ABSTRACT
The lockdown imposed to combat the COVID-19 pandemic produced a historic fall in air pollution in cities like Barcelona. This exceptional situation offered a unique context in which to examine the effects of air pollutants on human health. The present study aims to determine and compare the oxidative stress biomarkers Th1/Th2 and inflammatory-related cytokines in healthy individuals first during lockdown and then six months after the easing of the restrictions on mobility. A prospective study of a representative sample of 58 healthy, non-smoking adults was carried out. During lockdown and six months post-easing of restrictions, blood samples were drawn to measure the percentage of eosinophils, levels of Th1/Th2 and inflammatory-related cytokines assessed by a multiplex assay (BioRad Laboratories S.A., Marnes-la-Coquette, France), and levels of 8-isoprostane, glutathione peroxidase activity, and myeloperoxidase (Cayman Chemical Co., Ann Arbor, MI, USA), to assess their value as biomarkers of oxidative stress. Six months after easing mobility restrictions, increases in the levels of 8-isoprostane (p < 0.0001), IL-1ß (p = 0.0013), IL-1ra (p = 0.0110), IL-4 (p < 0.0001), IL-13 (p < 0.0001), G-CSF (p = 0.0007), and CCL3 (p < 0.0001) were recorded, along with reductions in glutathione peroxidase (p < 0.0001), IFN-γ (p = 0.0145), TNFα (p < 0.0001), IP-10 (p < 0.0001), IL-2 (p < 0.0001), IL-7 (p < 0.0001), basic FGF (p < 0.0001), CCL4 (p < 0.0001), and CCL5 (p < 0.0001). No significant differences were observed in the rest of the biomarkers analyzed. The reduction in environmental pollution during the COVID-19 lockdown significantly lowered the levels of oxidative stress, systemic inflammation, and Th2-related cytokines in healthy people.
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Introduction: Trough blood levels (C0) of tacrolimus are used to adjust drug dosage, but they do not consistently correlate with clinical outcomes. Measurement of residual gene expression of nuclear factor of activated T cell (NFAT)-regulated genes (NFAT-RGE) has been proposed as a pharmacodynamic biomarker to assess the degree of immunosuppression in certain solid organ transplantations, but little is known regarding lung transplant recipients (LTR). Our primary objective is to correlate tacrolimus blood levels with NFAT-RGE. Methods: NFAT-RGE and tacrolimus C0 and peak (C1.5) levels were determined in 42 patients at three, six and 12 months post-transplantation. Results: Tacrolimus C0 did not exhibit a correlation with NFAT-RGE, whereas C1.5 did. Besides, over 20% of measurements indicated high levels of immunosuppression based on the below 30% NFAT-RGE threshold observed in many studies. Among those measurements within the therapeutic range, 19% had an NFAT-RGE<30%. Conclusion: Consequently, a subset of patients within the tacrolimus therapeutic range may be more susceptible to infection or cancer, potentially benefiting from NFAT-RGE and tacrolimus peak level monitoring to tailor their dosage. Further quantitative risk assessment studies are needed to elucidate the relationship between NFAT-RGE and the risk of infection, cancer, or rejection.
Subject(s)
Immunosuppressive Agents , Lung Transplantation , NFATC Transcription Factors , Tacrolimus , Humans , Tacrolimus/therapeutic use , Tacrolimus/pharmacokinetics , Tacrolimus/blood , Lung Transplantation/adverse effects , Male , NFATC Transcription Factors/genetics , NFATC Transcription Factors/metabolism , Middle Aged , Female , Immunosuppressive Agents/therapeutic use , Adult , Aged , Transplant Recipients , Drug Monitoring/methods , Graft Rejection/immunology , Graft Rejection/genetics , Gene Expression Regulation/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolismABSTRACT
Introduction: Chronic rejection is a major complication post-transplantation. Within lung transplantation, chronic rejection was considered as airway centred. Chronic Lung Allograft Dysfunction (CLAD), defined to cover all late chronic complications, makes it more difficult to understand chronic rejection from an immunological perspective. This study investigated the true nature, timing and location of chronic rejection as a whole, within mouse lung transplantation. Methods: 40 mice underwent an orthotopic left lung transplantation, were sacrificed at day 70 and evaluated by histology and in vivo µCT. For timing and location of rejection, extra grafts were sacrificed at day 7, 35, 56 and investigated by ex vivo µCT or single cell RNA (scRNA) profiling. Results: Chronic rejection originated as innate inflammation around small arteries evolving toward adaptive organization with subsequent end-arterial fibrosis and obliterans. Subsequently, venous and pleural infiltration appeared, followed by airway related bronchiolar folding and rarely bronchiolitis obliterans was observed. Ex vivo µCT and scRNA profiling validated the time, location and sequence of events with endothelial destruction and activation as primary onset. Conclusion: Against the current belief, chronic rejection in lung transplantation may start as an arterial response, followed by responses in venules, pleura, and, only in the late stage, bronchioles, as may be seen in some but not all patients with CLAD.
