Comparison of Two Types of Electrodes for Measuring Submental Muscle Activity During Swallowing.

PURPOSE: This study aimed to investigate the potential of a newly developed small electrode to accurately record muscle activity during swallowing. MATERIAL AND METHODS: This study included 31 healthy participants. The participants underwent swallowing trials with three types of material. The recordings involved the following conditions: 1) swallowing saliva, 2) swallowing 3 mL water, and 3) swallowing 5 mL water. Two types of electrodes, a conventional electrode (CE) and a newly developed small electrode (NE), were symmetrically positioned on the skin over the suprahyoid muscle group, starting from the center. From the surface electromyography data, the swallowing duration (s), peak amplitude, and rising time (duration from swallowing onset to peak amplitude: s) were measured. Additionally, the equivalence of characteristics of the waveform of muscle activities was calculated by using the variance in both the upper and lower confidence limits in duration and rising time. RESULTS: No significant differences in baseline, swallowing duration or rising time between the CE and NE were observed for any swallowing material. The peak amplitude was significantly higher for the NE than for the CE for all swallowing materials. The CE and NE displayed no significant difference in the equivalence of characteristics of the waveform of muscle activities for any swallowing material. CONCLUSIONS: The gold-plated small electrodes utilized in this study indicated the ability to record the same characteristics of muscle activity as conventional electrodes. Moreover, it was able to capture the muscle activity of each muscle group with improved sensitivity in a narrow area, such as under the submandibular region, with more precision than that of conventional electrodes.

[TWO CASES OF LARYNGEAL EDEMA CAUSED BY SUBLINGUAL ALLERGEN IMMUNOTHERAPY].

Sublingual immunotherapy is a widely used treatment, and serious adverse reactions such as anaphylaxis are rare. We report two cases of laryngeal edema as adverse reactions to sublingual immunotherapy, which could be continued due to a change in the administration method. Case 1 presents a 15-year-old male suspected to have had anaphylaxis due to the dust at the age of 6 years. He started treatment with Miticure® and developed laryngeal edema 30 minutes after taking the 10000JAU dose on the 10th day. laryngeal edema was treated with intravenous infusion. Case 2 presents a 48-year-old woman. She started treatment with Cidacure® and developed respiratory distress and laryngeal edema 1 hour after taking the 5000JAU dose on the 5th day. she had resolved mildly without therapeutic intervention. In both cases, the patients were switched to sublingual spitting, resumed with the initial dose cautiously, and were able to continue. Sublingual immunotherapy is a safe treatment, but sudden adverse reactions may occur. Laryngeal symptoms may be treated by changing to the sublingual spitting method, but laryngeal findings should be examined, and the dosage should be carefully increased.

Residual nasal polyp tissue following dupilumab therapy is associated with periostin-associated fibrosis.

PURPOSE: Dupilumab, an anti-interleukin-4 receptor alpha monoclonal antibody, is a new treatment for severe uncontrolled chronic rhinosinusitis with nasal polyps. However, data on the effect of dupilumab on histological changes in nasal polyp tissue are lacking. We aimed to investigate the effect of dupilumab on real-life clinical conditions and nasal polyp tissues from patients with eosinophilic chronic rhinosinusitis (ECRS), which is a refractory subtype. METHODS: We conducted an open-label, prospective, observational, single-centre study on 63 patients with refractory ECRS on the basis of the criteria of the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study. These patients had a history of surgery and received dupilumab for 24 weeks. Patient-reported sinonasal symptoms, T&T olfactometry and nasal polyp scores were prospectively evaluated. In 23 patients with residual nasal polyps following dupilumab treatment, changes in systemic and local periostin expression, and total collagen deposition in nasal polyp tissues were investigated before and after dupilumab administration. RESULTS: Dupilumab rapidly improved sinonasal symptoms and reduced the nasal polyp score 24 weeks after initiation. 40 (63.5%) patients had resolution of nasal polyps, but the reduction was limited in the remaining 23 (36.5%) patients. Periostin expression in serum and nasal lavage fluid was decreased, whereas periostin and the total collagen deposition area in subepithelial tissues in residual nasal polyps were enhanced after dupilumab administration. CONCLUSION: Dupilumab improves sinonasal symptoms and reduces the nasal polyp score in refractory ECRS. Periostin-associated tissue fibrosis may be involved in the differential effect of dupilumab on nasal polyp reduction.

