Abstract
Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by alveolar wall destruction and persistent airflow restriction and inflammation, and is mostly caused by smoking cigarettes. Patients with COPD often have additional problems in organs and tissues other than the lung, which contributes to the heterogeneity of the disease.
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Many of these so-called comorbidities are related to the brain, including anxiety, depression and cognitive impairment. These brain-related comorbidities negatively affect the treatment of COPD and may have a relation with phases of acute worsening of disease symptoms, i.e. exacerbations, which are often induced by opportunistic bacterial or viral infections. By increasing the understanding about how the lungs and brain are interacting in COPD, treatment strategies can be improved. In this thesis, the occurrence of brain-related comorbidities and current treatment options in COPD patients have been reviewed. Using a Dutch pharmacy database, it was demonstrated that treatments for anxiety and depression occur more often in COPD patients as compared to several other chronic diseases. Furthermore, two mouse models of COPD have been used to evaluate the impact of both lung damage (emphysema) and inflammatory processes in the lung and blood circulation on the brain. The inflammatory processes in the lungs have been induced by administering lipopolysaccharide, a bacterial component, locally in the lungs. This technique has been optimized and presented in this thesis. Findings from the murine COPD models indicate a possible important involvement of inflammation in both the lungs and blood circulation in COPD-related brain problems. In both models of COPD, several behavioral and cognitive impairments have been observed, and the findings suggest that the induced lung pathologies including emphysema and pulmonary inflammation can lead to brain function impairment. The vessels that protect the brain from toxic substances in the blood circulation (i.e. blood-brain barrier) were affected in both models, suggesting that the blood-brain barrier might play an important role in COPD-related brain problems. A nutritional intervention enriched with anti-inflammatory and neuroprotective properties, including omega-3 fatty acids, prebiotics, tryptophan and vitamin D, resulted in improving the immune system balance. There were indications that this diet can improve behavior and the integrity of the blood-brain barrier. This nutritional intervention can potentially be a valuable addition to current treatment strategies in COPD. This thesis contributes to the awareness of brain problems in COPD, and to understanding the involvement of inflammation.
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