Inflammatory and repair serum biomarker pattern: association to clinical outcomes in COPD.
BACKGROUND
The relationship between serum biomarkers and clinical expressions of COPD is limited. We planned to further describe this association using markers of inflammation and injury and repair.


METHODS
We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years. Serum levels of Interleukins 6,8 and16, tumor necrosis factor alpha (TNF α) [inflammatory panel], vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) [injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18) and monocyte chemotactic protein 1 (MCP-1/CCL2) [chemoattractant panel] were measured. We related the pattern of the biomarker levels to minimal clinically important differences (MCID) using a novel visualization method [ObServed Clinical Association Results (OSCAR) plot].


RESULTS
Levels of the inflammatory markers IL-6, TNF α were higher and those of injury and repair lower (p < 0.01) with more advanced disease (GOLD 1 vs. 4). Using the OSCAR plot, we found that patients in the highest quartile of inflammatory and lowest quartile of injury and repair biomarkers level were more clinically compromised and had higher mortality (p < 0.05).


CONCLUSIONS
In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival.
Pulmonary-Critical Care Medicine Division, St Elizabeth's Medical Center, Boston, MA 02115, USA. vpinto@copdnet.org
Victor
V
Pinto-Plata
Ciro
C
Casanova
Hana
H
Müllerova
Juan P
JP
de Torres
Henneth
H
Corado
Nerea
N
Varo
Elizabeth
E
Cordoba
Salah
S
Zeineldine
Hildegarde
H
Paz
Rebeca
R
Baz
Miguel
M
Divo
Felipe
F
Cortopassi
Bartolome R
BR
Celli
D000368:Aged; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D019742:Chemokines, CC / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D017079:Exercise Tolerance / Q000502:physiology; D005260:Female; D006801:Humans; D019410:Interleukin-16 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008168:Lung / Q000503:physiopathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000503:physiopathology* / Q000523:psychology; D011788:Quality of Life / Q000523:psychology; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D015415:Biomarkers; C111792:CCL18 protein, human; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019742:Chemokines, CC; D016207:Cytokines; D019410:Interleukin-16; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9