The European respiratory journal. Supplement最新文献

{"title":"How T-lymphocytes are activated and become activators by cell-cell interaction.","authors":"J M Dayer","doi":"10.1183/09031936.03.00000403b","DOIUrl":"https://doi.org/10.1183/09031936.03.00000403b","url":null,"abstract":"Immunological descriptions support the role of direct contact between T-lymphocytes and monocytes at the site of inflammatory lesions. The following will therefore focus on the role of direct contact between stimulated T-lymphocytes and monocytes in the production of cytokines and cytokine inhibitors, as well as matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP) by monocytes. The role of T-lymphocytes and polymorphonuclear neutrophils (PMN), endothelial cells and fibroblast-like cells will also be discussed. Blocking the interaction between T-lymphocytes and monocytes may provide a useful approach to therapeutic intervention.","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"44 ","pages":"10s-15s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00000403b","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048043","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":"Proteolysis in the lung.","authors":"S D Shapiro","doi":"10.1183/09031936.03.00000903a","DOIUrl":"https://doi.org/10.1183/09031936.03.00000903a","url":null,"abstract":"Pulmonary emphysema is a major component of the morbidity and mortality of chronic obstructive pulmonary disease (COPD), a condition that has become the fourth leading cause of death in the USA, and is becoming epidemic worldwide. Emphysema is defined as enlargement of peripheral airspaces of the lung including respiratory bronchioles, alveolar ducts and alveoli, accompanied by destruction of the walls of these structures. The pathogenesis of emphysema can be dissected into three interrelated events: 1) chronic exposure to cigarette smoke may lead to inflammatory cell recruitment within the terminal airspaces of the lung; 2) these inflammatory cells release elastolytic proteinases that damage the extracellular matrix of the lung; and 3) ineffective repair of elastin and perhaps other extracellular matrix components result in pulmonary emphysema.\u0000\u0000Inherited deficiency of α1‐antitrypsin (α1‐AT), the primary inhibitor of neutrophil elastase (NE), predisposes individuals to early onset emphysema, and intrapulmonary instillation of elastolytic enzymes in experimental animals causes emphysema. Together, these findings led to the elastase/antielastase hypothesis for the pathogenesis of emphysema, which was proposed ∼40 yrs ago and remains the prevailing concept today. While the capacity of NE to initiate emphysema in patients deficient in α1‐AT is clear, the proteinases involved in the pathogenesis of the common form of emphysema associated with cigarette smoking is more complicated. In addition to NE, neutrophil primary granules contain other elastolytic serine proteinases including, cathepsin G and proteinase 3, and secondary granules possess matrix metalloproteinases; MMP‐8, a collagenase and MMP‐9, a 92 kDa gelatinase. While, macrophages are prominent inflammatory cells in smokers' lungs, the capacity of macrophages to degrade elastin was controversial until cysteine proteinases including cathepsins S and L were identified (K the most potent elastase has not been identified in lung macrophages). The author's group identified several MMPs produced by alveolar and interstitial …","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"44 ","pages":"30s-32s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00000903a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048502","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":"Epithelial apoptosis in the initiation of lung fibrosis.","authors":"B D Uhal","doi":"10.1183/09031936.03.00000303","DOIUrl":"https://doi.org/10.1183/09031936.03.00000303","url":null,"abstract":"This work was supported by PHS HL‐45136, by the American Heart Association and by the MSU Foundation.\u0000\u0000Apoptosis in the lung is a relatively new area of research that is receiving increasing attention. A growing body of evidence indicates that apoptosis is controlled in a tissue- and cell type-specific manner; for this reason, the regulation of apoptosis in specific cell types of the lung is currently an area of intensive research 1. This article provides evidence supporting the viewpoint that apoptosis of alveolar epithelial cells is a key event in the initiation of fibrotic lesions, and will discuss a working hypothesis to explain possible mechanisms by which epithelial apoptosis can lead to lung fibrogenesis.\u0000\u0000Recent evidence implicates important roles for apoptosis in animal models of lung injury/repair or remodelling and in lung biopsies from patients with a variety of lung disorders. For example, apoptosis plays a critical role in postnatal lung development 2 and in the normal resolution of lung inflammation by the regulated removal of unneeded cells such as granulocytes, without the release of damaging histotoxins 3. Dexamethasone has been known for many years to induce apoptosis in some leukocyte subsets, and apoptosis is an important mechanism underlying the anti-inflammatory action of this and other glucocorticoids 4. Considerable literature now supports a role for apoptosis in the remodelling of lung tissue after acute lung injury, both for the clearance of excess epithelial stem cells after hyperplastic repair 5 and for the normal removal of excess mesenchymal cells from resolving lesions 6. Extensive apoptosis is found in the lungs of patients with idiopathic pulmonary fibrosis (IPF) 7, 8 and in animals of this disease 9, 10. Recent evidence also suggests a role for apoptosis in the tissue remodelling …","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"44 ","pages":"7s-9s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00000303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048042","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":"The pharmacoepidemiology of COPD: recent advances and methodological discussion.","authors":"P Burney, S Suissa, J B Soriano, W M Vollmer, G Viegi, S D Sullivan, L M Fabbri, D D Sin, P Ernst, D Coultas, J Bourbeau, D W Mapel, K Weiss, T McLaughlin, D Price, M C J M