Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease.
CONCLUSIONS
This study explores the use of measuring plasma biomarkers at exacerbation of chronic obstructive pulmonary disease (COPD), providing insight into the underlying pathogenesis of these important events.


BACKGROUND
The use of measuring C-reactive protein (CRP) to confirm exacerbation, or to assess exacerbation severity, in COPD is unclear. Furthermore, it is not known whether there may be more useful systemic biomarkers.


OBJECTIVE
To assess the use of plasma biomarkers in confirming exacerbation and predicting exacerbation severity.


METHODS
We assessed 36 biomarkers in 90 paired baseline and exacerbation plasma samples from 90 patients with COPD. The diagnosis of exacerbation fulfilled both health care use and symptom-based criteria. Biomarker concentrations were related to clinical indices of exacerbation severity. Interrelationships between biomarkers were examined to gain information on mechanisms of systemic inflammation at exacerbation of COPD.


RESULTS
To confirm the diagnosis of exacerbation, the most selective biomarker was CRP. However, this was neither sufficiently sensitive nor specific alone (area under the receiver operating characteristic curve [AUC], 0.73; 95% confidence interval, 0.66-0.80). The combination of CRP with any one increased major exacerbation symptom recorded by the patient on that day (dyspnea, sputum volume, or sputum purulence) significantly increased the AUC to 0.88 (95% confidence interval, 0.82-0.93; p<0.0001). There were no significant relationships between biomarker concentrations and clinical indices of exacerbation severity. Interrelationships between biomarkers suggest that the acute-phase response is related, separately, to monocytic and lymphocytic-neutrophilic pathways.


CONCLUSIONS
Plasma CRP concentration, in the presence of a major exacerbation symptom, is useful in the confirmation of COPD exacerbation. Systemic biomarkers were not helpful in predicting exacerbation severity. The acute-phase response at exacerbation was most strongly related to indices of monocyte function.
Hurst
John R
JR
Academic Unit of Respiratory Medicine, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK.
Donaldson
Gavin C
GC
Perera
Wayomi R
WR
Wilkinson
Tom M A
TM
Bilello
John A
JA
Hagan
Gerry W
GW
Vessey
Rupert S
RS
Wedzicha
Jadwiga A
JA
D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D011379:Prognosis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood*; D012720:Severity of Illness Index
D015415:Biomarkers; D002097:C-Reactive Protein