Epidemiology Research Group

​The first part of the project is a prospective multi-centre matched cohort study. The study included 391 SARS-CoV-2 RT-PCR positive (PCR+) and 703 negative (PCR-) participants in South-Eastern Norway (Telemark and Agder counties) from February to December 2020. 

Possible predictors of SARS-CoV-2 total antibody persistence were assessed. The SARS-CoV-2 total antibody levels against spike protein were measured three to five months after PCR. The groups were matched by residency and time for the PCR test; 212 PCR+ participants were included in follow-up measurements at 10 to 12 months.

The results indicate that the level of SARS-CoV-2 total antibodies against spike protein persists for the vast majority of non-vaccinated PCR+ persons at least 10 to 12 months after mild COVID-19. 

In the second part of the project we assess the quantitative IgG against spike protein together with nucleocapsid antibodies at 12 and 24 months after the first PCR test. With this analysis we can detect symptomatic/asymptomatic infections both in vaccinated and non-vaccinated PCR+ and PCR- participants and assess the humoral protective immunity in these different groups.

In the third part of the study we applied a Test-Negative Design (TND) with population controls to assess risk factors for COVID-19. Population controls (the Telemark-Study in 2018) are used and compared to PCR+ and PCR- negative participants to assess risk factors.

• ​Prinsipal investigator, PhD-main supervisor Anne Kristin M. Fell, Associate professor at the Institute of Health and Society, University of Oslo (UiO), senior physician at the Dep. of Occupational and Environmental Medicine, (Telemark Hospital). 
• Co-supervisor PhD-candidate TH: Hege Kersten, MSc, Ass. Prof. at the Institute of pharmacology, UIO and is Head of the research department at TH. 
• Co-supervisor PhD-candidate TH: Yngvar Tveten MD, PhD, specialist in medical microbiology and internal medicine.  
• Coordinator Agder Randi Eikeland, MD, Ass. Prof. Faculty of Health & Sport Sciences, University of Agder (UiA), Norway, specialist in neurology.  
• Harald Reiso, MD, PhD, specialist in general medicine and community health.  
• Kristine Karlsrud Berg,​​ MD, resident in medical microbiology at Sørlandet Hospital (SH).

• ​Prof. Neil Pearce, MSc, London School of Hygiene and Tropical Medicine, UK, Professor of Epidemiology and Biostatistics.  
• Prof. Emeritus Jan Vandenbrouke, MD, the University of Leiden, NL and the University of Aalborg, DK,  specialist in internal medicine, MSc in Epidemiology. 
• Ingeborg Aaberge, MD, PhD, specialist director at NIPH, specialist in immunology, transfusion, and medical microbiology. 
• Prof. Emeritus Johny Kongerud, MD Dep. of Respiratory Medicine, Oslo University Hospital and UiO, a specialist in pulmonary medicine. 
• Svein Arne Nordbø, MD, Ass. Prof. Dep. of clinical and molecular medicine, NTNU, specialist in medical microbiology. 

1. ​Sarjomaa M, Eikeland R, My Diep L, Tveten Y, Reiso H, Thilesen C, Nordbø SA,  Berg KK, Aaberge I, Pearce N, Kersten H, Vandenbroucke JP, Fell AKM.
   Longitudinal follow-up study of SARS-CoV-2 antibody persistence. ECCMID 2022 Portugal, poster.
2. Sarjomaa M, Diep LM, Zhang C, Tveten Y, Reiso H, Thilesen C, Nordbø SA, Berg KK, Aaberge I, Pearce N, Kersten H, Vandenbroucke JP, Eikeland R, Fell AKM. SARS-CoV-2 antibody persistence after five and twelve months: A cohort study from South-Eastern Norway. PLoS One. 2022 Aug 10;17(8):e0264667. doi: 10.1371/journal.pone.0264667. eCollection 2022. PMID: 35947589
   
3. Sarjomaa MA, Zhang C, Tveten Y, Kersten H, Reiso H,  Eikeland R,  View Kongerud J, Berg KK, Thilesen C,  Nordbø SA, Aaberge IS, Vandenbroucke JP,  Pearce JP, Fell AKMF. Risk factors for SARS-CoV-2 infection: A test-negative case-control study with additional population controls. medRxiv 2023.03.15.23287300; doi: https://doi.org/10.1101/2023.03.15.23287300 Sarjomaa MA, Zhang C, Tveten Y, Kersten H, Reiso H,  Eikeland R,  View Kongerud J, Berg KK, Thilesen C,  Nordbø SA, Aaberge IS, Vandenbroucke JP,  Pearce JP, Fell AKMF. Risk factors for SARS-CoV-2 infection: A test-negative case-control study. European Respiratory Society congress 2023, Milano, poster.
   

