| 1. |
- Bertelsen, R. J., et al.
(author)
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Clinical markers of asthma and IgE assessed in parents before conception predict asthma and hayfever in the offspring
- 2017
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 47:5, s. 627-638
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Journal article (peer-reviewed)abstract
- Background: Mice models suggest epigenetic inheritance induced by parental allergic disease activity. However, we know little of how parental disease activity before conception influences offspring's asthma and allergy in humans.Objective: We aimed to assess the associations of parental asthma severity, bronchial hyperresponsiveness (BHR), and total and specific IgEs, measured before conception vs. after birth, with offspring asthma and hayfever.Methods: The study included 4293 participants (mean age 34, 47% men) from the European Community Respiratory Health Survey (ECRHS) with information on asthma symptom severity, BHR, total and specific IgEs from 1991 to 1993, and data on 9100 offspring born 1972–2012. Adjusted relative risk ratios (aRRR) for associations of parental clinical outcome with offspring allergic disease were estimated with multinomial logistic regressions.Results: Offspring asthma with hayfever was more strongly associated with parental BHR and specific IgE measured before conception than after birth [BHR: aRRR = 2.96 (95% CI: 1.92, 4.57) and 1.40 (1.03, 1.91), respectively; specific IgEs: 3.08 (2.13, 4.45) and 1.83 (1.45, 2.31), respectively]. This was confirmed in a sensitivity analysis of a subgroup of offspring aged 11–22 years with information on parental disease activity both before and after birth.Conclusion & Clinical Relevance: Parental BHR and specific IgE were associated with offspring asthma and hayfever, with the strongest associations observed with clinical assessment before conception as compared to after birth of the child. If the hypothesis is confirmed in other studies, parental disease activity assessed before conception may prove useful for identifying children at risk for developing asthma with hayfever.
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| 2. |
- Pape, K., et al.
(author)
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Parental occupational exposure pre- and post-conception and development of asthma in offspring
- 2020
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In: International journal of epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 49:6, s. 1856-1869
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Journal article (peer-reviewed)abstract
- Background: While direct effects of occupational exposures on an individual's respiratory health are evident, a new paradigm is emerging on the possible effects of preconception occupational exposure on respiratory health in offspring. We aimed to study the association between parental occupational exposure starting before conception and asthma in their offspring (at 0-15 years of age). Methods: We studied 3985 offspring participating in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Their mothers or fathers (n = 2931) previously participated in the European Community Respiratory Health Survey (ECRHS). Information was obtained from questionnaires on parental job history pre- and post-conception which was linked to an asthma-specific job-exposure matrix (JEM). We assessed the association between parental occupational exposure and offspring asthma, applying logistic regression models, clustered by family and adjusted for study centre, offspring sex, parental characteristics (age, asthma onset, place of upbringing, smoking) and grandparents' level of education. Results: Parental occupational exposure to microorganisms, pesticides, allergens or reactive chemicals pre-conception or both pre- and post-conception was not related to offspring asthma; in general, subgroup analyses confirmed this result. However, maternal exposure both pre- and post-conception to allergens and reactive chemicals was associated with increased odds for early-onset asthma in offspring (0-3 years of age); odds ratio 1.70 (95% CI: 1.02-2.84) and 1.65 (95% CI: 0.98-2.77), respectively. Conclusions: This study did not find evidence that parental occupational exposure, defined by an asthma JEM before conception only or during pre- and post-conception vs non-exposed, was associated with offspring asthma.
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| 3. |
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| 4. |
- Accordini, S., et al.
(author)
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A three-generation study on the association of tobacco smoking with asthma
- 2018
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 47:4, s. 1106-1117
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Journal article (peer-reviewed)abstract
- 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.
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| 5. |
- Dratva, J., et al.
