Exploring the relationship between plasma substance P and glottal incompetence in the elderly.

We speculated that increased blood-plasma levels of Substance P may serve as an indicator of glottal incompetence, which is usually indicated by reduced maximum phonation time. We performed an initial study to test the plausibility of this hypothesis. Patients with dysphonia caused by glottal incompetence were asked to perform vocal exercises for six months to reduce glottal incompetence and we compared the plasma concentration of Substance P before and after the vocal exercise to detect correlation between maximum phonation time and plasma concentration of Substance P. Based on the results, we further hypothesized that patients exhibiting dysphonia with maximum phonation time less than 14 s, in particular less than 10 sec, caused by glottal incompetence may have increased plasma concentration of Substance P with the results of elevated thresholds of cough reflex associated with subclinical aspiration in airways. Further study is needed on patients with decreased Substance P levels, with low scores on Activities of Daily Living and who are hospitalized with aspiration pneumonia.

Computed tomography findings of paranasal sinuses in patients with eosinophilic granulomatosis with polyangiitis: Comparison with other eosinophilic sinus diseases and clinical relevance of their severity.

BACKGROUND: Although paranasal sinuses are one of the most representative organs affected by eosinophilic granulomatosis with polyangiitis (EGPA), they have not been studied sufficiently. The aim of this study was to compare computed tomography (CT) findings in paranasal sinuses of EGPA with those of other eosinophilic sinus diseases and elucidate the clinical relevance of their severity. METHODS: CT findings of paranasal sinuses in EGPA patients prior to therapeutic intervention (n = 30) were evaluated using the Lund-Mackay staging (LMS) system and compared with those of three control diseases [(NSAID-exacerbated respiratory disease (N-ERD), aspirin-tolerant asthma, and eosinophilic chronic rhinosinusitis without asthma (ECRS)]. We divided EGPA patients into three groups based on their LMS scores and examined their association with disease manifestation. RESULTS: Total scores of the LMS system in EGPA were significantly lower than those of N-ERD and ECRS without asthma. There was a large variation in total LMS scores in EGPA, suggesting considerable heterogeneity of their sinus lesions. Although EGPA with low LMS system scores showed only minor findings in maxillary and anterior ethmoid regions, those with high LMS system scores were characterized by high scores in the ostiomeatal complex. However, the frequencies of patients with a Five-Factor Score ≥2 and with cardiac involvement were significantly higher for EGPA with low LMS system scores. CONCLUSIONS: Although paranasal sinus lesions in EGPA were less severe than those of other eosinophilic sinus diseases, their milder CT findings may be associated with a higher frequency of extra-respiratory organ involvement.

Exploring the Relation between Glottal Closure and Plasma Substance P: A Study Protocol.

Glottal incompetence, i.e., reduced ability to produce effective glottal closure, is a problem often associated with aging. The study protocol is presented to determine whether blood substance P (SP) serves as an indicator of glottal closure function among the elderly. SP is involved in the neuromuscular mechanisms of cough; reduced concentration of SP may be a marker for increased risk of aspiration pneumonia. The antihypertensive angiotensin-converting enzyme inhibitor, which also inhibits degradation of SP, has been found to be effective in preventing aspiration pneumonia by strengthening the cough reflex. In this study, we will employ National Hospital Organization self-controlled vocal exercise (NHOEx), which has been shown to improve glottal closure by strengthening the laryngeal adduction muscles. We hypothesize that improved glottal closure by NHOEx may lead to the increase in the plasma concentration of SP, which reflects effective cough reflex. Maximum phonation time (MPT), an indicator of glottal closure, will be measured to assess improvement of glottis-closing function. The study will include 180 patients over 65 years old with dysphonia, dysphagia, or MPT of less than 15 seconds. Based on the speculation that the improved MPT may be associated with changes in SP expression, we will measure the plasma SP before and after 6-month treatment of glottal incompetence using NHOEx. The goal is to verify the reliability of SP as an indicator for glottal closure and swallowing function. Measurement of plasma SP may be helpful for earlier detection of subjects with higher risk of aspiration pneumonia among the elderly.

Vocal Hygiene Education Program Reduces Surgical Interventions for Benign Vocal Fold Lesions: A Randomized Controlled Trial.

OBJECTIVES/HYPOTHESIS: Vocal fold polyps and nodules are common benign laryngeal lesions. Currently, the Japanese health insurance system covers surgical interventions. However, the establishment of more cost-effective conservative methods is required, because healthcare costs are viewed as a major concern, and the government and taxpayers are demanding more economical, effective treatments. In this situation, more suitable vocal hygiene education may be important for the success of cost-effective conservative treatment. In this study, we developed a novel reinforced vocal hygiene education program and compared the results of this program with those of previous methods of teaching vocal hygiene. STUDY DESIGN: Multicenter randomized controlled trial. METHODS: Patients who visited a National Hospital Organization (NHO) hospital for the surgical indication of hoarseness were included in the study. Before undergoing surgery, 200 patients with benign vocal fold lesions (vocal fold polyps/nodules) were enrolled and randomly allocated to the NHO-style vocal hygiene educational program (intervention group) or control education program (control group). Two months after enrollment, the patients in both groups underwent laryngeal fiberscopic examinations to determine whether the benign lesions had resolved or whether surgery was indicated for the vocal fold polyps/nodules. RESULTS: After 2 months, in the intervention group, the proportion of lesion resolution (61.3%) was significantly greater than that in the control group (26.3%) (P < .001, Fisher exact test). CONCLUSIONS: Our results clearly indicate that the quality and features of the education program could affect the outcome of the intervention. We found that a reinforced vocal hygiene education program increased the rate of the resolution of benign vocal fold polyps and nodules in a multicenter randomized clinical trial. LEVEL OF EVIDENCE: 1b Laryngoscope, 2593-2599, 2018.

