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STUDY OBJECTIVES: Insomnia and snoring are common sleep disorders. The aim was to investigate the association of having a combination of insomnia symptoms and snoring with comorbidity and daytime sleepiness. METHODS: The study population comprised 25,901 participants (16–75 years, 54.4% women) from 4 Swedish cities, who answered a postal questionnaire that contained questions on snoring, insomnia symptoms (difficulties initiating and/or maintaining sleep and/or early morning awakening), smoking, educational level, and respiratory and nonrespiratory disorders. RESULTS: Snoring was reported by 4,221 (16.2%), while 9,872 (38.1%) reported ≥ 1 insomnia symptom. A total of 2,150 (8.3%) participants reported both insomnia symptoms and snoring. The association with hypertension (adjusted odds ratio [OR], 1.4; 95% confidence interval [CI], 1.2–1.6), chronic obstructive pulmonary disease (adjusted OR, 1.8; 95% CI, 1.3–2.4), asthma (adjusted OR, 1.9; 95% CI, 1.6–2.3), daytime sleepiness (adjusted OR, 7.9; 95% CI, 7.1–8.8), and the use of hypnotics (adjusted OR, 7.5; 95% CI, 6.1–9.1) was highest for the group with both insomnia symptoms and snoring. CONCLUSIONS: Participants with both snoring and insomnia run an increased risk of hypertension, chronic obstructive pulmonary disease, asthma, daytime sleepiness, and use of hypnotics. It is important to consider snoring in patients seeking medical assistance for insomnia and, vice versa, in patients with snoring inquiring about insomnia. CITATION: Hägg SA, Ilieva E, Ljunggren M, et al. The negative health effects of having a combination of snoring and insomnia. J Clin Sleep Med. 2022;18(4):973–981.

Summary 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.

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.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.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.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.

Background: Asthma is common worldwide and a large part of subjects with asthma have concomitant allergic multimorbidity in the form of rhinitis and/or eczema. Objective: The aim of this study is to investigate whether the presence of allergic multimorbidity in asthma relates to allergic sensitization, allergic and respiratory symptoms, quality of life, inflammatory markers, lung function, use of medication and background factors. Methods: A total of 437 asthmatics from the (GA(2)LEN) cross-sectional survey in Sweden were grouped depending on the presence of rhinitis and/or eczema. The impact of allergic multimorbidity was assessed in terms of allergic sensitization, allergic and respiratory symptoms, quality of life, type-2 inflammatory markers (exhaled nitric oxide, eosinophil activation markers, periostin), lung function, use of medication and background factors. Results: Subjects with asthma, rhinitis and eczema were more likely to be sensitized to seasonal allergens (67% vs 32%, P < .001), food allergens (54% vs 18%, P < .001) and to have a higher degree of sensitization than subjects with only asthma (23% vs 10%, P < .001). Subjects with allergic multimorbidity more often had allergic reactions to food (28% vs 10%, P = .002), more respiratory symptoms and anxiety/depression (40% vs, 14%, P < .001) than subjects with only asthma, despite having similar levels of type 2 inflammatory markers. Individuals with allergic multimorbidity were more likely to be diagnosed with asthma before the age of 12 (48% vs 27%, P = .016) and to have maternal heredity for allergy (53% vs 33%, P = .011) than subjects with only asthma. Conclusion and clinical relevance: Asthmatics with allergic multimorbidity are more likely to be sensitized to seasonal aeroallergens, food allergens and they have a higher degree of sensitization compared with those with only asthma. Allergic multimorbidity is associated with respiratory and allergy symptoms, anxiety and/or depression.

STUDY OBJECTIVES: Exposure to traffic noise increases the risk of sleeping disturbance, but little is known about the effect of traffic-related air pollution on insomnia symptoms. We aimed to investigate the separate associations of self-reported proximity to traffic and traffic noise with insomnia. METHODS: This is a cross-sectional study of the population included in the Respiratory Health in Northern Europe study, consisting of randomly selected men and women born between 1945 and 1973, from 7 Northern European centers. Hearing traffic noise in the bedroom, bedroom window proximity to traffic, and insomnia symptoms were self-reported. Bedroom window proximity to traffic was used as a surrogate for exposure to traffic-related air pollution. The following insomnia symptoms were assessed: difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening. RESULTS: A total of 12,963 individuals was included. Traffic noise was positively associated with all three insomnia symptoms: difficulty initiating sleep (odds ratio [OR] = 3.54; 95% confidence interval [CI]: 1.85, 6.76), difficulty maintaining sleep (OR = 2.95; 95% CI: 1.62, 5.37), and early morning awakening (OR = 3.25; 95% CI: 1.97, 5.37). Proximity to traffic without disturbing noise was associated with difficulty initiating sleep (OR = 1.62; 95% CI: 1.45, 1.82). CONCLUSIONS: This study adds further support to the identification of traffic noise as a risk factor for insomnia. Proximity to traffic without being exposed to noise was associated with an increased risk of difficulty initiating sleep. Our findings indicate that insomnia may be associated with both traffic noise and traffic-related air pollution. CITATION: Janson E, Johannessen A, Holm M, et al. Insomnia associated with traffic noise and proximity to traffic—a cross-sectional study of the Respiratory Health in Northern Europe III population. J Clin Sleep Med. 2020;16(4):545–552.

