• Yael Strulovici-Barel, Michelle R Staudt, Anja Krause, Cynthia Gordon, Ann E Tilley, Ben-Gary Harvey, Robert J Kaner, Charleen Hollmann, Jason G Mezey, Hans Bitter, Sreekumar G Pillai, Holly Hilton, Gerhard Wolff, Christopher S Stevenson, Sudha Visvanathan, Jay S Fine, and Ronald G Crystal.
• Department of Genetic Medicine, Weill Medical College of Cornell University, New York, New York.
• Thorax. 2016 Dec 1; 71 (12): 1137-1144.

IntroductionIncreasing 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.MethodsPulmonary 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.ResultsCompared 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.ConclusionsPulmonary 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 NumberNCT00974064; NCT01776398.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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