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Pathogenesis of COPD

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https://www.readbyqxmd.com/read/29351446/mechanisms-and-consequences-of-oxidative-stress-in-lung-disease-therapeutic-implications-for-an-aging-populace
#1
Louise Hecker
The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility...
December 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351437/metabolic-reprogramming-in-the-pathogenesis-of-chronic-lung-diseases-including-bpd-copd-and-pulmonary-fibrosis
#2
Haifeng Zhao, Phyllis A Dennery, Hongwei Yao
The metabolism of nutrient substrates including glucose, glutamine and fatty acids provides acetyl-CoA for the tricarboxylic acid cycle to generate energy, and metabolites for the biosynthesis of biomolecules including nucleotides, proteins, and lipids. It has been shown that metabolism of glucose, fatty acid, and glutamine plays important roles in modulating cellular proliferation, differentiation, apoptosis, autophagy, senescence, and inflammatory responses. All these cellular processes contribute to the pathogenesis of chronic lung diseases, including bronchopulmonary dysplasia, chronic obstructive pulmonary disease, and pulmonary fibrosis...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29338832/exhaled-air-molecules-and-chronic-obstructive-pulmonary-disease
#3
Yan Zheng, Jun Wang, Qiu Gen Li
Chronic airway inflammation,a main pathologic process of chronic obstructive pulmonary disease (COPD),can trigger inflammation cells and airway structure cells to produce bioactive molecules,which play key roles in the pathogenesis of COPD and are also an efficient indicators for the diagnosis and treatment of COPD. This article reviews the important roles of these exhaled air molecules in the diagnosis and treatment of COPD,with an attempt to offer new strategies in the management of COPD.
December 20, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/29335020/ensemble-genomic-analysis-in-human-lung-tissue-identifies-novel-genes-for-chronic-obstructive-pulmonary-disease
#4
Jarrett D Morrow, Michael H Cho, John Platig, Xiaobo Zhou, Dawn L DeMeo, Weiliang Qiu, Bartholome Celli, Nathaniel Marchetti, Gerard J Criner, Raphael Bueno, George R Washko, Kimberly Glass, John Quackenbush, Edwin K Silverman, Craig P Hersh
BACKGROUND: Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) significantly associated with chronic obstructive pulmonary disease (COPD). However, many genetic variants show suggestive evidence for association but do not meet the strict threshold for genome-wide significance. Integrative analysis of multiple omics datasets has the potential to identify novel genes involved in disease pathogenesis by leveraging these variants in a functional, regulatory context...
January 15, 2018: Human Genomics
https://www.readbyqxmd.com/read/29314863/bacterial-derived-neutrophilic-inflammation-drives-lung-remodeling-in-a-mouse-model-of-copd
#5
Bradley W Richmond, Rui-Hong Du, Wei Han, John T Benjamin, Riet van der Meer, Linda Gleaves, Marshall Guo, Austin McKissack, Yongqin Zhang, Dong-Sheng Cheng, Vasiliy V Polosukhin, Timothy S Blackwell
Loss of secretory immunoglobulin A (SIgA) is common in the small airways of patients with chronic obstructive pulmonary disease (COPD) and may contribute to disease pathogenesis. Using mice that lack SIgA in the airways due to genetic deficiency of polymeric immunoglobulin receptor (pIgR-/- mice), we investigated the role of neutrophils in driving the fibrotic small airway wall remodeling and emphysema that develops spontaneously in these mice. By flow cytometry, we found an increase in the percentage of neutrophils among CD45+ cells in the lungs, as well as an increase in total neutrophils, in pIgR-/- mice compared to wild-type (WT) controls...
