Respiratory Viruses in Lung Transplant Recipients: A Critical Review and Pooled Analysis of Clinical Studies

Abstract

Lung transplant recipients present an increased risk for severe complications associated with respiratory infections. We conducted a review of the literature examining the clinical relationship between viral respiratory infection and graft complications. Thirty-four studies describing the clinical impact of influenza, respiratory syncytial virus, parainfluenza, human metapneumovirus, rhinovirus, enterovirus, coronavirus, bocavirus or adenovirus were identified. The detection rate of respiratory viral infection ranged from 1.4% to 60%. Viruses were detected five times more frequently when respiratory symptoms were present [odds ratio (OR) = 4.97; 95% CI = 2.11-11.68]. Based on available observations, we could not observe an association between respiratory viral infection and acute rejection (OR = 1.35; 95% CI = 0.41-4.43). We found a pooled incidence of 18% (9/50) of bronchiolitis obliterans syndrome (BOS) in virus-positive cases compared to 11.6% (37/319) in virus-negative cases; however, limited number of BOS events did not allow to confirm the association. Our review confirms a causal relationship between respiratory viruses and respiratory symptoms, but cannot confirm a link between respiratory viruses and acute lung rejection. This is related in part to the heterogeneity and limitations of available studies. The link with BOS needs also to be reassessed in appropriate prospective studies.

Clinical features of post-infectious bronchiolitis obliterans in children undergoing long-term azithromycin treatment

“…The causal agents of BO include adenovirus, influenza virus, measles virus and Mycoplasma pneumoniae (13). Adenovirus is the leading infectious cause of BO worldwide (14). In the present study, 37.5% of patients (6/16) were infected with adenovirus.…”

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

“…The occurrence of adenoviremia has been reported to be less than 10% of adult patients after kidney, heart, or liver transplantation; although the symptoms of HAdV infection are usually mild, and invasive infection does not correlate with organ rejection (157), severe and even fatal courses have also been described (158,159). Studies in patients undergoing lung transplantation showed that pulmonary infection with HAdV can correlate with significantly elevated rates of rejection, bronchiolitis obliterans, and mortality (160)(161)(162). In line with the epidemiology of HAdV infections, detection of this virus appears to be more common in pediatric SOT recipients (155,163), with reported rates of HAdV infection ranging from 3.5% to 38% after liver transplantation (164,165), from 7% to 50% after lung and heart transplantation (166)(167)(168), and from 4% to 57% after intestinal or multivisceral transplantation (169,170).…”

Small airways diseases, excluding asthma and COPD: an overview

“…Cytomegalovirus (CMV) pneumonia and CMV mismatch between CMV-positive donor and CMV-negative receivers have been associated with BOS in some [100], but not all, studies [101]. Community-acquired respiratory virus infections have also been associated with BOS [102], although a recent meta-analysis did not confirm this association [103], probably due to the heterogeneity of published studies. Gastro-oesophageal reflux disease (GORD) is a risk factor for BOS and retrospective studies suggest that surgical fundoplication in the first 3 months after transplantation prevents BOS [104], and that fundoplication may improve lung function in patients with established BOS [105].…”