The European respiratory journal. Supplement最新文献

{"title":"Chronic obstructive pulmonary disease as a systemic disease: an epidemiological perspective.","authors":"H Andreassen,&nbsp;J Vestbo","doi":"10.1183/09031936.03.00000203","DOIUrl":"https://doi.org/10.1183/09031936.03.00000203","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) has been increasingly recognised as a systemic disease. The hormonal, metabolic and musculoskeletal implications of the generalised processes involving oxidative stress, inflammatory mediators, cytokines, and endocrine hormones have only begun to be understood. Only a few studies have looked into the epidemiology of inflammatory markers in patients with chronic obstructive pulmonary disease. Common extrapulmonary effects of chronic obstructive pulmonary disease include skeletal muscle dysfunction, wasting and osteoporosis. The resulting effects of a systemic inflammation can be measured at specific extrapulmonary organs such as skeletal muscle or in more general terms using body composition, body weight or derived measures, and only a few studies have set the parameters in an epidemiological context. Nevertheless, these studies indicate an association between inflammatory markers and forced expiratory volume in one second not only in subjects with severe chronic obstructive pulmonary disease. Also, it is increasingly clear that systemic markers in chronic obstructive pulmonary disease have important effects on prognosis.</p>","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"46 ","pages":"2s-4s"},"PeriodicalIF":0.0,"publicationDate":"2003-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00000203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24079590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix metalloproteinases in lung repair.","authors":"W C Parks","doi":"10.1183/09031936.03.00001203","DOIUrl":"https://doi.org/10.1183/09031936.03.00001203","url":null,"abstract":"The aims of this article are to discuss current concepts of the function of matrix metalloproteinases (MMPs), with an emphasis on identification of authentic substrates. Focusing on matrilysin (MMP‐7), it is demonstrated how a single extracellular proteinase can regulate key and common functions of epithelial biology, namely defence against microorganisms, re-epithelialisation in response to injury and acute inflammation. Using findings from models of acute lung injury, the mechanism of matrilysin's action in these processes, that is, the proteins it acts upon to facilitate specific biological processes is discussed.\u0000\u0000Despite their specialisation to serve distinct functions, the epithelium of different tissues respond similarly to injury and infection and regulate inflammation by equivalent mechanisms. By forming a barrier and releasing antimicrobial products, epithelia provide the first line of defence against invading pathogens. Following injury, epithelial cells initiate a programmed series of coordinated responses to restore tissue integrity. By their production of chemoattractants, adhesion molecules, and other proteins, epithelial cells recruit and confine inflammatory cells to sites of injury. Though seemingly divergent processes, the epithelial programmes regulating repair, defence and inflammation may have co-evolved, particularly with respect to the genes selectively induced. After all, injury provides an opportunity for infection, which can lead to injury; both events being proinflammatory. Hence, many of the epithelial products associated with any one of these events are likely common to all. Matrilysin (MMP‐7), is an example of a protein that functions in defence, repair, and as shown here, inflammation.\u0000\u0000MMPs comprise a family of 23 (currently) related, yet distinct enzymes. MMPs are secreted or anchored to the cell surface 1, 2, thereby confining their catalytic activity to membrane proteins or proteins within the secretory pathway or extracellular space. As their name suggests, MMPs are thought to be responsible for the turnover and degradation of connective …","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"44 ","pages":"36s-38s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00001203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress as an initiator of cytokine release and cell damage.","authors":"J D Crapo","doi":"10.1183/09031936.03.00000203a","DOIUrl":"https://doi.org/10.1183/09031936.03.00000203a","url":null,"abstract":"<p><p>This article characterised the role of oxidative stress in mediating pathological reactions in the lung and the unique antioxidant defences that the lung possesses. The impact of redox balance in regulating inflammatory and immune reactions were discussed, and the impact of enhancing lung antioxidant capacity in animal models of asthma and chronic obstructive pulmonary disease were characterised.</p>","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"44 ","pages":"4s-6s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00000203a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting apoptosis in the control of inflammation.","authors":"H U Simon","doi":"10.1183/09031936.03.00000603b","DOIUrl":"https://doi.org/10.1183/09031936.03.00000603b","url":null,"abstract":"Apoptosis is the most common form of physiological cell death and serves to eliminate cells that are genomically altered and therefore potentially harmful to the body, senescent or become replaced by functionally different cell types. It is defined by morphological criteria, including chromatin condensation, nuclear fragmentation, plasma membrane blebbing, organelle disruption, loss of adhesion and rounding (in adherent cells), and cell shrinkage. Apoptosis is required for normal development and maintenance of tissue homeostasis, and its dysregulation is associated with various pathological conditions. For instance, there is often too little apoptosis in cancer and there is usually too much apoptosis in neurodegeneration and acquired immune deficiency syndrome. In inflammatory responses, delayed apoptosis of inflammatory cells contributes to their accumulation in order to efficiently eliminate the pathogen. This article provides a short overview regarding dysregulated apoptosis associated with inflammation.