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Objective: To develop and validate the Reflux Sign Assessment-10 (RSA-10) for documenting the physical findings of laryngopharyngeal reflux disease (LPRD)., Methods: Patients with LPRD at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring and asymptomatic individuals were consecutively recruited from two European hospitals. Three experienced otolaryngologists rated RSA-10 in patients and controls for assessing internal validity. RSA-10 was rated within a 7-day period to assess test-retest reliability. Internal consistency was measured using Cronbach's α in patients and controls. Convergent validity was evaluated through a correlation analysis between RSA-10 and Reflux Finding Score (RFS). Interrater reliability was evaluated by comparing the RSA-10 evaluations of the three otolaryngologists through Fleiss kappa. Pre- to posttreatment change of RSA-10 was evaluated to assess responsiveness to change. The RSA-10 thresholds were examined by receiver operating characteristic analysis., Results: Fifty-five patients completed the pre- to posttreatment evaluations from January 2020 to December 2023. A total of 115 asymptomatic individuals completed the study. RSA-10 reported high internal consistency reliability (α = 0.822) and test-retest reliability (r s  = 0.725). The RSA-10 scores of patients were significantly higher than those of controls (p = 0.001), suggesting high internal validity. RSA-10 was significantly correlated with the RFS (r s  = 0.771). The interrater reliability was adequate for sub- and total RSA-10 scores (k = 0.708). RSA-10 significantly improved from baseline to 3-month posttreatment (p = 0.001). An RSA-10 > 13 may be suggestive of LPRD. Both RSA-10 > 13 and Reflux Symptom Score-12 > 11 were associated with a sensitivity of 92.7% and a specificity of 97.3%., Conclusion: The RSA-10 is a reliable and valid clinical instrument for documenting the most prevalent laryngeal and extra-laryngeal findings associated with LPRD., Level of Evidence: 3 Laryngoscope, 134:3981-3988, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective(s): To conduct a preliminary investigation into the relationship between specific SNP variants, type II inflammation, and the effectiveness of dupilumab therapy and surgery in patients with CRS., Methods: In this prospective study, 48 subjects were enrolled, comprising 32 CRS patients and 16 healthy controls. The CRS patients were subjected to either dupilumab therapy or endoscopic surgery according to EPOS guidelines. SNP variants were identified using the TaqMan SNP genotyping technique. The identified SNP profiles were compared between the control group and CRS patients, and their potential influence on treatment outcomes was evaluated. Treatment responses were assessed based on symptom scores, such as SS-I, SNOT-22, disease progression using the NPS findings, and SNP profiles at a 6-month follow-up. The primary measures included the Nasal Polyp Score, Smell Identification Test (SIT) score, and SNOT-22 outcomes., Results: Dupilumab therapy and surgery significantly decreased NPS, with the last showing superior results. However, dupilumab therapy resulted in a significantly improved SIT score. Significant differences were observed in SNP profiles, particularly with rs1800629 (TNFA), rs2856838 (IL1a), rs17561 (IL1a), and rs1805011 (IL4R). In particular, the expression of rs2856838 and rs1805011 variants in the dupilumab group was associated with significantly better SIT and SNOT-22 outcomes than non-expressors. Also, the surgery group patients expressing the rs2856838 variant reported significant improvements in SNOT-22 scores., Conclusion: These preliminary findings suggest that SNP genotypes may guide personalized treatment strategies for CRS. Further larger prospective studies are required to confirm these initial observations., Level of Evidence: 2 Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: The immune microenvironment of HPV-associated (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) (HPV+OPSCCs) differs from that of HPV-independent oropharyngeal cancers (HPV-independent OPSCCs). The literature on the subject is very abundant, demanding an organized synthesis of this wealth of information to evaluate the hypothesis associating the favorable prognosis of HPV+OPSCC patients with a different immune microenvironment. A systematic review of the literature was conducted regarding the microenvironment of HPV+OPSCCs., Data Source: MEDLINE/PubMed, Embase, and Cochrane Library databases., Review Methods: A literature search was performed following PRISMA guidelines (Moher D. PLoS Med. 2009). The PEO (Population, Exposure, and Outcome) framework is detailed as follows: P: patients with oropharyngeal squamous cell carcinomas, E: human papillomavirus (HPV), and O: histological and immunological composition of the tumoral microenvironment (TME). No meta-analysis was performed., Results: From 1,202 studies that were screened, 58 studies were included (n = 6,474 patients; n = 3,581 (55%) HPV+OPSCCs and n = 2,861(45%) HPV-independent OPSCCs). The presence of tumor-infiltrating lymphocytes (TIL), CD3+ in 1,733 patients, CD4+ in 520 patients, and CD8+ (cytotoxic T lymphocytes (CTL)) in 3,104 patients, and high levels of PD-L1 expression in 1,222 patients is strongly correlated with an improved clinical outcome in HPV+OPSCCs., Conclusion: This systematic review provides the most comprehensive information on the immune microenvironment of HPV+OPSCCs to date. Tumor-infiltrating lymphocytes and PD-L1 expression are associated with a favorable prognosis. B, CD8+ and resident memory cells densities are higher in HPV+OPSCCs. The importance of myeloid lineages is still a matter of debate and research., Level of Evidence: NA Laryngoscope, 134:1507-1516, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR., Methods: Forty-eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician., Results: After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non-specific laryngeal and extra-laryngeal symptoms and signs that can be evaluated with validated patient-reported outcome questionnaires and clinical instruments. