Hospitalizations and outpatient visits for rhinovirus-associated acute respiratory illness in adults.

BACKGROUND: Rhinovirus is linked to asthma exacerbations and chronic obstructive pulmonary disease exacerbations in adults. The severity and rates of rhinovirus acute respiratory illnesses (ARIs) in adults are uncertain. OBJECTIVES: We sought to determine rhinovirus-associated ARI rates in adults presenting for care in multiple settings and identify factors associated with rhinovirus detection. METHODS: This prospective, population-based cohort enrolled Tennessee residents 18 years or older in the emergency department (ED), outpatient clinics, or hospitalized for ARI from December 2008 to May 2010. Nasal/throat swabs were collected and tested for rhinovirus and other viruses by using RT-PCR. Rates of ED visits and hospitalizations were calculated and rhinovirus-positive and rhinovirus-negative patients were compared. RESULTS: Among 2351 enrollees, rhinovirus was detected in 247 (11%). There were 7 rhinovirus-associated ED visits and 3 hospitalizations per 1000 adults annually. Patients with rhinovirus, compared with virus-negative ARI, were more likely to present with wheezing (odds ratio [OR], 1.7; 95% CI, 1.23-2.35; P < .001), to be a current smoker (OR, 2.31; 95% CI, 1.68-3.19) or live with a smoker (OR, 1.72; 95% CI, 1.10-2.67), have a history of chronic respiratory disease (OR, 1.61; 95% CI, 1.17-2.22), and were less likely to be hospitalized versus seen in the outpatient setting (OR, 0.58; 95% CI, 0.41-0.83). CONCLUSIONS: Rhinovirus is associated with a substantial number of ED visits and hospitalizations for ARIs in adults. There may be modifiable factors that can reduce the likelihood of presenting with rhinovirus-associated ARIs.

Human rhinovirus C infections in pediatric hematology and oncology patients.

Children with cancer and HSCT recipients are at high risk for common viral infections. We sought to define the viral etiology of ARI and identify risk factors. Nasal wash samples were collected from pediatric hematology-oncology patients and HSCT recipients with ARI during the 2003-2005 winter seasons. Real-time RT-PCR was performed to detect Flu A, influenza B, RSV, PIV 1-3, human MPV, and HRV. HRV specimens were sequenced and genotyped. Seventy-eight samples from 62 children were included. Viruses were detected in 31 of 78 samples (40%). HRV were detected most frequently, in 16 (52%) including five HRVC; followed by seven (22%) RSV, five (16%) Flu A, four (13%) MPV, and two (6%) PIV2. There was a trend toward higher risk of viral infection for children in day care. Only 8% of the study children had received influenza vaccine. HRV, including the recently discovered HRVC, are an important cause of infection in pediatric oncology and HSCT patients. Molecular testing is superior to conventional methods and should be standard of care, as HRV are not detected by conventional methods.

Human rhinovirus C: Age, season, and lower respiratory illness over the past 3 decades.

BACKGROUND: Human rhinoviruses (HRVs) cause common colds, and the recently discovered HRV-C is increasingly associated with lower respiratory illness among populations such as children and asthmatic patients. OBJECTIVE: To determine how HRV-C is associated with respiratory illness and to evaluate changes in prevalence and species over 2 decades. METHODS: A prospective study of children younger than 5 years was performed at the Vanderbilt Vaccine Clinic over a 21-year period. Nasal-wash specimens from children presenting with upper or lower respiratory illness at acute care visits were tested for HRV and HRV-positives genotyped. Demographic and clinical features were compared between children with or without HRV, and with different HRV species. RESULTS: HRV was detected in 190 of 527 (36%) specimens from a population of 2009 children from 1982 through 2003. Of these, 36% were HRV-C. Age (P = .039) and month of illness (P < .001) were associated with HRV infection and HRV species. HRV-C was significantly associated with lower respiratory illness, compared with HRV-A (P = .014). HRV-A and HRV-C prevalence fluctuated throughout the 21-year period; HRV-C was more prevalent during winter (P = .058). CONCLUSIONS: HRV-C is not a new virus but has been significantly associated with childhood lower respiratory illness in this population for several decades. Temporal changes in virus prevalence occur, and season may predict virus species. Our findings have implications for diagnostic, preventive, and treatment strategies due to the variation in disease season and severity based on species of HRV infection.

