Publications by authors named "Thorarinn Gislason"

189 Publications

Breathlessness across generations: results from the RHINESSA generation study.

Thorax 2021 Jun 14. Epub 2021 Jun 14.

Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.

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.
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http://dx.doi.org/10.1136/thoraxjnl-2021-217271DOI Listing
June 2021

Chronic airflow obstruction and ambient particulate air pollution.

Thorax 2021 May 11. Epub 2021 May 11.

Medicine, Obafemi Awolowo University, Ile-Ife, Osun, Nigeria.

Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM) using negative binomial regression. The prevalence of CAO was not independently associated with PM but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised.
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http://dx.doi.org/10.1136/thoraxjnl-2020-216223DOI Listing
May 2021

The coexistence of asthma and COPD: risk factors, clinical history and lung function trajectories.

Eur Respir J 2021 Apr 16. Epub 2021 Apr 16.

Unit of Epidemiology and Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.

Rationale: Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.

Objectives: Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history, and lung function trajectories from early adulthood to the late sixties of middle aged subjects having asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111), or none of these (n=3477).

Methods: Interview data and prebronchodilator FEV and FVC were obtained during three clinical examinations in 1991-1993, 1999-2002, and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68, according to the presence of fixed airflow obstruction (postbronchodilator FEV/FVC below the lower limit of normal), a lifetime history of asthma, and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics, and risk factors of these phenotypes were estimated.

Main Results: Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9 and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.

Conclusions: The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.
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http://dx.doi.org/10.1183/13993003.04656-2020DOI Listing
April 2021

Increased respiratory morbidity associated with exposure to a mature volcanic plume from a large Icelandic fissure eruption.

Nat Commun 2021 04 12;12(1):2161. Epub 2021 Apr 12.

Chief Epidemiologist, Directorate of Health, Centre for Health Threats and Communicable Diseases, Reykjavík, Iceland.

The 2014-15 Holuhraun eruption in Iceland was the largest fissure eruption in over 200 years, emitting prodigious amounts of gas and particulate matter into the troposphere. Reykjavík, the capital area of Iceland (250 km from eruption site) was exposed to air pollution events from advection of (i) a relatively young and chemically primitive volcanic plume with a high sulphur dioxide gas (SO) to sulphate PM (SO) ratio, and (ii) an older and chemically mature volcanic plume with a low SO/SO ratio. Whereas the advection and air pollution caused by the primitive plume were successfully forecast and forewarned in public advisories, the mature plume was not. Here, we show that exposure to the mature plume is associated with an increase in register-measured health care utilisation for respiratory disease by 23% (95% CI 19.7-27.4%) and for asthma medication dispensing by 19.3% (95% CI 9.6-29.1%). Absence of public advisories is associated with increases in visits to primary care medical doctors and to the hospital emergency department. We recommend that operational response to volcanic air pollution considers both primitive and mature types of plumes.
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http://dx.doi.org/10.1038/s41467-021-22432-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042009PMC
April 2021

Severe volcanic SO exposure and respiratory morbidity in the Icelandic population - a register study.

Environ Health 2021 02 27;20(1):23. Epub 2021 Feb 27.

Chief Epidemiologist, Directorate of Health, Centre for Health Threats and Communicable Diseases, Barónsstigur 57, 101, Reykjavík, Iceland.

Background: The Holuhraun volcanic eruption September 2014 to February 2015 emitted large amounts of sulfur dioxide (SO). The aim of this study was to determine the association between volcanic SO gases on general population respiratory health some 250 km from the eruption site, in the Icelandic capital area.

Methods: Respiratory health outcomes were: asthma medication dispensing (AMD) from the Icelandic Medicines Register, medical doctor consultations in primary care (PCMD) and hospital emergency department visits (HED) in Reykjavík (population: 215000) for respiratory disease from 1 January 2010 to 31 December 2014. The associations between daily counts of health events and daily mean SO concentration and high SO levels (24-h mean SO > 125 μg/m3) were analysed using generalized additive models.

