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 a...

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Main Authors: Theresa A. Laguna, Cynthia B. Williams, Myra G. Nunez, Cole Welchlin-Bradford, Catherine E. Moen, Cavan S. Reilly, Chris H. Wendt
Format: Article
Language:English
Published: BMC 2018-01-01
Series:Respiratory Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12931-017-0713-8
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author Theresa A. Laguna
Cynthia B. Williams
Myra G. Nunez
Cole Welchlin-Bradford
Catherine E. Moen
Cavan S. Reilly
Chris H. Wendt
author_facet Theresa A. Laguna
Cynthia B. Williams
Myra G. Nunez
Cole Welchlin-Bradford
Catherine E. Moen
Cavan S. Reilly
Chris H. Wendt
author_sort Theresa A. Laguna
collection DOAJ
description 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.
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spelling doaj.art-b32dcc037e1940a5b7902b7b7dba73022022-12-22T02:46:05ZengBMCRespiratory Research1465-993X2018-01-011911910.1186/s12931-017-0713-8Biomarkers of inflammation in infants with cystic fibrosisTheresa A. Laguna0Cynthia B. Williams1Myra G. Nunez2Cole Welchlin-Bradford3Catherine E. Moen4Cavan S. Reilly5Chris H. Wendt6Minnesota CF Center, Department of Pediatrics, University of Minnesota Masonic Children’s HospitalMinnesota CF Center, Department of Pediatrics, University of Minnesota Masonic Children’s HospitalMinnesota CF Center, Department of Pediatrics, University of Minnesota Masonic Children’s HospitalMinnesota CF Center, Department of Pediatrics, University of Minnesota Masonic Children’s HospitalMinnesota CF Center, Department of Pediatrics, University of Minnesota Masonic Children’s HospitalSchool of Public Health, Division of Biostatistics, University of MinnesotaDepartment of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Minnesota and Veterans Administration Medical CenterAbstract 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.http://link.springer.com/article/10.1186/s12931-017-0713-8InflammationLung functionInfectionPediatricsBronchoalveolar lavage fluid
spellingShingle Theresa A. Laguna
Cynthia B. Williams
Myra G. Nunez
Cole Welchlin-Bradford
Catherine E. Moen
Cavan S. Reilly
Chris H. Wendt
Biomarkers of inflammation in infants with cystic fibrosis
Respiratory Research
Inflammation
Lung function
Infection
Pediatrics
Bronchoalveolar lavage fluid
title Biomarkers of inflammation in infants with cystic fibrosis
title_full Biomarkers of inflammation in infants with cystic fibrosis
title_fullStr Biomarkers of inflammation in infants with cystic fibrosis
title_full_unstemmed Biomarkers of inflammation in infants with cystic fibrosis
title_short Biomarkers of inflammation in infants with cystic fibrosis
title_sort biomarkers of inflammation in infants with cystic fibrosis
topic Inflammation
Lung function
Infection
Pediatrics
Bronchoalveolar lavage fluid
url http://link.springer.com/article/10.1186/s12931-017-0713-8
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AT colewelchlinbradford biomarkersofinflammationininfantswithcysticfibrosis
AT catherineemoen biomarkersofinflammationininfantswithcysticfibrosis
AT cavansreilly biomarkersofinflammationininfantswithcysticfibrosis
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