[DEVELOPMENT AND VALIDATION OF QUALITY OF LIFE QUESTIONNAIRE FOR PARENT BURDEN OF CHILDREN WITH FOOD ALLERGY].

OBJECTIVE: Quality of life (QOL) questionnaires for parents of children with food allergies have been developed in the United States and Europe. However, no original Japanese QOL questionnaire has been developed till date. We aimed to develop an original questionnaire to evaluate the QOL in parents of children with food allergies in Japan. METHODS: We collected QOL-related questions from parents of children with food allergies aged 0-15 years, and created a primary questionnaire. Responses to the primary questionnaire were obtained from the parents again, and question items were reduced using factor analysis to create a secondary questionnaire comprising eight items. In addition to the secondary questionnaire, responses to the Food Allergy QOL Questionnaire-Parent Form (FAQLQ-PF) Japanese version, Parent reported Health-Related QOL in children and adolescents (KINDL) and Health-related QOL (SF-8) were obtained from parents to assess the validity of the secondary questionnaire. RESULTS: A total of 407 parents completed all questionnaires. The secondary questionnaire scores were positively correlated with those of FAQLQ-PF and weakly negatively correlated with the KINDL and SF-8 mental component summary scores. Parents of children with food allergies with ≥3 culprit foods or severe reactions to daily foods, a history of anaphylaxis, and those carrying adrenaline autoinjectors scored higher and had lower QOL. CONCLUSION: The developed original questionnaire is a valid QOL questionnaire for Parents of children with food allergies.

Prognostic value of pretreatment inflammatory biomarkers in patients with laryngeal cancer.

OBJECTIVES: The systemic inflammatory response is strongly involved in the progression of malignant tumors, and it is useful for predicting survival time and determining therapeutic effects. The inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are used to assess post-treatment survival and recurrence in various malignant tumors.(Walsh et al., 2005; Burt et al., 2011; Smith et al., 2009) 1,2,3 These indicators may be effective as predictive markers for head and neck malignancies. METHODS: The participants were 125 glottic laryngeal and supraglottic cancer cases who received primary treatment in our department from 2010 to 2016. The NLR, LMR, and PLR for each patient were calculated in addition to the association with overall survival (OS) rate, disease-specific survival (DSS) rate, and laryngeal preservation rate for tumor location, T and N classification, TNM stage classification, treatment, and smoking. We investigated whether inflammatory biomarkers are useful for predicting prognosis. RESULTS: The cutoff values for NLR, LMR, and PLR on the ROC curve were 1.88, 5.57, and 108, respectively. Multivariate analysis with LMR 5.57 as the cutoff value showed significant differences in OS, DSS, and laryngeal preservation. However, setting the cutoff values for NLR 1.88 and PLR 108 showed significant differences only in OS and laryngeal preservation. CONCLUSION: LMR may be a total survival predictor of laryngeal cancer, including OS, DSS, and laryngeal preservation.

Impact of IL-17-producing γδ T cells on chronic otitis media induced by nontypeable Haemophilus influenzae in a mouse model.

Nontypeable Haemophilus influenzae (NTHi) is considered a major pathogen underlying middle ear infection. This study aimed to investigate the impact of IL-17 on chronic otitis media (COM) induced by NTHi in mice. NTHi was inoculated into the tympanic bulla with eustachian tubal obstruction. Middle ear effusions (MEEs) and tissues were collected on days 3, 14, and at 1, 2, and 6 months after injection. The expression of interleukin-17A (IL-17A) in MEEs was significantly elevated compared to that in the control group at the translational and transcriptional levels during the experiments. The quantities of IL-17-producing γδ T cells were significantly increased compared to that in the control group during COM, but that of Th17 cells did not. Depletion of γδ T cells by anti-γδ T-cell receptor (TCR) monoclonal antibody (mAb) administration significantly decreased the bacteria counts and the concentrations of IL-1ß, IL-6, IL-17A, TNF-α, and IL-10 in MEEs. Our results suggest that IL-17 may play an important role in prolonging the inflammation in the middle ear in COM and that IL-17-producing γδ T cells may contribute to the exacerbated inflammatory response in the middle ear. In this study, anti-γδ TCR mAb administration was found to improve chronic middle ear inflammatory conditions.