Results: After the eruption began, AMD was higher than before (129.4 vs. 158.4 individuals per day, p < 0.05). For PCMD and HED, there were no significant differences between the number of daily events before and after the eruption (142.2 vs 144.8 and 18.3 vs 17.5, respectively). In regression analysis adjusted for other pollutants, SO was associated with estimated increases in AMD by 0.99% (95% CI 0.39-1.58%) per 10 μg/m at lag 0-2, in PCMD for respiratory causes 1.26% (95% CI 0.72-1.80%) per 10 μg/m SO at lag 0-2, and in HED by 1.02% (95% CI 0.02-2.03%) per 10 μg/m SO at lag 0-2. For days over the health limit, the estimated increases were 10.9% (95% CI 2.1-19.6%), 17.2% (95% CI 10.0-24.4%) for AMD and PCMD. Dispensing of short-acting medication increased significantly by 1.09% (95% CI 0.49-1.70%), and PCMD for respiratory infections and asthma and COPD diagnoses and increased significantly by 1.12% (95% CI 0.54-1.71%) and 2.08% (1.13-3.04%).

Conclusion: High levels of volcanic SO are associated with increases in dispensing of AMD, and health care utilization in primary and tertiary care. Individuals with prevalent respiratory disease may be particularly susceptible.
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http://dx.doi.org/10.1186/s12940-021-00698-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916308PMC
February 2021

[Diseases connected with work in hay in Iceland. Causes and scientific studies].

Laeknabladid 2021 Mar;107(3):130-136

Landspitali University Hospital, Faculty of Medicine.

Diseases connected with work in hay have been known in Iceland for a long time. In 1981 scientific studies of these diseases were started in Iceland at the request of the Farmers Union. The results of these studies are summarized in this article. In studies of hay a great amount of storage mites, moulds and thermophilic actinomycetes (microlyspora faeni) were found in addition to allergens from mice and pollen. Symptoms caused by hay dust were mainly from nose and eyes in people with positive skin tests, but cough, dyspnea and fever were equally common in those with negative skin tests. The most common causes of allergy in farming families were storage mites and cattle, but allergy to cats, dogs and grass pollen were less common rurally than in the Reykjavik area. When comparing individuals working in heavy hay dust with those working in cleaner air, the former group had a higher likelihood of having a positive precipitin test against micropolyspora faeni, fever after work in hay and airway obstruction. It was shown that Icelandic farmers were more likely to get emphysema than other people irrespective of smoking. In a large study of homes in the Reykjavik area almost no mites were found. In spite of this, positive specific IgE tests against dust mites were equally common as in Uppsala, Sweden, where dust mites were found in 16% of homes. In further studies it was found, that 57% of people in the study had been more and less exposed to hay dust. They had either been raised on a farm, been on a farm in the summer during childhood or owned horses and fed them with hay. We have argued that cross allergy to storage mites may be the cause of a rather common allergy to house dust mites. A new study of middle-aged individuals has shown that allergy to storage mites is a little more common in the Reykjavik area than in Aarhus, Bergen or Uppsala. The most likely explanation is that they have more often been exposed to hay dust.
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http://dx.doi.org/10.17992/lbl.2021.03.626DOI Listing
March 2021

Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity.

Sleep 2021 05;44(5)

Interdisciplinary Center of Sleep Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Study Objectives: Patients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample.

Methods: 1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates.

Results: Patients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009).

Conclusions: Time-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients.

Clinical Trial Information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966.
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http://dx.doi.org/10.1093/sleep/zsab018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120337PMC
May 2021

Nasal symptoms increase the risk of snoring and snoring increases the risk of nasal symptoms. A longitudinal population study.

Sleep Breath 2021 Jan 19. Epub 2021 Jan 19.

Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.

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.
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http://dx.doi.org/10.1007/s11325-020-02287-8DOI Listing
January 2021

Effect of Obstructive Sleep Apnea and Positive Airway Pressure Therapy on Cardiac Remodeling as Assessed by Cardiac Biomarker and Magnetic Resonance Imaging in Nonobese and Obese Adults.

Hypertension 2021 Mar 19;77(3):980-992. Epub 2021 Jan 19.

Cardiovascular Division, Department of Medicine (J.C., PM., A.H., M.R.-K., Z.H., J.L., J.A.C.), Perelman School of Medicine, University of Pennsylvania School of Medicine, Philadelphia.

