Multi analyte profiling and variability of inflammatory markers in blood and induced sputum in patients with stable COPD.
BACKGROUND
We analyzed serial concentrations of multiple inflammatory mediators from serum and induced sputum obtained from patients with stable COPD and controls. The objective was to determine which proteins could be used as reliable biomarkers to assess COPD disease state and severity.


METHODS
Forty-two subjects; 21 with stable COPD and 21 controls, were studied every 2 weeks over a 6-week period. Serum and induced sputum were obtained at each of 3 visits and concentrations of 19 serum and 22 sputum proteins were serially assessed using multiplex immunoassays. We used linear mixed effects models to test the distribution of proteins for an association with COPD and disease severity. Measures of within- and between-subject coefficients of variation were calculated for each of the proteins to assess reliability of measurement.


RESULTS
There was significant variability in concentrations of all inflammatory proteins over time, and variability was greater for sputum proteins (median intra-subject coefficient of variation 0.58) compared to proteins measured in serum (median intra-subject coefficient of variation 0.32, P = 0.03). Of 19 serum proteins and 22 sputum proteins tested, only serum CRP, myeloperoxidase and VEGF and sputum IL-6, IL-8, TIMP-1, and VEGF showed acceptable intra and inter-patient reliability and were significantly associated with COPD, the severity of lung function impairment, and dyspnea.


CONCLUSIONS
Levels of many serum and sputum biomarkers cannot be reliably ascertained based on single measurements. Multiple measurements over time can give a more reliable and precise estimate of the inflammatory burden in clinically stable COPD patients.
Aaron
Shawn D
SD
Department of Medicine, The Ottawa Health Research Institute, University of Ottawa, Ottawa, ON, Canada. saaron@ohri.ca
Vandemheen
Katherine L
KL
Ramsay
Timothy
T
Zhang
Chun
C
Avnur
Zafrira
Z
Nikolcheva
Tania
T
Quinn
Anthony
A
D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007118:Immunoassay; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D040081:Protein Array Analysis / Q000379:methods; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013183:Sputum / Q000276:immunology; D013997:Time Factors
D015415:Biomarkers; D018836:Inflammation Mediators