A platform for collaborations in respiratory research in Sweden
Population-based cohort studies on sleep and sleep disordered breathing in women (SHE) and men (MUSTACHE). The studies include questionnaire data, objective sleep measurements, anthropometrics, laboratory- and cardiometabolic data.
The population-based cohort study “Sleep and Health in Women” (SHE) was initiated in April 2000, when a postal questionnaire was sent to randomly selected females aged > 20 years from the population registry of Uppsala. The questionnaire included questions on snoring, sleep disturbances, daytime symptoms, lifestyle factors, anthropometric variables, medical history, menstrual cycle, menopause and pregnancy. The response rate was 71.6%, with a total of 7,051 women responding to the questionnaire. Of the total study population aged 70 years and younger (n = 6,112), a random sample of 170 women from the entire study population and a random sample of 230 snorers participated in the second phase of the study. The second phase of the study, initiated in 2003, included a whole-night polysomnography, questionnaires, anthropometric measurements, blood sampling, blood pressure measurements, an ECG and an oral glucose tolerance test (OGTT).
In 2010, the first phase of the follow-up study was initiated when a new questionnaire was sent out to all the women answering the baseline questionnaire and were still alive. The response rate was 80,4% (n=5,193). In the second phase of the follow-up study, initiated in 2011, the participants in the second phase of the baseline study were asked to perform a new polysomnography, as well as a carotid artery ultrasound, blood sampling, anthropometric measurements, blood pressure measurements and an ECG and to answer new questionnaires. Out of the 400 original participants, 273 accepted the invitation. An additional 127 women, randomly selected from the participants answering the questionnaire in the follow-up study, also participated in the second phase of the follow-up study.
The Men in Uppsala; a Study of sleep, Apnoea and Cardiometabolic Health (MUSTACHE) study was initiated in 2016, and was created as a matched male cohort (n=400) to the preexisting female population-based cohort SHE (see above). Men participating in the community-based study Epi-Health during 2011-2015 (n=9,377), matched with the women in SHE by age and BMI, were recruited. If no match could be recruited among the Epi-Health participants (n=59) a matching man was recruited from the community. The 400 men were investigated with a whole night polysomnography, questionnaires, anthropometric measurements and blood pressure measurement. All participants in the SHE and MUSATCHE cohorts have been investigated with identical protocols.
Anchor: Main sub-projectsIt has been suggested that there are independent associations between different sleep disturbances and dementia. The results from a recent meta-analysis revealed that compared with individuals without sleep disturbances, subjects who reported sleep disturbances had a higher risk of incident all-cause dementia, vascular dementia and Alzheimer disease. When analyzing the subtypes of sleep disturbances, also sleep disordered breathing was associated with a higher incidence of all-cause dementia, vascular dementia and Alzheimer disease. However, sleep disturbances including sleep disordered breathing were evaluated mainly based on self-reports without confirming OSA with objective measurements of breathing during sleep. We hypothesize that OSA is associated with impaired cognitive performance. Another hypothesis is that this association is that the apnea-hypopnea index during REM-sleep (REM-OSA) is more closely related to cognitive impairment than AHI during non-REM sleep.
The primary aim is to determine the relationship between obstructive sleep apnea and cognitive impairment. We also aim to identify the OSA phenotype that is most affected by cognitive decline.
Department of Medical Sciences, Uppsala University (UU)
Respiratory, allergy and sleep research
Prof Eva Lindberg, MD (PI)
Xiao Tan, post-doc
Dr Med Sci Mirjam Ljunggren, MD
Clinical Epidemiology
Prof Johan Sundström, MD
Department of Public Health and Caring Sciences, UU, Geriatrics
Prof Lena Kilander, MD
Department of Surgical Sciences, UU, Functional Pharmacology and neuroscience
Assoc prof Christian Benedict
Sleep impairment, including sleep disordered breathing, insomnia and short sleep duration is highly prevalent in patients with cardiometabolic disease. The relationship is probably bidirectional and there is a need for prospective analyses to gain insight into cause-effect relationship.