It is unknown whether obesity modifies the effect of obstructive sleep apnea (OSA) and positive airway pressure (PAP) therapy on cardiac remodeling and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. We compared NT-proBNP and cardiac magnetic resonance imaging in adults without OSA (n=56) and nonobese (n=73; body mass index <30 kg/m) and obese (n=136; body mass index ≥30 kg/m) adults with OSA. We also investigated these traits in nonobese (n=45) and obese (n=78) participants with OSA adherent to 4 months of PAP treatment. At baseline, left ventricular mass to end-diastolic volume ratio, a measure of left ventricular concentricity, was greater in both nonobese and obese participants with OSA compared with those without OSA. Participants with OSA and obesity exhibited reduced phasic right atrial function. No significant differences in baseline NT-proBNP were observed across groups. The effect of PAP treatment on NT-proBNP and left atrial volume index was significantly modified by obesity. In nonobese participants, PAP therapy was associated with a decrease in NT-proBNP (<0.0001) without a change in left atrial volume index, whereas in obese participants, PAP was associated with an increase in left atrial volume index (=0.006) without a change in NT-proBNP. OSA was associated with left ventricular concentric remodeling independent of obesity and right atrial dysfunction in participants who were obese. PAP treatment was associated with reduced NT-proBNP in nonobese participants with OSA, but left atrial enlargement in obese participants with OSA, suggesting that PAP-induced reduction in BNP release (which is known to occur during obstructive apnea episodes) may lead to volume retention in obese participants with OSA. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01578031.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878363PMC
March 2021

The design of RIP belts impacts the reliability and quality of the measured respiratory signals.

Sleep Breath 2021 Jan 7. Epub 2021 Jan 7.

Department of Engineering, Reykjavik University, Reykjavik, Iceland.

Purpose: Evaluate the effect of respiratory inductance plethysmography (RIP) belt design on the reliability and quality of respiratory signals. A comparison of cannula flow to disposable cut-to-fit, semi-disposable folding and disposable RIP belts was performed in clinical home sleep apnea testing (HSAT) studies.

Methods: This was a retrospective study using clinical HSAT studies. The signal reliability of cannula, thorax, and abdomen RIP belts was determined by automatically identifying periods during which the signals did not represent respiratory airflow and breathing movements. Results were verified by manual scoring. RIP flow quality was determined by examining the correlation between the RIP flow and cannula flow when both signals were considered reliable.

Results: Of 767 clinical HSAT studies, mean signal reliability of the cut-to-fit, semi-disposable, and disposable thorax RIP belts was 83.0 ± 26.2%, 76.1 ± 24.4%, and 98.5 ± 9.3%, respectively. The signal reliability of the cannula was 92.5 ± 16.1%, 87.0 ± 23.3%, and 85.5 ± 24.5%, respectively. The automatic assessment of signal reliability for the RIP belts and cannula flow had a sensitivity of 50% and a specificity of 99% compared with manual assessment. The mean correlation of cannula flow to RIP flow from the cut-to-fit, semi-disposable, and disposable RIP belts was 0.79 ± 0.24, 0.52 ± 0.20, and 0.86 ± 0.18, respectively.

Conclusion: The design of RIP belts affects the reliability and quality of respiratory signals. The disposable RIP belts that had integrated contacts and did not fold on top of themselves performed the best. The cut-to-fit RIP belts were most likely to be unreliable, and the semi-disposable folding belts produced the lowest-quality RIP flow signals compared to the cannula flow signal.
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http://dx.doi.org/10.1007/s11325-020-02268-xDOI Listing
January 2021

Changes in sleepiness and 24-h blood pressure following 4 months of CPAP treatment are not mediated by ICAM-1.

Sleep Breath 2021 Jan 6. Epub 2021 Jan 6.

Division of Sleep Medicine, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.

Objective: Continuous positive airway pressure (CPAP) therapy reduces circulating intercellular adhesion molecule 1 (ICAM-1) in adults with obstructive sleep apnea (OSA). ICAM-1 levels may affect the daytime sleepiness and elevated blood pressure associated with OSA. We evaluated the association of changes from baseline in ICAM-1 with changes of objective and subjective measures of sleepiness, as well as 24-h ambulatory blood pressure monitoring (ABPM) measures, following 4 months of CPAP treatment.

Methods: The study sample included adults with newly diagnosed OSA. Plasma ICAM-1, 24-h ABPM, Epworth Sleepiness Scale (ESS), and psychomotor vigilance task (PVT) were obtained at baseline and following adequate CPAP treatment. The associations between changes in natural log ICAM-1 and changes in the number of lapses on PVT, ESS score, and 24-h mean arterial blood pressure (MAP) were assessed using multivariate regression models, controlling for a priori baseline covariates of age, sex, BMI, race, site, smoking status, physical activity, anti-hypertensive medications, AHI, and daily hours of CPAP use.

