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

The effect of farming environment on asthma; time dependent or universal?

Funding Information: MJA holds investigator-initiated grants from Pfizer and Boehringer-Ingelheim for unrelated research. He has undertaken an unrelated consultancy for and received assistance with conference attendance from Sanofi. He has also received a speaker’s fee from GSK. The other authors have no conflicts of interest to declare that are relevant for the content of this article. Funding Information: The ECRHS/RHINE/RHINESSA study was supported by grants from The Faculty of Health, Aarhus University, Denmark (Project No. 240008), The Wood Dust Foundation (Project No. 444508795), The Danish Lung Association, the Swedish Heart and Lung Foundation, the Swedish Association Against Asthma and Allergy, the Swedish Association against Heart and Lung Disease, the Swedish Council for Working Life and Social Research, The Bror Hjerpstedt Foundation, The Vårdal Foundation for Health Care and Allergic Research, The Norwegian Research Council (Grant Nos. 214123, 230827/F20, 228174 and 135773/330), The Norwegian Asthma and Allergy Association, HelseVest Norway (Grant No. 911 631), The Icelandic Research Council, The University of Iceland Research Fund, The Icelandic GP’s Research Fund, The Estonian Science Foundation (Grant No. 4350), The Estonian Research Council (Grant No. PUT562), Melbourne University, National Health & Medical Research Council of Australia, SEPAR Spain, Sociedad Española de Neumologia y Cirugía Toracica Spain and Horizon2020 PHC1 (Grant No. 633212). For further information about funding sources, please consult www.rhinessa.net . Vivi Schlünssen and Cecilie Svanes are members of the COST BM1201 network. Publisher Copyright: © 2022, Springer Nature B.V.The increasing prevalence of asthma is linked to westernization and urbanization. Farm environments have been associated with a lower risk of asthma development. However, this may not be universal, as the association differs across birth cohorts and farming methods. The aim of this study was to investigate the associations of farm upbringing with asthma in different generations and at different times in history. The study population consisted of three generations: 13,868 subjects participating in the ECRHS in 2010, their 9,638 parents, and their 8,885 offspring participating in RHINESSA in 2013. Information on place of upbringing and self-reported ever asthma was provided via questionnaires. Logistic regression was performed including subgroup analysis stratified by generation and birthyear into ten-year-intervals. The prevalence of asthma increased from 8% among grandparents to 13% among parents and to 18% among offspring. An overall analysis showed an inverse association of farm upbringing on the risk of asthma (OR = 0.64; 95%CI 0.55–0.74). Subgroup analysis stratified into ten-year-intervals showed a tendency towards a more pronounced inverse association between growing up on a farm and asthma among subjects born in the 1940s (0.74; 0.48–1.12), 1950s (0.70; 0.54–0.90) and 1960s (0.70; 0.52–0.93). For subjects born in 1970 and thereafter this association appeared less consistent. While growing up on a farm was associated with a reduced risk of developing asthma in participants born between 1945–1999, this was mainly driven by generations born from 1945 to 1973.Peer reviewe

Previous tuberculosis infection associated with increased frequency of asthma and respiratory symptoms in a Nordic–Baltic multicentre population study

Background Tuberculosis (TB) infection induces profound local and systemic, immunological and inflammatory changes that could influence the development of other respiratory diseases; however, the association between TB and asthma is only partly understood. Our objective was to study the association of TB with asthma and respiratory symptoms in a Nordic–Baltic population-based study. Methods We included data from the Respiratory Health in Northern Europe (RHINE) study, in which information on general characteristics, TB infection, asthma and asthma-like symptoms were collected using standardised postal questionnaires. Asthma was defined based on asthma medication usage and/or asthma attacks 12 months prior to the study, and/or by a report of ≥three out of five respiratory symptoms in the last 12 months. Allergic/nonallergic asthma were defined as asthma with/without nasal allergy. The associations of TB with asthma outcomes were analysed using logistic regressions with adjustments for age, sex, smoking, body mass index and parental education. Results We included 8379 study participants aged 50–75 years, 61 of whom reported having had TB. In adjusted analyses, participants with a history of TB had higher odds of asthma (OR 1.99, 95% CI 1.13–3.47). The associations were consistent for nonallergic asthma (OR 2.17, 95% CI 1.16–4.07), but not for allergic asthma (OR 1.20, 95% CI 0.53–2.71). Conclusion We found that in a large Northern European population-based cohort, persons with a history of TB infection more frequently had asthma and asthma symptoms. We speculate that this may reflect long-term effects of TB, including direct damage to the airways and lungs, as well as inflammatory responses