In the follow-up study of the SHE cohort we aim to analyze long-term evolution of sleep-disordered breathing, insomnia and daytime sleepiness in women.
We further aim to:
Department of Medical Sciences, Uppsala University (UU)
Respiratory, allergy and sleep research
Mirjam Ljunggren, MD, PhD (PI)
Professor Eva Lindberg, MD, former PI for the cohorts
Associate Professor Jenny Theorell-Haglöw,
Associate Professor Xingwu Zhou, Statistician
Baz Delshad, MD, PhD student
Associate Professor Össur Emilsson
Cardiology
Associate Professor Emil Hagström, MD
Other collaborators
Karl Franklin, professor, Department of Surgery, Umeå University
Christian Benedict, Associate professor, Department of Pharmaceutical Biosciences, UU
Timo Leppänen, Associate professor, University of Eastern Finland
Sleep disturbances are frequent in the general population, with insomnia and obstructive sleep apnea (OSA) among the most common. Insomnia is prevalent in 10-15 % of general population and is more prevalent in women than men. OSA show a prevalence of 3-7% of adult men and 2-5% of adult women. Daytime symptoms such as sleepiness or tiredness are common complaints both in insomnia and in OSA. Other shared symptoms may include repeated awakenings, daytime concentration problems and fatigue. Sleep disturbances and psychological distress, such as anxiety and depressive symptoms are interconnected and multifactorial. To what extent snoring or OSA contribute to the relationship between insomnia and psychological distress is not fully elucidated. In addition, it is not clear if objective measures of sleep relate to psychological distress and if there is a gender difference.
The overall aim of this project is to assess the effect of sleep disturbances, as well as gender differences in objectively measured sleep, on psychological distress.
Department of Medical Sciences, Uppsala University (UU)
Respiratory, allergy and sleep research
Associate Professor Jenny Theorell-Haglöw (PI)
Professor Eva Lindberg, MD, former PI for the cohorts
Mirjam Ljunggren, MD, PhD
Galileo Frustaci, MD, PhD student
Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity, including hypertension, coronary artery disease, arrhythmias and stroke. The pathogenesis of cardiovascular complications in OSA is incompletely understood, but a multifactorial etiology is likely. Possible underlying pathophysiological mechanisms include an increase in sympathoadrenal activity, systemic inflammation caused by intermittent hypoxemia and impaired glucose tolerance. Despite the increasing awareness of OSA and the negative longterm health effects when left untreated, OSA still remains significantly underdiagnosed. Furthermore, limited data is available on long-term evolution of sleep-disordered breathing. In a previous study in men, we found that sleep-disordered breathing became significantly worse over time. Comparable data for women are still absent.
In the SHE study 400 women, with an oversampling of snorers, performed full polysomnography during 2002-2004. The prevalence of OSA was high with almost 6% of the women fulfilling the criteria of severe OSA. Ten years later, 264 of the original sample were investigated with an identical procedure. Changes in apnoea-hypopnea index between baseline and follow-up will be analysed. Predictors for deterioration and improvement that will be analysed include age group, baseline BMI, change in BMI, smoking, cardiovascular diseases, weight gain and lung function.
We aim to study the long-term evolution of obstructive sleep apnea (OSA) in women as well as predictors for deteriorating and improving OSA over time.
Baz Delshad, MD, PhD student
Mirjam Ljunggren, MD, PhD
Eva Lindberg, MD, PhD
Jenny Theorell-Haglöw, PhD
Department of medical sciences, Respiratory, Allergy and Sleep Research, Uppsala University.
Anchor: Funders• Swedish Research Council
• Swedish Heart-Lung Foundation
We welcome potential collaborators to any of our sub-projects. Please contact the project lead for sub-project you are interested in or write to any of the contact persons below.
