Upregulation of neuropeptides and infant obstructive airway disorder in
post-RSV wheezing and NEHI
Abstract
Obstructive airway disorders are common in infancy and early childhood.
The leading example of such disorder is post-viral wheezing,
predominantly the well characterized disorder that follows respiratory
syncytial virus (RSV) infection and leads to intermittent, long-term
wheezing. The underlying mechanisms of the airway reactivity related to
RSV infection have been extensively studies and are associated with
dysregulation of the nonadrenergic-noncholinergic (NANC) system, via
upregulation of neurotransmitters, typically Substance P. Neuroendocrine
hyperplasia of infancy (NEHI), while a less common entity, is a disorder
of infancy characterized by more severe and long-term obstructive airway
disease. NEHI is pathophysiologically characterized by abundance of
neuroendocrine cells in the airways containing the neuroimmune mediator
bombesin, the release of which is presumed to be the driver of the
persistent small airway obstruction and functional air-trapping. Here we
review the NANC and NEC neurotransmitter systems and their studied roles
in pulmonary diseases with a focus on their role in lung development,
and subsequent various pediatric lung diseases. We focus on the
juxtaposition of the separate neuroimmune mechanisms underlying the
pathogenesis of post-RSV recurrent wheezing and NEHI persistent small
airway obstruction. We finally raise the question whether substance P is
indeed specific to post-RSV infection and bombesin to NEHI and then
propose a unifying concept of post-viral spectrum of respiratory
disorders that may encompass these two entities and possibly others.