Weight loss in nintedanib-treated patients with idiopathic pulmonary fibrosis.

Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF). Weight loss is recognized as an adverse event during nintedanib treatment, and is a common complication exploitable as a prognostic indicator of IPF. Here, we report a single-center, retrospective cohort study to assess body weight changes during nintedanib therapy in patients with IPF. Sixty-one patients treated with nintedanib for >6 months were included (45 males, mean age ± standard deviation 73.1 ± 7.4 years). Baseline body weight and body mass index were 60.1 ± 12.0 kg and 23.2 ± 3.5 kg/m2, respectively. Mean weight loss during the first 6 months of nintedanib treatment was significant (-3.2 ± 3.4 kg, p < 0.0001) with Common Terminology Criteria for Adverse Events (CTCAE) grades 0,1,2 or 3 of 30, 17, 13 and 1, respectively. Pulmonary function test records 6 months before nintedanib administration were available in a subset of patients (n = 40). Significant differences in weight change over the 6 months before-vs-after nintedanib administration were also observed in these patients [mean differences -2.5 ± 3.4 kg, 95% confidence interval (CI) -3.6, -1.4, p < 0.0001]. Multivariate analysis showed that only baseline body weight was significantly associated with weight loss of CTCAE grade ≧2 (odds ratio 0.921, 95% CI 0.854, 0.994). Median follow-up from starting nintedanib was 34.8 months. There was a significant difference in overall survival between patients with CTCAE grade ≧2-vs-grade<2 (median survival of 25.5 months and 55.2 months, p = 0.014). In the model adjusting for age, sex and lung function, weight loss CTCAE grade ≧2 was an independent predictor for all-cause mortality (hazard ratio 2.448, 95% CI 1.080-5.551). In conclusion, weight loss is an important issue for the management of patients with IPF treated with nintedanib.

Effects of oral health-related quality of life on total mortality: a prospective cohort study.

BACKGROUND: The effects of oral health on mortality have been reported; however, the association between mortality and Oral Health-Related Quality of Life (OHQOL) is unknown. We investigated the effect of OHQOL on total mortality in a cohort consisting of dentists. METHODS: In this cohort study, we analyzed data from the Longitudinal Evaluation of Multi-phasic, Odonatological and Nutritional Associations in Dentists study. We conducted a baseline survey of general and oral health factors. We called for 31,178 participants and collected responses from 10,256 participants. We followed up with 10,114 participants (mean age ± standard deviation, 52.4 ± 12.1 years; females, 8.9%) for 7.7 years, until March 2014, to determine the average total mortality. OHQOL was assessed using the General Oral Health Assessment Index (GOHAI). The total score was divided into quartiles (Q1 ≤ 51.6, Q2 = 51.7-56.7, Q3 = 56.8-59.9, and Q4 = 60.0), with higher GOHAI scores indicating better OHQOL (score range, 12-60). The association between OHQOL and total mortality was analyzed using the Cox proportional hazards model. RESULTS: We documented 460 deaths. Males with low GOHAI scores possessed a remarkably high risk of total mortality. The multivariate adjusted-hazard ratios (aHRs), were 1.93 (95% confidence interval [CI], 1.07 - 3.48) for Q1, 1.69 (95% CI, 0.90 - 3.17) for Q2, and 0.65 (95% CI, 0.29 - 1.46) for Q3, relative to Q4 (trend p = 0.001). The aHRs in the multivariate model with all background variables were 1.69 (95% CI, 1.15-2.46) for Q1, 1.53 (95% CI, 1.04-2.27) for Q2, and 1.09 (95% CI, 0.71-1.70) for Q3, relative to Q4 (trend p = 0.001). In females, there was no significant association between the quartiles, in both the multivariate-adjusted model (trend p = 0.52) and multivariate-adjusted model with all background variables (trend p = 0.79). CONCLUSIONS: A lower OHQOL indicated an increased risk of total mortality in dentists. OHQOL may be used as an indicator for selecting treatment plans and personalized care interventions, thus contributing to increased healthy life expectancy. TRIAL REGISTRATION: Aichi Cancer Center, Nagoya University Graduate School of Medicine, and Hiroshima University (Approval numbers: 33, 632-3, 8-21, and E2019-1603).

