​The COVID-19 study in Telemark and Agder - COVITA

​Forskningsgruppen har sitt utspring i befolkningsundersøkelsen ‘Telemarkstudien’ som ble initiert ved Sykehuset Telemark i 2013. Forskningsgruppen for epidemiologi ble etablert i 2022 med Anne Kristin M. Fell som leder og Hans Ivar Hanevold som nestleder. Gruppen har en bred portefølje av epidemiologiske forskningsprosjekter. Gruppen hadde i 2022 fem doctoral research fellows.​

The researchteam was founded on the populationsurvey in The Telemark Study , initiated by Telemark Hospital in 2013. The researchteam of Epidemyology was establisher in 2022. Head of the group is Anne Kristin M Fel, and Deputy head is Hans Ivar Hanevold. I 2022 the team had five doctoral research fellows.  ​​

About the study

​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.

Project​eam

• ​Prinsipal investigator, PhD-main supervisor Anne Kristin M. Fell, MD, Associate professor at the Institute of Health and Society, University of Oslo (UiO), senior physician at the Dep. of Occupational and Environmental Medicine, TH. 
• 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).

​Research cooperators

• ​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. 

Publications

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

​​

The Telemark study

​This is the ​mots exten​​sive​ study of its kind in Norway, and is the first medical ​​investigation to ​​survey respiratory diseases and impact over time among ​adults over time in Telemark. In the first part of The Telemark Study we gained new knowledge about ​causes to respiratory diseases ​and cronical respiratory diseases. The results dre attention both nati​​onal and international.  ​

Projectmanager ​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) 

The project is funded by Telemark Hospital ​​with grants from Norges Astma og Allergiforbund, Norsk forening for Lungemedisin og Sigrid Wolmars legat.

​About The Telemark Study

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 up to 50%. The Telemark study, is a large population survey among adults born between 1963 and 1997 and living in the Telemark area. The study aims to work for 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 work, information on nutrition and physical activity and, in addition, clinical data and a biobank that provides new knowledge about why respiratory disease occurs. 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.

Research cooperators

• ​Professor emeritus Kjell Torén, MD, Dep. of Occupational and Environmental Medicine/University of Gothenburg, Sweden.
• Epidemiologist Paul Henneberger, 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, Lungemedisinsk avdeling, Rikshospitalet Oslo Universitetssykehus, Institutt for klinisk medisin, UiO. 
• Professor Johan Hellgren, MD, øre-nese-hals avdelingen, Sahlgrenska Universitetssykehus i Gøteborg/Universitetet i Gøteborg, Sverige.
  
  

Subproject I of The Telemark Study

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

​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 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.

Supervisors research

Main supervisor: Professor emeritus, Johny Kongerud, MD, Dep. of Respiratory Medicine, OUS, Rikshospitalet, Oslo, Norway.

Co-supervisors 

• ​Anne Kristin M. Fell, MD, 1. amanuensis II, avdeling for arbeidsmedisin, STHF, Avdeling for Samfunnsmedisin og global helse, institutt for helse og samfunn, UiO. 
• Øystein L. Holla, PhD, Seksjon for medisinsk genetikk, STHF.
• Jens Kristoffer Hertel, PhD, Senter for sykelig overvekt, SiV.

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. 

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

Nikola Zivadinovic overlege, avdeling for arbeidsmedisin, Sykehuset Telemark, PhD kandidat. 

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 included 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.

Main supervisor

 Anne Kristin M. Fell, overlege, 1. amanuensis II, avdeling for arbeidsmedisin, STHF, Avdeling for Samfunnsmedisin og global helse, institutt for helse og samfunn, UiO. 

Co-supervisors

• ​Regine Abrahamsen, overlege, PhD, avdeling for arbeidsmedisin, STHF. 
• 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, overlege, PhD, avdeling for arbeidsmedisin, STHF.

