![]() ![]() This perspective explores the complexity of coughing and suggests hypotheses about the unique evolutionary basis for the human cough reflex. Involvement of the upper and/or lower airways play pathogenetic roles in cough development and the association of allergy represent an important contributing factor for cough exacerbation. Persistent cough is one of the most common medical complaints that impacts the quality of life and is responsible for a significant proportion of annual ambulatory medical visits and medical expenses in the United States. For both types of cough, the motor responses are identical and via coordinated, precisely-timed and sequential respiratory events orchestrated by complex neuromuscular networking of the diaphragm, chest and abdominal respiratory muscles, the glottis and parts of the brain. TRPA 1, another excitatory ion channel, has been referred to as the "irritant receptor" and its activation also induces cough. The airways do not normally manifest nociceptive pain from a stimulus but the only consistent response that capsaicin and lung inflammation provoke in healthy human airways is cough. The mechanism for the latter type of cough is analogous to induced pain after tissue injury and, it is controlled by the identical transient receptor potential vanilloid cation channel (TRPV 1). Supposedly, its origin dates back when prehistoric humans began living in close proximity to each other and were at risk for infectious respiratory diseases or irritant-induced lung injury. The second type of cough reflex, a chemosensory type, is carried by unmyelinated C fibers. This became necessary as the larynx moves closer to the opening of the esophagus as human ancestors adapt phonation over olfaction beginning less than 10 million years ago. A mechanosensory-induced cough reflex conveys through branches of myelinated Aδ nerve fibers is not chemically reactive (i.e., capsaicin, bradykinin) possibly, its evolution is to prevent the harmful effects of aspiration of gastric or particulate contents into the lungs. This review dissects the complex human cough reflex and suggests hypotheses about the evolutionary basis for the reflex. ![]()
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