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Research
Pack Years and Lower Lung Function is Associated With Ultra-short Telomeres in Copd: Evidence From Lung Tissue
Nedime Serakinci
Near East University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1884-0839
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Chronic obstructive pulmonary disease (COPD) is driven by a complicated mix of factors such as lifestyle and environmental exposures. Tobacco smoking is the main risk factor for forming chronic inflammation in COPD. Association between cigarette smoking and the role of telomere shortening in COPD has been studied mainly based on the assessment of mean telomere length on leukocytes instead of lung tissue where the primary damage occurs. Here we investigate this association in bronchoalveolar samples by using a new assay that specifically evaluates critically short telomeres, namely, ultra-short telomeres that have sizes less than 1.5kb.
Methods
The study was carried out on materials from the patients eligible for bronchoscopy as well as mild to severe persistent airway obstruction, defined as a post-bronchodilator ratio of less than 70%. Bronchial washing (BW) and leukocyte samples were collected from 32 patients diagnosed with COPD. Telomere length evaluation was done with isolated DNA using Universal STELA to specifically identify the presence of ultra-short telomeres in samples. A t-Student, ANOVA, Chi2, and Paired Sample T-test were used to test differences in means and proportions in statistical analysis. Two-tailed p-values ≤ 0.05 were considered significant
Results
The location of BW did not show a significant difference when compared in terms of the presence of ultra-short telomeres (p>0.05). Higher total pack-years was found amongst patients with ultra-short telomeres (32 packyears versus 16 packyears; p=0.045), lower lung function (FEV1%) (51% versus 82%; p<0.001) when compared with subjects with telomere length more than 1.5kbs in BW. An increasing number of total pack-years, older age and lower FEV1% was observed through the groups comprising subjects with ultra-short telomeres in both BW and leukocytes, subjects with ultra-short telomeres only in BW and subjects with telomeres longer than 1.5kbs(all p<0.01)
Conclusions
Our results emphasize the role of ultra-short telomeres in COPD, in vivo, especially when the lung tissue instead of leukocytes is investigated. Additionally, our results demonstrated a dose-response association between pack-years of smoking, low lung function, and ultra-short telomere length in COPD.
Keywords
Chronic obstructive pulmonary disease (COPD), bronchoalveolar, short telomeres, namely, ultra-short telomeres
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Research
Pack Years and Lower Lung Function is Associated With Ultra-short Telomeres in Copd: Evidence From Lung Tissue
Nedime Serakinci
Near East University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1884-0839
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 24 Jun, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Medical Genetics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Chronic obstructive pulmonary disease (COPD) is driven by a complicated mix of factors such as lifestyle and environmental exposures. Tobacco smoking is the main risk factor for forming chronic inflammation in COPD. Association between cigarette smoking and the role of telomere shortening in COPD has been studied mainly based on the assessment of mean telomere length on leukocytes instead of lung tissue where the primary damage occurs. Here we investigate this association in bronchoalveolar samples by using a new assay that specifically evaluates critically short telomeres, namely, ultra-short telomeres that have sizes less than 1.5kb.
Methods
The study was carried out on materials from the patients eligible for bronchoscopy as well as mild to severe persistent airway obstruction, defined as a post-bronchodilator ratio of less than 70%. Bronchial washing (BW) and leukocyte samples were collected from 32 patients diagnosed with COPD. Telomere length evaluation was done with isolated DNA using Universal STELA to specifically identify the presence of ultra-short telomeres in samples. A t-Student, ANOVA, Chi2, and Paired Sample T-test were used to test differences in means and proportions in statistical analysis. Two-tailed p-values ≤ 0.05 were considered significant
Results
The location of BW did not show a significant difference when compared in terms of the presence of ultra-short telomeres (p>0.05). Higher total pack-years was found amongst patients with ultra-short telomeres (32 packyears versus 16 packyears; p=0.045), lower lung function (FEV1%) (51% versus 82%; p<0.001) when compared with subjects with telomere length more than 1.5kbs in BW. An increasing number of total pack-years, older age and lower FEV1% was observed through the groups comprising subjects with ultra-short telomeres in both BW and leukocytes, subjects with ultra-short telomeres only in BW and subjects with telomeres longer than 1.5kbs(all p<0.01)
Conclusions
Our results emphasize the role of ultra-short telomeres in COPD, in vivo, especially when the lung tissue instead of leukocytes is investigated. Additionally, our results demonstrated a dose-response association between pack-years of smoking, low lung function, and ultra-short telomere length in COPD.
Figure 1
Figure 2
Figure 3