Laryngopharyngeal Symptoms and Laryngopharyngeal Reflux Disease: Diagnostic Testing and Clinical Approach Based on the San Diego Consensus

Abstract

Background:

The San Diego Consensus for Laryngopharyngeal Symptoms (LPS) and Laryngopharyngeal Reflux Disease (LRPD) offers a modern interdisciplinary paradigm that focuses on symptoms and aligns evaluation with underlying mechanisms of disease.

Purpose:

This review uses the San Diego Consensus as the framework to discuss who should be tested for reflux, timing and selection of diagnostic testing, and practical diagnostic algorithms in patients with LPS and LPRD. Patient reported outcome measures are useful to characterize LPS, quantify symptom burden and monitor response, but are not specific for a diagnosis of LPRD. Patients presenting with both LPS and typical esophageal symptoms have higher pretest probability of LPRD, and time limited empiric acid suppressive agents and alginates may be appropriate. In contrast, upfront objective testing is recommended in isolated LPS prior to long-term acid suppressive therapy. Laryngoscopy or stroboscopy can identify alternative etiologies of LPS. Esophagoscopy can demonstrate conclusive reflux evidence, but diagnostic yield is low. pH-impedance monitoring, especially with hypopharyngeal sensors, assesses reflux mechanisms when investigating LPS, and can provide numbers of reflux episodes irrespective of acidity as well as proximal extent of these episodes. High-resolution manometry does not provide a diagnosis of LPRD but serves to rule out motility disorders that mimic LPS. Prolonged wireless pH monitoring may be appropriate when typical esophageal reflux symptoms coexist. The evaluation of LPS requires a paradigm shift away from reflexive attribution to reflux and toward a structured diagnostic approach that systematically considers alternative etiologies of LPS.

1 |. Introduction

The terminology used to describe upper esophageal, throat and airway symptoms has historically blurred the distinction between upper aerodigestive symptoms and reflux-related pathology, contributing to diagnostic uncertainty, extended empiric treatment, and ultimately increased healthcare costs. The term laryngopharyngeal reflux (LPR) is applied to a variety of throat and airway complaints without standardized diagnostic criteria or objective evidence of reflux, despite its widespread use in clinical practice in both otolaryngology and gastroenterology [1, 2]. Overinclusive labeling of symptoms as LPR has resulted in healthcare utilization exceeding that seen in typical gastroesophageal reflux disease (GERD), largely due to repeated therapeutic trials and diagnostic testing [3–5]. Meanwhile, patient quality of life is adversely affected regardless of whether a reflux diagnosis is ultimately confirmed. The San Diego Consensus for Laryngopharyngeal Symptoms (LPS) and Laryngopharyngeal Reflux Disease (LRPD) addresses this gap by offering a modern, interdisciplinary framework that focuses on symptoms and aligns evaluation with underlying mechanisms of disease [6].

The San Diego Consensus Working Group defines LPS as recurrent throat and/or upper airway symptoms occurring at least twice weekly for 8 weeks or longer, which may or may not result from retrograde flow of gastric contents into the upper esophagus, pharynx, or larynx [6]. Common LPS include cough, regurgitation, throat pain or soreness, throat clearing, excess phlegm, and voice changes or hoarseness [6]. These symptoms are heterogeneous, and do not necessarily carry the same weight for association with LPRD. LPS can be broadly segregated into episodic (cough, throat clearing, regurgitation) and continuous (throat pain, excess phlegm, voice changes); the former may relate to reflux episodes more often than the latter. Importantly, LPS do not equate to LPRD, which requires both troublesome LPS and objective evidence of a reflux mechanism. This distinction is clinically important, as observational studies indicate that many patients labeled as having LPR demonstrate normal objective reflux testing, highlighting the need for precise classification [5–7].

A series of three technical reviews expand in detail the literature underlying the San Diego consensus statements [6]. In this review, the second of the series, we use the San Diego Consensus as the framework to further discuss who should be tested for reflux, timing and selection of diagnostic testing, and practical diagnostic algorithms [6]. This approach highlights the role of multidisciplinary collaboration in evaluation to optimize outcomes in patients with LPS and LPRD. Two other reviews will discuss presentation/terminology and management/interdisciplinary considerations.

1.1 |. Patient Stratification: Who Should be Tested?