​​​​​

Chronic respiratory diseases such as asthma and COPD are among our major public diseases. In addition, the proportion of patients who receive poor treatment is more than 50%. The Telemark study, is a large population survey among adults born between 1963 and 1997 and living in the Telemark area. The overall study aim is to contribute to better treatment and prevention of respiratory disease. We have collected data from the general population in Telemark, which is a county with a relatively high proportion of disabled people, a slightly lower average level of education than elsewhere in Norway and a large proportion of industrial workers and craftsmen. Unique to the Telemark Study is extensive mapping of exposure in the environment and at work, information on nutrition and physical activity and, and clinical data as well as a biobank that provides new knowledge about why respiratory disease occurs and mechanisms. We also have permission to link our data to national registers to shed light on opportunities for better treatment and prevention of disease in the respiratory tract. In addition, the study generates new insight into what can be done to prevent reduced quality of life and dropout from working life.

​The Telemark study started in 2013. At the time, approximately 48.000 random inhabitants of Telemark county aged 16 to 50 received a postal questionnaire. The questionnaire contained questions about occupational history, respiratory symptoms, doctor-diagnosed asthma, smoking habits and possible risk and influencing factors. In a sub-study, all participants with physician-diagnosed asthma and a corresponding number of random people without asthma were invited to further medical examinations. This involved answering a questionnaire, a breath test (spirometry with reversibility testing), filling in the form 'asthma control test questionnaire' (ACT), measurement of nitrogen in exhaled air (fractionated exhaled nitric oxide) and blood samples. In 2018, all those who responded in 2013 (n=16,099) were invited to a 5-year follow-up. We also invited new participants from the same age group. The Telemark-study database now contains data from approximately 22.500 participants.

• ​Professor emeritus Kjell Torén, MD, Dep. of Occupational and Environmental Medicine/University of Gothenburg, Sweden.
  
• Epidemiologist Paul Henneberger, MSC, PhD, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health (NIOSH), Morgantown, USA.
• Kai Gustavsen is the user representative and works as a chief adviser at Norwegian Astma- and Allergi association (NAAF).
• Professor emeritus, Johny Kongerud, MD, Dep. of Respiratory disease, Rikshospitalet Oslo Universitetssykehus, Institutt for klinisk medisin, UiO. 
  
• Professor Johan Hellgren, MD, Dep. Otolaryngology , Sahlgrenska Universitetssykehus i Gøteborg/Universitetet i Gøteborg, Sverige.
  
  
  
  

Influence of asthma and body mass index on respiratory symptoms, lung function, and work ability: A general population study in Telemark

​Geir Klepaker, Senior Phy​sician​​, PhD, Department of Occupational Medicine (Telemark Hospital)​. ​

Although asthma and obesity are associated with negative lung health effects, a possible interaction between the two conditions is little studied. Sickness absence and self-assessed work ability can be used to describe the functional level in patients with asthma and obesity. 

For patients with asthma, the level of function will depend on how well the symptoms are managed and controlled, overall symptom burden and lung function. Patients with obesity may also have reduced ability to work and increased sickness absence due to increased weight. Work ability assessed using the 'Work ability score (WAS)' has not previously been examined in patients with both asthma and obesity. Exposure to vapour, gas, dust and fumes (VGDF) is linked to asthma and worsening of asthma. There are few studies of changes in respiratory symptoms due to changes in body mass index (BMI) or occupational exposure to VGDF. 

A better understanding of the combined effects of asthma and obesity can help design new and more personalized treatment and follow-up for patients with both asthma and elevated BMI.The aim of the study was to investigate the occurrence of self-reported respiratory symptoms, work ability and lung function in patients with asthma in relation to BMI. 

