Association between pulmonary function and sputum biomarkers in cystic fibrosis.
BACKGROUND
Sputum biomarkers of infection and inflammation are noninvasive measures that enable quantification of the complex pathophysiology of cystic fibrosis (CF) lung disease. Validation of these biomarkers as correlates of disease severity is a key step for their application.


OBJECTIVE
We constructed a large database from four multicenter studies to quantify the strength of association between expectorated sputum biomarkers and FEV(1.)


METHODS
FEV(1) (range, 25-120% predicted) and quantitative data on expectorated sputum biomarkers including free neutrophil elastase, IL-8, neutrophils, Pseudomonas aeruginosa, and Staphylococcus aureus were obtained from 269 participants (ages, 9-54 years) from 33 centers. Cross-sectional and longitudinal statistical analyses were performed to estimate associations between the markers and FEV(1), including the use of multivariable analyses.


RESULTS
Elastase was negatively correlated with FEV(1) (correlation [r] = -0.35; 95% confidence interval [CI]: -0.46, -0.22). On average, patients with CF who differed in their elastase measurements by 0.5 log differed in their FEV(1) values by -7.3% (95% CI: -9.7, -4.6). Neutrophil counts and IL-8 were also each negatively correlated. In a multivariable regression, elastase and neutrophil counts were able to explain the majority of variation in FEV(1). Elastase was further shown to have a significant longitudinal association with FEV(1), specifically a -2.9% decline in FEV(1) (95% CI: -5.0, -0.9) per 1-log increase in elastase. Although correlated with FEV(1), bacterial densities were unable to explain clinically meaningful differences in FEV(1) within and across patients.


CONCLUSIONS
These data support the role of sputum biomarkers as correlates of disease severity in a diverse CF population.
Mayer-Hamblett
Nicole
N
Department of Pediatrics, University of Washington, 4800 Sand Point Way N.E., Box 5371, Seattle, WA 98105-0371, USA. nicole.hamblett@seattlechildrens.org
Aitken
Moira L
ML
Accurso
Frank J
FJ
Kronmal
Richard A
RA
Konstan
Michael W
MW
Burns
Jane L
JL
Sagel
Scott D
SD
Ramsey
Bonnie W
BW
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007958:Leukocyte Count; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D012189:Retrospective Studies; D013183:Sputum / Q000737:chemistry* / Q000166:cytology* / Q000382:microbiology
D015415:Biomarkers; D016209:Interleukin-8; D019272:Leukocyte Elastase