Allergen-specific immunotherapy enhances CD8+ CD25+ CD137+ regulatory T cells and decreases nasal nitric oxide.

BACKGROUND: 4-1BB (CD137), a member of the inducible tumor necrosis factor receptor (TNFR) family, is expressed on regulatory T (Treg) cells and regulates Treg cells to control allergic inflammation. Pam3CSK4, a synthetic TLR2 ligand that can expand CD8+ Treg function, is a promising adjuvant for allergen immunotherapy (IT). We examined whether Dermatophagoides pteronyssinus (Der p) IT and Pam3CSK4 could enhance CD8+  CD25+  CD137+ Treg suppressive function to decrease nasal nitric oxide (nNO) levels. METHODS: Nasal symptom scores, nNO levels, PBMCs, and inferior turbinate biopsies were obtained from 40 mite-sensitive perennial allergic rhinitis (PAR) patients before and after one year of Der p IT and 30 non-allergic control subjects. CD137 expression on CD8+  CD25+ T cells and suppressive function of CD8+  CD25+  CD137+ Tregs was measured using flow cytometry. Cytokine levels were analyzed by ELISA. Inducible nitric oxide synthase production by nasal epithelial cells after co-culturing with CD8+  CD25+  CD137+ T cells was analyzed by Western blotting. RESULTS: Der p IT improved nasal symptom scores, decreased nNO levels, and increased CD137 expression on CD8+ T cells in PBMCs and nasal mucosa. Pam3CSK4 expanded the CD8+  CD25+  CD137+ population in PBMCs. Pam3CSK4-stimulated CD8+  CD25+  CD137+ Tregs induced IL-10 and TGF-ß and suppressed CD4+  CD25- T-cell proliferation mainly by cell contact inhibition. CD8+  CD25+  CD137+ Tregs cultured with nasal epithelial cells suppressed Der p 2-induced iNOS production. Silencing CD137 in sorted CD8+  CD25+ T cells decreased Pam3CSK4-activated Foxp3 expression. CONCLUSION: Der p IT expanded CD8+  CD25+  CD137+ Tregs and decreased nNO levels. Induced CD137 expression on CD8+  CD25+ Tregs by Pam3CSK4 stimulation may help suppress allergic inflammation during IT.

Nasal nitric oxide is a useful biomarker for acute unilateral maxillary sinusitis in pediatric allergic rhinitis: A prospective observational cohort study.

BACKGROUND: Nasal nitric oxide (nNO) could be a biomarker for nasal passage inflammation and sinus ostial patency. We have aimed to investigate the nNO concentration and the effect of antibiotic therapy in children with perennial allergic rhinitis (PAR) children with/without acute bacterial sinusitis. METHODS: We enrolled a cohort of 90 and 31 children with PAR, without and with acute unilateral maxillary sinusitis, and 79 normal children. Acute bacterial maxillary sinusitis was diagnosed based on clinical signs and symptoms, radiographic examination and nasal fibroendoscopy. Rhinitis control assessment test (RCAT), rhinomanometry, nNO and fractional exhaled NO (FENO) measurements were performed before and 2 weeks after antibiotic therapy. RESULTS: We found significantly higher mean nNO levels, FENO values, and total nasal resistance in children with PAR than in normal children (p â€‹< â€‹0.05). Acute unilateral maxillary sinusitis was associated with lower lesion-side nNO levels, higher FENO values, total nasal resistance, and poor RCAT scores (p â€‹< â€‹0.05). In multivariate analysis, age, IgE, and acute maxillary sinusitis were significant factors influencing nNO levels in children with PAR. The lesion-side nNO levels, FENO values, total nasal resistance, and RCAT scores were reversed after antibiotic therapy (p â€‹< â€‹0.05). The lesion-side nNO levels were significantly correlated to nasal obstructive scores (r â€‹= â€‹0.59, p â€‹< â€‹0.05) and expiratory nasal resistance (r â€‹= â€‹-0.54, p â€‹< â€‹0.05) in the acute maxillary sinusitis. A cut-off nNO value of 538 â€‹ppb showed 100% sensitivity and 94.9% specificity, to predict PAR from normal children. An nNO value of 462 â€‹ppb showed 100% sensitivity and 100% specificity to discriminate between the lesion-side and the unaffected sinus-side in PAR children with acute unilateral maxillary sinusitis. CONCLUSIONS: We conclude that the obstruction of NO from the sinus into the nasal passage is the likely explanation for the decreased lesion-side nNO levels in acute unilateral maxillary sinusitis. nNO is a non-invasive biomarker with high sensitivity to diagnose and monitor treatment responses of PAR patients with acute rhinosinusitis. Both nNO and FENO levels return to baseline following antibiotic therapy, supporting the "one airway one disease" concept.

