Proteomic profiling identifies novel circulating markers associated with bronchiectasis in cystic fibrosis

Abstract

Purpose: Evaluate bronchiectasis change over 1 year in children with cystic fibrosis (CF) and find blood proteins associated with bronchiectasis.

Experimental design: Pilot study of CF children who had chest computed tomography (CT) scans and blood collected during times of clinical stability. Blood plasma was analyzed for 1129 proteins using SOMAmer®, the SOMAscan proteomics platform. Bronchiectasis was measured on two CT scans collected 1 year apart. Spearman's rank estimated the correlations between outcomes. Clinical relevance was defined as |r| >0.40.

Results: There were 26 children included: mean age 11.3 years (SD 2.4 years), mean Brody Bronchiectasis score 0.65 (SD 0.83), mean airway count 14.3 (SD 5.7) per CT slice. Brody bronchiectasis change over 1 year ranged from -1.0 to 1.9 and airway count change over one year ranged from -7.7 to 13.5 airways per slice. Proteins related to inflammation and extracellular matrix degradation were associated with cross-sectional and longitudinal structural changes.

Conclusions and clinical relevance: Imaging outcomes were more strongly correlated with circulating proteins than age or spirometry values. The unique SOMAscan proteomic platform identifies several novel proteins in blood that are associated with bronchiectasis and that may serve as clinically useful biomarkers in children with CF.

Keywords: Cystic fibrosis; Extracellular matrix; Lung Injury.