Biomarkers of inflammation in infants with cystic fibrosis

Theresa A Laguna, Cynthia B Williams, Myra G Nunez, Cole Welchlin-Bradford, Catherine E Moen, Cavan S Reilly, Chris H Wendt, Theresa A Laguna, Cynthia B Williams, Myra G Nunez, Cole Welchlin-Bradford, Catherine E Moen, Cavan S Reilly, Chris H Wendt

Abstract

Background: 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. Our objective was to investigate three targeted biomarkers in a population of asymptomatic CF infants.

Methods: Urine, 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.

Results: Urinary 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.

Conclusions: Cathepsin B and CCSP show promise as biomarkers of inflammation in CF infants. Further study is needed.

Keywords: Bronchoalveolar lavage fluid; Infection; Inflammation; Lung function; Pediatrics.

Conflict of interest statement

Ethics approval and consent to participate

Ethics approval and consent was obtained from the University of Minnesota Institutional Review Board (IRB#0809 M45601 and IRB#0812 M55581).

Consent for publication

Not applicable

Competing interests

The authors declare they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Urinary cathepsin B concentration is higher in CF infants compared to healthy control infants (p = 0.005)
Fig. 2
Fig. 2
ROC curve for the ability of urinary cathepsin B concentration to distinguish between CF and healthy, control infants
Fig. 3
Fig. 3
A positive, significant association between CF infant plasma CCSP and concentration and CF infants BALF concentration was observed (p = 0.046)
Fig. 4
Fig. 4
CF infants had a significantly higher CCSP concentration measured in BALF compared to that in adult CF sputum (p = 3.868e-0.6)
Fig. 5
Fig. 5
a CF infant BALF cathepsin B concentration was significant lower than that in adult sputum (p = 0.002), and (b) CF infant urinary cathepsin B concentration was significantly lower than that in adult urine (p = 0.022)

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