Treatment of severe acute lung allograft rejection with OKT3 and temporary extracorporeal membrane oxygenation bridging.

OBJECTIVES: The use of OKT3 for treatment of advanced high-grade acute rejection episodes eventually can result in cytokine release and consecutive pulmonary edema. Temporary extracorporeal membrane oxygenation (ECMO) bridging can be used to overcome this crucial period before the beneficial effects of OKT3 can be observed. METHODS: We summarize our experience with three patients, who underwent lung transplantation and presented with severe acute rejection episodes. OKT3 had to be initiated due to insufficient response to standard rejection therapy with corticosteroids. Upon initiation of OKT3 treatment, a massive life-threatening deterioration of lung function in spite of heavily invasive respirator treatment was seen and temporary ECMO support was imperative to support graft function. Results of this treatment were retrospectively reviewed. RESULTS: In all cases femoro-femoral veno-arterial ECMO was used for support of the impaired graft and after a period of 4-5 days led to a massive improvement of graft function. In the further course two patients could be discharged from hospital and are still alive 30 and 36 months, respectively, after the described incident. One patient died 4 months later due to liver failure. CONCLUSIONS: We conclude that the use of ECMO support in patients experiencing significant side effects from OKT3 therapy is a useful and effective therapeutic tool to overcome the initial critical period until the lung has sufficiently recovered.     

Analysis of cytokine pattern in exhaled breath condensate of lung transplant recipients with bronchiolitis obliterans syndrome

Introduction  

Exhaled breath condensate (EBC) analysis is a promising method for investigating airway pathology. In this pilot study we tested the cytokine pattern of EBC of lung transplant patients with and without clinical evidence of bronchiolitis obliterans syndrome (BOS).     

Initial experience with oral valganciclovir for pre-emptive cytomegalovirus therapy after lung transplantation

BACKGROUND: The most common opportunistic viral pathogen after lung transplantation is cytomegalovirus (CMV). Oral valganciclovir, a prodrug of ganciclovir, has been introduced as a potential drug for prophylaxis and treatment of CMV infection and disease in lung transplantation. The goal of this study was to describe our initial experience with oral valganciclovir for pre-emptive treatment of CMV infections after lung transplantation. METHODS AND PATIENTS: We summarize our experience with 19 patients who underwent lung transplantation and received pre-emptive oral valganciclovir therapy in the situation of positive CMV polymerase chain reaction (PCR) in either plasma or bronchoalveolar lavage. None of the patients presented with manifest CMV disease. Treatment dosage of valganciclovir was 450 mg to 1800 mg daily, depending on renal function and white blood count. Treatment was continued until the CMV PCR became negative, in any case for a period of at least 14 days. RESULTS: Three patients received two courses of pre-emptive oral valganciclovir; 16 patients were treated once. Eleven patients (57.9%) were treated because of a positive plasma CMV PCR; in eight patients (42.1%) the PCR was positive only in bronchoalveolar lavage. Therapy was initiated 896 +/- 1186 days (range, 108-3911) after transplantation with a mean CMV PCR of 45,536 +/- 149,294 copies (range, 426-706,000). In all cases the PCR fell below detectability (<400 copies) after a period of 22 +/- 10 days of treatment (range, 7-50 days). Mild to moderate leucopenia was observed in seven patients (36.8%) during treatment. None of the patients developed new onset of other potentially drug-related disorders such as neutropenia, anemia, deterioration of renal function or gastrointestinal disorder. CONCLUSIONS: Pre-emptive therapy with oral valganciclovir for CMV infections detected by PCR in either plasma or bronchoalveolar lavage after lung transplantation seems to be efficacious and safe. However, regular blood counts should be performed to detect developing leucopenia.     

