Materiały źródłowe

• #1 Pathogenesis of Chronic Obstructive Pulmonary Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713323/

  The current paradigm for the pathogenesis of chronic obstructive pulmonary disease is that chronic airflow limitation results from an abnormal inflammatory response to inhaled particles and gases in the lung. Airspace inflammation appears to be different in susceptible smokers and involves a predominance of CD8+ T lymphocytes, neutrophils, and macrophages. […] The pathogenesis of COPD is therefore strongly linked to the effects of cigarette smoke on the lungs. […] Studies have begun to characterize the lung inflammation in COPD in terms of its type, site, and degree, and the relationship to severity of disease. […] The mechanism by which CD8+ T lymphocytes accumulate in the airways of the lungs in COPD is not fully understood. […] The role of T cells in the pathogenesis of COPD is not fully understood.

• #2 Chronic obstructive pulmonary disease – Wikipedia

  https://en.wikipedia.org/wiki/Chronic_obstructive_pulmonary_disease

  Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory symptoms (shortness of breath, cough, sputum production or exacerbations) due to abnormalities of the airways (bronchitis, bronchiolitis) or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction. […] COPD develops as a significant and chronic inflammatory response to inhaled irritants which ultimately leads to bronchial and alveolar remodelling in the lung known as small airways disease. Thus, airway remodelling with narrowing of peripheral airway and emphysema are responsible for the alteration of lung function. […] The most common cause of COPD is tobacco smoking. Other risk factors include indoor and outdoor air pollution including dust, exposure to occupational irritants such as dust from grains, cadmium dust or fumes, and genetics, such as alpha-1 antitrypsin deficiency.

• #3 COPD – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/copd/symptoms-causes/syc-20353679

  Chronic bronchitis. In this condition, the bronchial tubes become inflamed and narrowed. As a result, the tubes thicken, making less room for air to pass through. Extra mucus caused by the irritation blocks the narrowed tubes even more. An ongoing cough results from trying to clear mucus from the airways. […] In the vast majority of people with COPD in the United States, the lung damage that leads to COPD is caused by long-term cigarette smoking. But there are likely other factors at play in developing COPD because not everyone who smokes gets COPD. One such factor may be gene changes that make some people more likely to develop the condition. […] In about 1% of people with COPD, the condition results from a gene change passed down in families. This is a genetic form of emphysema. This gene lessens the levels of a protein called alpha-1-antitrypsin (AAT) in the body. […] Low levels of this protein, a condition called alpha-1-antitrypsin (AAT) deficiency, can cause liver damage, lung conditions such as COPD or both.

• #4 Chronic obstructive pulmonary disease (COPD) – Etiology | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/7/aetiology

  The hallmark of COPD is chronic inflammation that affects central and peripheral airways, lung parenchyma and alveoli, and pulmonary vasculature. […] The inflammatory and structural changes in the lung increase with disease severity and persist after smoking cessation. […] Evidence suggests that the host response to inhaled stimuli generates the inflammatory reaction responsible for the changes in the airways, alveoli, and pulmonary blood vessels. […] Oxidative stress and an excess of proteases amplify the effects of chronic inflammation. […] Airway remodeling thickens the epithelium, lamina propria, smooth muscle, and adventitia of airways less than 2 mm in diameter, leading to progressive loss of patent terminal and transitional bronchioles. […] Elastin breakdown and subsequent loss of alveolar integrity causes emphysema.

• #5 Pathogenesis of Chronic Obstructive Pulmonary Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713323/

  Increased numbers of activated neutrophils are found in sputum from patients with COPD. […] Cigarette smoking is known to increase circulating neutrophil leukocyte count and to cause sequestration of neutrophils in the lung capillaries. […] There is a 5- to 10-fold increase in the numbers of macrophages in the airways, lung parenchyma, and bronchoalveolar lavage fluid (BALF) in patients with COPD. […] Many of the inflammatory mediators that are expressed in COPD are controlled by the transcription factor nuclear factor (NF)-B, which is upregulated in alveolar macrophages in patients with COPD and in airway cells in patients with mild/moderate COPD in comparison with control nonsmokers. […] In general, with increasing severity of COPD there is a further enhancement of the inflammatory response.

• #6 Mechanisms, Pathophysiology and Currently Proposed Treatments of Chronic Obstructive Pulmonary Disease

  https://www.mdpi.com/1424-8247/14/10/979

  The imbalance between proteases and their inhibitors plays a crucial role in COPD pathogenesis. Proteases, including neutrophil elastase (NE) and proteinase 3, degrade connective tissue components, especially elastin, leading to emphysema. […] The increase in elastolytic enzymes, such as MMPs, induces ECM degradation and alveolar wall destruction. Alveolar macrophages are pivotal to COPD development, because even after smoking cessation, their dysfunction may continue to contribute to disease progression.

• #7 Pathogenesis of Chronic Obstructive Pulmonary Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713323/

  Increased numbers of activated neutrophils are found in sputum from patients with COPD. […] Cigarette smoking is known to increase circulating neutrophil leukocyte count and to cause sequestration of neutrophils in the lung capillaries. […] There is a 5- to 10-fold increase in the numbers of macrophages in the airways, lung parenchyma, and bronchoalveolar lavage fluid (BALF) in patients with COPD. […] Many of the inflammatory mediators that are expressed in COPD are controlled by the transcription factor nuclear factor (NF)-B, which is upregulated in alveolar macrophages in patients with COPD and in airway cells in patients with mild/moderate COPD in comparison with control nonsmokers. […] In general, with increasing severity of COPD there is a further enhancement of the inflammatory response.

• #8 Mechanisms, Pathophysiology and Currently Proposed Treatments of Chronic Obstructive Pulmonary Disease

  https://www.mdpi.com/1424-8247/14/10/979

  The imbalance between proteases and their inhibitors plays a crucial role in COPD pathogenesis. Proteases, including neutrophil elastase (NE) and proteinase 3, degrade connective tissue components, especially elastin, leading to emphysema. […] The increase in elastolytic enzymes, such as MMPs, induces ECM degradation and alveolar wall destruction. Alveolar macrophages are pivotal to COPD development, because even after smoking cessation, their dysfunction may continue to contribute to disease progression.

• #9 Chronic Obstructive Pulmonary Disease (COPD): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/297664-overview

  Cigarette smoke causes neutrophil influx, which is required for the secretion of MMPs; this suggests, therefore, that neutrophils and macrophages are required for the development of emphysema. […] Studies have also shown that in addition to macrophages, T lymphocytes, particularly CD8+, play an important role in the pathogenesis of smoking-induced airflow limitation. […] To support the inflammation hypothesis further, a stepwise increase in alveolar inflammation has been found in surgical specimens from patients without COPD versus patients with mild or severe emphysema. Indeed, mounting evidence supports the concept that dysregulation of apoptosis and defective clearance of apoptotic cells by macrophages play a prominent role in airway inflammation, particularly in emphysema.

