Perelman School of Medicine at the University of Pennsylvania

Center for Sleep and Circadian Neurobiology

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International Collaborations

The Center for Sleep and Circadian Neurobiology has developed a number of international efforts in collaborative research and training for research. The major efforts are:

University of Iceland

The CSCN has a longstanding collaboration with the Sleep Center at the University of Iceland in Reykjavik, directed by Dr. Thorarinn Gislason. The CSCN has jointly developed the Icelandic Sleep Apnea Cohort and have several publications on this. PhD students—Erna Sif Arnardottir and Erla Bjornsdottir—were jointly mentored by Dr. Gislason and faculty at the University of Pennsylvania. Read More

Iceland is a small, independent country in the middle of the Atlantic. It has a population of around 320,000. Home sleep studies are done at five different locations around the island. All individuals prescribed CPAP therapy, however, go to the Sleep Center in Reykjavik, University of Iceland, to be evaluated by Dr. Thorarinn Gislason and his team. There is one governmental payer for health care. This combination makes it ideal for clinical research studies in sleep apnea. Working in collaboration with Dr. Gislason, Dr. Bryndis Benediktsdottir, Dr. Erna Sif Arnardottir, Dr. Erla Bjornsdottir and Dr. Sigurður Júlíusson, we developed a prospective cohort of consecutive patients with OSA referred for CPAP therapy.

Thorarinn Gislason (right on back row), Erna Arnardottir (fourth from right, back row); Richard Schwab (third from left, back row); Allan Pack (second from right, back row) and other members of Icelandic team at Tinglavir. Tinglavir is at the intersection of the North American and European plates in the earth’s surface. It is a very important historic site in Iceland. It was the seat of the first democratic parliament in the world.

Studies conducted in Iceland have focused on the following: a) different clinical subtypes of OSA; b) relative role of obesity and OSA in determining molecular consequences of disease; c) biomarkers; d) insomnia in patients with OSA; and e) determinants of CPAP adherence.

This has been, and continues to be, a highly productive collaboration. It has been supported by NIH grants. Initially this was an R01 (A Family Linkage Study of Obstructive Sleep Apnea) and later by projects within a Program Project Grant directed by Dr. Pack (Endophenotypes of Sleep Apnea and Role of Obesity). A new Program Project Grant (Individual Differences in Obstructive Sleep Apnea) has just been funded by the National Heart, Lung and Blood Institute for 5 years. The University of Iceland is a collaborative site in this program. As part of this effort, we have obtained, in collaboration with deCODE Genetics, genotype data in 5,000 patients with OSA. However, using GWAS analysis with this group of cases and more than 100,000 controls, no genome-wide association has yet been identified.

 

Publications

Phan TS, Li JK, Segers P, Reddy-Koppula M, Akers SR, Kuna ST, Gislason T, Pack AI, Chirinos JA. Aging is Associated With an Earlier Arrival of Reflected Waves Without a Distal Shift in Reflection Sites. J Am Heart Assoc. 2016 Aug 29;5(9). pii: e003733. PubMed PMID: 27572821.

Björnsdóttir E, Benediktsdóttir B, Pack AI, Arnardottir ES, Kuna ST, Gíslason T, Keenan BT, Maislin G, Sigurdsson JF. The Prevalence of Depression among Untreated Obstructive Sleep Apnea Patients Using a Standardized Psychiatric Interview. J Clin Sleep Med. 2016 Jan;12(1):105-12. PubMed PMID: 26350608; PubMed Central PMCID: PMC4702203.

Bjornsdottir E, Keenan BT, Eysteinsdottir B, Arnardottir ES, Janson C, Gislason T, Sigurdsson JF, Kuna ST, Pack AI, Benediktsdottir B. Quality of life among untreated sleep apnea patients compared with the general population and changes after treatment with positive airway pressure. J Sleep Res. 2015 Jun;24(3):328-38. PubMed PMID: 25431105; PubMed Central PMCID: PMC4439289.

Arnardottir ES, Lim DC, Keenan BT, Maislin G, Benediktsdottir B, Juliusson S, Pack AI, Gislason T. Effects of obesity on the association between long-term sleep apnea treatment and changes in interleukin-6 levels: the Icelandic Sleep Apnea Cohort. J Sleep Res. 2015 Apr;24(2):148-59. PubMed PMID: 25359691; PubMed Central PMCID: PMC4351148.