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h., Conclusion: A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR., Level of Evidence: 5 Laryngoscope, 134:1614-1624, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Pediatric inferior turbinate hypertrophy (PedTH) is a frequent and often overlooked cause or associated cause of nasal breathing difficulties. This clinical consensus statement (CCS) aims to provide a diagnosis and management framework covering the lack of specific guidelines for this condition and addressing the existing controversies., Methods: A clinical consensus statement (CCS) was developed by a panel of 20 contributors from 7 different European and North American countries using the modified Delphi method. The aim of the CCS was to offer a multidisciplinary reference framework for the management of PedTH on the basis of shared clinical experience and analysis of the strongest evidence currently available., Results: A systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria was performed. From the initial 96 items identified, 7 articles were selected based on higher-evidence items such as randomized-controlled trials, guidelines, and systematic reviews. A 34-statement survey was developed, and after three rounds of voting, 2 items reached strong consensus, 17 reached consensus or near consensus, and 15 had no consensus., Conclusions: Until further prospective data are available, our CCS should provide a useful reference for PedTH management. PedTH should be considered a nasal obstructive disease not necessarily related to an adult condition but frequently associated with other nasal or craniofacial disorders. Diagnosis requires clinical examination and endoscopy, whereas rhinomanometry, nasal cytology, and questionnaires have little clinical role. Treatment choice should consider the specific indications and features of the available options, with a preference for less invasive procedures., Level of Evidence: 5 Laryngoscope, 134:1437-1444, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To investigate the clinical patterns and disease evolution of laryngopharyngeal reflux (LPR) patients., Methods: Patients with LPR diagnosed by hypopharyngeal-esophageal impedance-pH monitoring were prospectively followed in three medical centers. Symptoms and findings were assessed with reflux symptom score (RSS) and reflux sign assessment (RSA). Patients were treated with 3-to 9-month diet and combination of proton pump inhibitors, alginate or magaldrate. Patients were followed for 3 years to determine the clinical evolution of symptoms over time. LPR that did not recur was defined as acute. Recurrent LPR consisted of reflux with one or several recurrences yearly despite successful treatment. Chronic LPR was reflux with a chronic course of symptoms. Predictive indicators of clinical evolution were investigated., Results: One hundred forty patients and 82 healthy individuals completed the evaluations. Among patients, 41 (29.3%), 57 (40.7%), and 42 (30.0%) had acute, recurrent, or chronic LPR respectively. Baseline quality of life-RSS (QoL-RSS) and RSS total scores were significantly higher in chronic LPR patients. The post-treatment decrease of QoL-RSS and RSS of acute LPR patients were significantly faster as compared to recurrent and chronic patients. QoL-RSS >5 reported adequate sensitivity (94.2) and specificity (75.3). QoL-RSS thresholds defined acute (QoL-RSS = 6-25), recurrent (QoL-RSS = 26-38), and chronic (QoL-RSS > 38) LPR., Conclusion: Baseline QoL-RSS may predict the clinical course of LPR patients: acute, recurrent, or chronic. A novel classification system that groups patients according to the longevity, severity, and therapeutic response of symptoms was proposed: the International Federation of Otorhinolaryngological Societies Classification of LPR., Level of Evidence: 3 Laryngoscope, 133:1073-1080, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To investigate the efficacy of low-fat, low-quick-release sugar, high-protein, alkaline, and plant-based diet as single treatment for patients with laryngopharyngeal reflux (LPR)., Study Design: Cross-over observational study., Methods: Patients with LPR diagnosis at the hypopharyngeal-esophageal multichannel intraluminal impedance-pH-monitoring were prospectively recruited from the reflux clinic of three University Hospitals. Patients were instructed to follow low-fat, low-quick-release sugar, high-protein, alkaline, and plant-based diet for 6 to 12 weeks. Pre- to post-treatment symptom and finding changes were evaluated with reflux symptom score (RSS) and reflux sign assessment. Findings were compared to those of a control period where patients did not receive any treatment or diet. Diet was evaluated with refluxogenic diet score (REDS)., Results: Fifty patients completed the study (19 males). Otolaryngological, digestive, and total RSS scores significantly improved from baseline to 6-week post-diet, while there were no significant changes during the control period. At 6-week post-diet, 37 (74%) patients reported significant symptom improvement or relief. Among them, symptoms continued to improve from 6 to 12 weeks in 27 cases, corresponding to a diet success rate of 54%. The REDS was predictive of the baseline RSS (P = .031)., Conclusion: Low-fat, low-quick-release sugar, high-protein, alkaline, and plant-based diet is an alternative cost-effective therapeutic approach for patients with LPR. Patients with higher REDS reported higher baseline symptom score., Level of Evidence: 3 Laryngoscope, 132:1916-1923, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To compare the 12-month evolution of voice quality outcomes in patients who benefited from types 1-2 transoral CO 2 laser cordectomy (TLC) for an early-stage vocal fold squamous cell carcinoma (VFSCC)., Study Design: Prospective uncontrolled study., Methods: Sixty patients with cT1 VFSCC were consecutively recruited from a single medical center. Thirty patients benefited from type 1 TLC, while type 2 TCL was performed in 30 patients. The following voice quality