Anchor: contactsEva Lindberg eva.lindberg@medsci.uu.se
Mirjam Ljunggren Mirjam.ljunggren@medsci.uu.se
Jenny Theorell-Haglöw jenny.theorell-haglow@medsci.uu.se
Svensson M, Lindberg E, Naessen T, Janson C. Risk factors associated with snoring in women with special emphasis on body mass index: a population-based study. Chest 2006; 129:933-41.
Svensson M, Holmström M, Broman JE, Lindberg E. Can anatomical and functional features in the upper airways predict sleep apnea? A population-based study in females. Acta Otolaryngol. 2006; 126:613-20.
Theorell-Haglöw J, Lindberg E, Janson C. What are the important risk factors for daytime sleepiness and fatigue in women? Sleep 2006; 29:751-7 (Comment in Editorial, Sleep 2006; 29: 738-40).
Lindberg E, Berne C, Franklin KA, Svensson M, Janson C. Snoring and daytime sleepiness as risk factors for hypertension and diabetes in women – a population-based study. Respir Med. 2007; 101:1283-90.
Theorell-Haglöw J, Berne C, Janson C, Lindberg E. Obstructive sleep apnoea is associated with decreased insulin sensitivity in females. Eur Respir J. 2008; 31:1054-60.
Svensson M, Franklin KA, Theorell-Haglöw J, Lindberg E. Daytime sleepiness relates to snoring independent of the apnea-hypopnea index in women from the general population. Chest 2008; 134:919-24. (Comment in Chest 2008; 136:648-9, author reply 649).
Sahlin C, Franklin KA, Stenlund H, Lindberg E. Sleep in women: Normal values of sleep stages and position, and the effect of age, obesity, sleep apnea, smoking, alcohol and hypertension. Sleep Med. 2009; 10:1025-30.
Kesek M, Franklin K, Sahlin C, Lindberg E. Heart rate variability during sleep and sleep apnoea in a population based study of 387 women. Clin Physiol Funct Imaging. 2009; 29:309-15.
Theorell-Haglöw J, Berne C, Janson C, Sahlin S, Lindberg E. Associations between short sleep duration and central obesity in women. Sleep 2010; 33:593-598. (Comment in Editorial, Sleep 2010; 33:773-4).
Theorell-Haglöw J, Berne C, Janson C, Lindberg E. The role of obstructive sleep apnea in metabolic syndrome: A population-based study in women. Sleep Med 2011; 12:329-34.
Svensson M, Venge P, Janson C, Lindberg E. Relationship between sleep-disordered breathing and markers of systemic inflammation in women from the general population. J Sleep Res 2012; 21: 147-54.
Theorell-Haglöw J, Berglund L, Janson C, Lindberg E. Sleep duration and central obesity in women – differences between short sleepers and long sleepers. Sleep Med. 2012; 13:1079-85.
Ljunggren M, Lindahl B, Theorell-Haglöw J, Lindberg E. Association between obstructive sleep apnea and elevated levels of type B natriuretic peptide in a community-based sample of women. Sleep. 2012; 35:1521-7.
Franklin KA, Sahlin C, Stenlund H, Lindberg E. Sleep apnoea is a common occurrence in females. Eur Respir J. 2013;41: 610-15.
Wesström J, Ulfberg J, Sundström-Poromaa I, Lindberg E. Periodic Limb Movements are Associated with Vasomotor Symptoms. J Clin Sleep Med 2014; 10:15-20.
Spörndly-Nees S, Åsenlöf P, Theorell-Haglöw J, Svensson M, Igelström H, Lindberg E. Leisure-time physical activity predicts complaints of snoring in women: a prospective cohort study over 10 years. Sleep Med. 2014; 15:415-21.
Theorell-Haglöw J, Berglund L, Berne C, Lindberg E. Both habitual short sleepers and long sleepers are at greater risk of obesity: a population-based 10-year follow-up in women. Sleep Med. 2014; 15(10):1204-11.
Bengtsson C, Jonsson L, Svensson M, Holmström M, Theorell-Haglöw J, Lindberg E. The impact of nasal obstruction on sleep quality – a community-based study of women. Eur Arch Otorhinolaryngol. 2015; 272: 97-103.
