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Lung Pathology (lung + pathology)
Selected AbstractsEffects of various anti-asthmatic agents on mite allergen-pulsed murine bone marrow-derived dendritic cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2005I. Machida Summary Background Dendritic cells (DCs) play an important role in the immune response and are critically involved in asthma. ,2 -agonists could potentially exacerbate type 2 T helper (Th2) cell-mediated immune response. Objectives To determine the effects of various anti-asthmatic agents on DCs function both in vitro and in vivo. Methods Murine bone marrow-derived DCs were pulsed with mite allergen in the presence of pranlukast, salbutamol, salmeterol or fluticasone. These DCs were then inoculated intranasally into naïve mice to induce allergic airway inflammation in vivo. Results Pranlukast reduced IL-10 and increased IL-12, while fluticasone reduced both IL-10 and IL-12 production by mite allergen-pulsed DCs. Allergic airway inflammation in pranlukast- and fluticasone-treated and mite allergen pulsed DCs-harbouring mice was attenuated and such response was associated with inhibition of Th2 response in the airway. Salbutamol did not alter cytokine production, while salmeterol reduced IL-12 production by mite allergen-pulsed DCs. Lung pathology in ,2 -agonist-harbouring mice was comparable with those of mite allergen-pulsed DCs-harbouring mice. Conclusions Our results indicate that leukotriene receptor antagonists and corticosteroids inhibit DCs-induced Th2 skewed immune response, and that short- and long-acting ,2 -agonists do not modify DCs-induced allergic airway inflammation. [source] The spectrum of pathological changes in severe acute respiratory syndrome (SARS)HISTOPATHOLOGY, Issue 2 2004O Y Cheung Aims:, To analyse the lung pathology of severe acute respiratory syndrome (SARS) and correlate the findings with the time sequence of the disease. Methods and results:, Ten patients with a clinical diagnosis of SARS, and virological confirmation of SARS coronavirus infection were identified. Histology in most cases showed diffuse alveolar damage, from early to late phases, and the changes corresponded to the time sequence. Other variable features include multinucleated giant cells, pneumocytes with cytomegaly and variable amounts of inflammatory cells and foamy macrophages. One case showed superimposed bronchopneumonia. No viral inclusions were found. Coronavirus particles were identified in pneumocytes by electron microscopy. Conclusions:, The predominant pathological process of SARS is diffuse alveolar damage and, in patients who die from the disease, there is evidence of organization and fibrosis. There are apparently no histological features specific for this disease, and the aetiological diagnosis depends on virological and ultrastructural studies. [source] Toll-like receptor and tumour necrosis factor dependent endotoxin-induced acute lung injuryINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2007Dieudonnée Togbe Summary Recent studies on endotoxin/lipopolysaccharide (LPS)-induced acute inflammatory response in the lung are reviewed. The acute airway inflammatory response to inhaled endotoxin is mediated through Toll-like receptor 4 (TLR4) and CD14 signalling as mice deficient for TLR4 or CD14 are unresponsive to endotoxin. Acute bronchoconstriction, tumour necrosis factor (TNF), interleukin (IL)-12 and keratinocyte-derived chemokine (KC) production, protein leak and neutrophil recruitment in the lung are abrogated in mice deficient for the adaptor molecules myeloid differentiation factor 88 (MyD88) and Toll/Interleukin-1 receptor (TIR)-domain-containing adaptor protein (TIRAP), but independent of TIR-domain-containing adaptor-inducing interferon-beta (TRIF). In particular, LPS-induced TNF is required for bronchoconstriction, but dispensable for inflammatory cell recruitment. Lipopolysaccharide induces activation of the p38 mitogen-activated protein kinase (MAPK). Inhibition of pulmonary MAPK activity abrogates LPS-induced TNF production, bronchoconstriction, neutrophil recruitment into the lungs and broncho-alveolar space. In conclusion, TLR4-mediated, bronchoconstriction and acute inflammatory lung pathology to inhaled endotoxin are dependent on TLR4/CD14/MD2 expression using the adapter proteins TIRAP and MyD88, while TRIF, IL-1R1 or IL-18R signalling pathways are dispensable. Further downstream in this axis of signalling, TNF blockade reduces only acute bronchoconstriction, while MAPK inhibition abrogates completely endotoxin-induced inflammation. [source] Effects of Ethanol on Cytokine Production After Surgery in a Murine Model of Gram-Negative PneumoniaALCOHOLISM, Issue 2 2008Claudia D. Spies Background:, Both alcohol abuse and surgery have been shown to impair immune function. The frequency of postoperative infectious complications is 2- to 5-fold increased in long-term alcoholic patients, leading to prolonged hospital stay. Following surgery, an increase in interleukin (IL)-6 