Browsing by Subject "EXPOSURE"

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  • Halonen, Jaana I.; Erhola, Marina; Furman, Eeva; Haahtela, Tari; Jousilahti, Pekka; Barouki, Robert; Bergman, Åke; Billo, Nils E.; Fuller, Richard; Haines, Andrew; Kogevinas, Manolis; Kolossa-Gehring, Marike; Krauze, Kinga; Lanki, Timo; Vicente, Joana Lobo; Messerli, Peter; Nieuwenhuijsen, Mark; Paloniemi, Riikka; Peters, Annette; Posch, Karl-Heinz; Timonen, Pekka; Vermeulen, Roel; Virtanen, Suvi M.; Bousquet, Jean; Antó, Josep M. (2021)
    In 2015, the Rockefeller Foundation-Lancet Commission launched a report introducing a novel approach called Planetary Health and proposed a concept, a strategy and a course of action. To discuss the concept of Planetary Health in the context of Europe, a conference entitled: “Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health” was held in Helsinki in December 2019. The conference participants concluded with a need for action to support Planetary Health during the 2020s. The Helsinki Declaration emphasizes the urgency to act as scientific evidence shows that human activities are causing climate change, biodiversity loss, land degradation, overuse of natural resources and pollution. They threaten the health and safety of human kind. Global, regional, national, local and individual initiatives are called for and multidisciplinary and multisectorial actions and measures are needed. A framework for an action plan is suggested that can be modified for local needs. Accordingly, a shift from fragmented approaches to policy and practice towards systematic actions will promote human health and health of the planet. Systems thinking will feed into conserving nature and biodiversity, and into halting climate change. The Planetary Health paradigm ‒ the health of human civilization and the state of natural systems on which it depends ‒ must become the driver for all policies.
  • Haarala, Anna Karoliina; Sinikumpu, Suvi-Paivikki; Vaaramo, Eeva; Jokelainen, Jari; Timonen, Markku; Auvinen, Juha; Pekkanen, Juha; Huilaja, Laura (2021)
    Data are insufficient on the protective effect of a farm environment in childhood regarding sensitization in middle age and new-onset sensitization in adulthood. A skin prick test (SPT) and questionnaire data from the Northern Finland Birth Cohort 1966 study (NFBC66) were used to investigate sensitization at age 46 years related to childhood living environment. A subpopulation of 3409 participants was analyzed to study factors related to new-onset sensitization between ages of 31 and 46 years. Data on complete SPTs were available for 5373 cohort members at age 46. Professional farming by parents (odds ratio (OR) 0.54; 95% confidence interval (CI) 0.43-0.68) and keeping of farm animals (OR 0.53; 95% CI 0.43-0.66) in infancy were associated with a lower risk of sensitization at age 46. Sensitization (OR 0.58; 95% CI 0.47-0.72) and polysensitization (OR 0.43; 95% CI 0.32-0.57) were less common in those who lived in a rural area in infancy compared to a city area. The childhood living environment had no effect on new-onset sensitization between ages 31 and 46. We conclude that living on a farm or in a rural environment in childhood had a protective effect on sensitization even in middle age, but these factors did not protect from new-onset sensitization in adults.