• #10 Novel aspects of pathogenesis and regeneration mechanisms in COPD | COPD

  https://www.dovepress.com/novel-aspects-of-pathogenesis-and-regeneration-mechanisms-in-copd-peer-reviewed-fulltext-article-COPD

  The importance of T-cells in emphysema development was recently proven in mice model with the demonstration that T-cells from cigarette smoke-exposed mice are able to transfer the diseased process, ie, tissue destruction, to unexposed mice. […] Recognition of the autoimmune component importance in the COPD development calls for epitope(s) identification. […] All these data stimulate discussion if autoimmune process in COPD is a causative process or just a consequence or even a coincidence.

• #11 Pathogenesis of Chronic Obstructive Pulmonary Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713323/

  Increased numbers of activated neutrophils are found in sputum from patients with COPD. […] Cigarette smoking is known to increase circulating neutrophil leukocyte count and to cause sequestration of neutrophils in the lung capillaries. […] There is a 5- to 10-fold increase in the numbers of macrophages in the airways, lung parenchyma, and bronchoalveolar lavage fluid (BALF) in patients with COPD. […] Many of the inflammatory mediators that are expressed in COPD are controlled by the transcription factor nuclear factor (NF)-B, which is upregulated in alveolar macrophages in patients with COPD and in airway cells in patients with mild/moderate COPD in comparison with control nonsmokers. […] In general, with increasing severity of COPD there is a further enhancement of the inflammatory response.

• #12 Novel aspects of pathogenesis and regeneration mechanisms in COPD | COPD

  https://www.dovepress.com/novel-aspects-of-pathogenesis-and-regeneration-mechanisms-in-copd-peer-reviewed-fulltext-article-COPD

  Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs. […] Several clinical features comprise COPDs such as chronic bronchitis, destruction of small airways, and enlargement/disorganization of alveoli, ie, loss of alveolar tissue. […] Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively. […] Autoimmunity also plays a role in COPD as it becomes increasingly accepted. Autoimmune mechanisms can explain the unregulated inflammatory process perpetuation that continues after smoking cessation, since the initial inflammation and environmental insults in lungs expose certain epitopes for the autoimmune attack.

• #13 Role of the inflammasome in chronic obstructive pulmonary disease (COPD) | Oncotarget

  https://www.oncotarget.com/article/17850/text/

  Some studies revealed that it is involved during airway inflammation typical of COPD. […] The development of COPD is caused by inhalation of noxious particles or gas, especially cigarette smoke (CS) that represents the first risk factor for this respiratory disorder. […] It is believed that lung inflammation in COPD patients reflects the site of deposition of irritants from CS and particles of air pollution, which can cause chronic inflammation in a long-term manner. […] The characteristic of COPD is an altered immune response followed by chronic lung inflammation. […] Emerging scientific evidence suggests that persistent Nod-like Receptor 3 (NLRP3) inflammasome activation may be involved in the onset of COPD pathogenesis. […] The inflammasome is a multimeric complex involved in caspase-1-dependent release of pro-inflammatory IL-1-like cytokines.

• #14 Mechanisms, Pathophysiology and Currently Proposed Treatments of Chronic Obstructive Pulmonary Disease

  https://www.mdpi.com/1424-8247/14/10/979

  The imbalance between proteases and their inhibitors plays a crucial role in COPD pathogenesis. Proteases, including neutrophil elastase (NE) and proteinase 3, degrade connective tissue components, especially elastin, leading to emphysema. […] The increase in elastolytic enzymes, such as MMPs, induces ECM degradation and alveolar wall destruction. Alveolar macrophages are pivotal to COPD development, because even after smoking cessation, their dysfunction may continue to contribute to disease progression.

• #15 Mechanisms, Pathophysiology and Currently Proposed Treatments of Chronic Obstructive Pulmonary Disease

  https://www.mdpi.com/1424-8247/14/10/979

  The imbalance between proteases and their inhibitors plays a crucial role in COPD pathogenesis. Proteases, including neutrophil elastase (NE) and proteinase 3, degrade connective tissue components, especially elastin, leading to emphysema. […] The increase in elastolytic enzymes, such as MMPs, induces ECM degradation and alveolar wall destruction. Alveolar macrophages are pivotal to COPD development, because even after smoking cessation, their dysfunction may continue to contribute to disease progression.

• #16 Chronic Obstructive Pulmonary Disease (COPD): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/297664-overview

  Pathologic changes in chronic obstructive pulmonary disease (COPD) occur in the large (central) airways, the small (peripheral) bronchioles, and the lung parenchyma. Most cases of COPD are the result of exposure to noxious stimuli, most often cigarette smoke. The normal inflammatory response is amplified in persons prone to COPD development. The pathogenic mechanisms are not clear but are most likely diverse. Increased numbers of activated polymorphonuclear leukocytes and macrophages release elastases in a manner that cannot be counteracted effectively by antiproteases, resulting in lung destruction. […] The primary offender has been found to be human leukocyte elastase, with synergistic roles suggested for proteinase-3 and macrophage-derived matrix metalloproteinases (MMPs), cysteine proteinases, and a plasminogen activator. Additionally, increased oxidative stress caused by free radicals in cigarette smoke, the oxidants released by phagocytes, and polymorphonuclear leukocytes all may lead to apoptosis or necrosis of exposed cells. Accelerated aging and autoimmune mechanisms have also been proposed as having roles in the pathogenesis of COPD.

• #17 Chronic Obstructive Pulmonary Disease (COPD) – Pulmonary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pulmonary-disorders/chronic-obstructive-pulmonary-disease-and-related-disorders/chronic-obstructive-pulmonary-disease-copd

  Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. […] Emphysema is destruction of lung parenchyma leading to loss of elastic recoil and loss of alveolar septa and radial airway traction, which increases the tendency for airway collapse. […] Inhalational exposures can trigger an inflammatory response in airways and alveoli that leads to disease in genetically susceptible people. The process is thought to be mediated by an increase in protease activity and a decrease in antiprotease activity. […] In patients with COPD, activated neutrophils and other inflammatory cells release proteases as part of the inflammatory process; protease activity exceeds antiprotease activity, and tissue destruction and mucus hypersecretion result.

• #18 Chronic Obstructive Pulmonary Disease (COPD) – Lung and Airway Disorders – MSD Manual Consumer Version

  https://www.msdmanuals.com/home/lung-and-airway-disorders/chronic-obstructive-pulmonary-disease-copd/chronic-obstructive-pulmonary-disease-copd

  Airflow obstruction in COPD causes air to become trapped in the lungs after a full exhalation, increasing the effort required to breathe. Also in COPD, the number of capillaries in the walls of the alveoli decreases. These abnormalities impair the exchange of oxygen and carbon dioxide between the alveoli and the blood. […] A rare cause of COPD is a hereditary condition in which the body does not produce enough of the protein alpha-1 antitrypsin. The main role of this protein is to prevent neutrophil elastase (an enzyme in certain white blood cells) from damaging the alveoli. Consequently, emphysema develops by early middle age in people with severe alpha-1 antitrypsin deficiency (also called alpha-1 antiprotease deficiency), especially in those who also smoke. […] COPD takes years to develop and progress.

