You are here

Article Text

Article menu

Download PDFPDF

Epidemiology
Original research
Awareness about laryngopharyngeal reflux disease among Chinese otolaryngologists: a nationwide survey
  1. Shuifang Xiao1,
  2. Jinrang Li2,
  3. Hongliang Zheng3,
  4. Xiangping Li4,
  5. Hui Yang5,
  6. Junbo Zhang1,
  7. Xiaoxia Peng6,
  8. Shuihong Zhou7,
  9. Chen Zhao8,
  10. Donghui Chen9,
  11. Xuping Xiao10,
  12. Li Shi11,
  13. Hui Huangfu12,
  14. Zhenfeng Tao13,
  15. Xiong Chen14,
  16. Yehai Liu15,
  17. Shenhong Qu16,
  18. Guangke Wang17,
  19. Ting Chen18,
  20. Xiaobo Cui19,
  21. Linli Tian20,
  22. Wensheng Zhou21,
  23. Hongyan Fang22,
  24. Yongwang Huang23,
  25. Guodong Yu24,
  26. Zhenqun Lin25,
  27. Liang Tang26,
  28. Jian He27,
  29. Ruixia Ma28,
  30. Zhaoyan Yu29
  1. 1Department of Otolaryngology, Head and Neck Surgery, Peking University First Hospital, Beijing, China
  2. 2Department of Otolaryngology, Head and Neck Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing, China
  3. 3Department of Otolaryngology, Head and Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
  4. 4Department of Otolaryngology, Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
  5. 5Department of Otolaryngology, Head and Neck Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
  6. 6Clinical Epidemiology and Evidence-based Medicine Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
  7. 7Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
  8. 8Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
  9. 9Department of Otolaryngology, Head and Neck Surgery, Jiangsu Province Hospital, Nanjing, Jiangsu, China
  10. 10Department of Otolaryngology, Head and Neck Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
  11. 11Department of Otolaryngology, Head and Neck Surgery, Xijing Hospital, Air Force Military Medical University, Xi'an, Shaanxi, China
  12. 12Department of Otolaryngology, Head and Neck Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
  13. 13Department of Otolaryngology, Head and Neck Surgery, Bethune International Peace Hospital, Shijiazhuang, Hebei, China
  14. 14Department of Otolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
  15. 15Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
  16. 16Department of Otolaryngology, Head and Neck Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China
  17. 17Department of Otolaryngology, Head and Neck Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, China
  18. 18Department of Otolaryngology, Head and Neck Surgery, Fujian Provincial Hospital, Fuzhou, Fujian, China
  19. 19Department of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China
  20. 20Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
  21. 21Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
  22. 22Department of Otolaryngology, Head and Neck Surgery, Chongqing General Hospital, Chongqing, China
  23. 23Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Tianjin Medical University, Tianjin, China
  24. 24Department of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
  25. 25Department of Otolaryngology, Head and Neck Surgery, Hainan Provincial People's Hospital, Haikou, Hainan, China
  26. 26Department of Otolaryngology, Head and Neck Surgery, The People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
  27. 27Department of Otolaryngology, Head and Neck Surgery, Gansu Provincial Hospital, Lanzhou, Gansu, China
  28. 28Department of Otolaryngology, Head and Neck Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
  29. 29Department of Otolaryngology, Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong Provincial ENT Hospital Affiliated to Shandong University, Jinan, Shandong, China
  1. Correspondence to Dr Shuifang Xiao; xiao_ent{at}163.com; Dr Jinrang Li; entljr{at}sina.com; Dr Hongliang Zheng; zheng_hl2004{at}163.com

Abstract

Objectives This study aimed to investigate the status of the current knowledge about laryngopharyngeal reflux disease (LPRD) among Chinese otolaryngologists.

Design Multi-centre cross-sectional survey.

Setting 220 medical centres in different regions of China.

Participants A total of 2254 otolaryngologists from 220 medical centres in China who were successfully on-site surveyed between November 2019 and December 2020.

Main outcome measures Awareness about LPRD included knowledge about risk factors, symptoms, laryngoscope signs, related diseases, current diagnostic methods and treatments.

Results The percentage of participants who had heard of LPRD was 96.4%, with academic conferences as the most common source of information (73.3%). The most commonly known risk factor, symptom, laryngoscope sign, related disease, diagnostic method and treatment were alcohol consumption (44.0%), pharyngeal foreign body sensation (66.9%), hyperaemia (52.4%), pharyngolaryngitis (54.8%), pH monitoring (47.6%) and medication (82.1%), respectively. Only 28.3% of all participants knew that 24 h pH or multichannel intraluminal impedance pH monitoring was the most accurate diagnostic test. As many as 73.1% of all participants knew that proton pump inhibitors were the first-line treatment drugs. An analysis of the overall status of awareness using a scoring system suggested that otolaryngologists were better aware owing to more access, working at 3A hospitals, and postgraduate or above educational background (all p<0.05).