  • Vepsäläinen, Henna; Skaffari, Essi; Wojtkowska, Katarzyna; Barlińska, Julia; Kinnunen, Satu Marjaana; Makkonen, Riikka Kyllikki; Heikkilä, Maria; Lehtovirta, Mikko; Ray, Carola Marie-Lousie; Suhonen, Eira; Nevalainen, Jaakko; Sajaniemi, Nina; Erkkola, Maijaliisa (2022)
    Background: Early childhood education and care (ECEC) centers are ideal venues for food education. As smartphones and tablets are becoming increasingly popular in ECEC centers, technology can be used to deliver such pedagogical content. Evidence suggests that video games can affect fruit and vegetable (FV) consumption among 9-to 12-year-old children, but studies among preschoolers are scarce. Objective: This paper describes the development of the Mole's Veggie Adventures app and its effectiveness in increasing FV acceptance among Finnish and Polish preschoolers aged 3 to 6 years. Methods: A multiprofessional team created an app to be used in ECEC centers in groups of 3 to 10 children. The app aimed to increase vegetable acceptance, and it was built using elements that support the development of self-regulation and social skills. Altogether, 7 Finnish and 4 Polish ECEC centers participated in the study. Before randomization, parents reported background factors and their children's willingness to taste different FVs. The ECEC professionals in the intervention arm were instructed to use the app at least once a week during the 3-to 4-week intervention period. The main outcomes in this unblinded, cluster-randomized study were FV acceptance and relative FV acceptance. The first was calculated as a sum variable describing the children's willingness to taste 25 different FVs, the second as FV acceptance divided by the number of FVs served. We used analysis of covariance to compare the FV acceptance and relative FV acceptance scores between the intervention and control groups at follow-up. Results: A total of 221 children were included in the analysis. At follow-up, the intervention group (115/221, 52%) had higher FV acceptance scores (baseline adjusted difference of mean 7.22; 95% CI 1.41-13.03) than the control group (106/221, 48%). The intervention effect was parallel for relative FV acceptance scores (baseline adjusted difference of mean 0.28; 95% CI 0.05-0.52). Conclusions: The Mole's Veggie Adventures app has the potential to increase FV acceptance among preschoolers and can be a valuable tool in supporting food education in ECEC centers. Furthermore, the app can be feasibly incorporated into preschool routines in countries with different educational environments. Trial Registration: NCT05173311; (JMIR Mhealth Uhealth 2022;10(1):e30352) doi: 10.2196/30352
  • Demmler, Joanne C.; Gosztonyi, Ákos; Du, Yaxing; Leinonen, Matti; Ruotsalainen, Laura; Järvi , Leena; Ala-Mantila, Sanna (2021)
    Background Air pollution is one of the major environmental challenges cities worldwide face today. Planning healthy environments for all future populations, whilst considering the ongoing demand for urbanisation and provisions needed to combat climate change, remains a difficult task. Objective To combine artificial intelligence (AI), atmospheric and social sciences to provide urban planning solutions that optimise local air quality by applying novel methods and taking into consideration population structures and traffic flows. Methods We will use high-resolution spatial data and linked electronic population cohort for Helsinki Metropolitan Area (Finland) to model (a) population dynamics and urban inequality related to air pollution; (b) detailed aerosol dynamics, aerosol and gas-phase chemistry together with detailed flow characteristics; (c) high-resolution traffic flow addressing dynamical changes at the city environment, such as accidents, construction work and unexpected congestion. Finally, we will fuse the information resulting from these models into an optimal city planning model balancing air quality, comfort, accessibility and travelling efficiency.
  • Odeh, Issam; Hussein, Tareq (2016)
    Knowledge of human activity patterns is needed in air pollution exposure and health risk assessment. However, human activity patterns have never been evaluated in the Eastern Mediterranean societies. Therefore, we investigated the activity pattern of 285 subjects (17-63 years) in Amman, Jordan during October to November, 2015. The subjects spent >80% of their time indoors during weekend days and >85% on workdays. They spent similar to 4.8% and similar to 5.7% in transportation during weekend days and workdays, respectively. Males had a different activity pattern than females on weekend days, but both genders had similar activity patterns on workdays. On workdays, males spent less time indoors than females. The activity pattern found in this study is a bit different than that for North Americans and Europeans, who spend more time indoors and in transit. The activity pattern found in this study was very different than that observed for Koreans, who spent about 59% and 67% indoors on workdays and weekend, respectively. The main outcomes of this survey can be utilized in human exposure studies. This study and the upcoming future studies have been encouraged and supported by the regional WHO office in Amman.
  • Maragkidou, Androniki; Jaghbeir, Omar; Hämeri, Kaarle; Hussein, Tareq (2018)
    In this study, we measured the concentrations of accumulation and coarse particles inside an educational workshop (March 31–April 6, 2015), calculated particle emission and losses rates, and estimated inhaled deposited dose. We used an Optical Particle Sizer (TSI OPS 3330) that measures the particle number size distribution (diameter 0.3–10 μm) and we converted that into particle mass size distribution (assuming spherical particles and unit density). We focused on two particle size fractions: 0.3–1 μm (referred as PN0.3−1 and PM0.3−1) and 1–10 μm (referred as PN1−10 and PM1−10). The occupants' activities included coffee brewing, lecturing, tobacco smoking, welding, scrubbing, and sorting/drilling iron. The highest concentrations were observed during welding with PN0.3−1 (PM0.3−1) was ∼1866 cm−3 (55 μg/m3) and PN1−10 (PM1−10) was ∼7 cm−3 (103 μg/m3). The lowest concentrations were observed during coffee brewing and metal turning with PN0.3−1 (PM0.3−1) was ∼22 cm−3 (0.7 μg/m3) and PN1−10 (PM1−10) was ∼0.5 cm−3 (4 μg/m3). The emissions rate of coarse particles was 85–1010 particles/hour × cm3 whereas that for submicron particle in the diameter range 0.3–1 μm was 5.7 × 104–9.3 × 104 particles/hour × cm3 depending on the activity and the ventilation rate. The coarse particles losses rate was 0.35–2.1 h−1 and the ventilation rate was 0.24–2.1 h−1. The alveolar received the majority and particles below 1 μm with a fraction of about 53% of the total inhaled deposited dose whereas the head/throat region received about 18%. This study is important for better understanding the health effects at educational workshops.