Furthermore, we have studied the extent to which asthma and elevated BMI are independently linked to symptoms, work ability and lung function and whether there is an interaction between asthma and BMI≥25 kg/m2. In a follow-up study, we have assessed the relationship between change in a burden score for respiratory complaints and change in BMI and occupational exposure to VGDF, and how this varied with gender and asthma status. The project is in its final phase with a PhD dissertation in February 2023.

​Publications

1. ​Klepaker G, Henneberger PK, Torén K, Brunborg C, Kongerud J, Fell AKM. Association of respiratory symptoms with body mass index and occupational exposure comparing sexes and subjects with and without asthma: follow-up of a Norwegian population study (the Telemark study). BMJ Open Respir Res. 2022 Mar;9(1).
2. Klepaker G, Henneberger PK, Hertel JK, Holla ØL, Kongerud J, Fell AKM. Influence of asthma and obesity on respiratory symptoms, work ability and lung function: findings from a cross-sectional Norwegian population study. BMJ Open Respir Res. 2021 Sep;8(1)
3. Klepaker G, Svendsen MV, Hertel JK, Holla ØL, Henneberger PK, Kongerud J, Fell AKM. Influence of Obesity on Work Ability, Respiratory Symptoms, and Lung Function in Adults with Asthma. Respiration. 2019;98(6):473-481. 

II. Incidence and risk factors for obstructive respiratory disease – the five-year follow-up of the Telemark Study

Associate Professor Nikola Zivadinovic Senior Phy​sician​​, Department of Occupational Medicine (Telemark Hospital)​, PhD-candidate. 

This project started in 2018 as a five-year follow-up of the baseline Telemark study. The project includes 16 099 subjects who participated in the baseline cohort and answered to the questionnaire in 2013. In addition 24 000 new subjects in the same age group (born 1963-97) who lived in Telemark in 2013 were asked to participate in the follow-up. This was done because it is well known from similar prospective studies that a substantial proportion is lost to follow-up. 

All subjects received a postal questionnaire. We have used validated, self-administered questionnaires for registration of respiratory symptoms, comorbidity, other possible confounders and exposure. Participants were also asked to list their occupational history. 

All occupations were first classified according to the 1988 International Standard Classification of Occupations (ISCO-88) and then connected with an asthma-specific job-exposure matrix (JEM) developed for the northern European Countries (N-JEM). The aim of this study is to estimate new onset of obstructive lung diseases in a period of five-year follow-up and give new and updated knowledge on risk factors associated with the development of obstructive lung diseases. Non-response was assessed at baseline and at 5-year follow-up. The last part of the study will study possible risk factors for asthma exacerbation.

Main supervisor

Anne Kristin M. Fell, Associate professor at the Institute of Health and Society, University of Oslo (UiO), Senior Physician at the Dep. of Occupational and Environmental Medicine, (Telemark Hospital)​

Co-supervisors

• ​Regine Abrahamsen, Senior Phy​sician, PhD, Dep. of Occupational and Environmental Medicine, (Telemark Hospital)​. 
• Professor emeritus, Johny Kongerud, MD, Lungemedisinsk avdeling, Rikshospitalet Oslo Universitetssykehus, Institutt for klinisk medisin, UiO. ​
  
• Professor Anthony Wagstaff, MD, Flymedisinsk institute, Oslo, UiO, Avdeling for Samfunnsmedisin og global helse, institutt for helse og samfunn, UiO.

Publications

1. ​Abstract: Loss to Five-year Follow-up in Telemark Study. Poster-presentation ved European Respiratory Society (ERS) Congress in October 2019, in Madrid.
2. Abstract: Occupational exposure and new onset asthma in the Telemark study: a five-year follow-up. Oral and poster-presentation online ved European Respiratory Society (ERS) Congress in October 2020, Vienna.
3. Zivadinovic N, Abrahamsen R, Pessonen M, Wagstaff A, Torén K, Henneberger PK, Kongerud J, Fell AKM. Loss to Five-year Follow-up in the population-based Telemark Study: risk factors and potential for bias” has been sent to BMJ Open and is waiting editorial decision.

​III. Occupational exposure, asthma, and respiratory work disability – a general population study in Telemark 

Regine Abrahamsen, Senior phy​sician​​, PhD, Department of Occupational Medicine (Telemark Hospital)​, PhD

About the subproject​

​The overall aim of the thesis was to estimate the prevalence of self-reported respiratory symptoms and physician-diagnosed asthma in Telemark. The study also aimed to identify possible occupations and specific exposures associated with respiratory health and respiratory work disability. A total of 16.099 subjects participated. 