Palm A, Janson C, Lindberg E. The impact of weight gain and obesity on development of sleep problems in a population-based sample. Sleep Med. 2015;16(5):593-7.
Amid-Hägg A, Torén K, Lindberg E. Role of sleep disturbances in occupational accidents among women. Scand J Work Environ Health. 2015;41(4):368-76.
Theorell-Haglöw J, Åkerstedt T, Schwarz J, Lindberg E. Predictors for development of excessive daytime sleepiness in women: a population-based 10-year follow-up. Sleep 2015; 38:1995-2003.
Ljunggren M, Byberg L, Theorell-Haglöw J, Lindahl B, Michaëlsson K, Lindberg E. Increased risk of heart failure in women with symptoms of sleep-disordered breathing. Sleep Med 2016; 17:32-37.
Åkerstedt T, Schwarz J,Gruber G, Lindberg E, Theorell-Haglöw J. The relation between polysomnography and subjective sleep and its dependence on age – poor sleep may become good sleep. J Sleep Res 2016; 25(5):565-570.
Spörndly-Nees S, Åsenlöf P, Lindberg E. High or increasing levels of physical activity protect women from future insomnia. Sleep Med. 2017;32:22-27.
Schwarz J, Åkerstedt T, Lindberg E, Gruber G, Fischer F, Theorell-Haglöw J. Age affects sleep microstructure more than sleep macrostructure. J Sleep Res. 2017; 26(3):277-287.
Sundbom F, Janson C, Malinovschi A, Lindberg E. Effects of Coexisting Asthma and Obstructive Sleep Apnea on Sleep Architecture, Oxygen Saturation, and Systemic Inflammation in Women. J Clin Sleep Med. 2018 Feb 15;14(2):253-259.
Ljunggren M, Lindberg E, Franklin KA, Öhagen P, Larsson M, Theorell-Haglöw J, Naessén T. Obstructive sleep apnea during REM-sleep is associated with early signs of atherosclerosis in women. Sleep. 2018 Jul 1;41(7). doi: 10.1093/sleep/zsy099.
Åkerstedt T, Schwarz J, Gruber G, Theorell-Haglöw J, Lindberg E. Women with both sleep problems and snoring show objective impairment of sleep. Sleep Med 2018; 51:80-84.
Amid Hägg S, Emilsson ÖI,Franklin KA,Janson C, Lindberg E. Nocturnal gastroesophageal reflux increases the risk of daytime sleepiness in women. Sleep Med 2019; 53:94-100.
Åkerstedt T, Schwarz J, Gruber G, Theorell-Haglöw J, Lindberg E. Short sleep-poor sleep? A polysomnographic study in a large population-based sample of women. J Sleep Res.2019; 28:e12812.
Sundström J, Söderholm M, Söderberg S, Alfredsson L, Andersson M, Bellocco R, Björck M, Broberg P, Eriksson M, Eriksson M, Forsberg B, Fransson EI, Giedraitis V, Theorell-Haglöw J, Hallqvist J, Hansson PO, Heller S, Håkansson N, Ingelsson M, Janson C, Järvholm B, Khalili P, Knutsson A, Lager A, Lagerros YT, Larsson SC, Leander K, Leppert J, Lind L, Lindberg E, Magnusson C, Magnusson PKE, Malfert M, Michaëlsson K, Nilsson P, Olsson H, Pedersen NL, Pennlert J, Rosenblad A, Rosengren A, Torén K, Wanhainen A, Wolk A, Engström G, Svennblad B, Wiberg B. Risk factors for subarachnoid haemorrhage: a nationwide cohort of 950 000 adults. Int J Epidemiol. 2019 Dec 1;48(6):2018-2025. doi: 10.1093/ije/dyz163.
Ljunggren M, Theorell-Haglöw J, Freyhult E, Sahlin C, Franklin KA, Malinovschi A, Janson C, Lindberg E. Association between proteomics and obstructive sleep apnea phenotypes in a community-based cohort of women. J Sleep Res. 2020 Aug;29(4):e13041.
