Cough Hypersensitivity Syndrome: A Few More Steps Forward

Abstract

Cough reflex is a vital protective mechanism against aspiration, but when dysregulated, it can become hypersensitive. In fact, chronic cough is a significant medical problem with a high degree of morbidity. Recently, a unifying paradigm of cough hypersensitivity syndrome has been proposed. It represents a clinical entity in which chronic cough is a major presenting problem, regardless of the underlying condition. Although it remains a theoretical construct, emerging evidence suggests that aberrant neurophysiology is the common etiology of this syndrome. Recent success in randomized clinical trials using a P2X3 receptor antagonist is the first major advance in the therapeutics of cough in the past 30 years; it at last provides a strategy for treating intractable cough as well as an invaluable tool for dissecting the mechanism underpinning cough hypersensitivity. Additionally, several cough measurement tools have been validated for use and will help assess the clinical relevance of cough in various underlying conditions. Along with this paradigm shift, our understanding of cough mechanisms has improved during the past decades, allowing us to continue to take more steps forward in the future.

Oto-tricho-tussia: An Unexpected Cause of Cough

“…e chronic cough hypersensitivity model suggests that peripheral inputs, such as viruses, allergens, and air pollutants, can upregulate host cough responses and prompt phenotypic switches in the sensory neurons, leading to a state of hyperresponsiveness. Sensory neurons can show an increased expression of transient receptor potential (TRP) ion channels [9]. e three cases above illustrate a cough reflex likely elicited from stimulation of the somatic sensory portion of the auricular branch of the vagus nerve (ABVN) innervating the external auditory canal.…”

Tos crónica por hipersensibilidad refleja: un nuevo paradigma con implicancias diagnósticas y terapéuticas

“…Así recientemente se reconoció la existencia de un síndrome de "tos por hipersensibilidad refleja o neuropatía" que se sustentó inicialmente en términos teóricos, pero que ha tenido considerables avances en su conocimiento fisiopatológico en los últimos años que le otorgan un soporte nosológico. 26,27 Tos por hipersensibilidad refleja.…”

“…Se define como una entidad clínica caracterizada por tos desencadenada por bajos niveles de estímulos térmicos, mecánicos y químicos o situaciones tan habituales como hablar, cantar, el ejercicio y stress 25,27,28 El término se ha propuesto para identificar a un grupo de pacientes con tos crónica no explicada por una causa precisa, a los que no se les ha encontrado ninguna razón para justificar la prolongación de su síntoma utilizando el protocolo diagnóstico clásico y no se resuelve con un tratamiento etiológico 28 . Generalmente la tos es seca o escasamente productiva con disfonía y sensación urgente de toser.…”

Drug-Induced Cough

“…Chronic cough is a multi-factorial disease with a neurological basis in adults (Morice et al 2014a, Song andMorice 2017). The recognition of angiotensinconverting enzyme inhibitors (ACEIs)-induced coughs (Sesoko and Kaneko 1985, Semple and Herd 1986, Morice et al 1987 has not only led to the clinical recommendation that drug should be considered as a potential cause of cough (Irwin et al 2018, Song et al 2018, Morice et al 2019, but also has provided an important clue to the notion that cough reflex hypersensitivity commonly underlies chronic cough in adults (Morice et al 2014a) ( Fig.…”