Previous studies have documented the transient increase in cough reflex sensitivity during URI.
Therefore, our subjects with URI were in a hypertussive state relative to their baseline. Because of the huge variation in cough sensitivity among the population, studies such as this one, assessing the effect of a pharmacologic intervention on cough reflex sensitivity,
must use each subject as his or her own control. Furthermore, the tremendous variation in
baseline cough reflex sensitivity among individuals renders comparison of small groups irrelevant. In other words, subjects in our acute URI group ar hypertussive relative to their own healthy baseline, not relative to the healthy volunteer group. The absence of a statistically-significant difference in baseline cough sensitivity between our two study
groups does not imply, therefore, a lack of a state of cough receptor hypersensitivity among the URI subjects. The question of whether guaifenesin has an inhibitory effect in other hypertussive states, such as with gastroesophageal reflux, cough-variant asthma, or with the use of angiotensin-converting enzyme inhibitors, awaits elucidation in future trials.
The mechanism by which guaifenesin inhibits cough reflex sensitivity remains speculative. Given its use as an anesthetic agent in horses, a central antitussive effect of guaifenesin may be suggested. However, if indeed cough inhibition by guaifenesin was predominantly central, one might expect antitussive activity to be demonstrated in some healthy volunteers as well, as has been shown with centrally acting antitussive agents such as codeine, dextromethorphan,
and baclofen.