Background: 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. Objective: 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. Methods: 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. Results: 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. Conclusions: 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. Kai Triebner has received a postdoctoral fellowship from the University of Bergen. Payam Dadvand is funded by a Ramón y Cajal fellowship (Grant: RYC-2012–10995) awarded by the Spanish Ministry of Economy and Finance. The present analyses are part of a project funded by the Norwegian Research Council (Grant: 228174). Co-ordination of the RHINESSA study has received funding from the Research Council of Norway (Grants No. 274767, 214123, 228174, 230,827 and 273838), ERC StG project BRuSH #804199, the European Union's Horizon 2020 research and innovation programme under grant agreement No. 633,212 (the ALEC Study WP2), the Bergen Medical Research Foundation, and the Western Norwegian Regional Health Authorities (Grants No. 912011, 911892 and 911631). Study centre Bergen has further received local funding from the above-named grants for study establishment and co-ordination and in addition from the World University Network, the Norwegian Labour Inspection, and the Norwegian Asthma and Allergy Association. Iana Markevych is supported from the “NeuroSmog: Determining the impact of air pollution on the developing brain” (Nr. POIR 040.04.00-1763/18-00) which is implemented as part of the TEAM-NET programme of the Foundation for Polish Science, co-financed from EU resources, obtained from the European Regional Development Fund under the Smart Growth Operational Programme. The funding sources were not involved in the conduct of the research and/or preparation of the article, in study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication.

Background Breathlessness is a major cause of suffering and disability globally. The symptom relates to multiple factors including asthma and lung function, which are influenced by hereditary factors. No study has evaluated potential inheritance of breathlessness itself across generations. Methods We analysed the association between breathlessness in parents and their offspring in the Respiratory Health in Northern Europe, Spain and Australia generation study. Data on parents and offspring aged ≥18 years across 10 study centres in seven countries included demographics, self-reported breathlessness, asthma, depression, smoking, physical activity level, measured Body Mass Index and spirometry. Data were analysed using multivariable logistic regression accounting for clustering within centres and between siblings. Results A total of 1720 parents (mean age at assessment 36 years, 55% mothers) and 2476 offspring (mean 30 years, 55% daughters) were included. Breathlessness was reported by 809 (32.7%) parents and 363 (14.7%) offspring. Factors independently associated with breathlessness in parents and offspring included obesity, current smoking, asthma, depression, lower lung function and female sex. After adjusting for potential confounders, parents with breathlessness were more likely to have offspring with breathlessness, adjusted OR 1.8 (95% CI 1.1 to 2.9). The association was not modified by sex of the parent or offspring. Conclusion Parents with breathlessness were more likely to have children who developed breathlessness, after adjusting for asthma, lung function, obesity, smoking, depression and female sex in both generations. The hereditary components of breathlessness need to be further explored., ME was supported by unrestricted grants from the Swedish Society for Medical Research and the Swedish Research Council (Dnr: 2019-02081). Coordination and establishment of the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) study has received funding from the Research Council of Norway (grant numbers 274767, 214123, 228174, 230827 and 273838), ERC StG project BRuSH (#804199), the European Union’s Horizon 2020 research and innovation programme (grant agreement number 633212) (the ALEC Study WP2), the Bergen Medical Research Foundation and the Western Norwegian Regional Health Authorities (grant numbers 912011, 911892 and 911631). Study centres have further received local funding from the following: Bergen: the above grants, World University Network (REF and Sustainability grants), Norwegian Labour Inspection, the Norwegian Asthma and Allergy Association. Albacete and Huelva: Sociedad Española de Patología Respiratoria (SEPAR) Fondo de Investigación Sanitaria (FIS PS09). Göteborg, Umeå and Uppsala: the Swedish Heart and Lung Foundation, the Swedish Asthma and Allergy Association. Reykjavik: Iceland University. Melbourne: NHMRC Project Grant ID1128450, Melbourne University. Tartu: the Estonian Research Council (grant number PUT562). Århus: The Danish Wood Foundation (grant number 444508795), the Danish Working Environment Authority (grant number 20150067134), Aarhus University (PhD scholarship). The RHINE study has received funding from Danish Lung Association, Estonian Science Foundation, Icelandic Research Council, Norwegian Research Council, Norwegian Asthma and Allergy Association, Swedish Asthma and Allergy Association, Swedish Heart and Lung Foundation and Vårdal Foundation for Health Care Science and Allergy Research. The coordination of the ECRHS has been supported by the European Union’s Horizon 2020 research and innovation programme (grant agreement number 633212) (the ALEC study), the Medical Research Council (ECRHS III) and the European Commission FP5 and FP7 (ECRHS I and II). ECRHS IV is being planned and the 10 RHINESSA study centres are funded by ERC StG project BRuSH (#804199) and by the European Union’s Horizon 2020 research and innovation programme (grant agreement number 874703) (the EPHOR project). Further funding agencies for ECRHS are reported elsewhere.

