Does Detection of Respiratory Viral Infection in Upper Respiratory Tract (URT) Predict Lower Respiratory Tract (LRT) Disease in Hematopoietic Cell Transplant (HCT) Patients?

BACKGROUND: HCT recipients are frequently infected with respiratory viruses (RVs) in the URT; however, diagnostic evaluation of the LRT by bronchoalveolar lavage (BAL) is less common. We sought to determine whether the detection of RVs in the URT is predictive of LRT detection and to identify factors that predict discordance between upper and lower RV detection. METHODS: HCT recipients with respiratory symptoms and LRT RV testing via multiplex PCR in BAL from July 2009 to October 2016 were included in the study. RV PCR results, including cycle threshold (CT) values, were compared with URT samples obtained within ±3 days. Logistic regression models were used to analyze risk factors for RV discordance between paired samples. RESULTS: Among 1,000 HCT recipients with BAL RV testing, 250 had URT testing within 3 days. In total, 75(30%) sample pairs were concordant for the same RV in both the URT and BAL (P/P); 132 (53%) were negative from both sites. Among 43 discordant pairs, 25 (10%) were only positive by URT but negative by BAL (P/N) and 18 (7%) were positive by BAL but negative by URT (N/P). In pairs with positive RV results in the URT or BAL, discordance was common for HMPV (44%), HRV (33%), and PIV-3 (28%); RSV was almost always concordant (92%) (Figure 1). In a multivariable model, the risk of discordance (P/N or N/P) was increased in the presence of a solitary nodule on radiography (OR 6.8; 95% CI 1.2–38.3) and with lymphocyte count >500/mm(3) (OR 3.1; 95% CI 1.08–9.0). Among P/P pairs, the median difference between CT values between URT and BAL samples was 0 (range −12 to +13), with 33 and 29% of subjects having lower and higher CT values (>4, ~1 log(10)) in the BAL, respectively (Figure 2). CONCLUSION: In symptomatic HCT recipients with RV PCR testing performed concurrently in the upper and lower tract, discordant results are relatively common, especially for HRV, HMPV, and PIV-3. The presence of a solitary nodule on imaging and the absence of lymphopenia are associated with discordant results, with BAL results more likely being negative in these situations. More than half of the P/P pairs had a >4 difference in CT values between URT and LRT samples. Taken together, these data suggest that RV testing in BAL can provide useful diagnostic information that may guide management in HCT recipients. DISCLOSURE: S. A. Pergam, MERCK: Consultant and Investigator, Consulting fee.