Independent exercise for glottal incompetence to improve vocal problems and prevent aspiration pneumonia in the elderly: a randomized controlled trial.

OBJECTIVES: To evaluate the effect of a self-controlled vocal exercise in elderly people with glottal closure insufficiency. DESIGN: Parallel-arm, individual randomized controlled trial. METHODS: Patients who visited one of 10 medical centers under the National Hospital Organization group in Japan for the first time, aged 60 years or older, complaining of aspiration or hoarseness, and endoscopically confirmed to have glottal closure insufficiency owing to vocal cord atrophy, were enrolled in this study. They were randomly assigned to an intervention or a control group. The patients of the intervention group were given guidance and a DVD about a self-controlled vocal exercise. The maximum phonation time which is a measure of glottal closure was evaluated, and the number of patients who developed pneumonia during the six months was compared between the two groups. RESULTS: Of the 543 patients enrolled in this trial, 259 were allocated into the intervention group and 284 into the control; 60 of the intervention group and 75 of the control were not able to continue the trial. A total of 199 patients (age 73.9 ±7.25 years) in the intervention group and 209 (73.3 ±6.68 years) in the control completed the six-month trial. Intervention of the self-controlled vocal exercise extended the maximum phonation time significantly ( p < 0.001). There were two hospitalizations for pneumonia in the intervention group and 18 in the control group, representing a significant difference ( p < 0.001). CONCLUSION: The self-controlled vocal exercise allowed patients to achieve vocal cord adduction and improve glottal closure insufficiency, which reduced the rate of hospitalization for pneumonia significantly. CLINICAL TRIAL: gov Identifier-UMIN000015567.

Differences in urinary leukotriene E4 levels and distribution of eosinophils between chronic rhinosinusitis patients with aspirin-intolerant and -tolerant asthma.

OBJECTIVE: Urinary leukotriene E4 (U-LTE4) concentrations are significantly elevated in patients with aspirin-intolerant asthma (AIA). However, the relationship between the clinicopathogenetic features of eosinophilic rhinosinusitis and U-LTE4 concentration remains unknown. Here we examined the relationship between U-LTE4 level and eosinophil in chronic rhinosinusitis. METHODS: We measured the U-LTE4 concentrations and eosinophil counts in ethmoidal and maxillary sinuses and peripheral blood in 30 asthmatic patients (including 15 AIA patients). RESULTS: Eosinophil counts in ethmoidal sinuses and peripheral blood were markedly higher in asthmatic patients than in controls. Although there were no significant differences between eosinophil counts in maxillary and ethmoidal sinuses for ATA group, eosinophil counts were higher in ethmoidal sinus compared to that in maxillary sinus in the AIA group (P<.05). Eosinophil counts were higher in the maxillary than in ethmoidal sinuses for control patients (P<.05). Despite low correlation between eosinophil counts in peripheral blood and eosinophil counts in maxillary sinus (rs=0.4323, P<.001), moderate correlation was observed between eosinophil counts in peripheral blood and eosinophil counts in ethmoidal sinus (rs=0.5249, P<.0001). Basal U-LTE4 concentrations were higher in AIA patients than in those with aspirin-tolerant asthma. Despite low correlation between eosinophil counts and U-LTE4 concentration in maxillary sinus (rs=0.3849, P<.01), moderate correlation was observed between eosinophil counts and U-LTE4 concentrations in ethmoidal sinus (rs=0.4736, P<.001). CONCLUSION: We describe the differences in U-LTE4 and other parameters in AIA compared to ATA, and correlation among parameters. We demonstrate that eosinophil-dominant inflammation starts in ethmoidal sinus clinicopathogenetically in CRS with asthma. U-LTE4 concentration was not exclusively associated with eosinophil counts in ethmoidal sinus. Eosinophils in ethmoidal sinus may be a major production site for CysLTs, particularly in AIA. CRS with AIA is assumed to be characterized by leukotriene-eosinophil cross-interaction in ethmoidal sinus.

Effect of fermented milk prepared with two probiotic strains on Japanese cedar pollinosis in a double-blind placebo-controlled clinical study.

