Exploration of challenging phenotypes in Chronic Obstructive Pulmonary Disease: Aspergillus fumigatus, bronchiectasis and asthma-COPD overlap

This project aims to unravel the role and mechanisms of Aspergillus fumigatus infection and sensitisation in COPD with regard to the development of bronchiectasis. We hypothesize that in COPD Aspergillus colonisation of the airways with reduced VDR expression, vitamin D deficiency and subsequent Aspergillus sensitization, are interacting hits which enhance inflammation, reduce tissue repair and are responsible for the development of bronchiectasis with impaired prognosis. As the group of Aspergillus-colonized or Aspergillus-sensitized patients may extent to 50% and 15% respectively of the severe COPD population, which often presents with repeated exacerbations despite maximal treatment, the need for a better understanding and possibly better treatment is obvious. The interactions between vitamin D and Aspergillus may explain why vitamin D supplementation alone is not effective to reduce airway inflammation in all COPD patients. However, it may open the avenue for interventions combining antifungal treatment with vitamin D supplementation in a particularly prevalent but yet not-recognized phenotype. Based on the results of this research project, we will be able to consider the need of a pilot randomized controlled trial in COPD bronchiectasis, but this is not part of the current application.