Conclusion Although the majority of Chinese otolaryngologists had heard of LPRD, their overall awareness about the disease was not encouraging. More efforts are needed to increase the knowledge about LPRD among this group of physicians.

Trial registration number ChiCTR1900025581

  • OTOLARYNGOLOGY
  • EPIDEMIOLOGY
  • Laryngology

Data availability statement

Data are available on reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2021-058852

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Strengths and limitations of this study

    • This prospective cross-sectional survey was carried out in up to 2254 otolaryngologists who worked in different hospitals around the whole China.

    • The whole surveys were all performed on-site under the supervision of designated surveyors.

    • The overall awareness status about laryngopharyngeal reflux disease knowledge was evaluated using a scoring scale basing on questions about risk factors, symptoms, laryngoscope signs, related diseases, current diagnostic methods and treatments of this disease.

    Introduction

    Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition of the upper aerodigestive tract tissues related to direct and indirect effects of gastric or duodenal content reflux.1 2 The incidence of LPRD is thought to be high. The studies conducted in the USA, the UK and Greece reported that the prevalence of this disease could reach 10%, 34.4% and 18.8%, respectively.3–5 A national multicentre epidemiological survey conducted in China found that the prevalence of LPRD was as high as 10.15% at the otolaryngology-head and neck surgery clinics.6 However, the frequency of a previous diagnosis of LPRD was found to be extremely low among those with positive symptoms, only 14.09%.6 Besides the non-specific symptoms and clinical signs which are easily to be confused with other laryngopharyngeal disorders.7 We hypothesised that an insufficient knowledge about this disease among the physicians might contribute a lot to such a low diagnosis rate. One small research performed by our group in Beijing preliminarily confirmed this hypothesis.8

    Beijing is an area with the highest level of medical knowledge in China. Therefore, the awareness about LPRD among otolaryngologists may be even worse in the whole country. The present survey was performed in different regions around the whole country with the aim to conduct a comprehensive investigation about the status of the awareness about LPRD among Chinese otolaryngologists. The results could be a valuable reference for making detailed plans to improve awareness about this disease in China.

    Materials and methods

    Study design

    This study was a multicentre cross-sectional survey designed by a core group including three study leaders (SX, JL and HZ) and one statistician (XP). The whole survey was conducted under the supervision of three study leaders between November 2019 and December 2020. One practising otolaryngologist was made in charge of the survey in the respective provincial district. The district leader and the three study leaders proposed and decided the final hospital lists where the survey was conducted according to the following criteria: (1) no more than nine hospitals in each provincial district; (2) the hospital lists in each district including both 3A and non-3A hospitals; (3) the hospital where the district leader was working not included; (4) the hospital lists could only be changed during the survey with the approval of all three study leaders; (5) hospitals in primary lists could be deleted or replaced if the local director refused the survey in his department, or if less than 80% of all otolaryngologists at this hospital successfully surveyed.

    Data collection

    The survey in each provincial district was conducted by a local team, which included the district leader and at least two assistants. All surveyors were trained to be familiar with the study process to ensure the consistency of implementation. All otolaryngologists who worked in included hospitals at the time of the survey were invited to fill out an identical anonymous questionnaire. Communication with others or access to relevant information was forbidden before and during the survey. A completed questionnaire was considered ineffective if the handwriting was not clear and the otolaryngologist refused to fill it again. All completed effective questionnaires were collected and checked by local teams and then uploaded to a designated database. The final data were checked, integrated, and analysed by three study leaders and their assistants.

    The English version of the questionnaire used in this study is shown in table 1. This contained 15 questions that could be divided into 3 parts: (1) personal information including educational background, years of working and professional title; (2) whether the respondent knew about LPRD, and if yes, what way(s) did he (she) knew about this disease (3 options were provided for this question, which were textbooks, literature and academic conferences) and (3) awareness about LPRD including risk factors, symptoms, laryngoscope signs, related diseases, diagnostic methods and treatments. All questions in part 3 did not have options. The respondents needed to write the answers they knew as much as possible.

    View this table:
    Table 1

    English version of the LPRD awareness questionnaire used in this study

    Quantifications for the status of awareness about LPRD

    A scoring scale based on all part 3 questions (questions 6–15) was used to comprehensively evaluate the awareness about LPRD. Each ‘right answer’ to the 10 questions scored one point. Here, the ‘right answers’ were defined by consensus among three study leaders according to the current literature:

    1. Question 6: Smoking, alcohol drinking, unhealthy eating habits, comorbid upper digestive disease, male sex, age, psychological pressure, obesity and tea or coffee drinking had been accepted as common risk factors for LPRD.2 6 9–11 A correct answer for this question was defined as the one that included at least three items of the aforementioned factors.