The fundamental diagnostic challenge in evaluating patients with LPS is distinguishing symptom-based presentation from proven disease [6]. Symptoms alone are insufficient to confirm reflux-mediated disease, and many conditions mimic or coexist with LPRD. LPS can arise from overlapping mechanisms, including direct mucosal exposure from refluxate, vagally mediated airway reflexes, and neurogenic, behavioral, or motility-related contributions [8, 9]. Esophageal dysfunction may influence airway symptoms via both direct contact or acidification (reflux pathway) and/or vagally mediated reflex arcs (reflex pathway) [9, 10]. Additionally, heightened cognitive-behavioral processes may perpetuate laryngeal hyperresponsiveness and hypervigilance [11]. Failure to address these neurobehavioral mechanisms may explain why fewer than half of patients with LPS respond to antisecretory treatment alone, the limited specificity of laryngoscopic findings for LPRD, and the suboptimal outcomes observed after anti-reflux surgery [5, 12–16].

Patients presenting with both LPS and typical esophageal symptoms have a higher pretest probability of GERD/LPRD [17, 18]. When alarm features (e.g., unintentional weight loss, odynophagia, hemoptysis, progressive dysphagia) are absent, targeted behavioral or medical therapy may be appropriate before invasive testing [6]. Time-limited empiric therapy with standard-dose proton pump inhibitor (PPI, e.g., omeprazole 20 mg twice daily) for 3 months, combined with alginate therapy and lifestyle modifications, is reasonable initial management [6, 19–27], reserving diagnostic work-up for patients with a suboptimal response [17, 18]. Patients with isolated LPS (chronic cough, throat clearing, dysphonia) without typical GERD symptoms (heartburn, regurgitation) have a lower pretest probability of reflux and substantially reduced response to empiric acid suppression compared to patients with typical GERD [6, 28]. A multicenter trial showed that only approximately 25% of patients with chronic unexplained cough have reflux as the primary driver, and patients with reflux-induced cough are more likely to report typical reflux symptoms (p = 0.031) [29]. This likely explains the limited efficacy of empiric antireflux therapy in this population.

In this context, advanced physiologic testing may help better characterize the relative contribution of reflux to symptoms, supporting a more individualized management approach by identifying the subset of patients with LPRD. Objective testing is strongly recommended for these patients before escalating to long-term acid suppression or surgical intervention, particularly given lower surgical response rates in this population [6, 30, 31].

1.2 |. Timing of Diagnostic Evaluation: When Should Testing Occur?

Upfront reflux testing has been shown to be cost saving for patients with isolated LPS; one study suggesting the average weighted cost was $1897.00 per patient for up-front testing compared to $3033.00 for initial twice daily therapy and $3366.00 for initial once daily therapy [21]. To that end, the San Diego Consensus recommends that in patients with isolated LPS without typical symptoms of reflux, acid-reducing medications are not recommended prior to demonstration of objective evidence of reflux [6, 13, 32].

Laryngoscopy, esophagoscopy and ambulatory reflux monitoring should be undertaken for patients with isolated LPS, those with confirmed LPRD who demonstrate a poor response to medical therapy, as well as patients with LPS or LPRD who are responsive to therapy yet require long-term management and/or are considering dose escalation, particularly if anti-reflux surgical interventions are being considered [6, 17, 21, 27]. Ambulatory reflux monitoring can help personalize therapy together with other adjuncts such as lifestyle modification, alginates or prokinetics [6, 33–37]. LPS should no longer be considered reflux-related in patients with negative results on esophageal physiologic studies, particularly those who have had a trial of acid-reducing therapy without success [6, 17, 21, 27].

1.3 |. Diagnostic Modalities and Approaches: How Should Testing be Performed?

The diagnostic workup for LPS should be guided by detailed history, individual risk factors, and whether alarm features are present. Available diagnostic modalities include laryngoscopy or stroboscopy, fluoroscopy, upper endoscopy, and esophageal physiologic testing (ambulatory reflux monitoring and esophageal manometry).

1.3.1 |. Patient Reported Outcome Measures

Symptom questionnaires are widely used to characterize LPS, quantify symptom burden, and monitor response to treatment in patients with suspected LPRD. They play an important role in the initial assessment of patients with LPS because they are easy to administer, low-cost, and feasible in both clinical and research settings. While these tools are accessible and clinically practical, their diagnostic performance varies considerably. These instruments measure symptom burden and quality of life but do not diagnose reflux disease, so they should be paired with objective testing or used to track severity and change in symptoms over time.