In a recent study we found that fathers’ but not mothers’ onset of overweight in puberty was associated with asthma in adult offspring. The potential impact on offspring’s adult lung function, a key marker of general and respiratory health, has not been studied. We investigated the potential causal effects of parents’ overweight on adult offspring’s lung function within the paternal and maternal lines. We included 929 offspring (aged 18–54, 54% daughters) of 308 fathers and 388 mothers (aged 40–66). Counterfactual-based multi-group mediation analyses by offspring’s sex (potential moderator) were used, with offspring’s prepubertal overweight and/or adult height as potential mediators. Unknown confounding was addressed by simulation analyses. Fathers’ overweight before puberty had a negative indirect effect, mediated through sons’ height, on sons’ forced expiratory volume in one second (FEV1) (beta (95% CI): −144 (−272, −23) mL) and forced vital capacity (FVC) (beta (95% CI): −210 (−380, −34) mL), and a negative direct effect on sons’ FVC (beta (95% CI): −262 (−501, −9) mL); statistically significant effects on FEV1/FVC were not observed. Mothers’ overweight before puberty had neither direct nor indirect effects on offspring’s lung function. Fathers’ overweight starting before puberty appears to cause lower FEV1 and FVC in their future sons. The effects were partly mediated through sons’ adult height but not through sons’ prepubertal overweight.

Background There are several surgical options for the management of pilonidal disease, including midline and off midline closure, but prospective studies are rare. The study hypothesis was that Karydakis flap surgery would result in shorter wound healing and fewer recurrences than excision of pilonidal sinus and suture in the midline. Methods A randomized clinical trial was conducted in two hospitals in Sweden between 2006 and 2015 to compare excision and suture in the midline with Karydakis flap surgery. Adult patients with a chronic pilonidal sinus disease were randomized 1:1 at the outpatient clinic without blinding. Power calculation based on recurrence of 2 per cent for Karydakis flap and 10 per cent for excision and primary closure in the midline required 400 patients with 90 per cent statistical power at 5 per cent significance assuming 10 per cent loss during follow-up. Participants were followed up until complete wound healing; late follow-up after 6–13 years was performed by telephone by two blinded assessors. The two co-primary outcomes were time to complete wound healing and recurrence rate. Results The study was terminated early at a planned interim analysis due slow recruitment and a significant difference in primary outcome. In total, 125 patients were randomized, of whom 116 were available for the present analysis. Median wound healing time was 49 days (95 per cent confidence interval (c.i.) 32 to 66) for excision with suture in the midline and 14 days (95 per cent c.i. 12 to 20) for Karydakis flap surgery (P Conclusion Karydakis flap surgery for pilonidal sinus disease led to a shorter wound healing time than excision and suture in the midline but no difference in recurrence rates. Registration number: NCT00412659 (http://www.clinicaltrials.gov)

Using one-night sleep recordings from 852 subjects all living in Uppsala, Sweden, the present study represents one of the largest polysomnography investigations into the association of the 29.53-day long lunar cycle with sleep among men and women and across a wide age range (22-81 years). Following the day after the new moon until the day of the full moon (also named the waxing period), the moon's illumination increases, and the timing of the meridian of the moon is gradually shifted from noontime toward midnight. In contrast, from the day after the full moon until the day of the new moon (also named the waning period), the moon's illumination decreases, and the timing of the meridian of the moon is gradually shifted from early night hours toward noontime. Thus, we focused on the contrast between the waxing and waning periods. Sleep duration was shorter on nights during the waxing period as compared to waning period (P

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 β = 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 β = 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.

Objective:. To evaluate the immediate effects of positive expiratory pressure therapy on oxygen saturation and ventilation after abdominal surgery. Background:. Positive expiratory pressure therapy to treat postoperative hypoxia is widespread, despite a lack of evidence of effect. Methods:. This randomized, sham-controlled, crossover trial investigated adults 1–2 days after abdominal surgery at Umeå University Hospital, Sweden. The intervention was positive expiratory pressure of 10–15 cm H2O. The control was a sham device. The investigations were ended with deep-breathing maneuvers. Outcomes were the gradient of changes in peripheral oxygen saturation and transcutaneous carbon-dioxide partial pressure (PtcCO2). Results:. Eighty patients were included and randomized and 76 patients were analyzed. Oxygen saturation increased from a baseline mean of 92% to 95%, P < 0.001, during positive expiratory pressure breathing, while PtcCO2 decreased from a mean of 36 to 33 mm Hg, P < 0.001. This was followed by apnea, oxygen desaturations to a mean of 89%, P < 0.001, and increased PtcCO2 before returning to baseline values. The changes in oxygen saturation and PtcCO2 did not differ from sham breathing or deep-breathing maneuvers. Conclusions:. Positive expiratory pressure breathing after abdominal surgery improves oxygen saturation during the maneuver because of hyperventilation, but it is followed by apnea, hypoventilation, and oxygen desaturation. The effect is not different from the expiration to a sham device or hyperventilation. It is time to stop positive expiratory pressure therapy after abdominal surgery, as there is no evidence of effect in previous trials, apart from the adverse effects reported here.

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. publishedVersion

Obstructive sleep apnoea and residual neuromuscular blockade are, independently, known to be risk factors for respiratory complications after major surgery. Residual effects of neuromuscular blocki ...

