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• W1966678873 abstract "Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous collection of conditions characterized by irreversible expiratory airflow limitation. The disease involves a multifaceted progressive inflammatory process leading to the development of mucus hypersecretion, tissue destruction, and disruption to the normal repair and defense mechanisms. The result is increased resistance to airflow in small conducting airways, change in lung compliance, and the premature collapse of airways during expiration that leads to air trapping. Neutrophils are necessary in healthy lungs; they are an important component of innate immunity, protecting healthy individuals against infection. However, in COPD, they play a role in the destructive processes that characterize the disease. They can be responsible for significant damage when they accumulate at sites of inflammation and are harmful to healthy tissue. In recent years, increased understanding of the role of neutrophils has led to improved knowledge of the pathogenesis of COPD and allowed new avenues of treatment to be investigated. Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous collection of conditions characterized by irreversible expiratory airflow limitation. The disease involves a multifaceted progressive inflammatory process leading to the development of mucus hypersecretion, tissue destruction, and disruption to the normal repair and defense mechanisms. The result is increased resistance to airflow in small conducting airways, change in lung compliance, and the premature collapse of airways during expiration that leads to air trapping. Neutrophils are necessary in healthy lungs; they are an important component of innate immunity, protecting healthy individuals against infection. However, in COPD, they play a role in the destructive processes that characterize the disease. They can be responsible for significant damage when they accumulate at sites of inflammation and are harmful to healthy tissue. In recent years, increased understanding of the role of neutrophils has led to improved knowledge of the pathogenesis of COPD and allowed new avenues of treatment to be investigated. Chronic obstructive pulmonary disease (COPD) is “a preventable and treatable disease with some significant extra-pulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.”1Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (GOLD). 2006. Available at: http://www.goldcopd.com. Accessed December 1, 2006.Google Scholar The causes are multifactorial, with genetic factors and environmental factors such as cigarette smoke, air pollution, and infection all playing a role. This disease is predominantly seen in individuals who smoke or who have quit smoking. Physiologically, the chronic airflow limitation is reflected by narrowing and blockage of the small airways, reducing expiratory flow, such that a slow forced expiration is required to empty the lungs. Airway obstruction occurs long before the patient is aware of symptoms because of its slowly progressive nature. The severity of COPD is defined in terms of the FEV1 expressed as a percentage of the normal volume with sex-matched and height-matched individuals.1Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (GOLD). 2006. Available at: http://www.goldcopd.com. Accessed December 1, 2006.Google Scholar COPD is currently the fourth leading cause of death in the United States and Europe,1Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (GOLD). 