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Viral respiratory infections are closely associated with wheezing illnesses and exacerbations of asthma throughout childhood, and yet there are a number of remaining questions pertaining to the specific nature of this relationship. Infection with an expanding list of respiratory viruses is an important cause of acute wheezing in infancy, and viruses are detected in most exacerbations of asthma throughout childhood. Furthermore, infants who develop severe viral respiratory infections are more likely to have asthma later in childhood. There has been progress in understanding the pathogenesis of viral respiratory illnesses, and this has led to new insights into how these processes might differ in asthma. Several host factors, including respiratory allergy and virus-induced interferon responses, modify the risk of virus-induced wheezing. In the absence of effective antiviral therapies, treatment of virus-induced wheezing and exacerbations of asthma can be challenging, and studies evaluating current treatment strategies are reviewed. Understanding the host-pathogen interactions that determine the severity of respiratory illnesses and long-term sequelae is likely to be of great help in identifying at-risk individuals, and in designing new and more effective treatments.

Background: There continues to be controversy on the most appropriate way to manage infants and young children with fever and documented RSV lower respiratory tract infection (LRTI). The objective of this study was to determine the usefulness of an abnormal white blood cell (WBC) count for predicting a concurrent serious bacterial infection in patients admitted with RSV LRTI., Methods: The medical records were reviewed of patients discharged with RSV LRTI during the 5 RSV seasons from July 1, 2000 through June 30, 2005. Data were collected on age and gender as well as temperature, complete blood count with manual differential and bacterial cultures obtained at admission., Results: The inclusion criteria was met by 1920 patients. There were 672 febrile patients who had a complete blood count and a bacterial culture. One (5.0%) of 20 patients with a WBC <5000 had a positive culture, 23 (4.7%) of 492 patients with a WBC 5000-14,999 had a positive culture, 5 (4.8%) of 105 patients with a WBC 15,000-19,999 had a positive culture, 2 (5.7%) of 35 patients with a WBC 20,000-24,999 had a positive culture, none of 11 patients with a WBC 25,000-29,999 had a positive culture and 3 (33%) of 9 patients with a WBC >30,000 had a positive culture. Overall, cultures were positive in 34 (5.1%; 95% CI: 3.4-6.8%) of the febrile patients tested and almost all (32; 94%) showed positive urine cultures., Conclusion: The probability of an abnormal WBC count <5000 and 15,000-30,000 being associated with a concurrent serious bacterial infection was very low and no different from that of a normal WBC count in febrile patients admitted with RSV LRTI.

Background: Viral respiratory tract infections cause significant morbidity and mortality. Respiratory viruses are suspected to play a role in the inception of asthma early in life. Respiratory syncytial virus (RSV) is the most common cause of infant bronchiolitis, which is associated with the development of childhood wheezing and asthma. However, it is not clear whether this association is "causal" or "circumstantial.", Methods: Animal models have been pivotal in studying the pathophysiology of viral respiratory infections. Various approaches to assessing airway inflammation and function have been used to define the mechanisms of virus-induced airway dysfunction and to address clinically relevant questions regarding the role of RSV in wheezing and asthma after bronchiolitis., Results: Viral lower respiratory tract infections alter airway function in humans and animals. The extent and duration of the alterations may depend on the virus itself, host factors and environmental factors. Animal studies demonstrated that viral infection induces airway hyperresponsiveness and enhances this alteration in the allergen-sensitized and exposed host. This altered airway function is mediated by immune and neurogenic inflammatory mechanisms. Recent studies in mice show that neonatal RSV infection sensitizes the newborn to develop an asthma-like phenotype on reinfection, providing further opportunities to investigate the role of RSV in postbronchiolitis wheezing and asthma in this animal model., Conclusions: Further studies are needed to fully establish the mechanisms underlying the pathophysiology of viral respiratory tract infections and to clarify their role in the inception and/or progression of chronic airway diseases such as asthma. The results of ongoing therapeutic studies promise to minimize the impact of such viral infections.