    2. Question 7: Reflux Symptom Index (RSI), proposed by Belafsky et al,12 included scores for the severity of nine common LPRD-related symptoms. A right answer for this question was defined as the one that included at least three of the nine symptoms in the RSI.

    3. Question 8: Reflux Finding Score (RFS), also proposed by Belafsky et al,13 included scores for the severity of eight common LPRD-related laryngoscope signs. A right answer for this question was defined as the one that included at least three of the eight laryngoscope signs.

    4. Question 9: Pharyngolaryngitis, vocal benign lesions, rhinitis or rhinosinusitis, laryngeal granuloma, laryngeal leukoplakia, cough, asthma, otitis media, obstructive sleep apnea syndrome, and malignant tumour were thought to be associated with LPRD.14–21 A right answer was defined as the one that included at least three of the aforementioned diseases.

    5. Question 10: RSI or RFS evaluations, pH or multichannel intraluminal impedance pH (MII-pH) monitoring, empiric therapeutic trial and pepsin detection were current accepted diagnostic methods for LPRD.2 22 23 A right answer was defined as the one that included at least two items of the aforementioned methods.

    6. Question 11: Behaviour modification, medication and operation were the currently accepted treatments for LPRD.2 24 A right answer was defined as the one that included at least two items of the aforementioned treatments.

    7. Question 12: The right answer was 13, as this was the most common cut-off score of RSI used in China.25

    8. Question 13: The right answer was 7, as this was the most common cut-off score of RFS used in China.26

    9. Question 14: The right answer was 24 h pH or MII-pH monitoring. Despite controversies, such examinations were thought to be the most accurate method for diagnosing LPRD.2 27

    10. Question 15: The right answer was proton pump inhibitors (PPIs). Despite controversies, such drugs were thought to be the first-line medication for treating LPRD.2 27

    Statistical analysis

    All statistical analyses were performed using SPSS V.20.0 for Windows (IBM). Continuous variables were expressed as mean±SD. The rate of awareness about LPRD was expressed as a percentage. The comparisons of awareness scores about LPRD among different groups of participants were all made using independent-sample t-tests. A p value less than 0.05 indicated a statistically significant difference.

    Results

    Medical institutions and personal information

    There were 265 medical institutions from 31 provincial administrative districts of China initially participated in this study. Fifty-six institutions from 15 districts withdrew before the survey was carried out. While at the same time, 13 institutions from 10 districts took the place of some withdrew institutions. Therefore, the survey was carried out in a total of 222 institutions, of which two were excluded because of fewer valid questionnaires (less than 80% of all otolaryngologists were successfully surveyed). Finally, 2254 effective questionnaires were collected from 220 hospitals in 27 provincial administrative districts. The flow diagram of the participated institutions is shown in figure 1. The numbers of hospitals and effective questionnaires according to geographical region are shown in table 2 and figure 2, suggesting that the survey covered all geographical regions and nearly all provincial administrative districts of China. The personal information of all 2254 otolaryngologists who were successfully surveyed is shown in table 3, including their hospital levels, educational background, working time and professional titles.

    Figure 1
    Figure 1

    The flow diagram of participating institutions.

    Figure 2
    Figure 2

    The provincial administrative districts with medical institutions participating in the study (marked in red).

    View this table:
    Table 2

    Numbers of hospitals and effective questionnaires according to geographical region

    View this table:
    Table 3

    Personal information of all 2254 otolaryngologists surveyed

    Rate of awareness about LPRD and the way(s) of knowing this disease

    Only 81 of 2254 otolaryngologists (3.6%) from 46 hospitals (range 1–7) had never heard of LPRD. Therefore, a total of 2173 otolaryngologists (96.4%) had heard about this disease. Among the three choices provided, academic conferences were the most common source of knowing LPRD (1653, 73.3%), followed by literature (1382, 61.3%) and textbooks (1350, 59.9%). The number of otolaryngologists who knew about LPRD via zero, one, two, and all three ways was 183 (8.1%), 608 (27.0%), 612 (27.2%) and 851 (37.8%), respectively.

    Status of awareness about LPRD risk factors, symptoms, laryngoscope signs and related diseases

    The most commonly known risk factor was alcohol drinking, followed by smoking, unhealthy eating habits and comorbid upper digestive disease. The most commonly known symptom was pharyngeal foreign body sensation, followed by stomach acid or heartburn, hoarseness and cough. The most commonly known laryngoscope sign was hyperaemia, followed by laryngeal oedema, granuloma and vocal cord oedema. The most commonly known LPRD-related disease was pharyngolaryngitis, followed by vocal benign lesions, rhinitis or rhinosinusitis and laryngeal granuloma. The details of the aforementioned results are shown in figure 3.