Intranasal Administration of IL-27 Ameliorates Nasal Allergic Responses and Symptoms.

BACKGROUND: Interleukin 27 (IL-27) is an initiator of the Th1 response and inhibits inflammatory responses. In a mouse model of asthma, administration of IL-27 reduced eosinophil numbers in bronchoalveolar lavage fluid and airway hyperresponsiveness. However, it is unclear whether administration of IL-27 can inhibit symptoms of allergic diseases and allergic rhinitis as a therapeutic agent. Therefore, we investigated the in vivo effect of IL-27 on nasal symptoms and allergic rhinitis. METHODS: Mice sensitized and challenged with ovalbumin (OVA) antigen received intranasal administration of IL-27. RESULTS: Intranasal administration of IL-27 significantly suppressed the number of sneezes and nasal rubbing movements, the number of eosinophils, OVA-specific T-cell responses in cervical lymph nodes, production of IL-4 and IL-5, and OVA-specific IgE in sera, compared with the administration of PBS alone. The production of IL-10 and IL-35, the percentage of CD25+Foxp3+ cells, and the gene expression of Foxp3 in mice that received intranasal administration of IL-27 were also significantly higher than those in mice that received only PBS. CONCLUSIONS: This study showed, for the first time, that intranasal administration of IL-27 inhibited nasal allergic responses and symptoms even after the establishment of allergic rhinitis and suggested that IL-27 is useful as an intranasal therapeutic agent.

Proton Pump Inhibitor Ameliorates Taste Disturbance among Patients with Laryngopharyngeal Reflux: A Randomized Controlled Study.

Patients with laryngopharyngeal reflux (LPR) were reported to suffer from hypogeusia that affects quality of life. Proton pump inhibitor (PPI) is a useful drug in the treatment of LPR, but its effect on hypogeusia is not known. We therefore assessed the effects of PPI or a histamine H2 receptor antagonist (H2 blocker) on hypogeusia among patients with LPR. Both PPI and H2 blocker could inhibit acid reflux. LPR was diagnosed with reflux finding score and reflux symptom index. The visual analogue scale (VAS) of taste disturbance symptoms and the gustatory tests were assessed before and 8 weeks after treatment with esomeprazole, a PPI (20 patients, aged 50.0 ± 1.7 years) or famotidine, a H2 blocker (20 patients, aged 47.1 ± 1.8 years). There were no significant differences in VAS scores and recognition thresholds for four basic tastes between the two groups before treatment. Only PPI therapy significantly decreased the VAS scores, suggesting the improvement of taste perception. Moreover, PPI therapy significantly decreased recognition thresholds for bitter taste in the anterior tongue (chorda tympani nerve area) and the thresholds in the posterior tongue (glossopharyngeal nerve area) for salty, sour, and bitter tastes. By contrast, H2-blocker therapy caused no significant changes of thresholds in the anterior tongue, but improved the threshold only for bitter in the posterior tongue, the value of which was however significantly higher than that in PPI group. In conclusion, PPI could ameliorate hypogeusia by improving bitter, salty, and sour tastes among patients with LPR.

A novel allergen-specific therapy with regulatory T cells induced by CD40-silenced dendritic cells.

BACKGROUND: We previously reported that dendritic cells (DCs) transfected with CD40 siRNA and pulsed by ovalbumin (OVA) (CD40-silenced OVA DCs) inhibited allergic responses through facilitation of regulatory T cells (Tregs). However, to our knowledge, no prior study has examined allergen-specific therapy by administration of siRNA-induced Tregs for the control of allergy. OBJECTIVE: We aimed to investigate the effect of Tregs induced in vitro on allergic responses and symptoms in vivo. METHODS: Mice were treated with Tregs (OVA DCs-induced Tregs) induced by CD40-silenced OVA DCs or Tregs (nonantigen DCs-induced Tregs) induced by DCs transfected with CD40 siRNA and pulsed with no antigen, and the effects of these Tregs on allergic responses were estimated. RESULTS: Administration of nonantigen DCs-induced Tregs prevented not only OVA-induced allergy but also keyhole limpet hemocyanin-induced allergy. Administration of OVA DCs-induced Tregs significantly reduced the number of sneezes and nasal rubbing movements, eosinophilia in the nasal mucosa, and the level of OVA-specific IgE in mice with OVA-induced allergy, compared with CD40-silenced nonantigen DC-induced Tregs in numbers 20 times greater, even in mice with established allergic rhinitis. Furthermore, Tregs induced by CD40-silneced DCs pulsed with Cry j 1, a major allergen of Japanese cedar pollen, inhibited Japanese cedar-induced allergy. CONCLUSIONS: This study shows for the first time that both antigen-independent Tregs and antigen-specific Tregs can be induced by siRNA, and that therapy with siRNA-induced Tregs inhibits allergic responses and symptoms. It also shows that antigen-specific Tregs have more potent effects in inhibiting allergic responses than antigen-nonspecific Tregs.

