Introduction
In infancy and early childhood neuropeptide released by nonadrenergic
and noncholinergic (NANC) nerves and by neuroendocrine cells (NEC) are
thought to play a significant pathogenetic role in lung diseases
characterized by airflow limitations1,2. A common
disorder in pediatric practice is early-childhood bronchial obstruction
which, when transient and intermittent, is largely attributed to
respiratory viruses3,4 . Predominant amongst those
involved in the first respiratory infection and underlying long-term
wheezing is respiratory syncytial virus (RSV). The pathogenetic
mechanisms inducing airway instability after RSV bronchiolitis are
attributed to neuroimmune inflammatory processes, at least in part
related to upregulation of the tachykinin neuropeptide substance P (Sub
P) and of its receptors neurokinin (NK)12,5,6. A
different disorder of infancy, associated with persistent airflow
limitation, is neuroendocrine hyperplasia of infancy (NEHI). This entity
is classified as diffuse interstitial lung disease but is characterized
physiologically by small airway obstruction, and almost never associated
with structural changes or signs of inflammation 7.
NEHI also is presumed to be driven by a neuroimmune mediator, bombesin,
released by pulmonary NEC 7. During the early stage of
embryonic development, NEC play a key role in growth and differentiation
whilst, at the time of birth, act as airway O2 sensors
involved in neonatal adaptation to extrauterine
life3,7,8. In infancy and early childhood, through the
release of neurotransmitters, NEC are thought to be have a role in the
pathogenesis of a variety of other airway disorders, including pulmonary
hypertension (PH), bronchopulmonary dysplasia (BPD), sudden infant death
syndrome (SIDS), congenital central hypoventilation syndrome (CCHS) and
cystic fibrosis (CF)9. The aim of this manuscript is
to briefly review and discuss the commonality and the differences among
these entities driven by neuroimmune mechanisms, with a focus on RSV
bronchiolitis and NEHI and propose a unifying paradigm between these two
distinct entities.