    Figure 3
    Figure 3

    The most commonly known LPRD risk factors (A), symptoms (B), laryngoscope signs (C), and related diseases (D). LPRD, laryngopharyngeal reflux disease.

    Status of awareness about LPRD diagnoses and treatments

    The most common answer for diagnostic methods was pH monitoring, followed by laryngoscopy, RSI or RFS evaluation, gastroscopy, empiric therapeutic trial and salivary pepsin test. The most common answer for treatment options was medication, followed by behavioural modifications and operation. The detailed results are shown in figure 4.

    Figure 4
    Figure 4

    The rates of awareness about LPRD diagnostic methods (A) and treatment methods (B). LPRD, laryngopharyngeal reflux disease; RFS, Reflux Finding Score; RSI, Reflux Symptom Index.

    The correct rate of awareness for the cut-off values of RSI and RFS was only 46.6% (1051/2254) and 44.9% (1012/2254), respectively. Only 28.3% (639/2254) of all participants knew about the use of 24-hour pH or MII-pH monitoring as a gold diagnostic test. As many as 73.1% (1647/2254) of all participants considered PPIs the first-line drugs.

    Overall status of awareness about LPRD

    The overall awareness scale score for all participants was 4.1±2.8, with a range of 0–10 (the score of 81 otolaryngologists who never heard of LPRD was considered as 0). The number of participants according to different scores is shown in figure 5. The data indicated that only 1.4% (32/2254) of all participants got full marks, and as many as 57.6% (1298/2254) of all participants could not even reach half marks (0–4).

    Figure 5
    Figure 5

    The numbers of participants according to different awareness scale scores.

    The awareness scale scores according to different ways of knowing this disease are shown in table 4. The data suggested that knowing this disease via either of the three ways could increase the final scores (all p<0.05). Moreover, the awareness scale scores were significantly higher for otolaryngologists who knew about this disease via two to three ways (vs those who knew about this disease via only 0 to one way) (p<0.05).

    View this table:
    Table 4

    Awareness scale scores according to different ways of knowing LPRD

    The awareness scale scores according to different personal information are shown in table 5. The data suggested that the scores were significantly higher in otolaryngologists who worked at 3A hospitals (vs non-3A hospitals) and with postgraduate or above educational backgrounds (vs undergraduate or below educational backgrounds) (both p<0.05). No significant differences were found in this score among otolaryngologists who had different professional titles and working times (both p>0.05).

    View this table:
    Table 5

    Awareness scale scores according to different personal information

    Discussion

    LPRD has gradually gained attention during the last decades,2 since Koufman systematically investigated the throat-related symptoms of gastro-oesophageal reflux disease (GERD) in 1991.3 LPRD symptoms could exist in the absence of typical GERD symptoms, as the laryngopharyngeal mucosa is more sensitive to acid reflux.6 28–30 However, unlike the widespread awareness about GERD among gastroenterologists, insufficient awareness about LPRD among otolaryngologists has been suggested in several small sample studies conducted in the UK, Europe and Beijing district of China.8 31 32 China is vast in territory, and the levels of medical knowledge differ significantly with regions. Therefore, this nationwide survey, including the largest sample size to date, comprehensively evaluated the status of awareness about LPRD among Chinese otolaryngologists.

    The most important finding of this study was that, although the majority of otolaryngologists surveyed had heard of LPRD, the overall status of awareness about LPRD was not encouraging: only very few otolaryngologists attained satisfactory scores. The insufficient awareness about LPRD was embodied in all aspects of this disease, including risk factors, symptoms, clinical signs, related diseases, diagnoses and treatments. This could undoubtedly cause great difficulties in the correct management of this disease. Therefore, the extremely low diagnosed rates of LPRD in Chinese patients might be attributed to a great extent to insufficient knowledge about this disease among otolaryngologists.

