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.