Results: Among 140 adults (83% men), mean (± SD) body mass index (BMI) was 31.5 ± 4.2 kg/m, and apnea-hyopnea index (AHI) was 36.8 ± 15.3 events/h. Sleepiness measures, although not ICAM-1 or ABPM measures, improved significantly following CPAP treatment. We observed no statistically significant associations between the change in ICAM-1 and changes in sleepiness, MAP, or other ABPM measures.

Conclusion: Changes in ICAM-1 levels were not related to changes in sleepiness or ABPM following CPAP treatment of adults with OSA. Future work should explore whether or not other biomarkers may have a role in mediating these treatment outcomes in adults with OSA.
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http://dx.doi.org/10.1007/s11325-020-02257-0DOI Listing
January 2021

Is snoring during pregnancy a predictor of later life obstructive sleep apnoea? A case-control study.

Sleep Med 2021 03 2;79:190-194. Epub 2020 Nov 2.

Sleep Research Group, Charles Perkins Centre, University of Sydney, Australia. Electronic address:

Background: Obstructive sleep apnoea (OSA) appears common in pregnancy. Complications of pregnancy such as gestational diabetes and hypertension predispose women to cardiometabolic disease in later life. It is unknown if snoring during pregnancy is a risk marker for later-life OSA.

Methods: We analysed data from N = 897 women in the Sleep Apnea Global Interdisciplinary Consortium (SAGIC), which recruited patients attending sleep clinics at 11 sites. There were 577 cases with current OSA and 320 controls. Cases were further categorised into mild, moderate, and severe OSA based on apnoea-hypopnoea index. Retrospective self-report of snoring during pregnancy was the exposure of interest and was reported by 2.9% of cases and 3.4% of controls.

Results: Multinomial regression demonstrated that snoring during a previous pregnancy was not significantly associated with mild (OR 0.34, 95% CI 0.09-1.25, p = 0.10), moderate (OR 0.69, 95% CI 0.21-2.19, p = 0.52), or severe OSA (OR 1.86, 95% CI 0.77-4.48, p = 0.17) compared to no snoring during pregnancy. Results were unchanged after adjustment for age, body mass index, and ethnicity. 79% of women reported current snoring but all who snored during pregnancy reported current snoring.

Conclusions: Women who snore during pregnancy continue snoring in later-life but do not appear more likely to develop OSA. These findings are limited by self-reported data, recall bias, and small numbers of women who reported snoring during pregnancy. A prospective study with objective measurement of sleep and snoring during pregnancy is needed to examine the links between sleep disorders in pregnancy with health in later life.
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http://dx.doi.org/10.1016/j.sleep.2020.10.023DOI Listing
March 2021

Prevalence and Population Attributable Risk for Chronic Airflow Obstruction in a Large Multinational Study.

Am J Respir Crit Care Med 2020 Nov 10. Epub 2020 Nov 10.

Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, Netherlands.

The Global Burden of Disease programme identified smoking, and ambient and household air pollution as the main drivers of death and disability from Chronic Obstructive Pulmonary Disease (COPD). To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a post-bronchodilator one-second forced expiratory volume to forced vital capacity ratio < lower limit of normal, and the relative risks associated with different risk factors. Local RR were estimated using a Bayesian hierarchical model borrowing information from across sites. From these RR and the prevalence of risk factors, we estimated local Population Attributable Risks (PAR). Mean prevalence of CAO was 11.2% in men and 8.6% in women. Mean PAR for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index (BMI), and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. While smoking remains the most important risk factor for CAO, in some areas poor education, low BMI and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.
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http://dx.doi.org/10.1164/rccm.202005-1990OCDOI Listing
November 2020

Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts.

Ann Am Thorac Soc 2021 02;18(2):238-246

Occupational and Environmental Medicine, School of Public Health and Community Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up. To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking. A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV and the FEV/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts. Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.
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http://dx.doi.org/10.1513/AnnalsATS.202002-113OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020720PMC
February 2021

A prospective study on the role of smoking, environmental tobacco smoke, indoor painting and living in old or new buildings on asthma, rhinitis and respiratory symptoms.

Environ Res 2021 01 28;192:110269. Epub 2020 Sep 28.

Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.

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.
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http://dx.doi.org/10.1016/j.envres.2020.110269DOI Listing
January 2021

Alzheimer's disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea.

Sleep 2021 03;44(3)

School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.

