scholarly journals Epigenetic Marker of Telomeric Age is Associated with Exacerbations and Hospitalizations in Chronic Obstructive Pulmonary Disease

Author(s):  
Ana I Hernández Cordero ◽  
Chen Xi Yang ◽  
Xuan Li ◽  
Stephen Milne ◽  
Virginia Chen ◽  
...  

Abstract Background: Chronic obstructive pulmonary disease (COPD) is an age-related condition that has been associated with early telomere attrition; the clinical implications of telomere shortening in COPD are not well known. In this study we aimed to determine the relationship of the epigenetic regulation of telomeric length in peripheral blood with the risk of exacerbations and hospitalization in patients with COPD. Methods: Blood DNA methylation profiles were obtained from 292 patients with COPD enrolled in the placebo arm of the Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated With Chronic Obstructive Pulmonary Disease study (MACRO) and who were followed for 1-year. We calculated telomere length based on DNA methylation markers (DNAmTL) and related this biomarker to the risk of exacerbation and hospitalization and health status (St. George respiratory questionary score [SGRQ]) over this time using a Cox proportional hazards model. We also used linear models to investigate the associations of DNAmTL with the rates of exacerbations and hospitalizations (adjusted for chronological age, lung function, race, sex, smoking, and body mass index).Results: Participants with short DNAmTL demonstrated increased risk of exacerbation (P=0.02) and hospitalization (P=0.03) compared to those with longer DNAmTL. DNAmTL age acceleration was associated with higher rates of exacerbation (P=1.35x10-04) and hospitalization (P=5.21x10-03) and poor health status (SGRQ) independent of chronological age (P=0.03).Conclusion: Telomeric age based on blood DNA methylation is associated with COPD exacerbation and hospitalization and thus is a promising biomarker for poor outcomes in COPD.

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ana I. Hernández Cordero ◽  
Chen Xi Yang ◽  
Xuan Li ◽  
Stephen Milne ◽  
Virginia Chen ◽  
...  

Abstract Background Chronic obstructive pulmonary disease (COPD) is an age-related condition that has been associated with early telomere attrition; the clinical implications of telomere shortening in COPD are not well known. In this study we aimed to determine the relationship of the epigenetic regulation of telomeric length in peripheral blood with the risk of exacerbations and hospitalization in patients with COPD. Methods Blood DNA methylation profiles were obtained from 292 patients with COPD enrolled in the placebo arm of the Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated with Chronic Obstructive Pulmonary Disease (MACRO) Study and who were followed for 1-year. We calculated telomere length based on DNA methylation markers (DNAmTL) and related this biomarker to the risk of exacerbation and hospitalization and health status (St. George Respiratory Questionnaire [SGRQ]) score over time using a Cox proportional hazards model. We also used linear models to investigate the associations of DNAmTL with the rates of exacerbation and hospitalization (adjusted for chronological age, lung function, race, sex, smoking, body mass index and cell composition). Results Participants with short DNAmTL demonstrated increased risk of exacerbation (P = 0.02) and hospitalization (P = 0.03) compared to those with longer DNAmTL. DNAmTL age acceleration was associated with higher rates of exacerbation (P = 1.35 × 10–04) and hospitalization (P = 5.21 × 10–03) and poor health status (lower SGRQ scores) independent of chronological age (P = 0.03). Conclusion Telomeric age based on blood DNA methylation is associated with COPD exacerbation and hospitalization and thus a promising biomarker for poor outcomes in COPD.


2020 ◽  
Vol 29 (2) ◽  
pp. 864-872
Author(s):  
Fernanda Borowsky da Rosa ◽  
Adriane Schmidt Pasqualoto ◽  
Catriona M. Steele ◽  
Renata Mancopes

