scholarly journals LINC01414/LINC00824 genetic polymorphisms in association with the susceptibility of chronic obstructive pulmonary disease

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.

2019 ◽  
Vol 9 ◽  
pp. 2235042X1882020 ◽  
Author(s):  
Irini Gergianaki ◽  
Ioanna Tsiligianni

Background: Although, both chronic obstructive pulmonary disease (COPD) and rheumatic diseases (RDs) are common, and each has significant impact on patients’ overall health/quality of life, their co-occurrence has received little attention, while 15% of COPD remains undiagnosed in RDs. Objective: To update the information regarding the comorbid state of RD/COPD (prevalence, incidence), to examine whether patients with RD have increased risk of developing COPD and vice versa, and what implications this comorbidity has on patients’ outcomes (mortality, hospitalizations, exacerbations). Methods: We performed a systematic literature review regarding the comorbidity of an RD (rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), primary Sjogren syndrome disease (pSS), and systemic sclerosis (SSc)) with COPD. From 2803 reports retrieved, 33 articles were further screened. Finally, 27 articles were included. Results: Robust evidence supports that COPD develops up to 68% more frequently in patients with RA, as compared to the general population. Similarly, COPD is increased in every other RD that was studied. Further, self-referred arthritis is more common in COPD patients versus non-COPD controls and a predictor of worst self-rated health status. Patients with inflammatory arthritis/COPD have increased mortality (threefold in RA-COPD, irrespectively of which is first diagnosed), hospitalizations, and emergency visits. Conclusion: COPD is more common in patients with RA, AS, PsA, SLE, pSS, and SSc; yet, the association, vice versa, warrants further investigation. Nevertheless, COPD/RDs coexistence has significant prognostic value for worst outcomes; therefore, awareness is required to track early identification, especially in primary care.


2021 ◽  
Vol 12 ◽  
Author(s):  
Nathalie Acevedo ◽  
Jose Miguel Escamilla-Gil ◽  
Héctor Espinoza ◽  
Ronald Regino ◽  
Jonathan Ramírez ◽  
...  

BackgroundChronic obstructive pulmonary disease (COPD) is associated with increased risk of severe COVID-19, but the mechanisms are unclear. Besides, patients with severe COVID-19 have been reported to have increased levels of several immune mediators.MethodsNinety-two proteins were quantified in 315 plasma samples from 118 asthmatics, 99 COPD patients and 98 healthy controls (age 40-90 years), who were recruited in Colombia before the COVID-19 pandemic. Protein levels were compared between each disease group and healthy controls. Significant proteins were compared to the gene signatures of SARS-CoV-2 infection reported in the “COVID-19 Drug and Gene Set Library” and with experimentally tested protein biomarkers of severe COVID-19.ResultsForty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11). These proteins are involved in chemokine signaling pathways related with response to viral infections and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 Related Gene Sets database. An increase of HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE has also been experimentally detected in patients with severe COVID-19.ConclusionsCOPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19. Our study suggests that COPD patients have a systemic dysregulation in chemokine networks (including HGF and CXCL9) that could make them more susceptible to severe COVID-19. Also, that IL-6 levels are increased in some asthmatic patients (especially in females) and this may influence their response to COVID-19. The findings in this study depict a novel panel of inflammatory plasma proteins in COPD patients that may potentially associate with increased susceptibility to severe COVID-19 and might be useful as a biomarker signature after future experimental validation.


2015 ◽  
Vol 3 (4) ◽  
pp. 655-660 ◽  
Author(s):  
Sava Pejkovska ◽  
Biserka Jovkovska Kaeva ◽  
Zlatica Goseva ◽  
Zoran Arsovski ◽  
Jelena Jovanovska Janeva ◽  
...  

BACKGROUND: Noninvasive mechanical ventilation (NIV) applies ventilator support through the patient’s upper airway using a mask.AIM: The aim of the study is to define factors that will point out an increased risk of NIV failure in patients with exacerbation of Chronic Obstructive Pulmonary Disease (COPD).PATIENTS AND METHODS: Patients over the age of 40, treated with NIV, were prospectively recruited. After data processing, the patients were divided into two groups: 1) successful NIV treatment group; 2) failed NIV treatment group.RESULTS: On admission arterial pH and Glasgow coma scale (GCS) levels were lower (pH: p < 0.05, GCS: p < 0.05), and Acute Physiology and Chronic Health Evaluation II (APACHE) score and PaCO2 were higher (p < 0.05) in the NIV failure group. Arterial pH was lower (p < 0.05) and PaCO2 and respiratory rate were higher (p < 0.05) after 1h, and arterial pH was lower (p < 0.05) and PaCO2 (p < 0.05), respiratory and heart rate were higher (p < 0.05) after 4h in the NIV failure group.CONCLUSION: Measurement and monitoring of certain parameters may be of value in terms of predicting the effectiveness of NIV treatment.