(author)
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Validation of self-reported figural drawing scales against anthropometric measurements in adults
- 2016
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In: Public Health Nutrition. - : Cambridge University Press (CUP). - 1368-9800 .- 1475-2727. ; 19:11, s. 1944-1951
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Journal article (peer-reviewed)abstract
- Objective: The aim of the present study was to validate figural drawing scales depicting extremely lean to extremely obese subjects to obtain proxies for BMI and waist circumference in postal surveys. Design: Reported figural scales and anthropometric data from a large population-based postal survey were validated with measured anthropometric data from the same individuals by means of receiver-operating characteristic curves and a BMI prediction model. Setting: Adult participants in a Scandinavian cohort study first recruited in 1990 and followed up twice since. Subjects: Individuals aged 38-66 years with complete data for BMI (n 1580) and waist circumference (n 1017). Results: Median BMI and waist circumference increased exponentially with increasing figural scales. Receiver-operating characteristic curve analyses showed a high predictive ability to identify individuals with BMI > 25.0 kg/m(2) in both sexes. The optimal figural scales for identifying overweight or obese individuals with a correct detection rate were 4 and 5 in women, and 5 and 6 in men, respectively. The prediction model explained 74% of the variance among women and 62% among men. Predicted BMI differed only marginally from objectively measured BMI. Conclusions: Figural drawing scales explained a large part of the anthropometric variance in this population and showed a high predictive ability for identifying overweight/obese subjects. These figural scales can be used with confidence as proxies of BMI and waist circumference in settings where objective measures are not feasible.
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| 6. |
- Kitaba, N. T., et al.
(author)
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Fathers' preconception smoking and offspring DNA methylation
- 2023
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In: Clinical Epigenetics. - : BioMed Central (BMC). - 1868-7075 .- 1868-7083. ; 15:1
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Journal article (peer-reviewed)abstract
- 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 < 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) < 0.05) in PRR5 and CENPP. Father's pubertal onset smoking was associated with 19 CpGs (FDR < 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 < 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 < 0.05), and all sites remained significant (p < 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.
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| 7. |
- Triebner, K., et al.
(author)
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Menopause Is Associated with Accelerated Lung Function Decline
- 2017
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In: American Journal of Respiratory and Critical Care Medicine. - : AMER THORACIC SOC. - 1073-449X .- 1535-4970. ; 195:8, s. 1058-1065
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Journal article (peer-reviewed)abstract
- Rationale: Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. Objectives: To study whether lung function decline, assessed by FVC and FEV1, is accelerated in women who undergo menopause. Methods: The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect. Measurements and Main Results: Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by -10.2 ml/yr (95% confidence interval [CI], -13.1 to -7.2) in transitional women and -12.5 ml/yr (95% CI, -16.2 to -8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV1 decline increased by -3.8 ml/yr (95% CI, -6.3 to -2.9) in transitional women and -5.2 ml/yr (95% CI, -8.3 to -2.0) in post-menopausal women. Conclusions: Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.
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| 8. |
- Accordini, S., et al.
(author)
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Prenatal and prepubertal exposures to tobacco smoke in men may cause lower lung function in future offspring: a three-generation study using a causal modelling approach
- 2021
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 58:4
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Journal article (peer-reviewed)abstract
- Mechanistic research suggests that lifestyle and environmental factors impact respiratory health across generations by epigenetic changes transmitted through male germ cells. Evidence from studies on humans is very limited. We investigated multigeneration causal associations to estimate the causal effects of tobacco smoking on lung function within the paternal line. We analysed data from 383 adult offspring (age 18-47 years; 52.0% female) and their 274 fathers, who had participated in the European Community Respiratory Health Survey (ECRHS)/Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study and had provided valid measures of pre-bronchodilator lung function. Two counterfactual-based, multilevel mediation models were developed with: paternal grandmothers' smoking in pregnancy and fathers' smoking initiation in prepuberty as exposures; fathers' forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), or FEV1/FVC z-scores as potential mediators (proxies of unobserved biological mechanisms that are true mediators); and offspring's FEV1 and FVC, or FEV1/FVC z-scores as outcomes. All effects were summarised as differences (Delta) in expected z-scores related to fathers' and grandmothers' smoking history. Fathers' smoking initiation in prepuberty had a negative direct effect on both offspring's FEV1 (Delta z-score -0.36, 95% CI -0.63--0.10) and FVC (-0.50, 95% CI -0.80--0.20) compared with fathers' never smoking. Paternal grandmothers' smoking in pregnancy had a negative direct effect on fathers' FEV1/FVC -0.57, 95% CI -1.09--0.05) and a negative indirect effect on offspring's FEV1/FVC (-0.12, 95% CI -0.21--0.03) compared with grandmothers' not smoking before fathers' birth nor during fathers' childhood. Fathers' smoking in prepuberty and paternal grandmothers' smoking in pregnancy may cause lower lung function in offspring. Our results support the concept that lifestyle-related exposures during these susceptibility periods influence the health of future generations.