  • Malanchini, Margherita; Smith-Woolley, Emily; Ayorech, Ziada; Rimfeld, Kaili; Krapohl, Eva; Vuoksimaa, Eero; Korhonen, Tellervo; Bartels, Meike; van Beijsterveldt, Toos C. E. M.; Rose, Richard J.; Lundstrom, Sebastian; Anckarsater, Henrik; Kaprio, Jaakko; Lichtenstein, Paul; Boomsma, Dorret I.; Plomin, Robert (2019)
    Background Maternal smoking during pregnancy (MSDP) has been linked to offspring's externalizing problems. It has been argued that socio-demographic factors (e.g. maternal age and education), co-occurring environmental risk factors, or pleiotropic genetic effects may account for the association between MSDP and later outcomes. This study provides a comprehensive investigation of the association between MSDP and a single harmonized component of externalizing: aggressive behaviour, measured throughout childhood and adolescence. Methods Data came from four prospective twin cohorts - Twins Early Development Study, Netherlands Twin Register, Childhood and Adolescent Twin Study of Sweden, and FinnTwin12 study - who collaborate in the EU-ACTION consortium. Data from 30 708 unrelated individuals were analysed. Based on item level data, a harmonized measure of aggression was created at ages 9-10; 12; 14-15 and 16-18. Results MSDP predicted aggression in childhood and adolescence. A meta-analysis across the four samples found the independent effect of MSDP to be 0.4% (r = 0.066), this remained consistent when analyses were performed separately by sex. All other perinatal factors combined explained 1.1% of the variance in aggression across all ages and samples (r = 0.112). Paternal smoking and aggressive parenting strategies did not account for the MSDP-aggression association, consistent with the hypothesis of a small direct link between MSDP and aggression. Conclusions Perinatal factors, including MSDP, account for a small portion of the variance in aggression in childhood and adolescence. Later experiences may play a greater role in shaping adolescents' aggressive behaviour.
  • Korpela, Katri; Salonen, Anne; Saxen, Harri; Nikkonen, Anne; Peltola, Ville; Jaakkola, Tytti; de Vos, Willem; Kolho, Kaija-Leena (2020)
    BACKGROUND The effects of antibiotics on infant gut microbiota are unclear. We hypothesized that the use of common antibiotics results in long-term aberration in gut microbiota. METHODS Antibiotic-naive infants were prospectively recruited when hospitalized because of a respiratory syncytial virus infection. Composition of fecal microbiota was compared between those receiving antibiotics during follow-up (prescribed at clinicians' discretion because of complications such as otitis media) and those with no antibiotic exposure. Fecal sampling started on day 1, then continued at 2-day intervals during the hospital stay, and at 1, 3 and 6 months at home. RESULTS One hundred and sixty-three fecal samples from 40 patients (median age 2.3 months at baseline; 22 exposed to antibiotics) were available for microbiota analyses. A single course of amoxicillin or macrolide resulted in aberration of infant microbiota characterized by variation in the abundance of bifidobacteria, enterobacteria and clostridia, lasting for several months. Recovery from the antibiotics was associated with an increase in clostridia. Occasionally, antibiotic use resulted in microbiota profiles associated with inflammatory conditions. CONCLUSIONS Antibiotic use in infants modifies especially bifidobacterial levels. Further studies are warranted whether administration of bifidobacteria will provide health benefits by normalizing the microbiota in infants receiving antibiotics.
