From U Colorado: Sputum Biomarkers of Inflammation and Lung Function Decline in Children with Cystic Fibrosis

http://www.ncbi.nlm.nih.gov/pubmed/22904182

Am J Respir Crit Care Med. 2012 Aug 16. [Epub ahead of print]

Sputum Biomarkers of Inflammation and Lung Function Decline in Children with Cystic Fibrosis.

Sagel SD, Wagner BD, Anthony MM, Emmett P, Zemanick ET.

Source

Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, United States.

Abstract

RATIONALE:

Progressive lung function decline is a defining feature of cystic fibrosis (CF). Since 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 three years in 35 CF children. Sputum was assayed for mediators related to proteolysis and a panel of inflammatory cytokines.

MEASUREMENTS AND MAIN RESULTS:

Sputum neutrophil elastase, TIMP-1 and TNF-a increased over time whereas neutrophil elastase antiprotease complexes (NEAPC) 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 either '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 while 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-1b, and declines in NEAPC and SLPI.

CONCLUSIONS:

In CF children, 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.