2006. Available at: http://www.goldcopd.com. Accessed December 1, 2006.Google Scholar and understanding its pathogenesis is key if we are to prevent it from becoming an even greater health problem worldwide. This review article looks at the role of neutrophils in stable COPD both in the lung and systemically, and the role of neutrophils in disease progression, bacterial colonization, and exacerbation.The neutrophil in stable COPDNeutrophilic inflammation in COPDAs early as 1983, studies involving bronchoalveolar lavage (BAL) showed that smokers have an increase in neutrophils in BAL compared with nonsmokers. It has been postulated that cigarette smoke induces macrophages to release neutrophil chemotactic factors such as IL-8. Levels of IL-8 have been shown to be higher in the sputum and bronchial washings of smokers compared with controls.2Bosken C.H. Hards J. Gatter K. Hogg J.C. Characterisation of the inflammatory reaction in the peripheral airways of cigarette smokers using immunocytochemistry.Am Rev Respir Dis. 1992; 145: 911-917Crossref PubMed Google Scholar Cigarette smoke also impairs ingestion of neutrophils by macrophages and decreases the ability of macrophages to phagocytose apoptotic cells. This leads to a cascade of events that damages central and peripheral airways along with terminal airspaces, causing the physiologic and clinical abnormalities described.Neutrophilic inflammation occurs in healthy lungs but is increased in many acute and chronic lung diseases, in particular acute bronchitis, adult respiratory distress syndrome, COPD, and severe asthma. Neutrophils are responsible for significant damage when they accumulate at sites of inflammation and are harmful to healthy tissue. The accumulation of neutrophils is a dynamic process that consists of recruitment from the bloodstream and clearance from the lungs as a result of phagocytosis of apoptotic cells. Epithelial cells are key regulators of neutrophil trafficking into the airway lumen, and neutrophils are attracted there from the vascular space by chemotactic factors such as IL-8, leukotriene B4 (LTB4), and TNF-α.The abnormal inflammatory response that occurs in COPD involves neutrophils along with other inflammatory cells including macrophages and CD8+ T lymphocytes, which play a role in producing structural changes in the airways. In emphysema, the neutrophil shifts the balance between protease and antiprotease in the lung in favor of lung destruction. The structural changes that ensue include loss of respiratory bronchioles, alveolar ducts, and alveoli. This leads to mucociliary dysfunction and reduced mucociliary clearance. In chronic bronchitis, inflammation is characterized by mucosal infiltration with neutrophils, macrophages, and lymphocytes, resulting in epithelial disruption, smooth muscle hypertrophy, and fibrosis.Distribution of neutrophils in the lung in COPDSputum and BAL of patients with COPD contain higher numbers of neutrophils than lung parenchyma, indicating rapid transport through the airways.3Keatings V.M. Collins P.D. Scott D.M. Barnes P.J. Differences in interleukin-8 and tumour necrosis factor-α in induced sputum from patients with chronic obstructive pulmonary disease or asthma.Am J Respir Crit Care Med. 1996; 153: 530-534Crossref PubMed Scopus (1218) Google Scholar Neutrophil numbers have been found to be greater in bronchial epithelium and lamina propria in smokers compared with controls, with neutrophil numbers higher in the small airways than large airways.4Pesci A. Majori M. Cuomo A. Borciani N. Bertacco S. Cacciani G. et al.Neutrophils infiltrating bronchial epithelium in chronic obstructive pulmonary disease.Respir Med. 1998; 92: 863-870Abstract Full Text PDF PubMed Scopus (61) Google Scholar, 5Battaglia S. Mauad T. van Schadewijk A.M. Vignola A.M. Rabe K.F. Bellia V. et al.Differential distribution of inflammatory cells in large and small airways in smokers.J Clin Pathol. 2006; (Aug 17 [epub ahead of print])PubMed Google Scholar Neutrophilic infiltration also occurs in the bronchial glands, causing these cells to act as producers of potent secretagogues.There are increased numbers of neutrophils and CD8+ T lymphocytes infiltrating the smooth muscle in the peripheral airways of patients with COPD compared with smokers and nonsmoking controls.6Baraldo S. Turato G. Badin C. Bazzan E. Beghe B. Zuin R. et al.Neutrophilic infiltration within the airway smooth muscle in patients with COPD.Thorax. 