Nocturnal Scratching and Quality of Sleep in Children with Atopic Dermatitis.

Itching due to atopic dermatitis causes sleep disorders in children, but its pathology is unknown. The aim of this study is to investigate nocturnal scratching as an indirect index of itching during sleep and its relationship with depth of sleep in children with atopic dermatitis. Nocturnal scratching was measured in a total of 20 children with atopic dermatitis, using a smartwatch installed with the application Itch Tracker. Depth of sleep was analysed using polysomnography. The severity of atopic dermatitis was scored using Eczema Area and Severity Index (EASI) and Patient-Oriented Eczema Measure (POEM). The number and time of nocturnal scratching measured by Itch Tracker had a significantly positive correlation with EASI scores, whereas POEM scores were not correlated with EASI scores. Mean sleep efficiency was 90.0% and scratching episodes (n = 67) started mainly during the awake stage or light sleep stages. In the scratching episodes that started during sleep stages (n = 34), the sleep stage changed to a lighter one or to the awake stage in 35.5% of episodes. Itch Tracker is applicable to measure nocturnal scratching in children. Nocturnal scratching can deteriorate quality of sleep by changing the sleep stage to a lighter one or to the awake stage.

A laser-assisted endoscopic approach to pyriform sinus fistula via fibrin glue cauterization.

In the past, the general treatment method for pyriform sinus fistula was its removal by open surgery; however, in recent years, endoscopic surgery has become more common. We report two cases where laser surgery was performed using an endoscope and recurrence was prevented using fibrin glue. Both cases involved 3-year-old girls who underwent laser ablation of a pyriform sinus fistula under an endoscope, after which the site was closed with fibrin glue. No recurrence was observed in either case, and the postoperative course was uneventful. This approach is presented as a non-invasive and effective treatment for pyriform sinus fistula.

Changes in clinical features of food-related anaphylaxis in children during 5 years.

Background: Despite being frequently recommended, adrenaline auto-injectors (AAIs) are insufficiently prescribed and used for the prehospital management of anaphylaxis. Objective: This study aimed to investigate recent changes in the clinical features and prehospital management of food-related anaphylaxis in children. Methods: We retrospectively compared the clinical features of children who were hospitalized for food-related anaphylaxis in 2013 and 2018. The patients' medical records were reviewed for causative foods, triggers, location, AAI prescription, and/or use, wheezing on admission, and treatment. Results: Overall, 62 consecutive patients (43 males; median age, 5.6 years) hospitalized in 2018 were compared with 57 patients (37 males; median age, 4.3 years) hospitalized in 2013. There were no significant differences between the cohorts in age, gender, causative foods, or wheezing on admission. Cow's milk, wheat, and egg represented over half of the causative foods in both groups. Compared with 2013, the incidence of anaphylaxis decreased at home but increased at nurseries and schools in 2018. Exercise was a significantly more common trigger for anaphylaxis in 2018. Furthermore, a significant increase was observed in AAI administration by lay helpers or the patients themselves and in ambulance transportation. After admission, intramuscular adrenaline was administered to 26 patients in 2013 and 12 patients in 2018. Patients receiving prehospital adrenaline were significantly less likely to require in-hospital adrenaline injections. Conclusion: Food-related anaphylaxis triggered by exercise and AAI use have increased. Hence, raising awareness and educating caregivers, patients, teachers, and medical professionals are essential for the optimal management of this disorder.

Effect of age on exercise-induced bronchoconstriction in children and adolescents with asthma.