• #19 Progress in the mechanism and targeted drug therapy for COPD | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-020-00345-x

  The pathogenesis of COPD remains unclear and has been generally suggested to be related to inflammation, oxidative stress, protease/anti-protease imbalance and decreased immunity. Smoking, biofuel smoke-induced oxidative stress and excessive protease production are major factors in COPD pathogenesis that cause alveolar cell death, destruction of the extracellular matrix in the alveolar region and loss of alveolar structure. […] The occurrence and development of COPD is a complex pathological process involving a variety of inflammatory cells, inflammatory mediators and related cell signalling pathways. COPD also regulates the goblet cell proliferation, mucoprotein (MUC) synthesis and mucus secretion. […] Oxidative stress is an important factor in COPD pathogenesis. An increased oxidative burden occurs in the lungs of patients with COPD, and oxidative stress may be involved in various the pathogenic processes, such as direct injury to lung cells, mucus hypersecretion, inactivation of antiproteases and enhancing lung inflammation through activation of redox-sensitive transcription factors.

• #20 Pathogenesis of Chronic Obstructive Pulmonary Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713323/

  The inflammatory response in the peripheral airways may play a role in the fibrosis that characterizes the small airways in patients with moderate/severe COPD. […] A large body of literature has been amassed to test the hypothesis that a proteaseantiprotease imbalance, leading to the breakdown of connective tissue components, particularly elastin, is the critical mechanism in the pathogenesis of emphysema in smokers. […] Together with destruction of elastin, inactivation of antiproteases is central to the proteaseantiprotease imbalance hypothesis. […] There is some evidence supporting the concept that an abnormality in elastin synthesis and repair may be involved in the pathogenesis of emphysema. […] Cigarette smoke is a complex mixture of more than 4,700 chemical compounds, including high concentrations of free radicals and other oxidants.

• #21 Pathogenesis of Chronic Obstructive Pulmonary Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713323/

  There is now considerable evidence of increased oxidative stress in smokers and in patients with COPD. […] The major antioxidants in respiratory tract lining fluid include mucin, reduced glutathione, uric acid, protein (largely albumin), and ascorbic acid. […] Studies have shown that glutathione is elevated in BALF from chronic smokers. […] Studies have suggested that susceptibility to COPD may be related to latent adenoviral infection. […] A hypothesis has been advanced that the alveolar cell loss in emphysema is due to apoptosis in response to cigarette smoke, mediated by blockade of the vascular endothelial growth factor (VEGF) receptor that occurs in emphysematous lungs. […] No single mechanism can account for the complex pathology in COPD.

• #22 Progress in the mechanism and targeted drug therapy for COPD | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-020-00345-x

  The pathogenesis of COPD remains unclear and has been generally suggested to be related to inflammation, oxidative stress, protease/anti-protease imbalance and decreased immunity. Smoking, biofuel smoke-induced oxidative stress and excessive protease production are major factors in COPD pathogenesis that cause alveolar cell death, destruction of the extracellular matrix in the alveolar region and loss of alveolar structure. […] The occurrence and development of COPD is a complex pathological process involving a variety of inflammatory cells, inflammatory mediators and related cell signalling pathways. COPD also regulates the goblet cell proliferation, mucoprotein (MUC) synthesis and mucus secretion. […] Oxidative stress is an important factor in COPD pathogenesis. An increased oxidative burden occurs in the lungs of patients with COPD, and oxidative stress may be involved in various the pathogenic processes, such as direct injury to lung cells, mucus hypersecretion, inactivation of antiproteases and enhancing lung inflammation through activation of redox-sensitive transcription factors.

• #23 Pathogenesis of Chronic Obstructive Pulmonary Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713323/

  There is now considerable evidence of increased oxidative stress in smokers and in patients with COPD. […] The major antioxidants in respiratory tract lining fluid include mucin, reduced glutathione, uric acid, protein (largely albumin), and ascorbic acid. […] Studies have shown that glutathione is elevated in BALF from chronic smokers. […] Studies have suggested that susceptibility to COPD may be related to latent adenoviral infection. […] A hypothesis has been advanced that the alveolar cell loss in emphysema is due to apoptosis in response to cigarette smoke, mediated by blockade of the vascular endothelial growth factor (VEGF) receptor that occurs in emphysematous lungs. […] No single mechanism can account for the complex pathology in COPD.

• #24 Pathogenesis of Chronic Obstructive Pulmonary Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713323/

  There is now considerable evidence of increased oxidative stress in smokers and in patients with COPD. […] The major antioxidants in respiratory tract lining fluid include mucin, reduced glutathione, uric acid, protein (largely albumin), and ascorbic acid. […] Studies have shown that glutathione is elevated in BALF from chronic smokers. […] Studies have suggested that susceptibility to COPD may be related to latent adenoviral infection. […] A hypothesis has been advanced that the alveolar cell loss in emphysema is due to apoptosis in response to cigarette smoke, mediated by blockade of the vascular endothelial growth factor (VEGF) receptor that occurs in emphysematous lungs. […] No single mechanism can account for the complex pathology in COPD.

• #25 Pathogenesis of Chronic Obstructive Pulmonary Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713323/

  The inflammatory response in the peripheral airways may play a role in the fibrosis that characterizes the small airways in patients with moderate/severe COPD. […] A large body of literature has been amassed to test the hypothesis that a proteaseantiprotease imbalance, leading to the breakdown of connective tissue components, particularly elastin, is the critical mechanism in the pathogenesis of emphysema in smokers. […] Together with destruction of elastin, inactivation of antiproteases is central to the proteaseantiprotease imbalance hypothesis. […] There is some evidence supporting the concept that an abnormality in elastin synthesis and repair may be involved in the pathogenesis of emphysema. […] Cigarette smoke is a complex mixture of more than 4,700 chemical compounds, including high concentrations of free radicals and other oxidants.

• #26 Chronic obstructive pulmonary disease (COPD) – Etiology | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/7/aetiology

  The hallmark of COPD is chronic inflammation that affects central and peripheral airways, lung parenchyma and alveoli, and pulmonary vasculature. […] The inflammatory and structural changes in the lung increase with disease severity and persist after smoking cessation. […] Evidence suggests that the host response to inhaled stimuli generates the inflammatory reaction responsible for the changes in the airways, alveoli, and pulmonary blood vessels. […] Oxidative stress and an excess of proteases amplify the effects of chronic inflammation. […] Airway remodeling thickens the epithelium, lamina propria, smooth muscle, and adventitia of airways less than 2 mm in diameter, leading to progressive loss of patent terminal and transitional bronchioles. […] Elastin breakdown and subsequent loss of alveolar integrity causes emphysema.

