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Basic mechanisms in COPD pathogenesis
S49 Telomere Attrition In Circulating White Blood Cells In Copd Relates To Lung Function And Outcomes
  1. Roberto A Rabinovich1,
  2. Gourab Choudhury1,
  3. Ramzi Lahkdar1,
  4. Ellen M Drost1,
  5. Liane McGlynn2,
  6. Jing Bai1,
  7. Paul G Shiels2,
  8. Bruce E Miller3,
  9. Ruth Tal-Singer3,
  10. Alvar Agusti4,
  11. William MacNee1
  1. 1Edinburgh Lung and the Environment Group Initiative (ELEGI), Centre for Inflammation and Research, Queens Medical Research Institute, Edinburgh, Edinburgh, UK
  2. 2University of Glasgow, College of Medical, Veterinary and Life Sciences Institute of Cancer Sciences, Glasgow, UK
  3. 3GlaxoSmithKline R and D, King of Prussia, Pennsylvania, USA
  4. 4Hospital Clinic, IDIBAPS, Universitat de Barcelona and CIBER Enfermedades Respiratorias, FISIB, Mallorca, Spain

Abstract

Introduction Increasing evidence suggests accelerated ageing as a pathogenic mechanism in COPD.

Methods and results Telomere length in circulating WBC, a marker of biological ageing, was assessed in 200 ex-smoker COPD patients (108 male, age 61.5 ± 6.4 years, FEV1 45.6 ± 17.1% predicted), 50 ex-smokers with normal lung function (27 male, age 59.9 ± 7.3 years, FEV1 109.1 ± 13.4%predicted) and 50 non-smoker healthy subjects (27 male, age 59.3 ± 8.3 years, FEV1 113.2 ± 13.1% predicted). TL was assessed by qPCR and expressed as relative T/S ratio.

TL was shorter in COPD (0.77 ± 0.2 relative T/S ratio) than in both ex-smokers (0.83 ± 0.2 relative T/S ratio) and non-smokers (0.84 ± 0.2 relative T/S ratio) (p < 0.05). Furthermore TL correlated negatively with age (r -0.17, p 0.007), emphysema score (r -0.217, p 0.001), number of exacerbations in the previous year to inclusion in the study (r -0.129, p 0.04), number of hospitalisations over 3 years follow-up (r -0.167, p 0.004) and positively with FEV1 (r 0.135, p = 0.03) and arterial oxygen saturation (r 0.161, p 0.01).

Conclusion COPD patients have evidence of premature ageing (shortened TL) compared to normal subjects irrespective of their smoking history. TL relates to FEV1, SatO2, exacerbation rate and hospitalisations.

The ECLIPSE study (GSK Study No. SCO104960, NCT00292552) was sponsored by GlaxoSmithKline.

https://doi.org/10.1136/thoraxjnl-2014-206260.55

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