Introduction The study aim was to examine the association of snoring and nocturnal gastro-oesophageal reflux (nGOR) with respiratory symptoms and lung function, and if snoring and/or nGOR associated with a steeper decline in lung function. Methods Data from the third visit of the European Community Respiratory Health Survey (ECRHS) was used for cross-sectional analysis. Pre- and post-bronchodilator spirometry was performed, and information on sleep, nGOR and respiratory symptoms was collected (n=5715). Habitual snoring and nGOR were assessed by questionnaire reports. Pre-bronchodilator spirometry from ECRHS I, II and III (20 years follow-up) were used to analyse lung function changes by multivariate regression analysis. Results Snoring and nGOR were independently associated with a higher prevalence of wheeze, chest tightness, breathlessness, cough and phlegm. The prevalence of any respiratory symptom was 79% in subjects with both snoring and nGOR versus 56% in those with neither (p, Middle-aged adults with habitual snoring have a steeper decline in lung function over 10 years compared to controls. Habitual snorers with nocturnal gastro-oesophageal reflux have a higher prevalence of nocturnal respiratory symptoms than controls. http://ow.ly/YsiK30odcMY

Background The pathophysiology of obstruction and swallowing dysfunction in snores and sleep apnea patients remains unclear. Neuropathy and to some extent myopathy have been suggested as contributing causes. Recently we reported an absence and an abnormal isoform of two cytoskeletal proteins, desmin, and dystrophin, in upper airway muscles of healthy humans. These cytoskeletal proteins are considered vital for muscle function. We aimed to investigate for muscle cytoskeletal abnormalities in upper airways and its association with swallowing dysfunction and severity of sleep apnea. Methods Cytoskeletal proteins desmin and dystrophin were morphologically evaluated in the uvula muscle of 22 patients undergoing soft palate surgery due to snoring and sleep apnea and in 10 healthy controls. The muscles were analysed with immunohistochemical methods, and swallowing function was assessed using videoradiography. Results Desmin displayed a disorganized pattern in 21 ± 13% of the muscle fibres in patients, while these fibers were not present in controls. Muscle fibres lacking desmin were present in both patients and controls, but the proportion was higher in patients (25 ± 12% vs. 14 ± 7%, p = 0.009). The overall desmin abnormalities were significantly more frequent in patients than in controls (46 ± 18% vs. 14 ± 7%, p

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.

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.

Background: 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. Methods: 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. Results: 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.Conclusion: 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.

International audience; BACKGROUND: Solar ultraviolet radiation (UVR) affects the body through pathways that exhibit positive as well as negative health effects such as immunoregulation and vitamin D production. Different vitamin D metabolites are associated with higher or lower concentrations of estrogens and may thus alter the female sex hormone balance. OBJECTIVE: To study whether exposure to UVR, as a modifiable lifestyle factor, is associated with levels of sex hormones (17β-estradiol, estrone, estrone 3-sulfate, testosterone, dehydroepiandrosterone sulfate), gonadotropins (follicle stimulating hormone, luteinizing hormone) as well as sex hormone binding globulin in postmenopausal women, and thus investigate whether managing UVR exposure can influence the hormone balance, with potential benefits for the biological aging process.METHODS: The study included 580 postmenopausal women from six European countries, participating in the European Community Respiratory Health Survey (2010-2014). Average UVR exposure during the month before blood sampling was estimated based on personal sun behavior and ambient levels. Hormone concentrations were measured in serum using state-of-the-art methods. Subsequently we applied linear mixed-effects models, including center as random intercept, hormone concentrations (one at a time) as outcome and UVR, age, skin type, body mass index, vitamin D from dietary sources, smoking, age at completed full-time education and season of blood sampling as fixed-effect predictors.RESULTS: One interquartile range increase in UVR exposure was associated with decreased levels of 17β-estradiol (-15.6 pmol/L, 95 % Confidence Interval (CI): -27.69, -3.51) and estrone (-13.36 pmol/L, 95 % CI: -26.04, -0.68) and increased levels of follicle stimulating hormone (9.34IU/L, 95 % CI: 2.91, 15.77) and luteinizing hormone (13.86 IU/daL, 95 % CI: 2.48, 25.25).CONCLUSIONS: Exposure to UVR is associated with decreased estrogens and increased gonadotropins in postmenopausal women, a status associated with osteoporosis, lung function decline and other adverse health effects. This study indicates that managing UVR exposure has potential to influence the hormone balance and counteract adverse health conditions after menopause.

ObjectiveHabitual snoring is associated with fatigue, headaches and low work performance. This cross-sectional study aimed to investigate if snoring is affected by environmental factors such as home dampness and exposure to air pollution.SettingGeneral population sample from four Swedish cities.Participants25 848 participants from the Swedish part of the epidemiological Global Asthma and Allergy and European network of excellence study carried out in 2008. The participants completed a postal questionnaire on snoring and, indoor and outdoor environmental exposure as well as potential confounders including smoking, weight, height and educational level.ResultsOf the participants, 4211 (16.3%) were habitual snorers. Habitual snorers reported water damage (8.3% vs 7.0% pConclusionSnoring is more prevalent in subjects reporting home dampness and air pollution. These association should be confirmed in further research using objective measurements and a longitudinal approach.

Objective: To evaluate the immediate effects of positive expiratory pressure therapy on oxygen saturation and ventilation after abdominal surgery. Background: Positive expiratory pressure therapy to treat postoperative hypoxia is widespread, despite a lack of evidence of effect. Methods: This randomized, sham-controlled, crossover trial investigated adults 1–2 days after abdominal surgery at Umeå University Hospital, Sweden. The intervention was positive expiratory pressure of 10–15 cm H2O. The control was a sham device. The investigations were ended with deep-breathing maneuvers. Outcomes were the gradient of changes in peripheral oxygen saturation and transcutaneous carbon-dioxide partial pressure (PtcCO2). Results: Eighty patients were included and randomized and 76 patients were analyzed. Oxygen saturation increased from a baseline mean of 92% to 95%, P < 0.001, during positive expiratory pressure breathing, while PtcCO2 decreased from a mean of 36 to 33 mm Hg, P < 0.001. This was followed by apnea, oxygen desaturations to a mean of 89%, P < 0.001, and increased PtcCO2 before returning to baseline values. The changes in oxygen saturation and PtcCO2 did not differ from sham breathing or deep-breathing maneuvers. Conclusions: Positive expiratory pressure breathing after abdominal surgery improves oxygen saturation during the maneuver because of hyperventilation, but it is followed by apnea, hypoventilation, and oxygen desaturation. The effect is not different from the expiration to a sham device or hyperventilation. It is time to stop positive expiratory pressure therapy after abdominal surgery, as there is no evidence of effect in previous trials, apart from the adverse effects reported here.

