Association between physical activity over a 10-year period and current insomnia symptoms, sleep duration and daytime sleepiness: a European population-based study.

OBJECTIVES: To explore the relationship between physical activity over a 10-year period and current symptoms of insomnia, daytime sleepiness and estimated sleep duration in adults aged 39-67. DESIGN: Population-based, multicentre cohort study. SETTING: 21 centres in nine European countries. METHODS: Included were 4339 participants in the third follow-up to the European Community Respiratory Health Survey (ECRHS III), who answered questions on physical activity at baseline (ECRHS II) and questions on physical activity, insomnia symptoms, sleep duration and daytime sleepiness at 10-year follow-up (ECRHS III). Participants who reported that they exercised with a frequency of at least two or more times a week, for 1 hour/week or more, were classified as being physically active. Changes in activity status were categorised into four groups: persistently non-active; became inactive; became active; and persistently active. MAIN OUTCOME MEASURES: Insomnia, sleep time and daytime sleepiness in relation to physical activity. RESULTS: Altogether, 37% of participants were persistently non-active, 25% were persistently active, 20% became inactive and 18% became active from baseline to follow-up. Participants who were persistently active were less likely to report difficulties initiating sleep (OR 0.60, 95% CI 0.45-0.78), a short sleep duration of ≤6 hours/night (OR 0.71, 95% CI 0.59-0.85) and a long sleep of ≥9 hours/night (OR 0.53, 95% CI 0.33-0.84) than persistently non-active subjects after adjusting for age, sex, body mass index, smoking history and study centre. Daytime sleepiness and difficulties maintaining sleep were not related to physical activity status. CONCLUSION: Physically active people have a lower risk of some insomnia symptoms and extreme sleep durations, both long and short.

SF-6D Normative Values Among Patients Undergoing Bariatric Surgery: Results Based on Real-World Evidence from the Scandinavian Obesity Surgery Registry (SOReg).

BACKGROUND: The SF-6D index can be used to calculate quality-adjusted life years in economic evaluations, which is required by reimbursement agencies and national advisory bodies, including the Swedish ones. However, despite that SF-36 has been largely applied among patients undergoing bariatric surgery, almost no study has accessed the short form six-dimensions (SF-6D) after bariatric surgery. AIM: To establish normative values for the SF-6D index among patients undergoing bariatric surgery. MATERIALS AND METHODS: All patients who received bariatric surgery in Sweden between 2011-01-01 and 2019-03-31 were obtained from the Scandinavian Obesity Surgery Registry (SOReg). Information includes patients' sociodemographic characteristics, details regarding the procedure, and postsurgical conditions. The SF-36 is applied at baseline and at follow-up years 1, 2, and 5. The multiple sequential imputation method was applied to handle missingness on SF-6D items. Based on the UK tariff, the SF-6D preference scores were calculated. The normative values for the mean (SD) SF-6D index were reported by timepoint and surgical complications for men and women, respectively. Multivariate analyses were applied to investigate how the SF-6D index is associated with timepoint, controlling for age, sex, BMI, and comorbidities in a stepwise manner. RESULTS: The SF-6D index increased at 1 year relative to baseline and was roughly maintained at the same level at 2 years. The normative value of the SF-6D index can be used in economic evaluations for bariatric surgery.

Gastroesophageal reflux and snoring are related to asthma and respiratory symptoms: Results from a Nordic longitudinal population survey.

AIM: To study if individuals with nocturnal gastroesophageal reflux (nGER) and habitual snoring are more likely to develop asthma and respiratory symptoms (i.e. wheeze, cough, chest tightness, breathlessness) than those without these conditions, and if these associations are additive. METHODS: We used data from the population-based prospective questionnaire study Respiratory Health in Northern Europe (RHINE) (11,024 participants), with data from 1999 and 2011. Participants with heartburn or belching after going to bed, at least 1 night/week, were considered to have nGER. Participants reporting loud snoring at least 3 nights/week were considered to have habitual snoring. Participants were grouped into four groups by their nGER and snoring status: "never"; "former"; "incident"; "persistent". Incident respiratory symptoms were analyzed among participants without respective symptom at baseline. RESULTS: Snoring and nGER were independently associated with incident asthma and respiratory symptoms. The risk of incident wheeze was increased in subjects with incident or persistent snoring (adjusted odds ratio (95 % CI): 1.44 (1.21-1.72)), nGER (2.18 (1.60-2.98)) and in those with both snoring and nGER (2.59 (1.83-3.65)). The risk of developing asthma was increased in subjects with incident or persistent snoring (1.44 (1.15-1.82)), nGER (1.99 (1.35-2.93)) and in those with both snoring and nGER (1.72 (1.06-2.77)). No significant interaction was found between snoring and nGER. A similar pattern was found for the incidence of all other respiratory symptoms studied, with the highest risk among those with both incident or persistent nGER and snoring. CONCLUSION: The risk of developing asthma and respiratory symptoms is increased among subjects with nGER and habitual snoring. These associations are independent of each other and confounding factors. Snoring and nGER together are additive on respiratory symptoms.

