To qualify as LPS, the panel agreed that symptoms must be frequent, occurring at least twice weekly, and present for more than 8 weeks^16–18. The group agreed that commonly cited “LPR” symptoms meeting criteria for LPS include (with the level of agreement in parentheses): cough (89%), regurgitation (89%), throat pain/sore throat (89%), throat clearing (86%), excess phlegm (82%), and hoarseness/voice change (80%)^16–18.

Although globus approached but did not reach agreement for inclusion as an LPS, the panel felt that globus is an important symptom warranting further evaluation and is often a negative predictor of reflux physiology^19–21. Several other symptoms that did not reach agreement to be considered LPS included tongue burning, nasal burning, post-nasal drip, halitosis, belching and dysphagia (Supplemental Table 2).

Importantly, all aforementioned symptoms are poorly specific for true LPRD. In other words, the presence of LPS does not equate to LPRD²².

Additionally, LPS can occur with esophageal reflux-like symptoms such as heartburn, regurgitation, or chest pain, or can occur independent of esophageal symptoms²³. Hence, early in the evaluation of LPS, the presence of esophageal symptoms should be assessed as the diagnostic and management algorithms differ for isolated LPS and LPS with concurrent esophageal reflux symptoms.

While the prevalence of LPS is high, the proportion of individuals found to have objective LPRD on diagnostic evaluation is low, approximately 35%²⁴. Thus, while many individuals experience LPS, true LPRD is much less common.

Therefore, both LPS and objective evidence of gastro-esophageal reflux are needed for a diagnosis of LPRD. Such evidence could include reflux metrics on esophageal testing or, in the setting of concurrent esophageal reflux symptoms, a positive response to a pharmacologic trial. Irrespective of symptom presentation, there was strong agreement that diagnostic evidence supporting the relationship between LPS and gastroesophageal reflux is required for all patients prior to invasive anti-reflux management.

Laryngoscopy was agreed by the expert panel to be a necessary step in evaluating LPS, primarily to rule out alternate laryngeal pathologies including neoplasia. However, findings on laryngoscopy alone cannot diagnose LPRD^{22, 25}. Laryngoscopic findings on white light examination such as infraglottic edema, interarytenoid mucosal hypertrophy, erythematous changes and post-cricoid mucosal edema are non-specific for LPRD and may result from other causes of laryngeal inflammation or be found in healthy, asymptomatic individuals²⁵. LPRD is often erroneously assumed to cause LPS despite changes in other vibratory parameters such as symmetry, amplitude, mucosal wave, and glottic closure, visualized by stroboscopy. In addition, benign vocal fold lesions are common, as are lesions of epithelial origin, such as keratotic, pre-malignant dysplastic and malignant lesions²⁶. All of these can present with dysphonia, chronic throat clearing, globus sensation and other irritative complaints often ascribed to LPRD²⁷. When LPS includes hoarseness that is not explained by white light flexible laryngoscopy, videostroboscopic examination should be performed to evaluate for other etiologies. Additionally, the panel suggested that laryngoscopic finding instruments such as the Reflux Finding Score (RFS) and the Reflux Sign Assessment (RSA) should not be used to diagnose LPRD, given their suboptimal specificity^28–30.

The diagnostic and management algorithms differ for concurrent esophageal symptoms with LPS versus isolated LPS. When gastroesophageal reflux is implicated as the etiology of LPS, either based on typical esophageal reflux symptoms or positive diagnostic testing, initial therapeutic trials can include anti-secretory therapy, as well as barrier alginate therapy and lifestyle optimization. The latter are low-risk strategies that may complement and enhance the effectiveness of anti-secretory therapy in patients with LPRD^31–33. A 3-month trial of standard-dose potent acid suppression such as PPI (e.g. omeprazole 20 mg) taken twice a day is considered adequate for the assessment of LPS symptom response. LPS have been shown to decrease with alginate therapy taken four times daily (after meals and before bedtime) compared to vocal hygiene and lifestyle management³⁴, and can augment acid suppression^{35, 36}. In patients with isolated LPS, acid-reducing medications are not recommended as first-line therapy without demonstration of diagnostic evidence of reflux^{37, 38}.

Using Lyon Consensus paradigms, upper GI endoscopy off acid suppressive therapy can establish GERD presence if Los Angeles grades B, C, D esophagitis and/or biopsy proven Barrett’s esophagus are encountered³⁹, and can raise suspicion that reflux may be contributing when found in patients with LPS. The presence of disrupted esophagogastric junction on endoscopy, such as hiatal hernia, may serve as adjunctive evidence for LPRD. The potential value of upper endoscopy was demonstrated in a recent multicenter study of patients presenting with LPS, where up to 47% of patients demonstrated erosive findings and/or hiatal hernia⁴⁰. Notably, these findings may be present both in patients with esophageal symptoms and those with isolated LPS. The expert panel, therefore, agreed that upper GI endoscopic evaluation for signs of esophageal mucosal injury may be of value in patients with LPS. Office-based transnasal esophagoscopy (TNE) has been shown to be similarly diagnostic for Barrett’s esophagus and certain other esophageal pathologies compared to standard upper endoscopy^41–43. While TNE may provide a convenient, point-of-care screening tool for esophageal signs of reflux or other pathologies, it should be performed by providers with specialized training in esophageal endoscopy to ensure proper identification of relevant findings.