Relationships between Lip Seal Strength, Tongue Pressure, and Daytime Sleepiness in Japanese Workers: A Cross-Sectional Study.

This cross-sectional study aimed to examine the relationships between lip seal strength, tongue pressure, and daytime sleepiness in Japanese workers. A self-administered questionnaire which comprised the Epworth Sleepiness Scale (ESS) was completed by 496 workers, and excessive daytime sleepiness was defined by an ESS score of 11 or over. Lip seal strength and tongue pressure were measured in all participants, and multiple regression analyses were performed to examine the effects of lip seal strength and tongue pressure on daytime sleepiness. The median ESS score was 5.0 (25th and 75th percentiles: 2.0 and 8.0), and 42 (8.5%) workers had excessive daytime sleepiness. The median lip seal strength was 13.5 N (11.4, 16.3), and the tongue pressure was 41.7 kPa (35.2, 48.3). Workers with higher ESS scores had significantly lower levels of lip seal strength than those without, following adjustments for age and body mass index (BMI) values (ß (95% confidence interval): -0.043 [-0.081, -0.004]). However, tongue pressure was not significantly associated with ESS score after adjustments for age and/or BMI. These results suggest that maintaining moderate lip seal strength may help prevent excessive daytime sleepiness in Japanese workers regardless of age or BMI.

Eosinophilic granulomatosis with polyangiitis developed after dupilumab administration in patients with eosinophilic chronic rhinosinusitis and asthma: a case report.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by eosinophil-rich granulomatous inflammation and small-to-medium vessel vasculitis associated with asthma, rhinosinusitis, and eosinophilia. EGPA is often difficult to distinguish from severe asthma and eosinophilic chronic rhinosinusitis (ECRS) in cases when there are no findings that suggest vasculitis. Dupilumab, an anti-IL-4Rα monoclonal antibody, is expected to be effective in eosinophilic airway inflammatory diseases, such as refractory asthma and chronic rhinosinusitis (CRS). Although transient eosinophilia and eosinophilic pneumoniae have been reported in patients with refractory asthma and CRS associated with dupilumab, few studies have examined the development of EGPA. CASE PRESENTATION: We report a case of a 61-year-old woman treated with dupilumab for refractory ECRS and eosinophilic otitis media (EOM) complicated by severe asthma. Although she had a previous history of eosinophilic pneumoniae and myeloperoxidase (MPO) ANCA positivity, there were no apparent findings of vasculitis before the initiation of dupilumab. After the second administration of dupilumab, several adverse events developed, including worsening of ECRS, EOM and asthma, and neuropathy. A blood test showed an eosoinophilia and re-elevation of MPO-ANCA levels after the administration of dupilumab. Therefore, dupilumab was discontinued owing to the development of EGPA, and prednisolone and azathioprine administration was initiated for a remission induction therapy. CONCLUSION: To the best of our knowledge, this is the first case report that suggests that dupilumab may directly trigger the manifestation of vasculitis in patients who were previously MPO-ANCA-positive. Although the precise mechanism of how dupilumab could trigger the development of EGPA requires further elucidation, measuring MPO-ANCA in patients with multiple eosinophilic disorders before the initiation of dupilumab might be helpful when considering the possibility of a latent EGPA. When administering dupilumab to patients with a previous history of MPO-ANCA positivity, clinicians must carefully monitor and collaborate with other specialists in the pertinent fields of study for appropriate usage.

Lip Seal Strength and Tongue Pressure among Japanese Male Workers: Comparison of Different Age Groups.

