BackgroundAscaris infections, with a worldwide prevalence above 10%, can cause respiratory pathology. However, long-term effects on lung function in humans are largely unknown.ObjectiveWe investigated the associations of Ascaris exposure with lung function, asthma, and DNA methylation.MethodsSerum Ascaris IgG antibodies were measured in 671 adults aged 18 to 47 years (46% women) from Aarhus, Bergen, and Tartu RHINESSA study centers. Seropositivity was defined as IgG above the 90th percentile. Linear and logistic regressions were used to analyze Ascaris seropositivity as associated with lung function and asthma, adjusted for age, height, and smoking and clustered by center. DNA methylation in blood was profiled by a commercial methylation assay.ResultsAscaris seropositivity was associated with lower FEV1 (−247 mL; 95% CI, −460, −34) and higher odds for asthma (adjusted odds ratio, 5.84; 95% CI, 1.67, 20.37) among men but not women, also after further adjusting for house dust mite sensitivity, consistent across study centers. At a genome-wide level, Ascaris exposure was associated with 23 differentially methylated sites in men and 3 in women. We identified hypermethylation of the MYBPC1 gene, which can regulate airway muscle contraction. We also identified genes linked to asthma pathogenesis such as CRHR1 and GRK1, as well as a differentially methylated region in the PRSS22 gene linked to nematode infection.ConclusionAscaris exposure was associated with substantially lower lung function and increased asthma risk among men. Seropositive participants had sex-specific differences in DNA methylation compared to the unexposed, thus suggesting that exposure may lead to sex-specific epigenetic changes associated with lung pathology. Ascaris infections, with a worldwide prevalence above 10%, can cause respiratory pathology. However, long-term effects on lung function in humans are largely unknown. We investigated the associations of Ascaris exposure with lung function, asthma, and DNA methylation. Serum Ascaris IgG antibodies were measured in 671 adults aged 18 to 47 years (46% women) from Aarhus, Bergen, and Tartu RHINESSA study centers. Seropositivity was defined as IgG above the 90th percentile. Linear and logistic regressions were used to analyze Ascaris seropositivity as associated with lung function and asthma, adjusted for age, height, and smoking and clustered by center. DNA methylation in blood was profiled by a commercial methylation assay. Ascaris seropositivity was associated with lower FEV1 (−247 mL; 95% CI, −460, −34) and higher odds for asthma (adjusted odds ratio, 5.84; 95% CI, 1.67, 20.37) among men but not women, also after further adjusting for house dust mite sensitivity, consistent across study centers. At a genome-wide level, Ascaris exposure was associated with 23 differentially methylated sites in men and 3 in women. We identified hypermethylation of the MYBPC1 gene, which can regulate airway muscle contraction. We also identified genes linked to asthma pathogenesis such as CRHR1 and GRK1, as well as a differentially methylated region in the PRSS22 gene linked to nematode infection. Ascaris exposure was associated with substantially lower lung function and increased asthma risk among men. Seropositive participants had sex-specific differences in DNA methylation compared to the unexposed, thus suggesting that exposure may lead to sex-specific epigenetic changes associated with lung pathology.

Ascaris

10.1016/j.jaci.2021.11.013

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Citations (20)

Exogenous female sex steroids may reduce lung ageing after menopause: A 20-year follow-up study of a general population sample (ECRHS)

Maturitas (2018)

Kai Triebner Simone Accordini Lucia Calciano Ane Johannessen Bryndís Benediktsdóttir

Highlights•Previous evidence suggests that menopause, or more specifically the associated lack of female sex steroids, is related to a decline in lung function.•This study investigated decline in lung function over 20 years in 275 users of hormone replacement therapy and 383 non-users from the general European public.•Taking exogenous female sex steroids for more than five years is related to a slower decline in respiratory function.AbstractObjectives: Menopause involves hypoestrogenism, which is associated with numerous detrimental effects, including on respiratory health. Hormone replacement therapy (HRT) is often used to improve symptoms of menopause. The effects of HRT on lung function decline, hence lung ageing, have not yet been investigated despite the recognized effects of HRT on other health outcomes.Study design: The population-based multi-centre European Community Respiratory Health Survey provided complete data for 275 oral HRT users at two time points, who were matched with 383 nonusers and analysed with a two-level linear mixed effects regression model.Main outcome measures: We studied whether HRT use was associated with the annual decline in forced vital capacity (FVC) and forced expiratory volume in one second (FEV1).Results: Lung function of women using oral HRT for more than five years declined less rapidly than that of nonusers. The adjusted difference in FVC decline was 5.6 mL/y (95%CI: 1.8 to 9.3, p = 0.01) for women who had taken HRT for six to ten years and 8.9 mL/y (3.5 to 14.2, p = 0.003) for those who had taken it for more than ten years. The adjusted difference in FEV1 decline was 4.4 mL/y (0.9 to 8.0, p = 0.02) with treatment from six to ten years and 5.3 mL/y (0.4 to 10.2, p = 0.048) with treatment for over ten years.Conclusions: In this longitudinal population-based study, the decline in lung function was less rapid in women who used HRT, following a dose-response pattern, and consistent when adjusting for potential confounding factors. This may signify that female sex hormones are of importance for lung ageing.