2018 ◽  
Vol 119 (5) ◽  
pp. 543-551 ◽  
Author(s):  
Arora R. Ingadottir ◽  
Anne M. Beck ◽  
Christine Baldwin ◽  
C. Elizabeth Weekes ◽  
Olof G. Geirsdottir ◽  
...  

AbstractLow energy and protein intakes have been associated with an increased risk of malnutrition in outpatients with chronic obstructive pulmonary disease (COPD). We aimed to assess the energy and protein intakes of hospitalised COPD patients according to nutritional risk status and requirements, and the relative contribution from meals, snacks, drinks and oral nutritional supplements (ONS), and to examine whether either energy or protein intake predicts outcomes. Subjects were COPD patients (n 99) admitted to Landspitali University Hospital in 1 year (March 2015–March 2016). Patients were screened for nutritional risk using a validated screening tool, and energy and protein intake for 3 d, 1–5 d after admission to the hospital, was estimated using a validated plate diagram sheet. The percentage of patients reaching energy and protein intake ≥75 % of requirements was on average 59 and 37 %, respectively. Malnourished patients consumed less at mealtimes and more from ONS than lower-risk patients, resulting in no difference in total energy and protein intakes between groups. No clear associations between energy or protein intake and outcomes were found, although the association between energy intake, as percentage of requirement, and mortality at 12 months of follow-up was of borderline significance (OR 0·12; 95 % CI 0·01, 1·15; P=0·066). Energy and protein intakes during hospitalisation in the study population failed to meet requirements. Further studies are needed on how to increase energy and protein intakes during hospitalisation and after discharge and to assess whether higher intake in relation to requirement of hospitalised COPD patients results in better outcomes.


2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Linyang Ye ◽  
Xi Huang ◽  
Qingxiang Wang ◽  
Hualing Yang ◽  
Dongmiao Cai ◽  
...  

A preferred reporting items for systematic reviews and meta-analyses-compliant meta-analysis was conducted to test the association of metabolic syndrome and its components with the risk of chronic obstructive pulmonary disease (COPD) based on observational studies. Literature retrieval, article selection and data extraction were done by two researchers independently. Total 16 articles (20 independent studies) were analyzed with 3915 COPD patients and 25,790 control participants. Overall analysis indicated that metabolic syndrome was significantly associated with 1.53-fold (95% confidence interval [CI]: 1.23–1.9, P<0.001) increased risk of COPD, with moderate heterogeneity (I2 = 74.3%). Of four metabolic components, hypertension was significantly associated with 1.55-fold (95% CI: 1.14–2.11, P=0.005) increased risk, and averaged levels of systolic blood pressure (weighted mean difference [WMD] = 3.626 mmHg, 95% CI: 1.537–5.714, P<0.001) and glucose (WMD = 2.976 mmol/l, 95% CI: 0.141–5.812; P=0.04) were significantly higher in COPD patients than in control participants, yet that of body mass index (WMD = −1.463 kg/m2, 95% CI: −2.716 to −0.211, P=0.022) were significantly lower. Gender, race, source of control participants, matched status and sample size were identified as accountable factors for significant heterogeneity. Altogether, the presence of metabolic syndrome, especially its component hypertension, was associated with significantly increased risk of COPD.


2015 ◽  
Vol 53 (2) ◽  
pp. 133-139 ◽  
Author(s):  
C.A. Buzea ◽  
G.A. Dan ◽  
Anca Rodica Dan ◽  
Caterina Delcea ◽  
M.I. Balea ◽  
...  

