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01.12.2018 | Research | Ausgabe 1/2018 Open Access

Respiratory Research 1/2018

Biomarkers of inflammation in infants with cystic fibrosis

Zeitschrift:
Respiratory Research > Ausgabe 1/2018
Autoren:
Theresa A. Laguna, Cynthia B. Williams, Myra G. Nunez, Cole Welchlin-Bradford, Catherine E. Moen, Cavan S. Reilly, Chris H. Wendt
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1186/​s12931-017-0713-8) contains supplementary material, which is available to authorized users.
Results have been previously presented as a poster presentation by Dr. Laguna at the North American Cystic Fibrosis Conference 2015 (Phoenix, AZ).

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.
Zusatzmaterial
Additional file 1: Cumulative data for targeted biomarkers in healthy control and CF infants. (PDF 49 kb)
12931_2017_713_MOESM1_ESM.pdf
Additional file 2: Plot of urinary cathepsin B concentration vs. urinary desmosine concentration. (JPEG 157 kb)
12931_2017_713_MOESM2_ESM.jpg
Additional file 3: Additional plots of inflammatory marker analysis. (JPEG 167 kb)
12931_2017_713_MOESM3_ESM.jpg
Additional file 4: Table summarizing the culture results for all CF infants. (PDF 34 kb)
12931_2017_713_MOESM4_ESM.pdf
Additional file 5: Additional plots of cytokine concentrations in CF infant BALF. (JPEG 134 kb)
12931_2017_713_MOESM5_ESM.jpg
Additional file 6: Plots summarizing the statistical analysis of FEV0.5 with targeted biomarkers. (JPEG 159 kb)
12931_2017_713_MOESM6_ESM.jpg
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