The Reflux Symptom Index (RSI) is the most commonly used questionnaire for LPS, but specificity for LPRD is low, and it does not reliably predict proximal reflux events or correlate with objective measures on pH-impedance monitoring, limiting its diagnostic utility [38–40]. The Reflux Symptom Score (RSS) was developed with reference to hypopharyngeal-esophageal multichannel intraluminal impedance-pH (HEMII-pH) monitoring as the physiologic reference standard, and shows high sensitivity and modestly improved specificity for reflux-related symptom patterns, with good correlation to proximal reflux burden and treatment response [38, 41]. Despite these advantages, current evidence on the RSS is insufficient to support its use as a standalone diagnostic tool for LPRD.

Esophageal-focused reflux questionnaires include the Gastroesophageal Reflux Disease Questionnaire (GERDQ), GERD Health Related Quality of Life (GERD-HRQL), and Frequency Scale for the Symptoms of GERD (FSSG). These were designed to assess typical GERD symptoms such as heartburn and regurgitation. These instruments show moderate sensitivity for esophageal reflux symptoms but have low specificity for LPRD [42]. Their utility lies primarily in identifying coexisting esophageal reflux symptoms rather than characterizing laryngopharyngeal pathology. Therefore, they may be helpful to distinguish patients with isolated LPS from those also exhibiting esophageal reflux symptoms.

The COuGH RefluX score was developed to characterize patients with LPS into low, medium or high likelihood categories for LPRD [43], with ~80% sensitivity and specificity for objective GERD evidence on testing [44]. Studies utilizing the score describe its potential for stratifying the diagnostic approach to LPS. Response to an empiric trial of PPI is highest when the score suggests high likelihood for reflux, and lowest with low likelihood scores where non-reflux mechanisms need to be considered [45]. Medium likelihood scores can prompt esophageal physiologic testing to evaluate for objective reflux evidence. The score requires evaluation for a hiatus hernia and is therefore not a pure clinical score. While further validation and outcome studies are needed, the COuGH RefluX score can shape the initial approach to LPS patients presenting for evaluation and management.

1.3.1.1 |. Laryngoscopy and Videostroboscopy.

Laryngoscopy is commonly used to assess patients with LPS. While it cannot be used to diagnose LPRD, the San Diego Consensus had 93% agreement that it plays an important role in identifying alternative etiologies of LPS and in excluding structural pathology and malignancy [6]. Disorders that could mimic LPS include inflammatory conditions associated with allergy, environmental exposure or smoking, as well as infectious processes.

Laryngoscopic findings that have historically been attributed to reflux include posterior commissure hypertrophy, laryngeal and arytenoid inflammation (erythema/edema), vocal fold edema, diffuse laryngeal edema, excess pharyngeal/laryngeal mucus, and vocal process granulomas [12]. Vocal fold granulomas deserve special mention because recent evidence challenges the assumption that they are LPRD related. Lee et al. demonstrated that over a third of patients (39%) with vocal fold granulomas were reflux-negative on pH-impedance monitoring, highlighting the importance of comprehensive evaluation [46]. In a randomized controlled trial published in 2006, Vaezi et al. demonstrated no therapeutic benefit of esomeprazole over placebo in patients with chronic posterior laryngeal inflammation, with response rates of 14.7% and 16.0%, respectively (p = 0.799) [28].

Several instruments have been developed to visually quantify laryngeal findings, including the Reflux Findings Score (RFS) and Reflux Sign Assessment (RSA). While these tools aim to standardize assessment, the San Diego consensus panel agreed that such findings are neither specific nor pathognomonic for LPRD (86% agreement). In fact, laryngeal changes such as erythema, edema, and interarytenoid hypertrophy can occur in healthy individuals or in the context of other inflammatory processes (79% agreement) [6].

When laryngoscopy is unrevealing in patients with hoarseness, the San Diego Consensus recommends videostroboscopy as an adjunctive evaluation tool, with 79% agreement. Videostroboscopy allows detailed assessment of vocal fold vibratory characteristics and can detect subtle mucosal or functional abnormalities not visible on standard laryngoscopy, thereby improving diagnostic accuracy in patients with voice complaints.