  • Weichert, I.; Romero-Ortuno, R.; Tolonen, J.; Soe, T.; Lebus, C.; Choudhury, S.; Nadarajah, C. V.; Nanayakkara, P.; Orru, M.; Di Somma, S. (2018)
    What is known and objectiveDrugs with anticholinergic properties increase the risk of falls, delirium, chronic cognitive impairment, and mortality and counteract procholinergic medications used in the treatment of dementia. Medication review and optimisation to reduce anticholinergic burden in patients at risk is recommended by specialist bodies. Little is known how effective this review is in patients who present acutely and how often drugs with anticholinergic properties are used temporarily during an admission. The aim of the study was to describe the changes in the anticholinergic cognitive burden (ACB) in patients admitted to hospital with a diagnosis of delirium, chronic cognitive impairment or falls and to look at the temporary use of anticholinergic medications during hospital stay. MethodsThis is a multi-centre observational study that was conducted in seven different hospitals in the UK, Finland, The Netherlands and Italy. Results and discussion21.1% of patients had their ACB score reduced by a mean of 1.7%, 19.7% had their ACB increased by a mean of 1.6%, 22.8% of DAP naive patients were discharged on anticholinergic medications. There was no change in the ACB scores in 59.2% of patients. 54.1% of patients on procholinergics were taking anticholinergics. Out of the 98 medications on the ACB scale, only 56 were seen. Medications with a low individual burden were accounting for 64.9% of the total burden. Anticholinergic drugs were used temporarily during the admission in 21.9% of all patients. A higher number of DAPs used temporarily during admission was associated with a higher risk of ACB score increase on discharge (OR=1.82, 95% CI for OR: 1.36-2.45, P What is new and conclusionThere was no reduction in anticholinergic cognitive burden during the acute admissions. This was the same for all diagnostic subgroups. The anticholinergic load was predominantly caused by medications with a low individual burden. More than 1 in 5 patients not taking anticholinergics on admission were discharged on them and similar numbers saw temporary use of these medications during their admission. More than half of patients on cholinesterase-inhibitors were taking anticholinergics at the same time on admission, potentially directly counteracting their effects.
  • Raju, Sajan C.; Viljakainen, Heli; Figueiredo, Rejane A. O.; Neuvonen, Pertti J.; Eriksson, Johan G.; Weiderpass, Elisabete; Rounge, Trine B. (2020)
    Background: The human microbiota contributes to health and well-being. Antimicrobials (AM) have an immediate effect on microbial diversity and composition in the gut, but next to nothing is known about their long-term contribution to saliva microbiota. Our objectives were to investigate the long-term impact of AM use on saliva microbiota diversity and composition in preadolescents. We compared the lifetime effects by gender and AMs. We used data from 808 randomly selected children in the Finnish Health In Teens (Fin-HIT) cohort with register-based data on AM purchases from the Social Insurance Institution of Finland. Saliva microbiota was assessed with 16S rRNA (V3-V4) sequencing. The sequences were aligned to the SILVA ribosomal RNA database and classified and counted using the mothur pipeline. Associations between AM use and alpha-diversity (Shannon index) were identified with linear regression, while associations between beta-diversity (Bray-Curtis dissimilarity) and low, medium or high AM use were identified with PERMANOVA. Results: Of the children, 53.6% were girls and their mean age was 11.7 (0.4) years. On average, the children had 7.4 (ranging from 0 to 41) AM prescriptions during their lifespan. The four most commonly used AMs were amoxicillin (n= 2622, 43.7%), azithromycin (n= 1495, 24.9%), amoxicillin-clavulanate (n= 1123, 18.7%) and phenoxymethylpenicillin (n= 408, 6.8%). A linear inverse association was observed between the use of azithromycin and Shannon index (b- 0.015,pvalue = 0.002) in all children, the effect was driven by girls (b- 0.032,pvalue = 0.001), while not present in boys. Dissimilarities were marked between high, medium and low users of all AMs combined, in azithromycin users specifically, and in boys with amoxicillin use. Amoxicillin and amoxicillin-clavulanate use was associated with the largest decrease in abundance ofRikenellaceae. AM use in general and phenoxymethylpenicillin specifically were associated with a decrease ofPaludibacterand pathways related to amino acid degradations differed in proportion between high and low AM users. Conclusions: A systematic approach utilising reliable registry data on lifetime use of AMs demonstrated long-term effects on saliva microbiota diversity and composition. These effects are gender- and AM-dependent. We found that frequent lifelong use of AMs shifts bacterial profiles years later, which might have unforeseen health impacts in the future. Our findings emphasise a concern for high azithromycin use, which substantially decreases bacterial diversity and affects composition as well. Further studies are needed to determine the clinical implications of our findings.
