Pulmonary Transplant Recipients Research Articles

Bronchopulmonary Penetration of Isavuconazole in Pulmonary Transplant Recipients (PBISA01): Protocol for a Phase IV Clinical Trial With a Single Treatment Arm.

BackgroundAspergillosis is the most frequently observed invasive fungal disease (IFD) in lung transplant recipients. Isavuconazole (ISA) has shown a better safety profile and noninferiority to voriconazole in the treatment of patients with IFD.ObjectiveThe aim of this study is to describe the bronchopulmonary pharmacokinetic profile of oral ISA by analyzing the degree of penetration in the epithelial lining fluid and alveolar macrophages in patients receiving lung transplantation with a diagnosis of IFD.MethodsA total of 12 patients aged ≥18 years receiving a lung transplant with an IFD diagnosis and indication for ISA treatment and follow-up bronchoscopy will be included in the study. After 5 days of treatment with ISA and before the treatment is discontinued, the patients will be randomized (1:1:1:1) to perform the scheduled bronchoscopy at various times after the administration of ISA (2, 4, 8, and 12 hours). In total, 4 blood samples will be obtained per patient: at 72 hours after treatment initiation, on the day of the bronchoscopy, at the time of the bronchoalveolar lavage (simultaneously), and at 7 days after treatment initiation, to analyze tacrolimus and ISA plasma levels. ISA concentrations will be measured in plasma, epithelial lining fluid, and alveolar macrophages by a high-performance liquid chromatography/UV coupled to fluorescence method.ResultsEnrollment for the PBISA01 trial began in October 2020 and was completed in October 2021. All samples will be analyzed once recruitment is complete, and the results are expected to be published in October 2022.ConclusionsThere are no clinical studies that analyze the bronchopulmonary penetration of ISA. Bronchoalveolar lavage performed routinely in the follow-up of lung transplant recipients constitutes an opportunity to analyze the bronchopulmonary penetration of ISA.Trial RegistrationEuropean Clinical Trials Register 2019-004240-30; www.clinicaltrialsregister.eu/ctr-search/trial/2019-004240-30/ESInternational Registered Report Identifier (IRRID)DERR1-10.2196/37275

Allograft Involvement by Lymphoproliferative Disorders after Lung Transplantation: Report from the PTLD.Int Survey

Few cases of graft posttransplant lymphoproliferative disease (PTLD) in pulmonary transplant recipients have been reported. Published data on PTLD are pooled to analyze and compare characteristics, predictors, and prognosis of pulmonary PTLDs arising in lung allograft recipients. PubMed and Google Scholar were searched for reports of lymphoproliferative disorders occurring within the graft in lung transplant recipients. Data from 23 studies were pooled and analyzed. Data from 137 patients (61 graft locations) with PTLD after lung transplantation were analyzed. Lung recipients with pulmonary graft PTLD were significantly more likely to have early-onset PTLD (70% vs 31%, respectively; P<.001). Lung graft PTLD also was associated with having tested negative for infection with Epstein-Barr virus before transplantation (P=.05). Log-rank test showed significantly higher survival rates for pulmonary transplant recipients with allograft complication than for recipients with PTLD elsewhere (P=.02). Pulmonary transplant recipients who show early symptoms of impaired graft function should be evaluated for a potential lung graft PTLD in addition to being assessed for risk of rejection. Further prospective studies with large populations of patients are needed to confirm these results.

Allograft involvement by lymphoproliferative disorders after lung transplantation: report from the PTLD. Int survey

Few cases of graft posttransplant lymphoproliferative disease (PTLD) in pulmonary transplant recipients have been reported. Published data on PTLD are pooled to analyze and compare characteristics, predictors, and prognosis of pulmonary PTLDs arising in lung allograft recipients. PubMed and Google Scholar were searched for reports of lymphoproliferative disorders occurring within the graft in lung transplant recipients. Data from 23 studies were pooled and analyzed. Data from 137 patients (61 graft locations) with PTLD after lung transplantation were analyzed. Lung recipients with pulmonary graft PTLD were significantly more likely to have early-onset PTLD (70% vs 31%, respectively; P<.001). Lung graft PTLD also was associated with having tested negative for infection with Epstein-Barr virus before transplantation (P=.05). Log-rank test showed significantly higher survival rates for pulmonary transplant recipients with allograft complication than for recipients with PTLD elsewhere (P=.02). Pulmonary transplant recipients who show early symptoms of impaired graft function should be evaluated for a potential lung graft PTLD in addition to being assessed for risk of rejection. Further prospective studies with large populations of patients are needed to confirm these results.