Obstructive sleep apnea (OSA) involves intermittent cessations of breathing during sleep. People with OSA can experience memory deficits and have reduced hippocampal volume; these features are also characteristic of Alzheimer's disease (AD), where they are accompanied by neurofibrillary tangles (NFTs) and amyloid beta (Aβ) plaques in the hippocampus and brainstem. We have recently shown reduced hippocampal volume to be related to OSA severity, and although OSA may be a risk factor for AD, the hippocampus and brainstems of clinically verified OSA cases have not yet been examined for NFTs and Aβ plaques. The present study used quantitative immunohistochemistry to investigate postmortem hippocampi of 34 people with OSA (18 females, 16 males; mean age 67 years) and brainstems of 24 people with OSA for the presence of NFTs and Aβ plaques. OSA severity was a significant predictor of Aβ plaque burden in the hippocampus after controlling for age, sex, body mass index (BMI), and continuous positive airway pressure (CPAP) use. OSA severity also predicted NFT burden in the hippocampus, but not after controlling for age. Although 71% of brainstems contained NFTs and 21% contained Aβ plaques, their burdens were not correlated with OSA severity. These results indicate that OSA accounts for some of the "cognitively normal" individuals who have been found to have substantial Aβ burdens, and are currently considered to be at a prodromal stage of AD.
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http://dx.doi.org/10.1093/sleep/zsaa195DOI Listing
March 2021

Smokers with insomnia symptoms are less likely to stop smoking.

Respir Med 2020 Aug - Sep;170:106069. Epub 2020 Jun 20.

Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.

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.
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http://dx.doi.org/10.1016/j.rmed.2020.106069DOI Listing
June 2021

Association between lung function decline and obstructive sleep apnoea: the ALEC study.

Sleep Breath 2021 Jun 6;25(2):587-596. Epub 2020 Jul 6.

Department of Sleep Medicine, Landspitali, Reykjavik, Iceland.

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.
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http://dx.doi.org/10.1007/s11325-020-02086-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195766PMC
June 2021

Low serum DHEA-S is associated with impaired lung function in women.

EClinicalMedicine 2020 Jun 6;23:100389. Epub 2020 Jun 6.

Inserm UMR-S 1168, VIMA, Villejuif, France.

Background: Emerging evidence suggests that androgens and estrogens have a role in respiratory health, but it is largely unknown whether levels of these hormones can affect lung function in adults from the general population. This study investigated whether serum dehydroepiandrosterone sulfate (DHEA-S), a key precursor of both androgens and estrogens in peripheral tissues, was related to lung function in adult women participating in the European Community Respiratory Health Survey (ECRHS).

Methods: Lung function and serum DHEA-S concentrations were measured in  = 2,045 and  = 1,725 women in 1999-2002 and in 2010-2013, respectively. Cross-sectional associations of DHEA-S levels (expressed as age-adjusted z-score) with spirometric outcomes were investigated, adjusting for smoking habits, body mass index, menopausal status, and use of corticosteroids. Longitudinal associations of DHEA-S levels in 1999-2002 with incidence of restrictive pattern and airflow limitation in 2010-2013 were also assessed.

Findings: Women with low DHEA-S (z-score<-1) had lower FEV1 (% of predicted, adjusted difference: -2.2; 95%CI: -3.5 to -0.9) and FVC (-1.7; 95%CI: -2.9 to -0.5) and were at a greater risk of having airflow limitation and restrictive pattern on spirometry than women with higher DHEA-S levels. In longitudinal analyses, low DHEA-S at baseline was associated with a greater incidence of airflow limitation after an 11-years follow-up (incidence rate ratio, 3.43; 95%CI: 1.91 to 6.14).

Interpretation: Low DHEA-S levels in women were associated with impaired lung function and a greater risk of developing airflow limitation later in adult life. Our findings provide new evidence supporting a role of DHEA-S in respiratory health.

Funding: EU H2020, grant agreement no.633212.
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http://dx.doi.org/10.1016/j.eclinm.2020.100389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280766PMC
June 2020

Regular Physical Activity Levels and Incidence of Restrictive Spirometry Pattern: A Longitudinal Analysis of 2 Population-Based Cohorts.

