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Pathogenesis of COPD

Christine M Freeman, Jeffrey L Curtis
Hallmarks of chronic obstructive pulmonary disease (COPD) include innate inflammation and remodeling of small airways that begin in early disease and the development of lung lymphoid follicles (LLF), indicative of adaptive immunity, in more spirometrically-severe stages. Common to these processes in all stages is orchestration by dendritic cells (DC). Recently improved understanding of the analogous lung DC subsets in humans and mice has allowed for better integration and interpretation of the experimental and clinical pathological literature...
October 21, 2016: American Journal of Respiratory Cell and Molecular Biology
Rachel Boxio, Julien Wartelle, Béatrice Nawrocki-Raby, Brice Lagrange, Laurette Malleret, Timothee Hirche, Clifford Taggart, Yves Pacheco, Gilles Devouassoux, Abderrazzaq Bentaher
BACKGROUND: In acutely injured lungs, massively recruited polymorphonuclear neutrophils (PMNs) secrete abnormally neutrophil elastase (NE). Active NE creates a localized proteolytic environment where various host molecules are degraded leading to impairment of tissue homeostasis. Among the hallmarks of neutrophil-rich pathologies is a disrupted epithelium characterized by the loss of cell-cell adhesion and integrity. Epithelial-cadherin (E-cad) represents one of the most important intercellular junction proteins...
October 17, 2016: Respiratory Research
Crystal N Marconett, Beiyun Zhou, Mitsuhiro Sunohara, Tiffany M Pouldar, HongJun Wang, Yixin Liu, Megan E Rieger, Evelyn Tran, Per Flodby, Kimberly D Siegmund, Edward D Crandall, Ite A Laird-Offringa, Zea Borok
Diseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to pathogenesis of these diseases. The distal lung alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. While cell type-specific markers, most prominently surfactant protein C (SFTPC), have allowed detailed lineage tracing studies of AT2 cell differentiation and their roles in disease, studies of AT1 cells have been hampered by lack of genes with expression unique to AT1 cells...
October 17, 2016: American Journal of Respiratory Cell and Molecular Biology
John W Upham, Yang Xi
Dendritic cells (DC) are potent antigen presenting cells. Because of their particular ability to initiate and regulate cell mediated and humoral immune responses, there is considerable interest in the role that DC play in the pathogenesis of various lung diseases, especially those in which there is an excessive immune response to specific antigens (as in asthma) or a deficient immune response (as in lung cancer). A number of DC subpopulations have been defined in the lungs including myeloid or conventional DC that initiate T-cell immunity and antibody production, and plasmacytoid DC that have an important role in anti-viral immunity and immune tolerance...
October 8, 2016: Chest
Vinciane Saint-Criq, Michael A Gray
Salt and fluid absorption and secretion are two processes that are fundamental to epithelial function and whole body fluid homeostasis, and as such are tightly regulated in epithelial tissues. The CFTR anion channel plays a major role in regulating both secretion and absorption in a diverse range of epithelial tissues, including the airways, the GI and reproductive tracts, sweat and salivary glands. It is not surprising then that defects in CFTR function are linked to disease, including life-threatening secretory diarrhoeas, such as cholera, as well as the inherited disease, cystic fibrosis (CF), one of the most common life-limiting genetic diseases in Caucasian populations...
October 6, 2016: Cellular and Molecular Life Sciences: CMLS
Hao Wang, Ting Yang, Diandian Li, Yanqiu Wu, Xue Zhang, Caishuang Pang, Junlong Zhang, Binwu Ying, Tao Wang, Fuqiang Wen
BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) and soluble urokinase-type plasminogen activator receptor (suPAR) participate in inflammation and tissue remolding in various diseases, but their roles in chronic obstructive pulmonary disease (COPD) are not yet clear. This study aimed to investigate if PAI-1 and suPAR were involved in systemic inflammation and small airway obstruction (SAO) in COPD. METHODS: Demographic and clinical characteristics, spirometry examination, and blood samples were obtained from 84 COPD patients and 51 healthy volunteers...
2016: International Journal of Chronic Obstructive Pulmonary Disease
Sophie Wecht, Mauricio Rojas
Mesenchymal stem cells (MSCs) are a populace of non-haematopoietic multipotent stromal cells, which have the ability to differentiate into tissue derived from a single germ layer. MSCs have been isolated from various sites, including adipose tissue, skeletal muscle, synovium, spleen, thymus, lung and amniotic fluid, but are most often isolated from bone marrow. MSCs have several valuable functions that make them a promising therapeutic option in the field of regenerative medicine, including the secretion of anti-inflammatory cytokines and growth factors, the migration of cells to the site of injury when administered and the ability to 'rescue' cells through the transfer of functional mitochondria...
