Doctoral defence: Ingrid Oit-Wiscombe "Genetic markers of enzymatics in the pathogenesis of chronic obstructive pulmonary disease as a systemic disease and the effects of antioxidant peptides"

On March 7th Ingrid Oit-Wiscombe will defend her thesis "Genetic markers of enzymatics in the pathogenesis of chronic obstructive pulmonary disease as a systemic disease and the effects of antioxidant peptides".

Supervisors:
Professor Alan Altraja, University of Tartu
professor Ursel Soomets (until January 2022), University of Tartu

Opponent:
Adjunct Professor and Senior Consultant Terttu Harju, Oulu University Hospital (Finland)

Summary:
Chronic obstructive pulmonary disease (COPD) is a relentlessly progressive disease, one of the 3 leading causes of deaths and morbidity worldwide [1]. COPD is projected to increase in the coming decades because of continued exposure to risk factors and aging [1,2]. The largest COPD burden is attributed to acute exacerbations (AE-COPD), characterized by sudden worsening of respiratory symptoms over ≤2 weeks [3].

Cigarette smoke, the main risk factor of COPD, causes inflammation and oxidative stress (OS) both in the airways and in the whole body [4]. OS is a key player in the development and progression of COPD [5]. Thus, a strategy to diagnose and prevent COPD via redox-inflammatory path is a critical priority.

We currently concentrated on systemic effects of COPD and showed that DNA damage and its reparation increased in peripheral blood cells, along with the progression of the airflow obstruction. The damage was even more severe amongst patients with AE-COPD, showing the incredible burden COPD brings about in the whole body. We also showed that some enzymes that fight the inflammation were expressed higher in COPD patients’ bloodstream, whereas other enzymes that facilitate resolving the inflammation were under-expressed. This overactivation of the redox-inflammatory axis and the inability to resolve it provides a new explanation for the vicious cycle of the development and progression of COPD. However, the expressions of not all enzymes changed as the airflow limitation progressed, raising questions as to what might be the associates of lung function decline and development of COPD.

Lastly, we found that synthetic antioxidants, new therapeutic potentials, despite increasing the level of certain antioxidant enzymes, also increased the expression of some pro-inflammatory enzymes. Therefore, these cannot possibly be used directly as themselves, but could serve as a lead for designing further COPD therapies.

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2023 [updated 2023;2 November 2023]. Available from: https://goldcopd.org/
2. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006 Nov;3(11):e442.
3. Ritchie AI, Wedzicha JA. Definition, Causes, Pathogenesis, and Consequences of Chronic Obstructive Pulmonary Disease Exacerbations. Clin Chest Med. 2020 Sep;41(3):421-438.
4. Bhalla DK, Hirata F, Rishi AK, et al. Cigarette smoke, inflammation, and lung injury: a mechanistic perspective. J Toxicol Environ Health B Crit Rev. 2009 Jan;12(1):45-64.
5. Brassington K, Selemidis S, Bozinovski S, et al. New frontiers in the treatment of comorbid cardiovascular disease in chronic obstructive pulmonary disease. Clin Sci (Lond). 2019 Apr 15;133(7):885-904.