NOR

I sin avhandling har Regine Abrahamsen og medarbeidere ett på data som ble samlet inn i første del av Telemarkstudien. Forekomsten av luftveisplager og astma i Telemark var ikke kjent før studien startet, men man visste at forbruket av medisiner for behandling av lungesykdommer i Telemark var over landsgjennomsnittet. Av de 16.099 som svarte på spørreskjemaet, hadde 11.5 % prosent av lege-diagnostisert astma. Dette er sammenlignbart med landsgjennomsnittet og understreker betydningen av å fokusere på mulige tiltak for å forebygge at folk blir syke og må behandles for sin lungesykdom. Videre svarte 30 % av voksne at de hadde allergi som førte til neseplager og 27 % at de hadde opplevd piping i brystet. I tillegg svarte to prosent at de hadde måttet bytte jobb på grunn av pustebesvær i forbindelse med sitt arbeide. Blant disse var det yrkene kokk, platearbeider, sveiser, gartner, frisør, renholder og ansatte på bondegård som hadde økt risiko for jobb-bytte, mens arbeid innenfor jordbruk, fiskeindustri, håndverk og handel var forbundet med økt risiko for å utvikle luftveisplager. Studien visste også at de som blir utsatt for melstøv, isocyanater, sveiserøyk, eksos og passiv røyking hadde en økt risiko for å utvikle enkelte luftveisplager. Denne kunnskapen er viktig for å bidra til mer effektiv forebygging av luftveisplager og astma blant voksne.

ENG

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.   

Hovedveileder: Anne Kristin Møller Fell, MD, 1. amanuensis II, avdeling for arbeidsmedisin, STHF, Avdeling for Samfunnsmedisin og global helse, institutt for helse og samfunn, Universitetet i Oslo. 

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

Publikasjoner:

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

Sykepleier Gølin F. Gundersen, Department of Occupational and Environmental Medicine, Telemark Hospital, Skien, Norway.

Regine Abrahamsen, MD, PhD, Department of Occupational and Environmental Medicine, Telemark Hospital, Skien, Norway. 

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.

Publikasjoner:

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. Forekomst og risikofaktorer for kronisk bihulebetennelse 

Overlege Ulrika S. Clarhed ved Øre-nese-hals avdelingen, Sahlgrenska Universitetssykehus i Gøteborg er PhD-stipendiat i prosjektet.

Omlag hver tiende innbygger i Telemark rapporterer at de har kronisk bihulebetennelse (KBB). KBB er definert som enten tett nese eller rennende nese over minst 12 uker. Ansiktssmerter og redusert/tap av luktesans kan også være til stede. KBB kan gi redusert livskvalitet blant annet grunnet søvnvansker. Tilstanden kan være både allergisk og ikke-allergisk, men for de fleste pasienter med er årsaken ukjent og årsaksfaktorene flere. Formålet med prosjektet er å kartlegge forekomsten av kronisk bihulebetennelse i relasjon til ulike kjente og hittil ukjente påvirkninger i arbeid og fritid. Telemarkstudien var den første studien som viste sammenheng mellom eksponering i arbeid og KBB: de som blir utsatt for metallstøv, rengjøringsmidler og stekos på jobben har økt risiko. I tillegg fant vi at astmatikere og røykere hadde mer bihulebetennelse enn andre. Det finnes få studier som har sett på sammenhengen mellom livsstilsfaktorer som vekt og KBB over tid. Vi undersøkte sammenhengen mellom nyoppstått KBB over en periode på 5 år og overvekt målt ved BMI. Tilsammen 5.769 personer, svarte på Telemarkstudiens spørreskjema og hadde gitt opplysninger om KBB, høyde og vekt i 2013 og 2018. Resultatene viser at overvekt definert som BMI over 25 kg/m2 gav 53 % høyere risiko for å utvikle KBB sammenliknet med normal vekt (BMI mellom 18.5 og 25). Det er viktig at leger som møter pasienter med KBB er klar over disse sammenhengene for å kunne gi god veiledning om arbeid, livsstil og vektreduksjon som en del av behandlingen av denne vanlige tilstanden. 

