PMID- 25306249
OWN - NLM
STAT- MEDLINE
DCOM- 20150417
LR  - 20211021
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 15
IP  - 1
DP  - 2014 Oct 12
TI  - The association of plasma biomarkers with computed tomography-assessed emphysema 
      phenotypes.
PG  - 127
LID - 10.1186/s12931-014-0127-9 [doi]
LID - 127
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is a phenotypically 
      heterogeneous disease. In COPD, the presence of emphysema is associated with 
      increased mortality and risk of lung cancer. High resolution computed tomography 
      (HRCT) scans are useful in quantifying emphysema but are associated with 
      radiation exposure and high incidence of false positive findings (i.e., nodules). 
      Using a comprehensive biomarker panel, we sought to determine if there was a 
      peripheral blood biomarker signature of emphysema. METHODS: 114 plasma biomarkers 
      were measured using a custom assay in 588 individuals enrolled in the COPDGene 
      study. Quantitative emphysema measurements included percent low lung attenuation 
      (%LAA) </= -950 HU, </= - 910 HU and mean lung attenuation at the 15th percentile on 
      lung attenuation curve (LP15A). Multiple regression analysis was performed to 
      determine plasma biomarkers associated with emphysema independent of covariates 
      age, gender, smoking status, body mass index and FEV1. The findings were 
      subsequently validated using baseline blood samples from a separate cohort of 388 
      subjects enrolled in the Treatment of Emphysema with a Selective Retinoid Agonist 
      (TESRA) study. RESULTS: Regression analysis identified multiple biomarkers 
      associated with CT-assessed emphysema in COPDGene, including advanced 
      glycosylation end-products receptor (AGER or RAGE, p < 0.001), intercellular 
      adhesion molecule 1 (ICAM, p < 0.001), and chemokine ligand 20 (CCL20, 
      p < 0.001). Validation in the TESRA cohort revealed significant associations with 
      RAGE, ICAM1, and CCL20 with radiologic emphysema (p < 0.001 after meta-analysis). 
      Other biomarkers that were associated with emphysema include CDH1, CDH 13 and 
      SERPINA7, but were not available for validation in the TESRA study. Receiver 
      operating characteristics analysis demonstrated a benefit of adding a biomarker 
      panel to clinical covariates for detecting emphysema, especially in those without 
      severe airflow limitation (AUC 0.85). CONCLUSIONS: Our findings, suggest that a 
      panel of blood biomarkers including sRAGE, ICAM1 and CCL20 may serve as a useful 
      surrogate measure of emphysema, and when combined with clinical covariates, may 
      be useful clinically in predicting the presence of emphysema compared to just 
      using covariates alone, especially in those with less severe COPD. Ultimately 
      biomarkers may shed light on disease pathogenesis, providing targets for new 
      treatments.
FAU - Carolan, Brendan J
AU  - Carolan BJ
AD  - Department of Medicine, National Jewish Health, 1400 Jackson St, Denver 80206, 
      CO, USA. CarolanB@NJHealth.org.
FAU - Hughes, Grant
AU  - Hughes G
FAU - Morrow, Jarrett
AU  - Morrow J
FAU - Hersh, Craig P
AU  - Hersh CP
FAU - O'Neal, Wanda K
AU  - O'Neal WK
FAU - Rennard, Stephen
AU  - Rennard S
FAU - Pillai, Sreekumar G
AU  - Pillai SG
FAU - Belloni, Paula
AU  - Belloni P
FAU - Cockayne, Debra A
AU  - Cockayne DA
FAU - Comellas, Alejandro P
AU  - Comellas AP
FAU - Han, Meilan
AU  - Han M
FAU - Zemans, Rachel L
AU  - Zemans RL
FAU - Kechris, Katerina
AU  - Kechris K
FAU - Bowler, Russell P
AU  - Bowler RP
LA  - eng
GR  - P30 ES005605/ES/NIEHS NIH HHS/United States
GR  - UL1 RR025780/RR/NCRR NIH HHS/United States
GR  - U01 HL089897/HL/NHLBI NIH HHS/United States
GR  - R01 HL095432/HL/NHLBI NIH HHS/United States
GR  - R01 HL089856/HL/NHLBI NIH HHS/United States
GR  - U01 HL089856/HL/NHLBI NIH HHS/United States
GR  - P20 HL113445/HL/NHLBI NIH HHS/United States
GR  - UL1 TR001082/TR/NCATS NIH HHS/United States
GR  - R01HL 095432/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Validation Study
DEP - 20141012
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (Biomarkers)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers/blood
MH  - Cohort Studies
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Phenotype
MH  - Pulmonary Emphysema/*blood/*diagnostic imaging
MH  - Tomography, X-Ray Computed/*standards
PMC - PMC4198701
EDAT- 2014/10/13 06:00
MHDA- 2015/04/18 06:00
PMCR- 2014/10/12
CRDT- 2014/10/13 06:00
PHST- 2014/05/29 00:00 [received]
PHST- 2014/10/03 00:00 [accepted]
PHST- 2014/10/13 06:00 [entrez]
PHST- 2014/10/13 06:00 [pubmed]
PHST- 2015/04/18 06:00 [medline]
PHST- 2014/10/12 00:00 [pmc-release]
AID - s12931-014-0127-9 [pii]
AID - 127 [pii]
AID - 10.1186/s12931-014-0127-9 [doi]
PST - epublish
SO  - Respir Res. 2014 Oct 12;15(1):127. doi: 10.1186/s12931-014-0127-9.