The reflex of coughing is initiated chemical and mechanical irritation of laryngeal and tracheobronchial receptors.1
Chemical receptors are sensitive to acid, heat, and capsaicin-like compounds via activation of the type-1 capsaicin receptor.
Additionally, there are multiple neural sensory receptors located within the external auditory canals, eardrums, paranasal sinuses, pharynx, diaphragm, pleura, pericardium, and stomach which are all capable of stimulating the coughing reflex. These are mechanical receptors that stimulate secondary to triggers such as touch or stretch.
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These sensory receptors are classified into one of three categories: rapidly adapting receptors, slow adapting stretch receptors, and C-fibers. Rapid adapting receptors are as the name implies myelinated quick response sensory neurons that respond within one to two seconds. These neurons have a conduction velocity of 4 to 18 meters per second. They are specialized for sensing collapse or narrowing of the airways, and responsive to dynamic changes in lung compliance. These receptors will become desensitized to prolonged inflation of the airways, and as such, are not able to moderate chronic inflation reflexes of the lungs. Such changes might include bronchospasm with constriction of the airway, mucous plugging with obstruction of the airways, or any other physiological changes in the biomechanics of the airways. Slow adapting stretch receptors are highly sensitive to mechanical forces acting on the airways as well. However, these neurons function much more slowly than their rapid-acting counterparts. They are found in the greatest density within the terminal bronchiole tree and alveoli of the lungs. As the name implies, these are associated with stretch sensation in the airway as seen in hyperinflation. These neurons do not sensitize to chronic hyperinflation. These are physiologically important in initiating the Hering-Breuer reflex at the terminal portion of inhalation to cease inhalation and induce exhalation once the lungs reach a physiological set volume to prevent barotrauma. C-fibers comprise the majority of afferent sensory innervation to the pulmonary system. They are unmyelinated neurons similar to somatic sensory nerves found elsewhere in the body with an average conduction velocity of two meters per second. Unlike rapid-acting receptors and slow-adapting stretch receptors, these neurons are relatively insensitive to mechanical stimulation providing only chemical irritation input to the central nervous system. Known chemical irritants include capsaicin, bradykinin, citric acid, hypertonic saline solution, and sulfur dioxide.
These sensory inputs from peripheral receptors travel afferently via cranial nerve X (the Vagus nerve) to the respiratory centers of the brain within the upper brain stem, medulla, and pons. While not yet fully understood, the cough center of the brain is not necessarily a centralized location. Rather it is a modulation of the inherent respiratory center of the brain.
The respiratory center of the brain is comprised of three neuron groupings: the dorsal and ventral medullary groups and the pontine grouping. The pontine grouping further sub-classified into the pneumotaxic and apneustic centers. The dorsal medulla is responsible for inhalation; the ventral medulla is responsible for exhalation, the pontine groupings are responsible for modulating the intensity and frequency of the medullary signals, while the pneumotaxic groups limit inhalation and the apneustic centers prolong and encourage inhalation. Each of these groups communicates with one another to concert the efforts as the pace making potential of respiration. All cough receptors project sensory input through the nucleus tractus solitarius to other parts of the respiratory networks. The pre-Botzinger complex specifically acts as a unique pattern generation center for the cough response. Parts of the caudal medullary raphe nucleus consisting primarily of the nucleus raphe obscurus and nucleus raphe magnus are essential for coughing as well. The net result of these generated intertwined action potentials results in an efferent signal generation that travels through the vagus, phrenic, and spinal motor nerves to the expiratory musculature of the diaphragm, intercostals, pharynx, and neck to produce a cough.
The mechanism of action for coughing can be subdivided into three overarching phases: the inspiration phase, the compression phase, and the expiratory phase. During the inspiration phase, inhalation occurs generating an increase in volume within the pulmonary system. This volume is necessary for generating enough air movement to be productive. The compression phase is marked by the closure of the larynx combined with contraction of muscles of exhalation including the intercostals, diaphragm, and abdominals leading to a net increase in intrathoracic pressure without any air movement occurring. The expiration phase is marked by the rapid opening of the glottis resulting in rapid, high volume expiratory airflow. This rapid airflow causes vibrations within the larynx and pharynx inducing the characteristic sounds of a cough. Throughout this process, airway compression occurs resulting in a net decrease in intrathoracic volume. After exhalation, rebound inhalation may occur, depending on the duration of a coughing episode as well as the volume of airflow movement, in compensation to developed hypoxia or reflexive inhalation.[4][13]
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These vagal sensory nerves begin primarily in the larynx, trachea, carina, and large intrapulmonary bronchi.
Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature regulate cough patterning and cough sensitivity.
The brainstem and higher brain control systems received these signals and activate the diaphragm, intercostal muscles, laryngeal muscles and the abdominal muscles.1
Effective cough depends on an intact afferent–efferent reflex arc, adequate expiratory and chest wall muscle strength, and normal mucociliary production and clearance.