24-Hour Multichannel Intraluminal Impedance-pH in Proton Pump Inhibitor Nonresponders vs Responders in Patients With Laryngopharyngeal Reflux.

OBJECTIVE: This study aimed to evaluate the characteristics of reflux in proton pump inhibitor (PPI) nonresponders vs responders in patients with laryngopharyngeal reflux (LPR) by using 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring. STUDY DESIGN: Prospective cohort study. SETTING: A tertiary care otolaryngology clinic. METHODS: Patients with typical LPR symptoms showing >1 proximal reflux episode were considered to have LPR and investigated prospectively. Patients were prescribed high-dose PPI twice daily and followed up for at least 2 months. Patients with LPR showing a ≥50% decrease in the follow-up reflux symptom index score during treatment periods as compared with pretreatment were defined as responders; others were defined as nonresponders. Various parameters in 24-hour MII-pH monitoring between nonresponders and responders with LPR were compared with Student's t test and receiver operating characteristic curve. RESULTS: Eighty patients were diagnosed with LPR and categorized as nonresponders (n = 19) and responders (n = 61). Proximal all reflux time and proximal longest reflux time in various MII parameters were higher in responders than in nonresponders (P = .0040 and .0216, respectively). Proximal all reflux time >0.000517% was a better cutoff value to predict responders with LPR as compared with the proximal longest reflux time >0.61 minutes (sensitivity + specificity: 1.317 vs 1.291). CONCLUSION: Proximal all reflux time in various 24-hour MII-pH monitoring parameters can be helpful to predict the response to PPI therapy in patients with LPR. These findings will help establish a personalized therapeutic scheme for patients with LPR.

Pharyngeal reflux episodes in patients with suspected laryngopharyngeal reflux versus healthy subjects: a prospective cohort study.

PURPOSE: This study aimed to analyze pharyngeal reflux episodes in patients with suspected LPR versus healthy subjects using 24-h MII-pH monitoring. METHODS: One hundred twenty-one patients who visited our clinic with a chief complaint of LPR-related symptoms and underwent 24-h MII-pH monitoring were enrolled prospectively. Also, 27 healthy subjects were enrolled and underwent 24-h MII-pH monitoring during the same period. We analyzed sensitivity, specificity, and accuracy comprehensively to determine appropriate cut-off values of pharyngeal reflux episodes in 24-h MII-pH monitoring to diagnose patients with LPR. RESULTS: Twenty-nine of 121 patients with suspected LPR showed no pharyngeal reflux episodes, while 92 showed more than one pharyngeal reflux event. In contrast, the 22 healthy subjects showed no pharyngeal reflux episodes, three showed one reflux event, and two showed two reflux events. A cut-off value of ≥ 1 showed best accuracy reflected by combined sensitivity and specificity values, while ≥ 2 demonstrated better specificity with slight loss of sensitivity and slightly lower overall accuracy, suggesting cut-off value of ≥ 1 pharyngeal reflux episodes is a good clinical indicator. CONCLUSION: A cut-off value of ≥ 1 in pharyngeal reflux episodes on 24-h MII-pH monitoring in patients with suspected LPR might be an acceptable diagnostic tool for LPR.

Tidal volume and stroke volume changes caused by respiratory events during sleep and their relationship with OSA severity: a pilot study.

PURPOSE: Breath-by-breath tidal volume (TV) and beat-by-beat stroke volume (SV) were continuously measured in patients with OSA undergoing polysomnography (PSG). The objectives were to (1) determine the changes in TV/SV in response to respiratory events and (2) assess the relationship between these changes and the disease severity. METHODS: From the PSG data of nine patients with OSA, six different types of respiratory events were identified, i.e., flow limitation (FL), respiratory effort related arousal (RERA), hypopnea with arousal only (Ha), hypopnea with desaturation only (Hd), hypopnea with arousal and desaturation (Had), and apnea. The measured TV and SV values during and after each respiratory event were compared with the pre-event baseline values. RESULTS: The mean TV/SV reductions during all hypopneas and apneas were 38.1%/4.2% and 70.5%/8.8%, respectively. Among three different hypopnea types, the reductions in TV during Hd and Had were significantly greater than those during Ha. The TV reductions during Ha and FL were similar. After RERA, Ha, Had, and apnea, there was an overshoot in TV and SV values, whereas there was no overshoot after FL and Hd. During RERA, there was no reduction in TV/SV. CONCLUSIONS: The changes in TV during and after each type of respiratory event were significantly different in most cases. The changes in SV between hypopnea and apnea were different with statistical significance. The AHI does not properly account for the ventilation losses caused by respiratory events. Thus, TV measurements might be useful in the future in assessing the OSA severity in conjunction with the AHI.