Synergic Effects of CD40 and CD86 Silencing in Dendritic Cells on the Control of Allergic Diseases.

BACKGROUND: We previously reported that siRNA-induced CD40-silenced dendritic cells (DCs) inhibit allergic responses and symptoms. However, more potent therapies are needed. To our knowledge, synergic effects of gene silencing in DCs by ≥2 siRNAs have not been reported to control allergic diseases. Therefore, we investigated the synergistic effects of the silencing of CD40 and CD86 in DCs on allergic responses. METHODS: Mice were treated with CD40/CD86-silenced DCs, which were transfected with CD40/CD86 siRNAs and pulsed with ovalbumin (OVA) antigen. The effects of these DCs on allergic symptoms and allergic responses were estimated. RESULTS: The administration of CD40/CD86-silenced OVA-pulsed DCs significantly inhibited the number of sneezes and nasal rubbing movements, the number of eosinophils in the nasal mucosa, and the level of OVA-specific IgE when compared with those for CD40- or CD86-silenced OVA-pulsed DCs alone (p < 0.01). These inhibitory effects were detected before sensitization as well as after the establishment of allergic rhinitis. CD40/CD86-silenced OVA-pulsed DCs did not inhibit KLH-induced allergies. Foxp3 gene expression was significantly upregulated in CD40-silenced DCs compared to in CD86-silenced DCs (p < 0.01). IL-4 production by T cells was suppressed more substantially when using CD86-silenced DCs than with CD40-silenced DCs (p < 0.01). CONCLUSIONS: These results indicate, for the first time, that siRNA-induced CD40/CD86-silenced antigen-specific DCs have greater inhibitory effects against allergic responses than those of CD40- or CD86-silenced antigen-specific DCs alone. This study also suggests that the synergic effects of gene silencing in DCs by ≥2 siRNAs are useful for the control of allergic diseases. Thus, owing to the synergistic effects, CD40 and CD86 silencing has the potential to substantially improve the treatment of allergic diseases.

Combined measurements of fractional exhaled nitric oxide and nasal nitric oxide levels for assessing upper airway diseases in asthmatic patients.

BACKGROUND: Despite the close linkage between rhinitis, chronic rhinosinusitis (CRS) and asthma, relevant biomarkers of both upper and lower airway inflammation are rare. METHODS: Patients with asthma (without upper airway disease [UAD; n = 24], with rhinitis [n = 25], CRS [n = 24], and nasal polyps [n = 2]), isolated rhinitis (n = 13), isolated CRS (n = 13), and 10 healthy controls were prospectively recruited. Fractional exhaled nitric oxide (NO) levels at 50 mL/s (FeNO50), nasal NO levels, Lund-Macay-scores of sinus computed tomography and an asthma control questionnaire (ACQ) were evaluated. RESULTS: Asthma was associated with higher FeNO50 levels irrespective of the UAD category. FeNO50 levels were higher in asthmatics with CRS (median: 54.0 ppb) than those with rhinitis (35.2 ppb, p = 0.02) and those without UAD (34.3 ppb, p = 0.002). Nasal NO levels were higher in rhinitis patients than other UAD categories, irrespective of the asthma concomitance. Nasal NO levels were higher in asthmatics with rhinitis (112.8 ppb) than those without UAD (67.2 ppb, p = 0.001) and those with CRS (57.6 ppb, p < 0.0001). A receiver-operating-characteristic curve analysis for detecting comorbid allergic rhinitis (AR) in asthmatics showed a high area under the curve (0.87). Nasal NO levels were positively correlated with FeNO50 levels (ρ = 0.56, p = 0.003) in asthmatics with rhinitis. In contrast, they were negatively correlated with the Lund-Macay (ρ = -0.46, p = 0.03) and ACQ scores (ρ = -0.52, p = 0.009) in asthmatics with CRS. CONCLUSIONS: Higher nasal NO levels reflect the presence of AR, irrespective of asthma concomitance. Higher FeNO50 levels reflect the presence of CRS and asthma. These NO measurements are useful for assessing comorbid UAD in asthmatics.