There has been much interest in the potential of using probiotic bacteria for treating allergic diseases. A double-blind, placebo-controlled study was conducted to examine the effectiveness of Lactobacillus GG (LGG) and L. gasseri TMC0356 (TMC0356) in alleviating Japanese cedar pollinosis (JCP), a seasonal allergic rhinitis caused by Japanese cedar pollen. Fermented milk prepared with the tested bacteria or placebo yoghurt was administered to 40 subjects with a clinical history of JCP for 10 weeks. Subjective symptoms, self-care measures and blood samples were compared between the two groups. Peripheral blood mononuclear cells (PBMCs) were collected from seven patients with JCP and in vitro cytokine production by the isolated PBMCs was analysed in the presence of heat-killed lactic acid bacteria. Consumption of the fermented milk significantly decreased the mean symptom score for nasal blockage after 9 weeks (P<0.05) and mean symptom-medication scores after 9 and 10 weeks when compared with the placebo group (P<0.01 and P<0.05 respectively). The tested strains of lactic acid bacteria affected cytokine production by isolated PBMCs in vitro in a strain-dependent manner. LGG significantly inhibited IL-4 and IL-5 production by PBMCs stimulated by both Cry j 1 and PHA. TMC0356 only suppressed IL-5 production stimulated by PHA. The fermented milk prepared with LGG and TMC0356 might be beneficial in JCP because of its effect on nasal blockage. The effects of LGG and TMC0356 might arise at least partly from their specific down-regulation of the human Th2 immune response.

[The methodological aspects of nasal and exhaled nitric oxide levels in adult Japanese asthmatics].

BACKGROUND: Because both allergic rhinitis and asthma are caused by eosinophilic airway inflammation, using the same method to measure the eosinophilic inflammation of both the upper and lower airway would be advantageous. The levels of nitric oxide in exhaled air (FeNO) and nasal air (nNO) are useful as noninvasive markers of eosinophilic airway inflammation. Although the off-line method of measuring these parameters is easier and more useful than the on-line method, studies using the off-line method are rare in Japan. METHODS: In Study 1, we measured the levels of nNO and FeNO in 9 healthy controls and 9 subjects with allergic rhinitis, to validate the methodology for using the off-line method to measure nNO. In Study 2, we measured the nNO and FeNO levels of and performed spirometry on 69 stable asthmatics treated with inhaled corticosteroid. RESULTS: In Study 1, nNO levels were significantly increased in patients with allergic rhinitis compared with healthy subjects (31.0 [20.8 to 41.2] versus 7.4 [0.0 to 14.8] ppb {median [95% confidence interval]}, p=0.018). The 69 patients with asthma that comprised the study population in Study 2 were classified as asthmatics with rhinitis (treatment-naïve, n=14; treated with antiallergic drugs, n=11; treated with intranasal corticosteroid, n=19) and asthmatics without rhinitis (n=15). Although FeNO did not differ among groups, nNO was significantly increased in treatment-naïve asthmatics with rhinitis compared with patients with asthma only (26.5 [17.1 to 35.9] versus 8.0 [-1.1 to 17.1] ppb, p=0.033). CONCLUSION: nNO levels measured by the off-line method are useful markers of allergic rhinitis.

Clinical features of asthmatic patients with increased urinary leukotriene E4 excretion (hyperleukotrienuria): Involvement of chronic hyperplastic rhinosinusitis with nasal polyposis.

BACKGROUND: The urinary leukotriene E4 (U-LTE4) concentration is significantly increased in patients with aspirin-intolerant asthma (AIA). However, the relationship between the clinicopathogenetic factors of asthma and the U-LTE4 concentration remains undetermined. OBJECTIVE: We sought to examine the clinical features of asthmatic patients with increased excretion levels of U-LTE4 (hyperleukotrienuria). METHODS: We measured the U-LTE4 concentrations in 137 asthmatic patients (including 64 patients with AIA) who were in clinically stable condition. A U-LTE4 concentration of 150 pg/mg creatinine or greater (mean U-LTE4 + 3 SDs of normal healthy control subjects) was indicative of hyperleukotrienuria. RESULTS: The basal concentration of U-LTE4 was significantly higher in the patients with AIA than in those with aspirin-tolerant asthma (ATA; median, 227.2 vs 90.3 pg/mg creatinine; P <.01). Compared with normal leukotrienuria in the patients with AIA, hyperleukotrienuria in the patients with AIA was associated with older age and decrease in pulmonary function. On the other hand, compared with normal leukotrienuria in the patients with ATA, hyperleukotrienuria in the patients with ATA was associated with severe asthma and chronic hyperplastic rhinosinusitis with nasal polyposis (CHRS/NP), which are well-known symptoms of the aspirin triad, as well as hypereosinophilia and anosmia. The patients with ATA with CHRS/NP excreted U-LTE4 at significantly high concentrations. There were significant decreases in the U-LTE4 concentrations before and after the sinus surgery in both the AIA and ATA groups (P <.05). CONCLUSION: Cysteinyl leukotrienes are not strictly associated with aspirin intolerance itself but rather with clinical features, such as CHRS/NP, that are similar to those seen in AIA. CHRS/NP might be involved in cysteinyl leukotriene overproduction in asthmatic patients.

A case of multiple neurofibroma of the larynx and cervical esophagus.

A case of multiple neurofibroma of the larynx and cervical esophagus is reported. Key points concerning the follow-up observations of this case are described.