• #27 Mechanisms, Pathophysiology and Currently Proposed Treatments of Chronic Obstructive Pulmonary Disease

  https://www.mdpi.com/1424-8247/14/10/979

  COPD is characterized by progressive airflow limitation that is not fully reversible, associated with an abnormal inflammatory response of the lungs to noxious particles or gases. Emphysema is the result of destruction of alveolar walls, which leads to reduced gas exchange, permanent airspace enlargement, loss of elastic recoil, hyperinflation, and expiratory flow limitation. […] In addition to inflammation, COPD is characterized by an imbalance between proteases and their inhibitors, oxidative stress, and infections that generate disease symptoms. […] Oxidative stress is the primary cause of COPD pathogenesis, triggering apoptosis, extracellular matrix remodeling, inactivation of protease inhibitors, mucus secretion, NF-κB activation, mitogen-activated protein kinase (MAPK) activation, chromatin remodeling, and pro-inflammatory gene transcription.

• #28 COPD – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/copd/symptoms-causes/syc-20353679

  Chronic obstructive pulmonary disease (COPD) is an ongoing lung condition caused by damage to the lungs. The damage results in swelling and irritation, also called inflammation, inside the airways that limit airflow into and out of the lungs. This limited airflow is known as obstruction. […] COPD is most often caused by long-term exposure to irritating smoke, fumes, dust or chemicals. The most common cause is cigarette smoke. […] In emphysema, the inner walls of the lungs’ air sacs called alveoli are damaged, causing them to eventually rupture. This creates one larger air space instead of many small ones and reduces the surface area available for gas exchange. […] Long-term exposure to irritants, such as from smoking, injures the lungs. This damage keeps air from moving in and out of the lungs freely, limiting their ability to provide oxygen to the bloodstream and take away carbon dioxide. The two main conditions that prevent effective airflow in the lungs are: Emphysema. This lung condition causes destruction of the fragile walls and elastic fibers of the alveoli.

• #29 Chronic obstructive pulmonary disease (COPD) – Etiology | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/7/aetiology

  Ciliary dysfunction and increased goblet cell size and number lead to excessive mucus secretion. […] Increased airway resistance is the physiologic definition of COPD. […] Decreased elastic recoil, fibrotic changes in lung parenchyma, and luminal obstruction of airways by secretions all contribute to increased airways resistance. […] Hyperinflation and destruction of lung parenchyma predispose patients with COPD to hypoxia, particularly during activity. […] Progressive hypoxia causes vascular smooth muscle thickening with subsequent pulmonary hypertension, which is a late development conveying a poor prognosis. […] Systemic inflammatory mediators may contribute to skeletal muscle wasting or cachexia, and initiate or worsen cardiac, metabolic, and skeletal comorbidities.

• #30 Chronic obstructive pulmonary disease (COPD) – Etiology | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/7/aetiology

  Ciliary dysfunction and increased goblet cell size and number lead to excessive mucus secretion. […] Increased airway resistance is the physiologic definition of COPD. […] Decreased elastic recoil, fibrotic changes in lung parenchyma, and luminal obstruction of airways by secretions all contribute to increased airways resistance. […] Hyperinflation and destruction of lung parenchyma predispose patients with COPD to hypoxia, particularly during activity. […] Progressive hypoxia causes vascular smooth muscle thickening with subsequent pulmonary hypertension, which is a late development conveying a poor prognosis. […] Systemic inflammatory mediators may contribute to skeletal muscle wasting or cachexia, and initiate or worsen cardiac, metabolic, and skeletal comorbidities.

• #31

  https://www.jci.org/articles/view/60324

  The induction of cell death in structural cells of the lung parenchyma (epithelial, endothelial, and possibly septal fibroblast cells) in response to cigarette smoke may be related to a loss of growth factors, oxidative stress injury, or intracellular response to stress imposed by noxious exposures. […] Investigation into the interactions between upstream and downstream events related to alveolar cell apoptosis during emphysema onset and progression led to the key finding of self-amplifying injury loops involving apoptosis, oxidative stress, and inflammation. […] There is growing evidence that pulmonary and systemic inflammation, key events in COPD, may change in nature as the disease progresses. […] This change in the nature of inflammation in the course of disease is highlighted by the temporary nature of NF-B activation in rodent lungs exposed to cigarette smoke.

• #32

  https://www.jci.org/articles/view/60324

  The induction of cell death in structural cells of the lung parenchyma (epithelial, endothelial, and possibly septal fibroblast cells) in response to cigarette smoke may be related to a loss of growth factors, oxidative stress injury, or intracellular response to stress imposed by noxious exposures. […] Investigation into the interactions between upstream and downstream events related to alveolar cell apoptosis during emphysema onset and progression led to the key finding of self-amplifying injury loops involving apoptosis, oxidative stress, and inflammation. […] There is growing evidence that pulmonary and systemic inflammation, key events in COPD, may change in nature as the disease progresses. […] This change in the nature of inflammation in the course of disease is highlighted by the temporary nature of NF-B activation in rodent lungs exposed to cigarette smoke.

• #33 Pathogenesis of Chronic Obstructive Pulmonary Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713323/

  There is now considerable evidence of increased oxidative stress in smokers and in patients with COPD. […] The major antioxidants in respiratory tract lining fluid include mucin, reduced glutathione, uric acid, protein (largely albumin), and ascorbic acid. […] Studies have shown that glutathione is elevated in BALF from chronic smokers. […] Studies have suggested that susceptibility to COPD may be related to latent adenoviral infection. […] A hypothesis has been advanced that the alveolar cell loss in emphysema is due to apoptosis in response to cigarette smoke, mediated by blockade of the vascular endothelial growth factor (VEGF) receptor that occurs in emphysematous lungs. […] No single mechanism can account for the complex pathology in COPD.

• #34

  https://www.jci.org/articles/view/60324

  The acute inflammatory response appears to be transient in nature and mediated by NF-B, likely counteracted by regulatory networks that dampen NF-Bdependent responses. […] Cigarette smoke disrupts alveolar maintenance, triggering apoptosis and autophagy; moreover, oxidants in tobacco and activated inflammatory and alveolar cells lead to extracellular matrix proteolysis, which further enhances inflammation and promote a feedback loop with apoptosis. […] A more complex picture of the mechanisms of alveolar destruction leading to emphysema has emerged in the past 12 years. […] We believe that mechanisms involved in the progression stage of COPD may be distinctly engaged in generating variable intermediate and clinically relevant disease phenotypes, such as emphysema, chronic airway disease (including chronic bronchitis and bronchiolitis), and systemic disease.

• #35 Pathogenesis of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke – Hikichi – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/32744

  Chronic obstructive pulmonary disease (COPD) is a common respiratory disease that is characterized by functional and structural alterations primarily caused by long-term inhalation of harmful particles. […] This review discusses the basic pathogenesis of COPD, with particular focus on an endogenous protective mechanism against oxidative stress via Nrf2, altered immune response of the airway inflammatory cells, exaggerated cellular senescence of the lung structural cells, and cell death with expanded inflammation. […] Recently, CS-induced mitochondria autophagy is reported to initiate programmed necrosis (necroptosis). […] This new cell death mechanism is of importance due to its ability to produce more inflammatory substances during the process of epithelial death, contributing to persistent airway inflammation that cannot be explained by apoptosis-derived cell death.

