Laryngopharyngeal reflux (LPR) refers to a chronic inflammatory condition caused by the reflux of gastric and duodenal contents into the upper aerodigestive tract, including the nasopharynx, oropharynx, laryngopharynx, and larynx. Gastric contents, including pepsin and gastric acid, as well as duodenal contents such as trypsin and bile acids, can damage the mucosa of the pharynx and larynx, leading to morphological changes in the tissue and associated symptoms and signs.
Etiology and Pathogenesis
The mechanisms underlying LPR are not fully understood. This condition results from a multifactorial process involving various mechanisms, sharing both connections and distinctions with the pathogenesis of gastroesophageal reflux disease (GERD). Several factors may contribute:
Relaxation of the upper and lower esophageal sphincters may result in mechanical dysfunction of the esophageal-pharyngeal barrier, allowing gastric and duodenal contents to reflux into the pharynx and larynx, causing mucosal damage.
The pharyngeal and laryngeal regions exhibit comparatively weak acid resistance due to the lack of carbonic anhydrase isoenzyme III in the mucosa. Pepsin, gastric acid, trypsin, and bile acids from the refluxed gastric and duodenal contents can damage epithelial cells in the pharyngeal and laryngeal mucosa, leading to chronic inflammation.
Stimulation of the distal esophagus by refluxed gastric and duodenal contents may trigger a vagus nerve reflex, resulting in symptoms such as throat itching, foreign body sensation, chronic cough, and an increase in pharyngeal secretions.
Unhealthy habits such as smoking and consuming alcohol, along with psychological factors such as anxiety and depression, as well as sleep disorders, may exacerbate the condition.
Increased negative intrathoracic pressure during obstructive sleep apnea episodes may promote the reflux of gastric and duodenal contents.
Helicobacter pylori infection may also be a contributing factor.
Clinical Symptoms
Common symptoms include throat dryness, throat pain, foreign body sensation in the throat, hoarseness, frequent throat clearing, throat itchiness, coughing, paroxysmal laryngospasm, and difficulty swallowing. In rare cases, LPR may trigger asthma attacks.
Reflux episodes tend to increase significantly after meals or when lying down, leading to a worsening of the above symptoms. Some patients may also experience varying degrees of GERD-related symptoms, such as acid regurgitation and heartburn.
Signs
Indirect laryngoscopy or fiberoptic (electronic) nasopharyngolaryngoscopy often reveals mucosal erythema and hyperplasia in the posterior commissure of the vocal cords, diffuse vocal cord congestion and edema, and the presence of viscous mucus adherence. Severe cases may present with vocal process granulomas, edema in the Reinke's space, obliteration of the laryngeal ventricle, contact ulcers, or subglottic stenosis.
Diagnosis
Diagnosis is primarily based on clinical history, symptoms, and signs observed during laryngoscopic examination. A preliminary diagnosis may also be made using the Reflux Symptom Index (RSI) and the Reflux Finding Score (RFS). An RSI score greater than 13 and/or an RFS score greater than 7 suggests a suspected diagnosis of LPR.
Currently, the following objective diagnostic methods are available:
24-hour Pharyngeal-Esophageal pH Monitoring
Diagnosis is indicated when there are three or more episodes of laryngopharyngeal acid reflux in a 24-hour period, a laryngopharyngeal pH of less than 4 for 1% or more of the total time, or a reflux area index (RAI) greater than 6.3.
Pharyngeal pH Monitoring
Diagnosis is supported when the Ryan Index exceeds 9.41 in the upright position and/or 6.79 in the supine position.
Gastroscopy
This is useful for both the diagnosis and differentiation of LPR.
Esophageal Manometry
This technique supports the identification of underlying causes and provides guidance for diagnosis and treatment.
Salivary Pepsin Detection
This can improve diagnostic accuracy.
Differential Diagnosis
LPR must be differentiated from GERD. GERD primarily manifests as heartburn and acid regurgitation, with relatively mild throat symptoms such as hoarseness or foreign body sensation. In GERD, pH monitoring and endoscopic examinations typically reveal esophageal abnormalities, while the laryngopharyngeal region may appear normal or exhibit minimal changes.
Treatment
Maintaining Healthy Habits and Lifestyle
Adopting lifestyle modifications plays an essential role in management. These include elevating the head of the bed, avoiding tight clothing, and remaining upright after meals. The dietary approach focuses on a high-protein, high-fiber, low-fat, and low-acid diet. Irritating foods should be avoided, and meals should be smaller and more frequent. It is recommended to stop eating 2 to 3 hours before bedtime and to chew food thoroughly to promote saliva secretion, which enhances esophageal clearance. Weight management is also important, with weight loss recommended for obese individuals. For those with obstructive sleep apnea (OSA), sleeping in a lateral position may be beneficial.
Pharmacological Treatment
Pharmacological options include proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs), H2 receptor antagonists (H2RAs), prokinetic agents, and gastric mucosal protectants. The first-line treatment typically involves a standard dose of PPIs for a recommended duration of 8–12 weeks. In patients with suboptimal response to PPIs or P-CABs, evaluation for factors such as esophageal hypersensitivity, psychological factors, and genetic polymorphisms of PPI-metabolizing enzymes should be considered. H2RAs may be an alternative for patients unable to tolerate PPIs, and they are particularly effective in controlling nighttime symptoms. Care should be taken to avoid medications that lower lower esophageal sphincter pressure or impair esophageal motility, such as β-adrenergic agonists, α-adrenergic antagonists, anticholinergic drugs, calcium channel blockers, diazepam, and dopamine.
Surgical Treatment
In cases where pharmacological treatment is ineffective or poorly tolerated, antireflux surgery may be considered. Laparoscopic or endoscopic fundoplication is a commonly performed procedure aimed at increasing lower esophageal pressure and reducing reflux.