OBJECTIVE: The relationship between exercise-induced bronchoconstriction (EIB) and exertional dyspnea in children and adolescents is yet to be fully established. This study examined whether indicators of fractional exhaled nitric oxide (FeNO), forced expiratory volume in 1 s (FEV1) percent predicted at baseline, and dyspnea are useful for predicting children and adolescents with EIB. METHODS: We enrolled 184 children and adolescents diagnosed with asthma (mean age 11.2 years); participants were divided into two groups according to age (12 years) and were subjected to a 6-min exercise challenge test. Lung function tests and modified Borg scale scores were used to examine perceptions of dyspnea at 0, 5 and 15 min after exercise. RESULTS: Among children, the maximum percentage drop in FEV1 after exercise correlated significantly with FeNO (adjusted ß = 2.3, P < 0.001) and with the perception of dyspnea at 5 min after exercise (adjusted ß = 1.9, P < 0.001). Among adolescents, the maximum percentage drop in FEV1 correlated with FeNO (adjusted ß = 2.7, P = 0.007) and with lung function (FEV1, percent predicted; adjusted ß = -0.28, P = 0.006). Children with EIB had significantly stronger dyspnea after exercise than did children without EIB. Adolescents even without EIB may experience more exertional dyspnea than children without EIB. CONCLUSIONS: Overall, our findings indicated that EIB was associated with FeNO and exertional dyspnea in asthmatic children. By contrast, EIB was associated with FEV1 percent predicted at baseline and FeNO but not with exertional dyspnea in asthmatic adolescents.

Unilateral Sensorineural Hearing Loss in Children Associated With Sjögren's Syndrome.

The occurrence of unilateral sensorineural hearing loss (SNHL) during school age is relatively rare and accounts for approximately 6% of all deafness in childhood. We present two cases involving children who were diagnosed with SNHL associated with Sjögren's syndrome (SS). Case 1: An eight-year-old girl with an approximately two-year clinical history of gradual hearing loss was diagnosed with SNHL associated with SS based on histological findings of inflammation in the salivary glands and the presence of serum anti-Sjögren's syndrome-A antibody. Case 2: An eight-year-old boy with acute idiopathic thrombocytopenic purpura in whom unilateral hearing loss, which was not associated with any problems in daily life, was detected during hospitalization and who was finally diagnosed with SNHL and SS. Steroid treatment was ineffective for both patients. The previously unrecognized combination of SNHL with SS should be considered in the diagnosis of unilateral SNHL, even in children.

Phase variation with altering phosphorylcholine expression of nontypeable Haemophilus influenzae affects bacteria clearance and mucosal immune response in the middle ear and nasopharynx.

OBJECTIVES: Nontypeable Haemophilus influenzae (NTHi) is a chief pathogen in both acute otitis media and otitis media with effusion. Phosphorylcholine (ChoP) is expressed on lipooligosaccharides, and ChoP has phase variation, which is related to its adhesion to and invasion of epithelial cells in the upper airway. However, little is known about the role of ChoP expression. We examined the kinetics of the mucosal clearance of NTHi from the nose and middle ear and the mucosal immune response to NTHi infection by comparing ChoP(+) and ChoP(-) strains in a mouse model of middle ear and nasal challenge. METHODS: Six-week-old male BALB/c mice were subjected to bacterial challenge in the middle ear and nasopharynx. Mice were inoculated with a suspension of a ChoP(+) strain or ChoP(-) strain of NTHi. On days 1, 3, and 7 after inoculation, the middle ear wash (MEW) and nasal wash (NW) were harvested from each group. The samples were used for bacterial counts and the supernatant was used to measure the level of cytokines and C-reactive protein (CRP). RESULTS: MEWs in the ChoP(+) strain group had significantly higher bacterial counts than those in the ChoP(-) strain group on day 1. However, bacteria were eradicated in the ChoP(+) strain group on day 7. NWs in the ChoP(+) strain group had higher bacterial counts than those in the ChoP(-) strain group during the experiment, however, there was no significant difference between the two strains. The levels of cytokines were significantly higher in the ChoP(-) strain group than in the ChoP(+) strain group in MEWs, but these cytokine levels were low in NWs. The CRP concentration in the ChoP(-) group was high on day 7 in the MEWs. In NWs, the CRP concentration was low in all groups during the experiment. CONCLUSION: ChoP expression of NTHi changes the organism susceptible to killing by CRP, and the ChoP(+) strain might be gradually eradicated from the middle ear via the CRP-complement cascade, but not from nasopharynx. Based on our findings, phase variation by altering Phosphorylcholine expression of nontypeable Haemophilus influenzae affects bacteria clearance and mucosal immune response in the middle ear and nasopharynx.