Influence of condensing equipment and temperature on exhaled breath condensate pH, total protein and leukotriene concentrations

BACKGROUND: Exhaled breath condensate analysis is an attractive but still not fully standardised method for investigating airway pathology. Adherence of biomarkers to various condensing surfaces and changes in condensing temperature has been considered to be responsible for the variability of the results. Our aims were to compare the efficacy of different types of condensers and to test the influence of condensing temperature on condensate composition. METHODS: Breath condensates from 12 healthy persons were collected in two settings: (1) by using three condensers of different type (EcoScreen, R-Tube, Anacon) and (2) by using R-Tube condenser either cooled to -20 or -70 degrees C. Condensate pH at standardised CO(2) level was determined; protein content was measured by the Bradford method and leukotrienes by EIA. RESULTS: Breath condensates collected using EcoScreen were more alkaline (6.45+/-0.20 vs. 6.19+/-0.23, p<0.05 and 6.10+/-0.26, p<0.001) and contained more protein (3.89+/-2.03 vs. 2.65+/-1.98, n.s. and 1.88+/-1.99 microg/ml, p<0.004) as compared to the other devices. Only parameters obtained with R-Tube and Anacon correlated. Condensing temperature affected condensate pH (5.99+/-0.20 at -20 degrees C and 5.82+/-0.07 at -70 degrees C, p<0.05) but not protein content. Leukotriene B(4) was not found in any sample and cysteinyl-leukotriene was not found in condensates collected with R-Tube or Anacon. CONCLUSION: Condenser type influences sample pH, total protein content and cysteinyl-leukotriene concentration. Condensing temperature influences condensate pH but not total protein content. These results suggest that adherence of the biomarkers to condenser surface and condensing temperature may play a role but does not fully explain the variability of EBC biomarker levels.     

Launching the Hungarian Lung Transplantation Program

The first successful lung transplantation was done in 1963 by James Hardy in the United States. The Vienna Lung Transplant program was launched in 1989 by Professor Walter Klepetko, and in 1996 lung transplantation became available in this center also for Hungarian patients. By 2013, conditions for full-scale Hungarian lung transplantation program were ripe. The Hungarian government invested 3 million Euros for infrastructural developments that made the operation and the perioperative care available. Besides funding, the professional training of medical personnel was also essential for this program to start. Hungarian specialists have had internship opportunities to study all aspects of lung transplantation at the Thoracic Surgery Department in Vienna. After successful preparations, the first lung transplantation in Hungary was performed on December 12, 2015.     

Bronchiolitis obliterans syndrome in lung transplant recipients

Bronchiolitis obliterans syndrome in lung transplant recipients. The leading cause of late graft loss after lung transplantation is bronchiolitis obliterans syndrome. The process is a manifestation of chronic rejection, and is characterized by an excessive fibroproliferation in the small airways, leading progressively to luminal obliteration and graft injury. Both alloantigen-dependent (acute rejection, histocompatibility) and alloantigen-independent (ischaemia-reperfusion injury, cytomegalovirus infection, gastroesophageal reflux disease) risk factors may contribute to the development of the disease. Early in the process, damage to the airway epithelium occurs, which then triggers a massive influx of alloreactive T-cells into the graft tissue. Activated T-cells release a wide range of cytokines and growth factors, which in turn are capable of stimulating cellular proliferation and matrix protein synthesis in fibroblasts as well as in airway smooth muscle cells. Clinically, a decline in lung functions together with nonspecific symptoms can usually be observed in these patients, while later in the disease course recurrent respiratory tract infections are more common. Up till now, no effective therapy is available for bronchiolitis obliterans syndrome, however, certain immunosuppressive regimens may slow down the progression of the disease.     

Severe mixed sleep apnea after bilateral lung transplantation in a cystic fibrosis patient: a case report

Background

Lung transplantation is the only treatment for end-stage lung disease in selected patients. After lung transplantation, patient recovery is often slow owing to severe underlying diseases in the patient producing hypoxemia before, during, and after surgery, as well as infections and rejection episodes. Postoperative breathing and ventillatory disorders are also associated with diaphragmatic dysfunction and/or phrenic nerve damage.