Early life exposures contributing to accelerated lung function decline in adulthood - a follow-up study of 11,000 adults from the general population.

Background: We aimed to assess whether exposure to risk factors in early life from conception to puberty continue to contribute to lung function decline later in life by using a pooled cohort comprising approx. 11,000 adults followed for more than 20 years and with up to three lung function measurements. Methods: Participants (20-68 years) in the ECRHS and NFBC1966 cohort studies followed in the periods 1991-2013 and 1997-2013, respectively, were included. Mean annual decline in maximum forced expired volume in 1 s (FEV1) and forced vital capacity (FVC) were main outcomes. Associations between early life risk factors and change in lung function were estimated using mixed effects linear models adjusted for sex, age, FEV1, FVC and height at baseline, accounting for personal smoking. Findings: Decline in lung function was accelerated in participants with mothers that smoked during pregnancy (FEV1 2.3 ml/year; 95% CI: 0.7, 3.8) (FVC 2.2 ml/year; 0.2, 4.2), with asthmatic mothers (FEV1 2.6 ml/year; 0.9, 4.4) (FEV1/FVC 0.04 per year; 0.04, 0.7) and asthmatic fathers (FVC 2.7 ml/year; 0.5, 5.0), and in women with early menarche (FVC 2.4 ml/year; 0.4, 4.4). Personal smoking of 10 pack-years contributed to a decline of 2.1 ml/year for FEV1 (1.8, 2.4) and 1.7 ml/year for FVC (1.3, 2.1). Severe respiratory infections in early childhood were associated with accelerated decline among ever-smokers. No effect-modification by personal smoking, asthma symptoms, sex or cohort was found. Interpretation: Mothers' smoking during pregnancy, parental asthma and early menarche may contribute to a decline of FEV1 and FVC later in life comparable to smoking 10 pack-years. Funding: European Union's Horizon 2020; Research Council of Norway; Academy of Finland; University Hospital Oulu; European Regional Development Fund; Spanish Ministry of Science and Innovation; Generalitat de Catalunya.

Prediction of quality-adjusted life years (QALYs) after bariatric surgery using regularized linear regression models: results from a Swedish nationwide quality register.

PURPOSE: To investigate whether the quality-adjusted life years (QALYs) of the patients who underwent bariatric surgery could be predicted using their baseline information. MATERIALS AND METHODS: All patients who received bariatric surgery in Sweden between January 1, 2011 and March 31, 2019 were obtained from the Scandinavian Obesity Surgery Registry (SOReg). Baseline information included patients' sociodemographic characteristics, details regarding the procedure, and postsurgical conditions. QALYs were assessed by the SF-6D at follow-up years 1 and 2. The general and regularized linear regression models were used to predict postoperative QALYs. RESULTS: All regression models demonstrated satisfactory and comparable performance in predicting QALYs at follow-up year 1, with R2 and relative root mean squared error (RRMSE) values of about 0.57 and 9.6%, respectively. The performance of the general linear regression model increased with the number of variables; however, the improvement was ignorable when the number of variables was more than 30 and 50 for follow-up years 1 and 2, respectively. Although minor L1 and L2 regularization provided better prediction ability, the improvement was negligible when the number of variables was more than 20. All the models showed poorer performance for predicting QALYs at follow-up year 2. CONCLUSIONS: Patient characteristics before bariatric surgery including health related quality of life, age, sex, BMI, postoperative complications within six weeks, and smoking status, may be adequate in predicting their postoperative QALYs after one year. Understanding these factors can help identify individuals who require more personalized and intensive support before, during, and after surgery.

Inflammatory bowel disease and asthma. Results from the RHINE study.