1.3.2 |. Upper Endoscopy

In the context of reflux symptoms, esophagogastroduodenoscopy (EGD) is often the first test performed when typical esophageal symptoms (heartburn, acid regurgitation, esophageal chest pain) do not respond to empiric treatment trials, when alarm symptoms (dysphagia, weight loss, anemia, family history of esophageal cancer) are present, or when isolated LPS are encountered [17]. The San Diego Consensus recommends esophageal testing that starts with EGD when invasive investigation is indicated in LPS presentations, both LPS associated with typical symptoms that persist despite empiric therapy, and isolated LPS, performed off acid suppressive therapy to increase the diagnostic yield of conclusive GERD evidence [6].

Conclusive evidence of GERD on EGD includes mucosal injury classified higher than grade B (erosions > 5 mm in length, not crossing over mucosal folds) using the Los Angeles (LA) grading system [17, 47]. A third of treatment naïve patients with typical symptoms have evidence of mucosal injury, which drops to < 10% in patients on acid suppressive therapy [48]. Histopathology proven Barrett’s esophagus confirms GERD presence and correlates with abnormal esophageal acid exposure [49], seen in approximately 10% of patients with conclusive GERD. This is defined as intestinal metaplasia with goblet cells extending proximally into the tubular esophagus from the squamocolumnar junction [17]. Peptic esophageal stricture is another endoscopic finding that is conclusive for GERD. These findings on upper endoscopy raise suspicion of laryngopharyngeal reflux disease (LPRD) in patients presenting with LPS. However, finding conclusive GERD on endoscopy alone does not confirm reflux-mediated causality in LPS [6].

A multicenter study of 756 patients presenting with LPS demonstrated mucosal injury classified higher than LA grade B in 7.4% and biopsy proven Barrett’s esophagus in 3.3% of patients [50]. The proportion of LA grades B, C, and D esophagitis reported in isolated LPS was 3.4%, substantially lower than the 8.9% found in LPS with concurrent typical symptoms. However, proportions with Barrett’s esophagus (4.3% and 2.9%, respectively) and peptic stricture (1.7% and 1.4%, respectively) were similarly low in the two groups [50]. These prevalence rates indicate that the overall diagnostic yield of EGD is low, and that EGD may serve to rule out GERD complications rather than provide a conclusive diagnosis [6].

In addition to esophageal mucosal changes, EGD can also identify disrupted EGJ morphology in the form of hiatus hernia, which provides adjunctive evidence for GERD and LPRD. Additionally, endoscopy can identify gastric inlet patch, an area of heterotopic gastric mucosa in the proximal esophagus, which can secrete acid and pepsin similar to gastric mucosa. This has been associated with globus [51], and endoscopic ablation has been demonstrated to improve symptoms in limited studies [52], which could be an option in carefully selected patients with refractory globus.

Unsedated transnasal esophagoscopy (TNE) is a practical, office-based alternative to EGD to identify Barrett’s esophagus and esophageal mucosal changes related to gastroesophageal reflux [53–55]. TNE can be effective when performed by individuals with expertise and specialized training in esophageal endoscopy and can identify additional pathologies that may mimic reflux, such as eosinophilic esophagitis.

1.3.3 |. Esophageal Manometry

Esophageal high-resolution manometry (HRM) is the current standard for assessment of esophageal primary peristalsis and sphincter function [56]. Esophageal motility disorders affecting the smooth muscle esophagus are hierarchically characterized by the Chicago Classification, now in its fourth iteration [57].

Manometry does not provide a diagnosis of GERD or LPRD. Rather, manometry serves to rule out achalasia and outflow obstruction disorders that can mimic reflux symptoms, to assess esophagogastric junction (EGJ) morphology and esophageal peristaltic performance that can impact reflux pathophysiology, and to evaluate for and diagnose behavioral disorders such as supragastric belching and rumination that can overlap with reflux disease. The latter requires special protocols that involve using an HRM catheter with impedance and post-prandial monitoring for 30–60 min after giving the patient a standardized meal [58, 59].

The Lyon Consensus 2.0 considers esophageal hypomotility (ineffective esophageal motility, absent contractility) and abnormal EGJ morphology (hiatus hernia) detected on HRM as adjunctive or supportive features for a GERD diagnosis when primary GERD metrics provide inconclusive results [17]. The most common use of HRM in LPS is to identify the proximal margin of the lower esophageal sphincter (LES) or upper esophageal sphincter (UES) for proper positioning of pH-impedance and HEMII-pH catheters, respectively [60, 61].