Abstract Patients with chronic obstructive pulmonary disease (COPD) have an increased risk for cardiac arrhythmias. Ventricular late potentials (VLP) on signal-averaged electrocardiography (SAECG) are associated with an increased risk for malignant ventricular arrhythmias. Our aim is to investigate the modifications of SAECG parameters and the presence of VLP as possible indicators of proarrhythmic substrate in patients with COPD. We prospectively enrolled 41 consecutive patients in the COPD group and 63 patients without any history of pulmonary disease, matched for age and hypertension history, in the control group. Pulmonary function tests, arterial blood gases, echocardiography, 24-hour Holter monitoring and SAECG were performed. We measured total filtered QRS duration (QRSf), duration of high frequency, low-amplitude signals < 40 V (HFLA40), and root mean square voltage in the last 40 ms (RMS40). VLP were considered if at least two of these parameters were abnormal. Results. We did not register any significant differences in QRSf, HFLA40 or RMS40 between the two groups. In the COPD group there was a non-significant higher percentage of patients with VLP in comparison with the control group. In the COPD patients we registered a significantly higher number of isolated premature ventricular beats and of combined complex ventricular arrhythmias, consisting of polymorphic PVC, couplets, triplets or nonsustained ventricular tachycardias. None of these arrhythmic parameters correlated with SAECG variables or with the presence of VLP. Conclusion. In COPD patients parameters measured on signal-averaged electrocardiography and ventricular late potentials analysis have little value in risk stratification for ventricular arrhythmias.


2016 ◽  
Vol 310 (11) ◽  
pp. L1011-L1027 ◽  
Author(s):  
P. Padmini S.J. Khedoe ◽  
Patrick C.N. Rensen ◽  
Jimmy F.P. Berbée ◽  
Pieter S. Hiemstra

Patients with chronic obstructive pulmonary disease (COPD) have an increased risk for cardiovascular disease (CVD). Currently, COPD patients with atherosclerosis (i.e., the most important underlying cause of CVD) receive COPD therapy complemented with standard CVD therapy. This may, however, not be the most optimal treatment. To investigate the link between COPD and atherosclerosis and to develop specific therapeutic strategies for COPD patients with atherosclerosis, a substantial number of preclinical studies using murine models have been performed. In this review, we summarize the currently used murine models of COPD and atherosclerosis, both individually and combined, and discuss the relevance of these models for studying the pathogenesis and development of new treatments for COPD patients with atherosclerosis. Murine and clinical studies have provided complementary information showing a prominent role for systemic inflammation and oxidative stress in the link between COPD and atherosclerosis. These and other studies showed that murine models for COPD and atherosclerosis are useful tools and can provide important insights relevant to understanding the link between COPD and CVD. More importantly, murine studies provide good platforms for studying the potential of promising (new) therapeutic strategies for COPD patients with CVD.


2021 ◽  
Author(s):  
Nathalie Acevedo ◽  
Jose Miguel Escamilla-Gil ◽  
Héctor Espinoza ◽  
Ronald Regino ◽  
Jonathan Ramírez ◽  
...  

AbstractBackgroundRespiratory diseases such as chronic obstructive pulmonary disease (COPD) have been associated with increased risk of severe SARS-CoV-2 infection, but the mechanisms and putative immune pathways are unclear. Besides, increased levels of several immune mediators in patients with severe coronavirus disease 19 (COVID-19) have been reported.ObjectiveTo perform an immunoproteomic profiling of dysregulated plasma proteins in patients with asthma and COPD and to evaluate their relationship with biomarkers of severe COVID-19.Methods92 protein biomarkers were quantified in 315 plasma samples from adult subjects (age 40-90 years) including 118 asthmatics, 99 COPD patients and 98 healthy controls, that have been recruited in two reference pneumology clinics in Colombia before the beginning of the COVID-19 pandemic.ResultsForty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 and CCL3 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11). Functional annotation revealed their enrichment in chemokine signaling pathways related with response to viral infections. Some of these proteins were found up-regulated upon SARS-Cov-2 infection of Calu-3 cells. Also, HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE have been found increased in patients with severe COVID-19. HGF, the most significant protein in this study as well as its correlated proteins could be associated with the increased risk of severe COVID-19 in COPD patients.ConclusionsAsthma and COPD patients have altered plasma levels of proteins that have been found associated with increased risk of severe COVID-19. The reasons for sharing these profiles with this infection are unknown, but our study suggest that adult patients with asthma and COPD have a systemic dysregulation in chemokine networks that could make them more susceptible to severe COVID-19.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhongqi Li ◽  
Xuhua Mao ◽  
Qiao Liu ◽  
Huan Song ◽  
Biyu He ◽  
...  

