphyromonas endodontalis, Treponema denticola, and Fretibacterium spp., but lower abundance of bacteria within the gram-positive phyla Firmicutes and Actinobacteria. Flossing and rinsing with mouthwash twice daily were associated with higher total abundance of bacteria in the Proteobacteria phylum but with lower bacterial diversity compared to those who never flossed or never used mouthwash. Conclusions A high frequency of self-reported gingival bleeding was associated with higher bacterial diversity than found in participants reporting no gingival bleeding and with higher total abundance of known periodontal pathogens such as Porphyromonas spp., Treponema spp., and Bacteroides spp.publishedVersio

Cow Farmers’ Homes Host More Diverse Airborne Bacterial Communities Than Pig Farmers’ Homes and Suburban Homes

Living on a farm has been linked to a lower risk of immunoregulatory disorders, such as asthma, allergy, and inflammatory bowel disease. It is hypothesized that a decrease in the diversity and composition of indoor microbial communities is a sensible explanation for the upsurge in immunoregulatory diseases, with airborne bacteria contributing to this protective effect. However, the composition of this potentially beneficial microbial community in various farm and suburban indoor environments is still to be characterized. We collected settled airborne dust from stables and the associated farmers’ homes and from suburban homes using electrostatic dust collectors (EDCs) over a period of 14 days. Then, quantitative PCR (qPCR) was used to assess bacterial abundance. The V3–V4 region of the bacterial 16S rRNA gene was amplified and sequenced using Ilumina MiSeq in order to assess microbial diversity. The Divisive Amplicon Denoising Algorithm (DADA2) algorithm was used for the inference of amplicon sequence variants from amplicon data. Airborne bacteria were significantly more abundant in farmers’ indoor environments than in suburban homes (p < 0.001). Cow farmers’ homes had significantly higher bacterial diversity than pig farmers’ and suburban homes (p < 0.001). Bacterial taxa, such as Firmicutes, Prevotellaceae, Lachnospiraceae, and Lactobacillus were significantly more abundant in farmers’ homes than suburban homes, and the same was true for beneficial intestinal bacterial species, such as Lactobacillus amylovorus, Eubacterium hallii, and Faecalibacterium prausnitzii. Furthermore, we found a higher similarity between bacterial communities in individual farmers’ homes and their associated cow stables than for pig stables. Our findings contribute with important knowledge on bacterial composition, abundance, and diversity in different environments, which is highly valuable in the discussion on how microbial exposure may contribute to the development of immune-mediated diseases in both children and adults.publishedVersio

Epigenome-wide association of father's smoking with offspring DNA methylation: a hypothesis-generating study

Epidemiological studies suggest that father’s smoking might influence their future children’s health, but few studies have addressed whether paternal line effects might be related to altered DNA methylation patterns in the offspring. To investigate a potential association between fathers’ smoking exposures and offspring DNA methylation using epigenome-wide association studies. We used data from 195 males and females (11–54 years) participating in two population-based cohorts. DNA methylation was quantified in whole blood using Illumina Infinium MethylationEPIC Beadchip. Comb-p was used to analyse differentially methylated regions (DMRs). Robust multivariate linear models, adjusted for personal/maternal smoking and cell-type proportion, were used to analyse offspring differentially associated probes (DMPs) related to paternal smoking. In sensitivity analyses, we adjusted for socio-economic position and clustering by family. Adjustment for inflation was based on estimation of the empirical null distribution in BACON. Enrichment and pathway analyses were performed on genes annotated to cytosine-phosphate-guanine (CpG) sites using the gometh function in missMethyl. We identified six significant DMRs (Sidak-corrected P values: 0.0006–0.0173), associated with paternal smoking, annotated to genes involved in innate and adaptive immunity, fatty acid synthesis, development and function of neuronal systems and cellular processes. DMP analysis identified 33 CpGs [false discovery rate (FDR)  < 0.05]. Following adjustment for genomic control (λ = 1.462), no DMPs remained epigenome-wide significant (FDR < 0.05). This hypothesis-generating study found that fathers’ smoking was associated with differential methylation in their adolescent and adult offspring. Future studies are needed to explore the intriguing hypothesis that fathers’ exposures might persistently modify their future offspring’s epigenome.publishedVersio