Ye L, Pien GW, Ratcliffe SJ, Björnsdottir E, Arnardottir ES, Pack AI, Benediktsdottir B, Gislason T. The different clinical faces of obstructive sleep apnoea: a cluster analysis. Eur Respir J. 2014 Dec;44(6):1600-7. PubMed PMID: 25186268.

Pak VM, Keenan BT, Jackson N, Grandner MA, Maislin G, Teff K, Schwab RJ, Arnardottir ES, Júlíusson S, Benediktsdottir B, Gislason T, Pack AI. Adhesion molecule increases in sleep apnea: beneficial effect of positive airway pressure and moderation by obesity. Int J Obes (Lond). 2015 Mar;39(3):472-9. PubMed PMID: 25042863; PubMed Central PMCID: PMC4302066.

Keenan BT, Maislin G, Sunwoo BY, Arnardottir ES, Jackson N, Olafsson I, Juliusson S, Schwab RJ, Gislason T, Benediktsdottir B, Pack AI. Obstructive sleep apnoea treatment and fasting lipids: a comparative effectiveness study. Eur Respir J. 2014 Aug;44(2):405-14. PubMed PMID: 24833762.

Björnsdóttir E, Janson C, Sigurdsson JF, Gehrman P, Perlis M, Juliusson S, Arnardottir ES, Kuna ST, Pack AI, Gislason T, Benediktsdóttir B. Symptoms of insomnia among patients with obstructive sleep apnea before and after two years of positive airway pressure treatment. Sleep. 2013 Dec 1;36(12):1901-9. PubMed PMID: 24293765; PubMed Central PMCID: PMC3825440.

Arnardottir ES, Janson C, Bjornsdottir E, Benediktsdottir B, Juliusson S, Kuna ST, Pack AI, Gislason T. Nocturnal sweating--a common symptom of obstructive sleep apnoea: the Icelandic sleep apnoea cohort. BMJ Open. 2013 May 14;3(5). PubMed PMID: 23674447; PubMed Central PMCID: PMC3657640.

Arnardottir ES, Maislin G, Jackson N, Schwab RJ, Benediktsdottir B, Teff K, Juliusson S, Pack AI, Gislason T. The role of obesity, different fat compartments and sleep apnea severity in circulating leptin levels: the Icelandic Sleep Apnea Cohort study. Int J Obes (Lond). 2013 Jun;37(6):835-42. PubMed PMID: 22964793; PubMed Central PMCID: PMC3537909.

Arnardottir ES, Maislin G, Schwab RJ, Staley B, Benediktsdottir B, Olafsson I, Juliusson S, Romer M, Gislason T, Pack AI. The interaction of obstructive sleep apnea and obesity on the inflammatory markers C-reactive protein and interleukin-6: the Icelandic Sleep Apnea Cohort. Sleep. 2012 Jul 1;35(7):921-32. PubMed PMID: 22754038; PubMed Central PMCID: PMC3369227.

Fedson AC, Pack AI, Gislason T. Frequently used sleep questionnaires in epidemiological and genetic research for obstructive sleep apnea: a review. Sleep Med Rev. 2012 Dec;16(6):529-37. PubMed PMID: 22425225.

Maislin G, Ahmed MM, Gooneratne N, Thorne-Fitzgerald M, Kim C, Teff K, Arnardottir ES, Benediktsdottir B, Einarsdottir H, Juliusson S, Pack AI, Gislason T, Schwab RJ. Single slice vs. volumetric MR assessment of visceral adipose tissue: reliability and validity among the overweight and obese. Obesity (Silver Spring). 2012 Oct;20(10):2124-32. PubMed PMID: 22395811; PubMed Central PMCID: PMC3743719.

Björnsdóttir E, Janson C, Gíslason T, Sigurdsson JF, Pack AI, Gehrman P, Benediktsdóttir B. Insomnia in untreated sleep apnea patients compared to controls. J Sleep Res. 2012 Apr;21(2):131-8. PubMed PMID: 21988168; PubMed Central PMCID: PMC3258454.

Arnardottir ES, Mackiewicz M, Gislason T, Teff KL, Pack AI. Molecular signatures of obstructive sleep apnea in adults: a review and perspective. Sleep. 2009 Apr;32(4):447-70. Review. PubMed PMID: 19413140; PubMed Central PMCID: PMC2663860.