Lip seal strength and tongue pressure are related to sarcopenia in older adults and are directly linked to the quality of life of workers after retirement. This study examined lip seal strength and tongue pressure among Japanese male workers by age. A self-administered questionnaire survey including alcohol consumption and smoking was conducted on 454 male workers. Height, weight, lip seal strength, and tongue pressure were also measured and then stratified by age (20s, 30s, 40s, 50s, and 60s and over). The mean (25th, 75th percentiles) lip seal strength and tongue pressure for all workers were 13.7 N (11.6, 16.4) and 41.7 kPa (35.2, 48.2), respectively. Both lip seal strength and tongue pressure were lowest in the 20s, at 12.1 N (9.6, 14.0) and 40.6 kPa (33.4, 47.6), respectively. The multiple regression analysis adjusted for smoking showed a significant positive association between lip seal strength and BMI for the 20s, 50s, and 60s and over, and a significant positive association between tongue pressure and BMI for the 30s, 40s, 50s, and 60s and over. To maintain oral health in older adults, it may be useful to measure workers' lip seal strength and tongue pressure and intervene at an earlier stage.

Successful Omalizumab Treatment of Rhinogenic Contact Point Headache Complicated by Severe Cedar Pollinosis: A Case Report.

Headache is one of the most common neurological disorders in children. The most common headache in children is a primary headache, including migraine and tension-type headache, but note that secondary headaches should be differentiated as a cause of headache in pediatric patients. The management of cedar pollinosis in pediatric patients is important because it can cause quality-of-life deficits in addition to nasal and ocular symptoms. Omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, is approved in Japan as an add-on treatment option for severe cedar pollinosis, but few studies have investigated its real-world clinical efficacy in pediatric patients with seasonal allergic rhinitis. We report the case of a 15-year-old male patient with cedar pollinosis who suffered from uncontrolled naso-ocular symptoms, facial pain, and headache despite using histamine H1-receptor antagonists and intranasal corticosteroid spray. A sinus computed tomography scan and nasal endoscopic findings showed a swollen inferior turbinate and nasal septum in contact with the nasal cavity ipsilateral to the headache. Application of local anesthesia to the contact points within the nasal cavity resulted in the rapid relief of headaches. Therefore, we diagnosed rhinogenic contact point headache triggered by cedar pollinosis and initiated the add-on therapy of omalizumab for seasonal allergic rhinitis. Three days after the administration of omalizumab, his naso-ocular symptoms, quality-of-life deficits, and headache improved markedly, accompanied by improved nasal endoscopic findings. Omalizumab was immediately effective for the treatment of rhinogenic contact point headaches complicated by severe cedar pollinosis in a pediatric patient.

Case Report: A 29-Year-Old Pregnant Woman at 24 Weeks of Gestation Presenting with Laryngotracheitis and COVID-19 Due to the R.1 Variant of SARS-CoV-2.

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was discovered in December 2019 in Wuhan, China. Coronavirus disease (COVID-19) mainly presents with lower respiratory tract symptoms. On the other hand, laryngotracheitis or croup shows barky cough and it is rare in adults. There were no reports of laryngotracheitis with COVID-19 in pregnant women. We report the case of a pregnant woman at 24 weeks of gestation presenting with acute laryngotracheitis and COVID-19 due to the R.1 variant of SARS-CoV-2. CASE REPORT A 29-year-old previously healthy woman at 24 weeks of gestation presented with hoarseness and sore throat without fever, of 1-day duration. Although she was treated by her primary care physician with nebulized epinephrine, her symptoms did not resolve. She came to our hospital the same day. On arrival at our department, she was tachypneic and had a 95% oxygen saturation. She had stridor and barking cough. Laryngeal endoscopy revealed edema under the vocal cords. She was hospitalized urgently. SARS-CoV-2 polymerase chain reaction (PCR) testing was positive and the E484K mutation was confirmed. She was treated with oral and inhaled corticosteroids. Two days after admission, her symptoms were improved. She was discharged 10 days after admission. Edema under the vocal cords was completely improved 24 days after discharge. There were no adverse effects on the pregnancy. CONCLUSIONS COVID-19 laryngotracheitis has a more severe disease course than other causes, especially in pregnancy. COVID-19 laryngotracheitis should be use corticosteroids to treatment. Prednisolone is recommended for laryngotracheitis with COVID-19 during pregnancy.