Annual changes in the prevalence of asthma may be related to air pollution in Fukuoka: 29†years of observation.

The relationship between the annual changes of the prevalence of bronchial asthma (BA) and that of concentrations of air pollutants has not been reported. We studied the annual prevalence of BA, remission of BA, and wheeze in children at the same five elementary schools in Fukuoka city, Japan, in October to November from 1988 to 2016 by the same methods using the same questionnaire. Annual changes in the prevalence of asthma among boys were related to changes in the air concentrations of NO (r=0.708), NO2 (r=0.665) suspended particulate matter (SPM) (r=0.803), and smoking rate (r=0.741), but there were no such relationships among girls. Annual changes in the prevalence of wheeze were related to changes of NO, NO2, SPM, and smoking rate among boys and girls (NO: r=0.650, 0.660; NO2: r=0.556, 0.490; SPM: r=0.582, 0.518; smoking rate: r=0.656, 0.593, respectively) (all of the above are significant with p<0.05). There was no relationship between remission of BA and any of the pollutants. Annual changes in the prevalence of boys' BA and boys' and girls' wheeze among first-grade children (age 6 or 7 years) in Fukuoka were correlated with changes in the concentration of air pollutants (SPM, NO, NO2 or smoking rate). Recent decrease of asthma prevalence in this area might be related to the decreasing tendency of air pollutant concentration. The causal relationship between the two will need to be verified in the future.

Pregnancy level of estradiol attenuated virus-specific humoral immune response in H5N1-infected female mice despite inducing anti-inflammatory protection.

Estradiol, a major female steroid produced during pregnancy, has been reported to protect ovariectomized animals against H1N1 influenza infections via its anti-inflammatory effects. However, it remains unclear why pregnant women with high gestational estradiol levels are highly susceptible to influenza infections. This study was aimed to investigate the effects of pregnancy level of estradiol on female immunity against H5N1 infection in Balb/c mice. A sex-dependent susceptibility to H5N1 infection (higher morbidity and higher mortality) was observed in both pregnant and non-pregnant female mice as compared to male mice. Subcutaneous implantation of estradiol pellets increased serum estradiol concentrations of non-pregnant female mice to the pregnancy level. These mice were protected from H5N1 infection through downregulation of pulmonary pro-inflammatory cytokines. However, the production of virus-specific antibodies after infection was significantly delayed in estradiol-implanted mice when compared to placebos. Virus-specific IgG-secreting and IL-4-secreting cells were also reduced in estradiol-implanted mice. Similarly, lower antibody titers to seasonal vaccine antigens were found in pregnant women as compared to non-pregnant females without hormone usage. Our results indicate that estradiol levels equivalent to those found during pregnancy have divergent effects on female immunity against influenza, highlighting the importance of vaccination during pregnancy to prevent severe influenza infections.

Interaction Between Regulatory T Cells and Antibody-Producing B Cells for Immune Responses at the Upper Respiratory Mucosa Against Nontypeable Haemophilus influenzae: In Vitro Assay Model.

