Adjunctive Nebulised N‐Acetylcysteine for Laryngopharyngeal Symptoms Persisting Despite Proton‐Pump‐Inhibitor Therapy: A Prospective Single‐Arm Interventional Study

OBJECTIVES: To quantify within-subject change in symptom, laryngoscopic and quality-of-life measures after 8 weeks of adjunctive nebulised N-acetylcysteine (NAC) in adults with laryngopharyngeal symptoms (LPS) persisting despite proton-pump-inhibitor (PPI) therapy, and to explore baseline predictors of response. DESIGN: Prospective, single-arm, pre-post interventional study. SETTING: Tertiary otolaryngology practice. PARTICIPANTS: Seventy-five adults with LPS persisting after ≥ 12 weeks of PPI therapy (baseline Reflux Symptom Index [RSI] ≥ 13 and Reflux Finding Score [RFS] ≥ 7); ambulatory reflux monitoring was not performed. MAIN OUTCOME MEASURES: Change in RSI (primary). Secondary: RFS, the 12-item Reflux Symptom Score (RSS-12) and the laryngopharyngeal reflux health-related quality-of-life instrument (LPR-HRQoL). Treatment response (≥ 50% RSI reduction or end-of-treatment RSI < 13) was modelled by logistic regression. RESULTS: All outcomes improved at Week 8: RSI -10.2 points (95% CI -11.2 to -9.2; Cohen's d_z = -2.33), RFS -6.1 (d_z = -1.88), RSS-12 - 33.9 (d_z = -1.30) and LPR-HRQoL +20.0 (d_z = +2.17) (all p < 0.001). Thirty-nine of 75 (52.0%) were responders. A twice-daily PPI regimen was independently associated with response (adjusted odds ratio [OR] 4.96, 95% CI 1.41-17.43; p = 0.012) and higher baseline RSI with non-response (adjusted OR 0.70 per point, 95% CI 0.56-0.87; p = 0.002). CONCLUSIONS: Nebulised NAC with saline was associated with large improvements across symptom, laryngoscopic and quality-of-life domains in adults with LPS persisting despite PPI therapy and was well tolerated. As the study was uncontrolled and the saline vehicle may itself relieve symptoms, efficacy requires confirmation in a randomised trial against nebulised saline.