Am J Epidemiol 2020 12;189(12):1521-1528

We estimated the association between regular physical activity and the incidence of restrictive spirometry pattern. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and physical activity were assessed in 2 population-based European cohorts (European Community Respiratory Health Survey: n = 2,757, aged 39-67 years; and Swiss Study on Air Pollution and Lung and Heart Diseases in Adults: n = 2,610, aged 36-82 years) first in 2000-2002 and again approximately 10 years later (2010-2013). Subjects with restrictive or obstructive spirometry pattern at baseline were excluded. We assessed the association of being active at baseline (defined as being physically active at least 2-3 times/week for ≥1 hour) with restrictive spirometry pattern at follow-up (defined as a postbronchodilation FEV1/FVC ratio of at least the lower limit of normal and FVC of <80% predicted) using modified Poisson regression, adjusting for relevant confounders. After 10 years of follow-up, 3.3% of participants had developed restrictive spirometry pattern. Being physically active was associated with a lower risk of developing this phenotype (relative risk = 0.76, 95% confidence interval: 0.59, 0.98). This association was stronger among those who were overweight and obese than among those of normal weight (P for interaction = 0.06). In 2 large European studies, adults practicing regular physical activity were at lower risk of developing restrictive spirometry pattern over 10 years.
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http://dx.doi.org/10.1093/aje/kwaa087DOI Listing
December 2020

Are symptoms of insomnia related to respiratory symptoms? Cross-sectional results from 10 European countries and Australia.

BMJ Open 2020 04 28;10(4):e032511. Epub 2020 Apr 28.

Department of Respiratory Medicine, Uppsala University, Uppsala, Sweden.

Objectives: To compare the prevalence of different insomnia subtypes among middle-aged adults from Europe and Australia and to explore the cross-sectional relationship between insomnia subtypes, respiratory symptoms and lung function.

Design: Cross-sectional population-based, multicentre cohort study.

Setting: 23 centres in 10 European countries and Australia.

Methods: We included 5800 participants in the third follow-up of the European Community Respiratory Health Survey III (ECRHS III) who answered three questions on insomnia symptoms: difficulties falling asleep (initial insomnia), waking up often during the night (middle insomnia) and waking up early in the morning and not being able to fall back asleep (late insomnia). They also answered questions on smoking, general health and chronic diseases and had the following lung function measurements: forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and the FEV/FVC ratio. Changes in lung function since ECRHS I about 20 years earlier were also analysed.

Main Outcome Measures: Prevalence of insomnia subtypes and relationship to respiratory symptoms and function.

Results: Overall, middle insomnia (31.2%) was the most common subtype followed by late insomnia (14.2%) and initial insomnia (11.2%). The highest reported prevalence of middle insomnia was found in Iceland (37.2%) and the lowest in Australia (22.7%), while the prevalence of initial and late insomnia was highest in Spain (16.0% and 19.7%, respectively) and lowest in Denmark (4.6% and 9.2%, respectively). All subtypes of insomnia were associated with significantly higher reported prevalence of respiratory symptoms. Only isolated initial insomnia was associated with lower FEV, whereas no association was found between insomnia and low FEV/FVC ratio or decline in lung function.

Conclusion: There is considerable geographical variation in the prevalence of insomnia symptoms. Middle insomnia is most common especially in Iceland. Initial and late insomnia are most common in Spain. All insomnia subtypes are associated with respiratory symptoms, and initial insomnia is also associated with lower FEV.
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http://dx.doi.org/10.1136/bmjopen-2019-032511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213858PMC
April 2020

Defining Extreme Phenotypes of OSA Across International Sleep Centers.

Chest 2020 09 15;158(3):1187-1197. Epub 2020 Apr 15.

Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, OH; Neuroscience Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH. Electronic address:

Background: Extreme phenotypes of OSA have not been systematically defined.

Research Question: This study developed objective definitions of extreme phenotypes of OSA by using a multivariate approach. The utility of these definitions for identifying characteristics that confer predisposition toward or protection against OSA is shown in a new prospective sample.

Study Design And Methods: In a large international sample, race-specific liability scores were calculated from a weighted logistic regression that included age, sex, and BMI. Extreme cases were defined as individuals with an apnea-hypopnea index (AHI) ≥ 30 events/hour but low likelihood of OSA based on age, sex, and BMI (liability scores > 90th percentile). Similarly, extreme controls were individuals with an AHI < 5 events/hour but high likelihood of OSA (liability scores < 10th percentile). Definitions were applied to a prospective sample from the Sleep Apnea Global Interdisciplinary Consortium, and differences in photography-based craniofacial and intraoral phenotypes were evaluated.

Results: This study included retrospective data from 81,338 individuals. A total of 4,168 extreme cases and 1,432 extreme controls were identified by using liability scores. Extreme cases were younger (43.1 ± 14.7 years), overweight (28.6 ± 6.8 kg/m), and predominantly female (71.1%). Extreme controls were older (53.8 ± 14.1 years), obese (34.0 ± 8.1 kg/m), and predominantly male (65.8%). These objective definitions identified 29 extreme cases and 87 extreme controls among 1,424 Sleep Apnea Global Interdisciplinary Consortium participants with photography-based phenotyping. Comparisons suggest that a greater cervicomental angle increases risk for OSA in the absence of clinical risk factors, and smaller facial widths are protective in the presence of clinical risk factors.

