Role of Aspergillus fumigatus and vitamin D signaling in the development of COPD-related Bronchiectasis.

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.