  • Leppilahti, Jussi; Majuri, Marja-Leena; Sorsa, Timo; Hirvonen, Ari; Piirilä, Päivi (2019)
    Introduction: Di-isocyanates TDI (toluene di-isocyanate), MDI (diphenylmethane di-isocyanate), and HDI (hexamethylene di-isocyanate) are the most common chemicals causing occupational asthma. Di-isocyanate inhalation has been reported to induce oxidative stress via reactive oxygen and nitrogen species leading to tissue injury. Glutathione transferases (GSTs) and N-acetyltransferases (NATs) are detoxifying enzymes whose general function is to inactivate electrophilic substances. The most important genes regulating these enzymes, i.e., GSTM1, GSTP1, GSTT1, NAT1, and NAT2 have polymorphic variants resulting in enhanced or lowered enzyme activities. Since inability to detoxify harmful oxidants can lead to inflammatory processes involving activation of bronchoconstrictive mechanisms, we studied whether the altered GST and NAT genotypes were associated with bronchial hyperreactivity (BHR) in patients with di-isocyanate exposure related occupational asthma, irrespective of cessation of di-isocyanate exposure, and adequacy of asthma treatment.Methods: Polymerase chain reaction (PCR) based methods were used to analyze nine common polymorphisms in GSTM1, GSTM3, GSTP1, GSTT1, NAT1, and NAT2 genes in 108 patients with diagnosed occupational di-isocyanate-induced asthma. The genotype data were compared with spirometric lung function and BHR status at diagnosis and in the follow-up examination on average 11 years (range 1–22 years) after the asthma diagnosis. Serum IgE and IL13 levels were also assessed in the follow-up phase.Results: An association between BHR and GSTP1 slow activity (Val105/Val105) genotype was demonstrated in the subjects at the follow-up phase but not at the diagnosis phase. Moreover, the patients with the GSTP1 slow activity genotype exhibited characteristics of Th-2 type immune response more often compared to those with the unaltered GSTP1 gene. Interestingly, all 10 patients with the GSTP1 slow activity genotype had both the GSTM3 slow activity genotype and the unaltered GSTT1 gene.Discussion: The results suggest associations of the low activity variants of the GSTP1 gene with BHR. The fact that these associations came up only at the follow-up phase when the subjects were not any more exposed to di-isocyanates, and used asthma medication, suggest that medication and environmental factors influence the presentation of these associations. However, due to the exploratory character of the study and relatively small study size, the findings remain to be confirmed in future studies with larger sample sizes.
  • Savelieva, Kateryna; Marttila, Tero; Lampi, Jussi; Ung-Lanki, Sari; Elovainio, Marko; Pekkanen, Juha (2019)
  • Vari, Heli; Roslund, Marja; Oikarinen, Sami; Nurminen, Noora; Puhakka, Riikka; Parajuli, Anirudra; Grönroos, Mira; Siter, Nathan; Laitinen, Olli; Hyöty, Heikki; Rajaniemi, Juho; Rantalainen, Anna-Lea; Sinkkonen, Aki; The ADELE Research Group (2021)
    There is evidence that polycyclic aromatic hydrocarbons (PAHs) and human gut microbiota are associated with the modulation of endocrine signaling pathways. Independently, studies have found associations between air pollution, land cover and commensal microbiota. We are the first to estimate the interaction between land cover categories associated with air pollution or purification, PAH levels and endocrine signaling predicted from gut metagenome among urban and rural populations. The study participants were elderly people (65-79 years); 30 lived in rural and 32 in urban areas. Semi-Permeable Membrane devices were utilized to measure air PAH concentrations as they simulate the process of bioconcentration in the fatty tissues. Land cover categories were estimated using CORINE database and geographic information system. Functional orthologues for peroxisome proliferator-activated receptor (PPAR) pathway in endocrine system were analyzed from gut bacterial metagenome with Kyoto Encyclopaedia of Genes and Genomes. High coverage of broad-leaved and mixed forests around the homes were associated with decreased PAH levels in ambient air, while gut functional orthologues for PPAR pathway increased along with these forest types. The difference between urban and rural PAH concentrations was not notable. However, some rural measurements were higher than the urban average, which was due to the use of heavy equipment on active farms. The provision of air purification by forests might be an important determining factor in the context of endocrine disruption potential of PAHs. Particularly broad-leaved forests around homes may reduce PAH levels in ambient air and balance pollution-induced disturbances within commensal gut microbiota. (C) 2020 The Author(s). Published by Elsevier Ltd.