Prevalence of allergic sensitization to storage mites in Northern Europe.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBACKGROUND: Allergic sensitization to storage mites has mostly been related to occupational exposures like farming, grain/cattle handling, whereas for non-occupational settings, storage mite sensitization has been attributed to cross-reactivity with house dust mite (HDM) allergens. OBJECTIVE: We aimed to describe the prevalence of allergic sensitization to storage mites, co-sensitization to HDM allergens and respiratory symptoms in Denmark, Iceland, Norway and Sweden. METHODS: The population comprised of 1180 participants born 1945-1972 of the third follow-up of the population-based cohort European Community Respiratory Health Survey (ECRHS) in Aarhus, Bergen, Reykjavik and Uppsala. A clinical examination included skin prick tests (SPT) to Lepidoglyphus destructor, Tyrophagus putrescentiae, Acarus siro and common inhalant allergens, as well as standardized interviews. RESULTS: 8% were sensitized to HDM and 10% to storage mite, with some variation by study centre: Reykjavik 13%, Bergen 8% and Aarhus 7%. In Uppsala, only L destructor (3%) was measured. Storage mite sensitization was higher among men (11%) than women (8%). Among storage mite sensitized, 44% were also sensitized to HDM. Storage mite sensitization was associated with asthma and nasal allergies, but not with age, education, pet keeping or place of upbringing. CONCLUSIONS AND CLINICAL RELEVANCE: In this Northern European population-based study, allergic sensitization to storage mite was as common as HDM sensitization. Storage mite sensitization was, independently of HDM sensitization, associated with respiratory symptoms and asthma. Our findings suggest that storage mite sensitization should be evaluated with regard to inclusion into the common inhalant allergen panel in Northern Europe.Landspitali University Hospital Research Fund University of Iceland Research Fund ResMed Foundation, California, USA Orkuveita Reykjavikur (Geothermal plant) Vegageroin (The Icelandic Road Administration (ICERA)) Swedish Heart-Lung Foundation Swedish Asthma and Allergy Association Swedish Association against Lung and Heart Disease Swedish Research Council for health, working life and welfare (FORTE) Research Council of Norway Western Norway Regional Health Authorities grant Bergen Medical Research Foundation Faculty of Health, Aarhus University Wood Dust Foundatio

Long-term exposure to low-level air pollution and greenness and mortality in Northern Europe. The Life-GAP project

Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.Background: Air pollution has been linked to mortality, but there are few studies examining the association with different exposure time windows spanning across several decades. The evidence for the effects of green space and mortality is contradictory. Objective: We investigated all-cause mortality in relation to exposure to particulate matter (PM2.5 and PM10), black carbon (BC), nitrogen dioxide (NO2), ozone (O3) and greenness (normalized difference vegetation index - NDVI) across different exposure time windows. Methods: The exposure assessment was based on a combination of the Danish Eulerian Hemispheric Model and the Urban Background Model for the years 1990, 2000 and 2010. The analysis included a complete case dataset with 9,135 participants from the third Respiratory Health in Northern Europe study (RHINE III), aged 40–65 years in 2010, with mortality follow-up to 2021. We performed Cox proportional hazard models, adjusting for potential confounders. Results: Altogether, 327 (3.6 %) persons died in the period 2010–2021. Increased exposures in 1990 of PM2.5, PM10, BC and NO2 were associated with increased all-cause mortality hazard ratios of 1.40 (95 % CI1.04–1.87 per 5 μg/m3), 1.33 (95 % CI: 1.02–1.74 per 10 μg/m3), 1.16 (95 % CI: 0.98–1.38 per 0.4 μg/m3) and 1.17 (95 % CI: 0.92–1.50 per 10 μg/m3), respectively. No statistically significant associations were observed between air pollution and mortality in other time windows. O3 showed an inverse association with mortality, while no association was observed between greenness and mortality. Adjusting for NDVI increased the hazard ratios for PM2.5, PM10, BC and NO2 exposures in 1990. We did not find significant interactions between greenness and air pollution metrics. Conclusion: Long term exposure to even low levels of air pollution is associated with mortality. Opening up for a long latency period, our findings indicate that air pollution exposures over time may be even more harmful than anticipated.Peer reviewe

A three-generation study on the association of tobacco smoking with asthma

Background: Mothers' smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers' smoking may have a similar effect, and biological plausibility that fathers' smoking during adolescence may influence offspring's health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma. Methods: Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged <= 51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents' (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines. Results: Fathers' smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01-2.01] and mothers' smoking during pregnancy (RRR = 1.27, 95% CI: 1.01-1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers' smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17-2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02-1.55). Conclusions: Fathers' smoking during early adolescence and grandmothers' and mothers' smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception