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Chronic Obstructive Pulmonary Disease (COPD)

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

Magnus Sköld

Professor/senior physician
Forskargrupp M Sköld
Department of Medicine, Solna (MedS), K2

Chronic Obstructive Lung Disease (COPD)

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.

COPD is a disease with a prevalence of 10% and 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 of the COSMIC patient cohort has recently been finished where symptom registration, spirometry and high resolution computed tomography have been performed. The study will, in particular, gain knowledge on predisposing factors for developing of airway obstruction in smokers.

Chronic airway obstruction associated to prematurity

There are a number of other risk factors besides smoking for development of  chronic airway obstruction. We are interested in early events, i.e. 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 post-docs, are now compiling data and performing experiments looking on various aspects of pulmonary complications in adult age 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. A number of epidemiological studies suggest that at least 20-25 % of all COP-patients have never smoked. 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 individuals. In this group, we will identify persons 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 in some patients, with the aim of collecting airways and lung samples. Molecular phenotyping including, 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.

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. In a recent study, based on ICD codes, the incidence in Sweden was estimated to 13.9/100.000, and the prevalence to 68/100.000 in the year 2015. The exact prevalence of IPF in Sweden is, however, unknown. There is 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 build-up a national registry including 25 pulmonary units throughout the country. We use the same registry platform as in Finland, which makes it possible to directly compare two health care 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 bronchoscopy. This sub-project will provide not only basic data on disease manifestations 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.

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

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

Ioanna Kotortsi, MD, PhD-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, PhD-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 Medicine Solna

Giovanni Ferrara, associated, MD, PhD, Professor, University of Alberta, Edmonton, AB, Canada

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

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

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

Margitha Dahl, RN, research nurse

Susanne Schedin, 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, Hesselmans stiftelse, Swedish Medical Research Council, Karolinska Institutet.

Recent Publications Magnus Sköld (since 2014)

Structural changes and antibody enrichment in the lungs are early features of anti-citrullinated protein antibody-positive rheumatoid arthritis.
Reynisdottir G, Karimi R, Joshua V, Olsen H, Hensvold AH, Harju A, et al
2014 Jan;66(1):31-9

Distribution of T-cell subsets in BAL fluid of patients with mild to moderate COPD depends on current smoking status and not airway obstruction.
Forsslund H, Mikko M, Karimi R, Grunewald J, Wheelock ÅM, Wahlström J, et al
Chest 2014 Apr;145(4):711-722

Lung cancer-associated myofibroblasts reveal distinctive ultrastructure and function.
Karvonen HM, Lehtonen ST, Sormunen RT, Lappi-Blanco E, Sköld CM, Kaarteenaho RL
J Thorac Oncol 2014 May;9(5):664-74

Lung density on high resolution computer tomography (HRCT) reflects degree of inflammation in smokers.
Karimi R, Tornling G, Forsslund H, Mikko M, Wheelock Å, Nyrén S, et al
Respir. Res. 2014 Feb;15():23

Shared immunological targets in the lungs and joints of patients with rheumatoid arthritis: identification and validation.
Ytterberg AJ, Joshua V, Reynisdottir G, Tarasova NK, Rutishauser D, Ossipova E, et al
Ann. Rheum. Dis. 2015 Sep;74(9):1772-7

Interleukin-26 in antibacterial host defense of human lungs. Effects on neutrophil mobilization.
Che KF, Tengvall S, Levänen B, Silverpil E, Smith ME, Awad M, et al
Am. J. Respir. Crit. Care Med. 2014 Nov;190(9):1022-31

Organisation of diagnosis and treatment of idiopathic pulmonary fibrosis and other interstitial lung diseases in the Nordic countries.
Bendstrup E, Hyldgaard C, Altraja A, Sjåheim T, Myllärniemi M, Gudmundsson G, et al
Eur Clin Respir J 2015 ;2():

Signs of immune activation and local inflammation are present in the bronchial tissue of patients with untreated early rheumatoid arthritis.
Reynisdottir G, Olsen H, Joshua V, Engström M, Forsslund H, Karimi R, et al
Ann. Rheum. Dis. 2016 09;75(9):1722-7

Linoleic acid-derived lipid mediators increase in a female-dominated subphenotype of COPD.
Balgoma D, Yang M, Sjödin M, Snowden S, Karimi R, Levänen B, et al
Eur. Respir. J. 2016 06;47(6):1645-56