has been shown to be associated with increased tissue injury and interleukin 1-(IL-10) is known to represent an anti-inflammatory signal. The purpose of this study was to test the hypothesis that several days of excess alcohol consumption results in more pronounced immunosuppression. We assume that alcoholic animals show increased levels of IL-10 in response to infection and increased IL-6 due to a more pronounced lung pathology. Methods:, Thirty-two female Balb/c mice were pretreated with ethanol (EtOH) at a dose of (3.8 mg/g body weight) or saline (NaCl) for 8 days. At day 8 of the experiment all mice underwent a median laparotomy. Two days postsurgery mice were either applicated 104 CFU Klebsiella pneumoniae or received sham-infection with saline. A total number of 4 groups (EtOH/K. pneumoniae; NaCl/K. pneumoniae; EtOH/Sham-infection, NaCl/Sham-infection) was investigated and a clinical score evaluated. Twenty-four hours later mice were killed; lung, spleen, and liver were excised for protein isolation and histological assessment. IL-6 and IL-10 levels were detected by ELISA. Results:, Alcohol-exposed mice exhibited a worsened clinical appearance. The histological assessment demonstrated a distinct deterioration of the pulmonary structure in alcohol-treated animals. In the lung, IL-6 and IL-10 was significantly increased in alcohol-exposed infected mice compared to saline-treated infected mice. The clinical score correlated significantly with IL-6 (r = 0.71; p < 0.01) and IL-10 levels (r = 0.64; p < 0.01) in the lung. Conclusions:, Ethanol treatment in this surgical model led to a more severe pulmonary infection with K. pneumoniae which was associated with more tissue destruction and increased levels of IL-6 and IL-10 and a worsened clinical score. [source] Exomphalos , a major or minor problem?PEDIATRIC ANESTHESIA, Issue 9 2002T. O'Neill Introduction The mortality and morbidity statistics associated with exomphalos major remain discouraging despite advances in management techniques (1). Congenital lung pathology, in particular pulmonary hypoplasia, and thoracic maldevelopment, have been strongly allied to this condition, accounting for the high incidence of pulmonary insufficiency necessitating prolonged ventilatory support in these infants (2). We discuss the respiratory issues in an infant with a particularly severe form of exomphalos major, and the impact of a comprehensive parental website devoted to the infants' management and progress. Case Report A female infant, born at 38 weeks' gestation, was referred for management of exomphalos major. Due to the extensive nature of the abdominal wall defect, primary surgical closure was impossible and initial management consisted of staged reduction by external compression of the exomphalos. This resulted in escalating cardiovascular and respiratory embarrassment, and was abandoned in favour of conservative treatment, whereby the sac was dressed and allowed to epithelialise. Thereafter the clinical course was characterised by chronic pulmonary insufficiency requiring prolonged ventilatory support. Ventilator dependence did not significantly decrease until lung growth occurred and the sitting position was adopted, enabling weaning from conventional ventilation to genuine BIPAP at 6 months. Currently, after 11 months, we are preparing her for entry into a home ventilation programme. Throughout this period, progress and realistic goals were discussed at multidisciplinary case conferences involving the parents. The interpreted medical management has subsequently been displayed by the parents on an elaborate, up-to-date website, which is part of a larger ,Mother Of Omphalocele' network. Although innovative, this highlights the fact that we the medical profession, should be vigilant with regard to potential public exposure of patient management. Whilst the Internet has become an integral part of our own continuing education, this case highlights a new aspect of how it may be used by our patients and their relatives to compare and contrast management policies in various institutions. [source] Familial neuroendocrine cell hyperplasia of infancy,,PEDIATRIC PULMONOLOGY, Issue 8 2010J. Popler MD Abstract Background Neuroendocrine cell hyperplasia of infancy (NEHI) is a recently described children's interstitial lung disease (chILD) disorder of unknown etiology. It manifests clinically with tachypnea, retractions, hypoxemia, and crackles. The characteristic radiographic appearance consists of pulmonary hyperexpansion and ground-glass densities on high-resolution computed tomography (HRCT). Lung histology shows hyperplasia of bombesin-immunopositive neuroendocrine cells within distal bronchioles and alveolar ducts without other identifiable lung pathology or developmental anomaly. Methods We describe four families with multiple siblings diagnosed with NEHI. Cases were identified at three pediatric centers. Inclusion criteria included clinical findings consistent with NEHI, lung biopsy confirmation in the index case, and a diagnostic HRCT