January 9, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29313708/human-lung-dna-methylation-quantitative-trait-loci-colocalize-with-copd-genome-wide-association-loci
#6
Jarrett D Morrow, Kimberly Glass, Michael H Cho, Craig P Hersh, Victor Pinto-Plata, Bartolome Celli, Nathaniel Marchetti, Gerard Criner, Raphael Bueno, George Washko, Augustine M K Choi, John Quackenbush, Edwin K Silverman, Dawn L DeMeo
RATIONALE: As the third leading cause of death in the United States, the impact of chronic obstructive pulmonary disease (COPD) makes identification of its molecular mechanisms of great importance. Genome-wide association studies have identified multiple genomic regions associated with COPD. However, genetic variation only explains a small fraction of the susceptibility to COPD and sub-genome-wide significant loci may play a role in pathogenesis. OBJECTIVES: Regulatory annotation with epigenetic evidence may give priority for further investigation, particularly for GWAS associations in non-coding regions...
January 9, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29288933/targeting-the-renin-angiotensin-system-as-novel-therapeutic-strategy-for-pulmonary-diseases
#7
REVIEW
Wan Shun Daniel Tan, Wupeng Liao, Shuo Zhou, Dan Mei, Wai-Shiu Fred Wong
The renin-angiotensin system (RAS) plays a major role in regulating electrolyte balance and blood pressure. RAS has also been implicated in the regulation of inflammation, proliferation and fibrosis in pulmonary diseases such as asthma, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Current therapeutics suffer from some drawbacks like steroid resistance, limited efficacies and side effects. Novel intervention is definitely needed to offer optimal therapeutic strategy and clinical outcome...
December 27, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29223853/role-of-mir-195-in-cigarette-smoke-induced-chronic-obstructive-pulmonary-disease
#8
Wenchao Gu, Yaping Yuan, Hua Yang, Hao Wu, Linxuan Wang, Zhijun Tang, Qiang Li
Chronic obstructive pulmonary disease (COPD) is regarded as a persistent respiratory symptom, mainly caused by cigarette smoking. Recent data have suggested that some miRNAs are involved in the pathogenesis of COPD. Here, we found that miR-195 was significantly upregulated in the lung tissues of patients with COPD compared to in never smokers. miR-195 expression was also upregulated in cigarette smoke (CS)-exposed mice. Lentivirus-mediated knockdown of miR-195 alleviated CS-induced lung pathological changes and reduced inflammatory cell infiltration as well as production of interleukin-6 and tumor necrosis factor-α in bronchoalveolar lavage fluid...
December 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29223018/targeting-oxidant-dependent-mechanisms-for-the-treatment-of-respiratory-diseases-and-their-comorbidities
#9
REVIEW
Neil C Thomson
Oxidative stress is implicated in the pathogenesis of respiratory diseases, such as COPD and its comorbidities, asthma, idiopathic pulmonary fibrosis and radiation pneumonitis. Antioxidants drugs, such as small molecule thiols, nuclear erythroid-2 related factor 2 activators and catalytic enzyme mimetics have been developed to target oxidant-dependent mechanisms. The therapeutic effects of antioxidants have been generally disappointing. A small number of antioxidants are approved for clinical use, such as the small molecule thiol N-acetyl-l-cysteine for chronic obstructive pulmonary disease, and in the United States, the superoxide dismutase mimetic AEOL 10150 for severe radiation pneumonitis...
December 6, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29218124/expression-of-toll-like-receptor-2-and-4-in-peripheral-blood-neutrophil-cells-from-patients-with-chronic-obstructive-pulmonary-disease
#10
Prashant Mani Tripathi, Surya Kant, Ravi Shanker Yadav, Ram Awadh Singh Kushwaha, Ved Prakash, Sayed Husian Mustafa Rizvi, Arshiya Parveen, Abbas Ali Mahdi, Iqbal Ahmad
Objectives: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality around the world. Preliminary studies have evaluated the association between innate immunity including Toll-like receptors (TLRs) and airway samples of patients with COPD. The role of TLRs in peripheral blood neutrophils is poorly understood. Hence, this study aimed to investigate the role of TLR2 and TLR4 in peripheral blood neutrophils of COPD patients. Methods: A total of 101 COPD cases and an equal number of healthy controls participated in this case-control study...
