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 minute 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 of interest. We collaborate with a number of highly skilled laboratories depending on our research questions, using various methods including immunohistochemistry, flow cytometry, PCR, cell culture techniques and omics methods. During the last year, the research group has also been involved in projects dealing with Covid-19.
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. 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.
Chronic Obstructive Lung Disease (COPD)
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 now been finished where symptom registration, spirometry and high-resolution computed tomography are 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. 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.
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 have identified persons with chronic airway obstruction who have never smoked. These individuals, and appropriate control groups, have been invited to each clinic for in-depth clinical characterization. Associating factors, including occupational and environmental, will be identified. Bronchoscopy have been 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. during 2023, patient inclusion was closed and compilation of data and additional analyses are now in progress.
Our research group are also involved in a 9-year follow-up of the main SCAPIS study which will take place from 2024. Spirometry, diffusion capacity and impulse oscillometry will then be performed.
Covid-10 projects
The research group are also involved in projects dealing with Covid-19. In the project “Pathphysiology, diagnosis and follow-up of Covid-19 and related diseases: an imaging approach, ImCOV, (PI Sven Nyren, associate professor, Dept Radiology, Karolinska University Hospital Solna and Mats Danielsson, professor, the Royal Institute of Technology (KTH) we aim to examine in what way imaging can be combined with patient related data to improve clinical decision-making in patients with Covid-19 and similar conditions by developing deep neural networks (AI).