lung dysfunction Dotaz Zobrazit nápovědu
Transplantace plic je v současnosti celosvětově uznávaným a etablovaným terapeutickým postupem u vybraných chronických plicních onemocnění v terminálním stadiu respiračního selhání. Na dlouhodobé přežívání pacientů po transplantaci plic má vliv mnoho faktorů, přičemž jedním z nejzásadnějších je rozvoj chronické dysfunkce plicního štěpu (chronic lung allograft dysfunction, CLAD). Předkládaný text shrnuje současné poznatky o histopatologickém obrazu CLAD a jeho klinické charakteristice. Dále popisuje retransplantaci plic jako jedinou možnost kauzální terapie, její možné komplikace a výsledky u standardních i urgentních pacientů čekajících na vhodný orgán s podporou extrakorporální membránové oxygenace. Významnou chirurgickou modalitou potenciálně vedoucí ke zlepšení stavu pacientů je fundoplikace. Indikace a výsledky tohoto chirurgického postupu jsou rozebrány v samostatné kapitole. Dále jsou nastíněny některé nechirurgické možnosti léčby, jejichž cílem je zpomalení progrese CLAD a probíhající výzkum zaměřený na prodloužení života těchto pacientů.
Lung transplantation has become a standardized and widely accepted treatment modality for selected end-stage lung diseases. Many factors influ- ence the long-term survival of patients after lung transplantation. One of the most important is clearly the development of chronic lung allograft dysfunction (CLAD). This review summarizes current knowledge of the histopathology of CLAD and its clinical characteristics. It also describes lung re-transplantation as the only causal therapy, its possible complications, and outcomes in standard and high-urgency patients awaiting a suitable organ with extracorporeal membrane oxygenation support. Fundoplication is an important surgical modality potentially leading to an improvement of the patients’ condition. The indications and outcomes of this surgical procedure are discussed in a separate chapter. In addition, several nonsurgical treatment options aimed at slowing the progression of CLAD are outlined, as well as ongoing research focused on extending the life of these patients.
American journal of respiratory and critical care medicine, ISSN 1073-449X vol. 159, no. 4, part 2, April 1999
S40 s. : il. ; 30 cm
BACKGROUND: Many lung transplants fail due to chronic lung allograft dysfunction (CLAD). We recently showed that transbronchial biopsies (TBBs) from CLAD patients manifest severe parenchymal injury and dedifferentiation, distinct from time-dependent changes. The present study explored time-selective and CLAD-selective transcripts in mucosal biopsies from the third bronchial bifurcation (3BMBs), compared to those in TBBs. METHODS: We used genome-wide microarray measurements in 324 3BMBs to identify CLAD-selective changes as well as time-dependent changes and develop a CLAD classifier. CLAD-selective transcripts were identified with linear models for microarray data (limma) and were used to build an ensemble of 12 classifiers to predict CLAD. Hazard models and random forests were then used to predict the risk of graft loss using the CLAD classifier, transcript sets associated with rejection, injury, and time. RESULTS: T cell-mediated rejection and donor-specific antibody were increased in CLAD 3BMBs but most had no rejection. Like TBBs, 3BMBs showed a time-dependent increase in transcripts expressed in inflammatory cells that was not associated with CLAD or survival. Also like TBBs, the CLAD-selective transcripts in 3BMBs reflected severe parenchymal injury and dedifferentiation, not inflammation or rejection. While 3BMBs and TBBs did not overlap in their top 20 CLAD-selective transcripts, many CLAD-selective transcripts were significantly increased in both for example LOXL1, an enzyme controlling matrix remodeling. In Cox models for one-year survival, the 3BMB CLAD-selective transcripts and CLAD classifier predicted graft loss and correlated with CLAD stage. Many 3BMB CLAD-selective transcripts were also increased by injury in kidney transplants and correlated with decreased kidney survival, including LOXL1. CONCLUSIONS: Mucosal and transbronchial biopsies from CLAD patients reveal a diffuse molecular injury and dedifferentiation state that impacts prognosis and correlates with the physiologic disturbances. CLAD state in lung transplants shares features with failing kidney transplants, indicating elements shared by the injury responses of distressed organs.