Measurement of Tryptase and CC16/Albumin in Nasal Lavage Fluid as a Screening Tool of Allergic Rhinitis.

BACKGROUND: There is no trial to make a diagnostic tool of allergic rhinitis (AR) utilizing biomarkers from nasal fluid. Base on previous studies, we selected following five biomarkers in nasal fluids that represent the characteristics of allergic reactions: tryptase, eosinophil cationic protein (ECP), interleukin 5 (IL-5), Clara cell protein 16 (CC16) and CC16-to-albumin ratio. OBJECTIVE: This study aimed to identify biomarkers in nasal discharge that may be used in biosensors to diagnose AR as an additional diagnostic tool. METHODS: Patients showed rhinorrhea and tested positive on allergic skin and specific immunoglobulin E (IgE) tests were included in the AR group. The non-AR group included individuals no dominant nasal symptoms and tested negative on allergy tests. Nasal lavage fluid samples were collected from all participants. Biomarkers in the samples were quantified using enzyme-linked immunosorbent assay. RESULTS: Forty-five patients with AR and 28 non-AR subjects were enrolled in this study. Comparing the concentrations of biomarkers, the concentrations of tryptase and IL-5 were significantly higher in the AR group than in the NAR group. And CC16 level and CC16-to-albumin ratio were significantly lower in the AR group. In the combination of tryptase or CC16-to-albumin ratio, the sensitivity was 90.7% and the specificity was 64.3% (p = 0.013). CONCLUSION: The combination of "tryptase or CC16-to-albumin" could be used as a screening tool for AR. Although this diagnostic method could not replace conventional diagnostic tools, we could consider the method we proposed as an additional screening tool for patients who could not undergo allergy tests.

Surgical management in a severe OSA patient diagnosed with Stickler syndrome.

Stickler syndrome is a genetic disorder of connective tissue. One of the major symptoms associated with this disorder is an oro-facial malformation, which may cause a submucous cleft or a complete cleft of the hard palate. A 32-year-old man diagnosed with Stickler syndrome and a submucosal cleft palate (SMCP) visited our hospital with a chief complaint of excessive daytime sleepiness. The patient was diagnosed with severe obstructive sleep apnea (OSA), and administration of a polysomnography test revealed an apnea-hypopnea index (AHI) of 30.9 events/hour (h). Auto-titrating continuous positive airway pressure was initiated to control the OSA symptoms and subsequently the patient showed some improvement. However, due to continuous velopharyngeal insufficiency symptoms, intravelar veloplasty was performed. Three months after surgery, the AHI had decreased to 12.4 events/h. Recent studies have described a greater risk for OSA in individuals with cleft palate, than in the general population. The present case demonstrates surgical success in a patient with OSA and SMCP, suggesting that palatal surgery may be considered an optional surgical treatment for OSA patients with SMCP.

Changes in Pharyngeal Baseline Impedance in Patients With Laryngopharyngeal Reflux.

