The aim of the prospective study presented here was to test the diagnostic significance of pepsin concentration in saliva and induced sputum in patients with chronic cough and to compare it with the established GerdQ questionnaire.
The reason why pepsin was investigated as a diagnostic marker for reflux-related cough is as follows: the enzyme is produced exclusively in the stomach. Therefore, its detection in saliva or sputum would be a direct indication of gastroesophageal reflux.
The research group therefore aimed to test the diagnostic significance of pepsin concentration in saliva or sputum as a simple, non-invasive marker for reflux-induced coughing – especially in cases of non-acid reflux, where classic tests such as GerdQ reach their limits. In this type of reflux, it is not acidic but alkaline (bitter, bilious) fluid that flows back into the oesophagus.
A total of 171 patients with chronic cough were included in the prospective study (DOI: ). The reflux-induced cough was diagnosed using a four-step protocol that included pH measurement and response to stepwise antireflux therapy. Sixty-seven cases of reflux-induced cough were diagnosed, 22 of which were acidic and 19 non-acidic. The remaining 104 subjects suffered from other forms of chronic cough.
Saliva and sputum samples were collected to determine pepsin concentrations. Participants also completed the GerdQ questionnaire.
Die Ergebnisse sprechen klar für die Pepsin-Testung im Speichel als gute Alternative zur Diagnostik des refluxinduzierten Hustens: Die mittlere Pepsinkonzentration im Speichel war bei betroffenen Patienten signifikant höher (132,5 ± 103,9 ng/mL) als bei nicht betroffenen Personen (30,05 ± 64,33 ng/mL; p < 0,001) sowie gegenüber Personen mit anderen chronischen Hustenformen (p < 0,001).
An optimal cut-off value of 76.10 ng/mL was identified for the saliva pepsin test. With an AUC (area under the curve, a measure of the diagnostic accuracy of a test) of 0.845, the saliva test showed high diagnostic significance for reflux-induced coughing. Sensitivity and specificity were 83.6% and 82.7%, respectively. The test thus significantly outperformed the GerdQ (p = 0.0008).
In contrast to the saliva sample, the pepsin concentration in induced sputum showed no significant diagnostic value. The concentrations averaged 0 ng/mL for reflux-induced cough and non-reflux-induced cough. The low significance was attributed, among other things, to proteolytic influences from dithiothreitol, which was used to prepare the sputum samples, as well as to the low amount of reflux entering the airways. Other pathophysiological factors such as cough reflexes and bronchial clearance could also influence the measurement.
In the subgroup with acidic reflux-induced cough, the AUC of the saliva test was 0.779; for non-acidic reflux-induced cough, it was even 0.830. In particular, in the case of non-acid reflux, the saliva test showed clear superiority over the questionnaire (p < 0.0001) compared to the GerdQ. The saliva pepsin concentration was significantly higher in both forms of reflux than in non-reflux-induced cough, but did not differ significantly between acid and non-acid cough.
GerdQ only achieved an AUC of 0.670 for reflux-related coughing. Its significance is particularly limited in patients with non-acidic reflux, as typical reflux symptoms may be absent. The saliva test offers a promising alternative here. Saliva collection is non-invasive, inexpensive and easy to perform; a significant advantage over pH measurement in the oesophagus, which is a fairly reliable but also complex and invasive diagnostic method.
The results show that the saliva pepsin test is a reliable tool for identifying reflux-induced cough, especially in non-acidic forms where the standard diagnostic procedure using questionnaires can fail. Its ease of use and high diagnostic accuracy argue in favour of wider application in routine clinical practice.