The Use of Inhaled N-Acetylcysteine for Laryngopharyngeal Reflux Disease: A Randomized Controlled Trial

Proton pump inhibitors (PPIs) are the mainstay of the medical treatment for laryngopharyngeal reflux disease (LPRD). However, extraesophageal symptoms of LPRD, such as globus, are often refractory to PPI treatment. Many kinds of adjunctive medications have been attempted to address those refractory cases. We aimed to study whether inhaled N-acetylcysteine (NAC), a mucolytic agent, has additive effects for the treatment of LPRD when used in conjunction with PPIs. Patients with reflux symptom index (RSI) greater than 13 and reflux finding scores (RFS) greater than 7 were prospectively enrolled and were randomly assigned to control or study group. Patients were treated with oral rabeprazole in the control group and with oral rabeprazole and inhaled NAC in the study group. Patients were followed once a month for 2 months with questionnaires and stroboscopic examination. At every follow-up, RSI and RFS were checked. The extent of improvements of RSI and RFS were evaluated and compared between two groups. With treatment, the mean RSI changed from 21.0 to 7.6 (P < 0.001) in control group and from 19.7 to 4.5 (P < 0.001) in study group. The mean RFS also changed from 12.9 to 7.1 (P < 0.001) in control group and from 13.5 to 6.9 (P < 0.001) in study group. For both RSI and RFS, the extents of improvement were not significantly different between two groups. In patients whose RSI improved less than nine at the first follow-up (poor early responders), RSI became significantly lower in the study group (4.6 ± 2.0) than in the control group (9.5 ± 4.6) at second follow-up (P = 0.019). In good early responders, however, RSI was not significantly different between the two groups in the second follow-up. In this study, there were no significant differences in the overall outcome between patients treated with inhaled NAC and PPI and those with PPI alone. Interestingly, some additional therapeutic effect of NAC appeared late for the patients with poor early response. Further studies are required to investigate the underlying mechanism for this.