Sleep Disturbance and Hyperactivity Detected by Actigraphy in Rats with Allergic Rhinitis or Attention-Deficit Hyperactivity Disorder.

Actigraphy is an easy and noninvasive method used to monitor human ultradian cycles. However, to our knowledge, it has been not applied to experiments with rodents. Therefore, using actigraphy, we assessed the ultradian cycles and behavior of rats. Rats with or without allergic rhinitis wore an actigraphy device, and triaxial acceleration was recorded. The counts that represent physical activity were lower from 8:00 to 20:00 than those from 20:00 to 8:00 in control rats, suggesting that their sleep phase was from 8:00 to 20:00 and their awake phase from 20:00 to 8:00. The counts from 8:00 to 10:00 were significantly higher in allergic rhinitis rats than in control rats (p < 0.01), suggesting the presence of difficulty with sleep induction in rats with allergic rhinitis. The counts from 18:00 to 20:00 were also significantly higher in allergic rhinitis rats than in control rats (p < 0.05), suggesting the presence of early awakening in rats with allergic rhinitis. Moreover, the counts were significantly higher in allergic rhinitis rats than in control rats from 20:00 to 8:00. These results suggest that rats with allergic rhinitis experienced hyperactivity disorder during the daytime. Additionally, hyperreactivity and difficulty with sleep induction were observed in 6-hydroxydopamine-lesioned rats, an animal model of attention-deficit hyperactivity disorder. This study shows for the first time that actigraphy can be successfully used for behavioral analysis in rodents. These rat models could be useful for analyzing the mechanisms involved in sleep disturbances and hyperactivity disorder.

Repair of Orbital Floor Fracture With Modified Transnasal Endoscopic Approach Through Anterior Space to Nasolacrimal Duct.

OBJECTIVES: Endoscopic approach provides excellent magnification and visualization, and a purely transnasal approach is minimally invasive method. However, it is very difficult to repair anterior and lateral fractures with the previous transnasal endoscopic approaches, since repair of orbital fractures is managed through the middle meatus and ostium from the posterior side of the nasolacrimal duct with side-viewing endoscope and curved instruments. Therefore, the authors used modified transnasal endoscopic approach as an alternative for repair of orbital floor fractures in order to effectively reach the lateral or anterior fracture of the orbital floor with straight endoscope and instruments endoscopically. METHODS: Modified transnasal endoscopic approach through anterior space to nasolacrimal duct was performed in patients with orbital floor fracture, when patients rejected extranasal approach and reconstruction could not be performed by the previous purely transnasal endoscopic approach. After removal of the medial maxillary bone, the lateral wall of nose was shifted in the medial direction to allow wider access to the maxillary sinus. The bone fragments entrapping the orbital content are removed carefully, and correction of periorbita is performed. After surgery, patients were asked whether they have symptoms and/or complications. RESULTS: This modified approach was performed in 15 patients (10 males and 5 females). Mean age at surgery was 37.6 years with a range between 17 and 67. Double vision disappeared in all patients. CONCLUSIONS: This novel approach appears to be a safe and effective technique for the repair of orbital floor fractures.

Intranasal administration of IL-35 inhibits allergic responses and symptoms in mice with allergic rhinitis.