outcomes were evaluated at baseline, 3-, 6-, and 12-month post-TLC: voice handicap index (VHI), GRBAS, speech rate, maximum phonation time (MPT), and acoustic parameters. Voice quality evolution was compared between type 1 and type 2 TLC., Results: Fifty-seven patients completed the evaluations. Type 1 TLC patients reported significant improvements of VHI, grade of dysphonia, and breathiness at 3-, 6-, and 12-month post-TLC. Speech rate and jitter values improved 6- and 12-month post-TLC. A few voice quality outcomes reported 3- or 6-month post-TLC improvements in type 2 TLC group, while VHI, grade of dysphonia improved at 6- and 12-month post-TLC. MPT significantly decreased at 6- and 12-month post-TLC, while there were no acoustic measurement changes in type 2 TLC., Conclusions: The effect of TLC on voice quality may depend on the type of TLC. Type 1 TLC was associated with faster voice quality improvements compared with type 2 TLC. VHI and dysphonia grade were identified as the most relevant tool of voice changes irrespective to the TLC type., Level of Evidence: 3 Laryngoscope, 132:1421-1426, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

The aim of this study is to investigate the clinical profile of patients who developed coronavirus disease 2019 (COVID-19) after full vaccination. Demographic, epidemiological and clinical data were collected through medical records and online patient-reported outcome questionnaire from patients who developed symptomatic SARS-CoV-2 infection, confirmed by nasopharyngeal swab, at least 2 weeks after completion of vaccination. A total of 153 subjects were included. The most frequent symptoms were: asthenia (82.4%), chemosensory dysfunction (63.4%), headache (59.5%), runny nose (58.2%), muscle pain (54.9%), loss of appetite (54.3%), and nasal obstruction (51.6%). Particularly, 62.3% and 53.6% of subjects reported olfactory and gustatory dysfunction, respectively. Symptom severity was mild or moderate in almost all cases. Chemosensory dysfunctions have been observed to be a frequent symptom even in subjects who contracted the infection after full vaccination. For this reason, the sudden loss of smell and taste could continue to represent a useful and specific diagnostic marker to raise the suspicion of COVID-19 even in vaccinated subjects. In the future, it will be necessary to establish what the recovery rate is in these patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:419-421, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To identify the most influential publications in laryngology since 2000., Study Design: Modified Delphi process., Methods: Samples of laryngologists drawn from editors of leading journals, organization officers, and thought leaders were invited to participate in a modified Delphi identification of influential laryngology papers. Influential was defined as follows: yielding meaningful practice changes, catalyzing further work as a foundation for an important topic, altering traditional views, or demonstrating durability over time. Quality and validity were not among the selection criteria. Each participant nominated 5 to 10 papers in Round 1. These nominations, augmented with papers from bibliometric analysis, were narrowed further in Round 2 as participants identified their top 20. The 40 papers with the most Round 2 votes were discussed by video conference and then subjected to Round 3 voting, with each participant again selecting their top 20 most influential papers. Final results were collated by the number of Round 3 votes., Results: Sixteen of 18 invited laryngologists participated overall (all 16 in Rounds 1 and 3; 14 in Round 2). Twenty-one papers were identified as most influential. One paper appeared on all 16 Round 3 lists; three papers with eight (50%) votes each were lasted to make the list. Eleven of these 21 focused on voice; three each related to cancer, airway, and swallowing; and one encompassed all of these clinical areas., Conclusions: This list of 21 influential laryngology papers serves to focus further research, provides perspective on recent advances within the field, and is an educational resource for trainees and practicing physicians., Level of Evidence: NA Laryngoscope, 132:406-412, 2022., (© 2021 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Nasal diseases are among the main motives for the early discontinuation of continuous positive airway pressure therapy and for long-term therapeutic compliance with mandibular advancement device. Although our clinical experience leads us to the belief that recumbency impacts nasal airflow in some patient populations, there is no consensus regarding the magnitude of this effect and the specific group of patients who are the most affected by this condition. In this study, we conducted a meta-analysis to assess the effect of the recumbent position on nasal resistance and nasal airflow., Review Methods: PubMed (Medline), Cochrane Library, EMBASE, Scopus, and SciELO databases were checked for relevant studies by two members of the YO-IFOS study group. The two authors extracted the data. The main outcome was expressed as the difference between nasal resistance and nasal airflow before and after recumbency., Results: Nine studies with a total population of 291 individuals were included in the meta-analysis for nasal resistance after recumbency. We found a statistically significant difference in nasal airway resistance of -0.18 Pa sec/cm 3 as compared to before and after recumbency through rhinomanometry (RMM) analysis. A subgroup analysis revealed a variation of -0.20 Pa sec/cm 3 for patients with snoring or sleep apnea and - 0.10 Pa sec/cm 3 for healthy individuals. Regarding nasal airflow measured with RMM, three studies (n = 32) in asymptomatic controls revealed a statistically significant difference of 47.33 ml/sec., Conclusions: Recumbency increases nasal resistance and diminishes nasal airflow. This finding is of utmost importance in snorers and sleep apnea patients. Laryngoscope, 132:6-16, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To investigate whether there is an impact of obesity and overweight on