Effect of comorbid gastroesophageal reflux disease on laryngopharyngeal reflux disease: Clinical characteristics and risk factors

Abstract

BACKGROUND

Research thoroughly examining how gastroesophageal reflux disease (GERD) affects clinical presentations in patients with laryngopharyngeal reflux disease (LPRD) and exploring the associated triggers is limited.

AIM

To investigate the effect of comorbid GERD on the clinical characteristics of patients with LPRD and determine risk contributors.

METHODS

In total, 150 patients with LPRD admitted between October 2022 and October 2024 were divided into the GERD (n = 74) or non-GERD (n = 76) group based on their comorbid GERD status. The clinical data collected included age, sex, body mass index (BMI), marital status, smoking, alcohol consumption, and eating habits in the 3-hour window before sleep. The following reflux-related symptoms were recorded: (1) Hoarseness/voice disorders; (2) Persistent throat clearing; (3) Excessive phlegm/postnasal drip; (4) Difficulty swallowing food or water; (5) Postprandial or supine coughing; (6) Breathing difficulties; (7) Bothersome cough; (8) Throat foreign body sensation; (9) Heartburn, chest pain; and (10) Stomach pain. The Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) tools were used. Binary logistic regression identified contributors to GERD in LPRD.

RESULTS

Compared with the non-GERD group, the GERD group, with a notably higher BMI, included greater proportions of older patients, female patients, smokers, and alcohol users and a higher prevalence of bothersome cough, heartburn, chest pain, and stomach pain; however, excessive phlegm or postnasal drip was less common. Additionally, patients with LPRD and comorbid GERD had notably higher RSI and RFS scores. Age (P = 0.017), sex (P = 0.029), smoking (P = 0.012), and alcohol consumption (P = 0.036) were significant triggers for GERD comorbidity in LPRD.

CONCLUSION

Comorbid GERD exacerbates clinical manifestations of patients with LPRD. Advanced age, female sex, smoking, and alcohol consumption predispose patients with LPRD to GERD development.

Key Words: Gastroesophageal reflux disease; Laryngopharyngeal reflux disease; Clinical characteristics; Risk factors; Regression analysis

Core Tip: This study enrolled 150 patients with laryngopharyngeal reflux disease (LPRD) and stratified them by gastroesophageal reflux disease (GERD) status (GERD group, n = 74; non-GERD group, n = 76) to assess the influence of GERD comorbidity on clinical manifestations while identifying possible risk determinants. GERD comorbidity significantly worsened symptoms in patients with LPRD, increased in flux event episodes, and aggravated flux severity. The independent risk factors included advanced age, female sex, smoking, and alcohol consumption.

INTRODUCTION

Laryngopharyngeal reflux disease (LPRD), characterized by mucosal inflammation in the laryngopharyngeal and upper aerodigestive tract, is mainly triggered by the retrograde movement of stomach contents into areas beyond the esophagus[1]. Patients with LPRD often present hoarseness, chronic cough, throat discomfort, a throat obstruction sensation, and excessive mucus obstruction, significantly compromising their health and diminishing overall life quality[2,3]. LPRD represents approximately 15.0% of otolaryngology outpatient visits[4]. Although the severity of LPRD can be evaluated using the Reflux Symptom Index (RSI) and Reflux Finding Score (RFS), the diagnosis is complicated by its nonspecific symptoms and clinical signs[5,6]. LPRD management is also challenging. Proton pump inhibitors (PPIs) are frequently employed as the first-choice treatment; however, their effectiveness varies as patients respond differently to antireflux medications, and symptoms were not mitigated in 40.0% of LPRD cases[7,8].

As a closely related condition, gastroesophageal reflux disease (GERD) is frequently diagnosed in conjunction with LPRD. Although GERD and LPRD can be diagnosed independently, they often interact and influence each other[9,10]. Studies have indicated that 10.0%–46.0% of patients with GERD also exhibit symptoms of LPRD, whereas 48.6%–52.7% of patients with LPRD are concurrently diagnosed with GERD[11,12]. GERD is defined by recurrent episodes of heartburn and regurgitation, along with complications specific to the condition. It affects approximately 20.0% of adults in high-income nations and is associated with an increased risk of esophagitis, esophageal strictures, Barrett’s esophagus, and esophageal adenocarcinoma[13]. Despite the established link between GERD and LPRD, no studies have comprehensively examined how GERD specifically influences the clinical presentation of LPRD and the associated risk factors. This study aimed to address this gap by examining the effect of GERD on LPRD. By elucidating the interplay between these two conditions, the findings may refine diagnostic approaches, enhance treatment strategies, and ultimately improve the delivery of more personalized and effective care to patients.

