Brain Hypoxia and Cerebrovascular Events:
The central nervous system (CNS) is significantly affected by hypoxia,
which can suppress the cough by various mechanisms, decreasing the
sensitivity of the peripheral cough receptors and the sensitivity of the
rostral and caudal parts of the nucleus solitaire. This nucleus is the
recipient of all visceral afferents and an essential part of the
regulatory centres of internal homeostasis, through its multiple
projections with cardiorespiratory and gastrointestinal regulatory
centres (25). The depressive effect of hypoxia on the nucleus solitaire
is mediated through the gamma-aminobutyric acid (GABA)-mediated pathway.
GABA is the major inhibitory neurotransmitter and can downregulate the
sensitivity of the cough reflex. Therefore, baclofen, which is a GABA
agonist, can decrease cough sensitivity to capsaicin in healthy
individuals (26). Besides, hypoxia may increase CNS levels of endogenous
opioids, thereby decreasing cough sensitivity by inhibiting the central
component of cough. Hypoxia can occur in many cardiovascular diseases.
Hypoxia-related impairment of the cough increases morbidity and
mortality in these conditions (27). The cough reflex can be assessed in
a comatose patient as part of Brainstem Responses Assessment Sedation
Score (BRASS) in the ICU by observing the patient’s response to tracheal
suctioning. It is considered positive when contraction of the abdominal
muscles is observed (28).
The cortex has its control over the cough. The ability to produce and
suppress cough voluntarily are examples of cortical control of cough.
Decreased strength of voluntary coughing may increase the risk of
aspiration and other pulmonary sequelae due to inadequate clearance of
aspirated material from the airways, as observed in patients with
brainstem or cerebral stroke associated with an abnormal laryngeal cough
reflex (29). Many patients with cerebral hemispheric stroke exhibit a
transient or prolonged disturbance of the laryngeal cough reflex (known
as ”brainstem shock”). This shock is characterised by generalised
transient or persistent neurologic dysfunction of one or more vital
neurologic functions, including respiratory drive, the reticular
activating system, or the laryngeal cough reflex. As a result, many
patients with severe or mild hemispheric strokes may develop impaired
consciousness and require intubation due to reduced respiratory drive
(30). Daniels et al. showed that 67% of their patients with stroke had
no cough response, and 38% had suffered aspiration (31). Therefore,
adding cough sensitivity testing to the clinical assessment of
swallowing function can significantly reduce the risk of aspiration
pneumonia in patients with cerebral or brainstem stroke (32). It also
helps monitor recovery from stroke and assesses postoperative recovery
of the laryngeal cough reflex after extubation (29).
Patients with dementia due to Lewy body disease have decreased cough
reflex sensitivity and central respiratory chemosensitivity, with
decreased activation of the insula associated with the urge-to-cough
(8). Patients with Parkinson’s disease also have decreased intensity of
both voluntary and reflex cough efforts with slightly increased cough
threshold. Fontana et al. found that, especially in early stages, a
motor rather than a sensory component of the cough reflex is involved,
mainly due to impaired central activation of motor units and reduced
neural control of expiratory muscles. This reflects the presence of
bradykinesia, which is one of the most important dysfunctions in these
patients (33). Parkinsonism is associated with decreased production of
dopamine and other neurotransmitters in the substantia nigra, which
affects the production of substance P in the C fibres of the vagal
sensory nerve in the cervical ganglia. Low substance P levels weaken the
swallowing reflex and suppress the cough reflex, leading to frequent
aspiration (34). Approximately 20% of deaths in patients with
Parkinsonism were related to pneumonia, likely due to the impaired cough
reflex and upper airway muscle dysfunction (35). Similarly, multiple
sclerosis, with its characteristic disseminated demyelination patches in
both the brain and spinal cord, may impair voluntary cough efficiency
and respiratory muscle strength due to bulbar dysfunction and damage to
the corticospinal tract in the spinal cord. The degree of impairment of
the cough reflex is inversely correlated with the degree of disability
of the patients (36).