  • Karvala, Kirsi; Uitti, Jukka; Taponen, Saara; Luukkonen, Ritva; Lehtimäki, Lauri (2018)
    Objective: To study the association between perceptions of various triggers of asthma and employment status. Methods: A questionnaire was administered to all those adults living in the city of Tampere, Finland, who were entitled to special reimbursement for asthma medication by the Social Insurance Institution (n = 2613). The response rate was 79%. The study population (n = 1657) consisted of individuals who worked full-time (n = 967), were unemployed (n = 197), had all-cause work disability (n = 334), or were retired due to old age (n = 159). Given a list of potential asthma triggers, the respondents were asked how often (never/sometimes/often) the trigger caused or worsened their asthma symptoms during leisure time. Results: After adjusting for background variables (age, sex, smoking, and professional status), frequency of asthma symptoms, and the use of asthma medication during the last year, any individual trigger identified as asthma-relevant was associated with having work disability (vs. working full-time). The highest odds ratio (OR) was found for vehicle exhaust (OR 5.0, CI 2.2-11.4). We found similar but less consistent associations between asthma trigger perceptions and unemployment. No elevated ORs were found regarding asthma trigger perceptions for old-age retirement. Conclusions: Perceptions of asthma triggers are associated with all-cause work disability. Our findings suggest that asthmatics have excess trigger perceptions that are not explained by asthma alone. Asthmatics need to be informed that inaccurate trigger perceptions may develop, and how they are induced, because unnecessary trigger avoidance may interfere with work life.
  • Päivinen, Marja; Keskinen, Kari; Putus, Tuula; Kujala, Urho M.; Kalliokoski, Pentti; Tikkanen, Heikki O. (2021)
    Background Respiratory symptoms are common in competitive swimmers. However, among these and in swimmers at other activity levels the swimming distance, the total spent time in swimming halls and their medical background varies. Our objectives were, first, to assess their medical histories and the associations with respiratory symptoms among swimmers in different activity groups and then second, to study the pulmonary function findings and related medications in competitive swimmers who exercise in swimming hall environments the most. Methods First, 1118 participants consisting of 133 competitive-, 734 fitness- and 251 occasional swimmers answered questionnaires concerning their medical background, their respiratory symptoms in connection to swimming distance and their amount of time spent in swimming halls. Secondly, in 130 competitive swimmers, pulmonary function was tested by spirometry and a specific questionnaire was used to assess respiratory symptoms, medical histories and prescribed medication. Results Respiratory symptoms were reported by 18% of the studied swimmers. Competitive swimmers had significantly more symptoms than fitness- and occasional swimmers. Naturally competitive swimmers swum more than 2000 m and stayed by the pool more than 90 min, longer than the other activity groups of swimmers. Spirometry testing showed airway obstruction in 15 swimmers, which was 12% of the 130 competitive swimmers. 21 of them, had physician-diagnosed asthma and 16 of these individuals had prescribed medication for it. Conclusions Competitive swimmers had the highest swimming hall exposure and reported significantly more respiratory symptoms. A high prevalence of airway obstruction findings in competitive swimmers with asthma and allergies suggests a need for future recommendations for regular testing and special medical care for competitive swimmers.
  • Twardziok, Monika; Schroder, Paul C.; Krusche, Johanna; Casaca, Vera I.; Illi, Sabina; Bock, Andreas; Loss, Georg J.; Kabesch, Michael; Toncheva, Antoaneta A.; Roduit, Caroline; Depner, Martin; Genuneit, Jon; Renz, Harald; Roponen, Marjut; Weber, Juliane; Braun-Fahrlander, Charlotte; Riedler, Josef; Lauener, Roger; Vuitton, Dominique Angele; Dalphin, Jean-Charles; Pekkanen, Juha; von Mutius, Erika; Schaub, Bianca; PASTURE Study Grp; Hyvarinen, Anne; Karvonen, Anne M.; Kirjavainen, Pirkka V.; Remes, Sami; Kaulek, Vincent; Dalphin, Marie-Laure; Ege, Markus; Pfefferle, Petra I.; Doekes, Gert (2017)
    Several studies report an important role of CD8(+) cytotoxic T-cells in atopy. Farm children show protection against atopy development, partly explained by CD4(+) T-cell subtypes. Additional effects of CD8(+) T-cells are unknown being investigated in this study within the PASTURE/EFRAIM birth cohort in PBMCs from farming and non-farming 6-year-old (N = 76) German children. CD3(+) CD8(+) CD25(+) T-cells were analyzed by flow cytometry. Genotyping of 17q21 locus-SNPs associated with childhood asthma was performed. No differences in CD8(+) T-cell subsets were seen between farmers and non-farmers regardless of asthma. Among farm children, asthmatics displayed increased CD3(+) CD8(low)(CD25(+)) T-cells compared to non-asthmatics. Asthmatic farm children exhibited a lower PI-induced stimulatory capacity of CD3(+) CD8(low)(CD25(+)) cells and a lower IFN-gamma secretion than non-asthmatic farm children. Among farm children with GSDMB and ORMDL3 risk alleles, asthmatics displayed higher CD3(+) CD8(low) cells than non-asthmatics. Our data indicates a specific role of CD8(low) T-cells in asthmatic farm children. (C) 2017 Elsevier Inc. All rights reserved.
