Lung transplantation is the only definitive mode of treatment for many forms of endstage pulmonary diseases; however, its success may be limited by several factors, including infections, acute rejection (AR), and chronic graft dysfunction termed bronchiolitis obliterans syndrome (BOS). Viral infections of the graft (including those from community acquired respiratory viruses and from persistently infecting viruses, such as herpesviruses) are responsible for organ infection/disease; in addition to direct sequelae, accumulating data suggest that viruses may be triggers for a cascade of events, including upregulation of allo-reactive cells, potentially leading to AR or chronic graft dysfunction. Community acquired respiratory viruses (CARV) have been increasingly recognized as common pathogens in lung transplantation (LT) and include the paramyxoviridae (respiratory syncytial virus, parainfluenza virus, human metapneumovirus), the orthomyxoviridae (influenza A and B), the picornaviridae (rhinovirus, enterovirus), the coronaviridae (coronavirus) and the adenoviridae (adenovirus). It has been suggested that LT recipients infected with CARV exhibit a high rate of progression to severe viral pneumonitis. Moreover, previous studies have evidenced that patients with CARV infection of the lower respiratory tract are predisposed to AR and high-grade BOS development, and, conversely, that patients with BOS are predisposed to CARV infections. Herpesviruses, mainly human cytomegalovirus (HCMV), are highly seroprevalent and are considered as potential pathogens causing direct and indirect effects in transplant recipients and establishing latency in various tissue, including lung. Whereas HCMV represents the main viral pathogen responsible for organ infection and disease, the role of other herpesviruses, including human herpesviruses 6 and 7 (HHV-6 and HHV-7) and Epstein-Barr virus (EBV) is less defined. The role of herpesviruses reactivation in LT in relation to the development of AR and chronic graft dysfunction remains controversial, as it seems that despite high viral loads detected in bronchoalveolar lavages (BAL), virus replication results not associated with the development of rejection, however data are conflicting and few studies have specifically investigated this issue. In this Chapter, the impact of viral pathogens, including CARV and persistently infecting viruses, on the clinical course and the onset of rejection and graft dysfunction will be analyzed reporting the results of the main studies published in literature and the experience of our Laboratory of Virology.
Impact of viral pathogens in lung transplant recipients
Costa C.;Bergallo M.;Solidoro P.;Cavallo R.
2011-01-01
Abstract
Lung transplantation is the only definitive mode of treatment for many forms of endstage pulmonary diseases; however, its success may be limited by several factors, including infections, acute rejection (AR), and chronic graft dysfunction termed bronchiolitis obliterans syndrome (BOS). Viral infections of the graft (including those from community acquired respiratory viruses and from persistently infecting viruses, such as herpesviruses) are responsible for organ infection/disease; in addition to direct sequelae, accumulating data suggest that viruses may be triggers for a cascade of events, including upregulation of allo-reactive cells, potentially leading to AR or chronic graft dysfunction. Community acquired respiratory viruses (CARV) have been increasingly recognized as common pathogens in lung transplantation (LT) and include the paramyxoviridae (respiratory syncytial virus, parainfluenza virus, human metapneumovirus), the orthomyxoviridae (influenza A and B), the picornaviridae (rhinovirus, enterovirus), the coronaviridae (coronavirus) and the adenoviridae (adenovirus). It has been suggested that LT recipients infected with CARV exhibit a high rate of progression to severe viral pneumonitis. Moreover, previous studies have evidenced that patients with CARV infection of the lower respiratory tract are predisposed to AR and high-grade BOS development, and, conversely, that patients with BOS are predisposed to CARV infections. Herpesviruses, mainly human cytomegalovirus (HCMV), are highly seroprevalent and are considered as potential pathogens causing direct and indirect effects in transplant recipients and establishing latency in various tissue, including lung. Whereas HCMV represents the main viral pathogen responsible for organ infection and disease, the role of other herpesviruses, including human herpesviruses 6 and 7 (HHV-6 and HHV-7) and Epstein-Barr virus (EBV) is less defined. The role of herpesviruses reactivation in LT in relation to the development of AR and chronic graft dysfunction remains controversial, as it seems that despite high viral loads detected in bronchoalveolar lavages (BAL), virus replication results not associated with the development of rejection, however data are conflicting and few studies have specifically investigated this issue. In this Chapter, the impact of viral pathogens, including CARV and persistently infecting viruses, on the clinical course and the onset of rejection and graft dysfunction will be analyzed reporting the results of the main studies published in literature and the experience of our Laboratory of Virology.
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