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Narrative Review of the Mechanisms and Treatment of Cough in Asthma, Cough Variant Asthma, and Non-asthmatic Eosinophilic Bronchitis

  • COUGH AND ASTHMA
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Abstract

Chronic cough is a debilitating condition affecting 10–12% of the general population and is one of the leading causes for referral to secondary care. Many conditions have been associated with chronic cough, including asthma, gastro-esophageal reflux disease and upper airways cough syndrome. Inflammatory airway conditions including cough variant asthma (CVA) and non-asthmatic eosinophilic bronchitis (NAEB) contribute to a significant proportion of presentations with chronic cough, with differing diagnostic criteria and different responses to commonly used asthma therapy for their respective diagnoses. Mechanistic studies in both animal models and humans have identified increased neuronal sensitivity and subsequent central sensitization. These mechanisms include inflammatory-mediated nociceptor sensitization and alterations of afferent nerve terminal excitability, phenotypic changes in the vagal afferent neurons over time, and central neuroplasticity resulting from increased synaptic signalling from peripheral afferents. The aim of this review is to discuss the mechanisms, neurophysiology, and management approaches currently available for patients presenting with chronic cough with underlying asthma, CVA, and NAEB and to shed a light on areas of further research required to elucidate the mechanisms of cough in this patient population.

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Abbreviations

UACS:

Upper airway cough syndrome

GERD:

Gastro-esophageal reflux disease

CVA:

Cough variant asthma

NAEB:

Non-asthmatic eosinophilic bronchitis

FEV1:

Forced expiratory volume in 1 s

SABA:

Short-acting β2-agonist

AHR:

Airway hyperresponsiveness

BAL:

Bronchoalveolar lavage

FeNO:

Fractional exhaled nitric oxide

LGIC:

Ligand-gated ion channels

GPCR:

G-protein-coupled receptors

VGIC:

Voltage-gated ion channels

TRPV:

Transient receptor potential vanillin

TRPA1:

Transient receptor potential ankyrin-1

NTS:

Nucleus tractus solitarius

DNIC:

Descending inhibitory control pathways

PGE2:

Prostaglandin E2

ATP:

Adenosine triphosphate

ASM:

Airway smooth muscle

CGRP:

Calcitonin gene-related peptide

BDNF:

Brain-derived neurotrophic factors

GCH:

Goblet cell hyperplasia

ICS:

Inhaled corticosteroid

LABA:

Long-acting beta-agonist

LAMA:

Long-acting muscarinic antagonists

LTRA:

Leukotriene receptor antagonists

VAS:

Visual analogue scale

RARs:

Rapidly adapting irritant receptors

LCQ:

Leicester Cough Questionnaire

BT:

Bronchial thermoplasty

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Authors and Affiliations

  1. Department of Medicine, McMaster University, Hamilton, ON, Canada

    Nermin Diab, Matthew Patel, Paul O’Byrne & Imran Satia

  2. Firestone Institute for Respiratory Health, St Joseph’s Healthcare, Hamilton, ON, Canada

    Nermin Diab & Imran Satia

  3. Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON, Canada

    Nermin Diab, Paul O’Byrne & Imran Satia

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  1. Nermin Diab
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  2. Matthew Patel
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Contributions

ND MP and IS made substantial contributions to the conception or design of the work; the acquisition and interpretation of data for the work; and drafting the work. All authors contributed to revising the work critically for important intellectual content and to the final approval of the version to be published.

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Correspondence to Nermin Diab.

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Conflict of interest

N.D. is currently supported by the Canadian Asthma, Allergy, and Immunology Foundation and Sanofi Genzyme, Canada. M.P. has no disclosures to report. P.O.B. reports grants and personal fees from AstraZeneca, personal fees from GSK, grants from Novartis, grants and personal fees from Medimmune, and personal fees from Chiesi, outside the submitted work. I.S. reports grants and personal fees from Merck Canada, grants and personal fees from GSK, and personal fees from AstraZeneca, Respiplus, and Genentech outside the submitted work. I.S. is currently supported by the E.J. Moran Campbell Early Career Award, Department of Medicine, McMaster University.

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Diab, N., Patel, M., O’Byrne, P. et al. Narrative Review of the Mechanisms and Treatment of Cough in Asthma, Cough Variant Asthma, and Non-asthmatic Eosinophilic Bronchitis. Lung 200, 707–716 (2022). https://doi.org/10.1007/s00408-022-00575-6

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