• #36

  https://www.jci.org/articles/view/60324

  Understanding the mechanism of this persistence might have a far-reaching impact on the design and implementation of regenerative therapies. […] The relentless lung injury due to oxidant exposure, along with the potential exhaustion of lung protective responses, ultimately leads to lung aging, with increased expression of markers of cellular senescence. […] The ultimate biological clock of cell turnover is controlled by telomerase, which preserves the shortening of ends of chromosomes during every round of mitosis. […] The contribution of shortened telomeres was recently unraveled in investigations with the telomerase reverse transcriptase-knockout mice, which showed increased sensitivity to alveolar injury and airspace enlargement due to cigarette smoke.

• #37 Novel aspects of pathogenesis and regeneration mechanisms in COPD | COPD

  https://www.dovepress.com/novel-aspects-of-pathogenesis-and-regeneration-mechanisms-in-copd-peer-reviewed-fulltext-article-COPD

  In addition to factors mentioned earlier, accelerated cell senescence has been implicated in the pathogenesis of COPD. […] COPD pathogenesis evolves with the disease exacerbations that are main drivers of health deterioration in patients with COPD. […] Inflammation-related contributors to lung tissue injury include cells and mediators of both initiative and adaptive immunity, ROS, imbalance of local proteolysis/antiproteolysis state, and other insults. […] It is well proven that lung tissue in every smoker is inflamed. […] Unbalanced proteolysis is a long-lived and simplified explanatory mechanism to explain processes within emphysematous lung. […] The role of proteolysis is proven and recognized from the very beginning, when emphysema was first described as an antiprotease deficiency-associated disease.

• #38 Pathogenesis of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke – Hikichi – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/32744

  Aging of the lungs results in the acquisition of senescence-associated secretory phenotypes (SASP) that are known to secrete inflammatory cytokines, chemokines, growth factors, and matrix metalloproteinases resulting in chronic low-grade inflammation. […] This review provides insights into CS-induced COPD pathogenesis, which contributes to a very complex disease. […] Investigating the mechanism of developing COPD, along with the availability of the particular inhibitors, will lead to new therapeutic approaches in COPD treatment.

• #39

  https://www.jci.org/articles/view/60324

  Understanding the mechanism of this persistence might have a far-reaching impact on the design and implementation of regenerative therapies. […] The relentless lung injury due to oxidant exposure, along with the potential exhaustion of lung protective responses, ultimately leads to lung aging, with increased expression of markers of cellular senescence. […] The ultimate biological clock of cell turnover is controlled by telomerase, which preserves the shortening of ends of chromosomes during every round of mitosis. […] The contribution of shortened telomeres was recently unraveled in investigations with the telomerase reverse transcriptase-knockout mice, which showed increased sensitivity to alveolar injury and airspace enlargement due to cigarette smoke.

• #40 Novel aspects of pathogenesis and regeneration mechanisms in COPD | COPD

  https://www.dovepress.com/novel-aspects-of-pathogenesis-and-regeneration-mechanisms-in-copd-peer-reviewed-fulltext-article-COPD

  Chronic obstructive pulmonary disease (COPD), a major cause of death and morbidity worldwide, is characterized by expiratory airflow limitation that is not fully reversible, deregulated chronic inflammation, and emphysematous destruction of the lungs. […] Several clinical features comprise COPDs such as chronic bronchitis, destruction of small airways, and enlargement/disorganization of alveoli, ie, loss of alveolar tissue. […] Several generally recognized mechanisms will be discussed shortly herein, ie, unregulated inflammation, proteolysis/antiproteolysis imbalance, and destroyed repair mechanisms, while novel topics such as deviated microbiota, air pollutants-related damage, and autoimmune process within the lung tissue will be discussed more extensively. […] Autoimmunity also plays a role in COPD as it becomes increasingly accepted. Autoimmune mechanisms can explain the unregulated inflammatory process perpetuation that continues after smoking cessation, since the initial inflammation and environmental insults in lungs expose certain epitopes for the autoimmune attack.

• #41 Novel aspects of pathogenesis and regeneration mechanisms in COPD | COPD

  https://www.dovepress.com/novel-aspects-of-pathogenesis-and-regeneration-mechanisms-in-copd-peer-reviewed-fulltext-article-COPD

  The importance of T-cells in emphysema development was recently proven in mice model with the demonstration that T-cells from cigarette smoke-exposed mice are able to transfer the diseased process, ie, tissue destruction, to unexposed mice. […] Recognition of the autoimmune component importance in the COPD development calls for epitope(s) identification. […] All these data stimulate discussion if autoimmune process in COPD is a causative process or just a consequence or even a coincidence.

• #42 Pathogenesis of Chronic Obstructive Pulmonary Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713323/

  Increased numbers of activated neutrophils are found in sputum from patients with COPD. […] Cigarette smoking is known to increase circulating neutrophil leukocyte count and to cause sequestration of neutrophils in the lung capillaries. […] There is a 5- to 10-fold increase in the numbers of macrophages in the airways, lung parenchyma, and bronchoalveolar lavage fluid (BALF) in patients with COPD. […] Many of the inflammatory mediators that are expressed in COPD are controlled by the transcription factor nuclear factor (NF)-B, which is upregulated in alveolar macrophages in patients with COPD and in airway cells in patients with mild/moderate COPD in comparison with control nonsmokers. […] In general, with increasing severity of COPD there is a further enhancement of the inflammatory response.

• #43

  https://www.jci.org/articles/view/60324

  The acute inflammatory response appears to be transient in nature and mediated by NF-B, likely counteracted by regulatory networks that dampen NF-Bdependent responses. […] Cigarette smoke disrupts alveolar maintenance, triggering apoptosis and autophagy; moreover, oxidants in tobacco and activated inflammatory and alveolar cells lead to extracellular matrix proteolysis, which further enhances inflammation and promote a feedback loop with apoptosis. […] A more complex picture of the mechanisms of alveolar destruction leading to emphysema has emerged in the past 12 years. […] We believe that mechanisms involved in the progression stage of COPD may be distinctly engaged in generating variable intermediate and clinically relevant disease phenotypes, such as emphysema, chronic airway disease (including chronic bronchitis and bronchiolitis), and systemic disease.

• #44 Progress in the mechanism and targeted drug therapy for COPD | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-020-00345-x

  The pathogenesis of COPD is closely related to the imbalance of protease/anti-protease, which leads to the destruction of the elastin framework. […] COPD pathology is characterised by airway remodelling and inflammatory cell infiltration by the neutrophils, CD8 T lymphocytes and activated macrophages. […] The inflammatory process of COPD is characterised by a continued migration of inflammatory cells (mainly neutrophils) from the blood vessel to the lungs. […] The transcription factor NF-B is studied in systemic inflammation and has been noticed in COPD patients. […] The phosphatidylinositol 3 kinase (PI3K) pathway is a major pathway regulating cell growth, proliferation, metabolism, survival and angiogenesis. […] Trx is a multifunctional protein consisting of 105 amino acids with a molecular weight of 12kDa and a highly conserved Cys-Gly-Pro-Cys active site.

