Exploring the clinical relevance of cough hypersensitivity syndrome

ABSTRACT

Introduction: Knowledge of the pathophysiology of cough has continued to advance over recent decades. Establishing anatomic-diagnostic protocols, based on the anatomy and distribution of vagus nerve pathways regulating the cough reflex, was the first breakthrough in modern clinical medicine for chronic cough. The unmet clinical need has prompted revised thinking regarding the pathophysiology of and the clinical approach to chronic cough.

Areas covered: The paradigm of cough hypersensitivity syndrome (CHS) has been recently proposed, wherein aberrant neuro-pathophysiology is a common etiology. This review covers major findings on chronic cough and cough hypersensitivity, particularly focused on recently-published studies and explores the clinical relevance and applicability of CHS based on current knowledge and discuss knowledge gaps and future research directions.

Expert opinion: This paradigm has provided new opportunities in managing chronic cough and evidence is accumulating to support the validity of CHS. It also warrants the re-appraisal of existing clinical evidence and investigation of how to refine our clinical strategy. While CHS highlights the importance of clinical thinking from the viewpoint of cough, the value of anatomic-diagnostic protocols should remain. Moreover, given the considerable heterogeneity in clinical presentation, cough-associated disease conditions, and treatment responses across different patients, precise molecular endotyping remains key to making further to advancing clinical practice .

KEYWORDS:

• Cough
• heterogeneity
• hypersensitivity

Article highlights

• The concept of cough hypersensitivity syndrome (CHS) has been proposed to address unmet clinical needs in patients with chronic cough. The clinical relevance of the CHS paradigm has been supported by clinical trials with cough neuromodulatory drugs or speech language therapy in patients with unexplained or chronic refractory cough.

• The paradigm of CHS highlights the importance of clinical thinking from the viewpoint of cough in patients presenting with chronic cough. Thus, this warrants the re-appraisal of existing clinical evidence and vigorous investigation of how to refine our clinical strategy.

• Key principles of anatomic-diagnostic protocols continue to be valid. However, several disease conditions previously considered as causes of cough are more likely to be cough-triggering or sensitizing conditions. Moreover, traditional diagnostic labels do not precisely explain specific components of mechanistic associations and causal relationships with cough. Therefore, it is a more reasonable approach in the clinic to identify ‘treatable traits’ than to make a diagnosis in patients with chronic cough. However, further studies are warranted to confirm (1) which traits are clinically relevant to cough and (2) how to predict specific treatment responses in the clinic.

• Given the heterogeneous mechanistic processes driving cough hypersensitivity across different patients and different clinical contexts, deciphering the specific ‘mechanisms’ driving cough hypersensitivity would be key to making further advances in clinical practice, particularly for patients with refractory cough.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

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Funding

This paper was not funded.