BACKGROUND: IL-35 was recently identified as an anti-inflammatory cytokine. We previously reported that recombinant fusion protein of murine IL-35 and human IgG1 Fc fragment (rIL-35) reduced Th2 cytokines (IL-4 and IL-5) in vitro. However, it is unclear whether IL-35 can attenuate nasal allergic responses and symptoms of allergic rhinitis in vivo. METHODS: To investigate the in vivo effect of IL-35 on allergic rhinitis in mice, mice were sensitized with ovalbumin (OVA). Intranasal administration of rIL-35 and intranasal challenge of OVA were then performed. Nasal symptoms were estimated after the last nasal challenge. Nasal tissue and cervical lymph nodes (CLN) were collected. OVA-specific IgE in sera, OVA-specific T cell response, and the production of cytokines (IL-4, IL-5, and IL-10) stimulated by the OVA antigen were measured. The transcription level of Foxp3 and the frequency of CD4+CD25+ regulatory T cells were also measured. RESULTS: rIL-35 significantly inhibited the number of sneezes and nasal rubbing movements. It also reduced the number of eosinophils in the nasal mucosa and significantly decreased the level of OVA-specific IgE, the OVA-specific T cell proliferation, and the production of IL-4 and IL-5. Furthermore, rIL-35 significantly increased the production of IL-10, the transcription level of Foxp3, and the frequency of CD4+CD25+ regulatory T cells. CONCLUSIONS: This study showed for the first time that rIL-35 inhibits nasal allergic responses and symptoms in mice, and that rIL-35 increases IL-10, Foxp3, and CD4+CD25+ regulatory T cells in CLN. This study also suggests that intranasal administration of IL-35 can attenuate allergic rhinitis.

Effect of Japanese cedar-specific sublingual immunotherapy on allergen-specific TH2 cell counts in blood.

BACKGROUND: The contribution of antigen-specific TH cells in peripheral blood to immunologic mechanisms underlying sublingual immunotherapy (SLIT) remains unclear, partly because of the lack of a standardized method for the analysis of this rare lymphocyte subset. OBJECTIVE: To clarify the role of antigen-specific TH cells during SLIT using a sensitive method analyzing activation marker CD154-positive TH cells with multicolor flow cytometry. METHODS: We assessed antigen-specific TH cells using multicolor flow cytometry based on the expression of the activation marker CD154 and intracellular cytokines in patients with Japanese cedar pollinosis receiving SLIT at baseline and during the first pollen season after the initiation of SLIT. RESULTS: A total of 18 patients between 12 and 44 years of age were enrolled in the present study. Of these, 8 patients received SLIT (SLIT group) and 10 patients received symptomatic treatment only (control group). Although seasonal pollen exposure significantly increased the number of Japanese cedar-specific interleukin 5- and interleukin 4-producing TH cells in the control group (P < .01 for both), SLIT ameliorated this increase in the SLIT group (P = .64 and P = .84, respectively). CONCLUSION: The present study indicates that allergen-specific TH2 cells in peripheral blood are involved in mechanisms underlying SLIT. The analysis of antigen-specific TH cells using multicolor flow cytometry based on the expression of the activation marker CD154 represents a sensitive and relatively simple, standardized method for monitoring peripheral antigen-specific TH cells during allergen-specific immunotherapy.

The case of huge simple pulmonary aspergilloma that responded remarkably to drug therapy.

The first choice of treatment for simple pulmonary aspergilloma is surgery, but in clinical practice, many cases find surgery difficult. We report a case of simple pulmonary aspergilloma in which significant improvement was observed with pharmacological treatment alone, despite initially presenting with a large fungus ball.

Association between the number of existing teeth and maintenance dialysis therapy: A cross-sectional study of adult male dentists.

Dental caries and periodontal disease are typical oral diseases frequently observed in patients with renal diseases. Tooth loss is an outcome of dental caries and periodontal disease, and the number of existing teeth is an indicator of oral health status. However, the association between the number of existing teeth and end-stage kidney disease (ESKD) has not been investigated in detail. This study aimed to investigate the association between oral health status, expressed by the number of existing teeth, and ESKD. We analyzed data from the second survey of the Longitudinal Evaluation of Multi-phasic, Odontological, and Nutritional Associations in Dentists, a cohort study conducted among members of the Japan Dental Association. From August 2016 to July 2017, self-administered questionnaires were mailed to 16,128 male dentists and 8,722 responded. Among them, 7,479 men with complete data on age, number of existing teeth, and ESKD were included in the analysis. Multivariate logistic regression analysis was conducted, with ESKD as the dependent variable and the number of existing teeth (≥23 teeth and <23 teeth) as the independent variable. Subgroup analysis by age (<65 years and ≥65 years) was also conducted. The <23 teeth group had a significantly higher rate of ESKD than did the ≥23 teeth group. After adjusting for age, body mass index, smoking habits, hypertension, and diabetes mellitus, there was no significant association between having <23 teeth and ESKD in all participants. However, the subgroup analysis revealed a significant association after adjustment for covariates in participants aged <65 years but not in those aged ≥65 years. In conclusion, having <23 teeth was associated with the risk of requiring maintenance dialysis therapy among Japanese men aged <65 years. Therefore, tooth loss may be associated with renal function decline.