Purpose To study changes in lung function among individuals with a risk of obstructive sleep apnoea (OSA), and if asthma affected this relationship. Methods We used data from the European Community Respiratory Health Survey II and III, a multicentre general population study. Participants answered questionnaires and performed spirometry at baseline and 10-year follow-up (n = 4,329 attended both visits). Subjects with high risk for OSA were identified from the multivariable apnoea prediction (MAP) index, calculated from BMI, age, gender, and OSA symptoms at follow-up. Asthma was defined as having doctor’s diagnosed asthma at follow-up. Primary outcomes were changes in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from baseline to follow-up. Results Among 5108 participants at follow-up, 991 (19%) had a high risk of OSA based on the MAP index. Participants with high OSA risk more often had wheeze, cough, chest tightness, and breathlessness at follow-up than those with low OSA risk. Lung function declined more rapidly in subjects with high OSA risk (low vs high OSA risk [mean ± SD]: FEV1 = − 41.3 ± 24.3 ml/year vs − 50.8 ± 30.1 ml/year; FVC = − 30.5 ± 31.2 ml/year vs − 45.2 ± 36.3 ml/year). Lung function decline was primarily associated with higher BMI and OSA symptoms. OSA symptoms had a stronger association with lung function decline among asthmatics, compared to non-asthmatics. Conclusion In the general population, a high probability of obstructive sleep apnoea was related to faster lung function decline in the previous decade. This was driven by a higher BMI and more OSA symptoms among these subjects. The association between OSA symptoms and lung function decline was stronger among asthmatics.

Purpose Humans have a preference for nasal breathing during sleep. This 10-year prospective study aimed to determine if nasal symptoms can predict snoring and also if snoring can predict development of nasal symptoms. The hypothesis proposed is that nasal symptoms affect the risk of snoring 10 years later, whereas snoring does not increase the risk of developing nasal symptoms. Methods In the cohort study, Respiratory Health in Northern Europe (RHINE), a random population from Denmark, Estonia, Iceland, Norway, and Sweden, born between 1945 and 1973, was investigated by postal questionnaires in 1999–2001 (RHINE II, baseline) and in 2010–2012 (RHINE III, follow-up). The study population consisted of the participants who had answered questions on nasal symptoms such as nasal obstruction, discharge, and sneezing, and also snoring both at baseline and at follow-up (n = 10,112). Results Nasal symptoms were frequent, reported by 48% of the entire population at baseline, with snoring reported by 24%. Nasal symptoms at baseline increased the risk of snoring at follow-up (adj. OR 1.38; 95% CI 1.22–1.58) after adjusting for age, sex, BMI change between baseline and follow-up, and smoking status. Snoring at baseline was associated with an increased risk of developing nasal symptoms at follow-up (adj. OR 1.22; 95% CI 1.02–1.47). Conclusion Nasal symptoms are independent risk factors for development of snoring 10 years later, and surprisingly, snoring is a risk factor for the development of nasal symptoms.

We studied associations between tobacco smoke, home environment and respiratory health in a 10 year follow up of a cohort of 11,506 adults in Northern Europe. Multilevel logistic regression models were applied to estimate onset and remission of symptoms. Current smokers at baseline developed more respiratory symptoms (OR = 1.39–4.43) and rhinitis symptoms (OR = 1.35). Starting smoking during follow up increased the risk of new respiratory symptoms (OR = 1.54–1.97) and quitting smoking decreased the risk (OR = 0.34–0.60). ETS at baseline increased the risk of wheeze (OR = 1.26). Combined ETS at baseline or follow up increased the risk of wheeze (OR = 1.27) and nocturnal cough (OR = 1.22). Wood painting at baseline reduced remission of asthma (OR 95%CI: 0.61, 0.38–0.99). Floor painting at home increased productive cough (OR 95%CI: 1.64, 1.15–2.34) and decreased remission of wheeze (OR 95%CI: 0.63, 0.40–0.996). Indoor painting (OR 95%CI: 1.43, 1.16–1.75) and floor painting (OR 95%CI: 1.77, 1.11–2.82) increased remission of allergic rhinitis. Living in the oldest buildings (constructed before 1960) was associated with higher onset of nocturnal cough and doctor diagnosed asthma. Living in the newest buildings (constructed 1986–2001) was associated with higher onset of nocturnal breathlessness (OR = 1.39) and rhinitis (OR = 1.34). In conclusion, smoking, ETS and painting indoor can be risk factors for respiratory symptoms. Wood painting and floor painting can reduce remission of respiratory symptoms. Smoking can increase rhinitis. Living in older buildings can be a risk factor for nocturnal cough and doctor diagnosed asthma. Living in new buildings can increase nocturnal dyspnoea and rhinitis. publishedVersion