OBJECTIVE: Few studies have investigated pharyngeal intraluminal baseline impedance (BI) levels in patients with laryngopharyngeal reflux (LPR). The aim of this study was to compare intraluminal BI levels between patients with LPR and healthy controls. STUDY DESIGN: Retrospective case series. SETTING: Tertiary care medical center. SUBJECTS AND METHODS: We conducted a retrospective analysis of 24-hour multichannel intraluminal impedance (MII)-pH monitoring results from patients with suspected LPR complaining of reflux symptoms. Patients with suspected LPR were divided into 2 groups according to the 24-hour MII-pH monitoring (LPR group: patients with symptoms with reflux events ≥1, symptom but no reflux [SNR] group: patients with symptoms but no reflux event). Healthy controls were recruited and also underwent 24-hour MII-pH monitoring. We compared the esophageal and pharyngeal BI levels and ratios between 3 groups. RESULTS: Pharyngeal BI levels in the LPR group were significantly higher than in the healthy controls. In addition, the pharyngeal BI levels in the SNR group were significantly higher than in the healthy controls. All ratios of pharyngeal to distal esophageal BI levels in the LPR and SNR group were significantly higher than in the healthy controls. However, there were no significant differences in esophageal BI levels and ratios between the 3 groups. CONCLUSION: We found that the pharyngeal BI levels were higher in patients with LPR than in healthy controls. In addition, the pharyngeal BI levels measured by 24-hour MII-pH monitoring in patients with LPR symptoms, but without a reflux episode, were higher than in the healthy controls.

Correlation of Nasal Fluid Biomarkers and Symptoms in Patients with Persistent Allergic Rhinitis.

OBJECTIVES: This study investigated whether the biomarkers present in nasal fluid reflect the severity of symptoms in patients with persistent allergic rhinitis (PAR). METHODS: We enrolled 29 PAR patients complaining of nasal symptoms and testing positive to skin prick test. Patients' total nasal symptom score (TNSS) was measured and their nasal lavage fluid (NALF) was collected. The levels of biomarkers including Clara cell protein 16 (CC16), tryptase, and interleukin 5 (IL-5) in NALF were determined via enzyme-linked immunosorbent assay (ELISA). RESULTS: PAR patients were classified into persistent mild and persistent moderate-to-severe groups according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. The CC16 alone was significantly negatively correlated with TNSS (P < .05). Further, the CC16 level was significantly lower in persistent moderate-to-severe group than persistent mild group of patients (P < .05). CONCLUSIONS: The levels of CC16 alone among several NALF biomarkers showed an inverse correlation with symptoms of PAR patients.

Impact of allergic rhinitis on quality of life after powered intracapsular tonsillectomy and adenoidectomy.

BACKGROUND: Allergic rhinitis (AR) has been reported to worsen quality of life (QoL) after adenotonsillectomy. Although powered intracapsular tonsillectomy and adenoidectomy (PITA) has been widely performed, it is not clear whether comorbid AR may worsen QoL in patients who undergo PITA. PURPOSE: To evaluate QoL after PITA in relation to AR. METHODS: Children undergoing PITA for sleep-disordered breathing were enrolled and divided into AR and non-AR groups. QoL was evaluated using serial applications of the Obstructive Sleep Apnea-18 (OSA-18) questionnaire and compared between the two groups. RESULTS: Of 151 enrolled patients, 73 were categorized into the AR and 78 into non-AR groups. After surgery, patients exhibited marked improvement in OSA-18 scores in both groups, with similar results at each follow-up. The degree of improvement in OSA-18 scores was less in the AR group 3 months after surgery; however, this difference was not significant 6 months after surgery. CONCLUSIONS: Although comorbid AR may initially appear to impede improvement in QoL after PITA, QoL was improved similarly 6 months after PITA, irrespective of AR status. In children with comorbid AR, PITA could be safely performed to treat sleep-disordered breathing without concerns regarding worsening of QoL.

The Relationship between Age-Related Hearing Loss and Cognitive Disorder.

BACKGROUND: Although the rates of occurrence of age-related diseases, including presbycusis and cognitive disorders, have increased with an increase in the geriatric population, the relationship between these two conditions remains unclear. OBJECTIVE: To investigate the association between presbycusis and cognitive disorder. SUBJECTS AND METHODS: A retrospective review of patient medical records was conducted at a single tertiary university hospital. This study enrolled 399 patients aged ≥65 years who were prescribed hearing aids for the chief complaint of hearing loss. For main outcomes and measures we used audiograms, the Korean Mini-Mental State Examination, and the Global Deterioration Scale (GDS). RESULTS: Of the 399 patients who were prescribed hearing aids for presbycusis, 45 (11.3%) had dementia and 354 (88.7%) did not have dementia. When the cognitive disorder group was divided into mild (1-4) and severe (5-7) subgroups based on the GDS scores, the threshold of hearing loss was significantly higher in the severe group than in the mild group (p < 0.05). The prevalence of dementia was significantly higher in patients with hearing loss for ≥10 years than in patients with hearing loss for <10 years (p < 0.05). CONCLUSION: Presbycusis and cognitive disorder are correlated. More severe and prolonged hearing loss is associated with a higher prevalence of cognitive disorder.

