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

Miller, E. Kathryn; Williams, John V.; Gebretsadik, Tebeb; Carroll, Kecia N.; Dupont, William D.; Mohamed, Yassir A.; Morin, Laura-Lee; Heil, Luke; Minton, Patricia A.; Woodward, Kimberly; Liu, Zhouwen; Hartert, Tina V.

BACKGROUND: Risk factors for severe human rhinovirus (HRV) associated infant illness are unknown. OBJECTIVES: To examine the role of HRV in infant respiratory illness, and assess viral and host risk factors for HRV disease severity. METHODS: We utilized a prospective cohort of term, previously healthy infants enrolled during an inpatient or outpatient visit for acute upper or lower respiratory illness during fall-spring months 2004-2008. Illness severity was determined using an ordinal bronchiolitis severity score with higher scores indicating more severe disease. HRV was identified by real-time RT-PCR. The VP4/VP2 region from HRV positive specimens was sequenced to determine species. RESULTS: Of 630 infants with bronchiolitis or URI, 162 (26%) had HRV; HRV was associated with 18% of bronchiolitis and 47% of URI. Among infants with HRV, 104 (64%) had HRV alone. Host factors associated with more severe HRV illness included maternal and family history of atopy (median score 3.5, IQR [1.0-7.8] vs. 2.0 [1.0-5.2], and 3.5 [1.0-7.5] vs.2.0 [0-4.0]). In adjusted analyses maternal history of atopy conferred an increase in risk for more severe HRV bronchiolitis (OR=2.39, 95% CI:1.14-4.99, p=0.02). In a similar model, maternal asthma was also associated with greater HRV bronchiolitis severity (OR=2.49, 95% CI: 1.10-5.67, p=0.03). Among HRV, 35% were HRVA, 6% HRVB, and 30% HRVC. CONCLUSION: HRV was a frequent cause of bronchiolitis and URI among previously healthy term infants requiring hospitalization or unscheduled outpatient visits. Substantial genetic diversity was seen amongst the HRV, and predominant groups varied by season and year. Host factors including maternal atopy were associated with more severe infant HRV illness.