Unit of Lung and Airway Research
Environmental impact on host defence in obstructive airway diseases
Inhaled substances are a major factor in the development of chronic obstructive pulmonary disease (COPD), which will be the third most common cause of death in the world in the near future according to the WHO. In industrialised countries, tobacco smoking is the main risk factor, while in developing countries open fires using wood and biofuel are are important risk factors. In recent years, around 15% of the COPD cases in industrialised countries have been related to work environment exposures, for example in construction and farming. This means that the work environment exposures are a considerable risk factor for a substantial number of patients with COPD, as this disease may affect as many 700 000 patients in Sweden alone.
Inhaled substances constitute a risk factor also in asthma, a disease that just like COPD is very common in industrialised countries. In Sweden the total number of patients with asthma is estimated to be around 1 000 000 and this disease displays features similar to those in COPD. For example, this is true for the development of chronic airflow obstruction in elderly patients. There is also a resemblance for comorbidities, such as an increased occurrence of chronic bronchitis and airway infections.
Airway infections affect the clinical course in both asthma and COPD, in particular for patients who also suffer from chronic bronchitis. Unfortunately, there is no specific treatment to counteract this increased susceptibility to infections. This is primarily due to the insufficient knowledge about the fundamental disease mechanisms at the cellular and molecular level.
It is well established that both asthma and COPD are characterised by a considerable accumulation of immune cells in the airways. This accumulation includes the most effective antibacterial immune cells in the body, namely macrophages and neutrophils. In these patients, there is an increased susceptibility to infections despite the increased amount of antibacterial cells being present. This makes it likely that, in both COPD and asthma, it is the coordinated antibacterial function of the immune cells that is missing rather than insufficient quantities of these cells. This may also be the case in chronic bronchitis.
It is known that host defence in asthma and COPD is altered when it comes to immune signaling via cytokines. Furthermore, there is evidence suggesting that this immunological disorder is linked to the function in the microbial receptors of the immune system. Our line of research is based on the idea that long-term exposure to environmental factors, such as smoke from burning biomass including tobacco, biofuel, organic dust, small particles, exhaust from combustion engines and certain metals, cause altered immune signaling in asthma and COPD, possibly in chronic bronchitis as well.
In our research unit, we characterise the effects of environmental factors on immune signaling in host defence against infections. We investigate this immune signaling mainly by comparing conditions in patients with airway disease to those of healthy controls, but also in model studies. We map the underlying cellular and molecular mechanisms in tissue, in primary and genetically modified cells from humans, as well as in animal models when required. Combining these studies, we hope to identify new cellular and molecular targets for diagnosis and monitoring, and ultimately for treatment and prevention of disease.