Subject(s)
Graft Rejection , Lung Transplantation , Animals , Lung Transplantation/adverse effects , Graft Rejection/immunology , Mice , Chronic Disease , Disease Models, Animal , Mice, Inbred C57BL , Lung/pathology , Lung/immunology , Male , Bronchiolitis Obliterans/etiology , Bronchiolitis Obliterans/immunology , Bronchiolitis Obliterans/pathologyABSTRACT
Background: Vascular endothelial growth factor-D (VEGF-D) is the most commonly used biomarker for diagnosing lymphangioleiomyomatosis (LAM). However, lung biopsy is often necessary as well; therefore, defining new biomarkers for LAM is crucial. The aim of this study was to describe the diagnostic accuracy of a variety of biomarkers. Methods: We assessed 13 analytes in serum related to extracellular matrix remodeling, lymphatic involvement and angiogenesis in a cohort of patients with LAM, comparing them with patients with other cystic lung diseases (OCLD) and healthy women. A scoring method based on the cut-point of each VEGF-D and metalloproteinase-2 (MMP-2) was used to evaluate the diagnostic performance of the marker combination. Results: A total of 97 subjects were recruited: 59 (61%) LAM patients, 18 (19%) OCLD patients, and 20 (20%) healthy female controls. MMP-2 was the only extracellular matrix remodeling biomarker able to differentiate LAM patients from OCLD and healthy patients. Serum MMP-2 was higher in LAM patients [median 578 (465-832) ng/ml] than in patients with OCLD and healthy controls [medians 360 (314-546) and 427 (365-513) ng/ml, respectively (p < 0.0001)]. The area under ROC curve (AUC) of MMP-2 was 0.785 and that of VEGF-D 0.815 (p = 0.6214). The sensitivity/specificity profiles of each biomarker (54/92% for MMP-2, 59/95% for VEGF-D) yielded a composite score (-6.36 + 0.0059 × VEGF-D + 0.0069 × MMP-2) with higher accuracy than each component alone (AUC 0.88 and sensitivity/specificity 79/87%). Conclusion: Combining MMP-2 and VEGF-D may increase diagnostic accuracy for LAM.
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Total lymphoid irradiation (TLI) is an alternative treatment for chronic lung allograft dysfunction (CLAD). However, data regarding its efficacy and tolerance are scarce. This study included patients with CLAD treated with TLI at our center between 2011 and 2018. Clinical characteristics before and after TLI and related complications were analyzed. Forty patients with CLAD (twenty-nine bronchiolitis obliterans syndrome [BOS], nine restrictive allograft syndrome [RAS], and two mixed) were included. Significant attenuation of the forced expiratory volume in 1-sec (FEV1 ) decline slope was observed in all phenotypes, in both the BOS and RAS. The median FEV1 12, 6, and 3 months pre-TLI were as follows: 1980 (IQR 1720-2560), 1665 (IQR 1300-2340) and 1300 (IQR 1040-1740) ml (p < .001), while the median FEV1 at 3, 6, and 12 months post-TLI was 1110 (IQR 810-1440), 1130 (IQR 860-1470), and 1115 (IQR 865-1490) ml (p = .769). No dropouts due to radiation toxicity were observed. The mean survival according to the Karnofsky Performance Status Scale (KPS) >70 or ≤70 at baseline was 1837 (IQR 259-2522) versus 298 (IQR 128-554) days (p < .0001), respectively. In conclusion, TLI may stop FEV1 decline in both BOS and RAS. Moreover, a good KPS score may be an important prognostic factor.