A cervical inlet patch is an area of heterotopic gastric mucosa in the proximal esophagus found on upper endoscopy that may secrete acid, mucus, or pepsin. Inlet patches can be associated with LPS and globus⁴⁴, and ablation of inlet patch has been shown to reduce LPS in small case series⁴⁵. Despite these observations, the panel could not reach agreement on the value of identifying and treating inlet patch to reduce LPS, as current evidence remains limited. Further research, including controlled studies of the impact of ablation, is needed to more clearly establish the importance of identifying this endoscopic finding in patients with LPS.

The diagnostic evaluation of whether LPS are potentially related to reflux first requires determining whether pathologic gastro-esophageal reflux is present. Although objective evidence of GERD on reflux testing in patients with LPS does not necessarily implicate reflux as causative of a patient’s LPS, the absence of GERD makes it unlikely that GERD is the mechanism underlying LPS or that anti-reflux therapies will improve LPS.¹⁶ Thus, ambulatory reflux monitoring has a role in multiple LPS settings to distinguish the presence of pathologic GERD, and determine the value of anti-reflux therapies.

Evidence of abnormal reflux burden is essential prior to endoscopic or surgical anti-reflux interventions as these are invasive, irreversible, and expensive. Since patients with isolated LPS have a lower pre-test likelihood of GERD, early ambulatory reflux monitoring can help to confirm or exclude GERD and thereby personalize management^{39, 46, 47}. In the absence of endoscopic evidence of GERD, ambulatory reflux monitoring is the reference standard for diagnosing LPRD. Ambulatory reflux monitoring is the next step in evaluating patients with LPS and concurrent esophageal symptoms who do not respond to empiric trials of anti-secretory and/or alginate therapy, in the absence of endoscopic evidence of GERD. Further, ambulatory reflux monitoring should be considered in patients requiring long-term medical anti-reflux management, primarily to confirm pathologic reflux burden prior to long term acid suppressive therapy, similar to recommendations in esophageal reflux symptoms⁴⁸.

The two primary modalities of reflux monitoring utilized to diagnose LPRD are 24-hour multichannel intraluminal impedance-pH monitoring and prolonged wireless pH monitoring, both performed off antisecretory therapy in unproven GERD²⁴ (Table 3). Each of these two modalities provides differing capabilities and value in the evaluation of LPS, and thus are not mutually exclusive. Both provide measurement of distal esophageal acid exposure time (AET). pH-impedance offers the added ability to detect proximal reflux events with greater detail depending on probe placement and catheter configuration, especially since hypopharyngeal events may be more likely to contribute to LPS. For both modalities, prospective and blinded trial data suggest a distal esophageal AET >6.0% is definitively abnormal and consistent with pathologic acid exposure, meeting criteria for proven GERD whereas distal esophageal AET <4.0% is considered physiologic, especially if present on all 4 days of a 96-hour prolonged wireless study^{49, 50 39}.

Early studies demonstrated that pH-impedance monitoring is superior to traditional esophageal pH monitoring in detecting proximal esophageal reflux events⁵¹. Hypopharyngeal reflux events were demonstrated using dual channel or hypopharyngeal-esophageal multichannel intraluminal impedance with dual pH (HEMII-pH) catheters, often occurring as weakly-acidic or non-acidic reflux episodes that have potential to predict treatment outcomes^51–54. These catheter configurations were able to identify pharyngeal reflux events in 81% of 42 patients with suspected reflux-mediated pathology in LPS, including 72% who tested negative for esophageal-only criteria, highlighting the diagnostic gap addressed by standard dual-channel pH-impedance monitoring. Identifying clinically relevant reflux episode thresholds requires further research, and the expert panel could not reach agreement for thresholds of >80 esophageal reflux events and >10 hypopharyngeal events to be considered abnormal.