November 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
Martin A Bewley, Kylie B R Belchamber, Kirandeep K Chana, Richard C Budd, Gavin Donaldson, Jadwiga A Wedzicha, Christopher E Brightling, Iain Kilty, Louise E Donnelly, Peter J Barnes, Dave Singh, Moira K B Whyte, David H Dockrell
Pulmonary inflammation and bacterial colonization are central to the pathogenesis of chronic obstructive pulmonary disease (COPD). Defects in macrophage phagocytosis of both bacteria and apoptotic cells contribute to the COPD phenotype. Small molecule inhibitors with anti-inflammatory activity against p38 mitogen activated protein kinases (MAPKs), phosphatidyl-inositol-3 kinase (PI3K) and Rho kinase (ROCK) are being investigated as novel therapeutics in COPD. Concerns exist, however, about off-target effects...
2016: PloS One
Adel Boueiz, Sharon M Lutz, Michael H Cho, Craig P Hersh, Russell P Bowler, George R Washko, Eitan Halper-Stromberg, Per Bakke, Amund Gulsvik, Nan M Laird, Terri H Beaty, Harvey O Coxson, James D Crapo, Edwin K Silverman, Peter J Castaldi, Dawn L DeMeo
RATIONALE: Emphysema has considerable variability in the severity and distribution of parenchymal destruction throughout the lungs. Upper lobe predominant emphysema has emerged as an important predictor of response to lung volume reduction surgery. Yet, aside from alpha-1 antitrypsin deficiency, the genetic determinants of emphysema distribution remain largely unknown. OBJECTIVES: To identify the genetic influences of emphysema distribution in non-alpha-1 antitrypsin deficient smokers...
September 26, 2016: American Journal of Respiratory and Critical Care Medicine
Gourab Choudhury, William MacNee
Ageing is defined as a progressive decline of homeostasis that occurs after the reproductive phase of life is complete, which is thought to arise because of impaired DNA repair following damage. This leads to an increased risk of disease or death. Ageing is one of the most important risk factors for most chronic diseases. Chronic obstructive pulmonary disease (COPD) represents an important component of the increasingly prevalent multiple chronic debilitating diseases that are a major cause of morbidity and mortality, particularly in the elderly...
September 13, 2016: COPD
Matteo Ferrando, Diego Bagnasco, Valeria Roustan, Giorgio Walter Canonica, Fulvio Braido, Ilaria Baiardini
Upper and lower obstructive lung diseases can induce sleep complaints and can be part of the pathogenesis of sleep breathing disorders. In fact, the physiological changes of the pattern of respiration during sleep, added to the airways disease can lead to symptomatic worsening of rhinitis, asthma and chronic obstructive pulmonary diseases (COPD); moreover, their functional and anatomical features can lead to sleep breathing disorders such as obstructive sleep apnea syndrome (OSAS). This review highlights the above-mentioned relationships and the effect of disease management on its comorbidities and the patient's quality of life...
August 2016: Journal of Thoracic Disease
Lingyan Yang, Wen-Cheng Wang, Shih-Chun Candice Lung, Zhelin Sun, Chongjun Chen, Jen-Kun Chen, Qiang Zou, Yu-Hsin Lin, Chia-Hua Lin
Although exposure to particulate matter with a diameter of <2.5μm (PM2.5) is associated with chronic obstructive pulmonary disease (COPD), the major components of PM2.5 in COPD pathogenesis are controversial. Here we employed the human lung epithelial cell line BEAS-2B to elucidate the association between COPD and the organic and water-soluble components of PM2.5. We found that the PM2.5 organic extract was a potential major risk factor for pulmonary epithelial barrier dysfunction through the depletion of proteins from the zonula occludens...
September 7, 2016: Science of the Total Environment
Malik Q Mahmood, David Reid, Chris Ward, Hans K Muller, Darryl A Knight, Sukhwinder S Sohal, Eugene H Walters
BACKGROUND AND OBJECTIVE: COPD is characterized by poorly reversible airflow obstruction usually due to cigarette smoking. Transforming growth factor (TGF)-β1 has been implicated in the pathogenesis of COPD, and in particular a process called epithelial mesenchymal transition (EMT), which may well be an intermediatory between smoking and both airway fibrosis and lung cancer. The downstream classical or 'canonical' TGF-β1 pathway is via the phosphorylated (p) Smad transcription factor system...
September 11, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
Nina Sun, Xiaofang Wei, Jingluan Wang, Zhaozhong Cheng, Weihong Sun
The imbalance of Th17/Treg cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Caveolin-1 (Cav-1) has been regarded as a potential critical regulatory protein in pathological mechanisms of chronic inflammatory respiratory diseases. Therefore, we investigated whether the loss of Cav-1 is involved in the homeostasis of Th17/Treg cells in COPD. We examined the expressions of plasma Cav-1 and circulating Th17, Treg cells, and the related cytokines in patients with COPD...