2004; 59: 308-312Crossref PubMed Scopus (117) Google Scholar It is thought that chronic inflammation contributes to changes in structure and contractility of airway smooth muscle, with chemokines such as IL-8 playing a role in smooth muscle proliferation and constriction.Transepithelial neutrophil migrationOnce neutrophils have matured in the bone marrow, they are released into the circulation. They continue to circulate until they become senescent and are cleared, or they are recruited to sites of inflammation. If this occurs, local arrest of the neutrophil occurs because of adherence to vascular endothelium at sites of inflammation, and they pass through the blood vessels and migrate into tissues.The process of neutrophil migration occurs through a series of steps controlled and coordinated by the interaction of adhesion molecules on the surface of the neutrophil and proteins secreted by the bronchial endothelial cells. The migration of neutrophils into the bronchial submucosa occurs via the bronchial circulation by a process of selectin-mediated cell rolling and capture followed by CD18-mediated adhesion and transmigration. Neutrophil adherence to the endothelium and subsequent migration out of postcapillary venules during systemic inflammation is largely dependent on B2-integrin (CD18), a neutrophil adhesion molecule. Upregulation of neutrophil adhesion molecules such as CD621 and macrophage antigen (MAC)-1 (CD11b/CD18) increases neutrophil-endothelial cell interaction.7Woolhouse I.S. Bayley D.L. Lalor P. Adams D.H. Stockley R.A. Endothelial interactions of neutrophils under flow in chronic obstructive pulmonary disease.Eur Respir J. 2005; 25: 612-617Crossref PubMed Scopus (28) Google Scholar In patients with COPD, neutrophils have been shown to have increased surface expression of MAC-1.8Noguera A. Busquets X. Sauleda J. Villaverde J.M. MacNee W. Agusti A.G. Expression of adhesion molecules and G proteins in circulating neutrophils in chronic obstructive pulmonary disease.Am J Respir Crit Care Med. 1998; 158: 1664-1668Crossref PubMed Scopus (150) Google Scholar This is important, because it is thought MAC-1 (CD11b/CD18) facilitates neutrophil adhesion via its endothelial counter receptor intercellular adhesion molecule 1 (ICAM-1).9Diamond M.S. Staunton D.E. de Fougerolles A.R. Stacker S.A. Garcia-Aguilar J. Hibbs M.L. et al.ICAM-1 (CD54): a counter-receptor for MAC-1 (CD11b/CD18).J Cell Biol. 1990; 111: 3129-3139Crossref PubMed Scopus (770) Google Scholar Exposure to IL-8 causes rapid mobilization of MAC-1 to the neutrophil surface10Huber A.R. Kunkel S.L. Todd R.F. Weiss S.J. Regulation of transendothelial neutrophil migration by endogenous interleukin-8.Science. 1991; 254: 99-102Crossref PubMed Scopus (652) Google Scholar (Fig 1).Neutrophils accumulate on the mucosal surface of large airways and in the lumen. In large airways, it is thought they reach the airway from the tracheobronchial circulation and migrate past postcapillary venules.11Pabst R. Tshernig T. Perivascular capillaries in the lung: an important but neglected vascular bed in immune reactions?.J Allergy Clin Immunol. 2002; 110: 209-214Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar Neutrophils from the circulation marginate in the pulmonary circulation and adhere to endothelial cells in the alveolar wall before passing into the alveolar space.12Hogg J.C. Walker B. Polymorphonuclear leucocyte traffic in lung inflammation.Thorax. 1995; 50: 819-820Crossref PubMed Scopus (19) Google Scholar The epithelial cells form a barrier lining the airway of the lung and are key regulators of neutrophil trafficking into the airway lumen.Chemokines involved in migration and upregulation of neutrophilsVarious chemokines stimulate upregulation of vascular adhesion molecules and increase neutrophilic uptake in areas where they are needed most. E-selectin, which is necessary for slowing down circulating neutrophils, is upregulated on endothelial cells in the airways of patients with COPD.13DiStefano A. Maestrelli P. Roggeri A. Turato G. Calabro S. Potena A. et al.Upregulation of adhesion molecules in the bronchial mucosa of subjects with chronic obstructive bronchitis.Am J Respir Crit Care Med. 1994; 149: 803-810Crossref PubMed Scopus (219) Google Scholar Numbers of circulating adhesion molecules are also increased in COPD. Adherent neutrophils migrate into the respiratory tract under the direction of IL-8, LTB4, TNF-α, GM-CSF, and nuclear factor-κB (NF-κB), a transcription factor.14Traves S.L. Culpitt S. Russell R.E.K. Barnes P.J. Donnelly L.E. Elevated levels of the chemokines GRO-α and MCP-1 in sputum samples from COPD patients.Thorax. 