The most common respiratory outcomes among the responders were nasal allergies (30%), wheezing (27%) and chronic cough (21%). The prevalence of physician-diagnosed asthma was 11.5% and 29% of these reported an asthma attack in the past 12 months.

Furthermore, results showed that 14.906 subjects had been ever employed. Among these, 49% had been exposed to vapurs, gas, dust or fumes at work and 247 subjects (2%) had changed their jobs due to respiratory symptoms at work. 

Occupational exposures associated with respiratory symptoms and disease were flour, diisocyanates, welding/soldering fumes, vehicle/motor exhaust and environmental tobacco smoking. 

High risk occupations associated with change of work was cooks/chefs, hairdressers, gardeners, welders, sheet metal workers, cleaners and agricultures labors. The results from the Telemark study confirm the need to implement preventative measures within high-risk occupations to reduce the burden of respiratory diseases and respiratory work disability.   

Main supervisor

Anne Kristin M. Fell, Senior phy​sician​​,  Department of Occupational Medicine (Telemark Hospital), Associate Professor at Department of Global Public Health and Primary Care​ at Faculty of Medicine​ (University og Oslo)​​

Co-supervisor

Professor emeritus, Johny Kongerud, MD, Lungemedisinsk avdeling, Rikshospitalet Oslo Universitetssykehus, Institutt for klinisk medisin, UiO. 

Publications

1. ​Abrahamsen R, Svendsen MV, Henneberger PK, Gundersen GF, Torén K, Kongerud J, Fell AKM. Non-response in a cross-sectional study of respiratory health in Norway. BMJ Open 2016;6:e009912 doi:10.1136/bmjopen-2015-009912
2. Fell AKM, Abrahamsen R, Henneberger PK, Svendsen MV, Andersson E, Torén K, Kongerud J. Breath-taking jobs: a case-control study of respiratory work disability by occupation in Norway. Occup Environ Med 2016;73(9):600-606.
3. Anne Kristin Fell, Martin Veel Svendsen, Jeong-Lim Kim, Regine Abrahamsen, Paul K Henneberger, Kjell Torén, Paul D Blanc, Johny Kongerud,. Exposure to second hand tobacco smoke and respiratory symptoms in non-smoking adults: cross-sectional data from the general population in Telemark, Norway BMC Public Health 2018 Jun 6;18(1):843.
4. Bergqvist J, Bove M, Andersson A, Schiöler L, Klepaker G, Abrahamsen R, Fell AKM, Hellgren J. Chronic rhinosinusitis associated with chronic bronchitis in a five-year follow-up: the Telemark study. BMC Pulm Med. 2022 Nov 9;22(1):406.

​IV. Dårlig kontrollert astma

​Nurse Gølin F. Gundersen, Department of Occupational Medicine (Telemark Hospital), Skien, Norway.

Regine Abrahamsen, Senior phy​sician​​, PhD, Department of Occupational Medicine (Telemark Hospital)​, PhD​

About the subproject​

Denne studien hadde som mål å identifisere risikofaktorer forbundet med dårlig astmakontroll målt med det standardiserte spørreskjemaet astma kontroll test (ACT). I tillegg ønsket vi å estimere andelene av pasienter med dårlig kontrollert astma som har tatt pusteprøve (spirometri), brukt astmamedisin, eller blitt undersøkt av en lungelege. I 2014–2015 deltok 326 personer i alderen 16-50 år som hadde selvrapportert lege-diagnostisert astma og tilstedeværelse av luftveissymptomer de foregående 12 månedene. En ACT-poengsum lavere enn 19 ble definert som dårlig kontrollert astma. Det var 113 personer (35 %) som rapporterte dårlig astmakontroll. Faktorer assosiert med dårlig kontrollert astma var: selvrapportert eksponering i arbeid for damp, gass, støv eller røyk i løpet de siste 12 månedene, kropp masseindeks større enn 30 kg/m2, å være kvinne, nåværende og tidligere røyking. Dårlig astmakontroll var også assosiert med redusert lungefunksjon. Videre rapporterte 13 % av deltakerne med dårlig astmakontroll at de ikke brukte astmamedisiner, 51 % ikke hadde blitt vurdert av lungelege og 20 % aldri hadde utført spirometri. Våre data er ikke fra en studie som følger pasientene over tid, derfor er det nødvendig med flere studier som kartlegger risikofaktorer og måler eksponering i arbeid. Resultatene våre antyder imidlertid at det er rom for forbedring med hensyn til bruk av spirometri og henvisning til lungelege når pasientens astma er utilstrekkelig kontrollert.