the clinical findings and therapeutic responses of patients with laryngopharyngeal reflux (LPR)., Study Design: Prospective uncontrolled., Methods: Patients with LPR-related symptoms and positive LPR diagnosis at the hypopharyngeal-esophageal multichannel intraluminal impedance pH-monitoring (HEMII-pH) were recruited from December 2017 to December 2020. Patients were treated with a combination of diet, proton pump inhibitors, and alginate for 3 to 6 months. The following outcomes were studied according to the weight of patients: HEMII-pH, gastrointestinal endoscopy features, symptoms, findings, and therapeutic response., Results: A total of 262 patients completed the study, accounting for 134, 85, and 43 patients with normal weight (body mass index [BMI] <25), overweight (BMI = 25-29.99), and obesity (BMI >30). Obese patients reported significant higher prevalence of gastroesophageal reflux disease (GERD), acid LPR, and a more severe LPR disease regarding the number of pharyngeal reflux events, reflux symptom score (RSS), and reflux sign assessment (RSA). RSS and RSA scores significantly improved from baseline to 3-month posttreatment irrespective of the patient weight group. Symptoms and signs continued to improve from 3 to 6-month posttreatment only in patients with a normal weight., Conclusion: Obesity is associated with a more severe LPR disease and a higher proportion of GERD and acid LPR. Obese LPR patients may require more frequently PPI-therapy regarding the higher prevalence of GERD., Level of Evidence: 3 Laryngoscope, 131:E2742-E2748, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: The aim of this study was to evaluate the correlations between the severity and duration of olfactory dysfunctions (OD), assessed with psychophysical tests, and the viral load on the rhino-pharyngeal swab determined with a direct method, in patients affected by coronavirus disease 2019 (COVID-19)., Study Design: Prospective cohort study., Methods: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and determination of the normalized viral load on nasopharyngeal swab within 10 days of the clinical onset of COVID-19., Results: Sixty COVID-19 patients were included in this study. On psychophysical testing, 12 patients (20% of the cohort) presented with anosmia, 11 (18.3%) severe hyposmia, 13 (18.3%) moderate hyposmia, and 10 (16.7%) mild hyposmia with an overall prevalence of OD of 76.7%. The overall median olfactory score was 50 (interquartile range [IQR] 30-72.5) with no significant differences between clinical severity subgroups. The median normalized viral load detected in the series was 2.56E+06 viral copies/10 6 copies of human beta-2microglobulin mRNA present in the sample (IQR 3.17E+04-1.58E+07) without any significant correlations with COVID-19 severity. The correlation between viral load and olfactory scores at baseline (R 2  = 0.0007; P = .844) and 60-day follow-up (R 2  = 0.0077; P = .519) was weak and not significant., Conclusions: The presence of OD does not seem to be useful in identifying subjects at risk for being super-spreaders or who is at risk of developing long-term OD. Similarly, the pathogenesis of OD is probably related to individual factors rather than to viral load and activity., Level of Evidence: 4 Laryngoscope, 131:2312-2318, 2021., (© 2021 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To investigate the prevalence and features of laryngopharyngeal reflux (LPR) in patients with primary burning mouth syndrome (BMS)., Study Design: Prospective uncontrolled study., Methods: Patients who visited our Departments of Otolaryngology-Head and Neck and Maxillofacial surgery with BMS were prospectively recruited from September 2018 to September 2020. Patients benefited from dental, maxillofacial, otolaryngological examinations, and hypopharyngeal-esophageal impedance pH-monitoring (HEMII-pH). Oral, pharyngeal, and laryngeal findings and symptoms were rated with Reflux Sign Assessment (RSA) and Reflux Symptom Score-12 (RSS-12). Patients were treated with a combination of diet, pantoprazole, and alginate., Results: From the 81 included patients, 76 reported >1 pharyngeal reflux events (93.8%), accounting for 35 (46.1%), 24 (31.6%), and 17 (22.3%) acid, mixed, and nonacid LPR, respectively. Thirty-two patients had both LPR and gastroesophageal reflux disease (GERD). Thirty-eight patients benefited from pepsin saliva measurement, which was positive in 86.8% of cases. The mean scores of mouth/tongue burning, RSS-12, and RSA significantly improved from pre- to post-treatment (P < .004). At 3-month post-treatment, 62.5% of patients reported an improvement of mouth/tongue burning score. Patients with both GERD and LPR reported higher baseline RSS-12 and RSA scores., Conclusion: Acid, weakly acid, and nonacid LPR may be involved in the development of BMS. The use of an appropriate treatment considering the reflux features is associated with an improvement of symptoms and findings., Level of Evidence: 4 Laryngoscope, 131:E2627-E2633, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc..)

Objectives/hypothesis: To assess the evolution of laryngeal and extralaryngeal symptoms and findings of laryngopharyngeal reflux (LPR) throughout a 3-month to 9-month treatment., Study Design: Prospective Controlled Study., Methods: One hundred twenty-seven LPR patients and 123 healthy individuals were enrolled from four European hospitals. Patients were managed with a 3-month personalized treatment considering the LPR characteristics at the impedance-pH monitoring. Regarding the clinical therapeutic response, treatment was adapted for 3 to 6 additional months. Symptoms and findings were assessed throughout the therapeutic course with the Reflux Symptom Score (RSS) and the short version of the Reflux Sign Assessment (sRSA). The relationship between patient and reflux characteristics, symptoms, and findings was assessed., Results: One hundred twenty-one LPR patients completed the study. LPR patients exhibited more laryngeal and extralaryngeal symptoms and findings than healthy individuals. RSS significantly improved from baseline to 6 weeks posttreatment and