Stability of cough reflex sensitivity during viral upper respiratory tract infection (common cold)

https://doi.org/10.1016/j.pupt.2014.05.004Get rights and content

Abstract

Cough is among the symptoms most commonly associated with an acute, viral upper respiratory tract infection (URI), such as the common cold. Two previous studies incorporating capsaicin cough challenge methodology have demonstrated that cough reflex sensitivity is transiently enhanced during URI. These studies used single measurements of cough reflex sensitivity during the URI period. To our knowledge, no previous studies have included multiple measurements of cough reflex sensitivity to capsaicin during a URI to evaluate the stability of this measure during the acute viral illness.

In the current methodological investigation, we performed capsaicin cough challenges in 42 subjects with URI who were otherwise healthy, adult, nonsmokers (25 female). Subjects were enrolled within 72 h of onset of illness and randomly assigned to 3 groups (n = 14 each) that underwent cough reflex sensitivity measurement (C2 and C5) at days 0 and 1 for group 1; days 2 and 3 for group 2; or days 4 and 5 for group 3. Each subject returned 4–8 weeks post-viral infection to establish a healthy baseline measurement (recovery).

Our results support that cough reflex sensitivity to capsaicin, as measured by C5, is a sensitive measure that remains stable during 6 days of a URI. These results suggest that cough reflex sensitivity measures in the presence of a URI provide a sensitive and reproducible approach that could be used in future investigations seeking to test experimental antitussive therapies.

Introduction

Cough is among the most common symptoms associated with an acute, viral upper respiratory tract infection (URI), otherwise known as the common cold or flu. Traditionally, efficacy of an antitussive therapy has relied on objective cough counting in a natural cold population. However, given the highly variable nature of cough in this context, identification of new treatments of acute cough in the natural setting remains a challenge. Consequently, the search for additional safe and effective therapeutic agents remains an area of active investigation [1], [2] as does the search for alternative methods for assessing their activity. In 1996, O'Connell and colleagues demonstrated that cough reflex sensitivity to inhaled capsaicin is transiently increased during URI in otherwise healthy persons, compared to their pre-illness baseline and post-recovery [3]. These observations were recently confirmed in a study of otherwise healthy, adult, non-smokers who underwent capsaicin cough challenge testing during acute URI and 4–8 weeks subsequently (post recovery) [4]. Both of these studies measured cough reflex sensitivity at a single time-point during the acute viral illness. To our knowledge, no one has previously performed multiple measurements of cough reflex sensitivity over the early days of a URI to evaluate the utility of such a model. The goal of this research was to determine if cough reflex sensitivity, as measured by C2 (concentration of capsaicin inducing 2 or more coughs) and C5 (concentration of capsaicin inducing 5 or more coughs), remains stable over 6 days of a URI, when subjects were enrolled within the first 3 days of the illness. If cough reflex sensitivity is stable over time, this methodology may provide a sensitive and reproducible measure for examining the effect of purported antitussive therapies in the setting of a URI.

Section snippets

Subjects

Forty-two (42) otherwise healthy, adult, non-smokers developing symptoms consistent with acute viral URI (common cold) were recruited and enrolled within 3 days of symptom onset. An acute URI was defined as an illness of acute onset typical of previous episodes of common cold for that subject, including some, but not necessarily all, of the standard symptoms of cough, sore throat, rhinorrhea, nasal/sinus congestion, and sneezing. Subjects with a history of allergic rhinitis in whom symptoms may

Results

A total of 42 subjects were enrolled in the study (n = 14 per group). Forty (40) subjects completed the study and were included in all analyses. Two subjects developed new colds prior to the recovery phase data collection and were excluded from all analyses.

Table 1 shows the demographics of study participants. No significant differences were observed between the groups based on age, sex, number of days sick at screening, or C2 and C5 concentrations during recovery phase.

As shown in Table 2,

Discussion

The assessment of cough in community-acquired common cold is difficult for a variety of reasons, including natural resolution of the infection, high inter-subject variability and the lack of standardized cough counting measures. This investigation provides an assessment of an induced cough model (inhaled capsaicin) conducted in subjects experiencing a common cold over several days and demonstrates that such a model may provide utility in the discernment of a therapeutic intervention aimed to

Acknowledgments

Financial support for this study was provided by Procter & Gamble. We are grateful to the following P&G employees for their various contributions to the study design, statistical analysis, and expert comments for this manuscript: J. David Hull, Lynn Jump, and Robert A. Lyon. We also acknowledge Angela Qu.

References (7)

There are more references available in the full text version of this article.

Cited by (15)

View all citing articles on Scopus

This study was supported by Procter & Gamble. The author presented this work in part at the European Respiratory Society annual meeting 24–28 September 2011 in Amsterdam.

View full text