Souhrn Prezervace dárcovských plic a snaha o bezpečné prodloužení času ischemie při zachování funkce je důležitým tématem, kterému se transplantační komunita věnuje dlouhodobě. Recentní publikace převážně torontského týmu zásadně ovlivňují dosavadní pohled na optimální podmínky prezervace a jejich výsledky představují vědecký základ pro posun od prezervace na ledu ke kontrolované hypotermii. Optimální podmínky prezervace jsou nutnou podmínkou pro bezpečné prodloužení ischemie. To s sebou nese další potenciál pro rozvoj oboru a možnost zlepšení dostupnosti jak samotné metody transplantace plic, tak jejích výsledků. Tento přehledový článek shrnuje zásadní poznatky v oblasti prezervace dárcovských plic od prvních experimentálních pokusů provedených před 30 lety po recentní studie a diskutuje jednotlivé aspekty, které změna standardu prezervace ovlivnila nebo pravděpodobně ovlivní.
Summary The preservation of donor lungs and the effort to safely extend ischemic time while maintaining function is an important topic that the transplant community has been addressing for a long time. Recent publications, mainly from the Toronto team, have fundamentally influenced the existing standard of optimal preservation conditions, and their results provide a scientific basis for the shift from ice preservation to controlled hypothermia. Optimal preservation conditions are a necessary prerequisite for the safe extension of ischemic time. This brings additional potential for the development of the field and the possibility to improve the availability of lung transplantations and their outcomes. This review summarizes the key findings in the area of donor lung preservation from the first experimental attempts conducted 30 years ago to recent studies and discusses the various aspects that the change in preservation standard has influenced or is likely to influence.
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- klinická studie jako téma MeSH
- lidé MeSH
- transplantace plic * MeSH
- uchovávání orgánů * MeSH
- Check Tag
- lidé MeSH
Acute cellular rejection (ACR) frequently occurs following lung transplantation (LuTx) and represents a risk factor for the development of chronic lung allograft dysfunction (CLAD) as well as long-term survival. The histopathological diagnosis of ACR carries a burden of interobserver variability. The widespread utilization and cost-effectiveness of immunohistochemistry (IHC) was proven beneficial in diagnosing rejection in human kidney transplantations and LuTx rat models. However, its potential for ACR detection in patients remains unexplored. We analyzed surface markers (CD3, CD4, CD8, CD20, CD68, CD47, PD-1, PD-L1, and CD31/PECAM-1) on lung tissue cryobiopsy samples collected within 6 months post-LuTx from 60 LuTx recipients, 48 of whom were diagnosed with ACR. Additionally, serum samples from 51 patients were analyzed using a multiplex bead-based Luminex assay. The cytokines and markers included PD-L1, IL2, TNFα, IFNγ, and Granzyme B. We observed a significant increase in PD-L1 tissue expression within the rejection group, suggesting a concerted effort to suppress immune responses, especially those mediated by T-cells. Furthermore, we noted significant differences in PECAM-1 levels between ACR/non-ACR. Additionally, peripheral blood C-reactive-protein levels tended to be higher in the ACR group, while Luminex serum analyses did not reveal any significant differences between groups. In conclusion, our findings suggest the potential value of PECAM-1 and PD-L1 markers in diagnosing ACR.
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- akutní nemoc MeSH
- antigeny CD274 * metabolismus krev MeSH
- antigeny CD31 * metabolismus MeSH
- biologické markery * krev metabolismus MeSH
- dospělí MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- plíce patologie MeSH
- rejekce štěpu * diagnóza krev MeSH
- senioři MeSH
- transplantace plic * škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
UNLABELLED: Primary graft failure occurs 15 to 30 % of the time after transplantation. Although there have been improvements in preserving the lungs in good condition, there have not been studies on the regulation of transcription factors. METHODS: We carried out an experimental study involving lung transplantation to indirectly evaluate reactive oxygen species (ROS) production and VEGF expression by competitive blockade of HIF-1alpha with chetomin. There were 5 groups: Group-1: Lung blocks were perfused with 0.9 % SSF, immediately harvested, and preserved. Group-2 (I-T): Immediate transplantation and then reperfusion for 1 h. Group-3 (I-R): Lung blocks were harvested and preserved in LPD solution for 6 h and reperfused for 1 h. Group-4 (DMSO): Lung blocks were treated for 4 h with DMSO, preserved for 6 h and transplanted to a receptor treated with DMSO. Group-5 (chetomin): Lung blocks were treated for 4 h with chetomin, preserved for 6 h and transplanted to a receptor treated with chetomin. ROS, mRNA, and protein levels of HIF-1alpha and EG-VEGF were determined. RESULTS: The DMSO and chetomin groups had significantly lower ROS levels. Compared with those in the I-R group, the chetomin group exhibited the lowest level of HIF-1alpha. CONCLUSIONS: Addition of chetomin to the donor and the receptor results in a significant reduction in HIF-1A, VEGF and ROS.
