Combined laryngopharyngeal reflux and obstructive sleep apnea (CLOSA) – Salivary pepsin test for laryngopharyngeal reflux in obstructive sleep apnea patients

Objectives: Reflux disease including gastroesophageal reflux and laryngopharyngeal reflux (LPR) is often found in obstructive sleep apnea (OSA) patients. Endoscopic examination is a gold standard diagnosis for reflux disease. However, the invasive procedure limits its widespread use. The pathophysiological characteristics of LPR are associated with refluxate components, of which pepsin is known to damage the tissues of the larynx and pharynx. Therefore, the detection of salivary pepsin to diagnose LPR becomes a potentially clinical application with noninvasiveness. In this study, we aimed to (1) validate the feasibility of salivary pepsin test for LPR in OSA patients, (2) establish the threshold of salivary pepsin in diagnosing LPR, and (3) explore the relationship between OSA and LPR. Materials and Methods: Seventy adult polysomnography-diagnosed OSA patients were enrolled. Reflux finding score (RFS) and salivary pepsin test were utilized to evaluate LPR. RFS is a set of eight objective laryngoscopic findings (total score: 0-26), with a total score of >7 as RFS-positive representing LPR-positive. The salivary pepsin concentration was detected by enzyme-linked immunosorbent assay with a standard protocol. Results: Salivary pepsin test was performed quickly and smoothly in all subjects with no discomfort or side effects. Based on RFS positive, the prevalence of LPR was up to 86% in our study population. There is a trend that the median salivary pepsin concentration in RFS-positive patients was higher than RFS-negative patients (14.9 ng/ml vs. 7.23 ng/ml). The cutoff point (2.3 ng/ml) of salivary pepsin concentration yielded a sensitivity of 93% in the diagnosis of LPR. Neither apnea/hypopnea index nor salivary pepsin concentration was different between LPR-positive versus LPR-negative groups and nonsevere versus severe OSA groups. Conclusion: LPR is highly prevalent in OSA patients. Salivary pepsin test could be an alternative to endoscopic findings for the diagnosis of LPR with noninvasiveness. The threshold of salivary pepsin concentration of 2.3 ng/ml offers 93% sensitivity in the diagnosis of LPR. The relationship between OSA and LPR is bidirectional and more likely to be an overlapping syndrome-combined laryngopharyngeal reflux and OSA (CLOSA). Pharmacologic therapy for LPR is needed in patients with CLOSA for comprehensive treatment.