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| 9. |
- Heldin, J., et al.
(author)
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Clinical Remission of Asthma and Allergic Rhinitis- in a Longitudinal Population Study
- 2022
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In: Journal of Asthma and Allergy. - 1178-6965. ; 15, s. 1569-1578
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Journal article (peer-reviewed)abstract
- Background: Although asthma and allergic rhinitis are chronic diseases, some patients experience periods of remission. Information on prognostic factors associated with the remission of asthma and allergic rhinitis is valuable in resource prioritization. This study investigated factors associated with the clinical remission of asthma and allergic rhinitis.Methods: In the Respiratory Health In Northern Europe (RHINE) study, data was collected with questionnaires in stage one (RHINE I, 1989-1992) and two follow-ups (RHINE II, 1999-2001 and RHINE III, 2010-2012) from Sweden, Norway, Denmark, Iceland and Estonia. Clinical remission was defined as having reported asthma or allergic rhinitis in RHINE I or RHINE II but not in RHINE III.Results: Of 13,052 participants, 975 (7.5%) reported asthma in RHINE I or RHINE II, and 3379 (25.9%) allergic rhinitis. Clinical remission of asthma and allergic rhinitis was found in 46.4% and 31.8%, respectively. Living in Estonia (OR (95% CI) 2.44 (1.22- 4.85)) and living in an apartment (1.45 (1.06-1.98)) were related to remission of asthma, while subjects reporting allergic rhinitis (0.68 (0.51-0.90)), asthma onset <= 12 years of age (0.49 (0.35-0.68)), receiving treatment with antibiotics for respiratory illness (0.64 (0.47- 0.87)) were less likely to have asthma remission. Factors related to a higher likelihood of remission of allergic rhinitis were no asthma at baseline, age >= 58 years in RHINE III, allergic rhinitis onset after 12 years of age, living in rural areas as a child, having only a primary school education and not being pregnant.Conclusion: Clinical remission was found in almost one-half of those with asthma and one-third of persons with allergic rhinitis. Coexisting allergic symptoms were associated with less clinical asthma remission. Age, asthma symptoms and environmental factors in childhood, such as living in a rural area, were found to influence the clinical remission of allergic rhinitis.
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| 10. |
- Johannessen, A., et al.
(author)
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Being overweight in childhood, puberty, or early adulthood: Changing asthma risk in the next generation?
- 2020
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 145:3
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Journal article (peer-reviewed)abstract
- Background: Overweight status and asthma have increased during the last decades. Being overweight is a known risk factor for asthma, but it is not known whether it might also increase asthma risk in the next generation. Objective: We aimed to examine whether parents being overweight in childhood, adolescence, or adulthood is associated with asthma in their offspring. Methods: We included 6347 adult offspring (age, 18-52 years) investigated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) multigeneration study of 2044 fathers and 2549 mothers (age, 37-66 years) investigated in the European Community Respiratory Health Survey (ECRHS) study. Associations of parental overweight status at age 8 years, puberty, and age 30 years with offspring's childhood overweight status (potential mediator) and offspring's asthma with or without nasal allergies (outcomes) was analyzed by using 2-level logistic regression and 2-level multinomial logistic regression, respectively. Counterfactual-based mediation analysis was performed to establish whether observed associations were direct or indirect effects mediated through the offspring's own overweight status. Results: We found statistically significant associations between both fathers' and mothers' childhood overweight status and offspring's childhood overweight status (odds ratio, 2.23 [95% CI, 1.45-3.42] and 2.45 [95% CI, 1.86-3.22], respectively). We also found a statistically significant effect of fathers' onset of being overweight in puberty on offspring's asthma without nasal allergies (relative risk ratio, 2.31 [95% CI, 1.23-4.33]). This effect was direct and not mediated through the offspring's own overweight status. No effect on offspring's asthma with nasal allergies was found. Conclusion: Our findings suggest that metabolic factors long before conception can increase asthma risk and that male puberty is a time window of particular importance for offspring's health. © 2019 The Authors
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