Sturkenboom, R Taylor, G W Hagan","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"43 ","pages":"1s-44s"},"PeriodicalIF":0.0,"publicationDate":"2003-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24048506","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":"Diagnosis and treatment of nosocomial pneumonia in ALI/ARDS patients.","authors":"J Y Fagon,&nbsp;J Chastre","doi":"10.1183/09031936.03.00421203","DOIUrl":"https://doi.org/10.1183/09031936.03.00421203","url":null,"abstract":"<p><p>Ventilator-associated pneumonia (VAP) is a common complication of the acute respiratory distress syndrome (ARDS) or acute lung injury (ALI), often leading to the development of sepsis, multiple organ failure, and death. However, the diagnosis of pulmonary infection in patients with ARDS/ALI is often difficult: the systemic signs of infection, such as fever, tachycardia, leukocytosis are nonspecific findings in such patients; a variety of causes other than pneumonia can explain asymmetric consolidation in patients with ARDS and marked asymmetry of radiographic abnormalities has also been reported in patients with uncomplicated ARDS. In 2003, physicians in charge of these patients have to identify patients with true bacterial lung infection, to select appropriate initial antibiotic therapy, to adjust therapy as soon as possible, and to withhold antibiotics in patients without VAP. To do that, a bacteriological strategy based on the use of quantitative cultures of specimen obtained with fibreoptic bronchoscopy performed before initiation or modification of antibiotic treatment seems better than a strategy based on clinical evaluation alone, lowering antibiotic consumption and improving outcome. When bronchoscopy is not available or contraindicated, a nonbronchoscopic strategy or a clinical strategy with reevaluation 3 days after initiation of treatment may be used. Antimicrobial treatment of VAP is a complex issue. Some general principles can be helpful for the selection of initial treatment: knowledge of most frequently identified responsible pathogens and their susceptibility patterns in the unit; prior duration of hospitalisation; previously prescribed antibiotics; information obtained by direct examination of pulmonary secretions; antibacterial activity and pharmacodynamic characteristics of antibiotics that could be used to treat this infection. Appropriateness of initial antimicrobial therapy is probably a major prognostic factor for patients with ventilator-associated pneumonia. Thus, before new antiboitics are administered, reliable pulmonary specimens must be obtained for direct examination and cultures.</p>","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"42 ","pages":"77s-83s"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00421203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22552413","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":"What has been learnt from P/V curves in patients with acute lung injury/acute respiratory distress syndrome.","authors":"S M Maggiore,&nbsp;J C Richard,&nbsp;L Brochard","doi":"10.1183/09031936.03.00004204","DOIUrl":"https://doi.org/10.1183/09031936.03.00004204","url":null,"abstract":"<p><p>Mechanical impairment of the respiratory system was recognised soon after the description of acute respiratory distress syndrome. The analysis of the pressure/volume (P/V) curve of the respiratory system contributed a lot to the understanding of the pathophysiology of acute lung injury and formed the basis for lung protection. The lower and upper inflection points were regarded as points of interest to avoid cyclic derecruitment and overdistension and to optimise ventilatory settings. However, because of the heterogeneity of lung injury, reducing the mechanical properties of the whole respiratory system to a single curve is a schematic approach, which makes interpretation difficult. New data suggest that alveolar re-inflation occurs along the whole P/V curve that can, therefore, be considered as a recruitment curve. The lower inflection point has no relationship with alveolar opening and closure and does not indicate the positive end-expiratory pressure needed to prevent alveolar collapse. The shape of the P/V curve gives information about the extension and the homogeneity of lung injury, indicating the possibility of lung recruitment. The upper inflection point, classically seen as the beginning of overdistension, may also indicate the end of recruitment. The pressure/volume curve offers the unique opportunity of evaluating alveolar recruitment/derecruitment at the bedside that can be helpful for the identification of optimal ventilatory settings and makes the curve a valuable tool for the ventilatory management of acute lung injury.</p>","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"42 ","pages":"22s-26s"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00004204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22553023","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":"Ventilator-induced lung injury.","authors":"J D Ricard,&nbsp;D Dreyfuss,&nbsp;G Saumon","doi":"10.1183/09031936.03.00420103","DOIUrl":"https://doi.org/10.1183/09031936.03.00420103","url":null,"abstract":"<p><p>During mechanical ventilation, high end-inspiratory lung volume (whether it be because of large tidal volume (VT) and/or high levels of positive end-expiratory pressure) results in a permeability type pulmonary oedema, called ventilator-induced lung injury (VILI). Previous injury sensitises lung to mechanical ventilation. This experimental concept has recently received a resounding clinical illustration after a 22% reduction of mortality was observed in acute respiratory distress syndrome patients whose VT had been reduced. In addition, it has been suggested that repetitive opening and closing of distal units at low lung volume could induce lung injury but this notion has been challenged both conceptually and clinically after the negative results of the Acute Respiratory Distress Syndrome clinical Network Assessment of Low tidal Volume and Elevated end-expiratory volume to Obviate Lung Injury (ARDSNet ALVEOLI) study. Experimentally and clinically, involvement of inflammatory cytokines in VILI has not been unequivocally demonstrated. Cellular response to mechanical stretch has been increasingly investigated, both on the epithelial and the endothelial side. Lipid membrane trafficking has been thought to be a means by which cells respond to stress failure. Alterations in the respiratory system pressure/volume curve during ventilator-induced lung injury that include decrease in compliance and position of the upper inflection point are due to distal obstruction of airways that reduce aerated lung volume. Information from this curve could help avoid potentially harmful excessive tidal volume reduction.