BACKGROUND: Asthma and inflammatory bowel disease (IBD) are common inflammatory diseases. The aim of this study was to investigate the associations of IBD with asthma and respiratory symptoms. METHODS: This study is based on 13,499 participants from seven northern European countries that filled in a postal questionnaire on asthma, respiratory symptoms, IBD including ulcerative colitis and Crohn's disease and various lifestyle variables. RESULTS: There were 195 participants with IBD. The prevalence of asthma (14.5 vs 8.1%, p = 0.001), different respiratory symptoms (range 11.9-36.8% vs range 6.0-18.6%, p < 0.005), non-infectious rhinitis (52.1 vs. 41.6%, p = 0.004) and chronic rhinosinusitis (11.6 vs 6.0%, p = 0.001) were higher in subjects with IBD than in those without IBD. In multivariable regression analysis, the association between IBD and asthma was statistically significant (OR 1.95 (95% CI 1.28-2.96)) after adjusting for confounders such as sex, BMI, smoking history, educational level and physical activity. There was a significant association between asthma and ulcerative colitis (adjusted OR 2.02 (95% CI 1.27-2.19)), and asthma but not Crohn's disease (adjusted OR 1.66 (95% CI 0.69-3.95)). A significant gender interaction was found with a significant association between IBD and asthma in women but not in men ((OR 2.72 (95% CI 1.67-4.46) vs OR 0.87 (95% CI 0.35-2.19), p = 0.038). CONCLUSIONS: Patients with IBD, particularly those with ulcerative colitis and female, have a higher prevalence of asthma and respiratory symptoms. Our findings indicate that it is important to consider respiratory symptoms and disorders when examining patients with manifest or suspected IBD.

Association between abdominal and general obesity and respiratory symptoms, asthma and COPD. Results from the RHINE study.

INTRODUCTION: Previous studies on the association between abdominal and general obesity and respiratory disease have provided conflicting results. AIMS AND OBJECTIVES: We aimed to explore the associations of abdominal obesity with respiratory symptoms, asthma, and chronic obstructive pulmonary disease independently from general obesity in women and men. METHODS: This cross-sectional study was based on the Respiratory Health in Northern Europe (RHINE) III questionnaire (n = 12 290) conducted in 2010-2012. Abdominal obesity was self-measured waist circumference using a sex-specific standard cut-off point: ≥102 cm in males and ≥88 cm in females. General obesity was defined as self-reported BMI ≥30.0 kg/m2. RESULTS: There were 4261 subjects (63% women) with abdominal obesity and 1837 subjects (50% women) with general obesity. Both abdominal and general obesity was independent of each other and associated with respiratory symptoms (odds ratio (OR) from 1.25 to 2.00)). Asthma was significantly associated with abdominal and general obesity in women, OR (95% CI) 1.56 (1.30-1.87) and 1.95 (1.56-2.43), respectively, but not in men, OR 1.22 (0.97-3.17) and 1.28 (0.97-1.68) respectively. A similar sex difference was found for self-reported chronic obstructive pulmonary disease. CONCLUSIONS: General and abdominal obesity were independent factors associated with respiratory symptoms in adults. Asthma and chronic obstructive pulmonary disease were independently linked to abdominal and general obesity in women but not men.

What is the significance of the Hill classification?

This study aimed to investigate the significance of Hill classification to predict esophagitis, Barrett's esophagus, gastroesophageal reflux disease (GERD) symptomatology, and future prescriptions of proton pump inhibitors in clinical practice. A total of 922 patients (546 women and 376 men; mean age 54.3 [SD 18.4] years) who underwent gastroscopy between 2012 and 2015 were analyzed. Patient questionnaire regarding symptoms were compared with endoscopy findings. A medical chart review was done that focused on the prescription of PPIs, additional gastroscopies, and GERD surgery in a 3-year period before the index gastroscopy and in a 6-year period afterward. In patients naïve to PPI prescriptions (n = 466), Hill grade III was significantly associated with esophagitis (AOR 2.20; 95% CI 1.00-4.84) and > 2 PPI prescriptions 6 year after the index gastroscopy (AOR 1.95; 95% CI 1.01-3.75), whereas Hill grade IV was significantly associated with esophagitis (AOR 4.41; 95% CI 1.92-10.1), with Barrett's esophagus (AOR 12.7; 95% CI 1.45-112), with reported heartburn (AOR 2.28; 95% CI 1.10-4.74), and with >2 PPI prescriptions (AOR 2.16; 95% CI 1.02-4.55). In patients 'non-naïve' to PPI prescription (n = 556), only Hill grade IV was significantly associated with esophagitis, reported heartburn, and with >2 PPI prescriptions. The gastroscopic classification in Hill grades III and IV is important in clinical practice because they are associated with esophagitis, Barrett's esophagus, symptoms of GERD, and prescriptions of PPIs, whereas a differentiation between Hill grades I and II is not.