1.3.4 |. Reflux Testing

Ambulatory reflux monitoring is the reference physiologic test for objectively quantifying reflux burden in patients evaluated for suspected reflux-mediated LPS, particularly when GERD is unproven and results will inform escalation to prolonged therapy or invasive anti-reflux interventions. The two dominant ambulatory modalities are 24-h catheter-based multichannel intraluminal impedance–pH monitoring and prolonged wireless pH monitoring (Table 1). Within contemporary GERD diagnostic frameworks, both quantify distal esophageal acid exposure time (AET). AET > 6% provides definitive evidence of pathologic acid reflux, whereas AET < 4% supports physiologic reflux, particularly when consistently < 4% across all 4 days of prolonged wireless recording [17, 62, 63].

TABLE 1 |.

Comparison of Ambulatory Reflux Monitoring Modalities.

Feature	Catheter pH	Impedance–pH	HEMII-pH	Wireless pH
Measures acid exposure	Yes	Yes	Yes	Yes
Detects non-acid reflux	No	Yes	Yes	No
Measures proximal extent	Limited	Yes	Yes	No
Detects gas reflux	No	Yes	Yes	No
Duration	24 h	24 h	24 h	48–96h
Patient tolerance	Moderate	Moderate	Lower	High
Recommended for:	Typical GERD	Isolated LPS	Research/complex LPS	Borderline GERD

Abbreviations: GERD, gastroesophageal reflux disease; HEMII-pH, hypopharyngeal-esophageal multichannel intraluminal impedance-pH; LPS: laryngopharyngeal symptoms.

1.3.4.1 |. Catheter Based Testing.

Catheter-based pH-impedance monitoring provides detailed characterization of refluxate. By combining impedance and pH sensors along the esophagus—and, with HEMII-pH, extending into the hypopharynx—this modality can distinguish acid from weakly acidic and nonacid reflux, differentiate liquid from gaseous events, and track proximal extent [64]. Hypopharyngeal profiling suggests that many hypopharyngeal events are weakly acidic/nonacid and frequently gaseous, which would be missed by pH-only testing [65]. pH-impedance outperforms conventional pH monitoring for nonacid and proximal reflux patterns relevant to extraesophageal symptoms [61, 66–68].

HEMII-pH may further increase detection of pharyngeal exposure; in adults with extraesophageal symptoms, normal endoscopy, and negative distal impedance-pH, 81% (17/21) had abnormal hypopharyngeal exposure on HEMII-pH⁶⁸. Proposed normative thresholds for HEMII-pH vary widely, and expert consensus groups have not agreed on clinically meaningful reflux-episode cutoffs for LPRD [6, 69, 70]. Impedance interpretation may incorporate mean nocturnal baseline impedance (MNBI) as a marker of mucosal integrity, although LPS-specific validation remains limited [71].

These diagnostic advantages come at a cost. Transnasal catheters are associated with patient discomfort and external visibility, which can alter eating, activity, sleep, and social behavior during the recording period [72, 73]. Catheter-based studies typically last 24 h, capturing only a single day’s physiology and potentially missing clinically important day-to-day variability. Automated impedance algorithms can over-detect proximal events; manual review has shown nearly 40% false positives for laryngopharyngeal reflux when automated analysis is used alone without manual oversight [74].

1.3.4.2 |. Wireless pH Monitoring.

Prolonged wireless pH monitoring offers improved patient tolerance and multi-day assessment of distal acid exposure that may better capture physiologic variability [75–77]. The capsule is attached to the distal esophageal mucosa during sedated endoscopy, eliminating the need for a nasal catheter. Patients generally report better tolerance, although chest pain and early capsule detachment occur in a subset of patients and overall cost is higher [73, 75, 78]. Multi-day recordings reduce false-negative sampling inherent to single-day studies and can be useful in variable or borderline physiology [79, 80]. In a large international cohort of patients with chronic laryngeal symptoms evaluated off acid suppression, diagnostic yield for GERD was 50% with prolonged wireless pH monitoring versus 27% with 24-h impedance-pH monitoring [81]. In one study, 30% of patients with functional heartburn on the first day of the study were found to have reflux disease by the end of the fourth study day [63, 82]. Among those who underwent both tests, concordance for GERD was only 40%, most often reflecting multiday GERD on wireless pH with no GERD detected on single-day impedance-pH monitoring [81]. These findings suggest that prolonged wireless monitoring may better capture physiologic variability and borderline disease cases in patients with LPS [78, 81, 82].