MATERIALS AND METHODS

Study population

The study included 150 patients diagnosed with LPRD who were admitted to Tiantai People's Hospital of Zhejiang Province between October 2022 and October 2024. Based on the presence of comorbid GERD, these patients were categorized into the GERD (n = 74) and non-GERD (n = 76) groups.

Inclusion and exclusion criteria

Inclusion criteria: (1) A definitive diagnosis of LPRD[14]; (2) Age: 18–80 years; (3) Laryngeal symptoms (e.g., throat discomfort, foreign body sensation, and hoarseness) that require laryngoscopy; (4) Absence of cognitive; (5) Communicative, or psychological impairments; and (6) Availability of complete case records.

Exclusion criteria: (1) Involvement in any other clinical trials within the 3 months preceding this study; (2) A medical history of surgical interventions involving the upper gastrointestinal tract; (3) Women who were either pregnant or breastfeeding at the time of the study; (4) Regular use of medications such as PPIs or gastrointestinal prokinetic agents; (5) Long-term use of estrogen-based pharmaceutical treatments; (6) Diagnosis of organic gastrointestinal disorders, including but not limited to esophageal diverticulum, achalasia, eosinophilic esophagitis, significant hiatal hernia, or esophageal spasms; (7) Abnormal laboratory test results, such as biochemical analyses, myocardial enzyme profiles, coagulation studies, preoperative screenings, or electrocardiograms; (8) History of dysphagia; and (9) Comorbid chronic respiratory or cardiovascular conditions.

Measurement indicators

Clinical characteristics: Demographic and lifestyle data, including age, sex, body mass index (BMI), marital status, smoking habits, alcohol consumption, and dietary patterns (e.g., eating habits in the 3-hour window before sleep), were systematically collected. Smoking was categorized as the use of at least one cigarette daily or weekly for a minimum of 3 months continuously or cumulatively. Alcohol consumption was defined as the intake of ≥ 1 Liang (50 mL of 50° liquor, equivalent to ≥ 20 g of pure ethanol) per month.

Scale assessments: Under the supervision of healthcare professionals, participants independently completed the Chinese version of the RSI questionnaire[15]. A total RSI score > 13.0 confirmed a clinical diagnosis of LPRD. Additionally, two experienced physicians evaluated laryngoscopic images using the RFS scale. The average score derived from their assessments served as the final RFS score, with > 7.0 indicating a clinical diagnosis of LPRD.

Statistical analysis

Continuous variables were statistically described using mean ± SE, and group comparisons were conducted using independent-sample t-tests. Between-group differences in categorical variables (summarized as percentages) were assessed using the χ² test. Data analysis was performed using IBM Statistical Package for the Social Sciences Statistics version 22.0 (IBM Corp., Armonk, NY, United States), whereas graphical representations were created using GraphPad Prism 7.0. A multivariate analysis of the risk factors for comorbid GERD in LPRD was conducted using the binary logistic regression model. Significance was set at P < 0.05.

RESULTS

Clinical characteristics

The GERD and non-GERD groups did not show significant differences in marital status or dietary behaviors, such as eating habits in the 3-hour window before sleep (P > 0.05). However, notable differences were observed in variables, including age, sex, BMI, smoking habits, and alcohol consumption (P < 0.05). Detailed comparisons are provided in Table 1.

Table 1 Patients’ clinical characteristics, n (%).

Factors	GERD group (n = 74)	Non-GERD group (n = 76)	χ2/t	P value
Age (years)	57.92 ± 8.58	54.78 ± 7.91	2.331	0.021
Gender			4.482	0.034
Male	34 (45.95)	48 (63.16)
Female	40 (54.05)	28 (36.84)
Body mass index (kg/m2)	23.05 ± 2.83	22.12 ± 2.68	2.067	0.041
Marital status			1.056	0.304
Married	52 (70.27)	59 (77.63)
Unmarried	22 (29.73)	17 (22.37)
Smoking			6.007	0.014
Yes	28 (37.84)	15 (19.74)
No	46 (62.16)	61 (80.26)
Alcohol consumption			5.830	0.016
Yes	19 (25.68)	8 (10.53)
No	55 (74.32)	68 (89.47)
Eating habits in the 3-hour window before sleep			0.973	0.324
Yes	63 (85.14)	60 (78.95)
No	11 (14.86)	16 (21.05)

GERD: Gastroesophageal reflux disease.