Background: Few prospective studies exist on respiratory health associations for home environment factors. Aims: To study associations between home environment factors and adult incident of respiratory symptoms, asthma and rhinitis. Methods: A cohort of 11,506 adults from Iceland, Norway, Sweden, Denmark and Estonia in the RHINE study participated in a questionnaire survey at baseline (1999-2000) and 10 years later (2010-2012), with questions on respiratory health and the home environment. Multiple logistic regression models were applied to estimate onset and remission of symptoms, adjusting for age, gender, smoking, BMI, education and dampness/mould at home. Results: Weekly environment tobacco smoke (ETS) (baseline or follow up) was associated with incidence of wheeze (OR=1.49, 95% CI 1.21-1.83), nocturnal cough (OR=1.31, 95%CI 1.09-1.58) and productive cough (OR=1.39, 95%CI 1.12-1.73), and floor painting at baseline was associated with productive cough (OR=1.64, 95%CI 1.15-2.32). Respiratory symptoms were generally less common in those living in building constructed after 1960. Building year 1961-1975: nocturnal cough (OR=0.83, 95%CI 0.70-0.99); building year 1976-1985: wheeze (OR=0.80, 95%CI 0.64-0.999), nocturnal cough (OR=0.78, 95%CI 0.65-0.94) and doctor diagnosed asthma (OR=0.67, 95%CI 0.49-0.91); building year 1986-2001: nocturnal cough (OR=0.75, 95%CI 0.62-0.90) and rhinitis symptoms (OR=1.34, 95%CI 0.62-0.90) (reference: building year ≤1960). Conclusions: ETS, floor painting and living in a house built before 1960 were all associated with higher incidence of respiratory symptoms among adults over a 10-year period. Living in newer buildings was associated with higher incidence of allergic rhinitis.

Publisher's version (útgefin grein), Aim: To investigate whether exposure to dampness and mold at home and at work induce sleep disturbances and daytime sleepiness among adults. Materials and methods: Associations between onset of sleep disturbances and dampness, mold and mold odor at home and at work were investigated in a cohort of 11,318 adults from the population in Iceland, Norway, Sweden, Denmark and Estonia. The participants answered a questionnaire at baseline and 10 years later, with questions on sleep disturbances, including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early morning awakening (EMA), insomnia symptoms, snoring and excessive daytime sleepiness (EDS). Multiple logistic regression models were applied to estimate associations adjusting for potential confounders including gender, age, smoking habit at baseline, change of smoking habit from baseline to follow up, BMI at baseline, change of BMI from baseline to follow up, education level at follow up, allergic rhinitis at baseline, doctor diagnosed asthma at baseline and chronic bronchitis at baseline. Results: Baseline floor dampness, visible mold and mold odor at home increased onset of DIS, DMS, EMA, insomnia symptoms and snoring during follow up (OR 1.29–1.87). Any sign of dampness at baseline increased onset of DIS (OR 1.28, 95%CI 1.06–1.55), DMS (OR 1.17, 95%CI 1.02–1.34) and insomnia symptoms (OR 1.18, 95%CI 1.03–1.36). Dampness at home during follow up increased onset of DIS, DMS, EMA, insomnia symptoms and EDS (OR 1.17–1.36). Dampness at work during follow up increased onset of DIS, EMA, insomnia symptoms and EDS (OR 1.16–1.34). Combined dampness at home and at work during follow up increased the risk of onset of DIS, DMS, EMA, insomnia symptoms and EDS (OR 1.29–1.74). Conclusions: Dampness and mold at home and at work can increase the development of insomnia symptoms, snoring and EDS among adults., The study was funded by the Icelandic Research Council, Landspitali University, Reykjavik, the Swedish Heart and Lung Foundation, the Vårdal Foundation for Health Care and Allergic Research, the Swedish Association Against Asthma and Allergy, the Swedish Council for Work Live and Social Research, the Swedish AFA Insurance (No. 467801100), the Bror Hjerpstedt Foundation, the Norwegian Research Council, the Norwegian Asthma and Allergy Association, the Danish Lung Association and the Estonian Science Foundation.

Publisher's version (útgefin grein), Objective: 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. Methods: 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). Results: 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. Conclusions: 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., We thank all participants, field workers and coordinators of the RHINE study and the ECRHS for their efforts as well as Ersilia Bifulco and Sandra Suske from the Core Facility for Metabolomics at the University of Bergen where the hormone measurements were performed. Further we are very grateful for the support of the Department of Applied Mathematics of the University of Málaga (Spain) and we want to thank Elinor Bartle for revising grammar and language.