A mechanistic role for type III IFN-λ1 in asthma exacerbations mediated by human rhinoviruses.

RATIONALE: Human rhinoviruses (HRV) are the leading cause of upper respiratory infections and have been postulated to trigger asthma exacerbations. However, whether HRV are detected during crises because upper respiratory infections often accompany asthma attacks, or because they specifically elicit exacerbations, is unclear. Moreover, although several hypotheses have been advanced to explain virus-induced exacerbations, their mechanism remains unclear. OBJECTIVES: To determine the role of HRV in pediatric asthma exacerbations and the mechanisms mediating wheezing. METHODS: We prospectively studied 409 children with asthma presenting with upper respiratory infection in the presence or absence of wheezing. Candidate viral and immune mediators of illness were compared among children with asthma with different degrees of severity of acute asthma. MEASUREMENTS AND MAIN RESULTS: HRV infections specifically associated with asthma exacerbations, even after adjusting for relevant demographic and clinical variables defined a priori (odds ratio, 1.90; 95% confidence interval, 1.21-2.99; P = 0.005). No difference in virus titers, HRV species, and inflammatory or allergic molecules was observed between wheezing and nonwheezing children infected with HRV. Type III IFN-λ(1) levels were higher in wheezing children infected with HRV compared with nonwheezing (P < 0.001) and increased with worsening symptoms (P < 0.001). Moreover, after adjusting for IFN-λ(1), children with asthma infected with HRV were no longer more likely to wheeze than those who were HRV-negative (odds ratio, 1.18; 95% confidence interval, 0.57-2.46; P = 0.66). CONCLUSIONS: Our findings suggest that HRV infections in children with asthma are specifically associated with acute wheezing, and that type III IFN-λ(1) responses mediate exacerbations caused by HRV. Modulation of IFN- λ(1) should be studied as a therapeutic target for exacerbations caused by HRV.

Influence of maternal asthma on the cause and severity of infant acute respiratory tract infections.

BACKGROUND: Respiratory syncytial virus (RSV) and rhinovirus infections are the most common significant infant respiratory tract illnesses and are associated with increased but differential risks of childhood asthma. OBJECTIVE: We sought to determine whether maternal asthma is associated with higher odds of infant respiratory tract infection with rhinovirus versus RSV and increased infection severity. METHODS: Mother-infant dyads were enrolled from 2004-2008 during an infant respiratory tract infection (104 with rhinovirus and 279 with RSV). Mothers were classified into mutually exclusive groups (atopic asthma, nonatopic asthma, and no asthma). We determined viral cause using PCR and the severity of the infant's respiratory tract infection using the bronchiolitis severity score. Adjusted relative odds of maternal asthma with viral cause were calculated by using logistic regression. Proportional odds models assessed the association of maternal asthma and infant infection severity. RESULTS: Infants with a mother with atopic asthma compared with infants whose mothers did not have asthma were more likely to have rhinovirus versus RSV infection (adjusted odds ratio, 2.42; 95% CI, 1.19-4.90). Similarly, among infants with rhinovirus, having a mother with atopic asthma was associated with increased infection severity (adjusted odds ratio, 3.10; 95% CI, 1.21-7.98). This relationship was not seen among infants with RSV. CONCLUSIONS: Clinically significant rhinovirus infection during infancy was more strongly associated with having a mother with atopic asthma than clinically significant RSV infection. Having a mother with atopic asthma was associated with increased severity of infant rhinovirus but not RSV infections. Infants with rhinovirus were more likely to have a familial atopic predisposition, which might partly explain the subsequent increased asthma risk.

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

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.

Human rhinovirus species associated with hospitalizations for acute respiratory illness in young US children.

