TY - JOUR
T1 - Evaluation of airway and circulating inflammatory biomarkers for cystic fibrosis drug development
AU - Jain, Raksha
AU - Baines, Arthur
AU - Khan, Umer
AU - Wagner, Brandie D.
AU - Sagel, Scott D.
N1 - Funding Information:
The authors report the following conflicts of interest relevant to this manuscript. A.B., R.J., U.K., and S.S. received grant support from the Cystic Fibrosis Foundation related to this project.RJ and SDS designed the study. AB, UK, and BDW analyzed the data. All authors interpreted the data. RJ and SDS prepared the manuscript. All authors reviewed the manuscript and approved the final version prior to submission. This research was supported by Cystic Fibrosis Foundation Therapeutics (AQUADEK12K1), and by NIH/NCATS Colorado CTSA #UL1 TR002535. Rebecca Baldermann and the lab technicians in the CTRC Core Laboratory for processing the biospecimens and performing the measurements of inflammation; CFF TDN Coordinating Center for oversight of the clinical trial; all of the study participants and their families.
Funding Information:
This research was supported by Cystic Fibrosis Foundation Therapeutics ( AQUADEK12K1 ), and by NIH / NCATS Colorado CTSA # UL1 TR002535 .
Funding Information:
The authors report the following conflicts of interest relevant to this manuscript. A.B., R.J., U.K., and S.S. received grant support from the Cystic Fibrosis Foundation related to this project.
Publisher Copyright:
© 2020
PY - 2021/1
Y1 - 2021/1
N2 - Introduction: Biomarkers of inflammation in blood and sputum can play a critical role in anti-inflammatory drug development in cystic fibrosis (CF). The objectives of this analysis were to examine relationships between airway and systemic measurements of inflammation, associations between inflammatory biomarkers and FEV1, differences in airway and systemic inflammation by baseline covariates, reproducibility of serum biomarkers, and to assess the effects of freezing and delayed processing on sputum analyte measurements. Methods: We analyzed baseline and serial concentrations of inflammatory markers in blood and induced sputum collected from individuals with CF ages 10 years and older who participated in a multicenter clinical trial. Results: Among circulating biomarkers, serum high sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) correlated most strongly with each other (rs = 0.85). Comparing sputum-based inflammation measurements, sputum neutrophil elastase and myeloperoxidase (MPO) were the most highly correlated (rs = 0.88). Markers most strongly correlated with ppFEV1 were serum hsCRP (rs = -0.55), SAA (rs =-0.58), and sputum neutrophil elastase (rs = -0.53). Within-subject standard deviation was consistently lower than between-subject standard deviation for all serum biomarkers. Serum calprotectin and MPO had the highest ratio of between-to-within subject variability. Freezing and delayed sputum processing were not associated with significant differences in measurements of sputum neutrophil elastase, IL-1β, or MPO. Conclusions: Among the biomarkers analyzed, serum hsCRP and sputum neutrophil elastase are promising candidates to include in CF anti-inflammatory clinical trials to avoid redundancy, minimize variation, and serve as correlates of lung disease severity and change.
AB - Introduction: Biomarkers of inflammation in blood and sputum can play a critical role in anti-inflammatory drug development in cystic fibrosis (CF). The objectives of this analysis were to examine relationships between airway and systemic measurements of inflammation, associations between inflammatory biomarkers and FEV1, differences in airway and systemic inflammation by baseline covariates, reproducibility of serum biomarkers, and to assess the effects of freezing and delayed processing on sputum analyte measurements. Methods: We analyzed baseline and serial concentrations of inflammatory markers in blood and induced sputum collected from individuals with CF ages 10 years and older who participated in a multicenter clinical trial. Results: Among circulating biomarkers, serum high sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) correlated most strongly with each other (rs = 0.85). Comparing sputum-based inflammation measurements, sputum neutrophil elastase and myeloperoxidase (MPO) were the most highly correlated (rs = 0.88). Markers most strongly correlated with ppFEV1 were serum hsCRP (rs = -0.55), SAA (rs =-0.58), and sputum neutrophil elastase (rs = -0.53). Within-subject standard deviation was consistently lower than between-subject standard deviation for all serum biomarkers. Serum calprotectin and MPO had the highest ratio of between-to-within subject variability. Freezing and delayed sputum processing were not associated with significant differences in measurements of sputum neutrophil elastase, IL-1β, or MPO. Conclusions: Among the biomarkers analyzed, serum hsCRP and sputum neutrophil elastase are promising candidates to include in CF anti-inflammatory clinical trials to avoid redundancy, minimize variation, and serve as correlates of lung disease severity and change.
KW - Biomarkers
KW - Cystic fibrosis
KW - Inflammation
KW - Lung function
KW - Sputum
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U2 - 10.1016/j.jcf.2020.06.017
DO - 10.1016/j.jcf.2020.06.017
M3 - Article
C2 - 32622665
AN - SCOPUS:85087210003
SN - 1569-1993
VL - 20
SP - 50
EP - 56
JO - Journal of Cystic Fibrosis
JF - Journal of Cystic Fibrosis
IS - 1
ER -