Abstract
BackgroundThere are urgent needs for clinically relevant biomarkers to identify children with cystic fibrosis (CF) at risk for more progressive lung disease and to serve as outcome measures for clinical trials. Our objective was to investigate three targeted biomarkers in a population of asymptomatic CF infants.MethodsUrine, blood and lung function data were collected for 2 years from clinically stable infants diagnosed with CF by newborn screening. A subset of CF infants had bronchoscopy with lavage performed at 6 months and 1 year. Urine was collected quarterly from healthy control infants. Expectorated sputum and urine were collected quarterly for 2 years from clinically stable CF adults. Desmosine, club cell secretory protein (CCSP) and cathepsin B concentrations were measured and compared. Mixed effects models were used to identify associations between biomarker concentrations and clinical characteristics. Receiver operator characteristic curves were generated to investigate the sensitivity and specificity of the biomarkers.ResultsUrinary cathepsin B was significantly higher in CF infants compared to healthy infants (p = 0.005). CF infant airway and urinary cathepsin B concentrations were significantly lower compared to adult CF subjects (p = 0.002 & p = 0.022, respectively). CF infant airway CCSP was significantly higher than adult CF subjects (p < 0.001). There was a significant correlation between CF infant plasma CCSP and BALF CCSP (p = 0.046). BALF CCSP was negatively associated with IL-8 (p = 0.017). There was no correlation between biomarker concentration and FEV0.5.ConclusionsCathepsin B and CCSP show promise as biomarkers of inflammation in CF infants. Further study is needed.
Highlights
There are urgent needs for clinically relevant biomarkers to identify children with cystic fibrosis (CF) at risk for more progressive lung disease and to serve as outcome measures for clinical trials
Detection and treatment of pulmonary decline is key to optimal long-term outcome; physiologic measures of lung function and radiologic outcomes fail to capture the inflammation and infection that begins in infancy and is often silent in CF [6,7,8]
Correlations of targeted biomarker concentrations with lung function and markers of infection and inflammation in CF infants There was no significant association between % neutrophils or absolute neutrophil count in BALF, BALF neutrophil elastase (NE) and club cell secretory protein (CCSP), Cathepsin B or desmosine concentrations (Additional file 3)
Summary
There are urgent needs for clinically relevant biomarkers to identify children with cystic fibrosis (CF) at risk for more progressive lung disease and to serve as outcome measures for clinical trials. Cathepsin B is an elastolytic cysteine protease that is linked to remodeling of extracellular matrix, bacterial infection and biofilm formation in the CF airways, involving Pseudomonas aeruginosa, a known pathogen in CF [10, 13,14,15,16]. These three targeted biomarkers may provide an objective measure of the degree of inflammation or tissue destruction occurring in the lung, and if so, would be invaluable both for clinical management and as surrogate endpoints for clinical trials
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