    Thorough knowledge of the disease among medical specialists is the primary requirement for its timely diagnosis and suitable treatment. Specifically, insufficient awareness about LPRD showed in this study could cause the following potential problems: (1) An insufficient awareness about the unspecific symptoms and laryngoscope signs might cause missed diagnoses, as this disease could be easily confused with some other laryngeal problems.7 On the contrary, this might also cause false diagnoses of LPRD, which showed that the use of empirical PPI therapy did not lead to any improvement in persistent throat symptoms in 16 weeks or 12 months.33 (2) An insufficient awareness about related diseases could cause poor efficacies or recurrences in treating such diseases, as antireflux therapy has been accepted in treating some of these diseases, such as laryngeal leukoplakia,34 laryngeal granuloma35 and cough.36 (3) Currently, no perfect diagnostic and treatment methods exist for LPRD: simple ones are not so accurate or effective, such as RSI or RFS evaluations (diagnosis) and behavioural changes (treatment), while accurate or effective ones are always invasive, such as pH-MII monitoring (diagnosis) or antireflux operations (treatment). Therefore, a reasonable practical algorithm is necessary for the efficient management of this disease.1 2 27 Insufficient awareness about its diagnostic and treatment methods may prevent otolaryngologists from providing reasonable advice. For example, few Chinese otolaryngologists knew about other treatments besides medication. This meant that they had no idea of treating patients who did not respond to medication. On the contrary, a simple dietary change was an alternative cost-effective therapeutic approach for some patients with LPRD.37 However, insufficient awareness about behavioural modifications might prevent otolaryngologists from giving clear advice on dietary changes.

    In this study, we found several potential factors that influenced the status of awareness about LPRD, including hospital level, educational background and number of ways of knowing this disease. Such results could be valuable references for making further plans in improving the overall status of awareness about LPRD in China. Specifically, otolaryngologists who work at low-level hospitals or with low educational backgrounds should be encouraged to study this disease. More ways should be provided for studying this disease, such as continuously updating textbooks to include the latest LPRD knowledge or holding more academic conferences about LPRD. These strategies may also help in facilitating timely diagnoses and suitable treatments for the large population of patients with LPRD in China.

    The main strengths of this study compared with others were as follows: First, the sample size was the largest to date; moreover, the surveyed otolaryngologists came from different levels of hospitals around the country. Second, the whole surveys were performed onsite under the supervision of designated surveyors. Therefore, the veracity of the results could be ensured to a great extent. Third, questions 6–15, which were the major part of our questionnaire, were all provided with no options. Therefore, the intimation effects could be avoided to a great extent.

    Several limitations also needed to be addressed. First, data from different regions were collected by different groups of surveyors; therefore, intergroup differences in study implementation could not be avoided. However, because China is a vast territory, conducting all surveys by one group was unrealistic and extremely expensive. Second, the calculation criteria of the awareness scale were made subjectively by three experts based on the current literature. This probably led to some subjective bias and controversies. However, no international guideline exists for the management of LPRD.38 Such evaluations could well reflect the overall status of awareness about this disease.

    Conclusion

    In summary, the results of this study suggested that the overall status of awareness about LPRD in Chinese otolaryngologists was not encouraging. More efforts are needed to increase such knowledge among this group of physicians, especially among those who work in low-level hospitals or have low educational backgrounds or few ways of studying this disease.

    Data availability statement

    Data are available on reasonable request.

    Ethics statements

    Patient consent for publication

    Ethics approval

    This study has been approved by the Ethics Committee of Peking University First Hospital with a ID of 2019-191. Participants gave informed consent to participate in the study before taking part.

    Acknowledgments

    We gratefully acknowledge all the medical staff who had involved in this study.