Objectives Smoking is associated with sleep disturbances. The aim of this study was to analyze whether sleep disturbances are predictors of smoking cessation and whether continued smoking is associated with the development of sleep disturbances. Methods A questionnaire was sent to randomly selected men and women in Northern Europe in 1999–2001 (RHINE II) and was followed up by a questionnaire in 2010–2012 (RHINE III). The study population consisted of 2568 participants who were smokers at baseline and provided data on smoking at follow-up. Insomnia symptoms were defined as having difficulty initiating and/or maintaining sleep and/or early morning awakening ≥3 nights/week. Multiple logistic regression analyses were performed to calculate odds ratios (OR). Results Subjects with difficulty initiating sleep (adjusted odds ratio; 95% confidence interval: 0.6; 0.4–0.8), difficulty maintaining sleep (0.7; 0.5–0.9), early morning awakening (0.6; 0.4–0.8), any insomnia symptom (0.6; 0.5–0.8) or excessive daytime sleepiness (0.7; 0.5–0.8) were less likely to achieve long-term smoking cessation after adjustment for age, BMI, pack-years, hypertension, diabetes, chronic bronchitis, rhinitis, asthma, gender and BMI difference. There was no significant association between snoring and smoking cessation. In subjects without sleep disturbance at baseline, continued smoking increased the risk of developing difficulty initiating sleep during the follow-up period compared with those that had quit smoking (adj. OR 1.7, 95% CI 1.2–2.3). Conclusions Insomnia symptoms and excessive daytime sleepiness negatively predict smoking cessation. Smoking is a risk factor for the development of difficulty initiating sleep. Treatment for sleep disturbances should be included in smoking-cessation programs.

Study objectives: To analyze the association between sleep-related symptoms and sleep length in parents and their children in relation to other risk factors in both generations. Method: The participants were parents (n = 5,855, age 54.3 ± 6.5 years, 45.2% men) who participated in the community-based Respiratory Health in Northern Europe (RHINE) study and one random member of their adult offspring (n = 5,855, age 30.2 ± 7.7 years, 41.5% men) who participated in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) study. Both generations responded to identical questionnaires on sleep symptoms, including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early morning awakening (EMA), snoring, nocturnal sweating, nocturnal gastroesophageal reflux (nGER), sleep time and excessive daytime sleepiness (EDS). Insomnia was defined as either, or both, DIS and DMS in combination with EDS. Results: All sleep variables except nocturnal sweating were more common in offspring whose parents had reported the same symptom. After adjusting for age, gender, BMI, smoking, physical activity, education, center and parents' total number of children, there were independent associations between sleep symptoms in parents and offspring for DIS (adj. OR, 95% CI: 1.52, 1.20–1.93), DMS (1.34, 1.15–1.56), snoring (1.45, 1.15,1.83), nGER (1.65, 1.15–2.37), insomnia (1.39, 1.13–1.73), short sleep time (9 h/night). Conclusion: The familiar aggregation of many sleep disturbances was not explained by investigated lifestyle and environmental factors. This supports a heritable factor in sleep problems.

Publisher's version (útgefin grein)., 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., This study was funded by the European Union's Horizon 2020 research and innovation program as part of the ALEC study (Ageing Lungs in European Cohorts study, grant no. 633212). The RHINESSA generation study also received funding by the Research Council of Norway (grant nos. 214123 and 228174), the Bergen Medical Research Foundation (Norway), the Western Norwegian Regional Health Authorities (grant nos. 912011, 911892, and 911631), the Norwegian Labour Inspection, the Norwegian Asthma and Allergy Association, the Danish Woods Foundation (grant no. 444508795), the Danish Working Environment Authority (grant no. 20150067134), the Swedish Lung Foundation, the Swedish Asthma and Allergy Association, and the Estonian Research Council (grant no. PUT562). The funding agencies had no direct role in the conduct of the study; the collection, management, statistical analysis, and interpretation of the data; and the preparation or approval of the manuscript.

Purpose Chronic obstructive pulmonary disease (COPD) is associated with several co-morbidities and non-infectious rhinitis (NIR) has emerged as a new possible co-morbidity. The primary aim of this study is to confirm a previously reported association between NIR and COPD in a multicentre population over time. The secondary aim is to investigate the course over time of such an association through a comparison between early- and late-onset COPD. Methods This study is part of the European Community Respiratory Health Survey (ECRHS). A random adult population from 25 centres in Europe and one in Australia was examined with spirometry and answered a respiratory questionnaire in 1998–2002 (ECRHS II) and in 2008–2013 (ECRHS III). Symptoms of non-infectious rhinitis, hay fever and asthma, and smoking habits were reported. Subjects reporting asthma were excluded. COPD was defined as a spirometry ratio of FEV1/FVC Results Non-infectious rhinitis was significantly more prevalent in subjects with COPD compared with no COPD (48.9% vs 37.1%, p Conclusion Non-infectious rhinitis was significantly more common in subjects with COPD at a mean age of 43. Ten years later, the association was weaker. The findings indicate that NIR could be associated with the early onset of COPD.

Proteomic-based technologies offer new opportunities to identify proteins that might reflect the cardiometabolic stress caused by different aspects of sleep-disordered breathing. We aimed to investigate whether severe obstructive sleep apnea and severe obstructive sleep apnea during rapid eye movement sleep are associated with changed levels of inflammatory and cardiac disease-related proteins in a population-based cohort of women. In the community-based "Sleep and Health in Women" (SHE) cohort study, 400 women underwent polysomnography, anthropometric measurements and blood sampling. Two proteomic assays (Olink Proseek(R)Inflammation panel and Olink Proseek(R)Cardiovascular II panel), each measuring 92 proteins, were analysed in a subsample of 253 women.p-Values were adjusted for multiple testing, with false discovery rate set at 10%. In unadjusted models, 57 proteins were associated with apnea-hypopnea index, 56 proteins with oxygen desaturation index and 64 proteins with rapid eye movement-apnea-hypopnea index. After adjustment for age, body mass index and plate, there were no significant associations between apnea-hypopnea index or oxygen desaturation index and any of the proteins. Severe obstructive sleep apnea during rapid eye movement sleep (rapid eye movement-apnea-hypopnea index >= 30) was associated with decreased levels of two anti-inflammatory proteins; Sirt2 (q-value .016) and LAP-TGF-beta(1)(q-value .016). There was also a negative association between rapid eye movement-apnea-hypopnea index of >= 30 and Axin1 (q-value .095), a protein thought to facilitate TGF-beta-signalling. We conclude that severe obstructive sleep apnea during rapid eye movement sleep is associated with low levels of Sirt2, LAP-TGF-beta(1)and Axin1, anti-inflammatory proteins involved in metabolic regulation and in the atherosclerotic process. For obstructive sleep apnea based on a whole night, the associations with cardiac and inflammatory proteins are weaker, and explained to a large extent by age and body mass index.

