Laryngeal Recalibration Therapy Improves Laryngopharyngeal Symptoms in Patients with Suspected Laryngopharyngeal Reflux Disease

Abstract

Background:

Laryngopharyngeal symptoms such as cough, throat clearing, voice change, paradoxic vocal fold movement or laryngospasm are hyper-responsive behaviors resulting from local irritation (e.g., refluxate) and heightened sympathetic tone. Laryngeal recalibration therapy (LRT) guided by a speech-language pathologist (SLP) provides mechanical desensitization and cognitive recalibration to suppress hyper-responsive laryngeal patterns. This study aimed to assess symptom response to LRT among patients with chronic laryngopharyngeal symptoms symptoms undergoing evaluation of gastroesophageal reflux disease (GERD).

Methods:

Adults with chronic laryngopharyngeal symptoms referred for evaluation of GERD to a single center were prospectively followed. Inclusion criteria included ≥2 SLP directed LRT sessions. Data from endoscopy, ambulatory reflux monitoring, and patient reported outcomes were collected when available. The primary outcome was symptom response.

Results:

Sixty-five participants completed LRT: mean age 55.4 years (SD 17.2), 46 (71%) female, mean body mass index 25.6kg/m² (6.8), mean of 3.7 (1.9) LRT sessions. Overall, 55 (85%) participants met criteria for symptom response. Specifically, symptom response was similar between those with isolated laryngopharyngeal symptoms (13/15 (87%)) and concomitant laryngopharyngeal/esophageal symptoms (42/50 (84%)). Among participants that underwent reflux monitoring, symptom response was similar between those with proven, inconclusive for, and no GERD (18/21 (86%), 8/9 (89%), 10/13 (77%)).

Conclusion:

85% of patients with chronic laryngopharyngeal symptoms referred for GERD evaluation that underwent LRT experienced laryngeal symptom response. Rates of symptom response were maintained across patients with or without proven GERD as well as patients with or without concomitant esophageal reflux symptoms. SLP directed LRT is an effective approach to incorporate into multi-disciplinary management of chronic laryngopharyngeal symptoms/laryngopharyngeal reflux disease.

Graphical Abstract

Introduction

Nearly 20% of US adults experience chronic laryngopharyngeal symptoms such as voice change, throat clearing, cough, globus, respiratory dysfunction and altered swallowing patterns.^1-4 These symptoms represent hyper-responsive behaviors that can result from local irritation and heightened sympathetic tone. One such irritant includes retrograde reflux of gastroesophageal contents to the hypopharynx and above, or gastroesophageal reflux disease (GERD), also commonly referred to as laryngopharyngeal reflux disease (LPRD). Despite traditional anti-reflux management these bothersome symptoms often persist.^5-10 Further, the chronicity of laryngeal dysfunction elevates cognitive awareness, often confounding deleterious habits and symptom burden.^11-13 Laryngeal-specific anxiety, perseveration and hypervigilance is associated with overall anxiety, depression and quality of life impairment. ^14-16

Laryngeal recalibration therapy (LRT) provided by a speech language pathologist (SLP) integrates mechanical desensitization techniques and cognitive recalibration principles to attenuate hyper-responsive laryngeal behaviors and cognitive processes. Mechanical desensitization leverages established therapies such as cough suppression to target aberrant laryngeal patterns. This is found to reduce symptoms, enhance heart rate variability and reduce vagal sensitivity. Altering communicative patterns similarly is found to optimize aerodynamic and acoustic production.^17,18 The approach is multi-pronged, mitigating repetitive vocal fold trauma from cough, throat clearing and tension-laden speaking patterns. Cognitive recalibration leverages principles from acceptance and commitment therapy to identify and recalibrate thoughts of laryngeal sensations. ^19-25

While the intersection of cognitive awareness, laryngeal symptom burden, and laryngeal responses represents an important therapeutic target, the current paradigm for patients with laryngopharyngeal symptoms and GERD largely ignores the interplay of psychological stressors and behavioral patterns on symptom burden.²⁶ This dearth of research and clinical gap is a tremendous missed opportunity to help patients. Thus, the aims of this study were to assess laryngopharyngeal symptom response to LRT among patients undergoing evaluation for GERD and compare symptom response among sub-groups with or without proven evidence of GERD, as well as sub-groups with or without concomitant esophageal reflux symptoms.

