Document Detail

Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers.
MedLine Citation:
PMID:  21680942     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Exacerbations of chronic obstructive pulmonary disease (COPD) are heterogeneous with respect to inflammation and etiology.
OBJECTIVES: Investigate biomarker expression in COPD exacerbations to identify biologic clusters and determine biomarkers that recognize clinical COPD exacerbation phenotypes, namely those associated with bacteria, viruses, or eosinophilic airway inflammation.
METHODS: Patients with COPD were observed for 1 year at stable and exacerbation visits. Biomarkers were measured in sputum and serum. Viruses and selected bacteria were assessed in sputum by polymerase chain reaction and routine diagnostic bacterial culture. Biologic phenotypes were explored using unbiased cluster analysis and biomarkers that differentiated clinical exacerbation phenotypes were investigated.
MEASUREMENTS AND MAIN RESULTS: A total of 145 patients (101 men and 44 women) entered the study. A total of 182 exacerbations were captured from 86 patients. Four distinct biologic exacerbation clusters were identified. These were bacterial-, viral-, or eosinophilic-predominant, and a fourth associated with limited changes in the inflammatory profile termed “pauciinflammatory.” Of all exacerbations, 55%, 29%, and 28% were associated with bacteria, virus, or a sputum eosinophilia. The biomarkers that best identified these clinical phenotypes were sputum IL-1β, 0.89 (area under receiver operating characteristic curve) (95% confidence interval [CI], 0.83–0.95); serum CXCL10, 0.83 (95% CI, 0.70–0.96); and percentage peripheral eosinophils, 0.85 (95% CI, 0.78–0.93), respectively.
CONCLUSIONS: The heterogeneity of the biologic response of COPD exacerbations can be defined. Sputum IL-1β, serum CXCL10, and peripheral eosinophils are biomarkers of bacteria-, virus-, or eosinophil-associated exacerbations of COPD. Whether phenotype-specific biomarkers can be applied to direct therapy warrants further investigation.
Mona Bafadhel; Susan McKenna; Sarah Terry; Vijay Mistry; Carlene Reid; Pranabashis Haldar; Margaret McCormick; Koirobi Haldar; Tatiana Kebadze; Annelyse Duvoix; Kerstin Lindblad; Hemu Patel; Paul Rugman; Paul Dodson; Martin Jenkins; Michael Saunders; Paul Newbold; Ruth H Green; Per Venge; David A Lomas; Michael R Barer; Sebastian L Johnston; Ian D Pavord; Christopher E Brightling
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  184     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-12-16     Completed Date:  2012-01-05     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  662-71     Citation Subset:  AIM; IM    
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MeSH Terms
Aged, 80 and over
Bacterial Infections / metabolism,  microbiology
Biological Markers / blood,  metabolism
Chemokine CXCL10 / blood
Cluster Analysis
Eosinophils / metabolism,  microbiology
Inflammation / metabolism,  microbiology
Interleukin-1beta / metabolism
Middle Aged
Polymerase Chain Reaction
Prospective Studies
Pulmonary Disease, Chronic Obstructive / blood,  metabolism,  microbiology*
ROC Curve
Severity of Illness Index
Sputum / metabolism,  microbiology
Grant Support
G0601369//Medical Research Council; G0801980//Medical Research Council; G0901786//Medical Research Council; //Medical Research Council
Reg. No./Substance:
0/Biological Markers; 0/Chemokine CXCL10; 0/Interleukin-1beta
Comment In:
Am J Respir Crit Care Med. 2011 Sep 15;184(6):625-6   [PMID:  21920921 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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