Subject(s)
Bronchiolitis Obliterans , Lung Transplantation , Humans , Bronchiolitis Obliterans/etiology , Lung Transplantation/adverse effects , Lymphatic Irradiation/adverse effects , Retrospective Studies , Lung , Phenotype , AllograftsABSTRACT
BACKGROUND: Venous thromboembolism (VTE) is a major complication after lung transplantation (LT). However, its pathophysiology remains unknown, and coagulation profiles have yet to be described. OBJECTIVE: The aim of this study was to longitudinally assess coagulation status after LT. METHODS: We performed a prospective study and described the coagulation profiles of 48 patients at 5 different time-points: before LT and at 24-72 h, 2 weeks, 4 months, and 1 year after LT. RESULTS: At baseline, almost all analyzed coagulation factors were within the normal range, except for FVIII, which was above the normal range. Von Willebrand factor (vWF) and FVIII were increased after LT and remained high at 1 year after transplantation. The cumulative incidence of VTE was 22.9%. Patients who developed VTE had higher FVIII activity 2 weeks after LT. CONCLUSIONS: This is the first study to describe coagulation profiles up to 1 year after LT. We show that most markers of a procoagulant state normalize at 2 weeks after LT, but that values of FVIII and vWF remain abnormal at 1 year. This problem has received little attention in the literature. Larger studies are necessary to confirm the results and to design appropriate prophylactic strategies.
Subject(s)
Blood Coagulation Tests , Lung Transplantation , Postoperative Complications/etiology , Venous Thromboembolism/etiology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Prospective StudiesABSTRACT
There are few published data on long-term treatment with sirolimus in lymphangioleiomyomatosis (LAM). The objective of this study was to describe the long-term effect of sirolimus in a series of LAM patients followed up in a referral centre, focusing on pulmonary function. We retrospectively reviewed a series of 48 patients with LAM diagnosed, followed up and treated with sirolimus in a single centre. Response to sirolimus was evaluated at 1 and 5 years. A negative sirolimus response was defined as an FEV1 decline greater than - 75 ml/year. A mixed-effects model was used to estimate the longitudinal changes in FEV1 (average slope), both as absolute (ml/year) and as predicted values (%predicted/year). From a total of 48 patients, 9 patients underwent lung transplantation and 4 died during the study. Mean (95% CI) FEV1 slope over 5 years was - 0.14 (- 26.13 to 25.85) ml/year in the whole LAM group, 42.55 (14.87 to 70.22) ml/year in the responder group, - 54.00 (- 71.60 to - 36.39) ml/year in the partial responder group and - 84.19 (- 113.5 to - 54.0) ml/year in the non-responder group. After 5 years of sirolimus treatment 59% had a positive response, 30% had a partial response and 11% had a negative response. Our study found that sirolimus treatment had a positive long-term effect on most LAM patients.
Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Lymphangioleiomyomatosis/drug therapy , Sirolimus/therapeutic use , Adult , Angiomyolipoma/complications , Angiomyolipoma/drug therapy , Antibiotics, Antineoplastic/adverse effects , Female , Follow-Up Studies , Forced Expiratory Volume/drug effects , Humans , Kaplan-Meier Estimate , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Lymphangioleiomyomatosis/complications , Middle Aged , Off-Label Use , Retrospective Studies , Sirolimus/adverse effects , Tertiary Care Centers , Time , Treatment OutcomeABSTRACT
BACKGROUND: In lung transplantation (LT), the length of ischemia time is controversial as it was arbitrarily stablished. We ought to explore the impact of extended cold-ischemia time (CIT) on ischemia-reperfusion injury in an experimental model. METHODS: Experimental, randomized pilot trial of parallel groups and final blind analysis using a swine model of LT. Donor animals (n=8) were submitted to organ procurement. Lungs were subjected to 6h (n=4) or 12h (n=4) aerobic hypothermic preservation. The left lung was transplanted and re-perfused for 4h. Lung biopsies were obtained at (i) the beginning of CIT, (ii) the end of CIT, (iii) 30min after reperfusion, and (iv) 4h after reperfusion. Lung-grafts were histologically assessed by microscopic lung injury score and wet-to-dry ratio. Inflammatory response was measured by determination of inflammatory cytokines. Caspase-3 activity was determined as apoptosis marker. RESULTS: We observed no differences on lung injury score or wet-to-dry ratio any given time between lungs subjected to 6h-CIT or 12h-CIT. IL-1ß and IL6 showed an upward trend during reperfusion in both groups. TNF-α was peaked within 30min of reperfusion. IFN-γ was hardly detected. Caspase-3 immunoexpression was graded semiquantitatively by the percentage of stained cells. Twenty percent of apoptotic cells were observed 30min after reperfusion. CONCLUSIONS: We observed that 6 and 12h of CIT were equivalent in terms of microscopic lung injury, inflammatory profile and apoptosis in a LT swine model. The extent of lung injury measured by microscopic lung injury score, proinflammatory cytokines and caspase-3 determination was mild.