    References

    1. ↵
      1. Lechien JR,
      2. Saussez S,
      3. Muls V, et al
      . Laryngopharyngeal reflux: a state-of-the-art algorithm management for primary care physicians. J Clin Med 2020;9:3618.doi:10.3390/jcm9113618pmid:http://www.ncbi.nlm.nih.gov/pubmed/33182684
      OpenUrlPubMed
    2. ↵
      1. Lechien JR,
      2. Akst LM,
      3. Hamdan AL, et al
      . Evaluation and management of laryngopharyngeal reflux disease: state of the art review. Otolaryngol Head Neck Surg 2019;160:762–82.doi:10.1177/0194599819827488pmid:http://www.ncbi.nlm.nih.gov/pubmed/30744489
      OpenUrlCrossRefPubMed
    3. ↵
      1. Koufman JA
      . The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope 1991;101:1–78.doi:10.1002/lary.1991.101.s53.1pmid:http://www.ncbi.nlm.nih.gov/pubmed/1895864
      OpenUrlCrossRefPubMedWeb of Science
    4. ↵
      1. Kamani T,
      2. Penney S,
      3. Mitra I, et al
      . The prevalence of laryngopharyngeal reflux in the English population. Eur Arch Otorhinolaryngol 2012;269:2219–25.doi:10.1007/s00405-012-2028-1pmid:http://www.ncbi.nlm.nih.gov/pubmed/22576243
      OpenUrlCrossRefPubMed
    5. ↵
      1. Spantideas N,
      2. Drosou E,
      3. Bougea A, et al
      . Laryngopharyngeal reflux disease in the Greek general population, prevalence and risk factors. BMC Ear Nose Throat Disord 2015;15:7.doi:10.1186/s12901-015-0020-2pmid:http://www.ncbi.nlm.nih.gov/pubmed/26696776
      OpenUrlPubMed
    6. ↵
      1. Xiao S,
      2. Li J,
      3. Zheng H, et al
      . An epidemiological survey of laryngopharyngeal reflux disease at the Otorhinolaryngology-Head and neck surgery clinics in China. Eur Arch Otorhinolaryngol 2020;277:2829–38.doi:10.1007/s00405-020-06045-0pmid:http://www.ncbi.nlm.nih.gov/pubmed/32449029
      OpenUrlPubMed
    7. ↵
      1. Ford CN
      . Evaluation and management of laryngopharyngeal reflux. JAMA 2005;294:1534–40.doi:10.1001/jama.294.12.1534pmid:http://www.ncbi.nlm.nih.gov/pubmed/16189367
      OpenUrlCrossRefPubMedWeb of Science
    8. ↵
      1. Zhang J,
      2. Xiao S,
      3. Du X, et al
      . Knowledge of laryngopharyngeal reflux disease among otolaryngologists in 3A hospitals in Beijing. J Int Med Res 2020;48:030006051988831.doi:10.1177/0300060519888311pmid:http://www.ncbi.nlm.nih.gov/pubmed/31774012
      OpenUrlPubMed
    9. ↵
      1. Saruç M,
      2. Aksoy EA,
      3. Vardereli E, et al
      . Risk factors for laryngopharyngeal reflux. Eur Arch Otorhinolaryngol 2012;269:1189–94.doi:10.1007/s00405-011-1905-3pmid:http://www.ncbi.nlm.nih.gov/pubmed/22207531
      OpenUrlCrossRefPubMed
    10. ↵
      1. Wong M-W,
      2. Bair M-J,
      3. Chang W-C, et al
      . Clinical and psychological characteristics in gastroesophageal reflux disease patients overlapping with laryngopharyngeal reflux symptoms. J Gastroenterol Hepatol 2019;34:1720–6.doi:10.1111/jgh.14651pmid:http://www.ncbi.nlm.nih.gov/pubmed/30851003
      OpenUrlPubMed
    11. ↵
      1. Hamdan A-latif,
      2. Nassar J,
      3. Dowli A, et al
      . Effect of fasting on laryngopharyngeal reflux disease in male subjects. Eur Arch Otorhinolaryngol 2012;269:2361–6.doi:10.1007/s00405-012-2038-zpmid:http://www.ncbi.nlm.nih.gov/pubmed/22576248
      OpenUrlPubMed
    12. ↵
      1. Belafsky PC,
      2. Postma GN,
      3. Koufman JA
      . Validity and reliability of the reflux symptom index (RSI). J Voice 2002;16:274–7.doi:10.1016/S0892-1997(02)00097-8pmid:http://www.ncbi.nlm.nih.gov/pubmed/12150380
      OpenUrlCrossRefPubMedWeb of Science
    13. ↵
      1. Belafsky PC,
      2. Postma GN,
      3. Koufman JA
      . The validity and reliability of the reflux finding score (RFS). Laryngoscope 2001;111:1313–7.doi:10.1097/00005537-200108000-00001pmid:http://www.ncbi.nlm.nih.gov/pubmed/11568561
      OpenUrlCrossRefPubMedWeb of Science
    14. ↵
      1. Parsel SM,
      2. Wu EL,
      3. Riley CA, et al
      . Gastroesophageal and Laryngopharyngeal Reflux Associated With Laryngeal Malignancy: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2019;17:1253–64.doi:10.1016/j.cgh.2018.10.028pmid:http://www.ncbi.nlm.nih.gov/pubmed/30366155
      OpenUrlPubMed
    15. ↵
      1. Suzuki M,
