It remains unclear, however, which children who have severe bronchiolitis (eg, an episode requiring hospitalization) will develop recurrent wheezing or asthma. Keywords:Bronchiolitis, Asthma, Respiratory syncytial virus, Rhinovirus, Wheezing, Vitamin D One of the earliest and most common infectious respiratory conditions of childhood is bronchiolitis.1,2A child who has severe bronchiolitis (eg, an episode requiring hospitalization) is at increased risk for recurrent wheezing of childhood and eventual asthma.3,4,5Estimates vary but approximately 80% to 90% of asthma begins before age 6 years, with 70% of children who have asthma having asthmalike symptoms before age 3 years.6,7Although many environmental and genetic factors may play a role in the pathway from bronchiolitis to asthma,3,8this article focuses on the viruses that have been linked to bronchiolitis and how these viruses may predict or contribute to future wheezing and asthma. The article also discusses vitamin D as an emerging risk factor for respiratory infections and wheezing. == Definitions of lower respiratory tract infection == In the United States, lower respiratory tract infections (LRTI) represent almost 60% of infant infectious disease hospitalizations9and bronchiolitis is the most common LRTI.10Despite its high frequency, bronchiolitis remains a clinical diagnosis11,12,13without a common international definition.10,14,15,16,17,18In 2006, the American Academy of Pediatrics defined bronchiolitis as a child younger than 2 years of age who has rhinitis, tachypnea, wheezing, cough, crackles, use of accessory muscles, and/or nasal flaring.10This definition is broad, and KT182 when children younger than 2 years of age present to care with symptoms suggestive of an LRTI, they receive various diagnostic labels, such as bronchiolitis, wheezing, cough, reactive airways disease, asthma, or pneumonia.19 As our understanding of LRTI evolves and we identify more clearly the risk factors for Lep children developing recurrent wheezing in preschool years (and asthma as they grow older), we may need to adjust our LRTI definitions. Indeed, based on 259 wheezing hospitalized children aged 3 to 35 months participating in a systemic corticosteroid and wheezing study in Finland, Jartti and colleagues18recently suggested KT182 that the diagnosis of bronchiolitis should be restricted either to children younger than 24 months of age who have their first episode of wheezing or to children younger than 12 months of age. == Bronchiolitis epidemiology == With its broad definition, bronchiolitis is the leading cause of hospitalization for infants in the United States20,21and the associated hospitalization costs are more than $500 million per year.22In a nationally representative sample, bronchiolitis hospitalization rates increased 2.4-fold from 1980 to 199620and in a KT182 Tennessee Medicaid database there was a 41% increase in bronchiolitis visits at all levels of care (ie, inpatient, emergency department [ED], and outpatient clinic) from 1996 to 2003.2 == Bronchiolitis pathogens == Respiratory syncytial virus (RSV) is the most common pathogen associated with bronchiolitis.1,23Although most children are infected with RSV by age 2 years,24,25relatively few children (<40%) develop clinically recognized bronchiolitis.24,26Among those children who develop bronchiolitis, most have a mild course; approximately 2% to 3% will be hospitalized20,27and less than 1% will be admitted to an ICU, intubated, or die.28,29,30,31 Other viruses that have been linked to bronchiolitis include rhinovirus (RV),32,33human metapneumovirus (hMPV),34influenza A/B,35,36parainfluenza (PIV),37and adenovirus.38,39Coronaviruses also have been linked to lower respiratory tract disease in children,40including the strains NL-6341or New Haven42and HKU1.43,44,45More recently discovered viruses include human bocavirus46,47,48,49and the polyomaviruses WU50and KI.51The clinical relevance of these two polyomaviruses is uncertain.52Furthermore, there is conflicting literature about the relevance of bacterial coinfection in children who have viral bronchiolitis, especially those children requiring intensive care.53,54,55,56 Although myriad infectious causes are associated with bronchiolitis, it remains unclear if the viral cause of a child's bronchiolitis illness is clinically relevant for either the short- or long-term care of the individual child. For short-term care, knowing the infectious cause identifies children who have influenza who may benefit from oseltamivir; it also helps cohort hospitalized children. Otherwise the current consensus is that knowledge of the viral etiologyamong those viruses with easily accessible point-of-care testing (eg, RSV and influenza)does not affect treatment of the individual patient.10As rapid microarray testing becomes less costly and more widely used, however, we are likely to learn much more about the short- and long-term implications of the diverse viruses linked to bronchiolitis. Indeed, these new data could markedly KT182 change current understanding and consensus. == Epidemiology of KT182 pathogens at different levels of care == Several studies have examined the epidemiology of different viruses associated with LRTI in hospitalized children,33,37,57,58,59,60,61but there are fewer studies investigating the epidemiology of viruses linked to bronchiolitis in children presenting to the ED or in outpatient clinics.62,63,64,65In this section,.