- MeSH
- alografty MeSH
- lidé MeSH
- plíce MeSH
- rejekce štěpu * genetika MeSH
- retrospektivní studie MeSH
- sliznice MeSH
- transplantace plic * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Transplanted lungs suffer worse outcomes than other organ transplants with many developing chronic lung allograft dysfunction (CLAD), diagnosed by physiologic changes. Histology of transbronchial biopsies (TBB) yields little insight, and the molecular basis of CLAD is not defined. We hypothesized that gene expression in TBBs would reveal the nature of CLAD and distinguish CLAD from changes due simply to time posttransplant. Whole-genome mRNA profiling was performed with microarrays in 498 prospectively collected TBBs from the INTERLUNG study, 90 diagnosed as CLAD. Time was associated with increased expression of inflammation genes, for example, CD1E and immunoglobulins. After correcting for time, CLAD manifested not as inflammation but as parenchymal response-to-wounding, with increased expression of genes such as HIF1A, SERPINE2, and IGF1 that are increased in many injury and disease states and cancers, associated with development, angiogenesis, and epithelial response-to-wounding in pathway analysis. Fibrillar collagen genes were increased in CLAD, indicating matrix changes, and normal transcripts were decreased-dedifferentiation. Gene-based classifiers predicted CLAD with AUC 0.70 (no time-correction) and 0.87 (time-corrected). CLAD related gene sets and classifiers were strongly prognostic for graft failure and correlated with CLAD stage. Thus, in TBBs, molecular changes indicate that CLAD primarily reflects severe parenchymal injury-induced changes and dedifferentiation.
Waterpipe tobacco smoking (WPS) inhalation has been shown to trigger endothelial dysfunction and atherosclerosis. However, the mechanisms underlying these effects are still unknown. Here, we assessed the impact and underlying mechanism of WPS exposure for one month on endothelial dysfunction using aortic tissue of mice. The duration of the session was 30 min/day and 5 days/week. Control mice were exposed to air. Inhalation of WPS induced an increase in the number of macrophages and neutrophils and the concentrations of protein, tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1beta, and glutathione in bronchoalveolar lavage fluid. Moreover, the concentrations of proinflammatory cytokines (TNF alpha, IL-6 and IL-1beta), adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin and P-selectin) and markers of oxidative stress (lipid peroxidation, glutathione, superoxide dismutase and nitric oxide) in aortic homogenates of mice exposed to WPS were significantly augmented compared with air exposed mice. Likewise, the concentration of galectin-3 was significantly increased in the aortic homogenates of mice exposed to WPS compared with control group. WPS inhalation induced vascular DNA damage assessed by comet assay and apoptosis characterized by a significant increase in cleaved caspase-3. While the aortic expression of phosphorylated nuclear factor kappaB (NF-kappaB) was significantly increased following WPS inhalation, the concentration of sirtuin 1 (SIRT1) was significantly decreased in WPS group compared with air-exposed group. In conclusion, our study provided evidence that WPS inhalation triggers lung injury and endothelial inflammation, oxidative stress and apoptosis which were associated with nuclear factor-kappaB activation and SIRT1 down-regulation.
