The association of plasma biomarkers with computed tomography-assessed emphysema phenotypes

Brendan J. Carolan, Grant Hughes, Jarrett Morrow, Craig P. Hersh, Wanda K. O'Neal, Stephen Rennard, Sreekumar G. Pillai, Paula Belloni, Debra A. Cockayne, Alejandro P. Comellas, Meilan Han, Rachel L. Zemans, Katerina Kechris, Russell P. Bowler

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 

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.

Original languageEnglish (US)
Pages (from-to)127
Number of pages1
JournalRespiratory Research
Volume15
DOIs
StatePublished - 2014
Externally publishedYes

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Emphysema
Biomarkers
Tomography
Phenotype
Chronic Obstructive Pulmonary Disease
Lung
Regression Analysis
Retinoids
Lung Neoplasms
Body Mass Index
Smoking
Mortality
Incidence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Carolan, B. J., Hughes, G., Morrow, J., Hersh, C. P., O'Neal, W. K., Rennard, S., ... Bowler, R. P. (2014). The association of plasma biomarkers with computed tomography-assessed emphysema phenotypes. Respiratory Research, 15, 127. https://doi.org/10.1186/s12931-014-0127-9

The association of plasma biomarkers with computed tomography-assessed emphysema phenotypes. / Carolan, Brendan J.; Hughes, Grant; Morrow, Jarrett; Hersh, Craig P.; O'Neal, Wanda K.; Rennard, Stephen; Pillai, Sreekumar G.; Belloni, Paula; Cockayne, Debra A.; Comellas, Alejandro P.; Han, Meilan; Zemans, Rachel L.; Kechris, Katerina; Bowler, Russell P.

In: Respiratory Research, Vol. 15, 2014, p. 127.

Research output: Contribution to journalArticle

Carolan, BJ, Hughes, G, Morrow, J, Hersh, CP, O'Neal, WK, Rennard, S, Pillai, SG, Belloni, P, Cockayne, DA, Comellas, AP, Han, M, Zemans, RL, Kechris, K & Bowler, RP 2014, 'The association of plasma biomarkers with computed tomography-assessed emphysema phenotypes', Respiratory Research, vol. 15, pp. 127. https://doi.org/10.1186/s12931-014-0127-9
Carolan, Brendan J. ; Hughes, Grant ; Morrow, Jarrett ; Hersh, Craig P. ; O'Neal, Wanda K. ; Rennard, Stephen ; Pillai, Sreekumar G. ; Belloni, Paula ; Cockayne, Debra A. ; Comellas, Alejandro P. ; Han, Meilan ; Zemans, Rachel L. ; Kechris, Katerina ; Bowler, Russell P. / The association of plasma biomarkers with computed tomography-assessed emphysema phenotypes. In: Respiratory Research. 2014 ; Vol. 15. pp. 127.
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abstract = "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 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.",
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AU - Carolan, Brendan J.

AU - Hughes, Grant

AU - Morrow, Jarrett

AU - Hersh, Craig P.

AU - O'Neal, Wanda K.

AU - Rennard, Stephen

AU - Pillai, Sreekumar G.

AU - Belloni, Paula

AU - Cockayne, Debra A.

AU - Comellas, Alejandro P.

AU - Han, Meilan

AU - Zemans, Rachel L.

AU - Kechris, Katerina

AU - Bowler, Russell P.

PY - 2014

Y1 - 2014

N2 - 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 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.

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 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.

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