Validation of the ERS standard citric acid cough challenge in healthy adult volunteers

Caroline E Wright,Alyn H Morice,Rachel L Thompson,Jennifer Jackson

doi:10.1186/1745-9974-6-8

Abstract

Protocols measuring cough sensitivity can vary in terms of nebuliser, tussive agent, single and dose response. A definitive method for measuring cough sensitivity needs to be established.The ERS guidelines recommend the KoKo DigiDoser (KD) delivery system. Study aim, was to compare the reproducibility of this citric acid (CA) cough challenge and previously established Mefar dosimeter (MD) protocol.39 (female 26) volunteers mean age (40.4 yrs) were randomised to either KD or MD. Intra-day and inter-day reproducibility was compared.We calculated the concentration of citric acid evoking 2 coughs (C2).The geometric mean C2 (95%CI) was similar for both KD and MD, of 263 (200,339) mM and 209 (151,288) mM respectively.The mean KD C2 was not significantly different. (F = 0.807, p = 0.93) from baseline over 1, 2, and 4 hrs however, the MD demonstrated significant variability (F = 7.85, P < 0.001)Measuring mean log C2 at baseline and at 2 weeks, the KD demonstrated a stronger intraclass correlation of log C2 at baseline with 2 week log C2, ICC = 0.70 than was shown with the Mefar, ICC = 0.41Administering CA from KD offers a reproducible cough challenge in healthy volunteers. The results correlate well with the MD challenge but offer greater intra-day and inter-day reproducibility.Trial RegistrationCurrent controlled trials ISRCTN98385033

Highlights

The methodology of citric acid cough challenge was first reported in humans over 50 yrs ago [1]
Recently Dicpinigaitis [14] published a paper on the short-term and long-term reproducibility of capsaicin cough challenge testing; this study used the KoKo DigiDoser delivery system
Reproducibility of the capsaicin cough challenge studied by Dicpinigaitis demonstrated that the change in log C2 in the short term group was 0.27 ± 0.29 mM 75% of patients studied showed a within 1 doubling dose change in C2 and 95% were within 2 doubling doses

Summary

Introduction

The methodology of citric acid cough challenge was first reported in humans over 50 yrs ago [1]. It was developed to allow for the quantification of cough reflex sensitivity and as a tool for the assessment of antitussive therapies. Since this time many different protocols have been published and these can vary greatly in terms of the nebuliser used, the tussive agent, single breath, single dose or dose response and even the method to count number of coughs required to attain a threshold. Citric acid is established as a tussive stimulus in cough challenge demonstrating both physiological alterations in cough reflex sensitivity as well as the pharmacological properties of antitussives

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Results

Conclusion