September 9, 2016: Inflammation
Shehab M Abd El-Kader, Osama H Al-Jiffri, Fadwa M Al-Shreef
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a main risk for morbidity, associated with alterations in systemic inflammation. Recent studies proved that morbidity and mortality of COPD is related to systemic inflammation as it contributes to the pathogenesis of atherosclerosis and cardiovascular disease. However, increase of inflammatory cytokines adversely affects quality of life, alteration in ventilatory and skeletal muscles functions. Moreover, exercise training has many beneficial effects in correction of the adverse effects of COPD...
June 2016: African Health Sciences
Małgorzata Pietrusińska, Aneta Pająk, Paweł Górski, Piotr Kuna, Janusz Szemraj, Agnieszka Goździńska-Nielepkowicz, Tadeusz Pietras
INTRODUCTION: The asthma- and chronic obstructive pulmonary disease (COPD)-related morbidity has been increasing during the recent years. Both asthma and COPD are diseases of inflammatory etiology. The increasing interest in the pathomechanisms involved in the development of obstructive pulmonary diseases seems to be fully justified. Recent research has attempted to determine the associations of microRNA with the pathogenesis of pulmonary diseases. AIM: To assess the expression of microRNA in the blood sera of patients diagnosed with bronchial asthma and chronic obstructive pulmonary disease in comparison with healthy subjects...
August 2016: Postȩpy Dermatologii i Alergologii
Maria E Laucho-Contreras, Maria Montes de Oca, Caroline A Owen
BACKGROUND: Although some patients with obstructive lung disease (OLD) have features of both asthma and chronic obstructive pulmonary disease (COPD), the term "asthma-COPD overlap syndrome (ACOS)" was coined only relatively recently. However, there are gaps in our knowledge of the clinical features, pathogenesis, prognosis, and management of ACOS patients. OBJECTIVES: To review the literature on ACOS to determine the extent to which the clinical features, pathologic mechanisms, clinical outcomes, and current therapeutic approaches for ACOS differ from those in patients with asthma alone or COPD alone...
September 6, 2016: Current Pharmaceutical Design
Roberto Rodriguez-Roisin, MeiLan K Han, Jørgen Vestbo, Jadwiga A Wedzicha, Prescott G Woodruff, Fernando J Martinez
The 2001 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Report defined five stages of spirometric severity (post-bronchodilator FEV1/FVC≥0.7): 0, and 1 (mild) to 4 (very severe). GOLD Stage 0 was defined by chronic cough and sputum production or chronic mucus hypersecretion (CMH) alone with preserved FEV1/FVC. Subsequently, GOLD 0 was discarded as further evidence of COPD development in subjects with GOLD 0 was not more likely to develop. When expanding symptomatic burden in GOLD 0 to include other chronic respiratory symptoms, such as dyspnea, wheeze, poor quality of life, limited physical activity, and 'COPD exacerbations-like' events needing health resources, symptomatic smokers with normal FEV1 resulted in larger risk of death...
September 6, 2016: American Journal of Respiratory and Critical Care Medicine
Koji Tamai, Harukazu Yoshimatsu, Toshiharu Saito, Hirofumi Matsuoka, Nobuhiko Okada, Yasuko Koma, Akiko Otsuka, Nao Oda, Sayaka Inoue, Sachie Kume, Yujiro Suzuki
BACKGROUND: Autoimmune involvement in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) has been proposed, and autoantibodies are a hallmark of autoimmunity. This study aimed to compare the autoantibody profiles of asthma and COPD, and the relationship between autoantibodies and features of these diseases. METHODS: We recruited 110 asthma patients and 92 COPD patients for a prospective study. Six autoantibody types were evaluated: antinuclear antibody, anti-cytoplasmic antibodies, rheumatoid factor, anti-cyclic citrullinated peptide antibody, myeloperoxidase-anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and proteinase 3-ANCA...
August 31, 2016: Allergology International: Official Journal of the Japanese Society of Allergology
Yunxiao Li, Ganggang Yu, Shaopeng Yuan, Chunting Tan, Jianlin Xie, Yasi Ding, Puqiao Lian, Lixia Fu, Qi Hou, Bo Xu, Haoyan Wang
BACKGROUND/AIMS: Epoxyeicosatrienoic acids (EETs) are metabolic products of free arachidonic acid (AA). EETs have anti-inflammatory activities. However, the effect of EETs on cigarette smoke-induced lung inflammation is not clear. Autophagy is believed to be involved in the pathogenesis of COPD. In addition, nuclear erythroid-related factor 2 (Nrf2), is thought to regulate antioxidant defenses in several lung diseases. Besides, interaction between EETs, autophagy and Nrf2 has been reported...
September 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
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