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.

Hovedveileder: professor Johan Hellgren, MD, øre-nese-hals avdelingen, Sahlgrenska Universitetssykehus i Gøteborg/Universitetet i Gøteborg, Sverige.

Biveiledere: 

• Professor: biveileder Kjell Torén, MD, Arbeids- og miljømedisinsk avdeling, Sahlgrenska Universitetssykehus i Gøteborg/Universitetet i Gøteborg, Sverige. 

• Biveileder 1. amanuensis II, Anne Kristin M. Fell, MD, avdeling for arbeidsmedisin, STHF, Avdeling for Samfunnsmedisin og global helse, institutt for helse og samfunn, UiO. 

Publikasjoner:

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

NOR

I dette prosjektet har vi benyttet målrettet neste-generasjons sekvensering for å undersøke sjeldne genetiske varianters effekt på sykdomsdebut blant pasienter med astma rekruttert gjennom Telemarkstudien. Sjeldne varianter med allelfrekvens < 1 % i 130 gener tidligere assosiert med astma har blitt kartlagt i et materiale på 576 pasienter. Ved å benytte Sequence Kernel Association Test (SKAT) har vi undersøke for en kumulativ effekt for de sjeldne variantene på sykdomsdebut. Da vi har tilgang på klinisk data på pasientene, har vi videre undersøk om det er kliniske signifikante forskjeller på pasienter med og uten sjeldne varianter i SKAT assosierte gener. Artikkel fra den siste delen av genstudien er under utarbeidelse. 

ENG

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

Samarbeidspartnere:

• Anne Kristin M. Fell, overlege, 1. amanuensis II, avdeling for arbeidsmedisin, STHF, Avdeling for Samfunnsmedisin og global helse, institutt for helse og samfunn, UiO.

• Øystein L. Holla, PhD, Seksjon for medisinsk genetikk, STHF.

• Øyvind L. Busk, PhD, Seksjon for medisinsk genetikk, STHF.

• Jens Kristoffer Hertel, PhD, Senter for sykelig overvekt, SiV.

Referanser:

5. 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.

Heritable subfertility? How assisted reproductive technologies influence the reproductive health of offspring

Hans Ivar Hanevik, Medisinsk ansvarlig overlege ved Fertilitetsavdelingen Sør, STHF og forsker ved Senter for fruktbarhet og helse, Folkehelseinstituttet

Prosjektet er finansiert av Sykehuset Telemark HF med del-finansiering fra Norges Forskningsråd gjennom ordningen Sentre for fremragende forskning, prosjekt nummer 262700.

NOR

Bakgrunnen for prosjektet er at det er kjent at barna til foreldre som har blitt behandlet med assistert befruktning, og/eller er subfertile, har en økt risiko for ulike helseplager. Denne studien vil etablere om den reproduktive helsen til barna også er påvirket negativt, og undersøke hvilke genetiske og epigenetiske mekanismer som i så tilfelle ligger til grunn. Prosjektet gjennomføres med data fra MoBa undersøkelsen ved Folkehelseinstituttet i Oslo, og er del av et større prosjekt (START-prosjektet) på Senter for Fruktbarhet og Helse (CeFH) der. CeFH er et Senter for Fremragende Forskning under Forskningsrådet, og jeg er ansatt både ved CeFH og STHF. Prosjektets hoved og delmål vil oppnås ved analyser av genetiske undersøkelser på 50000 komplette mor/far/barn trioer, epigenetiske undersøkelser av 2000 slike trioer og innsamling av nye kliniske data fra unge voksne som ble født inn i MoBa kohorten. Med sitt omfattende datatilfang har studien styrke til å kunne kontrollere for ulike bakenforliggende faktorer som fram til i dag har umuliggjort solide konklusjoner i liknende studier.

ENG

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.

Samarbeidspartnere:

• Senter for fruktbarhet og helse, Folkehelseinstituttet, Oslo

• Spiren Fertilitetsklinikk, Trondheim

Publikasjoner:

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.

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