2002; 57: 590-595Crossref PubMed Scopus (299) Google Scholar, 15Tanino M. Betsuyaku T. Takeyabu K. Tanino Y. Yamaguchi E. Miyamoto K. et al.Increased levels of interleukin-8 in BAL fluid from smokers susceptible to pulmonary emphysema.Thorax. 2002; 57: 405-411Crossref PubMed Scopus (123) Google Scholar Neutrophil influx is also dependent on the presence of macrophage-derived matrix metalloproteinase (MMP)–12. Release of MMP-12 from macrophages via an auto-feedback loop causes macrophages to release TNF-α, resulting in a neutrophil influx. Once neutrophils are beyond the endothelial barrier, chemotactic signals lead to their accumulation near mucosal epithelial cells and in the lumen of the airway (Fig 2).Fig 2Chemokine upregulation of neutrophils in COPD. Release of cytokines contributes to recruitment of neutrophils and their degranulation, thus furthering inflammation. MPO, Myeloperoxidase.View Large Image Figure ViewerDownload Hi-res image Download (PPT)IL-8 is produced by neutrophils, monocytes, alveolar macrophages, pulmonary epithelium, smooth muscle airway cells, eosinophils, and fibroblasts. It induces the release of myeloperoxidase from neutrophils and contributes to further recruitment of inflammatory cells, helping to sustain inflammation. TNF-α is released from T lymphocytes, mast cells, and epithelial cells. It plays a role in controlling cellular migration and permeability and stimulates the secretion of GM-CSF, IL-6, and IL-8. TNF-α also activates transcription factor NF-κB, which activates IL-8 gene expression in epithelial cells and macrophages.16Chung K.F. Cytokines in chronic obstructive pulmonary disease.Eur Respir J. 2001; 18: 50-59Crossref Google Scholar LTB4 stimulates chemotaxis, neutrophil degranulation, release of lysosomal enzymes, and generates reactive oxygen species (ROS).Consequences of neutrophils in the airwayThe role of neutrophils in the front line of cellular host defense against microorganisms relies in part on respiratory bursting. This term describes their ability to generate large amounts of O2– and related ROS through activation of nicotinamide adenine dinucleotide phosphate oxidase on the plasma membrane. Oxygen-derived free radicals (eg, O2– and H2O2) serve as intracellular signaling molecules for a variety of chemokines, including LTB4, TNF-α,17Woo C.H. Eom Y.W. Yoo M.H. You H.J. Han H.J. Song W.K. et al.Tumour necrosis factor-α generates reactive oxygen species via cytosolic phospholipase A2-linked cascade.J Biol Chem. 2000; 275: 32357-32362Crossref PubMed Scopus (213) Google Scholar IL-1, and TGF-β1, as well as various other growth factors.Neutrophils and macrophages degranulate, resulting in the release of elastases that stimulate macrophages to release LTB4,18Hubbard R.C. Fells G. Gadek J. Pacholok S. Humes J. Crystal R.G. Neutrophil accumulation in the lung in α1-antitrypsin deficiency: spontaneous release of leukotriene B4 by alveolar macrophages.J Clin Invest. 1991; 88: 891-897Crossref PubMed Scopus (181) Google Scholar cathepsin G, ROS, and proteinases.19Tetley T.D. Macrophages and the pathogenesis of COPD.Chest. 2002; 121: 156s-159sCrossref PubMed Scopus (170) Google Scholar These proteinases and ROS damage the epithelium,20Noguera A. Batle S. Miralles C. Iglesias J. Busquets X. MacNee W. et al.Enhanced neutrophil response in chronic obstructive pulmonary disease.Thorax. 2001; 56: 432-437Crossref PubMed Scopus (201) Google Scholar reduce ciliary beat frequency, stimulate mucus secretion by goblet cells,21Nadel J.A. Role of neutrophil elastase in hypersecretion during COPD exacerbations, and proposed therapies.Chest. 