Host and viral factors associated with severity of human rhinovirus-associated infant respiratory tract illness

Abstract

Background: Risk factors for severe human rhinovirus (HRV)-associated infant illness are unknown.

Objectives: We sought to examine the role of HRV infection in infant respiratory tract illness and assess viral and host risk factors for HRV-associated disease severity.

Methods: We used a prospective cohort of term, previously healthy infants enrolled during an inpatient or outpatient visit for acute upper or lower respiratory tract illness during the fall-spring months of 2004-2008. Illness severity was determined by using an ordinal bronchiolitis severity score, with higher scores indicating more severe disease. HRV was identified by means of real-time RT-PCR. The VP4/VP2 region from HRV-positive specimens was sequenced to determine species.

Results: Of 630 infants with bronchiolitis or upper respiratory tract illnesses (URIs), 162 (26%) had HRV infection; HRV infection was associated with 18% of cases of bronchiolitis and 47% of cases of URI. Among infants with HRV infection, 104 (64%) had HRV infection alone. Host factors associated with more severe HRV-associated illness included a maternal and family history of atopy (median score of 3.5 [interquartile range [IQR], 1.0-7.8] vs 2.0 [IQR, 1.0-5.2] and 3.5 [IQR, 1.0-7.5] vs 2.0 [IQR, 0-4.0]). In adjusted analyses maternal history of atopy conferred an increase in the risk for more severe HRV-associated bronchiolitis (odds ratio, 2.39; 95% CI, 1.14-4.99; P = .02). In a similar model maternal asthma was also associated with greater HRV-associated bronchiolitis severity (odds ratio, 2.49, 95% CI, 1.10-5.67; P = .03). Among patients with HRV infection, 35% had HRVA, 6% had HRVB, and 30% had HRVC.

Conclusion: HRV infection was a frequent cause of bronchiolitis and URIs among previously healthy term infants requiring hospitalization or unscheduled outpatient visits. Substantial viral genetic diversity was seen among the patients with HRV infection, and predominant groups varied by season and year. Host factors, including maternal atopy, were associated with more severe infant HRV-associated illness.

Fig 1

Risk factors for HRV-associated infant respiratory tract disease severity. Solid vertical lines represent ORs, and bars represent 95% CIs.

Fig 2

A, Seasonality of HRV-associated respiratory tract illness in infants by HRV species over a 4-year period. Frequency is defined as the number of infections with HRV species. Percent is defined as the proportion of each HRV species over the total of HRV-positive specimens. B, Seasonality of HRV-associated respiratory tract illness in infants by HRV species by year. Frequency is defined as the number of infections with HRV species. Percent is defined as the proportion of each HRV species over the total of HRV-positive specimens. U, Untyped.

Fig 3

Phylogenetic tree depicting relationships between known HRV serotypes and novel HRVC species. The bar indicates the mean distance of 0.05 nucleotide substitutions per site. Published HRV strains are designated by HRV and a black circle. Sequences identified in this study are designated by number. The numbers in parentheses after the label of these sequences indicates how many additional specimens contained each virus.