Predictive Value of Respiratory Viral Detection in the Upper Respiratory Tract for Infection of the Lower Respiratory Tract With Hematopoietic Stem Cell Transplantation

Abstract

Background: Hematopoietic cell transplant (HCT) recipients are frequently infected with respiratory viruses (RVs) in the upper respiratory tract (URT), but the concordance between URT and lower respiratory tract (LRT) RV detection is not well characterized.

Methods: Hematopoietic cell transplant candidates and recipients with respiratory symptoms and LRT and URT RV testing via multiplex PCR from 2009 to 2016 were included. Logistic regression models were used to analyze risk factors for LRT RV detection.

Results: Two-hundred thirty-five HCT candidates or recipients had URT and LRT RV testing within 3 days. Among 115 subjects (49%) positive for a RV, 37% (42 of 115) had discordant sample pairs. Forty percent (17 of 42) of discordant pairs were positive in the LRT but negative in the URT. Discordance was common for adenovirus (100%), metapneumovirus (44%), rhinovirus (34%), and parainfluenza virus type 3 (28%); respiratory syncytial virus was highly concordant (92%). Likelihood of LRT detection was increased with URT detection (oods ratio [OR] = 73.7; 95% confidence interval [CI], 26.7-204) and in cytomegalovirus-positive recipients (OR = 3.70; 95% CI, 1.30-10.0).

Conclusions: High rates of discordance were observed for certain RVs. Bronchoalveolar lavage sampling may provide useful diagnostic information to guide management in symptomatic HCT candidates and recipients.

Keywords: diagnostics; hematopoietic stem cell transplantation; respiratory viruses.

Figure 1.

Results of upper respiratory tract (URT) and lower respiratory tract (LRT) sample testing with concordance or discordance by specific virus (represented as result from URT/LRT with N = negative and P = positive). Data are shown for subjects with a bronchoalveolar lavage ±3 days (A) or ±1 day (B) from the URT test. Sample pairs negative in both URT and LRT (N/N) are not represented here. Adeno, adenovirus; FluA, influenza A; FluB, influenza B; HCoV, human coronavirus; HMPV, human metapneumovirus; PIV, parainfluenza viruses 1–4 ; HRV, human rhinovirus; RSV, respiratory syncytial virus.

Figure 2.

Distribution of copathogens and alternate diagnoses in subjects with concordant positive pairs (N = 73) and discordant pairs (N = 42). No significant differences between copathogens and alternate diagnoses in subjects with concordant P/P versus discordant results was observed by Fisher's exact test. DAH, diffuse alveolar hemorrhage.

Figure 3.

Sensitivity, specificity, and predictive values for lower respiratory tract (LRT) infection based on cycle threshold (Ct) values in the upper respiratory tract (URT). (A) Receiver operating characteristic (ROC) curve of Ct values in the URT. The Ct values for patients with negative testing in the URT was set to 40, above the upper limit of assay detection. (B) Positive and negative predictive values (PPV and NPV, respectively) for LRT infection based on Ct values in the URT. Patients with adenovirus detected in the plasma at the time of diagnosis of LRT involvement by bronchoalveolar lavage (N = 4) were excluded from the analysis.