Objectives: Neuromuscular injuries are suggested to contribute to upper airway collapse and swallowing dysfunction in patients with sleep apnea. Neurotrophins, a family of proteins involved in surv ...

Obstructive sleep apnea (OSA) is related to postoperative complications and is a common disorder. Most patients with sleep apnea are, however, undiagnosed, and there is a need for simple screening tools. We aimed to investigate whether STOP-Bang and oxygen desaturation index can identify subjects with OSA.In this prospective, observational multicenter trial, 449 adult patients referred to a sleep clinic for evaluation of OSA were investigated with ambulatory polygraphy, including pulse oximetry and the STOP-Bang questionnaire in 4 Swedish centers. The STOP-Bang score is the sum of 8 positive answers to Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index35 kg/m, Age50 years, Neck circumference40 cm, and male Gender.The optimal STOP-Bang cutoff score was 6 for moderate and severe sleep apnea, defined as apnea-hypopnea index (AHI) ≥15, and the sensitivity and specificity for this score were 63% (95% CI, 0.55-0.70) and 69% (95% CI, 0.64-0.75), respectively. A STOP-Bang score of2 had a probability of 95% (95% CI, 0.92-0.98) to exclude an AHI15 and a STOP-Bang score of ≥6 had a specificity of 91% (95% CI, 0.87-0.94) for an AHI15. The items contributing most to the STOP-Bang were the Bang items. There was a positive correlation between AHI versus STOP-Bang and between AHI versus oxygen desaturation index, Spearman ρ 0.50 (95% CI, 0.43-0.58) and 0.96 (95% CI, 0.94-0.97), respectively.STOP-Bang and pulse oximetry can be used to screen for sleep apnea. A STOP-Bang score of2 almost excludes moderate and severe OSA, whereas nearly all the patients with a STOP-Bang score ≥6 have OSA. We suggest the addition of nightly pulse oximetry in patients with a STOP-Bang score of 2-5 when there is a need for screening for sleep apnea (ie, before surgery).

Objective: Some studies of women with polycystic ovary syndrome (PCOS) report increased prevalence of hypertensive disorders in pregnancy, while others do not. Several of these studies do not control for obesity. We aimed to study whether PCOS is associated with hypertensive disorders in pregnancy and whether it is dependent on body mass index (BMI). Study design: We present a cross-sectional analysis of 3732 women from Denmark, Estonia, Iceland, Norway and Sweden, born in 1945–72, who participated in the Respiratory Health In Northern Europe (RHINE) study and answered an extensive women's health questionnaire on menstruation, PCOS, infertility, pregnancy history and childbirth. The main outcome measurement was hypertensive disorders of pregnancy. We adjusted for smoking, age, infertility treatment and study center. Effect modification by BMI was assessed. Results: PCOS was related to hypertensive disorders in pregnancy with a relative risk (RR) of 1.62 (95% CI 1.09–2.42). This relationship was found among underweight women with a BMI of 2 [RR = 5.2 (95% CI 1.66–16.5)] and obese women with a BMI of ≥30 kg/m 2 [RR = 2.36 (95% CI 1.29–4.31)], but not among normal-weight women, BMI 18.5–25 kg/m 2 [1.08 (0.53–2.20)], or overweight women, BMI 25–30 kg/m 2 [1.24 (0.50–3.08)] (p-interaction = 0.041). Conclusion: Polycystic ovary syndrome is associated with hypertensive disorders in pregnancy. This association only occurs among underweight and obese women and not among normal-weight and slightly overweight women.

The molecular mechanisms of obstructive sleep apnea (OSA), in particular the gene expression patterns in whole blood of patients with OSA, can shed more light on the underlying pathophysiology of OSA and suggest potential biomarkers. In the current study, we have enrolled thirty patients with untreated moderate-severe OSA together with 20 BMI, age, and sex-matched controls and 15 normal-weight controls. RNA-sequencing of whole blood and home sleep apnea testing were performed in the untreated state and after three and twelve months of continuous positive airway pressure (CPAP) treatment. Analysis of the whole blood transcriptome of the patients with OSA revealed a unique pattern of differential expression with a significant number of downregulated immune-related genes including many heavy and light chain immunoglobulins and interferon-inducible genes. This was confirmed by the gene ontology analysis demonstrating enrichment with the biological processes associated with various immune functions. Expression of these genes was recovered after three months of CPAP treatment. After 12 months of CPAP treatment, the overall gene expression profile returns to the initial, untreated level. In addition, we have confirmed the importance of choosing BMI-matched controls as a reference group as opposed to normal-weight healthy individuals based on the significantly different gene expression signatures between these two groups.