Methods

Study Design and Subjects

Adults with chronic laryngopharyngeal symptoms (more than 8 weeks of throat clearing, mucus in throat, sore throat, dysphonia, cough) referred for evaluation of LPRD who underwent two or more sessions of SLP-directed LRT at a single center were prospectively followed. Patients were seen by one of four laryngology-specialized SLPs at the Center for Voice and Swallowing at the University of California San Diego. Exclusion criteria included dysphagia focused SLP therapy, pulmonary etiology in the absence of objective GERD, asynchronous SLP sessions, and/or surgical anti-reflux intervention between sessions. Subjects were not excluded if they switched SLP provider between therapies. The Institutional Review Board approved the study.

Laryngeal Recalibration Therapy

The basic tenants of LRT are to reduce cough/throat-clearing, enhance laryngeal hygiene, restore voice function, regulate breathing, improve swallowing efficiency and alleviate associated cognitive burdens. LRT consists of mechanical desensitization and cognitive recalibration. Mechanical desensitization focuses on well-known laryngeal suppression techniques (i.e. pursed lip breathing to suppress throat clearing or cough) and changing voice production by means of acoustic and aerodynamic techniques. Mechanical desensitization also involves breath coordination, when deemed appropriate by SLP, which utilizes heart rate variability biofeedback training to recalibrate vagal response with breath, working to re-establish normal sensations in the digestive system and throat. Cognitive recalibration uses relaxation and conceptualization of symptoms to rework thought patterns around chronic laryngeal behavior(s). Throughout LRT aerodynamic, acoustic and vagal tone metrics are captured. These include the GRBAS (Grade, Roughness, Breathiness, Aesthenia, & Strain) scale, mean phonation time (MPT), S/Z ratio, and forced vital capacity (FVC).

Data Collection

Data collected included demographics, use of antisecretory medications, findings from upper GI endoscopy including presence of absence of erosive esophagitis, cervical inlet patch, and hiatal hernia, findings from ambulatory reflux monitoring [96 hour wireless pH monitoring; Medtronic, Minneapolis, MN, USA] performed off acid suppression, number of SLP directed LRT sessions, % of symptom improvement (no improvement (<10%), minimal (10 to 30%), moderate (30 to 60%), near complete (70 to 90%), complete (>90%)), patient reported outcomes (PROs) including the reflux symptom index (RSI) score²⁷, voice-related quality of life (V-RQOL), voice handicap index (VHI) ²⁸, laryngeal cognitive affective tool (LCAT) ¹⁵, as well as acoustic and aerodynamic function including the GRBAS scale, MPT, S/Z ratio, and FVC. MPT and S/Z ratio are aerodynamic measures of vocal cord function. They are used in combination with instrumental and perceptual assessments to determine glottic competence. The data also reflects broadly on laryngeal function in the sense that prolonged voice times such as a sustained vowel or voiced "z" can be seen as pathologic tension irrespective of glottal closure. Conversely, hypersensitivity associated with LPRD may surface as disengagement where prolonged voice segments are unexpectedly shortened.

Outcomes & Definitions

The primary outcome was symptom response. A priori symptom response was based on % of symptom improvement. Symptom response included those with moderate, near or complete improvement at the end of LRT. Symptom non-response included those with no or minimal improvement at the end of LRT.

Sub-group analyses were performed among patients with or without concomitant esophageal reflux symptoms defined as troublesome heartburn, regurgitation or non-cardiac chest pain.

Sub-group analyses were performed among patients with or without elevated acid exposure time defined as acid exposure time greater than 4.0%. In a secondary analysis proven GERD was defined according to Lyon Consensus as two or more days of acid exposure time greater than 6.0%, no GERD defined as four days with acid exposure time less than 4.0%, with the remainder as inconclusive GERD.

