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Idiopathic pulmonary fibrosis (IPF)

Research group Magnus Sköld

Professor/överläkare

Magnus Sköld

Telefon: 08-517 748 43
Enhet: Forskargrupp M Sköld
E-post: Magnus.Skold@ki.se

Our research group focus on clinical research on common respiratory disorders. We study well characterized patient cohorts carefully phenotyped and we use various laboratory techniques, collaborating with a number of laboratories both within Karolinska Institutet and other universities including international.

Characterization of the patients is crucial and includes symptoms (questionnaires), lung function tests (spirometry, body plethysmography, diffusion capacity, and impulse oscillometry), imaging (Chest X-ray and computer tomography), 6 minutes walk test, echocardiography and blood chemistry. Sampling of biological material from the lung is performed by bronchoscopy where tissues and cells from the large and from the small airways are harvested.

We are interested in exploring inflammatory mechanisms in the lung and systemically in common respiratory disorders. Specifically the link between the inflammatory response and development of structural changes (remodeling) in the lung is explored. We collaborate with a number of highly skilled labs depending on our research questions, using a various methods including immunohistochemistry, flow cytometry, PCR, cell culture techniques and omics methods.

Idiopathic pulmonary fibrosis (IPF)

Idiopathic pulmonary fibrosis (IPF) is a deadly, progressive form of lung fibrosis, with a reported median survival of 2-5 year. The disease is characterized by progressive cough and dyspnoea and the disease result in increased healthcare resources utilization and high direct medical costs. An estimation of incidence is 7-16/100.000 and a prevalence of 14-42 /100.000. The prevalence of IPF in Sweden is, however, unknown and there is therefore a need to establish new tools to characterize this disease to enable a rational allocation of resources inside the national health-care program. We also need to build up a solid platform to enable translational research to detect new biomarkers and new therapy targets.

The program will target the goal to create a national registry for IPF and a highly qualified translational centre for the diagnosis and care of IPF and rare lung diseases in Stockholm. We have started to build-up a national registry including pulmonary departments throughout the country. We use the same registry platform as in Finland, wich makes it possible to directly compare two health systems. In addition, the set up of a biobank to collect biological samples from patients with IPF for research purposes is in progress. Currently, we collect blood cells and serum/plasma, but in a near future we are planning to include samples from the upper and lower respiratory tract and tissue obtained by bronchoscopic cryobiopsies. This sub-project will provide not only basic data on incidence and prevalence of IPF in Sweden, but also, in a longer perspective, shed light on inflammatory and fibrotic mechanisms on this devastating model of an interstitial lung disease.

Chronic Obstructive Pulmonary Disease (COPD)

COPD is a disease with a prevalence of 10% and it is increasing with age. The patients experience dyspnoea, cough but have also significant co-morbidities and systemic manifestations. There are obvious gender differences both in the epidemiology and in the clinical presentation of the disease. In addition, manifestations of COPD caused by chronic cigarette smoking also vary between different individuals of the same sex. This leads to the consequence that COPD patients differ in particular with regard to emphysema, bronchitis, bronchiolitis, reversibility of bronchodilators rate of exacerbations and systemic involvement. The reasons for development of these various responses to cigarette-smoke exposure are largely unknown.

Smoking-associated COPD

In a cohort of 40 COPD-patients, 40 smokers with normal lung function and 40 neversmokers (Karolinska COSMIC study) we have made significant attempts, by performing bronchoscopy, to characterize inflammation and structural changes in various levels in the airways as well as in the systemic circulation. A 9-year follow-up has recently been initiated where the COSMIC cohort are invited to the clinic for symptoms registration, spirometry and high resolution computed tomography. The study will, in particular, gain knowledge on predisposing factors for developing of airway obstruction in smokers.

