King's College London

Research portal

Utility of cough provocation tests in chronic cough and respiratory diseases: A comprehensive review and introduction of new reference ranges for the capsaicin test

Research output: Contribution to journalArticlepeer-review

Heikki Olavi Koskela, Hanna Maria Nurmi, Surinder Singh Birring

Original languageEnglish
Pages (from-to)833-849
Number of pages17
JournalAllergy, Asthma and Immunology Research
Issue number6
PublishedNov 2021

Bibliographical note

Publisher Copyright: Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

King's Authors


Cough provocation tests (CPTs) are an objective measurement of the sensitivity of the cough reflex arc. However, they are not established in clinical practice because a large variability of response in healthy subjects limits their diagnostic value. There is a paucity of studies that have investigated CPT reference ranges in healthy subjects. This systematic review describes the variability of the responses to CPTs in healthy subjects and factors that influence it. A new analysis of 134 healthy subjects was conducted to create reference ranges for single-breath capsaicin CPT by calculating the interquartile ranges for the provocative concentration of capsaicin to induce 2 and 5 coughs. Female subjects had a more sensitive cough reflex than male counterparts. The ability of CPTs to distinguish various respiratory diseases from healthy subjects was also reviewed. Cough sensitivity was consistently heightened in the following groups: unselected patients with chronic, refractory, or recurrent cough, unexplained chronic cough, gastro-esophageal reflux-associated cough, cough-variant asthma, lower airway symptoms induced by chemical irritants, and fibrotic interstitial lung diseases. In the following groups, hypersensitivity of the cough reflex was present in those individuals whose symptom profile was predominated by cough: asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis, and sarcoidosis. In the following conditions, patients usually cough in order to expectorate mucus from their airways, not because of a hypersensitive cough reflex arc: productive cough, asthma, upper airway cough syndrome, COPD, bronchiectasis, cystic fibrosis, and chronic respiratory infections. CPTs have the potential to identify patients with chronic respiratory symptoms due to cough reflex hypersensitivity, thereby providing a targeted approach for therapy.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454