Interpretation: This objective definition can be applied in sleep centers throughout the world to consistently define OSA extreme phenotypes for future studies on genetic, anatomic, and physiologic pathways to OSA.
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http://dx.doi.org/10.1016/j.chest.2020.03.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478234PMC
September 2020

Dampness and mold at home and at work and onset of insomnia symptoms, snoring and excessive daytime sleepiness.

Environ Int 2020 06 6;139:105691. Epub 2020 Apr 6.

Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.

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.
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http://dx.doi.org/10.1016/j.envint.2020.105691DOI Listing
June 2020

Body mass index and weight change are associated with adult lung function trajectories: the prospective ECRHS study.

Thorax 2020 04 25;75(4):313-320. Epub 2020 Feb 25.

Department of Public Health, Section for Environment Occupation and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark.

Background: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS).

Methods: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations.

Results: In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25-1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had -1011 mL (95% CI -1.259 to -763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (<-0.25 kg/year) exhibited an attenuation of FVC and FEV declines. We found no association between weight change profiles and FEV/FVC decline.

Conclusion: Moderate and high weight gain over 20 years was associated with accelerated lung function decline, while weight loss was related to its attenuation. Control of weight gain is important for maintaining good lung function in adult life.
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http://dx.doi.org/10.1136/thoraxjnl-2019-213880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231449PMC
April 2020

Sleep time and sleep-related symptoms across two generations - results of the community-based RHINE and RHINESSA studies.

Sleep Med 2020 05 10;69:8-13. Epub 2020 Jan 10.

Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

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 (<6 h/night) (2.51, 1.72-3.68) and EDS (1.48, 1.26,1.72). There were no independent relationships between symptoms in parents and offspring for EMA, nocturnal sweating or long 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.
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http://dx.doi.org/10.1016/j.sleep.2019.12.017DOI Listing
May 2020

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 04;16(4):545-552

Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden.

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.
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http://dx.doi.org/10.5664/jcsm.8274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161445PMC
April 2020

Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis.

Nat Commun 2020 01 20;11(1):393. Epub 2020 Jan 20.

deCODE genetics/Amgen, Inc., Reykjavik, Iceland.

Asthma is one of the most common chronic diseases affecting both children and adults. We report a genome-wide association meta-analysis of 69,189 cases and 702,199 controls from Iceland and UK biobank. We find 88 asthma risk variants at 56 loci, 19 previously unreported, and evaluate their effect on other asthma and allergic phenotypes. Of special interest are two low frequency variants associated with protection against asthma; a missense variant in TNFRSF8 and 3' UTR variant in TGFBR1. Functional studies show that the TNFRSF8 variant reduces TNFRSF8 expression both on cell surface and in soluble form, acting as loss of function. eQTL analysis suggests that the TGFBR1 variant acts through gain of function and together with an intronic variant in a downstream gene, SMAD3, points to defective TGFβR1 signaling as one of the biological perturbations increasing asthma risk. Our results increase the number of asthma variants and implicate genes with known role in T cell regulation, inflammation and airway remodeling in asthma pathogenesis.
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http://dx.doi.org/10.1038/s41467-019-14144-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971247PMC
January 2020

Prevalence of allergic sensitization to storage mites in Northern Europe.

Clin Exp Allergy 2020 03 11;50(3):372-382. Epub 2019 Dec 11.

Department of Clinical Science, University of Bergen, Bergen, Norway.

Background: Allergic sensitization to storage mites has mostly been related to occupational exposures like farming, grain/cattle handling, whereas for non-occupational settings, storage mite sensitization has been attributed to cross-reactivity with house dust mite (HDM) allergens.

Objective: We aimed to describe the prevalence of allergic sensitization to storage mites, co-sensitization to HDM allergens and respiratory symptoms in Denmark, Iceland, Norway and Sweden.

Methods: The population comprised of 1180 participants born 1945-1972 of the third follow-up of the population-based cohort European Community Respiratory Health Survey (ECRHS) in Aarhus, Bergen, Reykjavik and Uppsala. A clinical examination included skin prick tests (SPT) to Lepidoglyphus destructor, Tyrophagus putrescentiae, Acarus siro and common inhalant allergens, as well as standardized interviews.

