Classification of the non-acid laryngopharyngeal reflux

Laryngopharyngeal reflux disease (LPRD) is currently defined as an inflammatory condition of the upper aerodigestive tract tissues related to the direct and indirect effects of gastroduodenal content reflux, which may induce morphologic changes in the upper aerodigestive tract.[1] The pH of gastric contents is lower, which mainly causes acid reflux, while the pH of duodenal contents is higher than that of gastric contents, which can cause weakly acid reflux or alkaline reflux. Because carbonic anhydrase in the esophageal mucosa can convert CO2, a product of cell metabolism, into bicarbonate, which plays a role in neutralizing gastric acid. Therefore, part of gastric acid reflux or duodenal contents reflux has a pH of less than 4 at the distal esophagus, but when it reaches the hypopharynx, the pH is greater than 4 and is converted to weakly acid or alkaline reflux. Therefore, using 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring, laryngopharyngeal reflux (LPR) events are divided into the following categories according to the difference of pH in hypopharynx[2]: (1) Acid LPR when pH was ≤4; (2) Weakly acid LPR when pH was 4 to 7; (3) Alkaline LPR when pH above 7. Both weakly acid and alkaline LPR were called non-acid reflux. According to the pH value of the distal esophagus and hypopharynx, non-acid reflux can be further divided into true non-acid reflux (pH >4 in both the distal esophagus and hypopharynx) and false non-acid reflux (pH ≤4 in the distal esophagus, but pH >4 in the hypopharynx) [Figure 1]. However, for each patient, the proportion of the true non-acid, false non-acid, and acid reflux of the LPR events is helpful to the develop a treatment plan. If true non-acid reflux events accounts for the majority of LPR events, then acid suppressive therapy is not the main one. If false non-acid reflux and acid reflux are dominant, then acid suppressive therapy is still very important. However, there are few studies on this classification of proportion in the literature, so we aimed to analyze the 24-h MII-pH data of 50 patients with suspected LPRD in order to understand the proportion of all kinds of LPR, which may be helpful to make the treatment plan of LPRD.Figure 1: Photos of 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring. (A) Acid LPR; (B) Weakly acid LPR; (C) Alkaline LPR; (D) True non-acid LPR; (E) False non-acid LPR. LPR: Laryngopharyngeal reflux.From January 2015 to January 2020, 50 inpatients or outpatients suspected of LPRD were monitored by 24-h MII-pH. The 24-h MII-pH monitoring was carried out according to the method we reported before.[3] The numbers of acid reflux events, true non-acid reflux, and false non-acid reflux events were counted. The percentage of the subtypes of the LPR events was calculated. Before 24-h MII-pH monitoring, a laryngologist routinely instructed patients to fill in the reflux symptom index (RSI), and scored the reflux finding score (RFS) according to the images of the patients' laryngoscope. If the RSI >13 and/or RFS >7, the patients were considered with positive LPR, thus as the candidates for 24 h MII-pH. Among the 50 patients, there were 37 male and 13 female, with an average age of 54.16 ± 11.45 years. There were 25 cases with Reinke space edemas, six cases with chronic pharyngitis, five cases with laryngeal contact granulomas, four cases with vocal cord polyps, three cases with chronic cough, three cases with paroxysmal laryngospasms, one case with laryngeal cyst and one case with subglottic stenosis. The mean RSI and RFS of the patients were 15.10 ± 6.32 and 10.24 ± 3.27, respectively. A total of 332 LPR events were detected by 24-h MII-pH. Of them, there were 83 acid reflux events (median 1 [0, 3]), 238 weakly acid reflux events (median 4.5 [2, 7]) and 11 alkaline reflux events (median 0 [0, 0]). The total number of non-acid reflux events (including weak acid reflux and alkali reflux events) was 249, of which, there were 31.3% (78/249) of true non-acid reflux and 68.7% (171/249) of false non-acid reflux. It has been reported that although most LPR events in normal subjects are acidic reflux, nearly 40% (133/332) of LPR events in LPRD patients are non-acidic events in the hypopharynx. In LPRD patients, 30% (100/332) of LPR events are acidic in the distal esophagus, but non-acidic in the hypopharynx.[2] It was also reported in the literature that a small pharyngeal impedance study of normal volunteers found that 75% of LPR events was non-acidic.[4] Most people believe that laryngopharyngeal acid reflux can cause symptoms, Mainie et al[5] found that some patients had persistent symptoms despite the use of proton pump inhibitor twice a day, and in about 35% of cases, symptoms were associated with non-acid reflux. Therefore, laryngopharyngeal non-acid reflux cannot be ignored. Our results showed that 75% (249/332) of the LPR events are non-acid reflux, and 68.7% (171/249) of them are false non-acid reflux, and true non-acid reflux is only 31.3% (78/249). Therefore, true non-acid reflux is only 23.5% (78/332) of all the LPR events, acid suppressive therapy is still the main treatment for LPRD patients. However, if the therapeutic effect is not good, attention should be paid to the effect of true non-acid reflux on the symptoms related to LPR. So we believe that the further classification of non-acid reflux is helpful to guide the treatment of LPRD. Conflicts of interest None.