Conclusion.
In infancy and early childhood neuropeptide released by nonadrenergic and noncholinergic (NANC) nerves and by neuroendocrine cells (NEC) play a significant pathogenetic role in a wide variety of lung diseases. An interesting observation is the different sequelae driven by two neuroimmune mediators, substance P and bombesin, respectively in post-RSV wheezing and NEHI. It would be interesting to explore whether these respective mediators are upregulated in both conditions, rather than specific to one or the other. The finding of long-term persistence of RSV in bone marrow may indicate that while absent in the lung, the virus’ long-term sequelae may be governed by persistent extrapulmonary immune activity. If one accepts that NEHI may be a sequel of RSV or other viral infection, while cognizant of the limitations imposed by absence of animal models of NEHI, it would be of interest to explore virus permanence in bone marrow of such patients. Finally, if persistent neurokinin activity constitutes the underlying factor determining some of these morbidities, blockers of these molecules may offer future specific therapeutic targets.
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Legends for Figures.
Figure 1. Bronchial smooth muscle tone is regulated by cholinergic bronchoconstrictor and the adrenergic bronchodilator neural pathways, but also by NANC nerves, which can be either inhibitory (i-NANC) or excitatory (e-NANC). E-NANC-mediated bronchoconstriction is under the control of a subpopulation of non-myelinated C-fiber primary afferent neurons which release Sub P. Bronchial smooth muscle tone is also increased by the pulmonary NEC cells, system localized in the airway epithelium that express a variety of bioactive substances including the neuropeptides bombesin. Vasoactive intestinal peptide (VIP) counteracts the bronchoconstrictive effect of Sub P and bombesin the bronchorelaxant, whilst norepinephrine (NE) inhibits the release of acetylcholine by the vagus nerve.
Figure 2. A. During and after RSV lower respiratory tract infection airway hyperresponsiveness, increased vascular permeability and neurogenic inflammation are largely attributed to substance P and its upregulated NK1 receptor. B. In NEHI, bombesin is thought to be involved in the pathogenesis of small airway obstruction, but is may also play a protective role against noxious agents, such as respiratory viruses.