Airway granulocytes potential CF biomarker for fungal lung disease

Researchers have found that accumulation in the airways of CXCR4⁺ granulocytes is associated with chronic colonisation by the fungus Aspergillus fumigatus.

Furthermore, in the study, levels of the granulocytes correlated with lung disease severity in patients with cystic fibrosis (CF), leading the team to suggest they could serve, not only as a biomarker, but also as a therapeutic target in the disease.

“Our findings […] further suggest that CXCR4⁺ airway granulocytes could also play a broader role in other chronic lung disease beyond cystic fibrosis, such as chronic obstructive pulmonary disease, where A. fumigatus is also found and associated with poor lung function,” they write in the European Respiratory Journal.

The study included 40 patients with CF and two control groups: eight patients with non-CF bronchiectasis and 10 healthy controls.

The team found that the percentage of CXCR4⁺ granulocytes was increased in CF patients in both the peripheral blood and the airways.

This was most marked in the airways, where sputum and bronchoalveolar lavage fluid (BALF) CXCR4⁺ percentages were significantly greater than controls. However, the team note that there was a wide range of values among CF patients, from around 25 to 100%, suggesting that disease-associated factors modulate percentages of the granulocytes.

To investigate further, they stratified patients according to whether they had colonisation of A. fumigatus or Candida albicans. While C. albicans colonisation did not correlate with any measure of CXCR4⁺ granulocyte percentages, CF patients positive for A. fumigatus colonisation had significantly higher percentages in both sputum and BALF than those who were negative. Patients with non-CF bronchiectasis also had significantly higher CXCR4⁺ percentages if they were positive for A. fumigatus colonization.

Furthermore, the researchers found that the percentage of CXCR4⁺ granulocytes in CF patients colonised with A. fumigatus was significantly inversely correlated with lung function according to forced expiratory volume in 1 second (FEV1).

The researchers, led by Dominik Hartl (University of Tubingen, Germany), explain that the clinical and functional relevance of CXCR4⁺ granulocytes was previously unknown.

Recruitment of granulocytes to the lungs can cause pulmonary tissue remodelling and immune receptor damage, and has been linked to the onset of bronchiectasis in CF patients.

“Consequently, therapeutic interference with granulocyte recruitment represents a promising approach in cystic fibrosis lung disease,” they comment.

Further studies will be needed to confirm the suitability of CXCR4⁺ granulocytes as a biomarker and/or therapeutic target, they conclude.

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