Sputum biomarkers of inflammation and lung function decline in children with cystic fibrosis.
BACKGROUND
Progressive lung function decline is a defining feature of cystic fibrosis (CF). Because airway inflammation plays a central role in CF lung disease, inflammatory biomarkers that can be used to monitor disease activity would be valuable.


OBJECTIVE
Examine longitudinal relationships between sputum biomarkers and lung function.


METHODS
In this prospective, longitudinal cohort study, sputum induction was performed annually over 3 years in 35 children with CF. Sputum was assayed for mediators related to proteolysis and a panel of inflammatory cytokines.


RESULTS
Sputum neutrophil elastase, tissue inhibitor of metalloproteinase-1, and TNF-α increased over time, whereas neutrophil elastase antiprotease complexes (NEAPCs) and secretory leukoprotease inhibitor (SLPI) significantly decreased over time. Higher detectable baseline neutrophil elastase was associated with more rapid lung function decline. Similar results for neutrophil elastase were observed in a validation cohort. When categorizing subjects as "rapid" or "slow" decliners, logistic regression demonstrated that the initial measurement of neutrophil elastase had the highest individual predictive value for subsequent lung function decline, whereas neutrophil elastase, IL-8, and IL-6 had the highest combined predictive value. Lung function decline was associated with increases in neutrophil counts, neutrophil elastase, and IL-1β and declines in NEAPCs and SLPI.


CONCLUSIONS
In children with CF, a single determination of sputum biomarkers, particularly neutrophil elastase, has predictive value for subsequent lung function decline, and longitudinal changes in sputum inflammatory biomarkers are related to lung function changes. Based on our results, sputum neutrophil elastase was the most informative biomarker to monitor disease activity.
Children's Hospital Colorado, 13123 E. 16th Avenue, Aurora, CO 80045, USA. scott.sagel@childrenscolorado.org
Scott D
SD
Sagel
Brandie D
BD
Wagner
Margaret M
MM
Anthony
Peggy
P
Emmett
Edith T
ET
Zemanick
D015415:Biomarkers / Q000032:analysis; D002648:Child; D003550:Cystic Fibrosis / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis*; D019272:Leukocyte Elastase / Q000032:analysis; D008168:Lung / Q000503:physiopathology*; D008297:Male; D011446:Prospective Studies; D059748:Proteolysis; D013183:Sputum / Q000737:chemistry / Q000276:immunology*
D015415:Biomarkers; D016207:Cytokines; D019272:Leukocyte Elastase