November 2017: Oman Medical Journal
https://www.readbyqxmd.com/read/29211494/exhaustion-of-airway-basal-progenitor-cells-in-early-and-established-copd
#11
Moumita Ghosh, York E Miller, Ichiro Nakachi, Jennifer B Kwon, Anna E Barón, Alexandra E Brantley, Daniel T Merrick, Wilbur A Franklin, Robert L Keith, R William Vandivier
RATIONALE: Up to 40% of smokers develop chronic obstructive pulmonary disease (COPD) over a period that spans decades. Despite the importance of COPD, much remains to be learned about susceptibility and pathogenesis, especially during early, pre-diagnostic stages of disease. Airway basal progenitor cells are crucial for lung health and resilience, because of their ability to repair injured airways. In COPD, the normal airway epithelium is replaced with increased basal and secretory (mucous) cells and decreased ciliated cells, suggesting that progenitors are impaired...
December 6, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29210751/chronic-obstructive-pulmonary-disease-and-lung-cancer-inter-relationships
#12
Abhishek Biswas, Hiren J Mehta, Erik E Folch
PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a well established risk factor for lung cancer. Newer studies reveal a myriad of other mechanisms, some proven and some putative, which may contribute to their association. RECENT FINDINGS: There is an ever-growing bundle of evidence that suggests a close association between persistent chronic inflammation and lung cancer. A few potential targets of genetic susceptibility locus for COPD and lung cancer have been suggested...
November 27, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/29207693/serum-uric-acid-in-chronic-obstructive-pulmonary-disease-a-hospital-based-case-control-study
#13
Rajlaxmi Sarangi, Nirupama Varadhan, Jyotirmayee Bahinipati, Asha Dhinakaran, Anandaraj, Kandasamy Ravichandran
Introduction: Airway inflammation and imbalance between oxidant/anti-oxidant mechanisms are postulated to play a major role in the pathogenesis and exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Previous studies on the role of serum Uric Acid (UA) in COPD subjects have been both confounding and inconclusive. Aim: To measure the serum UA levels among COPD subjects and to correlate with different stages of the disease. Materials and Methods: The study included 39 stable COPD subjects (21 males, 18 females; 13 smokers, 26 nonsmokers; age group; 40 to 60 years) and compared with 46 control subjects from the general population...
September 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/29205062/microrna-150-protects-against-cigarette-smoke-induced-lung-inflammation-and-airway-epithelial-cell-apoptosis-through-repressing-p53-microrna-150-in-cs-induced-lung-inflammation
#14
H Xue, M X Li
Cigarette smoke (CS) exposure is an important risk factor for chronic obstructive pulmonary disease (COPD). MicroRNA-150 (miR-150) is involved in several inflammatory diseases. However, little is known about the role of miR-150 in the pathogenesis of COPD. In this study, we established a CS-related mouse model of COPD and evaluated the impact of miR-150 on CS-induced lung inflammation. We further investigated the effects of miR-150 overexpression on pro-inflammatory cytokine production and apoptosis in airway epithelial cells exposed to CS extract (CSE)...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29203722/what-do-polymorphisms-tell-us-about-the-mechanisms-of-copd
#15
REVIEW
Yan Li, Michael H Cho, Xiaobo Zhou
COPD (chronic obstructive pulmonary disease) is characterized by irreversible lung airflow obstruction. Cigarette smoke is the major risk factor for COPD development. However, only a minority number of smokers develop COPD, and there are substantial variations in lung function among smokers, suggesting that genetic determinants in COPD susceptibility. During the past decade, genome-wide association studies and exome sequencing have been instrumental to identify the genetic determinants of complex traits, including COPD...