Introduction The oral cavity and pharynx have a rich sensory system composed of specialized receptors. The integrity of oropharyngeal sensation is thought to be fundamental for safe and efficient swallowing. Chronic obstructive pulmonary disease (COPD) patients are at risk for oropharyngeal sensory impairment due to frequent use of inhaled medications and comorbidities including gastroesophageal reflux disease. Objective This study aimed to describe and compare oral and oropharyngeal sensory function measured using noninstrumental clinical methods in adults with COPD and healthy controls. Method Participants included 27 adults (18 men, nine women) with a diagnosis of COPD and a mean age of 66.56 years ( SD = 8.68). The control group comprised 11 healthy adults (five men, six women) with a mean age of 60.09 years ( SD = 11.57). Spirometry measures confirmed reduced functional expiratory volumes (% predicted) in the COPD patients compared to the control participants. All participants completed a case history interview and underwent clinical evaluation of oral and oropharyngeal sensation by a speech-language pathologist. The sensory evaluation explored the detection of tactile and temperature stimuli delivered by cotton swab to six locations in the oral cavity and two in the oropharynx as well as identification of the taste of stimuli administered in 5-ml boluses to the mouth. Analyses explored the frequencies of accurate responses regarding stimulus location, temperature and taste between groups, and between age groups (“≤ 65 years” and “> 65 years”) within the COPD cohort. Results We found significantly higher frequencies of reported use of inhaled medications ( p < .001) and xerostomia ( p = .003) in the COPD cohort. Oral cavity thermal sensation ( p = .009) was reduced in the COPD participants, and a significant age-related decline in gustatory sensation was found in the COPD group ( p = .018). Conclusion This study found that most of the measures of oral and oropharyngeal sensation remained intact in the COPD group. Oral thermal sensation was impaired in individuals with COPD, and reduced gustatory sensation was observed in the older COPD participants. Possible links between these results and the use of inhaled medication by individuals with COPD are discussed.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoman Zhou ◽  
Yunjun Zhang ◽  
Yutian Zhang ◽  
Quanni Li ◽  
Mei Lin ◽  
...  

Abstract Objective Chronic obstructive pulmonary disease (COPD) is a complicated multi-factor, multi-gene disease. Here, we aimed to assess the association of genetic polymorphisms in LINC01414/ LINC00824 and interactions with COPD susceptibility. Methods Three single nucleotide polymorphisms (SNPs) in LINC01414/LINC00824 was genotyped by Agena MassARRAY platform among 315 COPD patients and 314 controls. Logistic analysis adjusted by age and gender were applied to estimate the genetic contribution of selected SNPs to COPD susceptibility. Results LINC01414 rs699467 (OR = 0.73, 95% CI 0.56–0.94, p = 0.015) and LINC00824 rs7815944 (OR = 0.56, 95% CI 0.31–0.99, p = 0.046) might be protective factors for COPD occurrence, while LINC01414 rs298207 (OR = 2.88, 95% CI 1.31–6.31, p = 0.008) risk-allele was related to the increased risk of COPD in the whole population. Rs7815944 was associated with the reduced risk of COPD in the subjects aged > 70 years (OR = 0.29, p = 0.005). Rs6994670 (OR = 0.57, p = 0.007) contribute to a reduced COPD risk, while rs298207 (OR = 7.94, p = 0.009) was related to a higher susceptibility to COPD at age ≤ 70 years. Rs298207 (OR = 2.54, p = 0.043) and rs7815944 (OR = 0.43, p = 0.028) variants was associated COPD risk among males. Rs7815944 (OR = 0.16, p = 0.031) was related to the reduced susceptibility of COPD in former smokers. Moreover, the association between rs298207 genotype and COPD patients with dyspnea was found (OR = 0.50, p = 0.016), and rs7815944 was related to COPD patients with wheezing (OR = 0.22, p = 0.008). Conclusion Our finding provided further insights into LINC01414/LINC00824 polymorphisms at risk of COPD occurrence and accumulated evidence for the genetic susceptibility of COPD.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Kek Pang ◽  
Ahmad Izuanuddin Ismail ◽  
Yoke Fun Chan ◽  
Adelina Cheong ◽  
Yoong Min Chong ◽  
...  

Abstract Background Available data on influenza burden across Southeast Asia are largely limited to pediatric populations, with inconsistent findings. Methods We conducted a multicenter, hospital-based active surveillance study of adults in Malaysia with community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and acute exacerbation of asthma (AEBA), who had influenza-like illness ≤10 days before hospitalization. We estimated the rate of laboratory-confirmed influenza and associated complications over 13 months (July 2018–August 2019) and described the distribution of causative influenza strains. We evaluated predictors of laboratory-confirmed influenza and severe clinical outcomes using multivariate analysis. Results Of 1106 included patients, 114 (10.3%) were influenza-positive; most were influenza A (85.1%), with A/H1N1pdm09 being the predominant circulating strain during the study following a shift from A/H3N2 from January–February 2019 onwards. In multivariate analyses, an absence of comorbidities (none versus any comorbidity [OR (95%CI), 0.565 (0.329–0.970)], p = 0.038) and of dyspnea (0.544 (0.341–0.868)], p = 0.011) were associated with increased risk of influenza positivity. Overall, 184/1106 (16.6%) patients were admitted to intensive care or high-dependency units (ICU/HDU) (13.2% were influenza positive) and 26/1106 (2.4%) died (2.6% were influenza positive). Males were more likely to have a severe outcome (ICU/HDU admission or death). Conclusions Influenza was a significant contributor to hospitalizations associated with CAP, AECOPD and AEBA. However, it was not associated with ICU/HDU admission in this population. Study registration, NMRR ID: NMRR-17-889-35,174.


