Lung allocation score: The Eurotransplant model versus the revised US model - a cross-sectional study

Both Eurotransplant (ET) and the US use the lung allocation score (LAS) to allocate donor lungs. In 2015, the US implemented a new algorithm for calculating the score while ET has fine-tuned the original model using business rules. A comparison of both models in a contemporary patient cohort was performed. The rank positions and the correlation between both scores were calculated for all patients on the active waiting list in ET. On February 6th 2017, 581 patients were actively listed on the lung transplant waiting list. The median LAS values were 32.56 and 32.70 in ET and the US, respectively. The overall correlation coefficient between both scores was 0.71. Forty-three per cent of the patients had a < 2 point change in their LAS. US LAS was more than two points lower for 41% and more than two points higher for 16% of the patients. Median ranks and the 90th percentiles for all diagnosis groups did not differ between both scores. Implementing the 2015 US LAS model would not significantly alter the current waiting list in ET

Immunological risk stratification of the bronchiolitis obliterans syndrome after lung transplantation

The development of chronic allograft rejection after lung transplantation (LTx) is the most common cause of poor long-term survival in lung transplant recipients. This rejection leads to obliteration of the bronchioli. Since this obliteration has a patchy distribution and normal lung tissue obtained by a transbronchial biopsy does not exclude rejection, a surrogate marker based on lung function decline is currently the gold standard: the presence of bronchiolitis obliterans syndrome (BOS). The exact mechanism of BOS is unknown but repetitive damage of (sub) epithelial cells seems important and may lead to a response from the immune system and eventually inflammation. Due to this response markers may be elevated or decreased. This thesis describes the identification of patients who are at risk for developing BOS using blood samples obtained during regular follow up visits. CD30 is expressed on Th2 cells and a soluble form (sCD30) is shed into the blood if Th2 cells are activated. In contrast to values prior to LTx, we demonstrated that sCD30 values after lung transplantation did not discriminate patients developing BOS. However, we demonstrated that high sCD30 values before LTx were suppressed after transplantation. We hypothesized that immunosuppressive drugs suppressed sCD30 values and demonstrated in atopic dermatitis (AD) patients, a mainly Th2 associated disease, that the immunosuppressive drug enteric coated mycophenolate sodium (EC-MPS) but not cyclosporine (CsA) indeed do suppress sCD30 values. The chemokine TARC binds to CCR4 expressed on Th2 cells. We demonstrated that TARC levels in patients developing BOS were lower compared to non-BOS patients. If TARC values were below the 325 pg/ml at the first month after LTx there is an increased risk of developing BOS. In our cohort of AD patients we demonstrated a correlation between TARC levels and parameters to evaluate disease activity not only during EC-MPS treatment but also during CsA. The mannose binding lectin (MBL) is an important player in innate immunity and plays a role in the elimination of viruses and bacteria. We demonstrated a correlation between low MBL values before and CMV reactivation after LTx. There was a trend between low MBL levels before transplantation and a superior survival rate after transplantation. No association was found between MBL values and the development of BOS. Natural Killer (NK) cells are one of the main cellular components of the innate immunity and play a role in the lysis of viral infected cells. The action of NK cells is controlled by activating and inhitory Killer Immunoglobulin-like receptors (KIRs). We demonstrated that KIR gene content of recipients, escpecially activating KIRs, is associated with BOS but not with the reactivation of CMV. In conclusion we found that MBL values, KIR genotype and TARC values are associated with the development of BOS and that the type of immune suppressive regimen applied after LTx may influence the applicability of possible biomarkers

Soluble CD30 measured after lung transplantation does not predict bronchiolitis obliterans syndrome in a tacrolimus/mycophenolate mofetil-based immunosuppressive regimen

BACKGROUND: The purpose of this study was to determine the utility of post-transplant serum soluble CD30 levels as a biomarker for the development of the bronchiolitis obliterans syndrome (BOS) after lung transplantation during a tacrolimus/mycophenolate mofetil-based regimen. METHODS: Soluble CD30 (sCD30) concentrations were measured prior to transplantation and in 175 samples taken after transplantation in 7 patients developing BOS and 7 non-BOS patients closely matched for age, underlying diseases, follow-up and gender. RESULTS: High pre-transplant sCD30 levels dropped significantly after lung transplantation, but in the post-transplant samples no differences could be detected between patients developing BOS or not, and no changes were found prior to or during the development of BOS. CONCLUSIONS: After transplantation, sCD30 levels are consistently suppressed, but BOS is not prevented, indicating that sCD30 cannot be used as a biomarker to predict BOS after transplantation in the regimen employed

Serum thymus and activation regulated chemokine levels post-lung transplantation as a predictor for the bronchiolitis obliterans syndrome.

The main reason for mortality after lung transplantation is the bronchiolitis obliterans syndrome (BOS), which represents chronic rejection. As soluble CD30, which is produced mainly by activated T helper 2 (Th2) cells, was shown to be related to development of BOS, we aimed to investigate the relation between development of BOS and Th2 chemoattractant thymus and activation regulated chemokine (TARC/CCL17). In 54 patients we measured serum TARC levels prior to transplantation by enzyme-linked immunosorbent assay, and in 44 of these patients sera were analysed at months 1, 2 and 3 after lung transplantation. In addition, longitudinal measurements were performed in sera from eight healthy controls and 14 patients, the latter taken over a period of 2 years post-transplantation from seven patients developing BOS plus seven clinically matched BOS-free patients. Median serum TARC levels post-transplantation of patients who developed BOS were significantly lower than those of the matched BOS-free patients (P = 0·05). A receiver operating characteristics analysis (area under the curve 0·77), together with a Kaplan–Meyer analysis, showed that serum TARC levels below 325 pg/ml in the first month post-transplantation can predict development of BOS post-transplantation (P = 0·001). In contrast, pretransplant serum TARC levels were not significantly different between patients developing BOS, BOS-free patients or healthy controls. In conclusion, pretransplantation serum TARC levels do not predict the development of BOS post-transplantation, but measurement of the serum TARC levels in the first month directly after transplantation can provide us with a tool to identify the group at risk of developing BOS

Polarization-sensitive imaging of diseased and healthy lungs with histological validation

Polarization-sensitive optical coherence tomography has been used to image two healthy and four diseased lungs ex vivo together with histology. Differences between lungs were found in alveoli size and airway smooth muscle thickness

Polarization-sensitive imaging of diseased and healthy lungs with histological validation

Polarization-sensitive optical coherence tomography has been used to image two healthy and four diseased lungs ex vivo together with histology. Differences between lungs were found in alveoli size and airway smooth muscle thickness