\u0000\u0000Delayed neutrophil apoptosis has been associated with several acute and chronic inflammatory diseases ( e.g. pneumonia, sepsis, cystic fibrosis) and appears to be largely mediated by excessive production of granulocyte colony­stimulating factor and granulocyte/macrophage colony­stimulating factor (GM‐CSF) 1. The induction of neutrophil apoptosis during the resolution of a neutrophilic inflammatory response can be mimicked in vitro by culturing the cells in the absence of sufficient concentrations of survival factors, a process called spontaneous apoptosis. Most studies have been performed on purified blood neutrophils, aiming to understand the molecular events that control apoptosis in these cells. Tyrosine kinases, the phosphoinositide 3‐kinase …","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"44 ","pages":"20s-21s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00000603b","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basic mechanisms of lung inflammation: executive summary of the first Lung Science Meeting of the European Respiratory Society at Taormina, Italy in 2003.","authors":"H J Hoffmann","doi":"10.1183/09031936.03.00000103b","DOIUrl":"https://doi.org/10.1183/09031936.03.00000103b","url":null,"abstract":"The contribution of structural changes and the biology of lung cells to pulmonary disease was emphasised and contrasted with the inflammatory response at the first Lung Science Conference held at Taormina, Italy 26–28 March 2003 (table 1⇓). Here the basic mechanisms of inflammation and their relevance to lung diseases are discussed. For more information on the intracellular events discussed, look at and listen to individual talks on the European Respiratory Society web page at http://www.ersnet.org/taormina.\u0000\u0000View this table:\u0000\u00001 \u0000Central messages from Taormina\u0000\u0000\u0000\u0000Both the environment (“the air we breathe and the food we eat”) and the genetic potential (correct gene products expressed at the right place at the right time) contribute to homeostasis in the lung as well as to pathological deviation. Examples of environmental factors that contribute to the development of pulmonary disease were cigarette smoke condensate 1, lipopolysaccharide 2 and diesel exhaust particles. The redox potential of the lungs 3 is critical to the response to environmental insults and the subsequent expression of lung diseases 4. Genetic contributions to risk factors were discussed for sarcoidosis 5 and idiopathic fibrosis in surfactant protein (SP)‐D variants 6.\u0000\u0000A wound inflicted upon the pulmonary epithelium will attempt to heal. Concurrently, the immune system will respond with an inflammatory response to protect against imminent infection. Among the stimulating talks on repair, growth and differentiation of structural cells, the description of how embryos heal wounds 7, 8 was most fascinating. Using green fluorescent protein­labelled actin in drosophila and zebra fish, video sequences of differentiating embryos and wounded embryos showed how the epithelial cells stretch and pull toward each other in an attempt to close a wound. At the ends of the wound, lamellipodia of cells meet and interdigitate to reform the intact epithelium. If the drosophila homologue transforming growth factor (TGF)‐β PUK …","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"44 ","pages":"1s-3s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00000103b","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of coagulation cascade proteases in lung repair and fibrosis.","authors":"R C Chambers","doi":"10.1183/09031936.03.00001003","DOIUrl":"https://doi.org/10.1183/09031936.03.00001003","url":null,"abstract":"The specific aims of this presentation are: 1) to review the evidence that activation of the coagulation cascade is a common feature of fibrotic lung disease and other respiratory conditions associated with excessive deposition of extracellular matrix; 2) to describe the profibrotic effects of coagulation proteases and the signalling receptors involved; and 3) to provide evidence that coagulation proteases and their signalling receptors contribute to experimentally induced lung fibrosis.\u0000\u0000The fragile architecture of the lung is constantly under threat from both external and internal insults. When these insults lead to damage of the extensive vascular network of the lung, activation of the coagulation cascade (fig. 1⇓) ensures that there is minimal blood loss by temporarily plugging damaged vessels with a stable clot consisting of aggregated platelets enmeshed in fibrin. However, excessive or smouldering activation of the coagulation cascade has been implicated in promoting lung inflammation and subsequent interstitial and alveolar fibrosis 1, 2. Intra-alveolar accumulation of fibrin occurs in the lungs of patients with pulmonary fibrosis 3, in acute lung injury and in the acute respiratory distress syndrome (ARDS) 4, in which rapid fibroproliferation and matrix synthesis can lead to the development of extensive fibrotic lesions. Bronchoalveolar lavage fluid from patients with ARDS has also been reported to contain tissue factor-factor VII/VIIa complexes that can trigger activation of the extrinsic coagulation cascade 4. Levels of active thrombin have been shown to be increased in the lungs of patients with pulmonary fibrosis associated with …","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"44 ","pages":"33s-35s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00001003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of signal transduction pathways involved in inflammation.","authors":"G Haegeman","doi":"10.1183/09031936.03.00000503a","DOIUrl":"https://doi.org/10.1183/09031936.03.00000503a","url":null,"abstract":"In order to target inflammatory processes effectively, it is necessary to understand, within an eukaryotic cell, how inflammatory reactions are generated and maintained. Therefore, this article will first concentrate on the signal transduction pathways and molecular mechanisms that drive inflammatory gene expression, followed by countering some of the published hypotheses that try to explain the inhibitory role of glucocorticoids. The current working model is included, which explains glucocorticoid action, and additionally points to an alternative or cooperative way of how to block inflammatory gene expression.