ABSTRACT
The clinical course of lung transplantation (LT) is diverse: some patients present chronic lung allograft dysfunction (CLAD) and progressive decline in pulmonary function, but others maintain normal spirometric values and active lives. OBJECTIVES: The aim of this study was to elucidate whether long-term LT survivors with normal spirometry achieve normal exercise capacity, and to identify predictive factors of exercise capacity. METHODS: This was a cross-sectional multicentre study, where bilateral LT recipients who survived at least 10â years after LT, with normal spirometry, no diagnosis of CLAD and modified Medical Research Council dyspnoea degree ≤2 underwent cardiopulmonary exercise testing (CPET). RESULTS: 28 LT recipients were included with a mean±sd age of 48.7±13.6â years. Oxygen uptake (V' O2 ) had a mean±sd value of 21.49±6.68â mL·kg-1·min-1 (75.24±15.6%) and the anaerobic threshold was reached at 48.6±10.1% of the V' O2max predicted. The mean±sd heart rate reserve at peak exercise was 17.56±13.6%. The oxygen pulse increased during exercise and was within normal values at 90.5±19.4%. The respiratory exchange ratio exceeded 1.19 at maximum exercise. The median (25-75th percentile) EuroQol-5D score was 1 (0.95-1), indicating a good quality of life. The median (25-75th percentile) International Physical Activity Questionnaire score was 5497 (4007-9832)â MET-min·week-1 with 89% of patients reporting more than 1500â MET-min·week-1. In the multivariate regression models, age, sex and diffusing capacity of the lung for carbon monoxide remained significantly associated with V' O2max (mL·kg-1·min-1); haemoglobin and forced expiratory volume in 1â s were significantly associated with maximum work rate (watts), after adjusting for confounders. CONCLUSION: We report for the first time near-normal peak V' O2 values during CPET and normal exercise capacity in long-term LT recipients without CLAD.
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BACKGROUND: Primary graft dysfunction (PGD) remains a major obstacle after lung transplantation. Ischemia-reperfusion injury is a known contributor to the development of PGD following lung transplantation. We developed a novel approach to assess the impact of increased pulmonary blood flow in a large porcine single-left lung transplantation model. MATERIALS: Twelve porcine left lung transplants were divided in two groups (n = 6, in low- (LF) and high-flow (HF) group). Donor lungs were stored for 24 h on ice, followed by left lung transplantation. In the HF group, recipient animals were observed for 6 h after reperfusion with partially clamping right pulmonary artery to achieve a higher flow (target flow 40-60% of total cardiac output) to the transplanted lung compared to the LF group, where the right pulmonary artery was not clamped. RESULTS: Survival at 6 h was 100% in both groups. Histological, functional and biological assessment did not significantly differ between both groups during the first 6 h of reperfusion. injury was also present in the right native lung and showed signs compatible with the pathophysiological hallmarks of ischemia-reperfusion injury. CONCLUSIONS: Partial clamping native pulmonary artery in large animal lung transplantation setting to study the impact of low versus high pulmonary flow on the development of ischemia reperfusion is feasible. In our study, differential blood flow had no effect on IRI. However, our findings might impact future studies with extracorporeal devices and represent a specific intra-operative problem during bilateral sequential single-lung transplantation.
