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.
- Smoking cessation
- COPD ÀÜ Mechanisms
- Tobacco and the lung
Statistics from Altmetric.com
Contributors Conception and design: RGC. Acquisition and data interpretation: YS-B, MRS, AK, CG, AET, BG-H, RJK, CH, JGM, HB, SS, SGP, HH, GW, CSS, SV, JSF and RGC. Drafting of the manuscript: YS-B, MRS, AK, AET and RGC.
Funding F. Hoffman-La Roche, National Institutes of Health (P50HL084936), (R01HL107882), (U01HL121828) (UL1 RR02414) and (UL1 TR000457).
Competing interests Hans Bitter, Sriram Sridhar, Sreekumar G. Pillai, Holly Hilton, Gerhard Wolff, Christopher S. Stevenson, Sudha Visvanathan and Jay S. Fine were all former employees of Hoffmann-La Roche.
Ethics approval Weill Cornell Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.