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).