Results: 8% were sensitized to HDM and 10% to storage mite, with some variation by study centre: Reykjavik 13%, Bergen 8% and Aarhus 7%. In Uppsala, only L destructor (3%) was measured. Storage mite sensitization was higher among men (11%) than women (8%). Among storage mite sensitized, 44% were also sensitized to HDM. Storage mite sensitization was associated with asthma and nasal allergies, but not with age, education, pet keeping or place of upbringing.

Conclusions And Clinical Relevance: In this Northern European population-based study, allergic sensitization to storage mite was as common as HDM sensitization. Storage mite sensitization was, independently of HDM sensitization, associated with respiratory symptoms and asthma. Our findings suggest that storage mite sensitization should be evaluated with regard to inclusion into the common inhalant allergen panel in Northern Europe.
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http://dx.doi.org/10.1111/cea.13536DOI Listing
March 2020

Differences in three-dimensional upper airway anatomy between Asian and European patients with obstructive sleep apnea.

Sleep 2020 05;43(5)

Division of Sleep Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

Study Objectives: This study evaluated differences in upper airway, soft tissues and craniofacial structures between Asians from China and Europeans from Iceland with OSA using three-dimensional magnetic resonance imaging (MRI).

Methods: Airway sizes, soft tissue volumes, and craniofacial dimensions were compared between Icelandic (N = 108) and Chinese (N = 57) patients with oxygen desaturation index (ODI) ≥ 10 events/h matched for age, gender, and ODI. Mixed effects models adjusting for height or BMI and residual differences in age and ODI were utilized.

Results: In our matched sample, compared to Icelandic OSA patients, Chinese patients had smaller BMI (p < 0.0001) and neck circumference (p = 0.011). In covariate adjusted analyses, Chinese showed smaller retropalatal airway size (p ≤ 0.002), and smaller combined soft tissues, tongue, fat pads, and pterygoid (all p ≤ 0.0001), but male Chinese demonstrated a larger soft palate volume (p ≤ 0.001). For craniofacial dimensions, Chinese demonstrated bigger ANB angle (p ≤ 0.0196), differently shaped mandibles, including shorter corpus length (p < 0.0001) but longer ramus length (p < 0.0001), and a wider (p < 0.0001) and shallower (p ≤ 0.0001) maxilla.

Conclusions: Compared to Icelandic patients of similar age, gender and ODI, Chinese patients had smaller retropalatal airway and combined soft tissue, but bigger soft palate volume (in males), and differently shaped mandible and maxilla with more bony restrictions. Results support an ethnic difference in upper airway anatomy related to OSA, which may inform targeted therapies.
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http://dx.doi.org/10.1093/sleep/zsz273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215269PMC
May 2020

The role of C-reactive protein levels on the association of physical activity with lung function in adults.

PLoS One 2019 23;14(9):e0222578. Epub 2019 Sep 23.

ISGlobal, Barcelona, Spain.

Objective: Regular physical activity may be associated with improved lung function via reduced systemic inflammation, although studies exploring this mechanism are rare. We evaluated the role of C-reactive protein in blood, which is a common marker of systemic inflammation, on the association of physical activity with forced expiratory volume in one second and forced vital capacity.

Methods: Cross-sectional data on spirometry, C-reactive protein levels and self-reported physical activity (yes/no; ≥2 times and ≥1hr per week of vigorous physical activity) were available in the European Community Respiratory Health Survey (N = 2347 adults, 49.3% male, 28-56 years-old). A subsample was also assessed 10 years later using the International Physical Activity Questionnaire, and tertiles of Metabolic Equivalent of Task-minutes per week spent in vigorous, moderate and walking activities were calculated (N = 671, 49.6% male, 40-67 years-old). Adjusted cross-sectional mixed linear regression models and the "mediate" package in "R" were used to assess the presence of mediation.

Results: Despite positive significant associations between nearly all physical activity metrics with forced expiratory volume in one second and forced vital capacity, there was no evidence that C-reactive protein levels played a role. An influence of C-reactive protein levels was only apparent in the smaller subsample when comparing the medium to low tertiles of moderate activity (mean difference [95% CIs]: 21.1ml [5.2, 41.9] for forced expiratory volume in one second and 17.3ml [2.6, 38.0] for forced vital capacity).

Conclusions: In a population of adults, we found no consistent evidence that the association of physical activity with forced expiratory volume in one second or forced vital capacity is influenced by the level of C-reactive protein in blood.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222578PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756522PMC
March 2020
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