continued to improve from 3 months to 6 months posttreatment. sRSA significantly improved from baseline to 3 months posttreatment. No further improvement was noted at 6 months posttreatment for pharyngeal and oral findings. Laryngeal findings continued to improve from 3 months to 6 months posttreatment. There was a significant association between patient stress level and RSS (P = .045). At 3 months posttreatment, 28.1% of patients had high or complete response, whereas 47.1% required 6 months or 9 months of treatment. Overall, 24.8% of patients had an LPR chronic course., Conclusions: Laryngeal and extralaryngeal symptoms and findings significantly improved throughout treatment in LPR patients. The improvement of laryngeal findings was slower. Regarding the low prevalence of some digestive or otolaryngological symptoms, a short version of the RSS could be developed., Level of Evidence: 3 Laryngoscope, 131:1332-1342, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To investigate worldwide practices of otolaryngologists in the management of laryngopharyngeal reflux (LPR)., Methods: An online survey was sent on the management of LPR to members of many otolaryngological societies. The following aspects were evaluated: LPR definition, prevalence, clinical presentation, diagnosis, and treatment., Results: A total of 824 otolaryngologists participated, spread over 65 countries. The symptoms most usually attributed to LPR are cough after lying down/meal, throat clearing and globus sensation while LPR-related findings are arytenoid erythema and posterior commissure hypertrophy. Irrespective to geography, otolaryngologists indicate lack of familiarity with impedance pH monitoring, which they attribute to lack of knowledge in result interpretation. The most common therapeutic regimens significantly vary between world regions, with a higher use of H2 blocker in North America and a lower use of alginate in South America. The duration of treatment also significantly varies between different regions, with West Asia/Africa and East Asia/Oceania otolaryngologists prescribing medication for a shorter period than the others. Only 21.1% of respondents are aware about the existence of nonacid LPR. Overall, only 43.2% of otolaryngologists believe themselves sufficiently knowledgeable about LPR., Conclusions: LPR knowledge and management significantly vary across the world. International guidelines on LPR definition, diagnosis, and treatment are needed to improve knowledge and management around the world., Level of Evidence: N.A. Laryngoscope, 131:E1589-E1597, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Objectives/hypothesis: To investigate the surgical, oncological, and functional outcomes of transoral robotic surgery (TORS) for the treatment of supraglottic squamous cell carcinoma., Study Design: Retrospective chart review., Methods: The charts of patients treated by TORS supraglottic laryngectomy (SGL) in an academic medical center were reviewed. The following outcomes were studied according to the tumor location: average robotic setup and operative times, mean estimated blood loss, postoperative complications, need of tracheotomy, refeeding characteristics, mean hospital stay, need of neck dissection and adjuvant therapy, 5-year local and regional controls, overall survival (OS), and disease-free survival (DFS)., Results: Seventy-five patients underwent TORS SGL. Tumors were classified as cT1 (32%), cT2 (52%), and cT3 (16%). Average robotic setup and operative times and the mean estimated blood loss were 15 minutes, 55 minutes, and 20 mL, respectively. The mean follow-up period ranged from 2 to 5 years. The 5-year OS and DFS were 80.2% and 94.3%, respectively. Overall, 34.6% of patients received adjuvant radiotherapy. The majority of patients (92%) restarted an oral diet within 24 to 48 hours postsurgery. Transient tracheotomy was performed in 8% of patients. Postoperative hemorrhages occurred in 12 patients (16.0%), lengthening the hospital stay (mean = 6.8 days). There were no outcome differences regarding the tumor location., Conclusions: TORS is an effective and safe therapeutic approach for early- and intermediate-stages cancers. Oncological outcomes may be quite similar to other surgical approaches, including transoral laser and open surgeries. Future randomized controlled studies are needed for comparing TORS SGL with other surgical procedures., Level of Evidence: 4 Laryngoscope, 131:1060-1065, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To assess the impact of diet on the saliva pepsin concentration of patients with laryngopharyngeal reflux (LPR)., Study Design: Non-controlled Prospective Study., Methods: Patients with positive LPR regarding hypopharyngeal-esophageal impedance-pH monitoring (HEMII-pH) were enrolled from three European Hospitals. Patients collected three saliva samples, respectively, in the morning (fasting), and 1 to 2 hour after lunch and dinner. Patients carefully detailed foods and beverages consumed during meals and before the pepsin samples. The 3-month treatment was based on the association of diet, proton pump inhibitors, alginate, or magaldrate regarding the HEMII-pH characteristics. Reflux Symptom Score (RSS) and Reflux Sign Assessment (RSA) were used for assessing the pre- to posttreatment clinical evolution. The Refluxogenic Diet Score and the Refluxogenic Score of a Dish (RESDI) were used to assess the refluxogenic potential of foods and beverages. The relationship between saliva pepsin concentration, HEMII-pH, RESDI, RSS, and RSA was investigated through multiple linear regression., Results: Forty-two patients were included. The saliva pepsin concentration of the 24-hour period of testing was significantly associated with foods and beverages consumed during the testing period and the evening dinner (r s = 0.973, P < .001). RSS and RSA significantly improved throughout treatment. The level of saliva pepsin in the morning was a negative predictive factor of the therapeutic response regarding RSA and RSS (P < .036)., Conclusions: Foods and beverages may significantly impact the saliva pepsin concentration of patients with