BACKGROUND: The contribution of human rhinovirus (HRV) to severe acute respiratory illness (ARI) is unclear. OBJECTIVE: To assess the association between HRV species detection and ARI hospitalizations. METHODS: Children <5 years old hospitalized for ARI were prospectively enrolled between December 2003 and April 2005 in 3 US counties. Asymptomatic controls were enrolled between December 2003 and March 2004 and between October 2004 and April 2005 in clinics. Nasal and throat swab samples were tested for HRV and other viruses (ie, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, and influenza virus) by reverse-transcription-polymerase chain reaction, and genetic sequencing identified HRV species and types. HRV species detection was compared between controls and patients hospitalized during months in which controls were enrolled. RESULTS: A total of 1867 children with 1947 ARI hospitalizations and 784 controls with 790 clinic visits were enrolled and tested for HRV. The HRV-A detection rate among participants ≥24 months old was 8.1% in the hospitalized group and 2.2% in the control group (P = .009), and the HRV-C detection rates among those ≥6 months old were 8.2% and 3.9%, respectively (P = .002); among younger children, the detection rates for both species were similar between groups. The HRV-B detection rate was ≤1%. A broad diversity of HRV types was observed in both groups. Clinical presentations were similar among HRV species. Compared with children infected with other viruses, children with HRV detected were similar for severe hospital outcomes and more commonly had histories or diagnoses of asthma or wheezing. CONCLUSIONS: HRV-A and HRV-C were associated with ARI hospitalization and serious illness outcomes.

Real-world comparison of two molecular methods for detection of respiratory viruses.

BACKGROUND: Molecular polymerase chain reaction (PCR) based assays are increasingly used to diagnose viral respiratory infections and conduct epidemiology studies. Molecular assays have generally been evaluated by comparing them to conventional direct fluorescent antibody (DFA) or viral culture techniques, with few published direct comparisons between molecular methods or between institutions. We sought to perform a real-world comparison of two molecular respiratory viral diagnostic methods between two experienced respiratory virus research laboratories. METHODS: We tested nasal and throat swab specimens obtained from 225 infants with respiratory illness for 11 common respiratory viruses using both a multiplex assay (Respiratory MultiCode-PLx Assay [RMA]) and individual real-time RT-PCR (RT-rtPCR). RESULTS: Both assays detected viruses in more than 70% of specimens, but there was discordance. The RMA assay detected significantly more human metapneumovirus (HMPV) and respiratory syncytial virus (RSV), while RT-rtPCR detected significantly more influenza A. We speculated that primer differences accounted for these discrepancies and redesigned the primers and probes for influenza A in the RMA assay, and for HMPV and RSV in the RT-rtPCR assay. The tests were then repeated and again compared. The new primers led to improved detection of HMPV and RSV by RT-rtPCR assay, but the RMA assay remained similar in terms of influenza detection. CONCLUSIONS: Given the absence of a gold standard, clinical and research laboratories should regularly correlate the results of molecular assays with other PCR based assays, other laboratories, and with standard virologic methods to ensure consistency and accuracy.

Viral respiratory tract infections and asthma: the course ahead.

Inquiries into the relationships between viral respiratory tract illnesses and the inception and exacerbation of asthma are being facilitated by recent advances in research approaches and technology. In this article we identify important knowledge gaps and future research questions, and we discuss how new investigational tools, including improved respiratory tract virus detection techniques, will permit current and future researchers to define these relationships and the host, virus, developmental, and environmental mechanisms that regulate them. A better understanding of these processes should facilitate the development of improved strategies for the prevention and treatment of virus-induced wheezing illnesses and asthma exacerbations and, possibly, the ultimate goal of discovering effective approaches for the primary prevention of asthma.

Respiratory Viruses Associated With Acute Wheezing in Hospitalized Young Children in Jordan.

A cross-sectional viral surveillance study of hospitalized children less than 2 years of old in Amman, Jordan, noted that respiratory syncytial virus and human metapneumovirus, but not human rhinovirus, were associated with higher odds of acute wheezing. Future longitudinal studies are needed to evaluate the association between early childhood viral acute respiratory infections and recurrent wheezing later in childhood.

