Respiratory Syncytial Virus in Hematopoietic Cell Transplant Recipients: Factors Determining Progression to Lower Respiratory Tract Disease

Respiratory syncytial virus (RSV) is an important pathogen in infants and young children but is also important in the elderly and in individuals with chronic obstructive pulmonary disease (COPD). It was recognized 25 years ago that RSV can cause severe disease in immunocompromised patients, especially those having undergone allogeneic hematopoietic stem cell transplantation (HSCT) [1– 3]. The early publications on this subject reported a very high mortality during lower respiratory tract disease. It has also been shown that RSV is an important nosocomial pathogen; therefore, infection control measures are very important in HSCT units. Over the last 2 decades, several studies on risk factors and outcome of HSCT have been published, and the article by Kim et al [4] in this issue of the Journal of Infectious Diseases adds important new information on the topic. Kim et al [4] included both allogeneic and autologous HSCT recipients, and there was no difference in the risk of progression to lower respiratory tract disease. Other articles have suggested that autologous HSCT recipients have lower risk for poor outcome [5–7]. However, a recent publication shows no difference in the risk for lower respiratory tract disease or mortality [8]. These different results might have to do with different treatments given before autologous HSCT, such as the use of monoclonal antibodies, or the increasing age of patients undergoing autologous transplants in recent years, although in the study by Kim et al, age was not a risk factor for lower respiratory tract disease. Other risk factors for lower respiratory tract disease found in the study by Kim et al [4] were being a smoker, having received total body irradiation, and severe lymphocytopenia, <0.1 × 10/L at the time of RSV infection. Lymphocytopenia has also been identified as a risk factor for outcome of RSV infection in previous studies [6, 9], as has contracting an RSV infection before stem cell engraftment. An important finding by Kim et al is that there was a gradual risk increase for lower respiratory tract disease as the lymphocyte count at diagnosis of RSV infection decreased. Furthermore, an absolute lymphocyte count of >1.0 × 10/L was completely protective against progression to lower respiratory tract disease. This finding allows risk stratification and thereby helps in patient management and in recruiting patients for future studies. The negative effect of smoking is interesting, because it has not previously been documented in immunocompromised individuals. This finding fits, however, with knowledge obtained in other contexts. It is well known that RSV disease severity is increased in infants exposed to smoking in the household. It has also been shown in vitro that the inhibitory antiviral effect of interferon-γ against RSV messenger RNA (mRNA), and protein expression is decreased by cigarette smoke [10]. The major controversy in management of RSV infection remains the effects of therapy with ribavirin or immune globulin. There has been no controlled clinical study of sufficient size to allow conclusions regarding efficacy. There have been several reports, mostly retrospective, on ribavirin therapy for RSV infection [6–8, 12–16]. The only existing controlled trial of aerosolized ribavirin in HSCT recipients was only able to recruit 14 patients [11]. In this study, there was a trend for lower viral loads in the ribavirin treated patients but no differences in outcome. Assessment of the impact of ribavirin Received and accepted 16 December 2013; electronically published 23 December 2013. Correspondence: Per Ljungman, MD, PhD, Department of Hematology, Karolinska University Hospital, S-14186 Stockholm, Sweden (per.ljungman@ki.se). The Journal of Infectious Diseases 2014;209:1151–2 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/infdis/jit833