Development of a Global Respiratory Severity Score for Respiratory Syncytial Virus Infection in Infants

Abstract

Background: Respiratory syncytial virus (RSV) infection in infants has recognizable clinical signs and symptoms. However, quantification of disease severity is difficult, and published scores remain problematic. Thus, as part of a RSV pathogenesis study, we developed a global respiratory severity score (GRSS) as a research tool for evaluating infants with primary RSV infection.

Methods: Previously healthy infants <10 months of age with RSV infections representing the spectrum of disease severity were prospectively evaluated. Clinical signs and symptoms were collected at 3 time points from hospitalized infants and those seen in ambulatory settings. Data were also extracted from office, emergency department, and hospital records. An unbiased data-driven approach using factor analysis was used to develop a GRSS.

Results: A total of 139 infants (84 hospitalized and 55 nonhospitalized) were enrolled. Using hospitalization status as the output variable, 9 clinical variables were identified and weighted to produce a composite GRSS. The GRSS had an area under the receiver operator curve of 0.961. Construct validity was demonstrated via a significant correlation with length of stay (r = 0.586, P < .0001).

Conclusions: Using routine clinical variables, we developed a severity score for infants with RSV infection that should be useful as an end point for investigation of disease pathogenesis and as an outcome measure for therapeutic interventions.

Keywords: Lower respiratory tract infection; respiratory severity score; respiratory syncytial virus; upper respiratory tract infection.

Figure 1.

The association between hospitalization status and the 2 leading factors derived from a factor analysis. Open circles represent nonhospitalized subjects, and solid circles represent hospitalized subjects. Factor 1 and factor 2 are the top 2 factors identified by principal component analysis and varimax rotation. A subsequent logistic regression analysis determined that only factor 1 was significantly associated with hospitalization; thus the global respiratory severity score is calculated on the basis of factor 1.

Figure 2.

Histogram of the global respiratory severity score (GRSS) for 139 infants. We used a score of 3.5 as the threshold to predict hospitalization (represented by the vertical broken line) and found that 14 infants were misclassified (shown in light grey shaded bars), of whom 6 with a GRSS ≤3.5 were hospitalized, and 8 with a GRSS of >3.5 were not hospitalized.

Figure 3.

Receiver operating characteristic (ROC) curve of the respiratory severity score in discriminating hospitalized from nonhospitalized subjects. Gray-shaded areas are 95% confidence intervals computed from 2000 stratified bootstrap replications. The area under the ROC curve is 0.961.

Figure 4.

The relationship between the global respiratory severity score (GRSS) and length of stay (LOS) for hospitalized subjects. Open circles represent nonhospitalized subjects shown as references (not included in correlation analyses), solid circles represent hospitalized subjects with a LOS of ≤6 days, and triangles represent hospitalized subjects with a LOS of >6 days.