2000; 117: 386s-389sCrossref PubMed Scopus (89) Google Scholar and increase the permeability of the bronchial mucosa. This results in airway edema and protein exudation in the airway.22Gompertz S. O'Brien C. Bayley D.L. Hill S.L. Stockley R.A. Changes in bronchial inflammation during acute exacerbations of chronic bronchitis.Eur Respir J. 2001; 17: 1112-1119Crossref PubMed Scopus (264) Google Scholar Neutrophil elastase and ROS have been shown to increase epithelial mucin mRNA and protein gene expression in vitro.23Takeyama K. Dabbagh K. Jeong Shim J. Dao-Pick T. Ueki I.F. Nadel J.A. Oxidative stress causes mucin synthesis via transactivation of epidermal growth factor receptor: role of neutrophils.J Immunol. 2000; 164: 1546-1552PubMed Google Scholar Patients with COPD have increased ROS production and increased gene expression of adhesion molecules on neutrophils compared with healthy smokers and nonsmokers.24Gustafsson A. Asman B. Bergstrom K. Cigarette smoking as an aggravating factor in inflammatory tissue-destructive diseases: increase tumour necrosis factor-alpha priming of peripheral neutrophils measured as generation of oxygen radicals.Int J Clin Lab Res. 2000; 30: 187-190Crossref PubMed Scopus (42) Google ScholarResolution of airway neutrophilic inflammationResolution of neutrophilic inflammation occurs by apoptosis of neutrophils, followed by their removal by macrophages using a phagocyte recognition mechanism.By its nature, apoptosis helps to minimize and prevent any permanent damage by neutrophilic inflammation. During apoptosis, neutrophils retain their granule contents and lose their ability to secrete them in response to secretagogues.25Haslett C. Granulocyte apoptosis and its role in the resolution and control of lung inflammation.Am J Respir Crit Care Med. 1999; 160: S5-S11Crossref PubMed Scopus (441) Google Scholar They also lose their phagocytic capacity. Neutrophil apoptosis involves attenuation of activation and degranulation, nuclear and cytoplasmic condensation, DNA fragmentation, dilation of the endoplasmic reticulum, and alterations in cell membrane composition, along with activation and leakage of cytochrome c from mitochondria. It has been hypothesized that increased concentrations of proneutrophilic factors in the airways prolong neutrophil survival, but this has not been found to be the case.26Rytila P. Plataki M. Bucchieri F. Uddin M. Nong G. Kinnula V.L. et al.Airway neutrophilia in COPD is not associated with increased neutrophil survival.Eur Respir J. 2006; 28: 1163-1169Crossref PubMed Scopus (30) Google ScholarIf neutrophils are not cleared efficiently by apoptosis, they are removed by the mucociliary escalator. Unfortunately, this results in the release of proteases and chemoattractants, which contributes to lung damage. In COPD, raised levels of GM-CSF, IL-8, and LTB4 will delay neutrophil apoptosis.27Barnes P.J. Shapiro S.D. Pauwels R.A. Chronic obstructive pulmonary disease: molecular and cell mechanisms.Eur Respir J. 2003; 22: 672-688Crossref PubMed Scopus (1075) Google Scholar In addition, the decreased mucociliary clearance in COPD leads to longer retention of apoptotic neutrophils. Consequently, the inflammation is self perpetuated: impaired phagocytosis leads to decreased neutrophil clearance and increased secondary necrosis. Neutrophilic retention then leads to a further decrease in mucociliary clearance and thus increased inflammation.Systemic neutrophils in COPDChronic obstructive pulmonary disease not only affects the airways but also has systemic manifestations such as an increased C-reactive protein and muscle wasting. Activation of peripheral blood neutrophils by cytokines has been shown to occur. This activation is thought to be related to disease severity, and to occur by leukocyte priming,28Koenderman L. Kanters D. Maesen B. Raaijmakers J. Lammers J. de Kruif J. et al.Monitoring of neutrophil priming in whole blood by antibodies isolated from a synthetic phage antibody library.J Leukoc Biol. 2000; 68: 58-64PubMed Google Scholar which is essential for neutrophil uptake into tissues. Systemic neutrophils of patients with COPD have enhanced chemotaxis and extracellular proteolysis and produce more ROS than those from nonsmokers and healthy smoker controls. Soluble TNF-α receptors have also been found in greater numbers in the peripheral blood of patients with COPD.29Vernooy J.H. Kucukayacan M. Jacobs J.A. Chavannes N. Buurman W. Dentener M. et al.Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumour necrosis factor receptors are increased in sputum.Am J Respir Crit Care Med. 2002; 166: 1218-1224Crossref PubMed Scopus (338) Google Scholar However, no difference has been found in apoptosis of neutrophils in peripheral blood between patients with stable COPD and controls.8Noguera A. Busquets X. Sauleda J. Villaverde J.M. MacNee W. Agusti A.G. Expression of adhesion molecules and G proteins in circulating neutrophils in chronic obstructive pulmonary disease.Am J Respir Crit Care Med. 1998; 158: 1664-1668Crossref PubMed Scopus (150) Google Scholar, 30Pletz M.W. Ioanas M. de Roux A. Burkhardt O. Lode H. Reduced spontaneous apoptosis in peripheral blood neutrophils during exacerbation of COPD.Eur Respir J. 2004; 23: 532-537Crossref PubMed Scopus (50) Google ScholarNeutrophils in progression of COPDDisease progression in COPD from mild to very severe1Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (GOLD). 2006. Available at: http://www.goldcopd.com. Accessed December 1, 2006.Google Scholar is associated with thickening of the airway wall by a process of repair or remodeling.31Hogg J.C. Chu F. Utokaparch S. Woods R. Elliot W.M. Buzatu L. et al.The nature of small airway obstruction in chronic obstructive pulmonary disease.N Engl J Med. 2004; 350: 2645-2653Crossref PubMed Scopus (2844) Google Scholar This disease progression is related to the degree to which the lumen is filled with mucous exudates and the extent of the inflammatory response.Cross-sectional studies have shown that the concentration of neutrophils in BAL fluid or sputum increases with reduced FEV1 and in patients with a longer history of smoking,32Di Stefano A. Capelli A. Lusuardi M. Balbo P. Vecchio C. Maestrelli P. et al.Severity of airflow limitation is associated with severity of airway inflammation is smokers.Am J Respir Crit Care Med. 1998; 158: 1277-1285Crossref PubMed Scopus (461) Google Scholar, 33Stanescu D. Sanna A. Veriter C. Kostianev S. Calcagni P. Fabbri L. et al.Airways obstruction, chronic expectoration and rapid decline in FEV1 in smokers are associated with increased levels of sputum in neutrophils.Thorax. 1996; 51: 267-271Crossref PubMed Scopus (364) Google Scholar indicating that subjects with greater airflow limitation have a greater neutrophilia than controls. Patients with COPD who are frequent exacerbators, that is, individuals who have more than 2.5 exacerbations per year, have a faster rise in sputum inflammatory markers (IL-6 and IL-8) over time, and more rapid decline in lung function.34Donaldson G.C. Seemungal T.A. Bhowmik A. Wedzicha J. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease.Thorax. 2002; 57: 847-852Crossref PubMed Scopus (1758) Google Scholar, 35Kanner R.E. Anthonisen N.R. Connett J.E. Lower respiratory illnesses promote FEV1 decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease.Am J Respir Crit Care Med. 2001; 164: 358-364Crossref PubMed Scopus (522) Google Scholar In these patients, higher sputum IL-6 and IL-8 levels are seen not only at exacerbation but also in the stable state compared with infrequent exacerbators.36Donaldson G.C. Seemungal T.A. Patel I.S. Bhowmik A. Wilkinson T.M. Hurst J.R. et al.Airway and systemic inflammation and decline in lung function in patients with COPD.Chest. 2005; 128: 1995-2004Crossref PubMed Scopus (362) Google ScholarAnother measure of disease severity is the amount of air trapping measured by computed tomography scanning, and neutrophilic inflammation of airway smooth muscle in smokers is related to air trapping.37Berger P. Laurent F. Begueret H. Perot V. Rouiller R. Raherison C. et al.Structure and function of small airways in smokers: relationship between air trapping and CT and airway inflammation.Radiology. 2003; 228: 85-94Crossref PubMed Scopus (47) Google Scholar Studies have also shown that high-resolution computed tomography indices of peripheral airways dysfunction correlate with neutrophil counts but not with severity of emphysema.38O'Donnell R.A. Peebles C. Ward J.A. Daraker A. Angco G. Broberg P. et al.Relationship between peripheral airway dysfunction, airway obstruction, and neutrophilic inflammation in COPD.Thorax. 