  • Czamara, Darina; Dieckmann, Linda; Roeh, Simone; Kraemer, Sarah; Rancourt, Rebecca C.; Sammallahti, Sara; Kajantie, Eero; Laivuori, Hannele; Eriksson, Johan G.; Räikkönen, Katri; Henrich, Wolfgang; Plagemann, Andreas; Binder, Elisabeth B.; Braun, Thorsten; Entringer, Sonja (2021)
    Background Glucocorticoids (GCs) play a pivotal role in fetal programming. Antenatal treatment with synthetic GCs (sGCs) in individuals in danger of preterm labor is common practice. Adverse short- and long-term effects of antenatal sGCs have been reported, but their effects on placental epigenetic characteristics have never been systematically studied in humans. Results We tested the association between exposure to the sGC betamethasone (BET) and placental DNA methylation (DNAm) in 52 exposed cases and 84 gestational-age-matched controls. We fine-mapped associated loci using targeted bisulfite sequencing. The association of placental DNAm with gene expression and co-expression analysis on implicated genes was performed in an independent cohort including 494 placentas. Exposure to BET was significantly associated with lower placenta DNAm at an enhancer of FKBP5. FKBP5 (FK506-binding protein 51) is a co-chaperone that modulates glucocorticoid receptor activity. Lower DNAm at this enhancer site was associated with higher expression of FKBP5 and a co-expressed gene module. This module is enriched for genes associated with preeclampsia and involved in inflammation and immune response. Conclusions Our findings suggest that BET exposure during pregnancy associates with few but lasting changes in placental DNAm and may promote a gene expression profile associated with placental dysfunction and increased inflammation. This may represent a pathway mediating GC-associated negative long-term consequences and health outcomes in offspring.
  • Hakomaki, Henriikka; Eskola, Sophia; Kokki, Hannu; Lehtonen, Marko; Räsänen, Juha; Laaksonen, Sakari; Voipio, Hanna-Marja; Ranta, Veli-Pekka; Kokki, Merja (2022)
    Buprenorphine is used during pregnancy for the treatment of opioid use disorder. Limited data exist on the central nervous system (CNS) permeation and distribution, and on the fetal exposure to buprenorphine. The aim of our study was to determine the extent of buprenorphine distribution to CNS in the pregnant sheep, and their fetus at steady-state, and their newborn lambs postdelivery, using three different dosing regimens. Twenty-eight pregnant ewes in late gestation received buprenorphine via 7-day transdermal patch releasing buprenorphine 20 mu g/h (n=9) or 40 mu g/h (n=11), or an extended-release 8 mg/week subcutaneous injection (n=8). Plasma, cerebrospinal fluid, and CNS tissue samples were collected at steady-state from ewes and fetuses, and from lambs 0.33 - 45 hours after delivery. High accumulation of buprenorphine was observed in all CNS tissues. The median CNS/plasma concentration-ratios of buprenorphine in different CNS areas ranged between 13 and 50 in the ewes, and between 26 and 198 in the fetuses. In the ewes the CNS/plasma-ratios were similar after the three dosing regimens, but higher in the fetuses in the 40 mu g/h dosing group, medians 65 - 122, than in the 20 mu g/h group, medians 26 - 54. The subcutaneous injection (theoretical release rate 47.6 mu g/h) produced higher concentrations than observed after 40 mu g/h transdermal patch dosing. The median fetal/maternal concentration-ratios in different dosing groups ranged between 0.21 and 0.54 in plasma, and between 0.38 and 1.3 in CNS tissues, respectively, with the highest ratios observed in the spinal cord. Buprenorphine concentrations in the cerebrospinal fluid were 8 - 13 % of the concurrent plasma concentration in the ewes and 28 % in the fetuses. Buprenorphine was quantifiable in the newborn lambs' plasma and CNS tissues two days postdelivery. Norbu-prenorphine was analyzed from all plasma, cerebrospinal fluid, and CNS tissue samples but was nondetectable or below the LLOQ in most. The current study demonstrates that buprenorphine accumulates into CNS tissues at much higher concentrations than in plasma in pregnant sheep, fetuses, and their newborn lambs even 45 hours after delivery.