Chronic airway obstruction associated to prematurity

Risk factors for chronic airway obstruction are low birth weight and premature birth. In collaboration with Sachs´ Childrens Hospital, Södersjukhuset, Stockholm, adult prematurely born children with and without bronchopulmonary dysplasia (PBD) are compared with mild asthmatics and matched healthy neversmokers in a cross-sectional study (LUNAPRE-study). Bronchoscopy, imaging, lung function tests, echocardiography is, among other methods, used. The study will explore one explanation to chronic airway obstruction not caused by tobacco smoke. The clinical part has recently been completed and a number of researchers, including PhD students and postdocs, are now compiling data and performing experiments looking on various aspects of pulmonary complications due to prematurity.

Chronic airway obstruction in neversmokers (BRONCHO-SCAPIS study)

Recently, it has become evident that chronic airway obstruction in never-smokers is more prevalent than previously known. In this national multicenter study we will identify factors associated with chronic airway obstruction in never-smokers and to determine the molecular mechanisms of this disease in order to find potential targets for intervention. Also, we will identify prognostic markers in early stages of disease.

This National project was in 2016 awarded the annual big research grant (SEK 15 000 000) from the Swedish Heart-Lung Foundation. The project are based on a national population-based cohort Swedish CArdioPulmonary bioImage Study (SCAPIS) including 30 000 well characterized persons. In this group, we will identify individuals with chronic airway obstruction who have never smoked. These patients, and appropriate control groups, will be invited to each clinic for in-depth clinical characterization. Associating factors, including occupational and environmental, will be identified. Bronchoscopy will be performed, with the aim of collecting airways and lung samples. Molecular phenotyping including identification of T cell subsets, immunohistochemistry and "omics" strategies will take place. A research network including six university hospitals in Sweden (Umeå, Uppsala, Stockholm, Linköping, Gothenburg, Lund) have been formed. In 2017, the first patients were screened in Stockholm and currently all six university sites are including.

The research group

Magnus Sköld, Group leader, Professor of Respiratory Medicine, MD, PhD, Department of Medicine Solna, Karolinska Institutet, Senior Consultant, Lung-Allergy Clinic, Karolinska University Hospital

Giovanni Ferrara, , MD, PhD, Associate Professor, Senior Consultant, Lung-Allergy Clinic, Karolinska University Hospital Solna

Reza Karimi, MD, PhD, Senior Consultant, Lung-Allergy Clinic, Karolinska University Hospital Solna

Ioanna Kotortsi, MD, Ph D-student, ST Respiratory Medicine, Lung-Allergy Clinic, Karolinska University Hospital Solna

Petra Um Bergström, PhD-student, MD, Senior Consultant, Pediatric Clinic, Sachs´ Childrens Hospital, Södersjukhuset, Stockholm

Ida Pesonen, MD, Ph D-student, ST Respiratory Medicine, Lung-Allergy Clinic, Karolinska University Hospital Solna

Melvin Pourbazargan, MD, PhD-student, ST Internal Medicine, Karolinska University Hospital Huddinge

Dimitrios Kalafatis, MSc, PhD-student, Division of Respiratory Medicine, Dept of Medicine Solna

Jing Gao, MD, PhD, post doc, Division of Respiratory Medicine, Dept Medicine Solna

Maria Ahlsén, PhD, national study co-ordinator BRONCHO-SCAPIS

Lisa Carlson, RN, research nurse, co-ordinator Swedish National IPF registry

Heta Merikallio, PhD, post doc, Division of Respiratory Medicine, Dept Medicine Solna

Heléne Blomqvist, research nurse, co-ordinator BRONCHO-SCAPIS, clinical part

Benita Engvall, BMA, co-ordinator BRONCHO-SCAPIS, laboratory part

Margitha Dahl, RN, research nurse

Emma Sundström, RN, research nurse

Charlotte Rivero, RN, research nurse

Eva-Marie Karlsson, research administrator

Funding

Swedish Heart-Lung Foundation, ALF Medicine (Karolinska Institutet and Stockholm County Council), Swedish Asthma and Allergy Foundation, King Gustaf V and Queen Victorias Freemasons Foundation, Swedish Medical Research Council, Karolinska Institutet.

Recent Publications Magnus Sköld

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Recent publications Giovanni Ferrara