However, wireless pH monitoring measures distal acid exposure only and cannot detect weakly acidic/nonacid reflux or provide information about proximal or hypopharyngeal exposure [83]. Thus, it cannot directly confirm or phenotype LPRD, but instead quantifies distal GERD burden as a surrogate risk factor for extraesophageal manifestations.

1.3.4.3 |. Reflux Testing Summary.

In line with the Lyon consensus 2.0, pH-impedance monitoring is the optimal tool for assessing reflux when investigating symptoms such as LPS in the absence of concomitant typical symptoms; not only does it assess the acid reflux burden, but it also measures the overall number of reflux events (irrespective of acidity) as well as the proximal reach of the refluxate, which is important when trying to attribute reflux with proximal and LPS symptoms. Further, pH-impedance monitoring can differentiate between liquid, gas and mixed reflux, all of which could conceivably contribute to LPS [64, 75]. Wireless-pH monitoring is also an option, but is more appropriate as a first line test in those with typical symptoms of reflux (heartburn, regurgitation), as it only measures acid and only in the distal esophagus. On the other hand, in patients who are unable to tolerate the catheter-based pH-impedance study, wireless-pH monitoring can be an alternative, with the proviso that its limitations are considered (namely, the inability to measure non-acid reflux or proximal reach of refluxate) [6, 75]. pH-only catheter-based monitoring is not recommended, particularly for the assessment of LPS.

Reflux monitoring studies provide the potential for evaluating the temporal relationship between symptoms and reflux episodes, particularly for episodic LPS such as cough, throat clearing, and regurgitation, as well as typical perceptive symptoms of heartburn and esophageal chest pain. The Symptom Index (SI) is defined as the proportion of symptoms that occur within 2 min of reflux episodes [84], where a threshold of ≥ 50% is considered positive [85]. The SI is not reliable when symptoms and/or reflux episode numbers are small (< 3), and another drawback is that the number of reflux episodes is not factored in. The Symptom Association Probability (SAP) takes the total number of symptoms and reflux episodes, as well as the number of reflux-related symptoms into account in a statistical calculation evaluating the probability that symptoms and reflux episodes are associated [86, 87]. A p < 0.05 corresponds to SAP > 95%, which is considered positive. The weakest link in these reflux-symptom association tests is the patient factor, impacting timing accuracy, underreporting, and misattribution of symptoms [88]. Studies using auditory monitors for identification of cough have demonstrated increased accuracy and also that reflux can sometimes be induced by cough rather than reflux triggering cough [29, 89]. In summary, reflux-symptom association tests are only useful when positive and are most reliable when both SI and SAP are positive and when numbers of reflux episodes and symptoms are robust.

Taken together, catheter-based pH-impedance (particularly HEMII-pH) and wireless pH monitoring should be regarded as complementary technologies in suspected LPRD. When the primary question is whether clinically significant GERD is present—especially with chronic laryngeal symptoms and nondiagnostic endoscopy—prolonged wireless pH monitoring off PPI offers superior comfort and higher diagnostic yield, particularly in borderline or discordant cases [73, 78, 81, 82]. When the goal is to directly measure hypopharyngeal exposure and characterize reflux events reaching the pharynx, HEMII-pH is the only available ambulatory platform that captures these pharyngeal-level events, albeit with greater patient burden and interpretive complexity [64, 90].

1.3.4.4 |. Testing Off or On Medications.

During ambulatory reflux monitoring, a key consideration is whether testing should be undertaken off or on acid-reducing therapy. International clinical guidelines emphasize that the decision should be guided by the clinical question: whether GERD is undiagnosed, or whether it has been confirmed (on endoscopy or previous pH testing) and symptoms persist despite optimized treatment [6, 17, 31]. When GERD has not yet been objectively confirmed, reflux monitoring is recommended off acid-reducing medicines. This is particularly relevant when investigating for LPRD [6]. PPIs and related drugs suppress gastric acid secretion, thus reducing esophageal acid exposure. As a result, testing while on medication can mask pathological reflux [91, 92]. Although breakthrough acid reflux can still be measured, if the test is negative, it primarily indicates that the acid suppressive therapy is functioning adequately. In other words, on-therapy testing cannot be used to ‘exclude’ GERD or LPRD when the result is negative.

On the other hand, pH testing on PPI therapy has an equally important role: to investigate patients with proven GERD who remain symptomatic despite optimal treatment. In this clinical context, the aim is not to establish the presence of GERD but to assess the cause of refractory symptoms. Abnormal pH-impedance metrics whilst on PPI therapy with persistent symptoms may guide treatment escalation in proven GERD cases.