Zoonotic helminth exposure and risk of allergic diseases: a study of two generations in Norway

Background: Animal and human studies indicate that definitive host helminth infections may confer protection from allergies. However, zoonotic helminths, such as Toxocara species (spp.), have been associated with increased allergies. Objective: We describe the prevalence of Toxocara spp. and Ascaris spp. seropositivity, and associations with allergic diseases and sensitisation, in two generations in Bergen, Norway. Methods: Serum levels of total IgG4, anti-Toxocara spp. IgG4 and Ascaris spp. IgG4 were established by ELISA in two cohorts; parents born 1945-1972 (n=171) and their offspring born 1969-2003 (n=264). Allergic outcomes and covariates were recorded through interviews and clinical examinations including serum IgEs and skin prick tests. Results: Anti-Ascaris spp. IgG4 was detected in 29.2% of parents and 10.3% of offspring, and anti-Toxocara spp. IgG4 in 17.5% and 8.0% of parents and offspring, respectively. Among offspring anti-Toxocara spp. IgG4 was associated with pet keeping before age 15 (OR=6.15; 95% CI=1.37-27.5) and increasing BMI (1.16[1.06-1.25] per kg/m2). Toxocara spp. seropositivity was associated with wheeze (2.97[1.45- 7.76]), hay fever (4.03[1.63-9.95]), eczema (2.89[1.08-7.76]) and cat sensitization (5.65[1.92-16.6]) among offspring, but was not associated with allergic outcomes among parents. Adjustment for childhood or current pet keeping did not alter associations with allergies. Parental Toxocara spp. seropositivity was associated with increased offspring allergies following a sex-specific pattern. Conclusions & Clinical Relevance: Zoonotic helminth exposure in Norway was less frequent in offspring than parents; however, Toxocara spp. seropositivity was associated with increased risk of allergic manifestations in the offspring generation, but not among parents. Changes in response to helminth exposure may provide insights into the increase in allergy incidence in affluent countries

Does parental farm upbringing influence the risk of asthma in offspring? : a three-generation study

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)Background: A farm upbringing has been associated with lower risk of asthma and methylation of asthma-related genes. As such, a farm upbringing has the potential to transfer asthma risk across generations, but this has never been investigated. We aimed to study the generational effects from a parental farm upbringing on offspring asthma. Methods: Our study involved three generations: 5759 participants from the European Community Respiratory Health Survey (ECRHS) study (born 1945–1971, denoted G1), their 9991 parents (G0) and their 8260 offspring (G2) participating in RHINESSA (Respiratory Health In Northern Europe, Spain and Australia). Questionnaire data were collected on G0 and G1 from G1 in 2010 and on G2 from themselves in 2013. The parental/grandparental place of upbringing was categorized: (i) both parents from farm; (ii) mother from farm, father from village/city; (iii) father from farm, mother from village/city; (iv) both parents from village or one parent from village and one from city; (v) both parents from city (reference group). Grandparental upbringing was equivalently categorized. Offspring asthma was self-reported and data were analysed using Cox-regression models with G2 age as the time scale. Results: A parental farm upbringing was not associated with offspring asthma when compared with city upbringing [hazard ratio (HR) 1.12, 95% confidence interval (CI) 0.74–1.69]. Findings remained similar when stratified by offspring upbringing and asthma phenotypes. Quantitative bias analyses showed similar estimates for alternative data sources. A grandparental farm upbringing was not associated with offspring asthma in either the maternal (HR 1.05, 95% CI 0.67–1.65) or paternal line (HR 1.02, 95% CI 0.62–1.68). Conclusions: This multigenerational analysis suggests no evidence of an association between parental/grandparental farm upbringing and offspring asthma

Parents' smoking onset before conception as related to body mass index and fat mass in adult offspring: Findings from the RHINESSA generation study