Pirfenidone and nintedanib modulate properties of fibroblasts and myofibroblasts in idiopathic pulmonary fibrosis.
Lehtonen ST, Veijola A, Karvonen H, Lappi-Blanco E, Sormunen R, Korpela S, et al
Respir. Res. 2016 Feb;17():14

Vital capacity and COPD: the Swedish CArdioPulmonary bioImage Study (SCAPIS).
Torén K, Olin AC, Lindberg A, Vikgren J, Schiöler L, Brandberg J, et al
Int J Chron Obstruct Pulmon Dis 2016 ;11():927-33

Idiopathic pulmonary fibrosis in Sweden: report from the first year of activity of the Swedish IPF-Registry.
Ferrara G, Carlson L, Palm A, Einarsson J, Olivesten C, Sköld M
Eur Clin Respir J 2016 ;3():31090

Safety and tolerability of acetylcysteine and pirfenidone combination therapy in idiopathic pulmonary fibrosis: a randomised, double-blind, placebo-controlled, phase 2 trial.
Behr J, Bendstrup E, Crestani B, Günther A, Olschewski H, Sköld CM, et al
Lancet Respir Med 2016 06;4(6):445-53

A retrospective chart review of pirfenidone-treated patients in Sweden: the REPRIS study.
Sköld CM, Janson C, Elf ÅK, Fiaschi M, Wiklund K, Persson HL
Eur Clin Respir J 2016 ;3():32035

Gender differences in the T-cell profiles of the airways in COPD patients associated with clinical phenotypes.
Forsslund H, Yang M, Mikko M, Karimi R, Nyrén S, Engvall B, et al
Int J Chron Obstruct Pulmon Dis 2017 ;12():35-48

The lung microbiota in early rheumatoid arthritis and autoimmunity.
Scher JU, Joshua V, Artacho A, Abdollahi-Roodsaz S, Öckinger J, Kullberg S, et al
Microbiome 2016 11;4(1):60

Translation and validation of the King's Brief Interstitial Lung Disease (K-BILD) questionnaire in French, Italian, Swedish, and Dutch.
Wapenaar M, Patel AS, Birring SS, Domburg RTV, Bakker EW, Vindigni V, et al
Chron Respir Dis 2017 May;14(2):140-150

Treatment of idiopathic pulmonary fibrosis: a position paper from a Nordic expert group.
Sköld CM, Bendstrup E, Myllärniemi M, Gudmundsson G, Sjåheim T, Hilberg O, et al
J. Intern. Med. 2017 02;281(2):149-166

Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin-lysoPA axis in COPD.
Naz S, Kolmert J, Yang M, Reinke SN, Kamleh MA, Snowden S, et al
Eur. Respir. J. 2017 06;49(6):

Measures of bronchodilator response of FEV1, FVC and SVC in a Swedish general population sample aged 50-64 years, the SCAPIS Pilot Study.
Torén K, Bake B, Olin AC, Engström G, Blomberg A, Vikgren J, et al
Int J Chron Obstruct Pulmon Dis 2017 ;12():973-980

Mutational status predicts the risk of thromboembolic events in lung adenocarcinoma.
Davidsson E, Murgia N, Ortiz-Villalón C, Wiklundh E, Sköld M, Kölbeck KG, et al
Multidiscip Respir Med 2017 ;12():16

Lung function development after preterm birth in relation to severity of Bronchopulmonary dysplasia.
Um-Bergström P, Hallberg J, Thunqvist P, Berggren-Broström E, Anderson M, Adenfelt G, et al
BMC Pulm Med 2017 Jun;17(1):97

Interleukin-26 Production in Human Primary Bronchial Epithelial Cells in Response to Viral Stimulation: Modulation by Th17 cytokines.
Che KF, Kaarteenaho R, Lappi-Blanco E, Levänen B, Sun J, Wheelock Å, et al
Mol. Med. 2017 10;23():247-257

Enhanced CD8+ cytolytic T cell responses in the peripheral circulation of patients with sarcoidosis and non-Löfgren's disease.
Parasa VR, Forsslund H, Enger T, Lorenz D, Kullberg S, Eklund A, et al
Respir Med 2018 05;138S():S38-S44