- MeSH
- glutathion metabolismus MeSH
- kouření vodní dýmky * škodlivé účinky MeSH
- myši MeSH
- nemoci cév * MeSH
- NF-kappa B metabolismus MeSH
- poškození plic * MeSH
- sirtuin 1 MeSH
- TNF-alfa MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Chronic lung rejection, also called chronic lung allograft dysfunction (CLAD), remains the major hurdle limiting long-term survival after lung transplantation, and limited therapeutic options are available to slow the progressive decline in lung function. Most interventions are only temporarily effective in stabilizing the loss of or modestly improving lung function, with disease progression resuming over time in the majority of patients. Therefore, identification of effective treatments that prevent the onset or halt progression of CLAD is urgently needed. As a key effector cell in its pathophysiology, lymphocytes have been considered a therapeutic target in CLAD. The aim of this review is to evaluate the use and efficacy of lymphocyte depleting and immunomodulating therapies in progressive CLAD beyond usual maintenance immunosuppressive strategies. Modalities used include anti-thymocyte globulin, alemtuzumab, methotrexate, cyclophosphamide, total lymphoid irradiation, and extracorporeal photopheresis, and to explore possible future strategies. When considering both efficacy and risk of side effects, extracorporeal photopheresis, anti-thymocyte globulin and total lymphoid irradiation appear to offer the best treatment options currently available for progressive CLAD patients. SIGNIFICANCE STATEMENT: Effective treatments to prevent the onset and progression of chronic lung rejection after lung transplantation are still a major shortcoming. Based on existing data to date, considering both efficacy and risk of side effects, extracorporeal photopheresis, anti-thymocyte globulin, and total lymphoid irradiation are currently the most viable second-line treatment options. However, it is important to note that interpretation of most results is hampered by the lack of randomized controlled trials.
- MeSH
- alografty MeSH
- antilymfocytární sérum * MeSH
- chronická nemoc MeSH
- lidé MeSH
- lymfocyty MeSH
- obliterující bronchiolitida * terapie MeSH
- plíce MeSH
- rejekce štěpu prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Autorka prezentuje případ nepoznaného tumoru plic u pacienta přijatého na neurologické oddělení. Až pitva objasnila příčinu potíží. V kazuistice se autorka zamýšlí nad paraneoplastickými projevy nádorů, dále zdůrazňuje nutnost provádění bočných snímků plic. Nakonec hodnotí současné možnosti časného záchytu karcinomu plic, vyšetřovací metody a jejich význam i omezení v diagnostice zhoubných novotvarů plic.
Author presents a case of an undiscovered lung tumour had by a patient accepted in the neurology department. Not until the autopsy was the cause of the trouble detected. In this case autor speculates about paraneoplastic manifestations of tumours and then she points out the necessity of taking side lung skiagrams. Finally she considers contemporal possibilities of an on-time detection of the lung cancer, examination methods and their importance as well as their limitations in the lung cancer diagnostics.
- Klíčová slova
- paraneoplastické projevy,
- MeSH
- bronchogenní karcinom diagnóza komplikace mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory plic diagnóza komplikace MeSH
- paraneoplastické neurologické syndromy diagnóza etiologie MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
sv.
- MeSH
- nemoci dýchací soustavy MeSH
- péče o pacienty v kritickém stavu MeSH
- Publikační typ
- periodika MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- pneumologie a ftizeologie
- urgentní lékařství
Intersticiální plicní procesy jsou rozsáhlou skupinou onemocnění, jejichž nedílnou součástí diagnostiky je vyšetření plic výpočetní tomografií (CT). Hodnocení rozsahu postižení je možné provádět vizuálně na základě zkušeností popisujícího lékaře, či automatickými vyhodnocovacími systémy. Cílem této pilotní studie je porovnat v České republice běžně používaný skórovací systém Dutka/Vašáková s automatickým systémem CALIPER Imbio, pilotně používaným Mayo Clinic Rochester, Minnesota.
An integral part of diagnosing interstitial lung disease is computed tomography of the lung. The extent of lung involvement may be assessed vy^th visual scoring systems, either based on experience of a radiologist or using automated software systems. The aim of the study was to compare the Dutka/Vasakova scoring system with automated system CALIPER Imbio pioneered at Mayo Clinic, Rochester, Minnesota.
- MeSH
- diagnóza počítačová MeSH
- idiopatická plicní fibróza * diagnostické zobrazování patologie MeSH
- intersticiální plicní nemoci diagnostické zobrazování patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- parenchymatická tkáň diagnostické zobrazování patologie MeSH
- pilotní projekty MeSH
- plíce diagnostické zobrazování patologie MeSH
- počítačová rentgenová tomografie metody MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- vyhodnocení orgánové dysfunkce MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