Emerging evidence suggests that parents' preconception exposures may influence offspring health. We aimed to investigate maternal and paternal smoking onset in specific time windows in relation to offspring body mass index (BMI) and fat mass index (FMI). We investigated fathers (n = 2111) and mothers (n = 2569) aged 39-65 years, of the population based RHINE and ECRHS studies, and their offspring aged 18-49 years (n = 6487, mean age 29.6 years) who participated in the RHINESSA study. BMI was calculated from self-reported height and weight, and FMI was estimated from bioelectrical impedance measures in a subsample. Associations with parental smoking were analysed with generalized linear regression adjusting for parental education and clustering by study centre and family. Interactions between offspring sex were analysed, as was mediation by parental pack years, parental BMI, offspring smoking and offspring birthweight. Fathers' smoking onset before conception of the offspring (onset ≥15 years) was associated with higher BMI in the offspring when adult (β 0.551, 95%CI: 0.174-0.929, p = 0.004). Mothers' preconception and postnatal smoking onset was associated with higher offspring BMI (onset <15 years: β1.161, 95%CI 0.378-1.944; onset ≥15 years: β0.720, 95%CI 0.293-1.147; onset after offspring birth: β2.257, 95%CI 1.220-3.294). However, mediation analysis indicated that these effects were fully mediated by parents' postnatal pack years, and partially mediated by parents' BMI and offspring smoking. Regarding FMI, sons of smoking fathers also had higher fat mass (onset <15 years β1.604, 95%CI 0.269-2.939; onset ≥15 years β2.590, 95%CI 0.544-4.636; and onset after birth β2.736, 95%CI 0.621-4.851). There was no association between maternal smoking and offspring fat mass. We found that parents' smoking before conception was associated with higher BMI in offspring when they reached adulthood, but that these effects were mediated through parents' pack years, suggesting that cumulative smoking exposure during offspring's childhood may elicit long lasting effects on offspring BMI.Co-ordination of the RHINESSA study has received funding from the Research Council of Norway (Grants No. 274767, 214123, 228174, 230827 and 273838), ERC StG project BRuSH #804199, the European Union's Horizon 2020 research and innovation program under grant agreement No. 633212 (the ALEC Study WP2), the Bergen Medical Research Foundation, and the Western Norwegian Regional Health Authorities (Grants No. 912011, 911892 and 911631). Study centres have further received local funding from the following: Bergen: the above grants for study establishment and co-ordination, and, in addition, World University Network (RDF and Sustainability grant), Norwegian Labour Inspection, and the Norwegian Asthma and Allergy Association. Albacete and Huelva: SEPAR. Fondo de Investigación Sanitaria (FIS PS09). Gøteborg, Umeå and Uppsala: the Swedish Lung Foundation, the Swedish Asthma and Allergy Association. Reykjavik: Iceland University. Melbourne: NHMRC, Melbourne University, Tartu: the Estonian Research Council (Grant No. PUT562). Århus: The Danish Wood Foundation (Grant No. 444508795), the Danish Working Environment Authority (Grant No. 20150067134). The RHINE study received funding by Norwegian Research Council, Norwegian Asthma and Allergy Association, Danish Lung Association, Swedish Heart and Lung Foundation, Vårdal Foundation for Health Care Science and Allergy Research, Swedish Asthma and Allergy Association, Swedish Lung Foundation, Icelandic Research Council, and Estonian Science Foundation. The co-ordination of ECRHS was supported by European Union's Horizon 2020 research and innovation program under grant agreement No. 633212 (the ALEC Study), the European Commission frameworks 5 and 7 (ECRHS I and II) and the Medical Research Council (ECRHS III)

Maternal preconception occupational exposure to cleaning products and disinfectants and offspring asthma

BACKGROUND: Emerging research suggests health effects in offspring after parental chemical exposures before conception. Many future mothers are exposed to potent chemicals at work, but potential offspring health effects are hardly investigated. OBJECTIVE: We sought to investigate childhood asthma in relation to mother's occupational exposure to cleaning products and disinfectants before conception. METHODS: The multicenter Respiratory Health In Northern Europe/Respiratory Health In Northern Europe, Spain and Australia generation study investigated asthma and wheeze starting at age less than 10 years in 3318 mother-offspring pairs. From an asthma-specific Job-Exposure Matrix and mothers' occupational history, we defined maternal occupational exposure to indoor cleaning agents (cleaning products/detergents and disinfectants) starting before conception, in the 2-year period around conception and pregnancy, or after birth. Never-employed mothers were excluded. Exposed groups include cleaners, health care workers, cooks, and so forth. Associations were analyzed using mixed-effects logistic regression and ordinary logistic regression with clustered robust SEs and adjustment for maternal education. RESULTS: Maternal occupational exposure to indoor cleaning starting preconception and continuing (n = 610) was associated with offspring's childhood asthma: odds ratio 1.56 (95% CI, 1.05-2.31), childhood asthma with nasal allergies: 1.77 (1.13-2.77), and childhood wheeze and/or asthma: 1.71 (95% CI, 1.19-2.44). Exposure starting around conception and pregnancy (n = 77) was associated with increased childhood wheeze and/or asthma: 2.25 (95% CI, 1.03-4.91). Exposure starting after birth was not associated with asthma outcomes (1.13 [95% CI, 0.71-1.80], 1.15 [95% CI, 0.67-1.97], 1.08 [95% CI, 0.69-1.67]). CONCLUSIONS: Mother's occupational exposure to indoor cleaning agents starting before conception, or around conception and pregnancy, was associated with more childhood asthma and wheeze in offspring. Considering potential implications for vast numbers of women in childbearing age using cleaning agents, and their children, further research is imperative

