Origin of Respiratory Virus-Induced Chronic Airway Dysfunction: Exploring Genetic, Developmental, and Environmental Factors in a Rat Model of the Asthmatic Phenotype
Despite recent advances, a detailed understanding of the origins of asthma remains elusive. Various lines of evidence suggest that genetic, environmental, and developmental factors contribute to the inception of asthma, but the complex interplay of these factors is only beginning to be elucidated. One central issue in the study of asthma is the role that acute environmental insults to the airways play in the eventual development of chronic airway physiological abnormalities. Animal models of chronic airway dysfunction can serve as important investigative tools with respect to these issues because they permit control and manipulation of genetic and developmental factors through the use of deﬁned animal strains evaluated at speciﬁc stages of development. Furthermore, the nature of the environmental insult, for example, a respiratory virus, is known, and the animals can be exposed to it in a speciﬁc and controlled manner. In this chapter, we discuss the potential roles of cytokine dysregulation and respiratory viral infection in the development of childhood asthma, and describe the use of a rat model of virus-induced chronic airway dysfunction to study the interactions of these two recognized risk factors.