OBJECTIVES: The aim of this study was to investigate the effect of regulatory T cells (Tregs) on B-cell immune responses against outer membrane protein (OMP) from nontypeable Haemophilus influenzae (NTHi) in vitro, to clarify its exact mechanism from an immunologic standpoint. METHODS: Mice were vaccinated intranasally with OMP to induce OMP-specific immune responses in the nasal mucosa. Mononuclear cells (MNCs) were collected from the nasal mucosa, and Tregs and helper T (Th) cells were isolated separately from the spleens of those mice. Three different cell culture groups were allocated: MNCs cocultured with Tregs, MNCs cocultured with Th cells, and MNCs cultured alone. At 24 and 72 hours after cell culture, the concentrations of various cytokines and antibodies in culture supernatants were measured to assess the effects of Tregs and Th cells on B-cell responses. Cytokine levels and specific anti-OMP antibody levels in culture media were determined using enzyme-linked immunosorbent assay. CD69 or CD80 expression on B220-positive cells was detected using flow cytometric analysis. RESULTS: Th1 and Th2 cytokine concentrations were significantly elevated in the 3 groups incubated with OMP from 24 to 72 hours. Additionally, interleukin-10 levels were significantly higher in the Treg and Th groups than in the control group. Levels of OMP-specific immunoglobulin A did not differ significantly among the groups. The ratios of CD69+B220+ B2 cells were nearly the same in the 3 groups; however, the ratio of CD80+B220+ B2 cells was higher in the control group than in the Treg and Th groups during incubation. CONCLUSIONS: Tregs and Th cells did not affect OMP-specific immunoglobulin A production in this study. However, these cells may partially inhibit B-cell functions, such as T-cell activation. These inhibitory effects may be related to interleukin-10.

Toll-like receptor 4 plays an important role to enhance bacterial clearance from the nose in synergy with triggering receptor expressed on myeloid cells (TREM)-1 expression on polymorphonuclear neutrophils.

OBJECTIVE: Acute rhinosinusitis (ARS) is among the most common infectious diseases. Neutrophils play a major role in innate host defenses against pathogenic microorganisms such as fungi and bacteria. Recently, in neutrophils, ligation of the triggering receptor expressed on myeloid cells (TREM)-1 was found to activate the full spectrum of neutrophil effector mechanisms, including the release of inflammatory mediators, degranulation, phagocytosis, and oxidative burst in synergy with Toll-like receptors (TLRs). In this study, we investigated the effect of TREM-1 on the functions of neutrophils in relation to TLR4 in a nasal and nasopharyngeal inflammation mouse model via nontypeable Haemophilus influenzae (NTHi) intranasal inoculation. METHODS: We used C3H/HeJ (TLR4-deficient) mice, which arose spontaneously and have non-functional TLR4 protein, and normal wild-type (WT) C3H/HeN mice. Mice were inoculated intranasally with NTHi (107 cfu/mouse) to investigate the effects of TLR4 on the function of Neutrophils. We examined the kinetics of bacterial clearance and inflammatory cell infiltration in nasal washes at 6, 12, 24, and 72 h after inoculation. The expression of TREM-1 on neutrophils, and TREM-1 mRNA expression in neutrophils in the nasal washes were examined by flow cytometric analysis and RT-PCR. RESULTS: Bacterial counts of NTHi from nasal washes were significantly lower in WT mice than in TLR4-mutant mice after inoculation. The numbers of inflammatory cells in nasal washes were significantly higher in WT mice at 6 h, 12 h, and 24 h after inoculation than in TLR4-deficient mice. The expression of TREM-1 protein on neutrophils and the mRNA levels were greater in WT mice than in TLR4-mutant mice. The concentrations of soluble TREM-1 in WT nasal washes were also significantly higher than in those of TLR4-deficient mice. CONCLUSION: TREM-1 may play an important role together with TLR4 in the nasopharyngeal clearance of NTHi by neutrophils. Further studies will need to clarify the innate immune responses of neutrophils via TLR4 to prevent NTHi infection.

Monophosphoryl lipid A enhances nontypeable Haemophilus influenzae-specific mucosal and systemic immune responses by intranasal immunization.