Background: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is often followed by recurrent wheezing episodes during childhood. The effect of postbronchiolitis wheezing on the well-being of the child is not known. This study aimed to determine the impact of RSV LRTI hospitalization before age 13 months on health-related quality of life (HRQoL) at age 3 years., Methods: HRQoL was measured in a previously described cohort of children with a history of RSV infection and compared with control term children from the open population. HRQoL was determined during the winter season in index and control children. We used a validated questionnaire, which measures the health status of children in 13 domains weighted by the impact of the health status problems on well-being. The lung domain was the focus of this study. In addition daily respiratory symptoms of the index children were recorded prospectively up to age 3 years and correlated with HRQoL scores., Results: HRQoL was lower in index children (n = 128) than in control children (n = 340) for the lung, gastrointestinal tract and sleeping domains. HRQoL scores for social and developmental domains were similar for index and control children. As anticipated the largest difference between index and control children was found in the lung domain (77.6 +/- 2.2 vs. 93.9 +/- 0.8, P < 0.01). HRQoL in the lung domain was lower during the winter than during the summer season (77.6 +/- 2.2 vs. 85.6 +/- 1.9, P < 0.01), which was explained by increased airway morbidity during the winter season. We found a high correlation between lung HRQoL scores and total number of wheezing days during follow-up., Conclusions: Postbronchiolitis wheezing has broad implications for long-term well-being of children. Decreased HRQoL was attributed to postbronchiolitis wheezing, but not to preexistent risk factors, such as premature birth. This study underscores the importance of developing new strategies to prevent and treat long term airway morbidity after RSV LRTI.

This review examines the relationship between severe pulmonary disease caused by respiratory syncytial virus (RSV) infection in infancy and later development of asthma or reactive airway disease (RAD). RSV infection accounts for 70% or greater of all cases of infantile bronchiolitis and has been linked to subsequent asthma or RAD, either directly or through a shared common predisposition. Several studies suggest that RSV bronchiolitis is an important factor in the development of asthma and possibly atopy, although the association is lost by the age of 13 years. The mechanism is as yet unclear, but murine models of RSV disease have identified many plausible causal explanations. Further study is necessary to determine the relative roles of RSV infection and genetic predisposition in explaining the association between RSV infection and asthma/RAD.

Treatment of respiratory syncytial virus bronchiolitis rests primarily on supportive care with oxygen and fluid management. Other therapies commonly used include bronchodilators, corticosteroids and ribavirin, when considered appropriate. Small studies have also suggested that exogenous surfactant, helium/oxygen mixtures (heliox) and combination therapies may offer clinical benefit as well. Management of bronchiolitis can be facilitated by (1) recognizing the risks and benefits of various therapies, (2) understanding the markers of disease severity and (3) gaining familiarity with the time course of viral replication compared with presentation of symptoms. Although oxygen administration and judicious fluid replacement are the only interventions proved to be of reliable benefit to infants with bronchiolitis, newer studies support a role for adjunctive therapies aimed at relieving airway obstruction, especially when administered very early in the course of the illness or given to infants with more severe disease.

There is now convincing evidence that children who develop lower respiratory symptoms during infection with respiratory syncytial virus (RSV) in early life are at increased risk of developing asthma-like symptoms during the school years. What determines this association is not well-understood, but increased likelihood of allergic sensitization plays a minor role, if any, as a determinant of post-RSV wheeze. Current evidence suggests that both genetic and environmental factors determine the type of immune response to the acute RSV infection and that this response, in turn, may affect the development of the control mechanisms involved in the regulation of airway tone. Many different cytokines appear to play a role in this acute immune response, including interferon-gamma; interleukins 8, 10 and 12; and cytokines produced by T helper (Th) 1 and Th2 cells. Because asthma is a heterogeneous condition, future studies will need to determine the potentially different role of RSV infection as a risk factor for these different asthma phenotypes. It is likely, however, that strategies for the prevention of RSV infection may play a role in the prevention of the subsequent development of persistent wheezing and asthma-like symptoms in childhood.