LPR. Patients with high-level saliva pepsin in the morning had lower therapeutic response compared with those with low-level saliva pepsin., Level of Evidence: 4 Laryngoscope, 131:350-359, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To investigate the profile of patients with laryngopharyngeal reflux (LPR) at hypopharyngeal-esophageal multichannel intraluminal impedance-pH (HEMII-pH) monitoring and the relationship between hypopharyngeal-proximal reflux episodes (HREs) and saliva pepsin concentration., Study Design: Prospective non-controlled., Methods: Patients were recruited from three European hospitals from January 2018 to October 2019. Patients benefited from HEMII-pH monitoring and saliva collections to measure saliva pepsin concentration in the same time. Saliva pepsin concentration was measured in the morning (fasting), after lunch, and after dinner. The LPR profile of patients was studied through a breakdown of the HEMII-pH findings over the 24 hours of testing. The relationship between the concentrations of saliva pepsin and 24-hour HREs was studied through linear multiple regression., Results: One hundred twenty-six patients completed the study. The HEMII-pH analyses revealed that 73.99% of HREs occurred outside 1-hour postmeal times, whereas 20.49% and 5.52% of HREs occurred during the 1-hour postmeal and nighttime, respectively. Seventy-four patients (58.73%) did not have nighttime HREs. Patients with both daytime and nighttime HREs had more severe HEMII-pH parameters and reflux symptom score compared with patients with only daytime HREs. There were no significant associations between HREs and saliva pepsin concentration., Conclusions: Unlike gastroesophageal reflux disease, HREs occur less frequently after meals and nighttime. The analysis of the HEMII-pH profile of the LPR patients has to be considered to develop future personalized therapeutic strategies., Level of Evidence: 4 Laryngoscope, 131:268-276, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To assess the usefulness of orofacial strength and voice quality as assessment of response to levodopa challenge test (LCT) used in the diagnosis of early idiopathic Parkinson disease (IPD)., Study Design: Controlled Prospective Study., Methods: From January 2014 to April 2019, patients with early IPD and healthy individuals were recruited and evaluated for clinical findings (Hoehn and Yahr scale; Unified Parkinson's Disease Rating Scale); Voice Handicap Index (VHI); grade of dysphonia, roughness, breathiness, asthenia, and strain and instability (GRBASI); maximal phonation time; phonation quotient; acoustic parameters; and orofacial muscle strength Oral Performance Instrument (IOPI; IOPI Medical, Woodinville, WA, USA) t) at baseline and 45 minutes after the levodopa intake (LCT)., Results: A total of 32 IPD patients and 20 healthy individuals completed the study. Healthy individuals exhibited better VHI, grade of dysphonia, breathiness, asthenia, strain, instability, and acoustic measurements (noise-related, tremor, F0 short- and mid-term and intensity short-term parameters) than healthy subjects. The mean values of muscle strength of lips, cheeks, fundamental frequency (F0), highest F0, and shimmer significantly improved from pre- to post-LCT in IPD patients. Healthy individuals did not exhibit significant changes of orofacial strength and voice quality assessment from pre- to post-LCT. Significant associations were found between clinical, orofacial strength, and some aerodynamic and acoustic measurements., Conclusion: Orofacial strength and acoustic voice quality measurements may be used as objective outcomes of the LCT responsiveness in patients with early IPD., Level of Evidence: 3A. Laryngoscope, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To investigate clinical and radiological features of olfactory clefts of patients with mild coronavirus disease 2019 (COVID-19)., Study Design: Prospective non controlled study., Methods: Sixteen COVID-19 patients were recruited. The epidemiological and clinical data were extracted. Nasal complaints were assessed through the 22-item Sino-Nasal Outcome Test. Patients underwent psychophysical olfactory testing, olfactory cleft examination, and computed tomography (CT) scans., Results: Sixteen anosmic patients were included. The mean Sniffin' Sticks score was 4.6 ± 1.7. The majority of patients had no endoscopical abnormality, with a mean olfactory cleft endoscopy score of 0.6 ± 0.9. The olfactory clefts were opacified in three patients on the CT scan. The mean radiological olfactory cleft score was 0.7 ± 0.8. There were no significant correlations between clinical, radiological, and psychophysical olfactory testing., Conclusions: The olfactory cleft of anosmic COVID-19 patients is free regarding endoscopic examination and imaging. The anosmia etiology is not related to edema of the olfactory cleft., Level of Evidence: 4 Laryngoscope, 130:2526-2531, 2020., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Objective: To investigate current practices of laryngologists and non-laryngologists in management of Laryngopharyngeal Reflux (LPR)., Methods: An online survey was sent to members of otolaryngology societies about LPR, and subgroup analysis was performed between laryngologists and non-laryngologists. This survey was conducted by the LPR Study Group of Young Otolaryngologists of the International Federation of Otolaryngological Societies., Results: A total of 535 otolaryngologists completed the survey. Among them, 127 were laryngologists and 408 were non-laryngologists. Collectively, symptoms most commonly attributed to LPR are cough after lying down/meal, throat clearing, and acid brash; most common findings are thought to be arytenoid erythema and posterior commissure hypertrophy. Respectively, 12.5% and 5% of non-laryngologists and laryngologists believe that ≥50% of LPR patients suffer from heartburn (P = .010). Non-laryngologists are more aware about some extra-laryngeal findings associated with LPR (eg, pharyngeal erythema) than laryngologists. Neither laryngologists nor non-laryngologists associated development of benign