2004; 59: 837-842Crossref PubMed Scopus (208) Google ScholarNeutrophil chemoattractants and disease severityTNF-α, IL-8, and IL-6 levels are all increased in induced sputum in patients with COPD, with levels of these chemokines increasing with increased obstruction.39Hacievliyagil S.S. Gunen H. Mutlu L.C. Karabulut A.B. Temel I. Association between cytokines in induced sputum and severity of chronic obstructive pulmonary disease.Respir Med. 2006; 100: 846-854Abstract Full Text Full Text PDF PubMed Scopus (80) Google ScholarBronchial biopsies of patients with mild/moderate COPD show an increased inflammatory cell infiltration in the bronchial mucosa in comparison with nonsmoking controls. This is predominated by T lymphocytes,13DiStefano A. Maestrelli P. Roggeri A. Turato G. Calabro S. Potena A. et al.Upregulation of adhesion molecules in the bronchial mucosa of subjects with chronic obstructive bronchitis.Am J Respir Crit Care Med. 1994; 149: 803-810Crossref PubMed Scopus (219) Google Scholar and the numbers of neutrophils in bronchial biopsies correlate with disease severity.3Keatings V.M. Collins P.D. Scott D.M. Barnes P.J. Differences in interleukin-8 and tumour necrosis factor-α in induced sputum from patients with chronic obstructive pulmonary disease or asthma.Am J Respir Crit Care Med. 1996; 153: 530-534Crossref PubMed Scopus (1218) Google Scholar The epithelial and nuclear expression of NF-κB is increased in mild/moderate COPD and to a lesser extent in smoking controls compared with nonsmoking controls.40Di Stefano A. Capelli A. Lusuardi M. Caramori G. Balbo P. Ioli F. et al.Decreased T-lymphocyte infiltration in bronchial biopsies of subjects with severe chronic obstructive pulmonary disease.Clin Expir Allergy. 2001; 31: 893-902Crossref PubMed Scopus (72) Google Scholar This is important because nuclear expression of NF-κB modulates the transcription of IL-6, IL-8, TNF-α, and ICAM-1 along with other cytokines,41Di Stefano A. Caramori G. Oates T. Lusuardi G. Gnemmi I. Ioli F. et al.Increased expression of nuclear factor KB in bronchial biopsies from smokers and patients with COPD.Eur Respir J. 2002; 20: 556-563Crossref PubMed Scopus (356) Google Scholar contributing to ongoing inflammation. Endothelial adhesion molecule 1, ICAM-1, and IL-8 are increased in mild/moderate disease in bronchial epithelium compared with smoking and nonsmoking controls,13DiStefano A. Maestrelli P. Roggeri A. Turato G. Calabro S. Potena A. et al.Upregulation of adhesion molecules in the bronchial mucosa of subjects with chronic obstructive bronchitis.Am J Respir Crit Care Med. 1994; 149: 803-810Crossref PubMed Scopus (219) Google Scholar providing further evidence for a mechanism of possible neutrophil recruitment.4Pesci A. Majori M. Cuomo A. Borciani N. Bertacco S. Cacciani G. et al.Neutrophils infiltrating bronchial epithelium in chronic obstructive pulmonary disease.Respir Med. 1998; 92: 863-870Abstract Full Text PDF PubMed Scopus (61) Google ScholarIn severe COPD, there are an increase of neutrophils and macrophages in the submucosa compared with smoking controls and decreased numbers of T lymphocytes in comparison with mild/moderate disease.40Di Stefano A. Capelli A. Lusuardi M. Caramori G. Balbo P. Ioli F. et al.Decreased T-lymphocyte infiltration in bronchial biopsies of subjects with severe chronic obstructive pulmonary disease.Clin Expir Allergy. 2001; 31: 893-902Crossref PubMed Scopus (72) Google Scholar This suggests a shift to cells possessing phagocytic and proteolytic activity with increasing severity of disease.42Rahman I. Skwarska E. MacNee W. Attenuation of oxidant/antioxidant imbalance during treatment of exacerbations of chronic obstructive pulmonary disease.Thorax. 1997; 52: 565-568Crossref PubMed Scopus (140) Google ScholarBacterial colonization in COPDBacterial colonization, in particular with Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, is a phenomenon occasionally seen in healthy smokers" @default.
