Update on viral infections in lung transplantation

Center for Allogeneic Stem Cell Transplantation, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Current opinion in pulmonary medicine (Impact Factor: 2.76). 03/2012; 18(3):264-70. DOI: 10.1097/MCP.0b013e3283521066
Source: PubMed


Lung transplantation is an established therapeutic option for patients with severe respiratory insufficiency. Graft dysfunction or rejection depends on the orchestrated prevention of infection(s) and the level of immune suppression. More recent reports underlined the role and pathogenicity of cytomegalovirus (CMV) infection in lung transplant recipients and the double-edged sword of maintaining antiviral immune responses versus guided immune suppression to avoid graft rejection. We present data concerning the nature of the cellular response to Epstein-Barr virus (EBV) and CMV, the subsequent use of cellular therapy in antiviral treatment modalities and discuss the role of H1N1 infection and other viral infections in lung transplantation recipients.
Patients after lung transplantation showed a similar susceptibility to H1N1 infections as compared to the local, healthy community. After initial recovery and oseltamivir treatment, lung transplantation patients developed bronchiolitis obliterans syndrome. The genetic background of lung transplant recipients, defined by polymorphism in immune molecules, contributes to increased risk of CMV disease; CMV induces local pro-inflammatory chemokines (CXCL10). Anti-CMV prophylaxis does not impact on anti-CMV-directed cellular immune responses, defined by IFNγ and TNFα production. Asymptomatic EBV carriers showed higher numbers of EBV-reactive T cells. High EBV load carriers showed T cells with immune-exhaustion markers and decreased IFNγ production. Anti-CMV-directed cellular therapy may aid to better manage CMV-associated complications after lung transplantation.
Pharmacological immune suppression, the genetic makeup of the patient as well as concurrent viral infections impact on the successful outcome of lung transplantation and call for more detailed immune-guided diagnostics and therapy.

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    ABSTRACT: Lung transplantation is the final treatment option in the end stage of certain lung diseases, once all possible conservative treatments have been exhausted. Depending on the indication for which lung transplantation is performed, it can improve the patient's quality of life (e.g., in emphysema) and/ or prolong life expectancy (e.g., in cystic fibrosis, pulmonary fibrosis, and pulmonary arterial hypertension). The main selection criteria for transplant candidates, aside from the underlying pulmonary or cardiopulmonary disease, are age, degree of mobility, nutritional and muscular condition, and concurrent extrapulmonary disease. The pool of willing organ donors is shrinking, and every sixth candidate for lung transplantation now dies while on the waiting list. We reviewed pertinent articles (up to October 2013) retrieved by a selective search in Medline and other German and international databases, including those of the International Society for Heart and Lung Transplantation (ISHLT), Eurotransplant, the German Institute for Applied Quality Promotion and Research in Health-Care (Institut für angewandte Qualitätsförderung und Forschung im Gesundheitswesen, AQUA-Institut), and the German Foundation for Organ Transplantation (Deutsche Stiftung Organtransplantation, DSO). The short- and long-term results have markedly improved in recent years: the 1-year survival rate has risen from 70.9% to 82.9%, and the 5-year survival rate from 46.9% to 59.6%. The 90-day mortality is 10.0%. The postoperative complications include acute (3.4%) and chronic (29.0%) transplant rejection, infections (38.0%), transplant failure (24.7%), airway complications (15.0%), malignant tumors (15.0%), cardiovascular events (10.9%), and other secondary extrapulmonary diseases (29.8%). Bilateral lung transplantation is superior to unilateral transplantation (5-year survival rate 57.3% versus 47.4%). Seamless integration of the various components of treatment will be essential for further improvements in outcome. In particular, the follow-up care of transplant recipients should always be provided in close cooperation with the transplant center.
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