Statistical Analysis

The target a priori sample size goal was 50 participants which would allow us to detect with 90% power a response rate 72% versus a null response rate of 50% (e.g., random chance), which we believed was a meaningful improvement. This power calculation assumed a two-sided exact test of a one-sample proportion with an alpha of 0.050 and was calculated using PASS 2020 (Kaysville, Utah).

The primary analysis assessed for rate of overall symptom response. Sub-group analyses compared symptom response between 1) participants with or without concomitant esophageal reflux symptoms, and 2) participants with or without proven GERD using chi-squared. Missing data were not imputed. Summaries are reported as frequency (percent) for categorical measures and mean (standard deviation) for continuous measures. Data were analyzed using R v4.2.0 (Vienna, Austria).

Results

A total of 65 participants completed LRT and are included in this study (Table 1): mean age 55.4 years (SD 17.2), 46 (71%) female, with a mean body mass index of 25.6kg/m² (SD 6.8). Symptom presentation included 79% dysphonia, 75% cough, 68% throat clearing and 62% vocal fatigue. Fifteen (23%) presented with isolated laryngopharyngeal symptoms and 50 (77%) presented with concomitant laryngopharyngeal and esophageal reflux symptoms including 55% regurgitation, 51% heartburn and 45% non-cardiac chest pain. Mean baseline RSI score was 24.5 (9.5); 88% of participants presented with an elevated RSI score. Mean baseline voice-related quality of life score was 21.7 (9.4) and mean baseline voice handicap index was 14.7 (9.1). Initial evaluation was by ENT for 58% of participants and by GI for 42%. Of the 55 participants that underwent upper GI endoscopy, cervical inlet patch and erosive esophagitis were each only seen in one participant and hiatal hernia was present in 25%. Of the 43 participants who underwent reflux monitoring, 28 (65%) had acid exposure time over 4.0%. According to Lyon consensus 2.0: 21 (49%) met criteria for proven GERD, 13 (30%) for No GERD, and 9 (21%) as inconclusive for GERD.

Table 1.

Baseline Characteristics of Participants

Baseline Characteristics	N=65
Age (years)	55.4 (17.2)
Female sex	46 (71%)
Body Mass Index (kg/m2)	25.6 (6.81)
Laryngopharyngeal Symptoms:	65 (100%)
Cough	49 (75%)
Throat Clearing	44 (68%)
Dysphonia	51 (79%)
Vocal Fatigue	40 (62%)
Globus	31 (48%)
Mucus in Throat	35 (54%)
Isolated Laryngopharyngeal Symptoms	15 (23%)
Concomitant Esophageal Reflux Symptoms	50 (77%)
Heartburn	33 (51%)
Regurgitation	36 (55%)
Chest Pain	29 (45%)
Initial Evaluation with ENT	38 (58%)
Initial Evaluation with Gastroenterology	27 (42%)
Proton pump inhibitor (PPI) use	46 (71%)
Endoscopic Findings (n=55)
Cervical Inlet Patch	1 (2%)
Hiatal hernia	14 (25%)
Erosive Esophagitis	1 (2%)
Objective evidence of GERD (Lyon 2.0 Criteria) (n=43)
Proven GERD	21 (49%)
Inconclusive for GERD	9 (21%)
No GERD	13 (30%)
Abnormal videofluoroscopy (n=14)	9 (64%)
Abnormal barium esophagram (n=34)	24 (71%)
History of Asthma	25 (38%)
History of Allergies	43 (66%)
Current Smoker	7 (11%)

Symptom Response

Participants underwent a mean of 3.7 (SD 1.9) LRT sessions with 53% undergoing 2 to 3 sessions, 39% undergoing 4 to 6 sessions, and 8% undergoing 7 or more sessions (Table 2). Overall 55 (85%) met criteria for symptom response including 17 (26%) with complete resolution, 19 (29%) with near complete resolution, and 19 (29%) with moderate response (Figure 1). Ten (15%) participants did not meet criteria for symptom response; 7 (11%) with minimal response and 3 (5%) with no response.

Table 2.