A novel group of rhinoviruses is associated with asthma hospitalizations.

BACKGROUND: Although recent studies have identified new group C human rhinoviruses (HRVCs), their spectrum of pediatric disease is unknown. OBJECTIVE: We sought to determine the presentation and burden of disease caused by HRVCs among young hospitalized children. METHODS: We conducted prospective population-based surveillance in 2 US counties among children less than 5 years of age hospitalized with acute respiratory illness or fever from October 2001 through September 2003. Nasal/throat swabs were obtained and tested for HRVs, as determined by means of RT-PCR and then characterized by means of partial sequencing. RESULTS: Of 1052 children enrolled and tested during the 2-year period, 167 (16%) had HRVs detected. Of 147 samples successfully sequenced, 64 were group A HRVs, 6 were group B HRVs, and 77 were HRVCs. Children with HRVCs were significantly more likely than those with group A HRVs to have underlying high-risk conditions, such as asthma (42% vs 23%, P = .023) and to have had a discharge diagnosis of asthma (55% vs 36%, P = .022). CONCLUSIONS: Overall, HRVCs were detected in 7% of children hospitalized for fever or respiratory conditions and constituted almost half of all rhinovirus-associated hospitalizations, suggesting that this novel group causes a substantial burden of pediatric disease.

Understanding the Association of Human Rhinovirus with Asthma.

Human rhinoviruses are ubiquitous seasonal pathogens. They have known associations with first onset of wheezing illnesses in children and with asthma exacerbations in patients of all ages. It is not yet certain whether human rhinoviruses play a direct role in the pathogenesis of asthma by activating deleterious inflammatory responses or if they only serve as a catalyst to accelerate the disease in genetically predisposed individuals. There have been previously demonstrated reductions in the development of the asthmatic phenotype with passive immunization against respiratory syncytial virus; however, in the case of rhinovirus, there are barriers to effective vaccine development, such as the lack of a common antigenic target due to alterations of surface markers among subtypes. It remains to be determined whether certain subtypes of human rhinovirus are more asthmagenic and therefore worthy of greater attention as vaccine candidates, but several studies have suggested that RV-C and certain RV-A strains may be more strongly linked with asthma.

Sequencing human rhinoviruses: direct sequencing versus plasmid cloning.

Human rhinoviruses (RV) are associated with the majority of viral respiratory illnesses in infants, children and adults. Over the last several years, researchers have begun to sequence the many different species and strains of RV in order to determine if certain species were associated with increased disease severity. There are a variety of techniques employed to prepare samples for sequencing. One method utilizes plasmid-cloning, which is expensive and takes several hours to complete. Recently, some investigators have instead used direct sequencing to sequence RV strains, allowing for omission of the time- and labor-intensive cloning step. This study formally compares and contrasts the sequencing results obtained from plasmid-cloning and direct Sanger sequencing of a 500 base pair PCR product covering the VP4/VP2 region of RV. A slightly longer sequence (by 65 base pairs on average) was obtained when specimens were plasmid-cloned, and the sequences were 86% similar. After trimming the extra base pairs from the cloned sequences, the sequences were 99.7% identical. Overall success of directly sequencing samples was similar to that of cloning, 5% on average failed for each technique. Therefore, in many instances, directly sequencing samples may be considered in lieu of the more expensive and time-consuming plasmid-cloning technique.

Urine Club Cell 16-kDa Secretory Protein and Childhood Wheezing Illnesses After Lower Respiratory Tract Infections in Infancy.