Kamble PG, Theorell-Haglöw J, Wiklund U, Franklin KA, Hammar U, Lindberg E, Eriksson JW. Sleep apnea in men is associated with altered lipid metabolism, glucose tolerance, insulin sensitivity, and body fat percentage. Endocrine 2020 Oct;70(1):48-57. doi: 10.1007/s12020-020-02369-3.
Ghilotti F, Bellocco R, Trolle Lagerros Y, Thorson A, Theorell-Haglöw J, Åkerstedt T, Lindberg E. Relationship between sleep characteristics and markers of inflammation in Swedish women from the general population. J Sleep Res. 2021 Apr;30(2):e13093.
Lind L, Zethelius B, Lindberg E, Pedersen NL, Byberg L. Changes in leisure-time physical activity during the adult life span and relations to cardiovascular risk factors-Results from multiple Swedish studies. PLoS One. 2021 Aug 19;16(8):e0256476. doi: 10.1371/journal.pone.0256476. eCollection 2021.
Benedict C, Franklin KA, Bukhari S, Ljunggren M, Lindberg E. Sex-specific association of the lunar cycle with sleep. Sci Total Environ. 2022 Jan 15;804:150222.
Emilsson ÖI, Yasiry HA, Theorell-Haglöw J, Ljunggren M, Lindberg E. Insufficient sleep and new onset of nocturnal gastroesophageal reflux among women: a longitudinal cohort study. J Clin Sleep Med. 2022 Jul 1;18(7):1731-1737. doi: 10.5664/jcsm.9928.
Ljunggren M, Naessén T, Theorell-Haglöw J, Franklin KA, Lindberg E. Rapid eye movement sleep apnea and carotid intima thickness in men and women: a SHE-MUSTACHE cohort study. J Sleep Res. 2022 Oct;31(5):e13599. doi: 10.1111/jsr.13599.
Sundbom F, Janson C, Ljunggren M, Lindberg E. Asthma and asthma-related comorbidity: effects on nocturnal oxygen saturation. J Clin Sleep Med. 2022 Nov 1;18(11):2635-2641.
Åkerstedt T, Schwarz J, Lindberg E, Theorell-Haglöw J. Total sleep time, sleep efficiency, and next day subjective sleepiness in a large group of women. Sleep Adv. 2022 Sep 7;3(1):zpac028. doi: 10.1093/sleepadvances/zpac028. eCollection 2022.
Johansson PJ, Crowley P, Axelsson J, Franklin K, Garde AH, Hettiarachchi P, Holtermann A, Kecklund G, Lindberg E, Ljunggren M, Stamatakis E, Theorell Haglöw J, Svartengren M. Development and performance of a sleep estimation algorithm using a single accelerometer placed on the thigh: an evaluation against polysomnography. J Sleep Res. 2023 Apr;32(2):e13725. doi: 10.1111/jsr.13725.
Åkerstedt T, Schwarz J, Theorell-Haglöw J, Lindberg E. What do women mean by poor sleep? A large population-based sample with polysomnographical indicators, inflammation, fatigue, depression, and anxiety. Sleep Med. 2023 Sep;109:219-225. doi: 10.1016/j.sleep.2023.06.029.
Ljunggren M, Zhou X, Theorell-Haglöw J, Janson C, Franklin KA, Emilsson Ö, Lindberg E. Sleep Apnea Indices Associated with Markers of Inflammation and Cardiovascular Disease: A Proteomic Study in the MUSTACHE Cohort. Ann Am Thorac Soc. 2024 Jan;21(1):165-169. doi: 10.1513/AnnalsATS.202305-472RL.
Tan X, Ljunggren M, Kilander L, Benedict C, Lindberg E. Obstructive sleep apnea during rapid eye movement sleep and cognitive performance in adults. Sleep Med. 2024 Jan;113:34-40. doi: 10.1016/j.sleep.2023.11.017. Epub 2023
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