      2. Saigusa H,
      3. Kurogi R, et al
      . Arousals in obstructive sleep apnea patients with laryngopharyngeal and gastroesophageal reflux. Sleep Med 2010;11:356–60.doi:10.1016/j.sleep.2009.09.008pmid:http://www.ncbi.nlm.nih.gov/pubmed/20226734
      OpenUrlCrossRefPubMed
    16. ↵
      1. Gong X,
      2. Wang X-Y,
      3. Yang L, et al
      . Detecting laryngopharyngeal reflux by immunohistochemistry of pepsin in the biopsies of vocal fold leukoplakia. J Voice 2018;32:352–5.doi:10.1016/j.jvoice.2017.06.010pmid:http://www.ncbi.nlm.nih.gov/pubmed/28756936
      OpenUrlPubMed
    17. ↵
      1. Chung JH,
      2. Tae K,
      3. Lee YS, et al
      . The significance of laryngopharyngeal reflux in benign vocal mucosal lesions. Otolaryngol Head Neck Surg 2009;141:369–73.doi:10.1016/j.otohns.2009.05.033pmid:http://www.ncbi.nlm.nih.gov/pubmed/19716016
      OpenUrlCrossRefPubMedWeb of Science
    18. ↵
      1. Michaudet C,
      2. Malaty J
      . Chronic cough: evaluation and management. Am Fam Physician 2017;96:575–80.pmid:http://www.ncbi.nlm.nih.gov/pubmed/29094873
      OpenUrlPubMed
    19. ↵
      1. Ren J-J,
      2. Zhao Y,
      3. Wang J, et al
      . PepsinA as a marker of laryngopharyngeal reflux detected in chronic rhinosinusitis patients. Otolaryngol Head Neck Surg 2017;156:893–900.doi:10.1177/0194599817697055pmid:http://www.ncbi.nlm.nih.gov/pubmed/28457223
      OpenUrlPubMed
    20. ↵
      1. Han H,
      2. Lv Q
      . Characteristics of laryngopharyngeal reflux in patients with chronic otitis media. Am J Otolaryngol 2018;39:493–6.doi:10.1016/j.amjoto.2018.05.010pmid:http://www.ncbi.nlm.nih.gov/pubmed/29880317
      OpenUrlPubMed
    21. ↵
      1. Marshall S,
      2. McCann AJ,
      3. Samuels TL, et al
      . Detection of pepsin and IL-8 in saliva of adult asthmatic patients. J Asthma Allergy 2019;12:155–61.doi:10.2147/JAA.S205482pmid:http://www.ncbi.nlm.nih.gov/pubmed/31213853
      OpenUrlPubMed
    22. ↵
      1. Magliulo G,
      2. Pace A,
      3. Plateroti R, et al
      . Laryngopharyngeal reflux disease in adult patients: tears and pepsin. J Biol Regul Homeost Agents 2020;34:715–20.doi:10.23812/19-437-L-26pmid:http://www.ncbi.nlm.nih.gov/pubmed/32536115
      OpenUrlPubMed
    23. ↵
      1. Iannella G,
      2. Di Nardo G,
      3. Plateroti R, et al
      . Investigation of pepsin in tears of children with laryngopharyngeal reflux disease. Int J Pediatr Otorhinolaryngol 2015;79:2312–5.doi:10.1016/j.ijporl.2015.10.034pmid:http://www.ncbi.nlm.nih.gov/pubmed/26586244
      OpenUrlPubMed
    24. ↵
      1. Lechien JR,
      2. Dapri G,
      3. Dequanter D, et al
      . Surgical treatment for laryngopharyngeal reflux disease: a systematic review. JAMA Otolaryngol Head Neck Surg 2019;145:655–66.doi:10.1001/jamaoto.2019.0315pmid:http://www.ncbi.nlm.nih.gov/pubmed/31046069
      OpenUrlPubMed
    25. ↵
      1. Li J,
      2. Zhang L,
      3. Zhang C, et al
      . Linguistic adaptation, reliability, validation, and responsivity of the Chinese version of reflux symptom index. J Voice 2016;30:104–8.doi:10.1016/j.jvoice.2013.12.006pmid:http://www.ncbi.nlm.nih.gov/pubmed/26292798
      OpenUrlPubMed
    26. ↵
      1. Peng L-li,
      2. Li J-rang,
      3. Zhang L-hong
      . [Study on the consistency of reflux score evaluated by three different level of throat physicians]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2013;48:461–4.pmid:http://www.ncbi.nlm.nih.gov/pubmed/24103167
      OpenUrlPubMed
    27. ↵
      1. Lechien J-R,
      2. Mouawad F,
      3. Bobin F, et al
      . Review of management of laryngopharyngeal reflux disease. Eur Ann Otorhinolaryngol Head Neck Dis 2021;138:257–67.doi:10.1016/j.anorl.2020.11.002pmid:http://www.ncbi.nlm.nih.gov/pubmed/33257265
      OpenUrlPubMed
    28. ↵
      1. Lechien JR,
      2. Bobin F,
      3. Muls V, et al
      . Gastroesophageal reflux in laryngopharyngeal reflux patients: clinical features and therapeutic response. Laryngoscope 2020;130:E479–89.doi:10.1002/lary.28482pmid:http://www.ncbi.nlm.nih.gov/pubmed/31876296
      OpenUrlPubMed
    29. ↵
      1. Sirin S,
      2. Öz F
