PT  - JOURNAL ARTICLE
AU  - Sara Pastor
AU  - Amparo Escribano
AU  - Silvia Castillo
AU  - Ana Reula
AU  - María Mercedes Navarro-García
AU  - Francisco Sanz
AU  - Estrella Fernandez-Fabrellas
AU  - Pilar Codoñer-Franch
AU  - Francisco Jose Dasi Fernandez
TI  - LSC Abstract – Increased oxidative stress leads to telomere shortening in children with alpha-1 antitrypsin deficiency
AID  - 10.1183/13993003.congress-2016.PP115
DP  - 2016 Sep 01
TA  - European Respiratory Journal
PG  - PP115
VI  - 48
IP  - suppl 60
4099  - http://erj.ersjournals.com/content/48/suppl_60/PP115.short
4100  - http://erj.ersjournals.com/content/48/suppl_60/PP115.full
SO  - Eur Respir J2016 Sep 01; 48
AB  - Background: Oxidative stress (OS) is involved in the pathophysiology of AATD (Escribano A. et al. Thorax 2015; 70:82-3). In addition, it has been shown that OS accelerates telomere shortening which is associated to higher emphysema risk in COPD patients.Rationale and aims: Since AATD is characterised by chronic OS, we hypothesise that telomere shortening would be accelerated in AATD patients and would be associated with higher risk of developing lung disease. This study is aimed to assess the OS profile, the enzymatic antioxidant defence mechanisms and telomere length (TL) in children with AATD and to study its association with AAT phenotypes.Methods: OS parameters, the activity of the main antioxidant enzymes and TL were prospectively measured in fifty-one children diagnosed with alpha-1 antitrypsin deficiency and thirty-eight control individuals.Results: AATD patients showed higher GSSG/GSH ratio (p=0.001; p<0.0001, respectively), malondialdehyde (p=0.004; p<0.0001), 8-OHdG (p<0.0001; p<0.0001) and oxidized proteins (p=0.01; p=0.002) than the control group, while total (p<0.0001; p<0.0001) and reduced glutathione levels (p <0.0001; p<0.0001) were decreased. Catalase activity was decreased (p=0.003; p<0.001) leading to the accumulation of H2O2 (p=0.04; p=0.001), which would explain the high levels of OS observed. TL is decreased in patients with AATD compared to control subjects (p<0.001).Conclusions: Increased OS lead to accelerated telomere shortening in AATD patients. An association between OS, TL and risk of developing lung/liver disease is observed.Funding: SEPAR 2013 and ISCIII (PI14/02162) grants.