A 32-Year-Old Man with Persistent Olfactory Dysfunction Following COVID-19 Whose Recovery Was Evaluated by Retronasal Olfactory Testing.

BACKGROUND Anosmia, which is loss of smell, is a recognized complication of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may persist after recovery from infection. Retronasal olfactory testing includes both subjective questionnaires and physiological tests that can be used to evaluate recovery of smell. This report presents the case of a 32-year-old man with persistent loss of smell following COVID-19 whose recovery was evaluated by retronasal olfactory testing. CASE REPORT The patient was a 32-year-old man with confirmed SARS-CoV-2 infection. He was aware of his olfactory dysfunction. Using the orthonasal test, a T&T Olfactometer 2 months after disease onset showed an olfactory threshold score of 2.2 points (mild decrease) and olfactory identification result of 3.4 points (moderate decrease). However, the retronasal intravenous olfactory test showed no response, indicating severe olfactory dysfunction. After 3 months of olfactory training and therapy with steroidal nasal drops (Fluticasone Furoate, 27.5 µg/day) and oral vitamins (Mecobalamin, 1500 µg/day), the patient's orthonasal test olfactory threshold score improved to 0.6 points (normal), and his olfactory identification result improved to 1.2 points (mild decrease). Although the retronasal intravenous olfactory test showed a weak response, a reaction did occur. At this time, the patient did not report any improvement in his symptoms. CONCLUSIONS This report has shown that in cases of persistent anosmia following COVID-19, retronasal olfactory testing can be used to evaluate recovery of the sense of smell.

A Rare Case of Elongated Styloid Process Fracture.

BACKGROUND An elongated styloid process occurs with Eagle syndrome and causes a variety of symptoms. Fracture of the elongated styloid process is a rare condition. With spontaneous fractures, appropriate treatment cannot be performed in many cases due to unexplained symptoms and indefinite complaints that are not thoroughly examined. CASE REPORT We encountered a case of fractured elongate styloid process reaching the hyoid bone. Based on the findings from cervical 3-dimensional computed tomography (3D-CT), we chose surgery using the transcervical approach instead of the intraoral approach. Symptoms resolved following surgery. CONCLUSIONS A fractured styloid process is a rare event, but it needs to be recognized. If drug therapy does not work, surgical treatment is needed and has been shown to be effective. Surgical therapies include an intraoral approach and a transcervical approach. In the case presented here, 3D-CT was very useful for diagnosis and surgery selection.

Primary Ciliary Dyskinesia with Refractory Chronic Rhinosinusitis.

BACKGROUND Primary ciliary dyskinesia (PCD) is a rare genetic disease associated with abnormalities in the structure and function of cilia. The common clinical presentation of PCD is characterized by otitis media, chronic rhinosinusitis (CRS), chronic bronchitis, and infertility due to impaired ciliary motility. PCD is a complex disease and its diagnosis is complicated. However, there are some clinical features that are strong indicators of PCD, namely situs inversus, chronic otitis media, CRS, and chronic bronchitis with wet cough. CASE REPORT A 49-year-old male who had already received 3 operations for refractory CRS presented with nasal discharge, post nasal discharge, and chronic wet cough. Since childhood, he had suffered from otitis media, rhinosinusitis, and bronchitis. He also had a family history of CRS. He was diagnosed as having male infertility at another hospital, but the details were unknown. We performed a fourth surgery and obtained the nasal mucosa for electron microscope analysis during the operation. The transmission electron microscopic findings of the nasal cilia revealed several abnormalities in structure including a central complex defect, microtubular disorganization, and an inner dynein arm defect. Based on these findings and clinical courses, we made the definitive diagnosis of PCD. CONCLUSIONS When faced with refractory CRS cases with characteristic clinical symptoms that are associated with otitis media, chronic bronchitis, and infertility, clinicians should consider the possibility of PCD.