Mapping the obesity problems scale to the SF-6D: results based on the Scandinavian Obesity Surgery Registry (SOReg).

BACKGROUND: Obesity Problem Scale (OP) is a widely applied instrument for obesity, however currently calculation of health utility based on OP is not feasible as it is not a preference-based measure. Using data from the Scandinavian Obesity Surgery Registry (SOReg), we sought to develop a mapping algorithm to estimate SF-6D utility from OP. Furthermore, to test whether the mapping algorithm is robust to the effect of surgery. METHOD: The source data SOReg (n = 36 706) contains both OP and SF-36, collected at pre-surgery and at 1, 2 and 5 years post-surgery. The Ordinary Least Square (OLS), beta-regression and Tobit regression were used to predict the SF-6D utility for different time points respectively. Besides the main effect model, different combinations of patient characteristics (age, sex, Body Mass Index, obesity-related comorbidities) were tested. Both internal validation (split-sample validation) and validation with testing the mapping algorithm on a dataset from other time points were carried out. A multi-stage model selection process was used, accessing model consistency, parsimony, goodness-of-fit and predictive accuracy. Models with the best performance were selected as the final mapping algorithms. RESULTS: The final mapping algorithms were based on OP summary score using OLS models, for pre- and post-surgery respectively. Mapping algorithms with different combinations of patients' characteristics were presented, to satisfy the user with a different need. CONCLUSION: This study makes available algorithms enabling crosswalk from the Obesity Problem Scale to the SF-6D utility. Different mapping algorithms are recommended for the mapping of pre- and post-operative data.

Development and performance of a sleep estimation algorithm using a single accelerometer placed on the thigh: an evaluation against polysomnography.

Accelerometers placed on the thigh provide accurate measures of daily physical activity types, postures and sedentary behaviours, over 24 h and across consecutive days. However, the ability to estimate sleep duration or quality from thigh-worn accelerometers is uncertain and has not been evaluated in comparison with the 'gold-standard' measurement of sleep polysomnography. This study aimed to develop an algorithm for sleep estimation using the raw data from a thigh-worn accelerometer and to evaluate it in comparison with polysomnography. The algorithm was developed and optimised on a dataset consisting of 23 single-night polysomnography recordings, collected in a laboratory, from 15 asymptomatic adults. This optimised algorithm was then applied to a separate evaluation dataset, in which, 71 adult males (mean [SD] age 57 [11] years, height 181 [6] cm, weight 82 [13] kg) wore ambulatory polysomnography equipment and a thigh-worn accelerometer, simultaneously, whilst sleeping at home. Compared with polysomnography, the algorithm had a sensitivity of 0.84 and a specificity of 0.55 when estimating sleep periods. Sleep intervals were underestimated by 21 min (130 min, Limits of Agreement Range [LoAR]). Total sleep time was underestimated by 32 min (233 min LoAR). Our results evaluate the performance of a new algorithm for estimating sleep and outline the limitations. Based on these results, we conclude that a single device can provide estimates of the sleep interval and total sleep time with sufficient accuracy for the measurement of daily physical activity, sedentary behaviour, and sleep, on a group level in free-living settings.

Clinical Remission of Asthma and Allergic Rhinitis - in a Longitudinal Population Study.

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.

Sequential Multiple Imputation for Real-World Health-Related Quality of Life Missing Data after Bariatric Surgery.