Hypoestrogenism

Vital capacity

10.1016/j.maturitas.2018.11.007

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Citations (13)

Female sex hormones and symptoms of obstructive sleep apnea in European women of a population-based cohort

PLoS ONE (2022)

Erla S. Sigurðardóttir Þórarinn Gíslason Bryndís Benediktsdóttir Steinar Hustad Payam Dadvand

Background The prevalence of obstructive sleep apnea is higher in women after menopause. This is suggested to be a result of an altered sex hormone balance but has so far not been confirmed in a population-based study. Objective To investigate whether serum concentration of estrogens and progesterone are associated with the prevalence of sleep apnea symptoms in middle-aged women of the general population. Methods We analyzed data from 774 women (40–67 years) from 15 study centers in seven countries participating in the second follow-up of the European Community Respiratory Health Survey (2010–2012). Multiple logistic regression models were fitted with self-reported symptoms of sleep apnea as outcomes and serum concentrations of various estrogens and progesterone as predictors. All analyses were adjusted for relevant covariates including age, BMI, education, study center, smoking habits, and reproductive age. Results Among all included women, a doubling of serum concentrations of estrone and progesterone was associated with 19% respectively 9% decreased odds of snoring. Among snorers, a doubling of the concentrations of 17β-estradiol, estrone and estrone 3-sulfate was associated with 18%, 23% and 17% decreased odds of breathing irregularly, and a doubling of the progesterone concentration was further associated with 12% decreased odds of waking up suddenly with a chocking sensation. Other evaluated associations were not statistically significant. Conclusions Middle-aged women with low serum estrogen and progesterone levels are more likely to snore and report symptoms of obstructive sleep apnea.

10.1371/journal.pone.0269569

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Describing the status of reproductive ageing simply and precisely: A reproductive ageing score based on three questions and validated with hormone levels

PLoS ONE (2020)

Kai Triebner Ane Johannessen Cecilie Svanes Bénédicte Leynaert Bryndís Benediktsdóttir

Most women live to experience menopause and will spend 4-8 years transitioning from fertile age to full menstrual stop. Biologically, reproductive ageing is a continuous process, but by convention, it is defined categorically as pre-, peri- and postmenopause; categories that are sometimes supported by measurements of sex hormones in blood samples. We aimed to develop and validate a new tool, a reproductive ageing score (RAS), that could give a simple and yet precise description of the status of reproductive ageing, without hormone measurements, to be used by health professionals and researchers.Questionnaire data on age, menstrual regularity and menstrual frequency was provided by the large multicentre population-based RHINE cohort. A continuous reproductive ageing score was developed from these variables, using techniques of fuzzy mathematics, to generate a decimal number ranging from 0.00 (nonmenopausal) to 1.00 (postmenopausal). The RAS was then validated with sex hormone measurements (follicle stimulating hormone and 17β-estradiol) and interview-data provided by the large population-based ECRHS cohort, using receiver-operating characteristics (ROC).The RAS, developed from questionnaire data of the RHINE cohort, defined with high precision and accuracy the menopausal status as confirmed by interview and hormone data in the ECRHS cohort. The area under the ROC curve was 0.91 (95% Confidence interval (CI): 0.90-0.93) to distinguish nonmenopausal women from peri- and postmenopausal women, and 0.85 (95% CI: 0.83-0.88) to distinguish postmenopausal women from nonmenopausal and perimenopausal women.The RAS provides a useful and valid tool for describing the status of reproductive ageing accurately, on a continuous scale from 0.00 to 1.00, based on simple questions and without requiring blood sampling. The score allows for a more precise differentiation than the conventional categorisation in pre-, peri- and postmenopause. This is useful for epidemiological research and clinical trials.