OBJECTIVE: Acute otitis media (AOM) is one of the most common infectious diseases in children. Nontypeable Haemophilus influenzae (NTHi) is Gram-negative bacteria that are considered major pathogens of AOM and respiratory tract infections. In this study, we used monophosphoryl lipid A (MPL), a toll-like receptor (TLR) 4 agonist, as an adjuvant to induce mucosal immune responses against NTHi to enhance bacterial clearance from the nasopharynx. METHODS: Mice were administered 10 µg outer membrane protein (OMP) from NTHi and 0, 10, or 20 µg MPL intranasally once a week for 3 weeks. Control mice were administered phosphate-buffered saline alone. After immunization, these mice were challenged with NTHi. At 6 and 12 h after bacterial challenge, the mice were killed and nasal washes and sera were collected. The numbers of NTHi- and OMP-specific antibodies were quantified by enzyme-linked immunosorbent assay. RESULTS: The MPL 10 and 20 µg group produced a significant reduction in the number of bacteria recovered from the nasopharynx at 12 h after bacterial challenge compared to the control group. OMP-specific IgA titers were also augmented in the MPL groups compared to the control and OMP groups. CONCLUSION: MPL is suitable for eliciting effective mucosal immune responses against NTHi in the nasopharynx. These results demonstrate the possibility of an adjuvant that involves stimulation of the innate immune system by TLR4 agonists such as MPL for mucosal vaccination.

Differential Effects of Prior Influenza Exposures on H3N2 Cross-reactivity of Human Postvaccination Sera.

BACKGROUND: Effectiveness of seasonal influenza vaccines mainly depends upon how well vaccine strains represent circulating viruses; mismatched strains can lead to reduced protection. Humans have complex influenza exposure histories that increase with age, which may lead to different postvaccination responses to emerging influenza variants. Recent observational studies also suggest that prior vaccination may influence the performance of current seasonal vaccines. METHODS: To elucidate the effects of age and influenza preexposures on cross-reactivity of vaccination-induced human antibodies, we generated antigenic maps based on postvaccination hemagglutination inhibition titers against representative H3 variants circulating during the 2015-2016, 2014-2015, and 2012-2013 influenza seasons. RESULTS: Antigenic maps determined using sera from subjects 18-64 and ≥65 years of age correlated well with each other but poorly with those determined using sera from children. Antigenic maps derived from human postvaccination sera with H1 influenza preexposure also correlated poorly with those derived from sera with neither H1 nor type B influenza preexposure, and the correlation lessened considerably over time. In contrast, antigenic maps derived from human postvaccination sera with only type B influenza preexposure consistently showed good correlation with those derived from sera with neither H1 nor type B influenza preexposure. CONCLUSIONS: Our results suggest an age-specific difference in human postvaccination responses. Our findings also suggest that prior exposure to H1 or type B influenza may differentially affect cross-reactivity of vaccination-induced H3-specific hemagglutination inhibition antibody responses, and consequently might affect vaccine effectiveness. Our study highlights the need to study the impact of prior exposure on influenza vaccine performance.

Accumulation of Regulatory T Cells and Chronic Inflammation in the Middle Ear in a Mouse Model of Chronic Otitis Media with Effusion Induced by Combined Eustachian Tube Blockage and Nontypeable Haemophilus influenzae Infection.

Nontypeable Haemophilus influenzae (NTHi) is associated with chronic otitis media (COM). In this study, we generated a murine model of COM by using eustachian tube (ET) obstruction and NTHi (10(7) CFU) inoculation into the tympanic bulla, and we investigated the relationship between regulatory T cells (Treg) and chronic inflammation in the middle ear. Middle ear effusions (MEEs) and middle ear mucosae (MEM) were collected at days 3 and 14 and at 1 and 2 months after inoculation. Untreated mice served as controls. MEEs were used for bacterial counts and to measure the concentrations of cytokines. MEM were collected for histological evaluation and flow cytometric analysis. Inflammation of the MEM was prolonged throughout this study, and the incidence of NTHi culture-positive MEE was 38% at 2 months after inoculation. The levels of interleukin-1ß (IL-ß), tumor necrosis factor alpha, IL-10, and transforming growth factor ß were increased in the middle ear for up to 2 months after inoculation. CD4(+) CD25(+) FoxP3(+) Treg accumulated in the middle ear, and the percentage of Treg in the MEM increased for up to 2 months after inoculation. Treg depletion induced a 99.9% reduction of bacterial counts in MEEs and also significantly reduced the ratio of NTHi culture-positive MEE. The levels of these cytokines were also reduced in MEEs. In summary, we developed a murine model of COM, and our findings indicate that Treg confer infectious tolerance to NTHi in the middle ear.

