Unit of lung and airway research

Inhaled substances and gases constitute important risk factors in the development of chronic obstructive pulmonary disease (COPD), which is now the third most common disease-related cause of death in the world according to the WHO, affecting more than 400 000 patients in Sweden alone. In industrialized countries, tobacco smoking is the main risk factor, while in developing countries, other types of burning of biomass, such as open fires using wood and biofuels indoors, are believed to be important risk factors.

Recent epidemiological studies indicate that between 5 and 15% of the COPD cases in industrialized countries relate to exposures in the work environment, such as construction and farming. This means that these environmental exposures account for a substantial number of patients with COPD. Additional types of environmental exposures may contribute to clinical cases as well, including air pollution such as combustion exhaust with particulate matter outdoors. 

Inhaled compounds constitute a risk factor in asthma as well, a chronic airway disease that is very common in industrialized countries. In Sweden, the total number of patients with asthma is estimated to be around as much as 1 000 000, although the mortality is very low. Apart from the latter, certain phenotypes of asthma display features that resemble those in COPD. One such feature is the development of chronic airflow limitation in elderly patients. Another such feature is the occurrence of comorbidities.

Airway infections affect the clinical course in both asthma and COPD, in some patients more than in others, especially in those who also suffer from chronic bronchitis or bronchiectasis. Unfortunately, there is currently no specific treatment that directly counteracts this susceptibility to infections. Most likely, this is due to the poor understanding of fundamental disease mechanisms at the cellular and molecular level.

It is well established that both asthma and COPD are characterized by a considerable accumulation of immunologically active leukocytes in the airways. This accumulation includes innate effector cells, such as neutrophils, eosinophils and macrophages, but also different subpopulations of adaptive immune cells, including both lymphocytes and lymphoid cells. The fact that there is an increased susceptibility to infections despite the increased number of innate effector cells represents an immunological paradox that is poorly understood. This makes it likely that, in both COPD and asthma, it is the coordination of antibacterial function rather than the quantity of these innate effector cells that is missing. This may also be the case in chronic bronchitis and in bronchiectasis, common comorbidities of asthma and COPD with similar immunological aberrations. Along these lines, there is ample evidence that immune signaling via cytokines from lymphocytes directs innate effector cells, and that critical regulators of this immune signaling can be released due to the stimulation of microbial receptors located on immunologically active cells in the exposed organ, whether antigen-presenting or structural cells.

Our line of research is based on the idea that long-term exposure to environmental compounds, such as smoke from burning biomass including tobacco, biofuel, organic dust, small particles, exhaust with particulate matter from combustion engines, causes detrimental alterations in important immune signaling leading to chronic airway disease. We think that these alterations impair the ability of the affected host to cope with microbial stimuli. To address these matters, we characterize the effects of environmental factors on immune signaling in host defence of the airways. We investigate this immune signaling by comparing conditions in patients with chronic airway disease to those of healthy controls, but also in model studies. We map the underlying cellular and molecular mechanisms primarily in relevant body fluids, in tissue, and in primary and genetically modified cells from humans. By combining these studies, we strive to identify new cellular and molecular targets for diagnosis and monitoring of chronic airway disease, ultimately for treatment and prevention as well.

• Th17-associated cytokines and host defense in smokers
• The IL-36 family of cytokines in chronic obstructive pulmonary disease
• Cadmium as a pathogenic factor in tobacco smokers