Fathers’ preconception smoking and offspring DNA methylation

Background: Experimental studies suggest that exposures may impact respiratory health across generations via epigenetic changes transmitted specifically through male germ cells. Studies in humans are, however, limited. We aim to identify epigenetic marks in offspring associated with father’s preconception smoking. Methods: We conducted epigenome-wide association studies (EWAS) in the RHINESSA cohort (7–50 years) on father’s any preconception smoking (n = 875 offspring) and father’s pubertal onset smoking &lt; 15 years (n = 304), using Infinium MethylationEPIC Beadchip arrays, adjusting for offspring age, own smoking and maternal smoking. EWAS of maternal and offspring personal smoking were performed for comparison. Father’s smoking-associated dmCpGs were checked in subpopulations of offspring who reported no personal smoking and no maternal smoking exposure. Results: Father’s smoking commencing preconception was associated with methylation of blood DNA in offspring at two cytosine-phosphate-guanine sites (CpGs) (false discovery rate (FDR) &lt; 0.05) in PRR5 and CENPP. Father’s pubertal onset smoking was associated with 19 CpGs (FDR &lt; 0.05) mapped to 14 genes (TLR9, DNTT, FAM53B, NCAPG2, PSTPIP2, MBIP, C2orf39, NTRK2, DNAJC14, CDO1, PRAP1, TPCN1, IRS1 and CSF1R). These differentially methylated sites were hypermethylated and associated with promoter regions capable of gene silencing. Some of these sites were associated with offspring outcomes in this cohort including ever-asthma (NTRK2), ever-wheezing (DNAJC14, TPCN1), weight (FAM53B, NTRK2) and BMI (FAM53B, NTRK2) (p &lt; 0.05). Pathway analysis showed enrichment for gene ontology pathways including regulation of gene expression, inflammation and innate immune responses. Father’s smoking-associated sites did not overlap with dmCpGs identified in EWAS of personal and maternal smoking (FDR &lt; 0.05), and all sites remained significant (p &lt; 0.05) in analyses of offspring with no personal smoking and no maternal smoking exposure. Conclusion: Father’s preconception smoking, particularly in puberty, is associated with offspring DNA methylation, providing evidence that epigenetic mechanisms may underlie epidemiological observations that pubertal paternal smoking increases risk of offspring asthma, low lung function and obesity

Fathers’ preconception smoking and offspring DNA methylation: A two generation study

Rationale Experimental studies suggest that exposures may impact respiratory health across generations via epigenetic changes transmitted specifically through male germ cells. Studies in humans are however limited. We aim to identify epigenetic marks in offspring associated with father’s preconception smoking.Methods We conducted epigenome-wide association studies (EWAS) in the RHINESSA cohort on father’s any preconception smoking (N=875 offspring) and father’s pubertal onset smoking &lt;15 years (N=304), using Infinium MethylationEPIC Beadchip arrays, adjusting for offspring age, maternal smoking and personal smoking. EWAS of maternal and offspring personal smoking were performed for replication.Results Father’s smoking commencing preconception was associated with methylation of blood DNA in offspring at two Cytosine-phosphate-Guanine sites (CpGs) (False Discovery Rate (FDR) &lt;0.05) in PRR5 and CENPP. Father’s pubertal onset smoking was associated with 19 CpGs (FDR &lt;0.05) mapped to 14 genes (TLR9, DNTT, FAM53B, NCAPG2, PSTPIP2, MBIP, C2orf39, NTRK2, DNAJC14, CDO1, PRAP1, TPCN1, IRS1 and CSF1R). These differentially methylated sites were hypermethylated and associated with promoter regions capable of gene silencing. Some of these sites were associated with offspring outcomes in this cohort including ever-asthma (NTRK2), ever-wheezing (DNAJC14, TPCN1), weight (FAM53B, NTRK2) and BMI (FAM53B, NTRK2) (P&lt; 0.05). Pathway analysis showed enrichment for gene ontology pathways including regulation of gene expression, inflammation and innate immune responses.Conclusion Father’s preconception smoking, particularly in puberty, is associated with offspring DNA methylation, providing evidence that epigenetic mechanisms may underly epidemiological observations that pubertal paternal smoking increases risk of offspring asthma, low lung function and obesity