Unit of Lung and Airway Research
Environmental impact on host defence in chronic airway obstruction and chronic bronchitis
Inhaled compounds are likely to be of importance for the development of chronic airway obstruction such as chronic obstructive pulmonary disease (COPD), now the 4th most common disease-related cause of death in the world according to the WHO. For COPD, smoke from tobacco and other types of biomass constitute important causative risk factors. However, recent studies suggest that exposure in the working environment, such as building or animal keeping, may also be important risk factors for developing COPD and its comorbidities chronic bronchitis and emphysema.
Inhaled compounds may also contribute to chronic airway obstruction in asthma, that together with COPD affect more than 10% of the population in industrialized countries like Sweden. Not surprising, asthma and COPD share certain features in the pathology and the comorbidities, such as chronic bronchitis and frequent infections. For both asthma and COPD, infections are closely linked to the clinical course of the patients.
In reality, chronic bronchitis is an important comorbidity both in asthma and COPD and it is linked to increased risk for infections. Unfortunately, there is no effective pharmacotherapy for the increased susceptibility to both bacterial and viral infections in these dirsorders.
It is known that both asthma and COPD are associated with an accumulation of leukocytes including innate effector cells in the airways. Macrophages and neutrophils as well as eosinophils may be accumulated and their products are likely to be involved in the pathogenic mechanisms driving disease. The fact that these innate effector cells are accumulated even when patients are free from clinical infections and bacteria are not detected may appear as paradoxical since these effector cells normally kill bacteria. This particular phenomenon emphasizes the possibility that it is the coordination of innate immunity that is at fault in asthma in COPD, presumably also in chronic bronchitis. Unfortunately, there is no established conceptual understanding of the mechanisms behind these phenomena.
There is evidence for alterations in immune signaling that are linked to asthma and COPD but not specifically for chronic bronchitis. There is also support for the idea that receptors for microbial compounds are dysregulated in these conditions. Our current research is centered around the idea that long-term exposure to environmental factors such as smoke from tobacco and other types of biomass, organic dust, small particles and nanoparticles, exhaust from combustion engines as well as certain metals, per se contributes to the dysregulation of the innate immune response in the airways of patients with asthma, COPD and chronic bronchitis.
In our research unit, we characterize environmental impact with reference to the above mentions factors and their effects on pulmonary host defence in human subjects with and without different types of chronic airway obstruction and chronic bronchitis. We utilize patient cohorts as well as population cohorts and, when needed, animal and primary cell models such as an unique human 3D airway model. We reveal the underlying cellular and molecular mechanisms of relevance. Ultimately, our studies may lead to the identification of critical pathogenic mechanisms and novel targets for diagnosis, monitoring and therapy of asthma, COPD and chronic bronchitis, all constituting patient groups with a substantial unmet medical need.
Head of Unit
|Karlhans Che||Assistant professor, Postdoc|
|Melissa Kovach||Senior researcher|
|Bettina Levänen||Senior lab manager|
|Anders Lindén||Professor/senior physician|
- 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
- Lung development and COPD