Details of Laryngeal Recalibration Therapy

Laryngeal Recalibration Therapy	N=65
Number of Sessions	3.7 (1.9)
Symptom Response	55 (85%)
Moderate	19 (29%)
Near Complete	19 (29%)
Resolved	17 (26%)
Symptom Non-Response	10 (15%)
Minimal	7 (11%)
None	3 (5%)
Baseline Reflux symptom index (RSI) (n=41)	24.5 (9.5)
Baseline Voice-related Quality of Life (n=35)	21.7 (9.4)
Baseline Voice Handicap Index (n=37)	14.7 (9.1)
Baseline Laryngeal Cognitive Affective Tool (n=3)	34.3 (7.0)
Baseline GRBAS (n=50)	2.2 (2.4)
Baseline Forced Vital Capacity (L) (n=13)	2.9 (1.0)
Baseline Mean Phonation Time (seconds) (n=36)	16.3 (9.4)
Baseline S/Z Ratio (n=34)	0.95 (0.4)

Figure 1. Symptom Response Following Laryngeal Recalibration Therapy.

Green bars represent participants meeting definition for response and purple bars represent participants meeting definition for non-response. Data is present for the overall cohort and amongst sub-groups.

Sub-Group Analyses (Figure 1)

Symptom response was similar between participants with isolated laryngopharyngeal symptoms (13/15 (87%)) and those with concomitant laryngopharyngeal & esophageal symptoms (42/50 (84%)). Similarly, symptom response was similar when comparing participants with acid exposure time on reflux monitoring greater than 4.0% (24/28 (86%)) to those with acid exposure time of 4.0% or lower (12/15 (80%)). When applying the Lyon Consensus 2.0 definitions for modern GERD symptom response was 86% (18/21) for those with proven GERD, 89% (8/9) for those inconclusive for GERD, and 77% (10/13) for those without evidence of GERD.

Factors Associated with Symptom Response (Table 3)

Table 3.

Variables Associated with Response to LRT

Variable	Responder (n=55)	Non- Responder (n=10)	P-value
Female	39 (70%)	7 (70%)	1.00
Age (years)	57.1 (17)	46.0 (16.5)	0.07
Body mass index (kg/m2)	25.8 (7.1)	24.3 (4.8)	0.43
PPI use	38 (69%)	8 (80%)	0.71
Elevated Acid Exposure Time (>4.0%)	24/36 (67%)	4/7 (57%)	0.68
Acid Exposure Time (%)	6.6% (5.0)	6.8% (5.8)	0.92
Baseline Symptoms
Cough	42 (76%)	7 (70%)	0.70
Dysphonia	42 (76%)	9 (90%)	0.68
Globus	25 (46%)	6 (60%)	0.50
Mucus in Throat	30 (55%)	5 (50%)	1.00
Throat Clearing	39 (71%)	5 (50%)	0.27
Vocal Fatigue	33 (60%)	7 (70%)	0.73
Dysphagia	29 (53%)	5 (50%)	1.00
Chest Pain	26 (47%)	3 (30%)	0.49
Heartburn	28 (51%)	5 (50%)	1.00
Regurgitation	30 (55%)	6 (60%)	1.00
Number of LRT Sessions	3.82 (1.93)	3.3 (1.49)	0.35
Baseline PRO Scores
Reflux Symptom Index	23.0 (8.3)	33.0 (12.2)	0.11
Voice Handicap Index	14.3 (9.61)	17.0 (4.47)	0.33
Voice-Related Quality of Life	21.2 (9.87)	24.8 (5.93)	0.29
Baseline Aerodynamic Function
GRBAS (n=50)	2.02 (2.43)	2.88 (2.03)	0.32
Mean Phonation Time (sec) (n=36)	17.4 (9.54)	9.2 (4.44)	<0.01
S/Z Ratio (n=34)	0.99 (0.35)	0.73 (0.22)	0.05
Forced Vital Capacity (L) (n=13)	3.0 (1.0)	2.0 (0.3)	0.03

There was an increase for greater symptom response with greater number of LRT sessions: 3 or fewer sessions (29/36 (81%)), 4 to 6 sessions (22/25 (88%)), and 7 or more sessions (4/4 (100%)). Patients with symptom response tended to be older than those without response (57.1 years (17) vs 46.0 years (16.5); p=0.07). Of note, PPI use was not associated with symptom response.