ABSTRACT
No disponible
Subject(s)
Humans , Coronavirus Infections/surgery , Pneumonia, Viral/surgery , Lung Transplantation , Betacoronavirus , Pandemics , Severe Acute Respiratory Syndrome/complicationsABSTRACT
BACKGROUND: In lung transplantation (LT), the length of ischemia time is controversial as it was arbitrarily stablished. We ought to explore the impact of extended cold-ischemia time (CIT) on ischemia-reperfusion injury in an experimental model. METHODS: Experimental, randomized pilot trial of parallel groups and final blind analysis using a swine model of LT. Donor animals (n=8) were submitted to organ procurement. Lungs were subjected to 6h (n=4) or 12h (n=4) aerobic hypothermic preservation. The left lung was transplanted and re-perfused for 4h. Lung biopsies were obtained at (i) the beginning of CIT, (ii) the end of CIT, (iii) 30min after reperfusion, and (iv) 4h after reperfusion. Lung-grafts were histologically assessed by microscopic lung injury score and wet-to-dry ratio. Inflammatory response was measured by determination of inflammatory cytokines. Caspase-3 activity was determined as apoptosis marker. RESULTS: We observed no differences on lung injury score or wet-to-dry ratio any given time between lungs subjected to 6h-CIT or 12h-CIT. IL-1ß and IL6 showed an upward trend during reperfusion in both groups. TNF-α was peaked within 30min of reperfusion. IFN-γ was hardly detected. Caspase-3 immunoexpression was graded semiquantitatively by the percentage of stained cells. Twenty percent of apoptotic cells were observed 30min after reperfusion. CONCLUSIONS: We observed that 6 and 12h of CIT were equivalent in terms of microscopic lung injury, inflammatory profile and apoptosis in a LT swine model. The extent of lung injury measured by microscopic lung injury score, proinflammatory cytokines and caspase-3 determination was mild.
Subject(s)
Lung Injury , Lung Transplantation , Reperfusion Injury , Animals , Caspase 3 , Cytokines , Ischemia/pathology , Lung/pathology , Lung Injury/etiology , Organ Preservation , Pilot Projects , Random Allocation , Reperfusion Injury/prevention & control , SwineABSTRACT
This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality.
Subject(s)
COVID-19/epidemiology , Lung Transplantation , Transplant Recipients , Adult , Antiviral Agents/therapeutic use , COVID-19/mortality , Drug Combinations , Drug Interactions , Humans , Lopinavir , Lung , Retrospective Studies , Ritonavir , SARS-CoV-2 , Spain/epidemiology , TacrolimusABSTRACT
In recent years, the utility of vascular complement factor 4d (C4d) deposition as diagnostic tool for antibody mediated rejection (AMR) after lung transplantation, has become a controversial issue. We aimed to pinpoint the problematic nature of C4d as biomarker with a simple experiment. We quantified C4d in broncho-alveolar lavage (BAL) of lung transplant patients with diverse post-transplant complications in 3 different settings of clinically clear cases of: 1/ chronic lung allograft dysfunction (CLAD); 2/ acute complications acute rejection (AR), lymphocytic bronchiolitis (LB), antibody-mediated rejection (AMR) and respiratory infection (INF); 3/ patients with parallel C4d immunostaining and Anti-HLA. All groups were compared to BAL of stable patients. C4d was measured via standard ELISA. C4d was increased in CLAD, predominantly in RAS (p = 0.0026) but not in BOS (p = 0.89). C4d was increased in all acute events, AR (p = 0.0025), LB (p < 0.0001), AMR (p = 0.0034), infections (p < 0.0001). In patients with parallel C4d immunostaining and serum HLA antibodies, C4d was increased in C4d-/HLA- (p = 0.0011); C4d-/HLA+ (p = 0.013); HLA+/C4d + (p = 0.0081). A correlation of systemic C-reactive protein (CRP) with C4d was found in all patients (r = 0.49; p < 0.0001). We hypothesize that free C4d in BAL may only be representative of a general immune response in the transplanted lung.
