PT  - JOURNAL ARTICLE
AU  - M de Vries
AU  - M E Martinus
AU  - N J Bekker
AU  - W Kooistra
AU  - R H Vedder
AU  - W Timens
AU  - M Van Den Berge
AU  - C Brandsma
TI  - Epigenetic clock analysis shows accelerated ageing in severe early onset COPD
AID  - 10.1183/13993003.congress-2022.4574
DP  - 2022 Sep 04
TA  - European Respiratory Journal
PG  - 4574
VI  - 60
IP  - suppl 66
4099  - http://erj.ersjournals.com/content/60/suppl_66/4574.short
4100  - http://erj.ersjournals.com/content/60/suppl_66/4574.full
SO  - Eur Respir J2022 Sep 04; 60
AB  - COPD has been proposed as a disease of accelerated ageing. Severe early onset (SEO-)COPD represents a specific subgroup of patients developing severe COPD at a relatively young age. Given the early onset and progressive nature of the disease in these patients, we hypothesize that accelerated ageing is an important contributor to the pathology of SEO-COPD. Here, we assessed accelerated ageing in (SEO-)COPD by estimating biological age using the epigenetic clock.DNA methylation data was generated by the MethylationEPIC array from lung tissue of 71 ex-smoking subjects including 14 non-COPD controls, 18 SEO-COPD patients (FEV1%pred <40%, age ≤55 years), 26 stage II/III COPD patients and 13 stage IV COPD patients (age >55 years). Biological age was estimated using the Horvath epigenetic clock. Accelerated ageing was calculated by subtracting chronological age from biological age. Differences in accelerated ageing between all groups were calculated using the Kruskal Wallis test followed by a Mann-Whitney U-test to compare the individual groups.The calculated accelerated age was significantly different between all groups (p=5.68x10^-4). Subsequent post-hoc analyses showed that only SEO-COPD was significantly different compared to control (p=2.03x10^-3) with an age acceleration of 9.3 years. SEO-COPD was also significantly different from stage II/III COPD (p=6.95x10^-5) and stage IV COPD with age >55 (p=1.97x10^-2), with an age acceleration of 2.9 and 5.7 years, respectively.Using the epigenetic clock, we show accelerated ageing in patients with SEO-COPD. This indicates that the biological age of SEO-COPD patients is increased and support the hypothesis that accelerated aging contributes to SEO-COPD pathology.FootnotesCite this article as Eur Respir J 2022; 60: Suppl. 66, 4574.This article was presented at the 2022 ERS International Congress, in session “-”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).