Reflux symptoms

Compared with the non-GERD group, the GERD group exhibited significantly fewer cases of excessive phlegm or postnasal drip. Conversely, the prevalence of bothersome cough, heartburn, chest pain, and stomach pain were higher in the GERD group than in the non-GERD group (P < 0.05). No significant intergroup differences were noted in other symptoms (P > 0.05). A detailed breakdown is shown in Table 2.

Table 2 Reflux symptoms in the two groups, n (%).

Symptoms	GERD group (n = 74)	Non-GERD group (n = 76)	χ2	P value
Hoarseness or voice disorders	2 (2.70)	8 (10.53)	3.688	0.055
Persistent throat clearing	26 (35.14)	17 (22.37)	2.988	0.084
Excessive phlegm or postnasal drip	4 (5.41)	13 (17.11)	5.107	0.024
Difficulty swallowing food or water	4 (5.41)	1 (1.32)	1.946	0.163
Postprandial or supine coughing	2 (2.70)	2 (2.63)	< 0.001	0.978
Breathing difficulties	2 (2.70)	1 (1.32)	0.368	0.544
Bothersome cough	21 (28.38)	10 (13.16)	5.298	0.021
Throat foreign body sensation	11 (14.86)	14 (18.42)	0.341	0.559
Heartburn, chest pain, and stomach pain	13 (17.57)	5 (6.58)	4.287	0.038

GERD: Gastroesophageal reflux disease.

Comparison of scale scores

The RSI and RFS scores were significantly higher in the GERD group than in the non-GERD group (P < 0.05). Graphical representations of these findings are shown in Figure 1.

Figure 1 Reflux Symptom Index and Reflux Finding Score of the two groups. A: Reflux Symptom Index scores. B: Reflux Finding Score. ^aP < 0.05; ^bP < 0.01, reflecting significant differences between groups. GERD: Gastroesophageal reflux disease; RFS: Reflux Finding Score; RSI: Reflux Symptom Index.

Risk factors for LPRD comorbid with GERD

Binary logistic regression analysis revealed that age (P = 0.017), sex (P = 0.029), smoking (P = 0.012), and alcohol consumption (P = 0.036) were significant risk factors for the coexistence of GERD and LPRD. The assignments and analysis results are detailed in Tables 3 and 4.

Table 3 Assignment table.

Factor	Variate	Assignment
Age (years)	X1	Continuous variable
Gender	X2	Male = 0, female = 1
Body mass index (kg/m2)	X3	Continuous variable
Marital status	X4	Married = 0, unmarried = 1
Smoking	X5	No = 0, yes = 1
Alcohol consumption	X6	No = 0, yes = 1
Eating habits in the 3-hour window before sleep	X7	No = 0, yes = 1
Gastroesophageal reflux disease	Y	No = 0, yes = 1

Table 4 Analysis of risk factors for comorbid gastroesophageal reflux disease in laryngopharyngeal reflux disease patients.

Factors	β	SE	Wald	P value	Odds ratio	95%CI
Age (years)	0.056	0.024	5.715	0.017	1.058	1.010-1.108
Gender	0.806	0.369	4.764	0.029	2.238	1.086-4.613
Body mass index (kg/m2)	0.092	0.067	1.890	0.169	1.097	0.961-1.251
Marital status	0.544	0.418	1.694	0.193	1.723	0.759-3.908
Smoking	1.027	0.409	6.310	0.012	2.793	1.253-6.224
Alcohol consumption	1.017	0.486	4.388	0.036	2.765	1.068-7.163
Eating habits in the 3-hour window before sleep	0.138	0.482	0082	0.774	1.148	0.446-2.956

DISCUSSION

GERD, a condition linked to extraesophageal syndromes, adversely affects nearly 14.0% of the global population, resulting in substantial healthcare expenses for patients[16]. The mechanisms underlying GERD are complex, involving transient relaxation of the lower esophageal sphincter (LES) and other dysfunctions related to LES pressure. These abnormalities facilitate the backflow of acidic substances, bile, pepsin, and pancreatic enzymes into the esophagus, leading to mucosal injury[17]. Given the hypersensitivity of peripheral and central sensory nerves, patients with GERD often suffer from chronic and persistent pain, with many showing poor response to PPIs[18]. Hence, this study intends to optimize GERD prevention and management in LPRD cases by examining how GERD influences the clinical features of LPRD and identifying potential triggers.