</p>","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"42 ","pages":"2s-9s"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00420103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22552500","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":"New advances in the use of noninvasive ventilation for acute hypoxaemic respiratory failure.","authors":"M Antonelli,&nbsp;M A Pennisi,&nbsp;G Conti","doi":"10.1183/09031936.03.00421003","DOIUrl":"https://doi.org/10.1183/09031936.03.00421003","url":null,"abstract":"<p><p>Noninvasive ventilation (NIV) includes various techniques for augmenting alveolar ventilation without an endotracheal airway. The theoretical advantages of this approach include avoiding the complications associated with endotracheal intubation, improving patient comfort, preserving airway defence mechanisms, speech and swallowing. The successful application of NIV in hypoxaemic acute respiratory failure (ARF) of varied etiologies has been extensively described but success rate is strictly dependent on ARF etiology and until today the application of NIV strategies in the setting of hypoxaemic ARF is controversial. Larger, controlled studies are required to clarify the role of NIV in the setting of hypoxaemic ARF. The correct choice of the patient ventilator interface is a crucial issue in noninvasive ventilation. The study of new interfaces could improve tolerability reducing the noninvasive ventilation failure rate.</p>","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"42 ","pages":"65s-71s"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00421003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22552411","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":"Evidence of biological efficacy for prolonged glucocorticoid treatment in patients with unresolving ARDS.","authors":"G U Meduri,&nbsp;P Carratu,&nbsp;A X Freire","doi":"10.1183/09031936.03.00420903","DOIUrl":"https://doi.org/10.1183/09031936.03.00420903","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is a disease of multifactorial etiology characterised by rapid development of severe diffuse and nonhomogenous inflammation of the pulmonary lobules causing life-threatening hypoxaemic respiratory failure. The current authors tested a therapeutic intervention on a previously defined pathophysiological model of ARDS. The model was defined by investigating, during the natural history of ARDS, the relationship among the three fundamental elements of a disease process pathogenesis, structural alterations, and functional consequences. In these studies, the present authors provided biological and morphological evidence indicating that ARDS patients failing to improve after 1 week of mechanical ventilation (unresolving ARDS) have intense and protracted (dysregulated) pulmonary and systemic inflammatory and neo-fibrogenetic activity. Nuclear factor-kappaB and the glucocorticoid receptor have diametrically opposed functions in regulating inflammation. This chapter will review recent data indicating that poor outcome in acute respiratory distress syndrome might be related in part to failure of the activated glucocorticoid receptors to downregulate the transcription of inflammatory cytokines despite elevated levels of circulating cortisol. In a small randomised study of patients with unresolving acute respiratory distress syndrome, the current authors have shown that prolonged glucocorticoid supplementation improved all aspects of glucocorticoid receptors function and enhanced glucocorticoid-mediated anti-inflammatory action by interfering with nuclear factor-kappaB activation.</p>","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"42 ","pages":"57s-64s"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00420903","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22553028","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":"The issue of dynamic hyperinflation in acute respiratory distress syndrome patients.","authors":"A Vieillard-Baron,&nbsp;F Jardin","doi":"10.1183/09031936.03.00420703","DOIUrl":"https://doi.org/10.1183/09031936.03.00420703","url":null,"abstract":"<p><p>Dynamic hyperinflation is produced by a diffuse expiratory flow limitation impairing exhalation under mechanical ventilation. It constitutes a serious clinical problem in patients exhibiting bronchial asthma or chronic obstructive pulmonary disease, when mechanical ventilation is required. But this phenomenon may also complicate respiratory support in acute respiratory distress syndrome (ARDS) patients. The presence of diffuse airflow limitation in ARDS patients has sometimes been noticed in the past, but its consequences have only recently been emphasised in a dynamic study, using bedside recording of flow/volume loops during respiratory support. More recently, by recording systematically a prolonged expiration, the current authors have observed a localised airflow limitation in a majority of ARDS patients, constituting another potential factor of dynamic hyperinflation under respiratory support. In the same report, the current authors' have emphasised the impact of this limitation on the shape of the pressure/volume loop. At a time when increasing respiratory support is proposed to improve carbon dioxide clearance in acute respiratory distress syndrome submitted to protective ventilation, dynamic hyperinflation may become a major clinical problem in this setting.</p>","PeriodicalId":77419,"journal":{"name":"The European respiratory journal. Supplement","volume":"42 ","pages":"43s-47s"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1183/09031936.03.00420703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22553026","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}