O.2.5 Human cytomegalovirus (HCMV) compartmentalization in pulmonary transplant recipients

O.2.5 Human cytomegalovirus (HCMV) compartmentalization in pulmonary transplant recipients

Post-transplant changes in exhaled nitric oxide (eNO) of pulmonary transplant recipients and the influence of mycophenolate (MMF)

The role of eNO in lung transplantation has emerged as a useful marker for allograft airway inflammation. eNO is produced by nitric oxide synthases including iNOS. This enzyme isoform is inhibited by Mycophenolate (MMF) in endothelial cells (Senda, 1995, Transplantation). It is not known if MMF can inhibit human respiratory epithelial iNOS. We therefore assessed the changes in eNO post-transplant and compared differences in eNO and lung function between patients treated with MMF and azathioprine (AZA). Methods; 28 lung transplant recipients entered into a randomised multi-centre trial of MMF vs. AZA were followed over 1 year. Single breath eNO was measured by chemi-luminescence within the first 10 days post op, 1 month and then at 3 monthly intervals as was lung function. We used a Logan LR 2000; a clinically significant intra-patient change is 2-3ppb using this method. 16 received MMF and 12 AZA (14 females and 14 males). There were no baseline differences in the eNO between MMF and AZA groups. There was a significantly lower first eNO (within 10 days of transplant) than at 1 month, 3 months and 6 months that was clinically and statistically significant (paired t-test); difference of means 3ppb p=0.002, 3 ppb p=0.002, 2.5 ppb p=0.001 respectively. There were no statistical nor clinically significant differences in eNO between any of the other time-points. There were no differences in FEV1 between MMF and AZA groups at any time point. eNO levels are depressed in the immediate post-transplant period but rise to baseline levels by one month possibly reflecting changes in immunosuppressant regimens. Researchers assessing eNO in pulmonary transplant recipients should not use early post-op eNO levels to establish a patients baseline. Treatment with MMF does not appear to reduce eNO levels or improve lung function at 1 year in pulmonary transplant recipients as compared to those treated with AZA. The long term follow up of these patients and the rates of chronic rejection are however awaited with interest.

Incidence and outcome of major non-pulmonary surgical procedures in lung transplant recipients.

Pulmonary transplant recipients are at high risk from various conditions requiring surgical intervention. As little is known about their exact incidence and course, we examined such procedures in detail. We have retrospectively analyzed major nonpulmonary surgical procedures performed in 124 consecutive patients who received an isolated lung transplant at the University of Vienna between 1989 and December 1995. Twenty-two patients underwent a total of 28 major interventions (22/124 = 17.7%), resulting in an incidence of one procedure every 5.8 patient years of follow-up. The mean interval between transplantation and intervention was 17.9 months (range 3 days to 62 months) with six interventions being carried out during the first month after transplantation. Fourteen emergency operations were performed, the remaining 14 procedures were carried out electively. Overall, 15 abdominal procedures, four thoracic, four orthopedic, two gynecological, one neurosurgical, one urological and one plastic surgery were performed. There was no intraoperative death. Perioperatively, five surgery related deaths were observed (5/28, related mortality 17.9%) with multiple organ failure as the cause of death in all cases. All of these deaths followed emergency operations (5/14 = 35.7%) and all were observed in patients with septic abdominal complications. In contrast, even very extensive procedures were performed electively without related mortality (0/14, P = 0.02). During the first month after transplantation, major surgery was associated with a 50% (3/6) mortality, for late interventions mortality was 9.1% (2/22; P = 0.047). Pulmonary transplant recipients showed a high incidence of conditions requiring surgical intervention. As expected, septic complications, especially during the immediate post transplant period, carried a very poor prognosis. However, it was reassuring to observe that even extensive surgical procedures could be performed safely without associated mortality in the elective setting.

Detection of Cytomegalovirus in Lung Allografts: Comparison of Histologic and Immunohistochemical Findings

Although the histologic manifestation of cytomegalovirus (CMV) is usually characteristic intracellular inclusions and cytomegaly, some investigators, using immunohistochemical or in situ hybridization techniques, have demonstrated the presence of histologically occult infections in certain tissues. A series of lung biopsy specimens from pulmonary transplant recipients were studied using a monoclonal antibody (CCH2) to CMV early viral antigen and the results were compared with routine histologic findings. Occult infection could not be demonstrated in any of these cases. These results may reflect the relative sensitivity of the monoclonal antibody used in this study, although other possible factors are discussed. The results suggest that, in lung allograft biopsy specimens, immunohistochemical analysis using monoclonal antibody CCH2 is not likely to increase significantly the yield of positive cases compared with examination of multiple levels of hematoxylin-and-eosin-stained sections. Additional studies are needed to compare the sensitivity of monoclonal antibodies to CMV antigens using a variety of sampling techniques and clinical settings.

Cyclosporine-associated hypertension in cardiopulmonary transplantation. The beneficial effect of nifedipine on renal function.

In a retrospective review of fifty heart, lung, and heart-lung recipients receiving cyclosporine, forty-six (92%) were hypertensive. This hypertension was managed with either prazosin (n = 29) or nifedipine (n = 17). Renal function was assessed by creatinine clearance estimation and found to be significantly better in those patients receiving nifedipine. (creatinine clearance = 60 ml/min [SEM 5.7] vs. 49 ml/min [SEM 2.7]; P less than 0.05). This observation suggests that nifedipine should be the drug of choice for the treatment of cyclosporine-associated hypertension in cardiac and pulmonary transplant recipients.