Methods

Herein we have reported a case of a 35-year-old man undergoing bilateral lung transplantation owing to worsening of chronic respiratory failure from cystic fibrosis. After uncomplicated surgery, weaning was delayed due to nighttime dyspnea and hypoxemia attributed to diaphragm dysfunction. After improvement of diaphragm function, the symptoms persisted, requiring noninvasive nocturnal ventilatory support. Polysomnography confirmed severe mixed sleep apnea.

Results

Effective treatment with noninvasive bi-level positive airway pressure spontaneous/timed mode (BiPAP S/T) ventilation during the nights rendered the patient symptom free. Polysomnography confirmed successful treatment.

Conclusion

Disordered breathing while sleeping is common after solid organ transplantation. BiPAP S/T ventilator therapy was effective to the treat dominantly central sleep apnea in our patient.     

Airway pathogens during the first year after lung transplantation: a single-center experience

After lung transplantation, a high level of immunosuppression is needed to prevent rejection. This demand renders recipients more sensitive to infections. As pulmonary infections are a major clinical problem during the first postoperative year after lung transplantation, preventive treatment and regular surveillance examinations are needed for immediate, adequate therapy. We describe the airway pathogens registered during the first posttransplantation year among our 12 lung transplant recipients since December 2008. Samples were obtained for microbiologic analysis from the upper and lower respiratory tracts and from serum as part of routine care. During the first year after transplantation the most frequent pathogens were fungi (Candida albicans 82%; Aspergillus 50%), Pneumocystis (8%), gram-negative bacteria (Pseudomonas spp 60%; Klebsiella 25%, Acinetobacter 17%; Escherichia Coli 17%; and Enterococcus faecalis 25%), and Staphylococcus aureus (50%, including methicillin-resistant strains 25%). This pathogen spectrum in the first postoperative year after lung transplantation was similar to other centers. Colonization with Pseudomonas or fungi presented early and was prevalent among our patients.     

Cytomegalovirus infection after solid-organ transplantation, its risk factors, direct and indirect effects and prevention strategies

The human cytomegalovirus is widely prevalent among human population and it is the most common viral pathogen that affects both the graft's and solid-organ transplant recipient's survival. The risk is highest in donor-seropositive, recipient-seronegative pairing transplantation. These recipients carry increased risk of developing symptomatic primary CMV infection; however, other risk factors may have an impact on cytomegalovirus activation as well: intensity of immunosuppression, type of organ transplanted, rejection and/or treatment for rejection, HLA-mismatch between recipient and donor, certain HLA-types of the recipient, female sex etc. Cytomegalovirus infection in transplant patients has been associated with both direct (symptoms) and indirect effects which are derived from the immunomodulating impact of the virus such as cellular effects and cytokine expression or systemic immune suppression leading to other opportunistic infections. Prevention of the direct and indirect effects of cytomegalovirus infection is the therapeutic goal in transplanted patients. Most transplant centers use either universal prophylaxis or preemptive therapy to prevent the infection. The advantages and disadvantages of these two preventive strategies and current evidence-based recommendations for preventing cytomegalovirus disease in solid-organ transplant recipients are discussed according to others' and the authors' own observations. According to recommendations of the American and Canadian Societies of Transplantation, most of the centers--after analyzing of the CMV-infection risk factors of the recipients--divide them into three groups: high-, moderate- and low-risk groups. The preventive strategy is attached to the risk-group type. In the high-risk group (R-/D+ and lung transplant patients) the use of the universal prophylaxis is necessary. The patients administered anti-lymphocyte antibodies (ATG, ALG or OKT3) need selective (subtype of universal) prophylaxis. Among the moderate-risk patients (R+/D+ or R+/D-) the doctors may choose either universal prophylaxis or preemptive therapy. Selection of a strategy requires consideration of patient-specific factors as well as practical considerations such as available resources. For avoidance of the indirect effects of CMV infection universal prophylaxis is preferred. The use of preventive proceedings in low-risk patients is the matter of the center's decision.