PMID- 28848918
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201017
IS  - 2372-952X (Print)
IS  - 2372-952X (Electronic)
IS  - 2372-952X (Linking)
VI  - 4
IP  - 2
DP  - 2017 Feb 8
TI  - Subtyping Chronic Obstructive Pulmonary Disease Using Peripheral Blood 
      Proteomics.
PG  - 97-108
LID - 10.15326/jcopdf.4.2.2016.0147 [doi]
AB  - Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder. COPD 
      patients may have different clinical features, imaging characteristics and 
      natural history. Multiple studies have investigated heterogeneity using 
      statistical methods such as unsupervised clustering to define different subgroups 
      of COPD based largely on clinical phenotypes. Some studies have performed 
      clustering using genetic data or limited numbers of blood biomarkers. Our primary 
      goal was to use proteomic data to find subtypes of COPD within clinically similar 
      individuals. In the Treatment of Emphysema with a gamma-Selective Retinoid 
      Agonist (TESRA) study, multiplex biomarker panels were run in serum samples 
      collected prior to randomization. After implementing an algorithm to minimize 
      missing values, the dataset included 396 COPD individuals and 87 biomarkers. 
      Using hierarchical clustering, we identified 3 COPD subgroups, containing 267 
      (67.4%), 104 (26.3%), and 25 (6.3%) individuals, respectively. The third cluster 
      had less emphysema on quantitative analysis of chest computed tomography scans 
      (p=0.03) and worse disease-related quality of life based on the St. George's 
      Respiratory Questionnaire (total score cluster 1: 45.6, cluster 2: 45.4, cluster 
      3: 56.6; p=0.01), despite similar levels of lung function impairment (forced 
      expiratory volume in 1 second (49.2%, 49.2%, 48.2 % predicted, respectively). 
      Enrichment analysis showed the biomarkers distinguishing cluster 3 mapped to 
      platelet alpha granule and cell chemotaxis pathways. Thus, we identified a 
      subgroup which has less emphysema but may have greater inflammation, which could 
      be potentially targeted with anti-inflammatory therapies.
FAU - Zarei, Sara
AU  - Zarei S
AD  - Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard 
      Medical School, Boston, Massachusetts.
AD  - San Juan Bautista School of Medicine, Caguas, Puerto Rico.
FAU - Mirtar, Ali
AU  - Mirtar A
AD  - University of California, San Diego.
FAU - Morrow, Jarrett D
AU  - Morrow JD
AD  - Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard 
      Medical School, Boston, Massachusetts.
FAU - Castaldi, Peter J
AU  - Castaldi PJ
AD  - Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard 
      Medical School, Boston, Massachusetts.
FAU - Belloni, Paula
AU  - Belloni P
AD  - Genentech, San Francisco, California.
FAU - Hersh, Craig P
AU  - Hersh CP
AD  - Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard 
      Medical School, Boston, Massachusetts.
LA  - eng
GR  - R01 HL130512/HL/NHLBI NIH HHS/United States
GR  - R01 HL094635/HL/NHLBI NIH HHS/United States
GR  - P01 HL105339/HL/NHLBI NIH HHS/United States
GR  - R01 HL126596/HL/NHLBI NIH HHS/United States
GR  - R01 HL124233/HL/NHLBI NIH HHS/United States
GR  - R01 HL125583/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20170208
PL  - United States
TA  - Chronic Obstr Pulm Dis
JT  - Chronic obstructive pulmonary diseases (Miami, Fla.)
JID - 101635411
PMC - PMC5559108
OTO - NOTNLM
OT  - biomarkers
OT  - cluster analysis
OT  - emphysema
OT  - inflammation
COIS- Dr. Hersh reports consulting fees from AstraZeneca, Concert Pharmaceuticals and 
      Mylan. Dr. Belloni is an employee of Genentech. Drs. Zarei, Mirtar, Morrow, and 
      Castaldi report no competing interests. Roche designed the TESRA trial and 
      collected the data. The funders had no role in the data analysis in this 
      manuscript, the writing of the manuscript or the decision to submit the 
      manuscript for publication.
EDAT- 2017/08/30 06:00
MHDA- 2017/08/30 06:01
PMCR- 2017/02/08
CRDT- 2017/08/30 06:00
PHST- 2017/08/30 06:00 [entrez]
PHST- 2017/08/30 06:00 [pubmed]
PHST- 2017/08/30 06:01 [medline]
PHST- 2017/02/08 00:00 [pmc-release]
AID - 10.15326/jcopdf.4.2.2016.0147 [doi]
PST - epublish
SO  - Chronic Obstr Pulm Dis. 2017 Feb 8;4(2):97-108. doi: 
      10.15326/jcopdf.4.2.2016.0147.