\u0000\u0000Although inflammatory processes produce different diseases, depending on the inflamed tissue or organ involved, all of these afflictions have common aspects or common cellular processes, such as the activation of a stress signalling pathway and the concomitant production of inflammatory cytokines. In order to understand the inflammatory process at the “molecular” level and thus devise more specific molecular targets for the development of novel anti­inflammatory drugs, the author's group has studied signal transduction pathways and gene regulatory mechanisms that drive the expression of inflammatory genes. In particular, they studied the induction of interleukin (IL)‐6 and other related gene promoters in mouse fibroblasts, in response to inflammatory stimuli such as tumour necrosis factor (TNF), and found that the transcription factor nuclear factor (NF)‐κB is crucial for transcriptional induction of these genes. This factor is a heterodimeric complex, composed of two subunits, a p50 deoxyribonucleic acid (DNA)‐binding subunit and a p65 DNA‐binding and transcriptionally active subunit. In the resting state of the cell, the NF‐κB complex is stored and kept inactive in the cell by an inhibitory molecule, IκB. As a result of various inflammatory stimuli, this inhibitor becomes subject to complete targeted degradation, releasing the NF‐κB complex, allowing it to migrate to the nucleus and to bind onto NF‐κB‐ responsive sequences present in various cellular promoters. …","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"44 ","pages":"16s-19s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00000503a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation and respiratory disease. Proceedings of the 1st ERS Lung Science Conference. Taormina, Italy, March 28-30, 2003.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"44 ","pages":"39s-60s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of airway epithelial damage: epithelial-mesenchymal interactions in the pathogenesis of asthma.","authors":"S T Holgate,&nbsp;D E Davies,&nbsp;S Puddicombe,&nbsp;A Richter,&nbsp;P Lackie,&nbsp;J Lordan,&nbsp;P Howarth","doi":"10.1183/09031936.03.00000803","DOIUrl":"https://doi.org/10.1183/09031936.03.00000803","url":null,"abstract":"The aims of this article are to understand the shortfalls in thinking of asthma purely as an atopic disorder, to gain insight into the epithelial abnormalities of asthma and how these interface with the environment, and to view asthma as a disease of airway wall restructuring that engages activation of the epithelial mesenchymal trophic unit (EMTU). Furthermore, based on these developments, possible novel therapeutic targets for chronic asthma are identified.\u0000\u0000It has long been recognised that T‐helper cell (Th) type‐2 airway inflammation underpins airway dysfunction in asthma. Atopy is also a key feature of this disease but accounts for <40% of the population attributable risk. Based on a careful pathological and functional assessment of chronic asthma, the authors propose that altered epithelial-mesenchymal communication is also fundamental to disease pathogenesis. A number of factors contribute to a thickened hyperresponsive airway that provides an ideal microenvironment for the persistence of Th2‐mediated inflammation, including a more susceptible epithelium to injury, delayed epithelial repair, an altered trajectory of epithelial repair to a mucus-secreting phenotype, generation of growth factors that drive mesenchymal cell proliferation and differentiation towards increased matrix deposition and smooth muscle, and the production of neural and vascular growth factors. Cytokines and mediators derived from infiltrating inflammatory cells interact with this EMTU to augment and prolong responses. The “remodelling” changes of asthma have been observed in childhood asthma and may, indeed, precede the development of the disease. The recent recognition that atopy per se is not a key factor in the initiation of asthma (although it is important in aggravating the disease) suggests that gene-environmental interactions involving similar processes to those occurring in branching morphogenesis are critical for the full asthma phenotype to develop.\u0000\u0000A recent National Institutes for Health Workshop and a European Respiratory Society Task Force both concluded that more work …","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"44 ","pages":"24s-29s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00000803","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute lung injury: how the lung inflammatory response works.","authors":"P A Ward","doi":"10.1183/09031936.03.00000703a","DOIUrl":"https://doi.org/10.1183/09031936.03.00000703a","url":null,"abstract":"The purpose of this article is to provide an overview of the lung inflammatory response in rodents. Topics to be discussed will be initiation of the inflammatory response 1, inflammatory products that are responsible for tissue damage, and the intrinsic pathways that regulate (depress) the inflammatory response leading to its containment 2.\u0000\u0000Acute lung injury in rodents (mice, rats) can be induced by intrapulmonary deposition of immunoglobulin (Ig)G immune complexes, which trigger an intense inflammatory response characterised by the influx of polymorphonuclear neutrophils (PMN), interstitial and alveolar oedema, and intra­alveolar haemorrhage 3. This model of acute inflammation has been extensively evaluated in order to understand how the acute inflammatory response is triggered. This inflammatory response is dependent on generation of the powerful complement activation product C5a. Generation of C5a in lung can be accomplished by activation of any one of the three pathways of complement activation (classical, alternative and lectin pathways). An altogether different pathway for C5a generation in lung involves cleavage of C5, which is produced by lung cells, …","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"44 ","pages":"22s-23s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00000703a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}