• #45 Role of the inflammasome in chronic obstructive pulmonary disease (COPD) | Oncotarget

  https://www.oncotarget.com/article/17850/text/

  Inflammation is central to the development of chronic obstructive pulmonary disease (COPD), a pulmonary disorder characterized by chronic bronchitis, chronic airway obstruction, emphysema, associated to progressive and irreversible decline of lung function. […] Emerging genetic and pharmacological evidence suggests that IL-1-like cytokines are highly detected in the sputum and broncho-alveolar lavage (BAL) of COPD patients, implying the involvement of the multiprotein complex inflammasome. […] So far, scientific evidence has focused on nucleotide-binding oligomerization domain-like receptors protein 3 (NLRP3) inflammasome, a specialized inflammatory signaling platform that governs the maturation and secretion of IL-1-like cytokines through the regulation of caspase-1-dependent proteolytic processing.

• #46 Role of the inflammasome in chronic obstructive pulmonary disease (COPD) | Oncotarget

  https://www.oncotarget.com/article/17850/text/

  Inflammation is central to the development of chronic obstructive pulmonary disease (COPD), a pulmonary disorder characterized by chronic bronchitis, chronic airway obstruction, emphysema, associated to progressive and irreversible decline of lung function. […] Emerging genetic and pharmacological evidence suggests that IL-1-like cytokines are highly detected in the sputum and broncho-alveolar lavage (BAL) of COPD patients, implying the involvement of the multiprotein complex inflammasome. […] So far, scientific evidence has focused on nucleotide-binding oligomerization domain-like receptors protein 3 (NLRP3) inflammasome, a specialized inflammatory signaling platform that governs the maturation and secretion of IL-1-like cytokines through the regulation of caspase-1-dependent proteolytic processing.

• #47 Pathological mechanism and targeted drugs of COPD | COPD

  https://www.dovepress.com/pathological-mechanism-and-targeted-drugs-of-copd-peer-reviewed-fulltext-article-COPD

  Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis, emphysema, and small airway obstruction. Incompletely reversible airflow limitation, inflammation, excessive mucus secretion and bronchial mucosal epithelial lesions are the main pathological basis of the disease. […] This paper summarizes the pathogenesis of COPD and clarifies the effect and mechanism of the latest targeted drugs for COPD. […] NLRP3 can promote production of interleukin-1 (IL-1) and interleukin-18 (IL-18). NLRP3 is an important factor in the migratory aggregation of macrophages and neutrophils and the generation of oxidative stress. Inhibition of NLRP3 inflammasome indirectly blocks the inflammatory effects of IL-1 and IL-18, which may be regarded as an ideal target for COPD treatment. […] COPD is an incurable chronic lung disease, which is also complicated by pulmonary heart disease and respiratory failure in some individuals with a tremendous burden on individuals and society.

• #48 Role of the inflammasome in chronic obstructive pulmonary disease (COPD) | Oncotarget

  https://www.oncotarget.com/article/17850/text/

  The persistent activation of NLRP3, as well as its overexpression into the recruited and in tissue-resident cells, may promote chronic diseases. […] High levels of IL-1 are found in the lungs of patients with COPD after CS exposure. […] Interestingly, NLRP3 is over-expressed in the lung of stable COPD patients rather than non-smokers and smokers with normal spirometry, implying the correlation of NLRP3 mRNA expression to the severity of airflow obstruction. […] However, the authors did not observe caspase-1 activation (cleavage in the active p10 form) in both human lung tissue and PBMCs obtained from stable COPD patients, suggesting that the high levels of IL-1 and IL-18 were driven by a different mechanism. […] Importantly, in this latter study, macrophages obtained from stable COPD patients phagocyte BAL-derived ASC specks triggering the secretion of IL-1 without the induction of NLRP3 assembly.

• #49 Role of the inflammasome in chronic obstructive pulmonary disease (COPD) | Oncotarget

  https://www.oncotarget.com/article/17850/text/

  The persistent activation of NLRP3, as well as its overexpression into the recruited and in tissue-resident cells, may promote chronic diseases. […] High levels of IL-1 are found in the lungs of patients with COPD after CS exposure. […] Interestingly, NLRP3 is over-expressed in the lung of stable COPD patients rather than non-smokers and smokers with normal spirometry, implying the correlation of NLRP3 mRNA expression to the severity of airflow obstruction. […] However, the authors did not observe caspase-1 activation (cleavage in the active p10 form) in both human lung tissue and PBMCs obtained from stable COPD patients, suggesting that the high levels of IL-1 and IL-18 were driven by a different mechanism. […] Importantly, in this latter study, macrophages obtained from stable COPD patients phagocyte BAL-derived ASC specks triggering the secretion of IL-1 without the induction of NLRP3 assembly.

• #50 Pathogenesis of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke – Hikichi – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/32744/html

  The molecular pathology underlying chronic obstructive pulmonary disease (COPD) is influenced by genetic background, cellular senescence, and chronic inhalation of harmful particles, such as those present in CS. […] The importance of Nrf2 is confirmed by CS-exposed Nrf2-deficient mice demonstrating a development of emphysematous lesion in the lungs. […] The disruption of the epithelial barrier and the reduction in E-cadherin expression induces epithelial-mesenchymal transition, consequently inducing the aberrant production of MMPs and growth factors, airway destruction, and remodeling. […] The most probable explanation for the age-associated changes in COPD is the intracellular and extracellular production of ROS. […] Cellular senescence also occurs in stem cells. […] The relationship between autophagy and programmed necrosis (necroptosis) involved in CS-induced cell death is a novel finding that reveals the mechanism of exaggerated inflammatory response that is not explained by apoptosis-derived cell death. […] Understanding the mechanism of cell death signaling, along with the availability of inhibitors, is now focused as a new therapeutic target in COPD.

• #51 Pathogenesis of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke – Hikichi – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/32744/html

  Chronic obstructive pulmonary disease (COPD) is a common respiratory disease that is characterized by functional and structural alterations primarily caused by long-term inhalation of harmful particles. Cigarette smoke (CS) induces airway inflammation in COPD, which is known to persist even after smoking cessation. This review discusses the basic pathogenesis of COPD, with particular focus on an endogenous protective mechanism against oxidative stress via Nrf2, altered immune response of the airway inflammatory cells, exaggerated cellular senescence of the lung structural cells, and cell death with expanded inflammation. […] Significant evidence shows that oxidative stress damages the lungs and contributes to COPD pathogenesis. It is possible that therapeutic administration of multiple antioxidants will be effective in the management of COPD.