10.1371/journal.pone.0235478

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Continuous Subcutaneous Hydrocortisone Infusion versus Oral Hydrocortisone Replacement for Treatment of Addison's Disease: A Randomized Clinical Trial

The Journal of Clinical Endocrinology & Metabolism (2014)

Marianne Øksnes Sigríður Björnsdóttir Magnus Isaksson Paal Methlie Siri Carlsen

Conventional glucocorticoid replacement therapy fails to mimic the physiological cortisol rhythm, which may have implications for morbidity and mortality in patients with Addison's disease.The objective of the study was to compare the effects of continuous sc hydrocortisone infusion (CSHI) with conventional oral hydrocortisone (OHC) replacement therapy.This was a prospective crossover, randomized, multicenter clinical trial comparing 3 months of treatment with thrice-daily OHC vs CSHI. From Norway and Sweden, 33 patients were enrolled from registries and clinics. All patients were assessed at baseline and after 8 and 12 weeks in each treatment arm.The morning ACTH level was the primary outcome measure. Secondary outcome measures were effects on metabolism, health-related quality of life (HRQoL), sleep, and safety.CSHI yielded normalization of morning ACTH and cortisol levels, and 24-hour salivary cortisol curves resembled the normal circadian variation. Urinary concentrations of glucocorticoid metabolites displayed a normal pattern with CSHI but were clearly altered with OHC. Several HRQoL indices in the vitality domain improved over time with CSHI. No benefit was found for either treatments for any subjective (Pittsburgh Sleep Quality Index questionnaire) or objective (actigraphy) sleep parameters.CSHI safely brought ACTH and cortisol toward normal circadian levels without adversely affecting glucocorticoid metabolism in the way that OHC did. Positive effects on HRQoL were noted with CSHI, indicating that physiological glucocorticoid replacement therapy may be beneficial and that CSHI might become a treatment option for patients poorly controlled on conventional therapy.

Crossover study

Cushing's disease

10.1210/jc.2013-4253

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Citations (116)

Menopause is associated with accelerated lung function decline in the longitudinal European community respiratory health survey

Epidemiology (2016)

Kai Triebner Bobette Matulonga Ane Johannessen Sandra Suske Luca Puggini

Background: Menopause is associated with profound changes of hormone levels, possibly affecting immunity and inflammation, which may impair lung function. To date the effect of menopause on the age dependent decline of lung function has not been investigated. Objectives: To study whether the slope of lung function decline, in terms of forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁) is steeper for women who undergo menopause. Methods: The European Community Respiratory Health Survey (ECRHS), a population-based longitudinal study, provided serum samples, repeated spirometric data and questionnaire information about respiratory and reproductive health. We measured follicle stimulating hormone (FSH) and luteinizing hormone (LH) to determine the menopausal status using latent class analysis based on these measurements and questionnaire data. The associations with lung function were analyzed using linear mixed effects models, adjusted for age, height and weight at each wave, as well as smoking habits and age at completed full-time education (N=978). Results: Postmenopausal status was associated with significantly accelerated FVC decline (Early postmenopause: -5.3 ml/year [95%CI (-7.6 to -3.0)] and Late postmenopause: -7.6 ml/year (-9.9 to -5.2) compared to women of the same age with regular menstruations. There was no association between menopause and FEV₁. Results were consistent across study centers and among never smokers. Conclusions: FVC decreased more strongly among postmenopausal women in this population-based study. Clinicians should be aware that respiratory health might deteriorate in women during reproductive aging.

Vital capacity

Longitudinal Study

10.1183/13993003.congress-2016.oa4998

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Citations (2)

Lifelong exposure to residential greenspace and the premenstrual syndrome: A population-based study of Northern European women

Environment International (2021)

Kai Triebner Iana Markevych Randi Jacobsen Bertelsen Bente Sved Skottvoll Steinar Hustad

