Project description:Diaphragm muscles in Chronic Obstructive Pulmonary Disease (COPD) patients undergo an adaptive fast to slow transformation that includes cellular adaptations. This project studies the signaling mechanisms responsible for this transformation. Keywords: other
Project description:Investigation of whole genome gene expression level changes of the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10, compared to the normal people and stable COPD patients. A five chip study using total RNA recovered from Peripheral Blood Mononuclear Cell of Peripheral Blood.Evaluating the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10 after the hospital admission, to compared with healthy controls or patients with stable COPD. Slides were scanned at 5 μm/pixel resolution using an Axon GenePix 4000B scanner (Molecular Devices Corporation) piloted by GenePix Pro 6.0 software (Axon). Scanned images (TIFF format) were then imported into NimbleScan software (version 2.5) for grid alignment and expression data analysis. Expression data were normalized through quantile normalization and the Robust Multichip Average (RMA) algorithm included in the NimbleScan software. The Probe level (*_norm_RMA.pair) files and Gene level (*_RMA.calls) files were generated after normalization.
Project description:Patients with chronic obstructive pulmonary disease (COPD) have elevated cardiovascular risk, and myocardial injury is common during severe exacerbations. Little is known about the prevalence, magnitude, and underlying mechanisms of cardiovascular risk in community-treated exacerbations.To investigate how COPD exacerbations and exacerbation frequency impact cardiovascular risk and myocardial injury, and whether this is related to airway infection and inflammation.We prospectively measured arterial stiffness (aortic pulse wave velocity [aPWV]) and cardiac biomarkers in 98 patients with stable COPD. Fifty-five patients had paired stable and exacerbation assessments, repeated at Days 3, 7, 14, and 35 during recovery. Airway infection was identified using polymerase chain reaction.COPD exacerbation frequency was related to stable-state arterial stiffness (rho = 0.209; P = 0.040). Frequent exacerbators had greater aPWV than infrequent exacerbators (mean ± SD aPWV, 11.4 ± 2.1 vs. 10.3 ± 2.0 ms(-1); P = 0.025). Arterial stiffness rose by an average of 1.2 ms(-1) (11.1%) from stable state to exacerbation (n = 55) and fell slowly during recovery. In those with airway infection at exacerbation (n = 24) this rise was greater (1.4 ± 1.6 vs. 0.7 ± 1.3 ms(-1); P = 0.048); prolonged; and related to sputum IL-6 (rho = 0.753; P < 0.001). Increases in cardiac biomarkers at exacerbation were higher in those with ischemic heart disease (n = 12) than those without (n = 43) (mean ± SD increase in troponin T, 0.011 ± 0.009 vs. 0.003 ± 0.006 ?g/L, P = 0.003; N-terminal pro-brain natriuretic peptide, 38.1 ± 37.7 vs. 5.9 ± 12.3 pg/ml, P < 0.001).Frequent COPD exacerbators have greater arterial stiffness than infrequent exacerbators. Arterial stiffness rises acutely during COPD exacerbations, particularly with airway infection. Increases in arterial stiffness are related to inflammation, and are slow to recover. Myocardial injury is common and clinically significant during COPD exacerbations, particularly in those with underlying ischemic heart disease.
Project description:Investigation of whole genome gene expression level changes of the dynamic gene profiling of peripheral blood mononuclear cells (PBMCs) from patients with AECOPD) on day1, 3 and 10, compared to the normal people and stable COPD patients.
Project description:BackgroundChronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar remodeling. Although the abnormalities are primarily prompted by chronic exposure to inhaled irritants, maladjusted and self-reinforcing immune responses are significant contributors to the development and progression of the disease. The p38 isoforms are regarded as pivotal hub proteins that regulate immune and inflammatory responses in both healthy and disease states. As a result, their inhibition has been the subject of numerous recent studies exploring their therapeutic potential in COPD.Main bodyWe performed a systematic search based on the PRISMA guidelines to find relevant studies about P38 signaling in COPD patients. We searched the PubMed and Google Scholar databases and used "P38" AND "COPD" Mesh Terms. We applied the following inclusion criteria: (1) human, animal, ex vivo and in vitro studies; (2) original research articles; (3) published in English; and (4) focused on P38 signaling in COPD pathogenesis, progression, or treatment. We screened the titles and abstracts of the retrieved studies and assessed the full texts of the eligible studies for quality and relevance. We extracted the following data from each study: authors, year, country, sample size, study design, cell type, intervention, outcome, and main findings. We classified the studies according to the role of different cells and treatments in P38 signaling in COPD.ConclusionWhile targeting p38 MAPK has demonstrated some therapeutic potential in COPD, its efficacy is limited. Nevertheless, combining p38 MAPK inhibitors with other anti-inflammatory steroids appears to be a promising treatment choice. Clinical trials testing various p38 MAPK inhibitors have produced mixed results, with some showing improvement in lung function and reduction in exacerbations in COPD patients. Despite these mixed results, research on p38 MAPK inhibitors is still a major area of study to develop new and more effective therapies for COPD. As our understanding of COPD evolves, we may gain a better understanding of how to utilize p38 MAPK inhibitors to treat this disease. Video Abstract.