Long-Term Outcome of Autotransplantation of a Complete Root Formed a Mandibular Third Molar.

Autogenous tooth transplantation is a procedure to reposition an autogenous tooth to another extraction area or surgically created recipient site. The autotransplantation procedures have been documented well in the literature, and the survival rate of the transplanted teeth was reported to be more than 90% after ten years. Therefore, autotransplantation might have been overlooked as a treatment option. The purpose of this case report is to evaluate the long-term (29-year) success and periodontal stability of the tooth autotransplantation from the mandibular third molar to the second molar. A 24-year old female presented to a clinic with a large caries lesion with periapical radiolucnecy on to tooth #18. The tooth was extracted with the site and treated with autogenous tooth transplantation from #17 with a complete root form. Endodontic treatment was completed 3 months post autotransplantation; the final prosthesis was placed 6 months postoperatively. The patient has shown excellent oral hygiene care and high compliance with the regular maintenance recall program. The transplanted tooth has been still functioning without any symptoms. Radiographic and clinical examinations revealed stable periodontal and endodontic conditions over the 29 years after the procedure. This case report showed the long-term success of autotransplantation of the mandibular third molar with a closed root apex to the second molar site. Autotransplantation can be an option when an adequate donor site is available to reconstruct the occlusion after the tooth extraction.

Tooth brushing, tooth loss, and risk of upper aerodigestive tract cancer: a cohort study of Japanese dentisits.

Previous studies have focused on the association between poor oral health and upper aerodigestive tract (UADT) cancer. However, whether toothbrushing and tooth loss are associated with UADT cancer risk is still unclear. Therefore, we investigated the association between toothbrushing or tooth loss and UADT cancer in the Longitudinal Evaluation of Multi-phasic, Odontological, and Nutritional Associations in Dentists (LEMONADE) cohort study. From 2001 to 2006, we recruited 20,445 dentists (mean age ± standard deviation, 51.8 ± 12.0 years; 1,607 women [7.9%]) and followed for incidence or mortality of UADT cancer through March 2014. Information on lifestyle and oral health was collected by the baseline questionnaire. The Cox proportional hazards model was used to estimate hazard ratios (HRs) for UADT cancer and corresponding 95% confidence intervals (CI) for brushing frequency and tooth loss with adjustment for covariates. During the mean follow-up of 9.5 years, we confirmed 62 incident or fatal cases of UADT cancer. Infrequent toothbrushing (< 2 times/day) was significantly associated with increased risk of UADT cancer (multivariate HR = 2.13, 95% CI: 1.04-4.37). On the contrary, tooth loss was not significantly correlated with UADT cancer risk; multivariate HR was 1.03 (95% CI: 0.41-2.61) for loss of 15-27 teeth and 1.37 (0.50-3.75) for that of 28 teeth compared to tooth loss of 0-14 teeth. In conclusion, Infrequent toothbrushing was significantly associated with the risk of UADT cancer.

Intranasal administration of regulatory dendritic cells is useful for the induction of nasal mucosal tolerance in a mice model of allergic rhinitis.