Comparison of Computed Tomography, Magnetic Resonance Imaging, and Positron Emission Tomography and Computed Tomography for the Evaluation Bone Invasion in Upper and Lower Gingival Cancers.

PURPOSE: Preoperative detection of bone invasion is important in cases of gingival cancer. The aim of this study was to compare the diagnostic value of 3 imaging methods for the detection of bone invasion in upper and lower gingival cancer: computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) and CT. MATERIALS AND METHODS: This retrospective cohort study enrolled patients who underwent a maxillectomy or a mandibulectomy for gingival cancer. Each preoperative image (CT, MRI, or PET/CT) was reviewed for the presence of bone invasion, and the possibility for bone invasion was graded. These results were verified with pathology reports. Sensitivity, specificity, positive predictive value, and negative predictive value for the detection of mandibular involvement in alveolar bone were calculated, and a receiver operating characteristics (ROC) curve analysis was performed. RESULTS: Forty patients (27 men and 13 women) were enrolled. Pathologic examination disclosed bone invasion in 25 of the 40 patients. Of these patients, 13 had maxillary and 12 had mandibular alveolus involvement. The diagnostic accuracy of CT (90.0%) was highest among the 3 modalities for the detection of bone invasion. In the ROC curve analysis, values for the area under the curve for upper gingival cancer were lower than those for lower gingival cancer. CONCLUSIONS: The 3 imaging methods were less sensitive for the detection of bone invasion in upper gingival cancer than in lower gingival cancer. Cases of upper gingival cancer should be evaluated more carefully for bone invasion before surgery.

Is epiglottis surgery necessary for obstructive sleep apnea patients with epiglottis obstruction?

OBJECTIVES/HYPOTHESIS: To examine the effect of epiglottis obstruction during drug-induced sleep endoscopy (DISE) on the surgical results of multilevel sleep surgery without epiglottic intervention. STUDY DESIGN: Cross-sectional study. METHODS: This investigation involved patients diagnosed with severe obstructive sleep apnea (OSA) based on preoperative polysomnography (PSG), who underwent DISE followed by multilevel OSA surgery without epiglottic intervention at Kyung Hee Medical Center (Seoul, South Korea) between March 2013 and July 2016. During DISE, obstruction patterns of the upper airway were evaluated using the velum, oropharynx, tongue base, epiglottis classification method. Follow-up PSG was performed 3 months after surgery to determine the success rate of multilevel surgery without epiglottic intervention. A comparison was done between the group with epiglottis obstruction and the group without epiglottis obstruction. RESULTS: Epiglottis obstruction was observed during DISE in 43.7% of patients. After application of exclusion criteria, 54 subjects were included (27 with and 27 without epiglottis obstruction). DISE revealed an association between epiglottis obstruction and tongue base collapse (P = .02). Comparing pre- and postoperative PSG findings, both groups exhibited improvement postoperatively. The success rate was 44.4% in the epiglottis obstruction group and 40.7% in the non-epiglottis obstruction group (P = .80). There was no difference in surgical success rates between the two groups. CONCLUSIONS: The prevalence of epiglottis obstruction requiring epiglottic surgery was lower than what was found during DISE. Sleep surgeons may consider staged epiglottic surgery in patients with epiglottis obstruction. LEVEL OF EVIDENCE: 3b Laryngoscope, 129:2658-2662, 2019.

Association Between Pepsin in the Saliva and the Subjective Symptoms in Patients With Laryngopharyngeal Reflux.

