Persistence of circulating endothelial microparticles in COPD despite smoking cessation

Thorax. 2016 Dec;71(12):1137-1144. doi: 10.1136/thoraxjnl-2015-208274. Epub 2016 Jul 26.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration number: NCT00974064; NCT01776398.

Keywords: COPD ÀÜ Mechanisms; Smoking cessation; Tobacco and the lung.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Capillaries / pathology
  • Cell-Derived Microparticles / pathology*
  • Endothelial Cells / pathology
  • Endothelium, Vascular / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Lung / blood supply
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / diagnostic imaging
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Respiratory Function Tests
  • Smoking Cessation / methods*
  • Tomography, X-Ray Computed

Associated data

  • ClinicalTrials.gov/NCT00974064
  • ClinicalTrials.gov/NCT01776398