Influence of family communication structure and vanity trait on consumption behavior: a case study of adolescent students in Taiwan.

The purpose of this research was to study the relationship between family communication structure, vanity trait, and related consumption behavior. The study used an empirical method with adolescent students from the northern part of Taiwan as the subjects. Multiple statistical methods and the SEM model were used for testing the hypotheses. The major findings were: (1) Socio-orientation has a significant effect on how physical appearance is viewed, and concept-orientation has a significant positive effect on achievement vanity. (2) how physical appearance is viewed has a significant positive effect on all dimensions of materialism, concerns about clothing, and use of cosmetics. (3) Achievement vanity has a significant positive relationship with price-based prestige sensitivity and concerns regarding clothing. The findings have implications for marketing theory as well as for practical applications in marketing.

Complement regulatory protein CD46 induces autophagy against oxidative stress-mediated apoptosis in normal and asthmatic airway epithelium.

Autophagy plays a major role in defending against oxidative stress in respiratory epithelial cells. The complement regulatory protein CD46 can enhance autophagy and decrease local complement activation at sites of inflammation. This study investigated the mechanism by which CD46 protects against oxidative stress-mediated apoptosis in respiratory epithelium in asthmatic patients. Nasal mucosa samples were obtained from 60 adults with mild asthma who received turbinectomy and 30 controls. A decreased expression of CD46 and increased apoptosis were noted in the damaged nasal epithelium from the asthmatic patients. Primary epithelial cells cultured with Dermatophagoides pteronyssinus 2 showed decreased CD46 and increased cleaved CASPASE-3A expressions. Crosslinking CD46 mAb could induce the formation of autophagosomes and LC3-II expression in primary epithelial cells. CD46 engagement could induce autophagy against hydrogen peroxide-induced epithelial cell death, whereas the autophagy inhibitor 3-methyladenine decreased this effect. In addition, CD46 engagement decreased the expressions of PRO-IL-1ß and NLRP3, enhanced the expression of scaffold protein GOPC, and diminished hydrogen peroxide-induced 8-OHdG, IL-1ß and IL-6 production. Silencing ATG5 in human lung epithelial A549 cells decreased CD46-activated autophagy with LC3-II. CD46 induced autophagy and decreased the oxidative stress-mediated apoptosis of respiratory epithelium, and this may offer a new therapeutic strategy to treat asthma.

Minimally invasive resection of olfactory neuroblastoma by transnasal endoscopy.

Olfactory neuroblastoma is rare. We conducted a retrospective study to review our experience with minimally invasive resection of olfactory neuroblastomas via a transnasal endoscopic technique, including an analysis of surgical outcomes. Our series included 5 patients-3 men and 2 women, aged 29 to 75 years (mean: 48). Surgical outcomes were evaluated on the basis of each patient's preoperative Dulguerov classification and postoperative evaluation on computed tomography and magnetic resonance imaging. One patient was treated with surgery alone, 3 with surgery plus radiotherapy, and 1 with surgery, radiotherapy, and chemotherapy. During follow-up of 18 to 115 months, all 5 patients remained alive and disease-free. We found that endoscopic resection of olfactory neuroblastoma is a feasible and effective procedure, even in patients with more aggressive stages of disease. We also believe that the Dulguerov classification is more useful than other classifications for clinical management and surgical planning. Long-term follow-up is necessary to look for late recurrence.