The premenstrual syndrome (PMS) causes clinically relevant psychological and physical symptoms in up to 20% of women of reproductive age. To date, no studies have investigated the relationship between PMS and residential surrounding greenspace, although a green living environment has been reported to have beneficial associations with overall and reproductive health. To investigate whether lifelong exposure to residential surrounding greenspace is associated with PMS and whether such an association is mediated by BMI, air pollution or physical activity. This study used data collected in 2013–2015 from 1069 Scandinavian women aged 18–49 years, participating in RHINESSA, a European multi-centre and population-based cohort. Satellite-derived Normalised Difference Vegetation Index was used as a proxy of greenspace. Presence of eight common PMS symptoms and their sum (PMS symptom count) were used as outcomes. The associations were assessed by adjusted multilevel logistic and negative binomial regressions. Subsequently we carried out mediation analyses for physical activity, BMI and air pollution exposure. Higher exposure to residential surrounding greenspace was associated with "Anxiety or tension" (Odds Ratio 0.82, 95% Confidence Interval (CI): 0.70 – 0.95), "Depression or hopelessness" (0.84, 0.73 – 0.98), "Difficulty with sleeping" (0.82, 0.68 – 1.00) and "Breast tenderness and abdominal bloating" (0.84, 0.71 – 0.99) before or around the start of the menstrual period. There was also an association with a lower PMS symptom count (Risk Ratio: 0.94, 95% CI: 0.91 – 0.99). These associations were robust to sensitivity analyses and were not mediated by BMI, physical activity or air pollution. Living in greener areas may be beneficial against PMS symptoms. Further studies are needed to confirm these novel findings and to explore the underlying biological mechanisms.

10.1016/j.envint.2021.106975

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Citations (13)

Late Breaking Abstract - Ultraviolet radiation and lung function in aging women: A European multi-centre study (ECRHS)

Epidemiology (2019)

Kai Triebner Steinar Hustad J. Bosch Barrera Xavier Basagaña Bryndís Benediktsdóttir

Background: Although studies have associated vitamin D status positively with lung function, the evidence on such an association between solar ultraviolet radiation (UVR) and lung function is non-existent. Objective: To investigate whether UVR exposure is associated with lung function in women and whether this is mediated by ovarian sex steroids. Methods: We used a population-based sample of 1614 women living across Europe (ECRHS cohort, 2010-2013) with an average age of 54 years. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured and personal UVR exposure was assessed, combining data on individual sun behaviour with satellite-derived data on ambient UVR. We fitted linear mixed effects models with study centre as random intercept, lung function as outcome and UVR exposure as predictor. We adjusted for age, weight, height, smoking, skin type, dietary vitamin D intake and age at completed education as socio-economic proxy. We carried out mediation analyses with estradiol, estrone, testosterone and progesterone, as potential mediators for the whole population and stratified by menopausal status. Results: UVR exposure was positively associated with FVC and FEV1. The adjusted point estimates for one interquartile range increase were 37.1mL (95% CI: 3.1 to 71.1mL) for FVC and 56.0mL (95% CI: 31.2 to 80.9mL) for FEV1. Results were similar after additional adjustment for season of spirometry, sunscreen use, sunbed use and air pollution. We did not find the investigated sex steroids to mediate the observed associations. Conclusions: Exposure to UVR is positively associated with lung function in aging women and this assocition is not mediated by sex steroids.

Interquartile range

Vital capacity

10.1183/13993003.congress-2019.oa1937

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Association of adult lung function with accelerated biological aging

Aging (2020)

Faisal I. Rezwan Medea Imboden André F.S. Amaral Matthias Wielscher Ayoung Jeong

Lung function, strongly associated with morbidity and mortality, decreases with age.This study examines whether poor adult lung function is associated with age accelerations (AAs).DNA methylation (DNAm) based AAs, lifespan predictors (GrimAge and plasminogen activator inhibitor 1-PAI1) and their related age-adjusted measures were estimated from peripheral blood at two time points (8-to-11 years apart) in adults from two cohorts: SAPALDIA (n=987) and ECRHS (n=509).Within each cohort and stratified by gender (except for estimators from GrimAge and PAI1), AAs were used as predictors in multivariate linear regression with cross-sectional lung function parameters, and in covariate-adjusted mixed linear regression with longitudinal change in lung function and meta-analysed.AAs were found cross-sectionally associated with lower mean FEV1 (Forced Expiratory Volume in one second) (AAresiduals:P-value=4x10 -4 ; Intrinsic Epigenetic AA:P-value=2x10 -4 ) in females at the follow-up time point only, and the same trend was observed for FVC (Forced Vital Capacity).Both lifespan and plasma level predictors were observed strongly associated with lung function decline and the decline was stronger in the follow-up time points (strongest association between FEV1 and DNAmAge GrimAge:P-value=1.25x10 -17 ).This study suggests that DNAm based lifespan and plasma level predictors can be utilised as important factors to assess lung health in adults.

Vital capacity

Cross-sectional study

10.18632/aging.102639

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Citations (28)