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• W1966678873 title "The neutrophil in chronic obstructive pulmonary disease" @default.
• W1966678873 cites W1907868111 @default.
• W1966678873 cites W1933597658 @default.
• W1966678873 cites W1966224713 @default.
• W1966678873 cites W1983701497 @default.
• W1966678873 cites W1984512240 @default.
• W1966678873 cites W1990674750 @default.
• W1966678873 cites W1991648511 @default.
• W1966678873 cites W1991740267 @default.
• W1966678873 cites W1995593745 @default.
• W1966678873 cites W2004963486 @default.
• W1966678873 cites W2011475548 @default.
• W1966678873 cites W2013451988 @default.
• W1966678873 cites W2015327085 @default.
• W1966678873 cites W2015373555 @default.
• W1966678873 cites W2029610924 @default.
• W1966678873 cites W2033380992 @default.
• W1966678873 cites W2038897809 @default.
• W1966678873 cites W2047625338 @default.
• W1966678873 cites W2050286820 @default.
• W1966678873 cites W2054316293 @default.
• W1966678873 cites W2054829155 @default.
• W1966678873 cites W2055415548 @default.
• W1966678873 cites W2059289753 @default.
• W1966678873 cites W2063598450 @default.
• W1966678873 cites W2072809295 @default.
• W1966678873 cites W2082993687 @default.
• W1966678873 cites W2086872426 @default.
• W1966678873 cites W2099004448 @default.
• W1966678873 cites W2099627512 @default.
• W1966678873 cites W2100662719 @default.
• W1966678873 cites W2101182707 @default.
• W1966678873 cites W2105166354 @default.
• W1966678873 cites W2107216684 @default.
• W1966678873 cites W2107865846 @default.
• W1966678873 cites W2108983987 @default.
• W1966678873 cites W2110265450 @default.
• W1966678873 cites W2110429416 @default.
• W1966678873 cites W2110947112 @default.
• W1966678873 cites W2112692443 @default.
• W1966678873 cites W2117837864 @default.
• W1966678873 cites W2117855473 @default.
• W1966678873 cites W2125562494 @default.
• W1966678873 cites W2126497058 @default.
• W1966678873 cites W2128759447 @default.
• W1966678873 cites W2129238234 @default.
• W1966678873 cites W2131829840 @default.
• W1966678873 cites W2132128923 @default.
• W1966678873 cites W2132742272 @default.
• W1966678873 cites W2138695842 @default.
• W1966678873 cites W2140295891 @default.
• W1966678873 cites W2141061213 @default.
• W1966678873 cites W2145466675 @default.
• W1966678873 cites W2146257741 @default.
• W1966678873 cites W2150285844 @default.
• W1966678873 cites W2150785864 @default.
• W1966678873 cites W2152132747 @default.
• W1966678873 cites W2152520891 @default.
• W1966678873 cites W2152702795 @default.
• W1966678873 cites W2154246576 @default.
• W1966678873 cites W2158351251 @default.
• W1966678873 cites W2158549296 @default.
• W1966678873 cites W2163984817 @default.
• W1966678873 doi "https://doi.org/10.1016/j.jaci.2006.12.640" @default.
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