or biopsy in other siblings. Results Each family had a proband diagnosed with NEHI based upon pathologic review, and at least one additional sibling diagnosed either by pathologic review or HRCT. All patients presented between 2 and 15 months of age. Both male and female children were affected. The majority of the patients underwent both HRCT and lung biopsy. There were no deaths among affected children. No environmental exposures or other potential etiologies were identified as a cause of presenting symptoms. Conclusions The familial occurrence of NEHI suggests the possibility of a genetic etiology for this disorder and highlights the importance of taking a complete family medical history for infants presenting with a suggestive clinical picture. Identification of familial NEHI patients allows for the opportunity to further our understanding of this disorder, its natural history, the phenotypic spectrum, and potential genetic causes. Pediatr. Pulmonol. 2010; 45:749,755. © 2010 Wiley-Liss, Inc. [source] Obliterative bronchiolitis in lung allografts removed at retransplant for intractable airway problemsRESPIROLOGY, Issue 4 2009Olufemi AKINDIPE ABSTRACT Background and objective: The role of large airway ischaemia, with resultant airway narrowing, in the development of post-lung transplant bronchiolitis obliterans has not been defined. A determination of clinical bronchiolitis obliterans syndrome (BOS), which is defined as a decline in FEV1 from a stable post-transplant baseline, is difficult in the setting of airway complications. The aim of this study was to assess the evidence for histological bronchiolitis obliterans in lung allografts removed during retransplantation for severe recurrent airway narrowing. Methods: Case records and histological findings in allograft lungs removed at retransplantation were retrospectively reviewed. Results: Five lung transplant recipients, who had undergone retransplantation because of severe recalcitrant airway stenosis, were identified. In each case, explant allograft lung pathology revealed evidence of bronchiolitis obliterans. Conclusions: There is a possible link between airway ischaemia, large airway stenosis and the development of bronchiolitis obliterans, which is the most common cause of death in lung transplant recipients after the first year. These findings may provide an impetus for evaluation of the role of bronchial artery revascularization techniques in the prevention of bronchiolitis obliterans. [source] Poster Session , Heart and lung pathologyAPMIS, Issue 2010Article first published online: 20 MAR 2010 No abstract is available for this article. [source] Cellular and molecular mechanisms in chronic obstructive pulmonary disease: an overviewCLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2004A. Di Stefano Summary In the last decade, the analysis of bronchial biopsies and lung parenchyma obtained from chronic obstructive pulmonary disease (COPD) patients compared with those from smokers with normal lung function and non-smokers has provided new insights on the role of the different inflammatory and structural cells, their signalling pathways and mediators, contributing to a better knowledge of the pathogenesis of COPD. This review summarizes and discusses the lung pathology of COPD patients with emphasis on inflammatory cell phenotypes that predominate in different clinical conditions. In bronchial biopsies, a cascade of events takes place during progression from mild-to-severe disease. T lymphocytes, particularly CD8+ cells and macrophages are the prevalent inflammatory cells in the lung of healthy smokers and patients with mild COPD, while total and activated neutrophils predominate in severe COPD. The number of CD4+, CD8+ cells and macrophages expressing nuclear factor-kappa B (NF-,B), STAT-4 and IFN-, proteins as well as endothelial adhesion molecule-1 in endothelium is increased in mild/moderate disease. In contrast, activated neutrophils (MPO+ cells) and increased nitrotyrosine immunoreactivity develops in severe COPD. In bronchial biopsies obtained during COPD exacerbations, some studies have shown an increased T cell and granulocyte infiltration. Regular treatment with high doses of inhaled glucocorticoids does not significantly change the number of inflammatory cells in bronchial biopsies from patients with moderate COPD. The profile in lung parenchyma is similar to bronchial biopsies. ,Healthy' smokers and mild/moderate diseased patients show increased T lymphocyte infiltration in the peripheral airways. Pulmonary emphysema is associated with a general increase of inflammatory cells in the alveolar septa. The molecular mechanisms driving the lymphocyte and neutrophilic prevalence in mild and severe disease, respectively, needs to be extensively studied. Up-regulation of pro-inflammatory transcription factors NF-,B and STAT-4 in mild, activated epithelial and endothelial cells in the more severe disease may contribute to this differential prevalence of infiltrating cells. [source] | ||||||||||||||||||||||