Proton Pump Inhibitor-unresponsive Laryngeal Symptoms Are Associated With Psychological Comorbidities and Sleep Disturbance: A Manometry and Impedance-pH Monitoring Study

Background/aims: Laryngeal symptoms are largely treated with empiric proton pump inhibitor (PPI) therapy if no apparent pathology shown on ear, nose, and throat evaluation and reflux-related etiologies are suspected. However, treatment response remains unsatisfactory. This study aimed to investigate the clinical and physiological characteristics of patients with PPI-refractory laryngeal symptoms.

Methods: Patients with persistent laryngeal symptoms despite PPI treatment for ≥ 8 weeks were recruited. A multidisciplinary evaluation comprising validated questionnaires for laryngeal symptoms (reflux symptom index [RSI]), gastroesophageal reflux disease symptoms, psychological comorbidity (5-item brief symptom rating scale [BSRS-5]) and sleep disturbance (Pittsburgh sleep quality index [PSQI]), esophagogastroduodenoscopy, ambulatory impedance-pH monitoring, and high-resolution impedance manometry were performed. Healthy asymptomatic individuals were also recruited for comparison of psychological morbidity and sleep disturbances.

Results: Ninety-seven adult patients and 48 healthy volunteers were analyzed. The patients had markedly higher prevalence of psychological distress (52.6% vs 2.1%, < 0.001) and sleep disturbance (82.5% vs 37.5%, < 0.001) than the healthy volunteers. There were significant correlations between RSI and BSRS-5 scores, and between RSI and PSQI scores ( = 0.26, = 0.010, and = 0.29, = 0.004, respectively). Fifty-eight patients had concurrent gastroesophageal reflux disease symptoms. They had more prominent sleep disturbances (89.7% vs 71.8%, < 0.001) than those with laryngeal symptoms alone but similar reflux profiles and esophageal motility.

Conclusions: PPI-refractory laryngeal symptoms are mostly associated with psychological comorbidities and sleep disturbances. Recognition of these psychosocial comorbidities may help optimize management in these patients.