Cytomegaloviral infection and other infections related to lung allograft survival

Purpose of review The use of better refined immunosuppression strategies and antimicrobial prophylaxis protocols in at-risk lung transplant recipients (LTR) has significantly reduced the burden of acute infection syndromes in the lung allograft. These strategies, however, have not eliminated the risk that infection poses for the lung allograft over time and particularly during periods of augmented immunosuppression. The purpose of this review is to focus on the potential for subclinical infection syndromes to negatively impact on lung allograft survival using human cytomegalovirus (HCMV) as an example of how improved diagnostic tools and therapeutic strategies can help us better understand and manage this problem. Recent findings Although early ganciclovir prophylaxis has dramatically reduced the occurrence of HCMV pneumonitis as a major infectious cause of early morbidity and mortality in LTR, subclinical HCMV reactivation is often detected in either the blood or bronchoalveolar lavage, and this has been associated with reduced long-term lung allograft survival. Increasingly, ongoing research has identified HCMV reactivation as both a marker of ongoing alloreactivity/inflammation and a significant contributor to these processes as evidenced by epidemiological association data and specific information from therapeutic intervention studies, respectively. The exact mechanisms underpinning these links are now beginning to be explored, and although they remain to be fully elucidated, both direct effects (viral cytopathogenic) and indirect effects (up-regulation of inflammatory milieu and specific CD8 immune control) are likely to be involved. Summary Initial clinical observations and recent molecular diagnostic tools have strongly focused both the qualitative and quantitative assessment of HCMV’s impact on lung allograft survival. The conceptual model of infection in the lung allograft that has evolved from these considerations now also gives us an excellent framework with which to better understand the interaction between the lung allograft and other relevant viral, bacterial, and fungal pathogens that may be both a marker of and a contributor to significant reductions in graft survival after lung transplantation.