Pack AI, Gislason T. Obstructive sleep apnea and cardiovascular disease: a perspective and future directions. Prog Cardiovasc Dis. 2009 Mar-Apr;51(5):434-51. Review. PubMed PMID: 19249449.

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Peking University (PKU)/University of Pennsylvania (Penn) Sleep Program - Beijing, China

There is a joint research/educational sleep medicine center in Beijing co-directed by Dr. Fang Han (PKU) and Dr. Allan Pack (Penn). This program has various components: a) implementation research on sleep apnea; b) annual symposium in China; c) development of training for sleep medicine physicians and sleep technologists. Read More

This Center is located at Peking University, Beijing; the leading university in China. It is primarily focused on the People’s Hospital. The overall mission of the Center is to be the leading research center in China in sleep medicine, to develop training for physicians and technologists in sleep medicine and to be a model for clinical care of patients with sleep disorders.

The Center is co-directed by Dr. Fang Han (PKU) and Dr. Allan Pack (Penn). There is an Oversight Committee with five members: Dr. Dongmen Chen (Dean of Innovation, PKU), Dr. Glen Gaulton (Vice Dean for International Programs, Penn), Dr. Fang Han (PKU), Mr. David Jiang (North American liaison for PKU) and Dr. Allan Pack (Penn).

A major initial effort has been, and is, in implementation research in new ways to diagnose and treat obstructive sleep apnea. Dr. Sam Kuna (Penn) is playing a leading role in this. Other members of the research team are Dr. Han, Liyue Xu (PKU), Lyz Kneeland (Penn), Rebecca Gallagher (Penn) and Brendan Keenan (Penn).

The group has done an initial study validating home studies with NOX equipment in Chinese subjects. This study is complete and a manuscript has been submitted. A study is ongoing to validate home sleep studies for diagnosis of OSA in patients with co-existing congestive heart failure and in patients with co-existing COPD. The research group in China and at the University of Pennsylvania have weekly GoToMeeting events to move the projects forward.

In addition, we are implementing a pilot program of a new path to diagnosis and management of OSA. This involves assessment of patients by tele-medicine and care management based on obtaining compliance and other data from CPAP machines. This study is ongoing.

The PKU/Penn Center is now organizing annual meetings in China. Two have been held (2015 and 2016). The programs for these meetings are below. These meetings have been well attended and have stimulated more collaborations in research.

PKU/Penn 2nd Annual Joint Symposium on Sleep Medicine

2016 Program

PKU/Penn 1st Annual Joint Symposium on Sleep Medicine

2015 Program

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Mahatma Gandhi Medical School (MGM)/University of Pennsylvania Sleep Center - Mumbai, India

MGM established an 8-bed sleep center in March 2014. The goals of the center are to provide high-level clinical sleep medicine, training of physicians and technologists in sleep medicine, and collaborative research. Currently the team at the University of Pennsylvania is conducting remote training of technologists. A research program studying obstructive sleep apnea in type 2 diabetic subjects is being initiated. Read More

The sleep center is a state of the art facility with 8 bedrooms for in-lab sleep studies, Sandman equipment, space for patient interviews, and a large conference room. The Center is directed by Dr. Aloke Banerjee. It was officially opened by Dr. Allan Pack in March 2014.

Currently, the University of Pennsylvania is assisting in a technology training program. One of the CSCN's senior technologists—Nadia Ali—spent some weeks in India and now carries out additional remote training by the web every 2 weeks. The goal is to train technologists so that they are prepared to successfully sit for the technologist training certificate in the United States.

Awareness of sleep disorders in India, both in the physician community and general public, is not high. To address this we collaborated with Dr. Banerjee, Dr. Sudhir Kadam and colleagues to put on a CME course for physicians in Mumbai about sleep medicine.

We are now starting a research project to assess prevalence of OSA in type 2 diabetics in India, and downstream consequences in terms of biomarkers. A grant application is being developed and we are collaborating in setting up a RedCap data base. Type 2 diabetes is a common problem in India and occurs in individuals at lower levels of obesity than in the United States population.

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University of Oxford

The CSCN actively collaborates with the Sleep and Circadian Neuroscience Institute in the Nuffield Department of Clinical Neurosciences at Oxford University in both research and education.

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