• #52 Progress in the mechanism and targeted drug therapy for COPD | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-020-00345-x

  The pathogenesis of COPD is closely related to the imbalance of protease/anti-protease, which leads to the destruction of the elastin framework. […] COPD pathology is characterised by airway remodelling and inflammatory cell infiltration by the neutrophils, CD8 T lymphocytes and activated macrophages. […] The inflammatory process of COPD is characterised by a continued migration of inflammatory cells (mainly neutrophils) from the blood vessel to the lungs. […] The transcription factor NF-B is studied in systemic inflammation and has been noticed in COPD patients. […] The phosphatidylinositol 3 kinase (PI3K) pathway is a major pathway regulating cell growth, proliferation, metabolism, survival and angiogenesis. […] Trx is a multifunctional protein consisting of 105 amino acids with a molecular weight of 12kDa and a highly conserved Cys-Gly-Pro-Cys active site.

• #53 Exploring Type 2 Inflammation in Chronic Obstructive Pulmonary Disease – European Medical Journal

  https://www.emjreviews.com/respiratory/symposium/exploring-type-2-inflammation-in-chronic-obstructive-pulmonary-disease/

  This symposium took place during the 2023 meeting of the European Respiratory Society (ERS), with a focus on targeting chronic obstructive pulmonary disease (COPD) with Type 2 inflammation, and the emerging biologic landscape. […] The role of Type 2 inflammation in the pathophysiology of COPD, and the evolving clinical landscape in COPD. […] Chronic inflammation may be triggered by tobacco smoke, toxic particles or gases, viruses or bacteria, or oxidative stress. […] This inflammation drives structural changes in the airways. […] The combination of structural changes in the airways and parenchymal destruction results in airflow limitation. […] The concept of COPD as a disease limited to the lungs, airways, and lung parenchyma has evolved. It is well known that systemic inflammation is present in COPD, including both pulmonary and extrapulmonary systems.

• #54 Chronic Obstructive Pulmonary Disease (COPD) – Respirology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.3.6.

  These changes in turn cause airflow limitation and lung hyperinflation, which when advanced may lead to gas exchange abnormalities, and in severe cases are followed by the development of pulmonary hypertension (due to hypoxic vasoconstriction, structural changes to the small pulmonary arteries, and loss of the pulmonary capillary bed) and cor pulmonale. […] Chronic inflammation, hypoxia, and physical inactivity cause COPD systemic effects, which include cachexia, skeletal muscle wasting, reduced bone density, anemia, and central nervous system abnormalities. COPD comorbidities (bronchiectasis, hypertension, ischemic heart disease, stroke, arrhythmias, diabetes mellitus, metabolic syndrome, anxiety, and depression) have adverse effects on the patients health status and prognosis. COPD increases the risk of lung cancer.

• #55 Chronic Obstructive Pulmonary Disease (COPD) – Respirology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.3.6.

  These changes in turn cause airflow limitation and lung hyperinflation, which when advanced may lead to gas exchange abnormalities, and in severe cases are followed by the development of pulmonary hypertension (due to hypoxic vasoconstriction, structural changes to the small pulmonary arteries, and loss of the pulmonary capillary bed) and cor pulmonale. […] Chronic inflammation, hypoxia, and physical inactivity cause COPD systemic effects, which include cachexia, skeletal muscle wasting, reduced bone density, anemia, and central nervous system abnormalities. COPD comorbidities (bronchiectasis, hypertension, ischemic heart disease, stroke, arrhythmias, diabetes mellitus, metabolic syndrome, anxiety, and depression) have adverse effects on the patients health status and prognosis. COPD increases the risk of lung cancer.

• #56 Chronic Obstructive Pulmonary Disease (COPD) – Respirology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.3.6.

  These changes in turn cause airflow limitation and lung hyperinflation, which when advanced may lead to gas exchange abnormalities, and in severe cases are followed by the development of pulmonary hypertension (due to hypoxic vasoconstriction, structural changes to the small pulmonary arteries, and loss of the pulmonary capillary bed) and cor pulmonale. […] Chronic inflammation, hypoxia, and physical inactivity cause COPD systemic effects, which include cachexia, skeletal muscle wasting, reduced bone density, anemia, and central nervous system abnormalities. COPD comorbidities (bronchiectasis, hypertension, ischemic heart disease, stroke, arrhythmias, diabetes mellitus, metabolic syndrome, anxiety, and depression) have adverse effects on the patients health status and prognosis. COPD increases the risk of lung cancer.

• #57 The role of pulmonary vascular endothelium in chronic obstructive pulmonary disease (COPD): Does endothelium play a role in the onset and progression of COPD?

  https://www.explorationpub.com/Journals/em/Article/1001199

  Chronic obstructive pulmonary disease (COPD) is an inflammatory lung pathology characterized by persistent airflow limitation and is the third leading cause of death globally. […] The mechanisms promoting endothelial dysfunction in the systemic and/or pulmonary circulation of COPD patients are different and include systemic inflammation, alteration of adhesion and pro-inflammatory molecules, oxidative stress, cellular senescence, and apoptosis. […] In COPD, endothelial dysfunction occurs in the early stages of the disease and worsens with pulmonary obstruction severity and during acute exacerbations. […] Understanding the mechanisms underlying the trafficking of leukocytes, neutrophils, cytokine, chemokine, and inflammatory molecules across the endothelium to the lung parenchyma, new treatments may be developed and the risk of COPD onset may be reduced. […] The mechanisms that promote endothelial dysfunction in the systemic and/or pulmonary circulation of COPD patients are different and include systemic inflammation, alteration of adhesion and pro-inflammatory molecules, oxidative stress, cellular senescence, and apoptosis.

• #58 COPD: Causes, Symptoms, Diagnosis, Treatment & Prevention

  https://my.clevelandclinic.org/health/diseases/8709-chronic-obstructive-pulmonary-disease-copd

  COPD can trap bacteria in your lungs, leading to infections. It can also prevent oxygen from getting into your body and carbon dioxide from getting out. This can lead to serious complications, including: Pneumonia. High levels of carbon dioxide in your blood (hypercapnia). Low levels of oxygen in your blood (hypoxemia). Respiratory failure. Pulmonary hypertension. Right-sided heart failure (cor pulmonale). Collapsed lung (pneumothorax). Polycythemia (making too many red blood cells). […] Theres no cure for COPD. Treatment focuses on improving your symptoms and reducing and treating exacerbations. Your provider may recommend: Smoking cessation programs. If you smoke, quitting can slow down the progression of COPD. Inhaled medications. Bronchodilators and steroids can reduce inflammation and open your airways.

• #59 Progress in the mechanism and targeted drug therapy for COPD | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-020-00345-x

  Trx expression in the sputum of COPD patients is positively correlated with the degree of hypoxia. […] Trx plays an important role in maintaining the body’s redox balance. […] Trx regulates MIF expression levels and inhibits inflammation caused by MIF. […] COPD pathogenesis is mainly related to the overexpression of inflammatory mediators and cytokines, the activation of inflammatory signalling pathways, the protease/anti-protease imbalance, and the oxidation-antioxidation imbalance. […] Trx plays an important role in the treatment of COPD. Its mechanism of action is highly unified with the pathogenesis of COPD, and it effectively inhibits the occurrence and development of COPD through a variety of mechanisms.