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- disulfidy MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa * metabolismus MeSH
- indolové alkaloidy MeSH
- krysa rodu rattus MeSH
- plíce metabolismus účinky léků MeSH
- potkani Sprague-Dawley MeSH
- reaktivní formy kyslíku * metabolismus MeSH
- transplantace plic * MeSH
- vaskulární endoteliální růstový faktor A * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- HIV infekce komplikace MeSH
- infekce dýchací soustavy etiologie imunologie klasifikace komplikace MeSH
- lidé MeSH
- oportunní infekce * etiologie imunologie klasifikace komplikace MeSH
- pneumocystová pneumonie diagnóza etiologie farmakoterapie patologie MeSH
- respirační syncytiální viry patogenita MeSH
- transplantace plic škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- intersticiální plicní nemoci * diagnóza terapie MeSH
- lidé MeSH
- progrese nemoci MeSH
- systémová sklerodermie * komplikace terapie MeSH
- transplantace plic MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Idiopathic pulmonary fibrosis (IPF) is a severe and currently incurable disease that is associated with irreversible fibrotic remodeling of the lung parenchyma. Pathological remodeling of the lung leads to damage of the alveolo-capillary barrier. There is a reduction in the diffusing capacity of the lungs for respiratory gases. Later, changes in the mechanical properties of lung tissue occur - their compliance decreases and respiratory work increases. Impaired respiratory gases exchange with restrictive ventilatory failure lead to tissue hypoxia and muscle weakness. Progressive respiratory insufficiency develops. The triggers of fibrotic remodeling of the lung are currently unknown, as are the pathomechanisms that keep this process active. IPF can only be slowed pharmacologically, not reversed. It is therefore very important to start its treatment as soon as possible. Early detection of IPF patients requires a multidisciplinary approach. Diagnosis, treatment initiation, and monitoring in specialized centers offer the best chance of slowing disease progression, enhancing quality of life, and extending patient survival. In addition to antifibrotic therapy, good lifestyle management, maintenance of physical fitness and treatment of associated chronic diseases such as diabetes and cardiac comorbidities are important. Lung transplantation is an option for some patients with IPF. This is a challenging treatment modality, requiring close collaboration with transplant centers and expert selection of suitable candidates, influenced, among other things, by the availability of suitable donor lungs. Our article aims to provide current information about IPF, focusing on its functional consequences and clinical manifestation. We discuss the molecular and cellular mechanisms potentially involved in IPF development, as well as the morphological changes observed in lung biopsies and high-resolution computed tomography (HRCT) images. Finally, we summarize the existing treatment options. Key words: Idiopathic pulmonary fibrosis, Lung biopsy, HRCT, Antifibrotic therapy, Lung transplantation.
- MeSH
- idiopatická plicní fibróza * terapie diagnóza patofyziologie patologie MeSH
- lidé MeSH
- plíce patologie patofyziologie MeSH
- transplantace plic MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Histologic evaluation of allograft biopsies after lung transplantation has several limitations, suggesting that molecular assessment using tissue transcriptomics could improve biopsy interpretation. This single-center, retrospective cohort study evaluated discrepancies between the histology of transbronchial biopsies (TBBs) with no rejection (NR) and T-cell mediated rejection (TCMR) by molecular diagnosis. The accuracy of diagnosis was assessed based on response to treatment. 54 TBBs from Prague Lung Transplant Program obtained between December 2015 and January 2020 were included. Patients with acute cellular rejection (ACR) grade ≥ 1 by histology received anti-rejection treatment. Response to therapy was defined as an increase in FEV1 of ≥ 10% 4 weeks post-biopsy compared to the pre-biopsy value. Among the 54 analyzed TBBs, 25 (46%) were concordant with histology, while 29 (54%) showed discrepancies. ACR grade 0 was found in 12 TBBs (22%) and grade A1 ≥ 1 in 42 TBBs (78%). Treatment response was present in 14% in the NR group and in 50% in the TCMR group (p = 0.024). Our findings suggest that low-grade acute cellular rejection is less likely to be associated with molecular TCMR, which might better identify lung transplant recipients who benefit from therapy.