Author(s):  
Marc Daniels ◽  
Jan Philipp Stromps ◽  
Wolfram Heitzmann ◽  
Jennifer Schiefer ◽  
Paul Christian Fuchs ◽  
...  

Abstract There is an increased risk for burn injuries associated with home oxygen therapy of patients with chronic obstructive pulmonary disease since 10 to 50 % of these patients continue to smoke. Enzymatic eschar removal of facial burns is gaining popularity but intubation of this specific patient group often leads to prolonged weaning and can require tracheostomy. This study dealt with the question if enzymatic debridement in these patients can also be performed in analgosedation. A selective review of the literature regarding burn trauma associated with home oxygen use in patients with COPD was performed, as well as a retrospective analysis of all patients with burn injuries associated with home oxygen use and chronic obstructive pulmonary disease that were admitted to the study clinic. In the literature 1746 patients with burns associated with home oxygen use are described, but none of them received enzymatic debridement. In this study seventeen patients were included. All three patients in this study with facial full-thickness burn injuries received enzymatic debridement. The mortality rate in this cohort was 17.6 % (3/17). Up to date, there is limited experience performing regional anesthesia debridement in patients with COPD. This is the first manuscript describing the use of enzymatic debridement in patients with COPD and home oxygen therapy. We could confirm other studies that intubation of these patients leads to prolonged ventilation hours and increases the probability for poor prognosis. Therefore, we described the treatment of enzymatic debridement in analgosedation without intubation.


Epigenomics ◽  
2021 ◽  
Author(s):  
XinXin Huo ◽  
SiHui Jin ◽  
YiGe Wang ◽  
Li Ma

Chronic obstructive pulmonary disease (COPD), a complex disease with polygenetic tendency, is one of the most important health problems in the world. Recently, in the study of the pathogenesis of the COPD, epigenetic changes caused by environmental factors, such as DNA methylation, started to attract more attention than genetic factors. In this review, we discuss the main features of DNA methylation, such as DNA methyltransferases and the methylation sites that modulate the DNA methylation level, and their roles in COPD progression. Finally, to promote new ideas for the prevention and treatment of COPD, we focus on the potential of DNA methylation as a COPD therapeutic target.


2017 ◽  
Vol 46 ◽  
pp. 11-15 ◽  
Author(s):  
Angelo Zinellu ◽  
Elisabetta Sotgiu ◽  
Alessandro G. Fois ◽  
Elisabetta Zinellu ◽  
Salvatore Sotgia ◽  
...  

2021 ◽  
Vol 11 (9) ◽  
pp. 919
Author(s):  
Asima Karim ◽  
Tahir Muhammad ◽  
Rizwan Qaisar

Patients with chronic obstructive pulmonary disease (COPD) present with an advanced form of age-related muscle loss or sarcopenia. Among multiple pathomechanisms of sarcopenia, neuromuscular junction (NMJ) degradation may be of primary relevance. We evaluated the circulating biomarkers of NMJ degradation, including c-terminal agrin fragment -22 (CAF22), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) as predictors of sarcopenia in COPD during pulmonary rehabilitation (PR). Male, 61–77-year-old healthy controls and patients of COPD (n = 77–84/group) were recruited for measurements of circulating CAF22, BDNF, and GDNF levels. Functional assessment and measurements of plasma biomarkers were performed at diagnosis and following six months of PR. CAF22 levels were elevated while BDNF and GDNF levels were reduced in COPD patients at diagnosis, which were incompletely restored to normal levels following PR. These biomarkers showed varying degrees of associations with indexes of sarcopenia and functional recovery during PR. Logistic regression revealed that the combined use of three biomarkers enhanced the diagnostic accuracy of sarcopenia better than single biomarkers. Altogether, measurements of plasma CAF22, BDNF, and GDNF may be helpful for the accurate diagnosis of sarcopenia and functional capacity in COPD during PR.


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