Asia Pac Allergy.  2014 Jan;4(1):3-13. 10.5415/apallergy.2014.4.1.3.

Changing the paradigm for cough: does 'cough hypersensitivity' aid our understanding?

• Song WJ
• Chang YS
• Morice AH

• KMID: 2397119
• DOI: http://doi.org/10.5415/apallergy.2014.4.1.3

Abstract

Chronic cough is a common reason for patients to seek medication attention. Over the last few decades, we have experienced significant clinical success by applying the paradigm of 'evaluating and treating the causes for chronic cough'. However, we still ask ourselves 'what underlies chronic cough. Indeed in a considerable proportion of patients cough is idiopathic, or unexplained despite vigorous evaluation. Commonly associated conditions such as rhinitis, eosinophilic bronchitis, asthma, or gastroesophageal acidic reflux may not be fundamental to cough, and thus may be triggers rather than causes. The cardinal feature of chronic cough is persistent upregulation the cough reflex, which may be driven by complex interactions between biologic, neurologic, immunologic, genetic, comorbid, and environmental factors. We suggest the new paradigm 'cough hypersensitivity syndrome' should finally bring us further advances in understanding and management of chronic cough.

Keyword

Cough; Respiratory hypersensitivity; Etiology; Pathophysiology

MeSH Terms

Asthma
Bronchitis
Cough*
Eosinophils
Humans
Hypersensitivity
Reflex
Respiratory Hypersensitivity
Rhinitis
Up-Regulation

Figure

• 

  Fig. 1 Schematic presentation on development of cough hypersensitivity. Key event may be the development of vagal neuronal hypersensitivity located in the airways. Commonly associated diseases like rhinitis, eosinophilic airway inflammation, or classical acidic reflux may be triggers to lower thresholds for peripheral cough reflex activation. Nasal afferent stimulation may not directly initiate cough reflex, but modulate (sensitize or desensitize) the cough reflex depending on the type of nasal stimulus. Gaseous reflux has been hypothesized to be a common factor to develop cough hypersensitivity. TRP, transient receptor potential.

• 

  Fig. 2 Paradigms for chronic cough. (A) Anatomic diagnostic protocol: chronic cough is considered as the outcome from causative diseases affecting anatomically relevant cough reflex pathways. (B) Cough hypersensitivity syndrome: chronic cough hypersensitivity is a common intrinsic mechanism for chronic cough. Commonly associated diseases are triggers or modulators for cough reflex pathways. GERD, gastroesophageal reflux disease.

• 

  Fig. 3 Captopril-induced cough reflex sensitization. Dose-response curve for capsaicin challenge up to a maximum response of 30 coughs/min; round, captopril; square, placebo. Values shown are mean and standard error of the mean. Reprinted from Morice AH, et al. Lancet 1987;2:1116-8, with permission of Elsevier [70].

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