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.