- MeSH
- biopsie MeSH
- dospělí MeSH
- imunosupresiva terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- plíce patologie MeSH
- rejekce štěpu * diagnóza patologie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- transplantace plic * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
BACKGROUND: The pathology of primary hemostasis is a common complication of extracorporeal membrane oxygenation (ECMO) support. Scientific data describing its changes in patients on short-term ECMO support and the ability and speed of the restoration of its functions are limited. AIMS: The aim of this study was to describe the pathology of primary hemostasis induced by short-term ECMO support and its development over time using PFA-200, ROTEM platelet, and von Willebrand factor (vWF) analyses. METHODS: In patients undergoing lung transplantation surgery using intraoperative veno-arterial ECMO support, blood samples were analyzed using the following tests: PFA-200, ROTEM platelet tests, vWF antigen, ristocetin cofactor (RCo), and collagen-binding protein (CB) before, during, and after ECMO support. RESULTS: Blood samples from 32 patients were analyzed. All 3 PFA-200 tests (COL/EPI, COL/ADP, and COL/P2Y) showed significant deterioration during ECMO support with rapid restoration after ECMO cessation (p < 0.05), suggesting an ECMO-induced primary hemostasis disorder. A significant increase of vWF antigen after ECMO cessation (p < 0.05) was found with an increase of RCo and CB levels, although it was not significant (p > 0.05). CONCLUSIONS: Short-term ECMO support induces primary hemostasis pathology. It occurs immediately after initiation but is rapidly restored after ECMO cessation, which is detectable by PFA-200. Despite there being persistent platelet dysfunction after ECMO cessation, as seen with the ROTEM platelet results, the increased levels of vWF antigen might explain the normal results of primary hemostasis detected by PFA-200.
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- časové faktory MeSH
- dospělí MeSH
- hemostáza * fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mimotělní membránová oxygenace * metody MeSH
- transplantace plic * MeSH
- von Willebrandův faktor metabolismus analýza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
Transplantace plic je dynamicky se rozvíjející metodou léčby pokročilých stadií plicních onemocnění parenchymového nebo cévního původu. Přes významný pokrok v této oblasti je dlouhodobé přežití příjemců transplantace plic kratší ve srovnání s ostatními transplantacemi solidních orgánů. Důvodem je skutečnost, že plíce jsou vysoce imunogenní, otevřený systém v neustálém kontaktu se zevním prostředím, což vede k vyššímu výskytu infekcí a imunitních komplikací. K odlišení jednotlivých typů poškození štěpu se v současnosti používá řada vyšetřovacích metod, počínaje funkčním vyšetřením plic a zobrazovacími metodami, následovanými mikrobiologickými, imunologickými a bioptickými vyšetřeními. Tyto klinické nástroje však postrádají citlivost k zachycení časné subklinické změny štěpu, která předchází její klinické manifestaci až o několik měsíců. Z nových biomarkerů je klinické implementaci nejblíže vyšetření volné cirkulující dárcovské DNA. Současný stav výzkumu této nejmodernější metody v oblasti transplantace plic je předmětem tohoto přehledového sdělení.
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- Klíčová slova
- volná cirkulující DNA dárce,
- MeSH
- biologické markery krev MeSH
- DNA analýza MeSH
- lidé MeSH
- rejekce štěpu * diagnóza etiologie klasifikace MeSH
- transplantace plic * dějiny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
There are limited data on referral rates and the number of patients with idiopathic pulmonary fibrosis (IPF) who are eligible for lung transplantation. The aim of the present study was to assess adherence to the consensus of the International Society for Heart and Lung Transplantation (ISHLT) for the referral of patients with IPF among Czech interstitial lung disease (ILD) centers. Czech patients who were diagnosed with IPF between 1999 and 2021 (n = 1584) and who were less than 65 years old at the time of diagnosis were retrospectively selected from the Czech Republic of the European Multipartner Idiopathic Pulmonary Fibrosis Registry (EMPIRE). Nonsmokers and ex-smokers with a body mass index (BMI) of <32 kg/m2 (n = 404) were included for further analyses. Patients with a history of cancer <5 years from the time of IPF diagnosis, patients with alcohol abuse, and patients with an accumulation of vascular comorbidities were excluded. The trajectory of individual patients was verified at the relevant ILD center. From the database of transplant patients (1999-12/2021, n = 541), all patients who underwent transplantation for pulmonary fibrosis (n = 186) were selected, and the diagnosis of IPF was subsequently verified from the patient's medical records (n = 67). A total of 304 IPF patients were eligible for lung transplantation. Ninety-six patients were referred to the transplant center, 50% (n = 49) of whom were referred for lung transplantation. Thirty percent of potentially eligible patients not referred to the transplant center were considered to have too many comorbidities by the reporting physician, 19% of IPF patients denied lung transplantation, and 17% were not referred due to age. Among Czech patients with IPF, there may be a larger pool of potential lung transplant candidates than has been reported to the transplant center to date.
- MeSH
- dodržování směrnic statistika a číselné údaje MeSH
- dospělí MeSH
- idiopatická plicní fibróza * chirurgie MeSH
- intersticiální plicní nemoci chirurgie MeSH
- konziliární vyšetření a konzultace * statistika a číselné údaje MeSH
- lidé středního věku MeSH
- lidé MeSH
- registrace MeSH
- retrospektivní studie MeSH
- senioři MeSH
- transplantace plic * statistika a číselné údaje MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