Further, baseline aerodynamic findings differed between those with symptom response compared to those without symptom response. These included a higher MPT (Responder 17.4 seconds (SD 9.5) vs non-responder 9.2 (4.4); p=0.009), a higher S/Z ratio (0.99 (0.35) vs 0.73 (0.22); p=0.05), and a higher FVC (3.0 (1.0) L vs 2.0 (0.3); p=0.03) (Figure 2).

Figure 2. Baseline Aerodynamic Measures in LRT Non-Responder versus Responder Groups.

Discussion

Hyper-responsive behaviors and heightened cognitive awareness are highly prevalent in patients with laryngopharyngeal symptoms, and can be modified by multi-disciplinary targeted interventions. Given the paucity of evidence for effective interventions in patients with laryngopharyngeal symptoms undergoing evaluation for GERD (also colloquially referred to as LPRD), we evaluated the efficacy of LRT provided by a specialized SLP, which combines altering mechanical patterns, desensitizing laryngeal tissues and providing symptom-specific cognitive restructuring (Figure 3). The treatment aims to restore healthful respiratory patterns, reduce mucosal abnormalities on the vocal folds, alleviate laryngeal tension and cognitive reconceptualization. In our study, symptom response to LRT was 85% - a response rate much higher than that of traditional anti-reflux interventions.^5-8 The response rates were similar and maintained among those with isolated laryngopharyngeal symptoms and those with concomitant laryngopharyngeal and esophageal symptoms, as well as those with or without objective GERD. The responder group, compared to the non-responders, had significantly more competent and coordinated speech subsystems at baseline. Thus, LRT is a highly effective, non-invasive, and accessible therapy provided by an SLP that should be incorporated in multi-disciplinary management of patients with laryngopharyngeal symptoms undergoing evaluation for GERD.

Figure 3. Laryngeal Recalibration Therapy (LRT).

LRT is provided by a specialized SLP and combines altering mechanical patterns, desensitizing laryngeal tissues and providing symptom-specific cognitive restructuring. The treatment aims to restore healthful respiratory patterns, reduce mucosal abnormalities on the vocal folds, alleviate laryngeal tension and cognitive reconceptualization.

While LRT is a newer treatment modality, it leverages well-established therapies in the fields of laryngology as well as mind-body interactions. For example, in a sham-controlled randomized controlled trial of 21 adults with refractory chronic cough, Slovarp et al. found that cough desensitization treatment led to improvements in symptoms when compared to controls.¹⁷ Schneider et al. demonstrated the effectiveness of 3 sessions of voice therapy in a retrospective cohort study of 18 patients with muscle tension dysphonia or vocal hyperfunction that was not responsive to anti-reflux therapy.²¹ Vashani et al. evaluated the effectiveness of voice therapy with omeprazole compared to omeprazole alone in 32 patients with GERD, diagnosed based on symptoms or endoscopy, and dysphonia. Patients who underwent voice therapy with omeprazole had significantly better outcomes when compared to those given omeprazole alone.²⁹ Though promising, these studies are limited by the small sample size and narrow target audience.

HRV biofeedback training is another, even less studied therapeutic that is gaining traction in management of chronic diseases. The rationale for its use stems from the idea that HRV is a measure of autonomic function and overall health, with high HRV indicating adaptability of the cardiac system to react to stressors.¹⁸ Evidence also suggests that a link exists between emotions and HRV, supporting the idea that HRV biofeedback training could improve vagal functioning, HRV and ultimately emotional regulation.¹⁸ These theories were supported in a systematic review by Fournie et al. evaluating 29 articles and found that HRV biofeedback was shown to be effective in patients with hypertension, inflammatory states, asthma disorders, depression, anxiety, sleep disturbance and pain and was associated with improved quality of life.¹⁸

