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      Tissue-Specific Ultra-Short Telomeres in Chronic Obstructive Pulmonary Disease

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          Telomere biology, especially tissue-specific ultra-short telomeres, might provide a strong contribution to our current knowledge in COPD development as well as a predictive marker for prognosis. To test this hypothesis, we investigated telomere lengths in lung tissue and leukocytes in patients diagnosed with COPD.

          Patients and Methods

          Thirty-two patients were included in the current study. All patients showed a post-bronchodilator ratio of less than 70% post-bronchodilator predicted value of forced expiratory volume in second (FEV1%), mean 56%; range [19% to 86%]. To be able to investigate ultra-short telomeres, universal single telomere length analysis (U-STELA) was used.


          Our results showed a higher level of the ultra-short telomere presence in bronchoalveolar lavage (BAL) cells when compared to leukocytes with statistical significance t(62)=5.771, p<0.00001. The FEV1% was lower in subjects with ultra-short telomeres in BAL (50.6% vs 81.6%: p<0.001) and in ultra-short telomeres in blood leukocytes (37.3% vs 58.5%: p=0.051) when compared to subjects without ultra-short telomeres in leukocytes. Furthermore, the patients who had ultra-short telomeres in BAL samples were significantly older (p=0.014) than patients who did not have ultra-short telomeres. Ultra-short telomeres in BAL (p=0.05) but not in leukocytes (p=0.33) were associated with FEV1% in a regressions model adjusting for age (p<0.0001), ever smoking (p<0.0001) and sex (p=0.71). The patients with ultra-short telomeres were graded higher in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification (p=0.006).


          This study emphasizes the need to investigate the correct tissue to get a representative evaluation of the stage or advancedness of COPD. To our knowledge, this is the first study to show that there is a correlation between the presence of ultra-short telomeres in lung tissue and COPD severity. Our results suggest that ultra-short telomeres are involved in the molecular pathogenesis of COPD and might be used as a tissue-specific predictive biomarker.

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          Most cited references 26

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          Oxidative stress and free radicals in COPD – implications and relevance for treatment

          Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants. Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation. When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD). In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi. ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells. This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options. Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD. Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases. In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented.
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            Increased airway epithelial and T-cell apoptosis in COPD remains despite smoking cessation.

            There is heterogeneity in the propensity of smokers to develop chronic obstructive pulmonary disease (COPD), and improved treatment strategies are hindered by limited understanding of COPD pathogenesis, especially as distinct from the effects of smoking per se. Although apoptosis is essential for tissue homeostasis, increased apoptosis may cause tissue damage and inflammation. This study addressed whether airway T-lymphocytes and airway epithelial cells (AEC) show an increased likelihood of undergoing apoptosis in COPD and if this was related to smoking. Apoptosis (7-amino-actinomycin D, Annexin, single-stranded DNA and caspase), Bcl-2, Bax and p53 were assessed in cells obtained from bronchial bushing and bronchoalveolar lavage from ex- and continuing smokers with COPD, and nonsmoking controls, using flow cytometry. A mean 87% increase in apoptosis of AEC and a 103% increase in T-lymphocyte apoptosis were found in COPD. There were no significant differences in apoptosis of AEC between current and ex-smokers with COPD. Apoptosis may contribute to chronic obstructive pulmonary disease pathogenesis, and continued excess apoptosis after smoking cessation may offer a new target for therapeutic interventions. Whether the persistence of increased apoptosis after smoking cessation results from changes in the pulmonary milleau after years of noxious insult, or whether some individuals have a natural predisposition toward increased apoptosis and possible development of chronic obstructive pulmonary disease remains to be determined.
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              Oxidative stress, redox signaling pathways, and autophagy in cachectic muscles of male patients with advanced COPD and lung cancer.

              Muscle dysfunction and wasting are predictors of mortality in advanced COPD and malignancies. Redox imbalance and enhanced protein catabolism are underlying mechanisms in COPD. We hypothesized that the expression profile of several biological markers share similarities in patients with cachexia associated with either COPD or lung cancer (LC). In vastus lateralis of cachectic patients with either LC (n=10) or advanced COPD (n=16) and healthy controls (n=10), markers of redox balance, inflammation, proteolysis, autophagy, signaling pathways, mitochondrial function, muscle structure, and sarcomere damage were measured using laboratory and light and electron microscopy techniques. Systemic redox balance and inflammation were also determined. All subjects were clinically evaluated. Compared to controls, in both cachectic groups of patients, a similar expression profile of different biological markers was observed in their muscles: increased levels of muscle protein oxidation and ubiquitination (p<0.05, both), which positively correlated (r=0.888), redox-sensitive signaling pathways (NF-κB and FoxO) were activated (p<0.05, all), fast-twitch fiber sizes were atrophied, muscle structural abnormalities and sarcomere disruptions were significantly greater (p<0.05, both). Structural and functional protein levels were lower in muscles of both cachectic patient groups than in controls (p<0.05, all). However, levels of autophagy markers including ultrastructural autophagosome counts were increased only in muscles of cachectic COPD patients (p<0.05). Systemic oxidative stress and inflammation levels were also increased in both patient groups compared to controls (p<0.005, both). Oxidative stress and redox-sensitive signaling pathways are likely to contribute to the etiology of muscle wasting and sarcomere disruption in patients with respiratory cachexia: LC and COPD.

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of Chronic Obstructive Pulmonary Disease
                30 October 2020
                : 15
                : 2751-2757
                [1 ]Department of Medical Genetics, Faculty of Medicine, Near East University , Nicosia, Cyprus
                [2 ]Department of Molecular Biology of Genetics, Arts and Sciences Faculty, Near East University , Nicosia, Cyprus
                [3 ]Department of Allergy Sleep and Respiratory Medicine, Near East University Hospital , Nicosia, Cyprus
                [4 ]Department of Biostatistics, Faculty of Medicine, Near East University , Nicosia, Cyprus
                [5 ]Section of Respiratory Medicine; Department of Internal Medicine, Sydvestjysk Hospital , Esbjerg, Denmark
                Author notes
                Correspondence: Nedime Serakinci Near East University , Faculty of Medicine, Department of Medical Genetics, Nicosia999058, North CyprusTel +90 392 675 1000 Ext 3017 Email
                © 2020 Cagsin et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (

                Page count
                Figures: 1, Tables: 5, References: 27, Pages: 7
                Original Research

                Respiratory medicine

                copd, ultra-short telomeres, bal, tissue-specific


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