Publications

1. Abrahamsen R, Gundersen GF, Svendsen MV, Klepaker G, Kongerud J, Fell AKM. Possible risk factors for poor asthma control assessed in a cross-sectional population-based study from Telemark, Norway. PLoS ONE 2020 15(5): e0232621.

​V. Occurence and ​​risk factors of  kronisk chronic sinusitis​

Ulrika S​​. Clarhed at Department of ​Ear, nose and Throat-diseases, Sahlgrenska Universitetssykehus in Gøteborg - is Research fellow in this project. 

About the subproject

​One in ten inhabitants of Telemark report that they have chronic rhinosinusitis (CRS). CRS is defined as either nasal congestion or runny nose for at least 12 weeks. Facial pain and reduced or loss of smell may also be present. CRS may result in a reduced quality of life due to, among other things, sleep difficulties. The condition can be both allergic and non-allergic, but for most patients the cause is unknown and causal factors may be multiple.

The purpose of the project is to estimate the incidence of chronic sinusitis in relation to exposure at work as well as lifestyle factors. The Telemark study was the first study to show a connection between exposure at work and CRS: those who are exposed to metal dust, cleaning agents and cooking fumes have an increased risk. In addition, we found that asthmatics and smokers had more CRS than others. 

There are few studies that have looked at the relationship between lifestyle factors such as weight and CHD over time. We investigated the relationship between new-onset CHD over a period of 5 years and obesity measured by BMI. A total of 5.769 people responded to the Telemark Study's questionnaire and had provided information about CRS, height and weight in 2013 and 2018. 

The results show that overweight defined as BMI over 25 kg/m2 gave a 53% higher risk of developing CRS compared to normal weight (BMI between 18.5 and 25). It is important that physicians who see patients with CRS are aware of these associations to be able to provide good guidance on exposure at work, lifestyle and weight reduction as part of the treatment of this common condition. The last part of the study will assess work ability and sick-leave in participants with CRS. 

Main supervisor

Professor Johan Hellgren, MD, Department of ​Otolaryngeology​, Sahlgrenska Hospital in Gøteborg/University in Gøteborg, Sverige.

Co-supervisors

• ​Professor Kjell Torén, MD, Department of Occupational and Environmental Medicine , Sahlgrenska Universitetssykehus in Gøteborg/University in Gøteborg, Sverige.
• Anne Kristin M. Fell, Senior Phy​sician​​, Associate Professor, Department of Occupational Medicine (Telemark Hospital), Department of Global Public Health and Primary Care​ at Faculty of Medicine​ (University og Oslo)​​

Publications

1. ​Clarhed UKE, Svendsen M, Schiöler L3, Kongerud J, Torén K, Hellgren J, Fell AK. Chronic rhinosinusitis related to occupational exposure - the Telemark population study. J Occup Environ Med 2018. DOI : 10.1097/JOM.0000000000001312
2. Clarhed UKE, Johansson H, Svendsen MV, Torén K, Fell AKM, Hellgren J. Occupational exposure and the risk of new-onset chronic rhinosinusitis - a prospective study 2013-2018. Rhinology. 2020 Jul 9. doi: 10.4193/Rhin20.104.
3. Clarhed UKE, Schiöler L, Torén K, Fell AKM, Hellgren J. BMI as a risk factor for the development of chronic rhinosinusitis: a prospective population-based study. Eur Arch Otorhinolaryngol. 2022 Mar 19. doi: 10.1007/s00405-022-07320-y. Epub ahead of print. PMID: 35305138.
4. Bergqvist J, Bove M, Andersson A, Schiöler L, Klepaker G, Abrahamsen R, Fell AKM, Hellgren J.Chronic rhinosinusitis associated with chronic bronchitis in a five-year follow-up: the Telemark study. BMC Pulm Med 2022 Nov 9;22(1):406. 