• #60 Pathogenesis of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke – Hikichi – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/32744

  Aging of the lungs results in the acquisition of senescence-associated secretory phenotypes (SASP) that are known to secrete inflammatory cytokines, chemokines, growth factors, and matrix metalloproteinases resulting in chronic low-grade inflammation. […] This review provides insights into CS-induced COPD pathogenesis, which contributes to a very complex disease. […] Investigating the mechanism of developing COPD, along with the availability of the particular inhibitors, will lead to new therapeutic approaches in COPD treatment.

• #61 Pathogenesis of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke – Hikichi – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/32744/html

  The molecular pathology underlying chronic obstructive pulmonary disease (COPD) is influenced by genetic background, cellular senescence, and chronic inhalation of harmful particles, such as those present in CS. […] The importance of Nrf2 is confirmed by CS-exposed Nrf2-deficient mice demonstrating a development of emphysematous lesion in the lungs. […] The disruption of the epithelial barrier and the reduction in E-cadherin expression induces epithelial-mesenchymal transition, consequently inducing the aberrant production of MMPs and growth factors, airway destruction, and remodeling. […] The most probable explanation for the age-associated changes in COPD is the intracellular and extracellular production of ROS. […] Cellular senescence also occurs in stem cells. […] The relationship between autophagy and programmed necrosis (necroptosis) involved in CS-induced cell death is a novel finding that reveals the mechanism of exaggerated inflammatory response that is not explained by apoptosis-derived cell death. […] Understanding the mechanism of cell death signaling, along with the availability of inhibitors, is now focused as a new therapeutic target in COPD.

• #62 Exploration of Multi-Aspect Development of Chronic Obstructive Pulmonary Disease Pathogenesis, Diagnosis, and Treatment Management | IntechOpen

  https://www.intechopen.com/chapters/83119

  Unregulated inflammation, oxidative/antioxidant imbalance, proteolytic/anti-proteolytic imbalance, and imbalance of cell damage/repair are recognized mechanisms. At the same time, microbiota bias, air-pollutant-related damage, and autoimmune processes in lung tissue are all underlying pathogenesis of COPD. Epigenetic regulation has also been implicated in the pathogenesis of COPD. […] The common symptom of AECOPD is transient dyspnea, sputum suppuration, and increased sputum volume. Mild symptoms also occur, such as nasal obstruction, wheezing, sore throat, cough, fever, chest tightness, fatigue, insomnia, or physical activity limitation. In most cases, exacerbation in inflammatory airway is triggered by infection. […] These mechanisms mentioned above work together to produce two major pathologies: small airway pressure elevation and emphysema, which cause persistent irreversible airflow limitation. COPD is a chronic disease with high morbidity and mortality, which is a serious threat to human health. Because of its complex etiology and pathogenesis, at present, there are still no effective targeted drugs and treatments. We should further study the cellular and molecular mechanisms in the pathogenesis of COPD in order to detect the disease early and delay disease progression.

• #63 Progress in the mechanism and targeted drug therapy for COPD | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-020-00345-x

  Trx expression in the sputum of COPD patients is positively correlated with the degree of hypoxia. […] Trx plays an important role in maintaining the body’s redox balance. […] Trx regulates MIF expression levels and inhibits inflammation caused by MIF. […] COPD pathogenesis is mainly related to the overexpression of inflammatory mediators and cytokines, the activation of inflammatory signalling pathways, the protease/anti-protease imbalance, and the oxidation-antioxidation imbalance. […] Trx plays an important role in the treatment of COPD. Its mechanism of action is highly unified with the pathogenesis of COPD, and it effectively inhibits the occurrence and development of COPD through a variety of mechanisms.

• #64 Exploration of Multi-Aspect Development of Chronic Obstructive Pulmonary Disease Pathogenesis, Diagnosis, and Treatment Management | IntechOpen

  https://www.intechopen.com/chapters/83119

  Unregulated inflammation, oxidative/antioxidant imbalance, proteolytic/anti-proteolytic imbalance, and imbalance of cell damage/repair are recognized mechanisms. At the same time, microbiota bias, air-pollutant-related damage, and autoimmune processes in lung tissue are all underlying pathogenesis of COPD. Epigenetic regulation has also been implicated in the pathogenesis of COPD. […] The common symptom of AECOPD is transient dyspnea, sputum suppuration, and increased sputum volume. Mild symptoms also occur, such as nasal obstruction, wheezing, sore throat, cough, fever, chest tightness, fatigue, insomnia, or physical activity limitation. In most cases, exacerbation in inflammatory airway is triggered by infection. […] These mechanisms mentioned above work together to produce two major pathologies: small airway pressure elevation and emphysema, which cause persistent irreversible airflow limitation. COPD is a chronic disease with high morbidity and mortality, which is a serious threat to human health. Because of its complex etiology and pathogenesis, at present, there are still no effective targeted drugs and treatments. We should further study the cellular and molecular mechanisms in the pathogenesis of COPD in order to detect the disease early and delay disease progression.

• #65 Pathogenesis of Chronic Obstructive Pulmonary Disease

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2713323/

  There is now considerable evidence of increased oxidative stress in smokers and in patients with COPD. […] The major antioxidants in respiratory tract lining fluid include mucin, reduced glutathione, uric acid, protein (largely albumin), and ascorbic acid. […] Studies have shown that glutathione is elevated in BALF from chronic smokers. […] Studies have suggested that susceptibility to COPD may be related to latent adenoviral infection. […] A hypothesis has been advanced that the alveolar cell loss in emphysema is due to apoptosis in response to cigarette smoke, mediated by blockade of the vascular endothelial growth factor (VEGF) receptor that occurs in emphysematous lungs. […] No single mechanism can account for the complex pathology in COPD.

• #66 Exploration of Multi-Aspect Development of Chronic Obstructive Pulmonary Disease Pathogenesis, Diagnosis, and Treatment Management | IntechOpen

  https://www.intechopen.com/chapters/83119

  Unregulated inflammation, oxidative/antioxidant imbalance, proteolytic/anti-proteolytic imbalance, and imbalance of cell damage/repair are recognized mechanisms. At the same time, microbiota bias, air-pollutant-related damage, and autoimmune processes in lung tissue are all underlying pathogenesis of COPD. Epigenetic regulation has also been implicated in the pathogenesis of COPD. […] The common symptom of AECOPD is transient dyspnea, sputum suppuration, and increased sputum volume. Mild symptoms also occur, such as nasal obstruction, wheezing, sore throat, cough, fever, chest tightness, fatigue, insomnia, or physical activity limitation. In most cases, exacerbation in inflammatory airway is triggered by infection. […] These mechanisms mentioned above work together to produce two major pathologies: small airway pressure elevation and emphysema, which cause persistent irreversible airflow limitation. COPD is a chronic disease with high morbidity and mortality, which is a serious threat to human health. Because of its complex etiology and pathogenesis, at present, there are still no effective targeted drugs and treatments. We should further study the cellular and molecular mechanisms in the pathogenesis of COPD in order to detect the disease early and delay disease progression.

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