H3N2 Mismatch of 2014-15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps.

The poor performance of 2014-15 Northern Hemisphere (NH) influenza vaccines was attributed to mismatched H3N2 component with circulating epidemic strains. Using human serum samples collected from 2009-10, 2010-11 and 2014-15 NH influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (HAI) antibody responses against recent H3 epidemic isolates. All three populations (children, adults, and older adults) vaccinated with the 2014-15 NH egg- or cell-based vaccine, showed >50% reduction in HAI post-vaccination geometric mean titers against epidemic H3 isolates from those against egg-grown H3 vaccine strain A/Texas/50/2012 (TX/12e). The 2014-15 NH vaccines, regardless of production type, failed to further extend HAI cross-reactivity against H3 epidemic strains from previous seasonal vaccines. Head-to-head comparison between ferret and human antisera derived antigenic maps revealed different antigenic patterns among representative egg- and cell-grown H3 viruses characterized. Molecular modeling indicated that the mutations of epidemic H3 strains were mainly located in antibody-binding sites A and B as compared with TX/12e. To improve vaccine strain selection, human serologic testing on vaccination-induced cross-reactivity need be emphasized along with virus antigenic characterization by ferret model.

Pili play an important role in enhancing the bacterial clearance from the middle ear in a mouse model of acute otitis media with Moraxella catarrhalis.

Moraxella catarrhalis is a Gram-negative aerobic diplococcus that is currently the third most frequent cause of bacterial acute otitis media (AOM) in children. In this study, we developed an experimental murine AOM model by inoculating M. catarrhalis in the middle ear bulla and studied the local response to this inoculation, and modulation of its course by the pili of M. catarrhalis. The pili-positive and pili-negative M. catarrhalis showed differences in bacterial clearance and infiltration of inflammatory cells in the middle ear. Pili-negative M. catarrhalis induced a more delayed and prolonged immune response in the middle ear than that of pili-positive M. catarrhalis. TLR2, -4, -5 and -9 mRNA expression was upregulated in neutrophils that infiltrated the middle ear cavity during AOM caused by both pili-positive and pili-negative bacteria. TLR5 mRNA expression and TLR5 protein in the neutrophils were induced more robustly by pili-positive M. catarrhalis. This immune response is likely to be related to neutrophil function such as toll-like 5-dependent phagocytosis. Our results show that mice may provide a useful AOM model for studying the role of M. catarrhalis. Furthermore, we show that pili play an important role in enhancing M. catarrhalis clearance from the middle ear that is probably mediated through neutrophil-dependent TLR5 signaling.

Bilateral endoscopic medial maxillectomy for bilateral inverted papilloma.

Inverted papilloma (IP) is a benign tumor of the nasal cavity and paranasal sinuses that is unilateral in most cases. Bilateral IP, involving both sides of the nasal cavity and sinuses, is extremely rare. This paper describes a large IP that filled in both sides of the nasal cavity and sinuses, mimicking association with malignancy. The tumor was successfully treated by bilateral endoscopic medial maxillectomy (EMM). The patient is without evidence of the disease 24 months after surgery. If preoperative diagnosis does not confirm the association with malignancy in IP, endoscopic sinus surgery (ESS) should be selected, and ESS, including EMM, is a good first choice of the treatment for IP.