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Fatal Asthma (fatal + asthma)
Selected AbstractsRhinovirus is not detectable in peripheral lung tissue after asthma deathRESPIROLOGY, Issue 2 2003Mark W. WATSON Objective: Viral infections are associated with both mild and severe exacerbations of asthma and may therefore be associated with asthma death. As such we hypothesized that it might be possible to detect rhinovirus (RV), the virus most frequently implicated in acute asthma, in lung tissue from patients who died from asthma. Methodology: We studied archival, wax-embedded lung tissue obtained postmortem from: (i) patients who died from asthma (n = 12), (ii) asthma patients with non-asthma-related death (n = 3), and (iii) non-asthmatic individuals who died from unrelated causes (n = 3). A validated reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect RV. To confirm RNA preservation, RT-PCR was used to detect expression of the constitutive gene adenine-phosphoribosyl-transferase (APRT). Sensitivity of the assay was assessed using wax-embedded RV-infected cells. Results: Sensitivity of RT-PCR for RV in wax-embedded sections was similar to previous studies (approximately 100 viral copies). Specimens used for study were predominantly of alveolar and small airway origin (< 2 mm). All tissues examined were negative for the presence of RV mRNA and positive for APRT mRNA. Conclusions: RV infection of the lower airway may be an uncommon cause of fatal asthma. Alternatively, RV may not extend to peripheral airways and more proximal tissue sampling or PCR assays for other viruses may be required to determine an association between viral respiratory tract infection and fatal asthma. [source] Airway proteoglycans are differentially altered in fatal asthmaTHE JOURNAL OF PATHOLOGY, Issue 1 2005Marcus de Medeiros Matsushita Abstract It has been suggested that airway remodelling is responsible for the persistent airway obstruction and decline in lung function observed in some asthmatic patients. The small airways are thought to contribute significantly to this functional impairment. Proteoglycans (PGs) are important components of the extracellular matrix (ECM) in the lungs. Besides controlling biophysical properties of the ECM, they play important roles in the regulation of some cytokines. Increased subepithelial PG deposition in the airways of mild asthmatics has been reported. However, there are no data on the PG content in small airways in asthma. This study has compared the content and distribution of PGs in large and small airways of patients who died of asthma with those in control lungs. Immunohistochemistry and image analysis were used to determine the content of lumican, decorin, biglycan, and versican in large (internal perimeter >6 mm) and small (internal perimeter ,6 mm) airways of 18 patients who had died of asthma (A) and ten controls (C). The results were expressed as PG area (µm2)/epithelial basement membrane length (µm). The main differences between asthmatics and controls were observed in the small airways. There was a significant decrease in decorin and lumican contents in the external area of small airways in asthmatics (decorin: A = 1.05 ± 0.27 µm, C = 3.97 ± 1.17 µm, p = 0.042; lumican: A = 1.97 ± 0.37 µm, C = 5.66 ± 0.99 µm, p = 0.002). A significant increase in versican content in the internal area of small and large airways in asthmatics was also observed (small: A = 7.48 ± 0.84 µm, C = 5.16 ± 0.61 µm, p = 0.045; large: A = 18.38 ± 1.94 µm, C = 11.90 ± 2.86 µm, p = 0.028). The results show that PGs are differentially expressed in the airways of fatal asthma and may contribute to airway remodelling. These data reinforce the importance of the small airways in airway remodelling in asthma. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] T cells and eosinophils in bronchial smooth muscle cell death in asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2009K. Solarewicz-Madejek Summary Background Bronchial smooth muscle cells (SMC) proliferate, express adhesion molecules, secrete cytokines and thus efficiently contribute to the pathogenesis of asthma. Objective The aim of the study was to investigate whether, and by which mechanism, T cells and eosinophils can cause death of airway SMC. Methods The T cell- and eosinophil-induced cell death was analysed in primary human bronchial SMC cultures as well as in bronchial biopsy specimens from non-asthmatic and asthmatic individuals. Results Bronchial SMC death showed characteristic morphological features of apoptosis in 3,6 days cultures with inflammatory cytokines (IFN-,, TNF-,), soluble death ligands [sFasL, TNF-related apoptosis-inducing ligand (TRAIL)] and activated T-helper type 1 (Th1) and Th2 cell supernatants. The recombinant eosinophil cationic protein induced SMC necrosis within 1 h. Resting SMC expressed the death receptors TNFR1, TNFR2, Fas, TRAILR1, TRAILR2 and membrane FasL as a death-inducing ligand. IFN-, and TNF-, up-regulated TNFR1, TNFR2, Fas and membrane FasL on SMC. TNF-, up-regulated TRAILR1 and TRAILR2; sFasL up-regulated TNFR2. The intracellular caspase-3 activation in SMC was significantly increased by IFN-,, sFasL, TRAIL, Th1 and Th2 cell supernatants. Increased expression of TRAIL in asthmatics, but not in non-asthmatic individuals was demonstrated in situ. The apoptosis receptors TRAILR1 and TRAILR2 were expressed in SMC and epithelial cells both in healthy and asthmatic biopsies. Prominent apoptosis of SMC was observed in fatal asthma, but not intermittent asthma biopses. Conclusion The demonstration of bronchial SMC death both by apoptosis and necrosis indicates the essential role of T cells and eosinophils in the bronchial tissue injury particularly in the severe asthma. [source] Inflammatory cell mapping of the respiratory tract in fatal asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2005S. De Magalhães Simões Summary Background The site and distribution of inflammation in the airways of asthmatic patients has been largely investigated. Inflammatory cells are distributed in both large and small airways in asthma. It has been demonstrated that distal lung inflammation in asthma may significantly contribute to the pathophysiology of the disease. The upper airways have also been implicated in the overall asthmatic inflammation. Although it is now accepted that lung inflammation is not restricted to the intrapulmonary airways in asthma, little is known about cell distribution in the other lung compartments and their relation to the intrapulmonary airways. Objective We aimed to map the inflammatory process in fatal asthma (FA), from the upper airways to the lung parenchyma. Methods Eosinophil, neutrophil, mast cell and lymphocyte content were determined in nasal mucosa, the trachea, intrapulmonary airways and parenchyma (peribronchiolar and distal) of 20 patients with FA and 10 controls. Results Eosinophil content was higher in all studied areas in FA compared with controls (P<0.02). Mast cell content was higher in the outer area of larger airways, small membranous bronchioles and in peribronchiolar parenchyma of FA compared with controls (P<0.04). CD3+, CD4+and CD20+cells showed increased content in FA intrapulmonary airways compared with controls (P<0.05). There was a positive correlation between CD4+cell content in nasal mucosa and larger airways in asthmatics. Increased neutrophil content was observed only in peribronchiolar parenchyma of FA (P=0.028). Conclusion Eosinophils present a widespread distribution within the respiratory tract in FA, from the nasal mucosa to the distal lung. The outer wall of small membranous bronchioles is the main site of inflammatory changes in FA. There is a localized distribution of alveolar inflammation at the peribronchiolar region for mast cells and neutrophils. Our findings provide further evidence of the importance of the lung periphery in the pathophysiology of FA. [source] | ||||||||||