One of the main challenges for the successful implementation of health-related quality of life (HRQoL) assessments is missing data. The current study examined the feasibility and validity of a sequential multiple imputation (MI) method to deal with missing values in the longitudinal HRQoL data from the Scandinavian Obesity Surgery Registry. All patients in the SOReg who received bariatric surgery between 1 January 2011 and 31 March 2019 (n = 47,653) were included for the descriptive analysis and missingness pattern exploration. The patients who had completed the short-form 36 (SF-36) at baseline (year 0), and one-, two-, and five-year follow-ups were included (n = 3957) for the missingness pattern simulation and the sequential MI analysis. Eleven items of the SF-36 were selected to create the six domains of SF-6D, and the SF-6D utility index of each patient was calculated accordingly. The multiply-imputed variables in previous year were used as input to impute the missing values in later years. The performance of the sequential MI was evaluated by comparing the actual values with the imputed values of the selected SF-36 items and index at all four time points. At the baseline and year 1, where missing proportions were about 20% and 40%, respectively, there were no statistically significant discrepancies between the distributions of the actual and imputed responses (all p-values > 0.05). In year 2, where the missing proportion was about 60%, distributions of the actual and imputed responses were consistent in 9 of the 11 SF-36 items. However, in year 5, where the missing proportion was about 80%, no consistency was found between the actual and imputed responses in any of the SF-36 items. Relatively high missing proportions in HRQoL data are common in clinical registries, which brings a challenge to analyzing the HRQoL of longitudinal cohorts. The experimental sequential multiple imputation method adopted in the current study might be an ideal strategy for handling missing data (even though the follow-up survey had a missing proportion of 60%), avoiding significant information waste in the multivariate analysis. However, the imputations for data with higher missing proportions warrant more research.

Asthma, allergic rhinitis and atopic dermatitis in association with home environment - The RHINE study.

We studied home environment exposures in relation to asthma, allergic rhinitis and atopic dermatitis among offspring of participants (parents) in the Respiratory Health in Northern Europe (RHINE) study (age ≤ 30 y). Totally 17,881 offspring from Iceland, Norway, Sweden, Denmark and Estonia were included. Home environment exposures, including dampness and mold, type of dwelling, construction year and indoor painting were registered through a questionnaire answered by parents in the first follow up (RHINE II). The parents reported ten years later with in the frame of RHINE III offspring's birth year and offspring's asthma, allergic rhinitis, atopic dermatitis. They also reported dampness and mold at home from RHINE II to RHINE III. The prevalence of offspring's asthma before 10 y, asthma after 10 y, allergic rhinitis at any age and atopic dermatitis at any age were 9.7 %, 4.3 %, 15.6 % and 17.3 %, respectively. Asthma before 10 y was related to any indoor painting at RHINE II (OR = 1.14, 95%CI (1.02, 1.29)). Asthma after 10 y was associated with dampness/mold at home (OR = 1.33-1.62) and living in the newest buildings (constructed in 1986-2001) (OR = 1.30, 95%CI (1.02, 1.66)). Allergic rhinitis was associated with living in newer buildings (constructed in 1961-2001) (OR = 1.16-1.24). Atopic dermatitis was associated with visible mold (OR = 1.35, 95%CI(1.12, 1.62)), dampness/mold at home (OR = 1.18-1.38), living in apartments (OR = 1.22, 95%CI(1.10, 1.35)) and living in newer buildings (constructed in 1961-2001) (OR = 1.14-1.25). There were dose-response effects of dampness and mold on offspring's asthma after 10 y and atopic dermatitis (20 years exposure vs. 10 years exposure). Older offspring had increased risk of developing asthma after 10 y and atopic dermatitis. In conclusion, home dampness and mold, living in apartments, living in newer buildings and indoor painting were associated with offspring's asthma or allergic diseases. Stronger health effects were found among offspring with prolonged exposure of dampness/mold.

Effects of a palaeolithic diet on obstructive sleep apnoea occurring in females who are overweight after menopause-a randomised controlled trial.