Abstract Objective Chronic obstructive pulmonary disease (COPD) and pulmonary tuberculosis (PTB) share a number of common risk factors, including innate immunity-related genetic factors. In the present study, we compared the role of genetic variations of the TLR4 gene in susceptibility to COPD and PTB and illuminated the underlying molecular mechanism of functional single-nucleotide polymorphisms (SNPs). Methods A population-based case control study was performed in a Chinese Han population and included 152 COPD cases, 1601 PTB cases and 1727 controls. Five SNPs in the TLR4 gene (rs10759932, rs2737190, rs7873784, rs11536889, and rs10983755) were genotyped using TaqMan allelic discrimination technology. We estimated the effects of SNPs using the odds ratio (OR) together with 95% confidence interval (CI). Dual-luciferase reporter vectors expressing different genotypes of SNPs were constructed and transfected into the human HEK 293 T cell line to explore their effects on potential transcription activity. Results After Bonferroni correction, the genetic polymorphisms of all five SNPs remained significantly associated with COPD, while rs10759932 and rs2737190 were also associated with PTB. Compared with rs10759932-TT, individuals carrying TC (OR: 0.42, 95% CI: 0.28–0.64) or CC (OR: 0.24, 95% CI: 0.09–0.63) had a significantly reduced risk of COPD. However, individuals carrying TC (OR: 1.28, 95% CI: 1.11–1.49) or CC (OR: 1.26, 95% CI: 0.98–1.62) had an increased risk of PTB. The OR (95% CI) for allele rs10759932-C was 0.45 (0.32–0.62) for COPD and 1.18 (1.07–1.32) for PTB. For rs2737190, heterozygous AG was related to a decreased risk of COPD (OR: 0.32, 95% CI: 0.21–0.49) and an increased risk of PTB (OR: 1.30, 95% CI: 1.11–1.52). The dual-luciferase reporter assay showed decreased transcription activity caused by rs10759932-C and rs2737190-G. Conclusion Genetic polymorphisms of rs10759932 and rs2737190 in TLR4 are significantly related to both COPD and PTB but with inverse effects. The altered transcription activity caused by mutations in these two loci may partly explain the observed relationship.


Medicina ◽  
2019 ◽  
Vol 55 (7) ◽  
pp. 358
Author(s):  
Angeli ◽  
Reboldi ◽  
Trapasso ◽  
Aita ◽  
Ambrosio ◽  
...  

Background and objectives: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Among extra-pulmonary manifestations of COPD, atrial fibrillation (AF) is commonly observed in clinical practice. The coexistence of COPD and AF significantly affects the risk of cardiovascular morbidity and mortality. Nonetheless, the mechanisms explaining the increased risk of vascular events and death associated to the presence of COPD in AF are complex and not completely understood. We analyzed data from an Italian network database to identify markers and mediators of increased vascular risk among subjects with AF and COPD. Materials and Methods: Cross-sectional analysis of the Umbria Atrial Fibrillation (Umbria-FA) Registry, a multicenter, observational, prospective on-going registry of patients with non-valvular AF. Of the 2205 patients actually recruited, 2159 had complete clinical data and were included in the analysis. Results: the proportion of patients with COPD was 15.6%. COPD patients had a larger proportion of permanent AF when compared to the control group (49.1% vs. 34.6%, p < 0.0001) and were more likely to be obese and current smokers. Other cardiovascular risk factors including chronic kidney disease (CKD), peripheral artery disease and subclinical atherosclerosis were more prevalent in COPD patients (all p < 0.0001). COPD was also significantly associated with higher prevalence of previous vascular events and a history of anemia (all p < 0.0001). The thromboembolic and bleeding risk, as reflected by the CHA2DS2VASc and HAS-BLED scores, were higher in patients with COPD. Patients with COPD were also more likely to have left ventricular (LV) hypertrophy at standard ECG than individuals forming the cohort without COPD (p = 0.018). Conclusions: AF patients with COPD have a higher risk of vascular complications than AF patients without this lung disease. Our analysis identified markers and mediators of increased risk that can be easily measured in clinical practice, including LV hypertrophy, CKD, anemia, and atherosclerosis of large arteries.


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