The Lyon Consensus 2.0 and the San Diego consensus statements recommend impedance-pH monitoring be performed on PPIs for patients with established GERD whose symptoms persist despite twice-daily therapy for 3 months. In this way, on-therapy testing can help distinguish between PPI-refractory GERD, reflux hypersensitivity, and non-reflux-related symptoms, whilst off PPI testing is used to confirm or exclude reflux disease [6, 17, 93]. It is important to recognize that disorders of gut-brain interaction, laryngeal hyperresponsiveness, hypervigilance syndromes, and behavioral disorders (supragastric belching, rumination syndrome) can overlap with objectively defined LPRD. Therefore, the mere presence of LPRD does not establish a causal relationship to LPS, and approaches directed toward non-reflux mechanisms for symptoms will need to be instituted if LPS persist despite adequate management of LPRD.

Recommendations for off acid-reducing therapy testing are to stop PPIs for at least 7 days before testing and H2RAs for at least 48 h before testing [30, 94]; however, symptom rebound on withdrawal of therapy, tolerability, and safety need to be taken into account [95].

1.4 |. When Reflux is Excluded: Alternative Diagnostic Pathways

Objective reflux testing that demonstrates physiologic distal acid exposure and absence of abnormal proximal reflux burden effectively rules out reflux as the primary driver of LPS. As such, continued reflux-directed therapy is unlikely to provide benefit and should be discontinued. Negative reflux testing should prompt a structured reassessment focused on alternative mechanisms such as laryngeal hypersensitivity syndromes (e.g., cough hypersensitivity), muscle tension dysphonia and functional voice disorders, esophageal motility or behavioral disorders, and psychological and cognitive-behavioral contributors (e.g., hypervigilance). Further, negative testing should not be interpreted as diagnostic failure, but rather a pivot point toward mechanism-based care. Continued escalation of acid suppression or surgical referral in the absence of objective reflux risks overtreatment, unnecessary cost and persistent symptoms.

2 |. Conclusions

The evaluation of LPS requires a paradigm shift away from reflexive attribution to reflux and toward a structured diagnostic approach that systematically considers alternative etiologies of LPS. LPS represents a heterogeneous symptom complex that is not synonymous with LPRD, and laryngoscopic findings alone are insufficient to establish a diagnosis of reflux disease. Objective evidence of pathologic reflux should therefore precede long-term antisecretory therapy or invasive interventions, particularly in patients with isolated LPS in the absence of typical esophageal complaints. The proposed diagnostic algorithm (Figure 1) provides a systematic framework for patient stratification based on symptom patterns, guiding appropriate testing and therapeutic decisions.

FIGURE 1 |.

Diagnostic Algorithm for Laryngopharyngeal Symptoms.

Despite substantial progress in defining LPRD through consensus-driven frameworks, important gaps remain. Key priorities include validation of hypopharyngeal reflux thresholds, improved characterization of the role of non-acid reflux in symptom generation, and identification of predictors of treatment response. Long-term outcomes studies evaluating symptom resolution, quality of life, medication discontinuation, and surgical outcomes following algorithm-driven care will be essential to validate this diagnostic approach and optimize management for patients with LPS and LPRD.

Importantly, patient education and shared decision-making are central to this paradigm, as is multidisciplinary collaboration across otolaryngology, gastroenterology, speech-language pathology, and related disciplines. Adoption of this structured approach has the potential to reduce unnecessary medications, improve diagnostic precision, and align treatment with underlying pathophysiology.

Summary.

• Overinclusive labeling of upper aerodigestive symptoms as laryngopharyngeal reflux has led to increased health care costs from repeated therapeutic trials and diagnostic testing.

• The San Diego Consensus defines laryngopharyngeal symptoms (LPS) as recurrent upper aerodigestive symptoms occurring at least twice weekly for 8 weeks or longer, and laryngopharyngeal reflux disease (LPRD) when LPS is associated with objective reflux evidence on diagnostic testing.

• Patients with both LPS and typical esophageal symptoms have a higher pretest probability of GERD/LPRD and may be appropriate for empiric treatment trials, reserving diagnostic testing for patients where symptom response is suboptimal or when reflux management needs to be escalated to invasive therapy.

• Patients with isolated LPS have a low pre-test probability of LPRD and benefit from upfront diagnostic testing to plan management strategy.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.