Background: Infants with lower respiratory tract infections (LRTIs) are at an increased risk of developing childhood wheezing illnesses (including asthma), but it is not currently possible to predict those at risk for these long-term outcomes. The current objective was to examine whether urine levels of club cell 16-kDa secretory protein (CC16) at the time of an infant LRTI are associated with the development of childhood wheezing illnesses. Methods: Prospective study of 133 previously healthy infants enrolled during a healthcare visit for a LRTI and followed longitudinally for childhood wheezing illnesses. Urine levels of CC16 at the time of enrollment were measured after validating a commercially available enzyme-linked immunosorbent assay kit for serum. The outcome of interest was parental report of subsequent childhood wheeze (defined as ≥1 episode of wheezing following the initial LRTI) at the 1-year follow-up visit. Logistic regression was used for the main analysis. Results: The median (interquartile range) urine levels of CC16 (ng/mg of creatinine) at the time of an infant LRTI were 11.1 (7.7-20.1) for infants with subsequent childhood wheeze and 13.4 (8.3-61.1) for those without (p = 0.11). In the main multivariate analysis using a logarithmic transformation of the urine levels of CC16, a twofold increase in urine levels of CC16 was associated with ∼30% decreased odds (OR = 0.74 [95% confidence interval (CI) 0.56-0.98], p = 0.04) of subsequent childhood wheeze after adjustment for potential confounders. Conclusions: An inverse association was found between urine levels of CC16 at the time of an infant LRTI and the odds of subsequent childhood wheeze. Urine CC16 may be a useful biomarker of the development of childhood wheezing illnesses after LRTIs in infancy.

Fetal alcohol exposure and temporal vulnerability: effects of binge-like alcohol exposure on the developing rat hippocampus.

Children with fetal alcohol syndrome (FAS) display altered performance in tasks of learning and memory, behaviours thought to be associated with the hippocampus. Altered hippocampal structure has been reported in some FAS children; therefore, a rat model system was used to determine whether the size and numbers of pyramidal cells in regions CA1 and CA3 of the hippocampal formation and granule cells in the dentate gyrus were altered by alcohol exposure during different periods of development. Rat pups were exposed to alcohol in utero during the second trimester-equivalent (E10-20), the first two trimesters-equivalent (E1-20), during the time of hippocampal pyramidal cell neurogenesis (E16-20), part of the third trimester-equivalent (P4-9), and all three trimesters-equivalent (E1-20+P4-9). Control animals (nutritional and untreated) were reared for all treatment conditions. All pups were perfused on P10. CA1 volume, pyramidal cell density, and number were reduced in pups treated with alcohol during the third trimester-equivalent, whether unique or as exposure during all three trimesters-equivalent. CA3 volume was reduced in alcohol-treated animals across all gestational ages; however, pyramidal cell density and number in this region were only reduced in animals treated with alcohol during the third trimester-equivalent. Volume of the dentate gyrus did not appear to be affected by alcohol treatment. Granule cell density and number in this region were reduced in animals treated with alcohol during the third trimester-equivalent. The third trimester-equivalent in the rat appears to be a developmental period during which the hippocampus is particularly susceptible to the effects of alcohol consumption. The resulting damage to the hippocampus may contribute to the behavioural deficits related to learning and memory noted in children with FAS.

Wheezing exacerbations in early childhood: evaluation, treatment, and recent advances relevant to the genesis of asthma.

Children who begin wheezing during early childhood are frequently seen by health care providers in primary care, in hospitals, and in emergency departments, and by allergists and pulmonologists. When a young child, such as the 2 year-old patient presented here, is evaluated for wheezing, a frequent challenge for clinicians is to determine whether the symptoms represent transient, viral-induced wheezing or whether sufficient risk factors are present to suspect that the child may experience recurrent wheezing and develop asthma. Most factors that influence prognosis are not mutually exclusive, are interrelated (ie, cofactors), and often represent gene-environment interactions. Many of these risk factors have been, and continue to be, investigated in prospective studies to decipher their relative importance with the goal of developing new therapies and interventions in the future. The etiologies of wheezing in young children, diagnostic methods, treatment, prognostic factors, and potential targets for prevention of the development of asthma are discussed.

The Argentina Premature Asthma and Respiratory Team (APART): objectives, design, and recruitment results of a prospective cohort study of viruses and wheezing in very low birth weight infants.