Successful treatment of eosinophilic otitis media associated with severe bronchial asthma with an anti-IL-5 monoclonal antibody, mepolizumab.

Eosinophilic otitis media (EOM), which is characterized by the accumulation of eosinophils in middle ear effusion and the middle ear mucosa, is a refractory type of otitis media that is often associated with asthma. Although an early diagnosis and appropriate treatment are necessary to prevent the progression of hearing loss in patients with EOM, there are currently no well-established treatments for this condition. We treated a 60-year-old male patient with asthma and EOM. The patient's asthma was poorly controlled, despite the use of high-dose inhaled corticosteroids, long-acting beta-agonist treatment, and the regular use of systemic corticosteroids. Mepolizumab, an anti-IL-5 monoclonal antibody, was started to treat the patient's refractory asthma. At 4 months after the initiation of mepolizumab treatment, the patient's asthma, hearing, and middle ear effusion improved. The present case suggests that mepolizumab therapy can control EOM and asthma.

Suppression of osteopontin functions by levocetirizine, a histamine H1 receptor antagonist, in vitro.

OBJECTIVES: Osteopontin (OPN), a multifunctional glycoprotein secreted from a wide variety of cells after inflammatory stimulation, is well accepted to contribute to the development of allergic diseases. However, the influence of histamine H1 receptor antagonists (antihistamines) on OPN functions is not well understood. The present study was undertaken to examine the influence of antihistamines on OPN functions in vitro. METHODS: Human nasal epithelial cells (5 × 10(5) cells) were stimulated with 250 ng/mL OPN in the presence of either desloratadine (DL), fexofenadine (FEX), or levocetirizine (LCT). The levels of OPN, GM-CSF, Eotaxin, and RANTES in 24 h culture supernatants were examined by ELISA. The influence of LCT on mRNA expression and transcription factor activation in cells were also examined by real-time RT-PCR and ELISA, respectively. KEY FINDINGS: The antihistamines examined significantly suppressed the production of GM-CSF, Eotaxin, and RANTES from cells after OPN stimulation. LCT also exhibited the suppression of mRNA expression for chemokines and transcription factor, NF- κ B and AP-1, activation, which were increased by the stimulation of cells with OPN. CONCLUSIONS: The suppressive activity of LCT on OPN functions on nasal epithelial cells may be responsible for the attenuating effect of the agent on allergic diseases.

Effect of histamine H1 receptor antagonists on TARC/CCL17 and MDC/CCL22 production from CD14+ cells induced by antigenic stimulation in vitro.

BACKGROUND: Thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) are accepted to be important molecules in the development and maintenance of allergic diseases. Although several types of histamine H(1) receptor antagonist (antihistamine) have been developed and used for the treatment of allergic diseases, the influence of antihistamines on TARC and MDC production is not well understood. OBJECTIVE: The present study was undertaken to examine the influence of antihistamines on TARC and MDC production from CD14+ cells after antigenic stimulation in vitro. METHODS: CD14+ cells prepared from patients with pollinosis to Japanese cedar pollen were stimulated with specific allergen extracted from Japanese cedar pollen (Cry j 1) in the presence of azelastine (AZE), ketotifen (KET), fexofenadine (FEX) and oxatomide (OXA) for 6 days. TARC and MDC levels in culture supernatants were examined by ELISA. We also examined the influence of FEX on TARC and MDC mRNA expression, phosphorylation of mitogen-activated protein kinases (MAPKs) and transcription factor activation in CD14+ cells after Cry j 1 stimulation. RESULTS: FEX at 250 ng/ml, which is almost equal to therapeutic blood levels, caused a significant inhibition of TARC and MDC production.However, AZE, OXA and KET required higher concentrations than their therapeutic blood levels to suppress production of these factors. FEX at 250 ng/ml also suppressed NF-κB activation, phosphorylation of p38 MAPK and extracellular signal-regulated kinases 1 and 2 and expression of mRNA for TARC and MDC. CONCLUSIONS: These results suggest that antihistamines, especially FEX, suppress CC chemokine production from CD14+ cells through interference with antigen-mediated signaling and result in favorable modification of allergic disease states or conditions.