Given the overlapping quality of life impairment, cognitive-affective processes, anxiety, and depression in patients with chronic laryngopharyngeal symptoms,^14,15,30 therapies should ideally target these constructs. Multiple studies, including a recent well-designed randomized placebo controlled trial of proton pump inhibitor, repeatedly demonstrate that acid suppression is not better than placebo for laryngeal symptom improvement.³¹ This is due to two important aspects. First, not all patients with laryngopharyngeal symptoms have GERD. Second, even in those with GERD the mechanisms of chronic persisting laryngopharyngeal symptoms involve hyper-responsive and cognitive mechanisms which are not addressable with acid suppression. Unfortunately, the literature evaluating cognitive interventions for laryngeal disorders is sparse. In irritable bowel syndrome, a highly prevalent disorder of brain-gut interaction, the research is more robust with a meta-analysis conducted by Black et al. demonstrating that several behavioral therapies were effective in improving symptoms, with the most evidence supporting the use of cognitive-behavioral therapy and gut-directed hypnotherapy.³² In supragastric belching, another upper gastroenterological disorder of brain-gut interaction, Glasinovic et al. evaluated the effectiveness of cognitive-behavioral therapy in 31 patients with supragastric belching and GERD and found that 16/31 had a reduction in supragastric belching by more than 50%.³³ This research suggests that cognitive-based therapies are efficacious in disorders of mind-body interaction. Our study is the first to demonstrate utility of these interventions in patients with chronic laryngeal disorders.

The compilation of evidence demonstrates that multi-pronged therapies targeting voice production, laryngeal suppression, breath coordination, swallowing and cognitive recalibration are effective for chronic laryngopharyngeal symptoms. Our study is the first of its kind to assess the efficacy of these interventions seamlessly integrated into one therapy, LRT. It is delivered by a specialty trained SLP, with most participants undergoing 2 to 3 sixty-minute sessions. Strengths of this study include a well-described cohort of patients undergoing an easily reproducible intervention that can be applied in a variety of clinical centers. Further, the sample size is large when compared to other studies in the field. In addition, LRT represents a novel new therapy that can be applied to a group of patients historically challenging to treat. Limitations of this study include the single-center study design, small sub-group sample sizes, and lack of long-term follow-up data. Future directions include a randomized controlled trial across centers assessing efficacy of LRT, as well as measurement of aerodynamic function before and after intervention.

In conclusion, we found that LRT was highly effective, achieving an 85% laryngeal symptom response, in patients with chronic laryngopharyngeal symptoms referred for LPRD evaluation. These findings were maintained in sub-groups comparing patients with or without objective GERD and with or without concomitant esophageal reflux symptoms. LRT administered by a specialized SLP is a highly effective, accessible and non-invasive intervention for patients with chronic laryngopharyngeal symptoms and should be incorporated in the multi-disciplinary management of these complex patients.

Study Highlights:

What is Known:

• Laryngopharyngeal symptoms are commonly attributed to gastroesophageal reflux disease though often refractory to anti-reflux management

• Laryngopharyngeal symptom burden results from hyper-responsive behaviors & cognitive processes

• Speech-language pathologist guided laryngeal recalibration therapy provides laryngeal mechanical desensitization and cognitive recalibration

What is New Here:

• The majority (85%) of patients referred for evaluation of laryngopharyngeal reflux disease that underwent laryngeal recalibration therapy experienced symptom response

• Symptom response was maintained across patients with/without proven GERD and with/without concomitant esophageal reflux symptoms

• Laryngeal recalibration therapy is an effective approach to incorporate into multi-disciplinary management of laryngopharyngeal reflux disease

Abbreviations:

LRT

Laryngeal recalibration therapy

SLP

Speech-language pathologist

LPRD

Laryngopharyngeal reflux disease

GERD

gastro-esophageal reflux disease

HRV

heart rate variability

Data Sharing Statement:

Data, analytic methods, and study materials will be made available to other researchers by request whose used of the proposed data has been approved. Data is available on request to mgreytak@health.ucsd.edu.