Subject(s)
Allografts/immunology , Biomarkers/metabolism , Bronchoalveolar Lavage Fluid/chemistry , Complement C4b/metabolism , Graft Rejection/immunology , Lung Transplantation , Peptide Fragments/metabolism , Respiratory System/metabolism , Adult , C-Reactive Protein/metabolism , Chronic Disease , Diagnosis, Differential , Female , HLA Antigens/immunology , Humans , Isoantibodies/metabolism , Male , Middle AgedABSTRACT
Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immune cells from the myeloid lineage. MDSCs expand in pathological situations, such as chronic infection, cancer, autoimmunity, and allograft rejection. As chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplantation (LTx), MDSCs may play a role in its pathophysiology. We assessed phenotype and frequency of MDSCs in peripheral blood from lung transplant recipients and its relationship to post-transplant complications and immunosuppression. Granulocytic (G)-MDSC were identified and quantified by flow cytometry of blood from 4 control subjects and 20 lung transplant patients (stable n = 6, infection n = 5; CLAD n = 9). G-MDSC functionality was assessed in vitro by their capability to block CD4 and CD8 T cell proliferation. More G-MDSC could be assessed using EDTA tubes compared to heparin tubes (p = 0.004). G-MDSC were increased in stable lung transplant recipients vs. non-transplant controls (52.1% vs. 9.4%; p = 0.0095). The infection or CLAD groups had lower G-MDSCs vs. stable recipients (28.2%p = 0.041 and 33.0%; p = 0.088, respectively), but were not different among CLAD phenotypes. G-MDSC tended to correlate with cyclosporine A and tacrolimus levels (r2 = 0.18; r2 = 0.17). CD4 and CD8 cells proliferation decreased by 50 and 80% if co-cultured with MDSCs (1:6 and 1:2 MDSC:T-cell ratio, respectively). In conclusion, circulating MDSCs are measurable, functional and have a G-MDSC phenotype in lung transplant patients. Their frequency is increased in stable patients, decreased during post-transplant complications, and related to level of immunosuppression. This study may pave the way for further investigations of MDSC in the context of lung transplantation.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Graft vs Host Reaction/immunology , Immune Tolerance/immunology , Lung Transplantation/adverse effects , Myeloid-Derived Suppressor Cells/immunology , Adult , Allografts , Cell Proliferation/physiology , Female , Humans , Immunosuppression Therapy , Lymphocyte Activation/immunology , Male , Middle Aged , Transplant Recipients , Young AdultABSTRACT
Introducción: La supervivencia del trasplante pulmonar (TP) viene condicionada fundamentalmente por el desarrollo de disfunción crónica del injerto (DCI). El retrasplante pulmonar (RP) es una alternativa para una población seleccionada con DCI. El objetivo del estudio fue revisar la experiencia de RP en nuestro centro. Pacientes y métodos: Se ha realizado un estudio retrospectivo de los pacientes sometidos a RP entre agosto de 1990 y julio de 2017. Resultados: Se realizaron 14 RP de un total de 998 (1,4%) TP. Doce RP se dieron por causa de DCI: 10 (71,4%) por síndrome de bronquiolitis obliterante y 2 (14,3%) por síndrome restrictivo del injerto. En 2 pacientes el RP se realizó en los 30 días siguientes al primer TP. En el RP por DCI el tiempo medio entre el TP y el RP fue de 48 meses. Tras el RP el tiempo medio de ventilación mecánica fue de 32 días. El incremento del FEV1 tras el RP fue del 24 ± 18%. Los mejores valores en la espirometría se observaron a los 7,3 meses. La supervivencia media de la serie fue de 43,8 meses, en los pacientes con síndrome de bronquiolitis obliterante fue de 63,4 meses mientras que en los pacientes con síndrome restrictivo del injerto fue de 19,5 meses. Solo un paciente de los 2 RP precoces sobrevivió a este. Conclusión: El RP es una opción terapéutica en pacientes seleccionados con DCI. Sin embargo, estos resultados no son reproducibles si el RP se realiza en los primeros días
Introduction: Long-term survival of lung transplantation (LT) patients is mainly limited by the development of chronic lung allograft dysfunction (CLAD). Lung retransplantation (LR) is an alternative for a selected population. The aim of this study was to review the LR experience in our center. Patients and methods: We conducted a retrospective study of patients undergoing LR between August 1990 and July 2017. Results: Fourteen LR out of a total of 998 (1.4%) LT were performed. Twelve patients (85.7%) underwent LR due to CLAD: 10 (71.4%) because of bronchiolitis obliterans syndrome and 2 (14.3%) due to restrictive allograft syndrome. LR was performed in 2 patients within 30 days of the first LT. In those who underwent LR due to CLAD, mean time between the first LT and LR was 48 months, and mean duration of invasive mechanical ventilation was 32 days. The increase in FEV1 after LR was 24 ± 18%. The best spirometry values were observed after 7.3 months. Mean survival of the cohort was 43.8 months. In patients with bronchiolitis obliterans syndrome, mean survival was 63.4 months, while in those with restrictive allograft syndrome, it was 19.5 months. Only 1 of the 2 early LR patients survived. Conclusion: LR is a therapeutic option in selected patients with CLAD, with acceptable survival. Indication for LR early after LT shows poor outcomes
