Glycoprotein A as a biomarker of pulmonary infection and inflammation in children with cystic fibrosis

Background: Serum Glycoprotein A (GlycA) levels are increased in a variety of inflammatory disease states. However, GlycA has not been previously evaluated in children with cystic fibrosis (CF). We assessed the relationship between GlycA and pulmonary infection, inflammation, bronchial wall thickening (BWT) and bronchiectasis in young children with CF.

Methods: From 95 patients, we obtained 311 paired serum and bronchoalveolar lavage (BAL) samples at multiple timepoints, with concurrent chest computed tomography on 168 occasions. Quantitative GlycA was determined using high‐throughput nuclear magnetic resonance metabolomic testing. Participants were considered to be infected if ≥1 significant proinflammatory organism was isolated from their BAL. The presence of free neutrophil elastase (NE) above the limit of detection was considered evidence of inflammation. The relationships between GlycA levels and infection state, inflammation, and bronchiectasis were examined using a generalized estimating equation approach.

Results: There was a positive relationship between GlycA (mean 1.01 mmol/L, range 0.68‐1.92 mmol/L) and being infected with one or more proinflammatory organisms, even after adjusting for age and gender (odds ratio [OR], 1.2 per 0.1 mmol/L, 95% confidence interval [CI], 1.02, 1.4, P = .03). There was also a positive relationship between GlycA and NE (unadjusted OR, 1.2 95% CI, 1.01, 1.4, P = .04), not significant after adjustment. GlycA concentration was associated with BWT but not bronchiectasis.

Conclusions: Although GlycA levels were higher on average in those who had an infection or neutrophilic inflammation, there was also considerable variability, limiting the clinical utility of this biomarker alone in determining early disease status in CF.

Authors: Ajay C. Kevat, Rosemary Carzino, Suzanna Vidmar, Sarath Ranganathan.

Published in Pediatric Pulmonology November 2019.