Human Rhinovirus Species C Infection in Young Children with Acute Wheeze Is Associated with Increased Acute Respiratory Hospital Admissions

Abstract

Rationale: Human rhinovirus species C (HRV-C) is the most common cause of acute wheezing exacerbations in young children presenting to hospital, but its impact on subsequent respiratory illnesses has not been defined. Objectives: To determine whether acute wheezing exacerbations due to HRV-C are associated with increased hospital attendances due to acute respiratory illnesses (ARIs). Methods: Clinical information and nasal samples were collected prospectively from 197 children less than 5 years of age, presenting to hospital with an acute wheezing episode. Information on hospital attendances with an ARI before and after recruitment was subsequently obtained. Measurements and Main Results: HRV was the most common virus identified at recruitment (n ¼ 135 [68.5%]). From the 120 (88.9%) samples that underwent typing, HRV-C was the most common HRV species identified, present in 81 (67.5%) samples. Children with an HRV-related wheezing illness had an increased risk of readmission with an ARI (relative risk, 3.44; 95% confidence interval, 1.17-10.17; P ¼ 0.03) compared with those infected with any other virus. HRV-C, compared with any other virus, was associated with an increased risk of a respiratory hospital admission before (49.4% vs. 27.3%, respectively; P ¼ 0.004) and within 12 months (34.6% vs. 17.0%; P ¼ 0.01) of recruitment. Risk for subsequent ARI admissions was further increased in atopic subjects (relative risk, 6.82; 95% confidence interval, 2.16-21.55; P ¼ 0.001). Admission risks were not increased for other HRV species. Conclusions: HRV-C-related wheezing illnesses were associated with an increased risk of prior and subsequent hospital respiratory admissions. These associations are consistent with HRV-C causing recurrent severe wheezing illnesses in children who are more susceptible to ARIs. Keywords: human rhinovirus; acute wheezing illnesses; hospital admissions; pediatricsNumerous studies have demonstrated that wheezing associated with certain viruses in early childhood is an independent risk factor for subsequent wheezing illnesses and the development of asthma (1-7). Most earlier reports focused on respiratory syncytial virus (RSV) bronchiolitis in infancy and recurrent wheezing (1-3, 8, 9), but more recent research has shown that wheezing episodes due to human rhinovirus (HRV) have a stronger association than RSV with further wheezing episodes and asthma in early childhood (4,5,7,9).Previously, HRV-A and -B (10-12) were the only known HRV species, but improved virological detection methods using polymerase chain reaction (PCR) and sequencing (13-15) have revealed another species of rhinovirus, C (16,17). A number of studies have shown that HRV-C is the most common HRV species associated with acute asthma attacks severe enough to result in children presenting to hospital (18-21), and further studies have shown that it also causes more severe asthma attacks than other rhinoviruses (22) and all other viruses (23).These studies raise the issue of whether HRV-C also influences subsequent acute wheezing e...

Rhinovirus and the developing lung

“…Our research group in Perth, Australia demonstrated that HRV-C species caused the majority of and more severe exacerbations in asthmatic children presenting to an emergency department when compared with other HRV species and other viruses [22]. More recent data from the same cohort has shown that preschool children presenting to ED with an HRV-C related wheezing illness had a two-fold risk of having both prior and subsequent respiratory admissions [99]. Of particular note, this risk increased to six-fold for children who were atopic at presentation but was not increased for any other HRV species or other viruses.…”

“…Studies examining the clinical impact of different HRV species in children with acute wheezing illnesses suggest that HRV-C may be more pathogenic than other known HRV species [22][23][24][97][98][99]. One study demonstrated that HRV-C was more common than HRV-A in children hospitalised with wheezing illnesses [24].…”

The impact of respiratory viruses on lung health after preterm birth

“…Hospitalisation with RV-related respiratory illness has been associated with a more than 3-fold increase in the rate of recurrent wheeze among healthy term-born infants during the following year [105]. Similarly, hospital presentation and/or admission with an RV-related wheezing illness in childhood is associated with a 3-fold increased risk of subsequent hospitalisation for another respiratory illnesses [106] as well as a more than 4-fold increased risk of subsequent asthma [100]. …”

Community-acquired respiratory viruses after lung transplantation: common, sometimes silent, potentially lethal

“…Persistent rhinovirus infection in particular may be a surrogate biological marker of over immunosuppression as suggested by the higher calcineurin inhibitor levels in the CARV group. Not all CARV are the same as nicely described in table 3, and further subdivision of the Picornavirus group in particular may bring additional insights regarding severity and persistence of symptoms noting a recent report of more severe symptoms in human rhinovirus type C 17. Finally, the authors avoid discussing the thorny clinical dilemma of whom to treat and how to treat.…”