Virus-induced airway dysfunction: pathogenesis and biomechanisms.
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.
Dakhama
Azzeddine
A
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO, USA. dakhamaa@njc.org
Lee
Young Mok
YM
Gelfand
Erwin W
EW
D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000503:physiopathology; D001990:Bronchiolitis, Viral / Q000150:complications* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D006801:Humans; D007223:Infant; D051379:Mice; D012135:Respiratory Sounds / Q000209:etiology* / Q000503:physiopathology; D018357:Respiratory Syncytial Virus Infections / Q000150:complications*; D018113:Respiratory Syncytial Virus, Human / Q000472:pathogenicity