title: Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype.
abstract: BACKGROUND
  Because chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, the identification of specific clinical phenotypes is key to developing more effective therapies. To explore if the persistence of systemic inflammation is associated with poor clinical outcomes in COPD we assessed patients recruited to the well-characterized ECLIPSE cohort (NCT00292552).
  
  
  RESULTS
  Six inflammatory biomarkers in peripheral blood (white blood cells (WBC) count and CRP, IL-6, IL-8, fibrinogen and TNF-α levels) were quantified in 1,755 COPD patients, 297 smokers with normal spirometry and 202 non-smoker controls that were followed-up for three years. We found that, at baseline, 30% of COPD patients did not show evidence of systemic inflammation whereas 16% had persistent systemic inflammation. Even though pulmonary abnormalities were similar in these two groups, persistently inflamed patients during follow-up had significantly increased all-cause mortality (13% vs. 2%, p<0.001) and exacerbation frequency (1.5 (1.5) vs. 0.9 (1.1) per year, p<0.001) compared to non-inflamed ones. As a descriptive study our results show associations but do not prove causality. Besides this, the inflammatory response is complex and we studied only a limited panel of biomarkers, albeit they are those investigated by the majority of previous studies and are often and easily measured in clinical practice.
  
  
  CONCLUSIONS
  Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.
authors.affiliation: Thorax Institute, Hospital Clinic, Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona and Centro de investigación en red de enfermedades respiratorias (CIBERES), Barcelona, Spain. alvar.agusti@clinic.ub.es
authors.forename: Alvar
authors.initials: A
authors.lastname: Agustí
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Edwards
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
authors.forename: William
authors.initials: W
authors.lastname: MacNee
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Miller
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Peter M A
authors.initials: PM
authors.lastname: Calverley
authors.forename: Emiel
authors.initials: E
authors.lastname: Wouters
authors.forename: Courtney
authors.initials: C
authors.lastname: Crim
authors.forename: Julie C
authors.initials: JC
authors.lastname: Yates
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.forename: Harvey O
authors.initials: HO
authors.lastname: Coxson
authors.forename: Per
authors.initials: P
authors.lastname: Bakke
authors.forename: Ruth J
authors.initials: RJ
authors.lastname: Mayer
authors.forename: Bartolome
authors.initials: B
authors.lastname: Celli
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007958:Leukocyte Count; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000473:pathology*; D012907:Smoking; D013147:Spirometry; D011795:Surveys and Questionnaires; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen; D002097:C-Reactive Protein