title: Persistence of circulating endothelial microparticles in COPD despite smoking cessation.
abstract: Increasing evidence links COPD pathogenesis with pulmonary capillary apoptosis. We previously demonstrated that plasma levels of circulating microparticles released from endothelial cells (EMPs) due to apoptosis are elevated in smokers with normal spirometry but low diffusion capacity, that is, with early evidence of lung destruction. We hypothesised that pulmonary capillary apoptosis persists with the development of COPD and assessed its reversibility in healthy smokers and COPD smokers following smoking cessation.
  
  
  
  Pulmonary function and high-resolution CT (HRCT) were assessed in 28 non-smokers, 61 healthy smokers and 49 COPD smokers; 17 healthy smokers and 18 COPD smokers quit smoking for 12 months following the baseline visit. Total EMP (CD42b-CD31+), pulmonary capillary EMP (CD42b-CD31+ACE+) and apoptotic EMP (CD42b-CD62E+/CD42b-CD31+) levels were quantified by flow cytometry.
  
  
  
  Compared with non-smokers, healthy smokers and COPD smokers had elevated levels of circulating EMPs due to active pulmonary capillary endothelial apoptosis. Levels remained elevated over 12 months in healthy smokers and COPD smokers who continued smoking, but returned to non-smoker levels in healthy smokers who quit. In contrast, levels remained significantly abnormal in COPD smokers who quit.
  
  
  
  Pulmonary capillary apoptosis is reversible in healthy smokers who quit, but continues to play a role in COPD pathogenesis in smokers who progressed to airflow obstruction despite smoking cessation.
  
  
  
  NCT00974064; NCT01776398.
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Yael
authors.initials: Y
authors.lastname: Strulovici-Barel
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Staudt
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Anja
authors.initials: A
authors.lastname: Krause
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Gordon
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Tilley
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York.|Department of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Ben-Gary
authors.initials: BG
authors.lastname: Harvey
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York.|Department of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kaner
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Charleen
authors.initials: C
authors.lastname: Hollmann
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York.|Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Mezey
authors.affiliation: Hoffmann-La Roche, Nutley, New Jersey, USA.|Novartis.
authors.forename: Hans
authors.initials: H
authors.lastname: Bitter
authors.affiliation: Hoffmann-La Roche, Nutley, New Jersey, USA.|Eli Lilly and Company.
authors.forename: Sreekumar G
authors.initials: SG
authors.lastname: Pillai
authors.affiliation: Hoffmann-La Roche, Nutley, New Jersey, USA.|PPD Labs.
authors.forename: Holly
authors.initials: H
authors.lastname: Hilton
authors.affiliation: Hoffmann-La Roche, Nutley, New Jersey, USA.|Achillion Pharmaceuticals, Inc.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolff
authors.affiliation: Hoffmann-La Roche, Nutley, New Jersey, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Stevenson
authors.affiliation: Hoffmann-La Roche, Nutley, New Jersey, USA.|Boehringer Ingelheim Pharmaceuticals.
authors.forename: Sudha
authors.initials: S
authors.lastname: Visvanathan
authors.affiliation: Hoffmann-La Roche, Nutley, New Jersey, USA.|Boehringer Ingelheim Pharmaceuticals.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Fine
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000328:Adult; D017209:Apoptosis; D002196:Capillaries / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000473:pathology*; D042783:Endothelial Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008168:Lung / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D012129:Respiratory Function Tests; D016540:Smoking Cessation / Q000379:methods*; D014057:Tomography, X-Ray Computed
keywords: COPD ÀÜ Mechanisms; Smoking cessation; Tobacco and the lung