BACKGROUND/OBJECTIVES: Obesity is the main risk factor for obstructive sleep apnoea, commonly occurring in females who are overweight after menopause. We aimed to study the effect of a palaeolithic diet on sleep apnoea in females with overweight after menopause from the population. METHODS: Seventy healthy, non-smoking females with a mean age of 60 years and a mean BMI of 33 kg/m2 were randomised to a palaeolithic diet or to a control low-fat diet according to Nordic Nutritional Recommendations, for 2 years. The apnoea-hypopnoea index was measured and daytime sleepiness was estimated during the intervention. RESULTS: The mean apnoea-hypopnoea index at baseline was 11.6 (95% CI 8.6-14.5). The mean weight loss was 7.2 kg (95% CI 5.3-9.2 kg) in the palaeolithic diet group and 3.9 kg in the control group (95% CI 1.9-5.9 kg); p < 0.021 for the group difference. The reduction in weight corresponded to a reduction in the apnoea-hypopnoea index in the palaeolithic diet group (r = 0.38, p = 0.034) but not in the control group (r = 0.08, p = 0.69). The apnoea-hypopnoea index was reduced in the palaeolithic diet group when the weight was reduced by more than 8 kg. Daytime sleepiness according to the Epworth Sleepiness Scale score and the Karolinska Sleepiness Scale score was unaffected by dietary group allocation. CONCLUSIONS: A substantial decrease in body weight of 8 kg was needed to achieve a reduction in sleep apnoea in this small trial of women who are overweight after menopause. The palaeolithic diet was more effective for weight reduction than a control low-fat diet and the reduction in sleep apnoea was related to the degree of weight decrement within this diet group. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00692536.

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

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.

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

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 17ß-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.

Premature menopause and autoimmune primary ovarian insufficiency in two international multi-center cohorts.

Objective: To investigate markers of premature menopause (<40 years) and specifically the prevalence of autoimmune primary ovarian insufficiency (POI) in European women. Design: Postmenopausal women were categorized according to age at menopause and self-reported reason for menopause in a cross-sectional analysis of 6870 women. Methods: Variables associated with the timing of menopause and hormone measurements of 17ß-estradiol and follicle-stimulating hormone were explored using multivariable logistic regression analysis. Specific immunoprecipitating assays of steroidogenic autoantibodies against 21-hydroxylase (21-OH), side-chain cleavage enzyme (anti-SCC) and 17alpha-hydroxylase (17 OH), as well as NACHT leucine-rich-repeat protein 5 were used to identify women with likely autoimmune POI. Results: Premature menopause was identified in 2.8% of women, and these women had higher frequencies of nulliparity (37.4% vs 19.7%), obesity (28.7% vs 21.4%), osteoporosis (17.1% vs 11.6%), hormone replacement therapy (59.1% vs 36.9%) and never smokers (60.1% vs 50.9%) (P < 0.05), compared to women with menopause ≥40 years. Iatrogenic causes were found in 91 (47%) and non-ovarian causes in 27 (14%) women, while 77 (39%) women were classified as POI of unknown cause, resulting in a 1.1% prevalence of idiopathic POI. After adjustments nulliparity was the only variable significantly associated with POI (odds ratio 2.46; 95% CI 1.63-3.42). Based on the presence of autoantibodies against 21 OH and SCC, 4.5% of POI cases were of likely autoimmune origin. Conclusion: Idiopathic POI affects 1.1% of all women and almost half of the women with premature menopause. Autoimmunity explains 4.5% of these cases judged by positive steroidogenic autoantibodies.

Rapid eye movement sleep apnea and carotid intima thickness in men and women: a SHE-MUSTACHE cohort study.

Rapid eye movement (REM) obstructive sleep apnea might be particularly harmful to the cardiovascular system. We aimed to investigate the association between sleep apnea during REM sleep and signs of atherosclerotic disease in the form of carotid intima thickness in a community-based sample of men and women and possible sex differences in this association. The association between sleep apnea during REM sleep and intima thickness was analysed cross-sectionally in women from the community-based "Sleep and Health in Women" (SHE) study (n = 253) and age- and body mass index (BMI)-matched men from the "Men in Uppsala; a Study of sleep, Apnea and Cardiometabolic Health" (MUSTACHE) study (n = 338). Confounders adjusted for were age, BMI, gender, alcohol, and smoking. All participants underwent a full-night polysomnography, high-resolution ultrasonography of the common carotid artery, anthropometric measurements, blood pressure measurements, and answered questionnaires. There was an association between sleep apnea during REM sleep and thicker carotid intima that remained after adjustment for confounding (adjusted ß = 0.008, p = 0.032). The intima was increased by 9.9% in the group with severe sleep apnea during REM sleep, and this association between severe sleep apnea during REM sleep and increased intima thickness remained after adjustment for confounders (adjusted ß = 0.043, p = 0.021). More women than men had severe sleep apnea during REM sleep; moreover, in sex-stratified analyses, the association between sleep apnea during REM sleep and intima thickness was found in women but not in men. We conclude that severe REM sleep apnea is independently associated with signs of atherosclerosis. When stratified by sex, the association is seen in women but not in men.