Wireless pH monitoring utilizes a single pH sensor positioned in the distal esophagus during sedated endoscopy that wirelessly transmits data to a recorder for up to 96-hours^{55, 56}. Given significant day-to-day variability in esophageal acid exposure, a major advantage of wireless pH testing is the capacity to monitor for prolonged periods and capture variability rather than relying solely on a 24-hour snapshot⁵⁷. When the goal is to achieve the highest diagnostic accuracy in demonstrating pathologic GERD, 96-hour prolonged wireless pH monitoring outperforms 24- or 48-hour studies in predicting need for acid suppressive and anti-reflux therapies, primarily because day-to-day variation in acid burden can confound shorter studies^{48, 58–60}. In a double-blind, multi-center trial of 100 patients with troublesome esophageal reflux symptoms and inadequate PPI response, participants with 0 days of an elevated AET had 10 times increased odds of stopping PPI when compared to those with 4 days of an elevated AET. When AET was elevated on two or more days, the odds ratio for predicting need to continue PPI treatment was 5.3 (95% CI 2.19–13.44)⁵⁰. Given these findings, recent guidance positions 96-hour wireless pH testing off anti-secretory therapy as the preferred test for unproven GERD⁶¹. Prolonged pH monitoring also provides a higher diagnostic yield of pathologic GERD in patients with LPS. In a recent multicenter international study of 813 patients, the diagnostic yield of GERD in patients referred for LPS was 50% on prolonged monitoring versus 27% on 24-h pH impedance monitoring, including HEMII-pH^{24, 62}.

Oropharyngeal pH testing (Restech Dx-pH probe, Respiratory Technology Corp, San Diego, CA) was introduced as a minimally invasive pharyngeal pH probe to detect pharyngeal acid, including aerosolized acid⁶³. However, this technique is not specific, cannot detect weakly-acidic or non-acidic reflux, has poor concordance with traditional pH-impedance monitoring, and does not correlate with clinical outcomes^64–67.

The expert panel agreed that both pH-impedance monitoring and wireless pH monitoring are diagnostic options for assessing LPS. pH-impedance monitoring provides information on mechanisms of LPS, especially isolated LPS, while prolonged wireless pH monitoring provides direction on the role of anti-reflux therapy in LPS. The panel reached near agreement in the value of HEMII-pH providing useful information when traditional esophageal reflux monitoring is inconclusive, and suspicion of a reflux-mediated mechanism remains high. The panel did not support oropharyngeal pH monitoring as a stand-alone tool in LPS evaluation.

The larynx is a critical intersection of breathing, communication and swallowing. These processes can become measurably disrupted⁶⁸ with pathologic reflux, stress, vagal sensitivity and sequelae from medical comorbidities^69–72. The term “laryngoresponders” was first coined by Aronson in 1990 to describe a predisposition, by physical makeup or personality, to manifest emotional distress through sensory changes in the larynx or voice. In recent years, various studies have shown the relationship between emotion and the larynx^73–76. A survey investigation of 1,217 adults found that 16% to 46% of the general population self-identified as laryngoresponsive⁷⁷. Laryngeal hyperresponse can manifest as repetitive laryngeal behaviors such as throat clearing or coughing, breath-holding, or as biomechanical strain at the vocal folds altering one’s voice quality or causing globus sensation. Laryngeal hypervigilance, defined as increased threat-induced attention to the larynx, and symptom-specific anxiety, defined as fear/worry about LPS and perceived consequences, are psychological processes that can influence LPS. The Laryngeal Cognitive Affective Tool (LCAT) is a validated patient reported outcome (PRO) instrument to distinguish candidates with elevated levels of hypervigilance and anxiety related to their LPS, and who may improve with behavioral intervention^{78, 79}.

Behavioral therapy can effectively address hyperresponsive laryngeal behaviors and laryngeal hypervigilance. SLPs specializing in voice and upper airway disorders offer interventions aimed at modifying dysregulated patterns using mechanical reorganization and healthful cognitive perspectives associated with LPS. There is precedent for these interventions working in individuals with confirmed reflux⁸⁰, isolated cough⁸¹, inducible laryngeal obstruction/paradoxical vocal fold movement^{82, 83} and muscle tension dysphonia⁸⁴. Laryngeal Recalibration Therapy (LRT)⁸⁵ is a novel structured approach that infuses traditional SLP techniques with heart rate variability biofeedback as well as acceptance and commitment therapy⁸⁶.

If psychological processes continue to impact LPS and/or patients experience incomplete relief after LRT or pharmacologic neuromodulation, cognitive behavioral therapy can be used to target and modify the specific cognitive (e.g., my symptoms will never get better), emotional (e.g. fear, worry), physiological (increased autonomic arousal), and behavioral (e.g., avoidance of foods, laryngeal hypervigilance) processes exacerbating symptoms and interfering with quality of life. Psychological interventions in this context are not designed to address comorbid general mental health disorders. Instead, they are focused on targeting psychological processes specifically impacting LPS and are delivered by a mental health professional with specialized health psychology training.

Pharmacologic neuromodulation may attenuate laryngeal hypersensitivity and may be considered in LPRD patients with suboptimal response to anti-secretory therapy or SLP intervention and in isolated LPS with negative esophageal testing. Current clinical evidence for neuromodulators, notably gabapentin and pregabalin, focus primarily on the treatment of chronic cough through mediation of vagal hypersensitivity⁸⁷. Tricyclic antidepressants, commonly prescribed for the treatment of functional GI disorders, should be used with caution because of anticholinergic effects which may cause dry mouth and aggravate LPS⁸⁸. While there is a paucity of data for selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors, they can be considered in individuals who have concomitant anxiety and depression.