VI. Astmagenetikk studien: Rare variants in asthma

​The understanding of rare genetic variants’ contribution to asthma is limited. In this study targeted next-generation sequencing was used to investigate the effect of rare variants in asthma-associated loci with age of asthma onset. 

Exons and flanking intron sequences of 130 genes in asthma-associated regions were sequenced in 576 Norwegian asthma patients. The Sequence Kernel Association Test (SKAT) was applied for cumulative rare variant association analysis with asthma onset as outcome. Clinical data on the patients were available, and we have further investigated clinical differences among carriers and non-carriers of rare-variants of SKAT associated genes. The manuscript is in preparation.

Research coworkers

• ​Anne Kristin M. Fell, Senior phy​sician​​, associate professor, Department of Occupational Medicine (Telemark Hospital), Department of Global Public Health and Primary Care​ at Faculty of Medicine​ (University og Oslo)​​​
• Øystein L. Holla, PhD, Department of Medical Genetics, (Telemark Hospital)​.
• Øyvind L. Busk, PhD​, Department of Medical Genetics, (Telemark Hospital)​.
  
• Jens Kristoffer Hertel, PhD, Department of Morbid Obesity (Vestfold Hospital).​

References​

1. ​Nordang GBN, Busk ØL, Klepaker G, Page CM, LeBlanc M, Holla ØL and Fell AKM. Targeted sequencing of 130 asthma candidate genes and association testing of rare variants with age of onset in Norwegian asthma patients. Abstract ERS Munchen, 2021.

My researcher project is called «Heritable subfertility? How assisted reproductive technologies influence the reproductive health of offspring “, and the background for the project is that children of parents who have undergone assisted reproduction and/or are subfertile, carry an increased risk of various healthrelated condidtions.

What this study will establish is if the reproductive health of the children thus concieved is also affected, and if so, what genetical and epigenetical mechanisms that cause this transgenerational transferral of risk.

The project uses data from the Norwegian Mother and Child Cohort Study (MoBa), and is part of a larger research project at the Centre for Fertility and Health, a centre of excellence at the National Institute of Public Health.

The main and secondary aims of the study will be achieved by analyzing genetical tests from about 50000 complete mother/father/child trios, epigenetical tests from 2000 of these trios, and by collecting clinical data from young adults born into the MoBa cohort. Due to its extensive dataset, this study has statistical power to control for several potential confounders that have prevented previous studies in the field from making firm conclusions.

• ​Senter for fruktbarhet og helse, Folkehelseinstituttet, Oslo
• Spiren Fertilitetsklinikk, Trondheim

1. In vitro-fertilisering – nye metoder, nye muligheter, nye mennesker. Hanevik HI, Hessen DO. Tidsskr Nor Laegeforen. 2022 Nov 7;142(16). doi: 10.4045/tidsskr.22.0578. Print 2022 Nov 8.
2. Early menopause and epigenetic biomarkers of ageing. Lee Y, Hanevik HI. Reprod Biomed Online. 2022 Dec;45(6):1313. doi: 10.1016/j.rbmo.2022.09.016. Epub 2022 Sep 24.
3. Associations between epigenetic age acceleration and infertility. Lee Y, Bohlin J, Page CM, Nustad HE, Harris JR, Magnus P, Jugessur A, Magnus MC, Håberg SE, Hanevik HI. Hum Reprod. 2022 Aug 25;37(9):2063-2074. doi: 10.1093/humrep/deac147.
4. IVF and human evolution. Hanevik HI, Hessen DO. Hum Reprod Update. 2022 Jun 30;28(4):457-479. doi: 10.1093/humupd/dmac014.
5. The demographics of assisted reproductive technology births in a Nordic country. Goisis A, Håberg SE, Hanevik HI, Magnus MC, Kravdal Ø. Hum Reprod. 2020 Jun 1;35(6):1441-1450. doi: 10.1093/humrep/deaa055.

​​

Anne Kristin M. Fell, senior physician, 1st amanuensis II. STHF, UiO

Britt Randem, head physician, Department of Occupational and Environmental Medicine, Oslo University Hospital, Ullevål

Bendik Christian Brinchmann, Norwegian Institute for the Working Environment