      . Laryngopharyngeal reflux concept: what is known and what should we focus on? Braz J Otorhinolaryngol 2019;85:133–5.doi:10.1016/j.bjorl.2019.01.001pmid:http://www.ncbi.nlm.nih.gov/pubmed/30709645
      OpenUrlPubMed
    30. ↵
      1. Wang L,
      2. Wang G,
      3. Li L, et al
      . Relationship between laryngopharyngeal reflux disease and gastroesophageal reflux disease based on synchronous esophageal and oropharyngeal Dx-pH monitoring. Am J Otolaryngol 2020;41:102441.doi:10.1016/j.amjoto.2020.102441pmid:http://www.ncbi.nlm.nih.gov/pubmed/32144021
      OpenUrlPubMed
    31. ↵
      1. Karkos PD,
      2. Thomas L,
      3. Temple RH, et al
      . Awareness of general practitioners towards treatment of laryngopharyngeal reflux: a British survey. Otolaryngol Head Neck Surg 2005;133:505–8.doi:10.1016/j.otohns.2005.06.013pmid:http://www.ncbi.nlm.nih.gov/pubmed/16213919
      OpenUrlCrossRefPubMed
    32. ↵
      1. Lechien JR,
      2. Mouawad F,
      3. Mortuaire G, et al
      . Awareness of European Otolaryngologists and general practitioners toward laryngopharyngeal reflux. Ann Otol Rhinol Laryngol 2019;128:1030–40.doi:10.1177/0003489419858090pmid:http://www.ncbi.nlm.nih.gov/pubmed/31257901
      OpenUrlPubMed
    33. ↵
      1. O'Hara J,
      2. Stocken DD,
      3. Watson GC, et al
      . Use of proton pump inhibitors to treat persistent throat symptoms: multicentre, double blind, randomised, placebo controlled trial. BMJ 2021;372:m4903.doi:10.1136/bmj.m4903pmid:http://www.ncbi.nlm.nih.gov/pubmed/33414239
      OpenUrlAbstract/FREE Full Text
    34. ↵
      1. Sezen Goktas S,
      2. Dogan R,
      3. Yenigun A, et al
      . A new approach to vocal cord leukoplakia and evaluation of proton pump ınhibitor treatment. Eur Arch Otorhinolaryngol 2019;276:467–71.doi:10.1007/s00405-018-05273-9pmid:http://www.ncbi.nlm.nih.gov/pubmed/30607560
      OpenUrlPubMed
    35. ↵
      1. Sadoughi B,
      2. Rickert SM,
      3. Sulica L
      . Granulomas of the membranous vocal fold after intubation and other airway instrumentation. Laryngoscope 2019;129:441–7.doi:10.1002/lary.27492pmid:http://www.ncbi.nlm.nih.gov/pubmed/30208219
      OpenUrlPubMed
    36. ↵
      1. Park HJ,
      2. Park YM,
      3. Kim J-H, et al
      . Effectiveness of proton pump inhibitor in unexplained chronic cough. PLoS One 2017;12:e0185397.doi:10.1371/journal.pone.0185397pmid:http://www.ncbi.nlm.nih.gov/pubmed/29016626
      OpenUrlPubMed
    37. ↵
      1. Lechien JR,
      2. Crevier-Buchman L,
      3. Distinguin L, et al
      . Is diet sufficient as laryngopharyngeal reflux treatment? A cross-over observational study. Laryngoscope 2021. doi:doi:10.1002/lary.29890. [Epub ahead of print: 04 Oct 2021].pmid:http://www.ncbi.nlm.nih.gov/pubmed/34606102
    38. ↵
      1. Lechien JR,
      2. Allen JE,
      3. Barillari MR
      . Management of laryngopharyngeal reflux around the world: an international study. Laryngoscope 2020;13:E1589–97.doi:10.1002/lary.29270
      OpenUrl

    Footnotes

    • SX, JL and HZ are joint first authors.

    • Contributors SX, JL, and HZ accept full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. Study conception and design: SX, JL, HZ, XL and HY. Study supervision: SX, JL and HZ. Material preparation and data collection: SX, JL, HZ, XL, HY, ZJ, XP, SZ, CZ, DC, XX, LS, HH, ZT, XC, YL, SQ, GW, TC, XC, LT, WZ, FH, YH, GY, ZL, LT, JH, RM and ZY. Analysis and interpretation of data: SX, JL, HZ, XL, HY, ZJ and XP. Manuscript writing: SX, JL, HZ and ZJ. All authors made critical revision for important intellectual content, read and approved the final manuscript. SX, JL, and HZ were the guarantors of current study.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Map disclaimer The inclusion of any map (including the depiction of any boundaries therein), or of any geographic or locational reference, does not imply the expression of any opinion whatsoever on the part of BMJ concerning the legal status of any country, territory, jurisdiction or area or of its authorities. Any such expression remains solely that of the relevant source and is not endorsed by BMJ. Maps are provided without any warranty of any kind, either express or implied.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.