Compared with the non-GERD group, the GERD group often experiences bothersome cough, heartburn, chest pain, and stomach pain but a lower prevalence of excessive phlegm or postnasal drip. This finding indicates that concurrent GERD can intensify symptoms in LPRD, particularly in terms of persistent cough, heartburn, chest pain, and stomach discomfort. A potential explanation is increased esophageal acid exposure, enhancing cough reflex sensitivity. Moreover, greater acidic reflux episodes in patients with LPRD and GERD further aggravate cough-related manifestations[19]. The GERD group had higher RSI and RFS scores than the non-GERD group, highlighting the aggravating effect of the GERD on the symptomatic presentation and clinical signs of LPRD. Shilpa et al[20] confirmed our findings, reporting the highest RSI scores in patients with LPRD complicated with GERD. A contributor could be TRPV1 activation in esophageal epithelial cells by GERD, which in turn leads to inflammation induction and vagally mediated cough reflex sensitization, thus worsening LPRD symptoms through esophagopharyngeal reflex mechanisms[21,22].

The proportions of older adults, female patients, patients with higher BMI, smokers, and alcohol users were greater in the GERD group than in the non-GERD group. Binary logistic regression further confirmed that age (P = 0.017), sex (P = 0.029), smoking (P = 0.012), and alcohol consumption (P = 0.036) independently predicted GERD development in patients with LPRD. These findings highlight that GERD is more likely to occur in older patients with LPRD, female patients, smokers, and alcohol drinkers. Specifically, older individuals often exhibit diminished LES function, impaired esophageal peristalsis, delayed gastric emptying, and a higher burden of comorbidities, which may compromise antireflux mechanisms and predispose them to GERD[23]. Conversely, women are more susceptible to hormonal (estrogen) influences that relax the LES, and their relatively shorter esophagus may further increase GERD susceptibility[24]. Smoking reduces LES pressure, stimulates gastric acid secretion, damages the mucosal barriers of the esophagus and throat, and decreases saliva production, which contribute to the risk of GERD[25,26]. Similarly, alcohol relaxes the LES, promotes gastric acid secretion, delays gastric emptying, and impairs mucosal barriers, thereby increasing the risk of GERD[25,26]. These findings align with the results of previous studies. For instance, Wang et al[27] identified female sex and smoking history as significant contributors to GERD. Lin et al[28] also reported that women are at greater risk of GERD than men, and advanced age, smoking, and alcohol consumption are strongly associated with GERD. Additionally, Sadafi et al[29] noted that obesity, physical inactivity, excessive sugar intake, and low dietary fiber intake further increase the risk of GERD.

Based on the above findings, a risk factor-based stratified intervention strategy is proposed: High-risk groups (e.g., older and female patients) should be monitored closely and promptly treated for GERD if symptoms arise. Smoking cessation and alcohol restriction should be prioritized, particularly in those experiencing GERD symptoms. Additionally, GERD guidelines recommend lifestyle adjustments, such as head-of-bed elevation, avoiding late-night meals, and PPI administration 30–60 minutes before meals rather than before sleep for better symptom control[30].

This study has some limitations. The single-center setting may introduce geographic bias because regional dietary differences could influence reflux rates. Thus, future multicenter studies across wider regions are needed. Additionally, retrospective data limitations prohibited the evaluation of the effect of hiatal hernia on research outcomes and the effects of GERD-LPRD on complications (e.g., esophageal strictures and Barrett’s esophagus). Future studies should include these evaluations to better control for confounders and provide more comprehensive clinical outcomes.

CONCLUSION

Taken together, the presence of GERD significantly aggravates clinical symptoms in patients with LPRD and increases the frequency and severity of reflux events. Advanced age, female sex, smoking, and alcohol consumption are key risk factors for the development of GERD in patients with LPRD. These insights can aid clinicians in identifying patients with high-risk LPRD and underscore the importance of lifestyle modifications, particularly smoking cessation and alcohol avoidance, to mitigate effectively the risk and manage GERD.