Classification of the Non-Acid Laryngopharyngeal Reflux
Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition of the upper aerodigestive tract tissues caused by the direct and indirect effects of gastroduodenal content reflux. This condition can lead to morphological changes in the upper aerodigestive tract. The pH of gastric contents is typically low, causing acid reflux, while the pH of duodenal contents is higher, leading to weakly acid or alkaline reflux. Carbonic anhydrase in the esophageal mucosa converts CO2, a product of cell metabolism, into bicarbonate, which neutralizes gastric acid. As a result, some gastric acid reflux or duodenal content reflux has a pH of less than 4 in the distal esophagus but becomes weakly acid or alkaline reflux with a pH greater than 4 when it reaches the hypopharynx.
Using 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring, laryngopharyngeal reflux (LPR) events are categorized based on the pH in the hypopharynx: (1) Acid LPR when pH is ≤4; (2) Weakly acid LPR when pH is between 4 and 7; (3) Alkaline LPR when pH is above 7. Both weakly acid and alkaline LPR are classified as non-acid reflux. 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).
The proportion of true non-acid, false non-acid, and acid reflux events in LPR patients is crucial for developing an effective treatment plan. If true non-acid reflux events dominate, acid suppressive therapy may not be the primary treatment. Conversely, if false non-acid reflux and acid reflux are predominant, acid suppressive therapy remains essential. However, there is limited research on this classification of proportion, prompting an analysis of 24-hour MII-pH data from 50 patients suspected of LPRD to understand the distribution of various LPR types.
From January 2015 to January 2020, 50 inpatients and outpatients suspected of LPRD underwent 24-hour MII-pH monitoring. The monitoring was conducted following a previously reported method. The numbers of acid reflux events, true non-acid reflux events, and false non-acid reflux events were counted, and the percentage of each subtype was calculated. Before the monitoring, patients were instructed to complete the Reflux Symptom Index (RSI), and the Reflux Finding Score (RFS) was determined based on laryngoscope images. Patients with an RSI >13 and/or RFS >7 were considered positive for LPR and were selected for 24-hour MII-pH monitoring.
The study included 37 male and 13 female patients, with an average age of 54.16 ± 11.45 years. Common conditions among the patients included Reinke space edema (25 cases), chronic pharyngitis (6 cases), laryngeal contact granulomas (5 cases), vocal cord polyps (4 cases), chronic cough (3 cases), paroxysmal laryngospasms (3 cases), laryngeal cyst (1 case), and subglottic stenosis (1 case). The mean RSI and RFS scores were 15.10 ± 6.32 and 10.24 ± 3.27, respectively.
A total of 332 LPR events were detected during the 24-hour MII-pH monitoring. These included 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 (weakly acid and alkaline) was 249, with 31.3% (78/249) classified as true non-acid reflux and 68.7% (171/249) as false non-acid reflux.
Previous studies have shown that while most LPR events in normal subjects are acidic, nearly 40% (133/332) of LPR events in LPRD patients are non-acidic in the hypopharynx. Additionally, 30% (100/332) of LPR events in LPRD patients are acidic in the distal esophagus but non-acidic in the hypopharynx. A small pharyngeal impedance study of normal volunteers found that 75% of LPR events were non-acidic. Despite the common belief that laryngopharyngeal acid reflux causes symptoms, some patients experience persistent symptoms even with twice-daily proton pump inhibitor use, with approximately 35% of cases associated with non-acid reflux.
The study’s results indicate that 75% (249/332) of LPR events are non-acid reflux, with 68.7% (171/249) being false non-acid reflux and 31.3% (78/249) being true non-acid reflux. True non-acid reflux accounts for only 23.5% (78/332) of all LPR events, suggesting that acid suppressive therapy remains the primary treatment for LPRD patients. However, if the therapeutic effect is insufficient, the impact of true non-acid reflux on LPR-related symptoms should be considered. Therefore, further classification of non-acid reflux is valuable for guiding LPRD treatment.
doi.org/10.1097/CM9.0000000000001223
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