Suppression of nitric oxide production from nasal fibroblasts by metabolized clarithromycin in vitro.

BACKGROUND: Low-dose and long-term administration of 14-membered macrolide antibiotics, so called macrolide therapy, has been reported to favorably modify the clinical conditions of chronic airway diseases. Since there is growing evidence that macrolide antibiotic-resistant bacteria's spreaders in the populations received macrolide therapy, it is strongly desired to develop macrolide antibiotics, which showed only anti-inflammatory action. The present study was designed to examine the influence of clarithromycin (CAM) and its metabolized materials, M-1, M-4 and M-5, on free radical generation from nasal polyp fibroblasts (NPFs) through the choice of nitric oxide (NO), which is one of important effector molecule in the development of airway inflammatory disease in vitro. METHODS: NPFs (5 × 105 cells/ml) were stimulated with 1.0 µg/ml lipopolysaccharide (LPS) in the presence of agents for 24 hours. NO levels in culture supernatants were examined by the Griess method. We also examined the influence of agents on the phosphorylation of MAPKs, NF-κB activation, iNOS mRNA expression and iNOS production in NPFs cultured for 2, 4, 8, and 12 hours, respectively. RESULTS: The addition of CAM (> 0.4 µg/ml) and M-4 (> 0.04 µg/ml) could suppress NO production from NPFs after LPS stimulation through the suppression of iNOS mRNA expression and NF-κB activation. CAM and M-4 also suppressed phosphorylation of MAPKs, ERK and p38 MAPK, but not JNK, which are increased LPS stimulation. On the other hand, M-1 and M-5 could not inhibit the NO generation, even when 0.1 µg/ml of the agent was added to cell cultures. CONCLUSION: The present results may suggest that M-4 will be a good candidate for the agent in the treatment of chronic airway inflammatory diseases, since M-4 did not have antimicribiological effects on gram positive and negative bacteria.

Tiotropium bromide inhibits TGF-ß-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro.

BACKGROUND: chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and structural alterations (ie, tissue remodeling) throughout the conducting airways, parenchyma, and pulmonary vasculature. Matrix metalloproteinases (MMPs) are extracellular degrading enzymes that play a critical role in inflammatory cell infiltration and tissue remodeling, but the influence of the agents that are used for the treatment of COPD on the production of MMPs is not well understood. PURPOSE: the present study aimed to examine the influence of tiotropium bromide hydrate (TBH) on the production of MMPs from lung fibroblasts (LFs) induced by transforming growth factor (TGF)-ß in vitro. METHODS: LFs, at a concentration of 5 × 10(5) cells·mL(-1), were stimulated with TGF-ß in the presence of various concentrations of TBH. MMP-1 and MMP-2 levels in culture supernatants were examined by enzyme-linked immunosorbent assay (ELISA), and MMP messenger ribonucleic acid (mRNA) expression was examined by real-time polymerase chain reaction (RT-PCR). The influence of TBH on TGF-ß signaling pathways was also analyzed by examining Smad activation and signaling protein phosphorylation by ELISA. RESULTS: TBH at more than 15 pg·mL(-1) inhibited the production of MMP-1 and MMP-2, but not tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2, from LFs, after TGF-ß stimulation. TBH also suppressed MMP mRNA expression through the inhibition of Smad activation and signaling protein, extracellular-signal-regulated kinase (ERK) 1 and 2, and c-Jun N-terminal kinase (JNK), phosphorylation. CONCLUSION: These results may suggest that TBH suppresses MMP production from LFs, through interference of TGF-ß-mediated signaling pathways and results in favorable modification of the clinical status of COPD.