Subject(s)
Humans , Male , Female , Adolescent , Young Adult , Adult , Middle Aged , Primary Graft Dysfunction/surgery , Lung Transplantation/adverse effects , Host vs Graft Reaction , Lung Transplantation/mortality , Retrospective Studies , Chronic Disease , ReoperationABSTRACT
We describe two cystic fibrosis patients infected with pandrug-resistant Burkholderia cepacia complex, with the exception of ceftazidime-avibactam, who received prophylaxis with this antibiotic during lung transplantation. Although both patients had a post-operative relapse of respiratory infection, one with positive blood cultures, ceftazidime-avibactam treatment yielded a favourable outcome. 12 months after transplantation, one patient presented an excellent clinical outcome. However, the other patient died 10 months later due to severe B. cepacia sinusitis with intracranial invasion.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Azabicyclo Compounds/therapeutic use , Burkholderia cepacia complex/drug effects , Ceftazidime/therapeutic use , Drug Resistance, Multiple, Bacterial , Lung Transplantation , Adult , Burkholderia cepacia complex/isolation & purification , Cystic Fibrosis/etiology , Drug Combinations , Humans , Male , Treatment OutcomeABSTRACT
INTRODUCTION: Long-term survival of lung transplantation (LT) patients is mainly limited by the development of chronic lung allograft dysfunction (CLAD). Lung retransplantation (LR) is an alternative for a selected population. The aim of this study was to review the LR experience in our center. PATIENTS AND METHODS: We conducted a retrospective study of patients undergoing LR between August 1990 and July 2017. RESULTS: Fourteen LR out of a total of 998 (1.4%) LT were performed. Twelve patients (85.7%) underwent LR due to CLAD: 10 (71.4%) because of bronchiolitis obliterans syndrome and 2 (14.3%) due to restrictive allograft syndrome. LR was performed in 2 patients within 30 days of the first LT. In those who underwent LR due to CLAD, mean time between the first LT and LR was 48 months, and mean duration of invasive mechanical ventilation was 32 days. The increase in FEV1 after LR was 24±18%. The best spirometry values were observed after 7.3 months. Mean survival of the cohort was 43.8 months. In patients with bronchiolitis obliterans syndrome, mean survival was 63.4 months, while in those with restrictive allograft syndrome, it was 19.5 months. Only 1 of the 2 early LR patients survived. CONCLUSION: LR is a therapeutic option in selected patients with CLAD, with acceptable survival. Indication for LR early after LT shows poor outcomes.
Subject(s)
Bronchiolitis Obliterans/surgery , Lung Transplantation , Primary Graft Dysfunction/surgery , Adolescent , Adult , Chronic Disease , Female , Hospital Units , Humans , Male , Middle Aged , Reoperation , Retrospective Studies , Spain , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: The aim of this study was to compare the pharmacokinetic profile, tolerability, and safety of a novel once-daily extended-release formulation of tacrolimus (LCPT) with that of once-daily prolonged-release tacrolimus (ODT) in stable adult lung transplant (LT) recipients. METHODS: Phase II, open-label, single-arm, single-center, prospective pilot pharmacokinetic study. Study population comprised 20 stable LT recipients receiving ODT, mean age 55.9 years (range, 38-67 years), 13 (65%) men. Patients were switched to LCPT in a 1:0.7 (mg/mg) conversion dose. Follow-up was 6 months, and cystic fibrosis patients were excluded. Two 24-hour pharmacokinetic profiles were obtained for each patient, the first on day -14 and the second on day +14 after switching to LCPT. Pharmacokinetic parameters and safety were compared. RESULTS: Mean (SD) area under the concentration-time curve from 0 to 24 hours was 253.97 (61.90) ng/mL per hour for ODT and 282.44 (68.2) ng/mL per hour for LCPT. Systemic exposure was similar in both (Schuirmann two 1-sided test). Mean (SD) dose was 5.05 (1.67) mg in ODT and 3.36 (1.03) mg in LCPT (P = 0.0002). Time to maximum concentration was 125 minutes for ODT and 325 minutes for LCPT (P < 0.001). Correlation between area under the concentration-time curve from 0 to 24 hours and C24 was 0.896 (r) for ODT and 0.893 (r) for LCPT. There were no differences in adverse effects. At 6 months, conversion dose was 1:0.59 (mg/mg) in patients with unchanged minimum plasma concentration target levels. CONCLUSIONS: Switching from ODT to LCPT was safe and well tolerated in stable LT recipients without cystic fibrosis. A significantly lower dose of LCPT allows similar bioavailability. A conversion ratio 1:0.6 could be enough to maintain similar target levels.