Human rhinovirus detection in the lower respiratory tract of hematopoietic cell transplant recipients: association with mortality

Seo, Sachiko; Waghmare, Alpana; Scott, Emily M; Xie, Hu; Kuypers, Jane M; Hackman, Robert C.; Campbell, Angela P.; Choi, Su-Mi; Leisenring, Wendy M.; Jerome, Keith R.; Englund, Janet A.; Boeckh, Michael

The study herein has both strengths and limitations. We examined a large number of cases of HRV RNA positive BALs and comparative cases with other viral lower respiratory diseases which allowed us to perform appropriate statistical analyses that carefully accounted for copathogens and stages of acute lung injury. Our study was not restricted to specific transplant types or time periods after HCT, however, a subgroup analysis of recent allogeneic transplant recipients showed similar results. Due to a lack of specific information about the severity of GvHD in some cases, the association between mortality after HRV LRI and GvHD remains unclear, although we used steroid dose as a surrogate marker for GvHD severity. Our largely unbiased approach of evaluating patients with pulmonary infiltrates by bronchoscopy and BAL and the availability of lung tissue are additional strengths. According to previous reports, approximately 30% of HRV URI cases were asymptomatic 4 and 5% of BAL sam-ples from asymptomatic HCT recipients included HRV LRI; 12 we therefore think that asymptomatic lower respiratory tract infection is only a minor factor in the present study. Other limitations include the lack of tissue immunohistochemical studies and the lack of direct viral quantitation, as well as our inability to adequately culture for HRV in autopsy or biopsy specimens. Currently available antibodies for HRV are serotype-specific. 31 Because we did not identify the HRV serotypes in our tissue samples, we could not perform immunohistochemistry to confirm tissue detection of HRV. Furthermore, we acknowledge that certain HRV strains (particularly HRV-C viruses) may not have been identified earlier in this study and would be unlikely to be successfully cultivated. Thus, infections with HRV-C might be underrepresented in the patients prior to 2008.