Serum biomarkers as predictors of lung function decline in chronic obstructive pulmonary disease.
BACKGROUND
Recent studies show that COPD patients exhibit low-grade systemic inflammation, and that plasma fibrinogen and high neutrophil counts are related to faster declines in lung function. We examined correlations between serum biomarkers and the decline of lung function in COPD patients.


METHODS
Baseline levels of 9 serum biomarkers (TIMP-1, alpha1-antitrypsin, MMP-9, TNF-alpha, TGF-beta, IL-6, IL-8, neutrophil elastase and CRP), fibrinogen and white blood cell counts (WCC) were measured in 96 COPD patients. Lung function was measured at the time of blood sampling and every 3-6 months during the observation period (median 25.0 months).


RESULTS
Twenty patients were rapid decliners of lung function and 53 patients were non-decliners. Neutrophil counts, serum CRP and MMP-9 were significantly higher in the rapid decliners (p<0.05). The annual change of % predicted FEV(1) was inversely correlated with MMP-9 (r=-0.288; p<0.01) and CRP (r=-0.354; p<0.005) (partial correlation coefficients adjusted for age, sex, cardiovascular disease, smoking history, and baseline % predicted FEV(1)). The remaining biomarkers were not correlated with the annual change of % predicted FEV(1).


CONCLUSIONS
Serum CRP and MMP-9 levels were related to FEV(1) decline. These markers are good candidates as predictors for rapid decline of FEV(1) in COPD patients. Additional long-term and larger size studies of COPD patients could help determine the exact roles for these biomarkers.
Higashimoto
Yuji
Y
Department of Respiratory Medicine and Allergology, Kinki University School of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511 Japan. yhigashi@med.kindai.ac.jp
Iwata
Takuya
T
Okada
Morihiro
M
Satoh
Hiroaki
H
Fukuda
Kanji
K
Tohda
Yuji
Y
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000503:physiopathology; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D012907:Smoking
D015415:Biomarkers; D018836:Inflammation Mediators; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9