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

doi:10.1186/s12931-017-0713-8

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

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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 6months 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 FEV_0.5. Conclusions: Cathepsin B and CCSP show promise as biomarkers of inflammation in CF infants. Further study is needed.

Original language	English (US)
Article number	6
Journal	Respiratory research
Volume	19
Issue number	1
DOIs	https://doi.org/10.1186/s12931-017-0713-8
State	Published - Jan 8 2018

Bibliographical note

Funding Information:
This work was supported by grants from the American Thoracic Society/ Cystic Fibrosis Foundation [ATS/CFF CF-08-001] and the National Institutes of Health [K12HD068322, UL1TR000114]. The ATS, CFF and NIH had no role in the design of the study and collection, analysis and interpretation of the data and in writing the manuscript.

Publisher Copyright:
© 2018 The Author(s).

Keywords

Bronchoalveolar lavage fluid
Infection
Inflammation
Lung function
Pediatrics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12931-017-0713-8

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5759377

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title = "Biomarkers of inflammation in infants with cystic fibrosis",

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 6months 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",

author = "Laguna, {Theresa A.} and Williams, {Cynthia B.} and Nunez, {Myra G.} and Cole Welchlin-Bradford and Moen, {Catherine E.} and Reilly, {Cavan S.} and Wendt, {Chris H.}",

note = "Funding Information: This work was supported by grants from the American Thoracic Society/ Cystic Fibrosis Foundation [ATS/CFF CF-08-001] and the National Institutes of Health [K12HD068322, UL1TR000114]. The ATS, CFF and NIH had no role in the design of the study and collection, analysis and interpretation of the data and in writing the manuscript. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

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doi = "10.1186/s12931-017-0713-8",

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T1 - Biomarkers of inflammation in infants with cystic fibrosis

AU - Laguna, Theresa A.

AU - Williams, Cynthia B.

AU - Nunez, Myra G.

AU - Welchlin-Bradford, Cole

AU - Moen, Catherine E.

AU - Reilly, Cavan S.

AU - Wendt, Chris H.

N1 - Funding Information: This work was supported by grants from the American Thoracic Society/ Cystic Fibrosis Foundation [ATS/CFF CF-08-001] and the National Institutes of Health [K12HD068322, UL1TR000114]. The ATS, CFF and NIH had no role in the design of the study and collection, analysis and interpretation of the data and in writing the manuscript. Publisher Copyright: © 2018 The Author(s).

PY - 2018/1/8

Y1 - 2018/1/8

N2 - 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 6months 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.

AB - 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 6months 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.

KW - Bronchoalveolar lavage fluid

KW - Infection

KW - Inflammation

KW - Lung function

KW - Pediatrics

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ER -

Biomarkers of inflammation in infants with cystic fibrosis

Abstract

Bibliographical note

Keywords

UN SDGs

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