lesions of the vocal folds with reflux. The management of LPR substantially differs between groups, with laryngologists indicating increased awareness of (impedance)-pH monitoring as well as the prevalence and treatment of nonacid/mixed LPR. Conversely, non-laryngologists are much more likely to include gastroenterology referral in their management of presumed LPR. Respectively, 44.8% and 27.6% of non-laryngologists and laryngologists believe themselves not sufficiently knowledgeable about LPR., Conclusions: Significant differences exist between laryngologists and non-laryngologists in diagnosis and treatment of LPR. Overall only one-third of responders believe themselves to be sufficiently educated about LPR., Level of Evidence: 4 Laryngoscope, 130:E539-E547, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To investigate the clinical features and the therapeutic response of laryngopharyngeal reflux (LPR) patients with or without gastroesophageal reflux disease (GERD)., Methods: Patients with LPR symptoms were enrolled from three European Hospitals. The diagnosis of LPR and GERD was made through impedance-pH monitoring (MII-pH). A gastrointestinal endoscopy was realized in patients with digestive complaints or ≥60 years old. The 3- to 6-month treatment was based on the association of diet, pantoprazole, alginate, and magaldrate regarding the MII-pH characteristics. Reflux Symptom Score (RSS) and Reflux Sign Assessment (RSA) were used to evaluate the clinical evolution throughout treatment. The gastrointestinal endoscopy findings, clinical features, and therapeutic response were compared between patients with LPR and GERD (LPR/GERD) and patients with LPR., Results: One hundred and eleven LPR patients were included, 54 being LPR/GERD. LPR/GERD patients had a higher number of proximal reflux episodes compared with LPR patients. The prevalence of esophagitis, hernia hiatal, and lower esophageal sphincter insufficiency did not differ between groups. The presence of GERD was strongly associated with acid LPR. Patients without GERD had a higher proportion of nonacid and mixed LPR compared with LPR/GERD patients. The pre- to posttreatment evolutions of RSS and RSA were quite similar in both groups, with the exception of the 3- to 6-month improvement of digestive symptoms, which was better in LPR/GERD group. The therapeutic success rates were 79.6% and 77.2% in GERD/LPR and LPR group, respectively., Conclusion: GERD is predictive of acid LPR. The clinical evolution and the therapeutic response rates were quite similar in both groups., Level of Evidence: 4 Laryngoscope, 130: E479-E489, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To investigate the relationship between the laryngopharyngeal reflux (LPR) episodes at the multichannel intraluminal impedance-pH monitoring (MII-pH) and the concentration of pepsin in the saliva of LPR patients., Methods: Patients with LPR were enrolled from the polyclinic of Poitiers, France. Patients benefited from 24-hour MII-pH that allowed a correlation study between reflux episodes and symptoms. Patients reported the occurrence of the critical symptoms during the testing period through a recording device. Simultaneously, they collected a first saliva sample 30 minutes after the symptoms and a second saliva collection a few hours after the first collection. The patient symptoms were assessed with reflux symptom score (RSS). The relationship between pepsin concentration in the saliva, symptoms, and the reflux episode characteristics at the MII-pH was investigated through multiple linear regression., Results: A total of 65 patients with LPR were recruited. The mean concentrations of the first and the second pepsin samples were 92.0 ± 108.1 and 101.8 ± 131.0, respectively. Peptest (RD Biomed, Milan, Italy) was positive in 51 LPR patients (78.5%). Concentrations of both pepsin samples were significantly correlated (P = 0.019). There was no significant association between pepsin concentrations in saliva samples, RSS, key symptoms during the test period, and MII-pH findings., Conclusion: The level of pepsin saliva concentration is not associated with the reflux episodes at the MII-pH. Future studies are needed to better understand the relationship between the extracellular pepsin concentration, mucosal inflammation, and related laryngopharyngeal symptoms., Level of Evidence: 4 Laryngoscope, 130:1278-1281, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To develop and validate the Reflux Symptom Score (RSS), a self-administered patient-reported outcome questionnaire for patients with laryngopharyngeal reflux (LPR)., Study Design: Prospective controlled study., Methods: A total of 113 patients with LPR were enrolled and treated with diet and 3 months of pantoprazole, alginate, and/or magaldrate depending on the LPR characteristics (acid, nonacid, or mixed). Eighty asymptomatic individuals completed the study. Patients and controls completed the RSS twice within a 7-day period to assess test-retest reliability. Internal consistency was measured using Cronbach's α for the RSS items in patients and controls. Validity was assessed by comparing the baseline RSS with the Reflux Symptom Index (RSI) and Voice Handicap Index (VHI). Seventy-seven patients completed the RSS at baseline and after 6 and 12 weeks of treatment to assess responsiveness to change. The RSS cutoff for determining the presence and absence of LPR was examined by receiver operating characteristic analysis., Results: Test-retest reliability (r s = 0.921) and internal consistency reliability (α = 0.969) were high. RSS exhibited high external validity indicated by a significant correlation with the RSI (r s = 0.831). Internal validity was excellent based on the higher RSS in patients compared with controls (P = .001). RSS, RSI, and VHI scores significantly improved from pre- to posttreatment, indicating a high responsiveness to change. RSS >13 can be considered suggestive of LPR-related symptoms. RSS was not influenced by the occurrence of gastroesophageal reflux disease, LPR subtypes, or patient characteristics., Conclusions: RSS is a self-administered patient-reported