Golan-Gerstl R.,Hebrew University of Jerusalem |
Wallach-Dayan S.B.,Hebrew University of Jerusalem |
Zisman P.,Hebrew University of Jerusalem |
Cardoso W.V.,Boston University |
And 3 more authors.
American Journal of Respiratory Cell and Molecular Biology | Year: 2012
A prominent feature of fibrotic tissue in general and of lungs in particular is fibroblast proliferation and accumulation. In patients overcoming fibrosis, apoptosis limits this excessive cell growth. We have previously shown resistance to Fas-induced apoptosis of primary lung fibroblasts from mice with bleomycin-induced lung fibrosis, their escape from immune surveillance, and continued accumulation in spite of overexpression of the Fas death receptor. Cellular FLICE-like inhibitory protein (c-FLIP) is a regulator of cell death receptor-induced apoptosis in many cell types. We aimed to determine c-FLIP levels in myofibroblasts from fibrotic lungs and to directly assess c-FLIP's role in apoptosis and proliferation of primary lung myofibroblasts. c-FLIP levels were determined by apoptosis gene array, flow cytometry, Western blot, and immunofluorescence before and after down-regulation with a specific small interfering RNA. Apoptosis was assessed by caspase cleavage in Western blot and by Annexin V affinity labeling after FACS and tissue immunofluorescence. Proliferation was assessed by BrdU uptake, also using FACS and immunofluorescence. We show that myofibroblasts from lungs of humans with idiopathic pulmonary fibrosis and from bleomycin-treated versus normal saline-treated mice up-regulate c-FLIP levels. Using the animal model, we show that fibrotic lung myofibroblasts divert Fas signaling from apoptosis to proliferation and that this requires signaling by TNF receptor-associated factor (TRAF) and NF-κB. c-FLIP down-regulation reverses the effect of Fas activation, causing increased apoptosis, decreased proliferation, and diminished recruitment of TRAF to the DISC complex. This indicates that c-FLIP is essential for myofibroblast accumulation andmay serve as a potential target to manipulate tissue fibrosis. Copyright © 2012 by the American Thoracic Society.
Tabaj G.C.,Pulmonary Medicine |
Fernandez C.F.,University of Chile |
Sabbagh E.,University of Chile
Respirology | Year: 2015
The 2013 American Thoracic Society/European Respiratory Society consensus classification update of the idiopathic interstitial pneumonias (IIP) included several important modifications to the organization and spectrum of the diseases that were proposed in an earlier multidisciplinary consensus document in 2002. The histopathology of the now 'major' and 'rare' IIP is presented here with exposition of the newly included entity of a distinctive upper lobe fibrotic lung disease referred to as idiopathic pleuroparenchymal fibroelastosis. The 'rare histological patterns' of acute fibrinous and organizing pneumonia and bronchiolocentric patterns of interstitial pneumonia are illustrated and discussed. For case report illustrating this review, see Respirology Case Reports http://dx.doi.org/10.1002/rcr2.108 © 2015 Asian Pacific Society of Respirology.
Gross A.,Pulmonary Medicine |
Diacon A.H.,University of Cape Town
Respiration | Year: 2011
Bronchoscopic transbronchial fine needle aspiration of the mediastinum is generally known as a safe procedure. Complications such as pneumothorax, pneumomediastinum, major bronchial haemorrhage and significant bleeding after a major vessel puncture are rare events. We report the first case, to our knowledge, of life-threatening cardiac tamponade following transbronchial fine needle aspiration in precarinal location. Copyright © 2011 S. Karger AG.
De Blasio F.,Clinic Center Private Hospital |
Polverino M.,Pulmonary Medicine
Therapeutic Advances in Respiratory Disease | Year: 2012
Chronic obstructive pulmonary disease (COPD) is a chronic condition that negatively affects several patient-centered outcomes. Among these, exercise capacity, dyspnea, and quality of life are the most relevant. In this article, factors contributing to exercise limitation, increase in exercise-induced dyspnea, quality of life deterioration, and other pathophysiological aspects in patients with COPD are analyzed in detail. Pulmonary rehabilitation (PR) is an evidence-based, multidisciplinary, and comprehensive intervention for patients with chronic respiratory diseases who are symptomatic and often have decreased daily life activities. PR has been clearly shown to induce favorable and long-lasting effects on all patient-centered outcomes. In addition, PR appears to have positive (even if not conclusively demonstrated) effects on other important outcomes in patients with COPD: number and severity of exacerbations, healthcare resource utilization, and survival. The organization of PR treatment, its components, outcome assessment, and future directions are discussed in light of the most robust scientific evidence. © The Author(s), 2012.
Bradshaw M.,Mayo Medical School |
Mansfield A.,Mayo Medical School |
Peikert T.,Pulmonary Medicine
Current Oncology Reports | Year: 2013
Malignant pleural effusions (MPEs) are a significant source of cancer-related morbidity. Over 150,000 patients in the United States suffer from breathlessness and diminished quality of life due to MPE each year. Current management strategies are of mostly palliative value and focus on symptom control; they do not address the pathobiology of the effusion, nor do they improve survival. Further elucidation of the pathophysiological mechanisms, coupled with the development of novel treatments such as intrapleural chemotherapeutics targeting this process, has the potential to greatly improve the efficacy of our current management options. Vascular endothelial growth factor-A (VEGF-A) has been implicated as a critical cytokine in the formation of malignant pleural effusions. Elevated levels of VEGF produced by tumor cells, mesothelial cells, and infiltrating immune cells result in increased vascular permeability, cancer cell transmigration, and angiogenesis. Therefore antiangiogenic therapies such as Bevacizumab, a monoclonal antibody targeting VEGF-A, may have a potential role in the management of malignant pleural effusions. Herein we review the pathogenesis and potential treatment strategies of malignant pleural effusions, with a focus on angiogenesis and antiangiogenic therapeutics. © 2013 Springer Science+Business Media New York.