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Associations of Sputum Biomarkers with Clinical Outcomes in People with Cystic Fibrosis

Authors :
Theodore G Liou
Natalia Argel
Fadi Asfour
Perry S Brown
Barbara A Chatfield
David R Cox
Cori L Daines
Dixie Durham
Jessica A Francis
Barbara Glover
My Helms
Theresa Heynekamp
John R Hoidal
Judy L Jensen
Christiana Kartsonaki
Ruth Keogh
Carol M Kopecky
Noah Lechtzin
Yanping Li
Jerimiah Lysinger
Osmara Molina
Craig Nakamura
Kristyn A Packer
Robert Paine
Katie R Poch
Alexandra L Quittner
Peggy Radford
Abby J Redway
Scott D Sagel
Rhonda D Szczesniak
Shawna Sprandel
Jennifer L Taylor-Cousar
Jane B Vroom
Ryan Yoshikawa
John P Clancy
J Stuart Elborn
Kenneth N Olivier
Frederick R Adler
Publication Year :
2022
Publisher :
Cold Spring Harbor Laboratory, 2022.

Abstract

BackgroundAirway inflammation promotes bronchiectasis and lung injury in cystic fibrosis (CF). Amplification of inflammation underlies pulmonary exacerbations of disease. We asked whether sputum inflammatory biomarkers provide explanatory information on pulmonary exacerbations.Patients and MethodsWe collected sputum from randomly chosen stable adolescents and adults and prospectively observed time to next exacerbation, our primary outcome. We evaluated relationships between potential biomarkers of inflammation, clinical characteristics and outcomes and assessed clinical variables as potential confounders or mediators of explanatory models. We assessed associations between the markers and time to next exacerbation using proportional hazard models adjusting for confounders.ResultsWe enrolled 114 patients, collected data on clinical variables [December 8, 2014 to January 16, 2016; 46% male, mean age 28 years (SD 12), mean percent predicted forced expiratory volume in 1 s (FEV1%) 70 (SD 22)] and measured 24 inflammatory markers. Half of the inflammatory markers were plausibly associated with time to next exacerbation. Age and sex were confounders while we found that FEV1% was a mediator.Three potential biomarkers of RAGE axis inflammation were associated with time to next exacerbation while six potential neutrophil-associated biomarkers indicate associations between protease activity or reactive oxygen species with time to next exacerbation.ConclusionPulmonary exacerbation biomarkers are part of the RAGE proinflammatory axis or reflect neutrophil activity, specifically implicating protease and oxidative stress injury. Further investigations or development of novel anti-inflammatory agents should consider RAGE axis, protease and oxidant stress antagonists.Tweetable abstractSputum from 114 randomly chosen people with CF show RAGE axis inflammation, protease and oxidative stress injury are associated with time to next pulmonary exacerbation and may be targets for bench or factorial design interventional studies. (242 characters)

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........62612a9ce0a2b7ff4eb4f5cb2469e1fa
Full Text :
https://doi.org/10.1101/2022.05.25.22275540