outcome questionnaire that demonstrates high reliability and excellent criterion-based validity. RSS can be used in diagnosing and monitoring LPR disease., Level of Evidence: 3b Laryngoscope, 130:E98-E107, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To investigate the role of laryngopharyngeal reflux (LPR) in the development of benign lesions of the vocal folds (BLVF)., Methods: PubMed, Cochrane Library, and Scopus were searched by three independent investigators for articles published between January 1990 and November 2018 providing substantial information about the role of LPR in the development of nodules, polyps, cysts, Reinke's edema, and sulcus vocalis. Inclusion, exclusion, diagnostic criteria and clinical outcome evaluation of included studies were analyzed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria., Results: Of the 155 relevant publications, 42 studies were included. Thirty-five were clinical studies and seven were experimental research studying the impact of reflux on vocal fold tissue. Only seven clinical studies utilized objective LPR diagnoses (pH monitoring), suggesting an association between LPR and the development of nodules, polyps, and Reinke's edema. These studies were characterized by a substantial heterogeneity due to discrepancies in inclusion/exclusion criteria, diagnostic methods, and clinical outcome evaluation. The few basic science studies on this topic support that LPR creates an environment that may predispose to BLVF through changes in defense mechanisms of the vocal folds, cell-to-cell dehiscence, inflammatory reaction of the vocal folds, and reaction to phonotrauma., Conclusions: Caustic mucosal injury from LPR could cause increased susceptibility of the vocal fold mucosa to injury and subsequent formation of nodules, polyps, or Reinke's edema. However, the heterogeneity and the low number of high-quality studies limit the ability to draw definitive conclusions. Future clinical and experimental studies are needed to better identify the role of reflux in development of BLVF. Laryngoscope, 129:E329-E341, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To investigate the therapeutic benefit of proton pump inhibitors (PPIs) over placebo in patients with laryngopharyngeal reflux (LPR) and to analyze the epidemiological factors of heterogeneity in the literature., Methods: An electronic literature search was conducted to identify articles published between 1990 and 2018 about clinical trials describing the efficiency of medical treatment(s) on LPR. First, a meta-analysis of placebo randomized controlled trials (RCTs) comparing PPIs versus placebo was conducted according to diet. The heterogeneity, response to PPIs, and evolution of clinical scores were analyzed for aggregate results. Second, a systematic review of diagnosis methods, clinical outcome of treatment, and therapeutic regimens was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement., Results: The search identified 1,140 relevant publications, of which 72 studies met the inclusion criteria for a total of 5,781 patients. Ten RCTs were included in the meta-analysis. The combined relative risk was 1.31 in favor of PPIs and increased to 1.42 when patients did not receive diet recommendations. Randomized controlled trials were characterized by a significant heterogeneity due to discrepancies in clinical therapeutic outcomes, diagnosis methods (lack of gold standard diagnostic tools), and therapeutic scheme. The epidemiological analysis of all articles supports the existence of these discrepancies in the entire literature. In particular, many symptoms and signs commonly encountered in LPR are not assessed in the treatment effectiveness. The lack of diagnosis precision and variability of inclusion criteria particularly create bias in all reported and included articles., Conclusion: This meta-analysis supports a mild superiority of PPIs over placebo and the importance of diet as additional treatment but demonstrates the heterogeneity between studies, limiting the elaboration of clear conclusions. International recommendations are proposed for the development of future trials. Laryngoscope, 129:1174-1187, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To identify the instruments for evaluating the clinical findings (ICFs) of laryngopharyngeal reflux (LPR) designed for use with regard to diagnosis and treatment effectiveness., Methods: The PubMed, Scopus, and Cochrane databases were used to search for subject headings following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Three investigators retrieved relevant studies published between 1990 and 2018 describing the evolution of laryngopharyngeal findings throughout LPR treatment. Issues of clinical relevance, that is, LPR diagnosis, treatments, and signs assessed for diagnosis or as therapeutic outcomes, were assessed. The investigators also evaluated the psychometric properties (conceptual model, content validity, consistency, reliability, concordance, convergent validity, known-groups validity, responsiveness to change, and interpretability) of the ICF. The risk of bias was assessed with the tool of the Clarity Group and Evidence Partners., Results: The search identified 1,227 publications with a total of 4,735 LPR patients; of these studies, 53 met the inclusion criteria. Of these 53 studies, we identified 10 unvalidated and six validated ICFs. None of the validated ICFs included all the psychometric properties. The main identified deficiencies related to ICF psychometric validation included variable construct validity, disparate and uncertain reliabilities, and a lack of interpretability. The lack of consideration of certain LPR laryngeal and extralaryngeal signs is the main weakness of ICFs, biasing content, and construct validities., Conclusion: The low specificity of LPR signs, the lack of consideration of many findings, and the absence of a gold standard for diagnosis constitute barriers to the further validation of these ICFs. Additional studies are needed to develop complete and reliable ICFs. Laryngoscope, 129:720-736, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)