  • Philips, Elise M.; Santos, Susana; Trasande, Leonardo; Aurrekoetxea, Juan J.; Barros, Henrique; von Berg, Andrea; Bergstroem, Anna; Bird, Philippa K.; Brescianini, Sonia; Chaoimh, Carol Ni; Charles, Marie-Aline; Chatzi, Leda; Chevrier, Cecile; Chrousos, George P.; Costet, Nathalie; Criswell, Rachel; Crozier, Sarah; Eggesbo, Merete; Fantini, Maria Pia; Farchi, Sara; Forastiere, Francesco; van Gelder, Marleen M. H. J.; Georgiu, Vagelis; Godfrey, Keith M.; Gori, Davide; Hanke, Wojciech; Heude, Barbara; Hryhorczuk, Daniel; Iniguez, Carmen; Inskip, Hazel; Karvonen, Anne M.; Kenny, Louise C.; Kull, Inger; Lawlor, Debbie A.; Lehmann, Irina; Magnus, Per; Manios, Yannis; Melen, Erik; Mommers, Monique; Morgen, Camilla S.; Moschonis, George; Murray, Deirdre; Nohr, Ellen A.; Andersen, Anne-Marie Nybo; Oken, Emily; Oostvogels, Adriette J. J. M.; Papadopoulou, Eleni; Pekkanen, Juha; Pizzi, Costanza; Polanska, Kinga; Porta, Daniela; Richiardi, Lorenzo; Rifas-Shiman, Sheryl L.; Roeleveld, Nel; Rusconi, Franca; Santos, Ana C.; Sorensen, Thorkild I. A.; Standl, Marie; Stoltenberg, Camilla; Sunyer, Jordi; Thiering, Elisabeth; Thijs, Carel; Torrent, Maties; Vrijkotte, Tanja G. M.; Wright, John; Zvinchuk, Oleksandr; Gaillard, Romy; Jaddoe, Vincent W. V. (2020)
    Author summaryWhy was this study done? Maternal smoking during pregnancy is an important risk factor for various birth complications and childhood overweight. It is not clear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy. The associations of paternal smoking with birth and childhood outcomes also remain unknown. What did the researchers do and find? We conducted an individual participant data meta-analysis using data from 229,158 families from 28 pregnancy and birth cohorts from Europe and North America to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. We observed that smoking in the first trimester only did not increase the risk of preterm birth and small size for gestational age but was associated with a higher risk of childhood overweight, as compared to nonsmoking. Reducing the number of cigarettes during pregnancy, without quitting, was still associated with higher risks of these adverse outcomes. Paternal smoking seems to be associated, independently of maternal smoking, with the risks of childhood overweight. What do these findings mean? Population strategies should focus on parental smoking prevention before or at the start of, rather than during, pregnancy. Future studies are needed to assess the specific associations of smoking in the preconception and childhood periods with offspring outcomes. Background Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. Methods and findings We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35],Pvalue = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15],Pvalue = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23],Pvalue <0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48],Pvalue <0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to = 10 to 5-9 and
  • Vähänikkilä, N.; Pohjanvirta, T.; Haapala, V.; Simojoki, H.; Soveri, T.; Browning, G. F.; Pelkonen, S.; Wawegama, N. K.; Autio, T. (2019)
    Mycoplasma bovis causes bovine respiratory disease, mastitis, arthritis and otitis. The importance of M. bovis has escalated because of recent outbreaks and introductions into countries previously free of M. bovis. We characterized the course of M. bovis infection on 19 recently infected dairy farms over 24 months. Our objective was to identify diagnostic tools to assess the efficacy of control measures to assess low risk infection status on M. bovis infected farms. PCR assays and culture were used to detect M. bovis, and in-house and BioX ELISAs were used to follow antibody responses. Cows and young stock were sampled on four separate occasions, and clinical cases were sampled when they arose. On 17 farms, a few cases of clinical mastitis were detected, mostly within the first eight weeks after the index case. Antibodies detected by in-house ELISA persisted in the serum of cows at least for 1.5 years on all farms, regardless of the M. bovis infection status or signs of clinical disease or subclinical mastitis on the farm. Six out of 19 farms became low risk as the infection was resolved. Our results suggest that, for biosecurity purposes, regular monitoring should be conducted on herds by screening for M. bovis in samples from cows with clinical mastitis and calves with pneumonia, in conjunction with testing young stock by screening longitudinally collected nasal swabs for M. bovis and sequential serum samples for antibody against recombinant antigen.