Vagal neuropathy:
Cough reflex hypersensitivity is manifested by the occurrence of
coughing attacks, often triggered by low-threshold stimuli to which the
patient is exposed during normal daily activities. Cough reflex
hypersensitivity is observed in all respiratory diseases (acute or
chronic) when cough is a predominant feature. At the same time,
neuroinflammation is one of the most important causes of cough reflex
hypersensitivity (17). Cranial nerves, including the vagus nerve, may be
affected by inflammatory neuropathic processes. The vagus nerve
extensively innervates the respiratory and digestive tracts. Dysfunction
of the vagus nerve can cause cough (18).
Chronic neuropathy of the laryngopharyngeal nerve, which is a branch of
the vagus nerve, manifests as symptoms of laryngeal irritation such as
chronic cough, stridor, pharyngeal irritation, dysphonia, and foreign
body sensation in the throat. In patients suffering from laryngeal
neuropathy, there is increased sensitization of the cough reflex with
abnormal neuropathic responses to receptor stimuli. Laryngopharyngeal
neuropathy can lead to alterations in the afferent branches of the
laryngeal and digestive reflex arcs. Consequently, various stimuli such
as acids may trigger the symptoms. This may be accompanied by
paradoxical vocal fold movements as part of a syndrome of irritated
larynx, in which hypersensitivity of afferent reflexes is a common
mechanism (19). Neuropathy of the vagus nerve may also affect other
motor branches of the vagus nerve and cause paresis or paralysis of the
vocal folds, paradoxical vocal fold movements, or other sensory branches
causing chronic cough and other symptoms such as scratchy throat, sore
throat, laryngeal paresthesias, and laryngospasm. These symptoms can be
aggravated and provoked by talking, laughing, irritating inhalants, and
palpation of the larynx (20).
Vagus nerve dysfunction may occur after viral infections or exposure to
irritants or may be caused by chronic diseases such as asthma. In
asthma, increased levels of substance P and neurokinin A in induced
sputum samples are indicative of neuronal activation of the airways.
Besides, levels of the neuropeptide calcitonin gene-related peptide
(NCRP) in bronchoalveolar lavage from children with chronic cough are
positively correlated with capsaicin cough reflex sensitivity. There is
increased expression of NCRP in the nerves supplying the airways in
patients with chronic cough (21). In diseases associated with persistent
coughs, such as idiopathic pulmonary fibrosis, there are high levels of
nerve growth factor in the airways of patients, which has important
neuroinflammatory consequences and maybe one of the factors responsible
for the chronicity of cough (22). Vitamin B12 deficiency can cause
sensory neuropathy leading to dysfunction of the pharynx and larynx,
which can trigger a chronic cough. Vitamin B12 supplementation can
improve histamine threshold and significantly increase cough threshold
in patients with chronic cough due to vitamin B12 deficiency but has no
significant effect on individuals without deficiency (23). Vitamin B12
deficiency-related cough should be kept in mind in patients treated with
proton pump inhibitors or cytotoxic drugs. Considering chronic cough as
a neuropathic disorder, just like neuropathic chronic pain, will
significantly change the possible strategies for the diagnosis and
management of chronic cough (24).
Neurological Conditions Associated with Diminished Cough
Reflex Sensitivity:
Because it is a reflex that predominantly involves the brainstem and is
modulated by the cerebral cortex, the cough may be diminished in various
neurologic disorders affecting both the peripheral and central nervous
systems. A diminished cough reflex (dystonia) is associated with a high
risk of developing pneumonia and an increased rate of morbidity and
mortality in these disorders.