BACKGROUND: Intranasally administered dendritic cells (DCs) migrate into blood and thymus to induce immune responses. Regulatory dendritic cells (DCs) are also useful agents for allergy control. However, to the best of our knowledge, the effects of intranasal administration of regulatory DCs on allergy have not been reported until now. Therefore, we examined the effects of intranasal route of administration of CD40-silenced DCs on allergic responses and compared these with the effects of other administration routes, based on our previous findings on the inhibitory effects of CD40-silenced DCs on allergic responses. METHODS: Mice with allergic rhinitis were treated intranasally, subcutaneously, intraperitoneally, or intravenously with CD40-silenced ovalbumin (OVA)-pulsed DCs that were transfected with CD40 siRNAs and pulsed with OVA antigen. The effects of these DCs on allergic reactions and symptoms were estimated. RESULTS: Intranasal, subcutaneous, intraperitoneal, or intravenous administration of OVA-pulsed CD40-silenced DCs inhibited allergic responses and symptoms in mice. Furthermore, intranasal administration of OVA-pulsed CD40-silenced DCs significantly reduced allergic symptoms and the number of eosinophils in the nasal mucosa compared with subcutaneous, intraperitoneal, or intravenous administration of these DCs. Intranasal administration of OVA-pulsed CD40-silenced DCs resulted in significantly up-regulated IL-10, IL-35, and Foxp3 expression, and enhanced the percentage of CD11c+CD40- and CD4+CD25+ cells within the cervical lymph nodes compared to subcutaneous, intraperitoneal, or intravenous routes of administration. CONCLUSIONS: We believe that this is the first report to demonstrate that regulatory DCs infiltrate into the cervical lymph nodes after intranasal administration of these cells and that intranasal administration of regulatory DCs is more effective for the induction of tolerance in the nasal mucosa than subcutaneous, intraperitoneal, or intravenous administration.

Longitudinal Evaluation of Multi-phasic, Odontological and Nutritional Associations in Dentists (LEMONADE Study): study design and profile of nationwide cohort participants at baseline.

BACKGROUND: To examine the association between oral health and general well-being, we are currently conducting a nationwide cohort study comprising members of the Japan Dental Association (JDA). Herein, we describe the study design and the profile of the participants at baseline. METHODS: From 2001 through 2006, the participants completed a baseline questionnaire that surveyed factors related to lifestyle, general health, and oral health. Morbidity and mortality have been monitored by using information from fraternal insurance programs operated by prefectural dental associations. All respondents provided written, informed consent for participation and the use of their insurance data. RESULTS: A total of 21,272 JDA members participated in the baseline survey (response rate, 36.2%). Their mean age +/- SD was 52.3 +/- 12.3 years; 8.0% were women. Among the respondents, 30.2% of men and 10.7% of women were current smokers; 73.5% of men and 44.8% of women were current drinkers. The cohort scored higher on oral health indices than did the general Japanese population: dentists were more likely to brush their teeth > or =3 times/day, to have > or =20 teeth, to have fewer lost teeth, to be free from periodontal diseases, and to have higher General Oral Health Assessment Index scores. There was, however, considerable inter-individual variation in scores on the indices. CONCLUSIONS: More than one-third of JDA members participated in the study. Their oral average health status was better than that of the general population. Nevertheless, it will be possible to compare morbidity and mortality between those with better and worse scores on oral health indices.

Japanese Cedar Pollen-Specific IgA in Nasal Secretions and Nasal Allergy Symptoms.

OBJECTIVE:: IgA-dependent degranulation of eosinophils and positive correlation between IgA and eosinophil cytotoxic protein levels in nasal secretions have been reported. However, the association between IgA and allergic reactions remains unclear. Therefore, we evaluated the changes in Japanese cedar-specific IgA levels and allergy symptoms after Japanese cedar pollen scattering in symptomatic and asymptomatic individuals sensitized to Japanese cedar pollen. METHODS:: Nasal secretion and serum samples were collected from 31 participants (21 symptomatic and 10 asymptomatic participants) in January (preseason) and March (peak season). Japanese cedar-specific IgA or IgE levels were measured using ELISA with diamond-like carbon-coated chips. RESULTS:: The ratio of Japanese cedar pollen-specific IgA to total IgA (rIgA) in the nasal secretions of symptomatic participants increased significantly in March compared with that in January ( P < .01); however, the ratio of specific IgE to total IgE (rIgE) in nasal secretions did not. rIgA in nasal secretions among asymptomatic participants also did not increase during pollen season. rIgA in nasal secretions was significantly correlated with nasal allergic symptoms (r = 0.82; P < .0001) with no significant correlation between rIgE and symptoms. CONCLUSIONS:: To our knowledge, this is the first study to show an association between nasal symptoms and rIgA in nasal secretions, suggesting that rIgA is useful as an antigen-specific biomarker for allergic rhinitis or pollinosis. Furthermore, rIgA values in nasal secretions do not increase in asymptomatic participants sensitized to Japanese cedar during the pollen season.