BACKGROUND: Asthma and wheezing account for a substantial disease burden around the world. Very low birth weight (VLBW, <1500 grams) infants are at an increased risk for the development of severe acute respiratory illness (ARI) and recurrent wheeze/asthma. The role of respiratory viruses in asthma predisposition in premature infants is not well understood. Preliminary evidence suggests that infection with human rhinovirus (RV) early in life may contribute to greater burden of asthma later in life. METHODS: A prospective cohort study of premature VLBW infants from Buenos Aires, Argentina, was enrolled year-round during a three-year period in the neonatal intensive care unit and followed during every ARI and with monthly well visits during the first year of life. Longitudinal follow-up up until age five years is ongoing. RESULTS: This report describes the objectives, design, and recruitment results of this prospective cohort. Two hundred and five patients were enrolled from August 2011 through January 2014, and follow-up is ongoing. A total of 319 ARI episodes were observed from August 2011 to July 2014, and 910 well visits occurred during this time period. CONCLUSIONS: The Argentina Premature Asthma and Respiratory Team (APART) is a unique cohort consisting of over 200 patients and over 1200 specimens who have been and will continue to be followed intensively from NICU discharge to capture baseline risk factors and every ARI, with interceding well visits during the first year of life, as well as longitudinal follow-up to age 5 years for asthma and atopy outcomes.

From sneeze to wheeze: what we know about rhinovirus Cs.

While the discovery of HRV-Cs is recent, there are no indications that they are new viruses, or that they are emerging in real-time. Genetically, HRV-Cs are most closely related to the members of HRV-A and HRV-B but even a small genetic difference can impart encompass significant changes to their clinical impact, complicated by a diverse human background of prior virus exposure and underlying host immune and disease variability. It is well known that HRVs are a major trigger of asthma exacerbations and HRV-Cs are now under investigation for their potential involvement in asthma inception. The newly described HRV-Cs account for a large proportion of HRV-related illness, including common colds and wheezing exacerbations. HRV-Cs are genetically diverse and appear to circulate with seasonal variation, exchanging dominance with HRV-A. Whether HRV-Cs are consistently more pathogenic or "asthmagenic" is unproven. Antigenic diversity complicates passive and active prophylactic interventions (i.e. antibodies or vaccines), so further identification and characterisation of individual types (and their neutralising antigens) is likely to inform future preventive strategies. In the meantime, new antivirals should benefit groups at risk of the most severe disease.

Viral etiologies of infant bronchiolitis, croup and upper respiratory illness during 4 consecutive years.

BACKGROUND: Prospective data on viral etiology and clinical characteristics of bronchiolitis and upper respiratory illness (URI) in infants are limited. METHODS: This prospective cohort enrolled previously healthy term infants during inpatient or outpatient visits for acute URI or bronchiolitis during September to May 2004 to 2008. Illness severity was determined using an ordinal bronchiolitis severity score. Common respiratory viruses were identified by real-time reverse-transcriptase polymerase chain reaction. RESULTS: Of 648 infants, 67% were enrolled during inpatient visits and 33% during outpatient visits. Seventy percent had bronchiolitis, 3% croup and 27% URI. Among infants with bronchiolitis, 76% had respiratory syncytial virus (RSV), 18% human rhinovirus (HRV), 10% influenza, 2% coronavirus, 3% human metapneumovirus and 1% parainfluenza virus. Among infants with croup, 39% had HRV, 28% parainfluenza virus, 28% RSV, 11% influenza, 6% coronavirus and none human metapneumovirus. Among infants with URI, 46% had HRV, 14% RSV, 12% influenza, 7% coronavirus, 6% parainfluenza virus and 4% human metapneumovirus. Individual viruses exhibited distinct seasonal, demographic and clinical expression. CONCLUSIONS: The most common infections among infants seeking care in unscheduled medical visits for URI or bronchiolitis were RSV and HRV. Demographic differences were observed between patients with different viruses, suggesting that host and viral factors play a role in phenotypic expression of viral illness.