OBJECTIVES: Our study was designed to further evaluate the relationships between the saliva pepsin level and the symptoms and quality of life of patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: A prospective cohort study without controls. SETTING: Tertiary teaching hospital. SUBJECTS AND METHODS: We analyzed 50 patients diagnosed with LPR by 24-hour multichannel intraluminal impedance pH monitoring. All subjects were instructed to collect saliva samples upon waking in the morning. The saliva pepsin levels were analyzed using enzyme-linked immunosorbent assay. The Reflux Symptom Index, Reflux Finding Score, Laryngopharyngeal Reflux-Health-Related Quality of Life, and Short Form 36 survey were administered. RESULTS: The pepsin was detected in the saliva of 41 patients with LPR (17.15 ± 20.42 ng/mL). Nine patients did not have pepsin in the saliva. There were no significant associations between the pepsin level in the saliva and Reflux Symptom Index, Laryngopharyngeal Reflux-Health-Related Quality of Life, or Short Form 36 of patients with LPR. CONCLUSION: The saliva pepsin level is not significantly correlated with LPR symptoms or quality of life in LPR patients. It may be true that there is no association between pepsin levels and LPR symptoms, but this lack of association does not prove the lack of pathophysiological effect.

Increased IL-17 and 22 mRNA expression in pediatric patients with otitis media with effusion.

OBJECTIVES: Middle ear effusion has been reported to be associated with immune responses in patients with otitis media with effusion (OME). Although various cytokines are involved in immunologic responses in patients with OME, no study to date has assessed the involvement of the pro-inflammatory cytokines interleukin (IL)-17 and IL-22. This study analyzed the levels of expression of IL-17 and IL-22 in the middle ear effusion of patients with OME. METHODS: Patients aged <11 years who were diagnosed with chronic OME and underwent ventilation tube insertion from May 2013 to August 2015 were enrolled. Effusion fluid samples were obtained during surgery and levels of IL-17 and IL-22 mRNAs assessed by real-time PCR. IL-17 and IL-22 mRNA levels were compared in patients with effusion fluid positive and negative for bacteria; in patients with and without accompanying diseases, recurrent disease, and re-operation; and relative to fluid characteristics. RESULTS: The study cohort included 70 pediatric patients, 46 boys and 24 girls, of mean age 4.31 ± 2.11 years. The levels of IL-17 and IL-22 mRNA were higher in patients with than without sinusitis, but only IL-22 mRNA levels differed significantly (p < 0.05). The level of IL-17 mRNA was significantly higher in patients who did than did not undergo T&A (p < 0.05). The level of IL-22 expression was significantly higher in mucoid and purulent middle ear fluid samples than in serous fluid samples (p < 0.05). CONCLUSION: IL-17 and IL-22 mRNAs are involved in the pathophysiology of OME and are significantly higher in subjects with than without accompanying diseases.

Optimal timing of saliva collection to detect pepsin in patients with laryngopharyngeal reflux.

OBJECTIVES/HYPOTHESIS: To determine salivary pepsin levels as a function of collection time. STUDY DESIGN: A prospective, case-control study. METHODS: We selected 57 patients with clinical symptoms and signs of laryngopharyngeal reflux who underwent 24-hour multichannel intraluminal impedance-pH (24h MII-pH) monitoring tests, and 12 control subjects without clinical symptoms and signs of laryngopharyngeal reflux. All subjects were instructed to collect saliva samples upon waking, 1 hour after each meal (3 times per day), and upon any occurrence of laryngopharyngeal reflux (LPR) symptoms. The pepsin levels in saliva were measured by using enzyme-linked immunosorbent assay. The Reflux Symptom Index survey was also administered. RESULTS: A total of 50 patients in whom LPR was diagnosed based on results of 24h MII-pH monitoring test were enrolled in the study. The average pepsin level upon waking was 17.2 ng/mL, which was significantly higher than that measured in samples collected at any other time (P < .005). Pepsin levels were higher in patients with LPR than those in controls. The Reflux Symptom Index scores were statistically different between these groups of subjects. CONCLUSIONS: The levels of total pepsin in saliva collected upon waking were significantly higher in the group of patients presenting with LPR symptoms and who demonstrated at least one episode of proximal esophageal reflux during 24h MII-pH monitoring. Furthermore, the average pepsin level upon waking was higher than that measured at any other time. Measuring pepsin levels in the saliva upon waking may be a useful method in the diagnosis of LPR. LEVEL OF EVIDENCE: 3b Laryngoscope, 126:2770-2773, 2016.