Project description:Chronic obstructive pulmonary disease (COPD) is а highly prevalent, complex and heterogeneous clinical condition which is associated with significant concomitant diseases. COPD and cardiovascular diseases (CVDs) often coexist due to the high prevalence of each of these pathological conditions separately as well as the common risk factors (particularly smoking), mechanisms of interaction and influence of systemic inflammation. In addition, decreased pulmonary function in COPD is closely associated with an increased risk of congestive CVDs. One of the most important pathophysiological markers of COPD-lung hyperinflation-plays a significant role in the appearance of functional limitations of the pumping function of the heart, creating unfavorable conditions by exerting a compression effect on the heart muscle. The latter was confirmed by significant correlation between the COPD severity according to GOLD classification and the basic dimensions of the heart chambers. Several decades ago, the term "microcardia" was commonly used and indicated a radiological sign of emphysema. Some studies demonstrated a close relationship between the chance of occurrence of CVD and the severity of pulmonary dysfunction. Such an association has been demonstrated for the whole spectrum of CVD-including cerebrovascular disease, congestive heart failure (CHF) and rhythm disturbances-and was detected in the early stages of the disease. A large proportion of patients with mild and moderate COPD die due to CVD, which is much more likely than deaths in the same group due to respiratory insufficiency. COPD patients have a higher rate of hospitalization and death, the cause of which are coronary heart disease (CHD), stroke and CHF. Treatment of COPD today is mainly determined by national and international clinical guidelines, which should pay more attention to the problems of the treatment of COPD patients with comorbid conditions.
Project description:Globally, cardiovascular diseases and chronic obstructive pulmonary disease (COPD) are the leading causes of the noncommunicable disease burden. Overlapping symptoms such as breathing difficulty and fatigue, with a lack of awareness about COPD among physicians, are key reasons for under-diagnosis and resulting sub-optimal care relative to COPD. Much has been published in the past on the pathogenesis and implications of cardiovascular comorbidities in COPD. However, a comprehensive review of the prevalence and impact of COPD management in commonly encountered cardiac diseases is lacking. The purpose of this study was to summarize the current knowledge regarding the prevalence of COPD in heart failure, ischemic heart disease, and atrial fibrillation. We also discuss the real-life clinical presentation and practical implications of managing COPD in cardiac diseases. We searched PubMed, Scopus, EMBASE, and Google Scholar for studies published 1981-May 2020 reporting the prevalence of COPD in the three specified cardiac diseases. COPD has high prevalence in heart failure, atrial fibrillation, and ischemic heart disease. Despite this, COPD remains under-diagnosed and under-managed in the majority of patients with cardiac diseases. The clinical implications of the diagnosis of COPD in cardiac disease includes the recognition of hyperinflation (a treatable trait), implementation of acute exacerbations of COPD (AECOPD) prevention strategies, and reducing the risk of overuse of diuretics. The pharmacological agents for the management of COPD have shown a beneficial effect on cardiac functions and mortality. The appropriate management of COPD improves the cardiovascular outcomes by reducing hyperinflation and preventing AECOPD, thus reducing the risk of mortality, improving exercise tolerance, and quality of life.
Project description:Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities. The main cause is smoking tobacco, but other factors have been identified. Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli. The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both. Comorbidities include ischaemic heart disease, diabetes, and lung cancer. Bronchodilators constitute the mainstay of treatment: β(2) agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids). Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification. Future research should be directed towards the development of agents that notably affect the course of disease.