Long-term smoking alters abundance of over half of the proteome in bronchoalveolar lavage cell in smokers with normal spirometry, with effects on molecular pathways associated with COPD.
Yang M, Kohler M, Heyder T, Forsslund H, Garberg HK, Karimi R, et al
Respir. Res. 2018 03;19(1):40

Proteomic profiling of lung immune cells reveals dysregulation of phagocytotic pathways in female-dominated molecular COPD phenotype.
Yang M, Kohler M, Heyder T, Forsslund H, Garberg HK, Karimi R, et al
Respir. Res. 2018 03;19(1):39

Best supportive care for idiopathic pulmonary fibrosis: current gaps and future directions.
Ferrara G, Luppi F, Birring SS, Cerri S, Caminati A, Sköld M, et al
Eur Respir Rev 2018 Mar;27(147):

Integration of multi-omics datasets enables molecular classification of COPD.
Li CX, Wheelock CE, Sköld CM, Wheelock ÅM
Eur. Respir. J. 2018 05;51(5):

Bronchoalveolar lavage (BAL) cells in idiopathic pulmonary fibrosis express a complex pro-inflammatory, pro-repair, angiogenic activation pattern, likely associated with macrophage iron accumulation.
Lee J, Arisi I, Puxeddu E, Mramba LK, Amicosante M, Swaisgood CM, et al
PLoS ONE 2018 ;13(4):e0194803

The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers.
Che KF, Tufvesson E, Tengvall S, Lappi-Blanco E, Kaarteenaho R, Levänen B, et al
Clin. Sci. 2018 05;132(9):959-983

Delay and inequalities in the treatment of idiopathic pulmonary fibrosis: the case of two Nordic countries.
Pesonen I, Carlson L, Murgia N, Kaarteenaho R, Sköld CM, Myllärniemi M, et al
Multidiscip Respir Med 2018 ;13():14

Long-term safety of pirfenidone: results of the prospective, observational PASSPORT study.
Cottin V, Koschel D, Günther A, Albera C, Azuma A, Sköld CM, et al
ERJ Open Res 2018 Oct;4(4):

An LC-MS/MS workflow to characterize 16 regio- and stereoisomeric trihydroxyoctadecenoic acids.
Fuchs D, Hamberg M, Sköld CM, Wheelock ÅM, Wheelock CE
J. Lipid Res. 2018 10;59(10):2025-2033

The bacteriology in adult patients with pneumonia and parapneumonic effusions: increased yield with DNA sequencing method.
Johansson N, Vondracek M, Backman-Johansson C, Sköld MC, Andersson-Ydsten K, Hedlund J
Eur. J. Clin. Microbiol. Infect. Dis. 2019 Feb;38(2):297-304

Patient journey and treatment patterns in adults with IPF based on health care data in Sweden from 2001 to 2015.
Sköld CM, Arnheim-Dahlström L, Bartley K, Janson C, Kirchgaessler KU, Levine A, et al
Respir Med 2019 Aug;155():72-78

The viral protein corona directs viral pathogenesis and amyloid aggregation.
Ezzat K, Pernemalm M, Pålsson S, Roberts TC, Järver P, Dondalska A, et al
Nat Commun 2019 05;10(1):2331

Pulmonary outcomes in adults with a history of Bronchopulmonary Dysplasia differ from patients with asthma.
Um-Bergström P, Hallberg J, Pourbazargan M, Berggren-Broström E, Ferrara G, Eriksson MJ, et al
Respir. Res. 2019 May;20(1):102

Patient journey and treatment patterns in adults with IPF based on health care data in Sweden from 2001 to 2015.
Sköld CM, Arnheim-Dahlström L, Bartley K, Janson C, Kirchgaessler KU, Levine A, et al
Respir Med 2019 Aug;155():72-78

Secretory anti-citrullinated protein antibodies in serum associate with lung involvement in early rheumatoid arthritis.
Roos Ljungberg K, Joshua V, Skogh T, Eklund A, Sköld CM, Svärd A, Catrina AI,Kastbom A.
Rheumatology 2019 (in press).

Visual and Quantitative Evaluation of Emphysema: A Case-Control Study of 1111 Participants in the Pilot Swedish CArdioPulmonary BioImage Study (SCAPIS).
Vikgren J, Khalil M, Cederlund K, Sörensen K, Boijsen M, Brandberg J, et al
Acad Radiol 2019 Jul;():