December 15, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29200281/discovery-and-optimization-of-thiazolidinyl-and-pyrrolidinyl-derivatives-as-inhaled-pde4-inhibitors-for-respiratory-diseases
#16
Laura Carzaniga, Gabriele Amari, Andrea Rizzi, Carmelida Capaldi, Renato De Fanti, Eleonora Ghidini, Gino Villetti, Chiara Carnini, Nadia Moretto, Fabrizio Facchinetti, Paola Caruso, Gessica Marchini, Loredana Battipaglia, Riccardo Patacchini, Valentina Cenacchi, Roberta Volta, Francesco Amadei, Alice Pappani, Silvia Capacchi, Valentina Bagnacani, Maurizio Delcanale, Paola Puccini, Silvia Catinella, Maurizio Civelli, Elisabetta Armani
Phosphodiesterase 4 (PDE4) is a key cAMP-metabolising enzyme involved in the pathogenesis of inflammatory disease and its pharmacological inhibition has been shown to exert therapeutic efficacy in chronic obstructive pulmonary disease (COPD). Herein we describe a drug discovery program aiming at the identification of novel classes of potent PDE4 inhibitors suitable for pulmonary administration. Starting from a previous series of benzoic acid esters, we explored the chemical space in the solvent-exposed region of the enzyme catalytic binding pocket...
December 4, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29193245/review-article-gastro-oesophageal-reflux-disease-in-asthma-and-chronic-obstructive-pulmonary-disease
#17
REVIEW
C Broers, J Tack, A Pauwels
BACKGROUND: When gastro-oesophageal reflux is causing symptoms or lesions in the oesophagus, this is referred to as gastro-oesophageal reflux disease (GERD). GERD can manifest itself through typical symptoms (heartburn, regurgitation) or may lead to extra-oesophageal symptoms. Extra-oesophageal manifestations of GERD gained increasing attention over the last decade, especially respiratory disorders, because of the prevalent co-occurrence with GERD. The role of GERD in the pathogenesis of respiratory disorders has become a topic of intense discussion...
November 29, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29184823/a-prospective-randomized-controlled-study-theophylline-on-oxidative-stress-and-steroid-sensitivity-in-chronic-obstructive-pulmonary-disease-patients
#18
R Ranjani, A T Sathiya Vinotha
Objective: Oxidative stress is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Corticosteroid fails to suppress inflammation and oxidative stress due to steroid resistance. Theophylline has an effect on histone deacetylase (HDAC) activity and improves steroid sensitivity in COPD. Given changes in oxidative stress associated with diminished corticosteroid effects, a clinical study in which antioxidants and free radicals are estimated can suggest a correlation between antioxidants, theophylline, and corticosteroid sensitivity...
July 2017: International Journal of Pharmaceutical Investigation
https://www.readbyqxmd.com/read/29181828/influence-of-inhaled-corticosteroids-on-bronchial-inflammation-and-pulmonary-function-in-chronic-obstructive-pulmonary-disease-with-moderate-obstruction
#19
Iza Toczyska, Ewa Zwolińska, Andrzej Chcialowski
Inflammation in the bronchial respiratory tract and lung parenchyma underlies the pathogenesis of chronic obstructive pulmonary disease (COPD). It consists of effector cell infiltration, changes in reticular basement membrane (RBM) thickness, and the content of inflammatory mediators. The aim of this study was to assess the influence of inhaled corticosteroids (ICS) on the number of inflammatory cells and RBM thickness in bronchial biopsies, and pulmonary function in patients with moderate COPD. Twenty four patients with newly diagnosed COPD were included into the study...
November 28, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29179729/deficiency-of-innate-like-t-lymphocytes-in-chronic-obstructive-pulmonary-disease
#20
Mariann Szabó, Veronika Sárosi, Zoltán Balikó, Kornélia Bodó, Nelli Farkas, Tímea Berki, Péter Engelmann
BACKGROUND: Based on the phenotypic and functional characteristics unconventional T-lymphocytes such as invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells link the innate and adaptive immune responses. Up to now data are scarce about their involvement in pulmonary disorders including chronic obstructive pulmonary disease (COPD). This study explores simultaneously the frequencies of iNKT and MAIT cells in the peripheral blood and sputum of stable and exacerbating COPD patients...
November 28, 2017: Respiratory Research
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