Tongue pressure plays an important role in swallowing function. The purpose of this study is to investigate whether decreased tongue pressure is associated with dysphagia and the development of pneumonia in the elderly requiring long-term care. Tongue pressure measurement and swallowing videoendoscopic (VE) examination were performed in 60 hospitalized elderly people (33 males and 27 females, with an average age of 84.3 years) to investigate the relationship with the clinical course. Factors related with dysphagia was analyzed by Fisher's exact test and one-way ANOVA, followed by multivariate logistic regression. The relationship between each variable and survival were analyzed by cox regression. Twenty-one patients had dysphagia by VE examination. Multivariate analysis showed that smaller BMI and reduced tongue pressure were significantly correlated with dysphagia. Smaller number of remaining teeth and dysphagia were significantly related to pneumonia-related death. No patients with tongue pressure of larger than 20 kpa died by pneumonia within one year, while in those with tongue pressure of smaller than 20 kpa, one-year cumulative survival rate by pneumonia was 44.3%. Decreased tongue pressure was significantly associated with dysphagia and may increase the risk of pneumonia-related death in the elderly requiring long-term care.

Objective: To describe the etiology of advanced cases of external auditory canal (EAC) cholesteatoma (EACC), and to report the surgical management and outcomes based on canalplasty depending on the extent of adjacent structures involvement around the EAC. Study Design: Retrospective case review. Setting: University hospital. Patients: Participants comprised 28 patients (12 males, 16 females) ranging in age from 9 to 86 years old. All patients presented with advanced-stage EACC (Naim's classification: stage III/IV). Intervention: Surgery ranged from simple bony meatoplasty with cartilage graft repair to more enlarged EAC canalplasty combined with tympanoplasty. Result: EACC was categorized as idiopathic in 22 patients and secondary EACC in six patients. Six patients with idiopathic EACC were receiving hemodialysis, one of whom showed bilateral pathology. Particularly in cases with epithelial invasion into the hypotympanum immediately adjacent to the jugular bulb, multi-layered repair including bone paste, post-auricular pedicled musculo-periosteal flap, auto cartilage, and temporalis muscle fascia were required. Five patients required revision surgery (17%), including one case of recurrent (reconstructed) cholesteatoma and three cases of perforation of the tympanic membrane. Conclusion: In the majority of our series, underlying diseases followed with microangiopathy and angiogenesis could be possible candidates in the etiology of EACC. Enlarged bony meatoplasty and multilayered reconstruction surgery brought about self-cleaning and dried the EAC in advanced-stage EACC.

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory airway disease accompanied by eosinophilic inflammation, the mechanisms of which are unknown. We recently found that CCL4/MIP-1β—a specific ligand for CCR5 receptors—was implicated in eosinophil recruitment into the inflammatory site and was substantially released from activated eosinophils. Moreover, it was found in nasal polyps from patients with ECRS, primarily in epithelial cells. In the present study, the role of epithelial cell-derived CCL4 in eosinophil activation was investigated. First, CCL4 expression in nasal polyps from patients with ECRS as well as its role of CCL4 in eosinophilic airway inflammation were investigated in an in vivo model. Furthermore, the role of CCL4 in CD69 expression—a marker of activated eosinophils—as well as the signaling pathways involved in CCL4-mediated eosinophil activation were investigated. Notably, CCL4 expression, but not CCL5, CCL11, or CCL26, was found to be significantly increased in nasal polyps from patients with ECRS associated with eosinophil infiltration as well as in BEAS-2B cells co-incubated with eosinophils. In an OVA-induced allergic mouse model, CCL4 increased eosinophil accumulation in the nasal mucosa and the bronchoalveolar lavage (BALF). Moreover, we found that CD69 expression was upregulated in CCL4-stimulated eosinophils; similarly, phosphorylation of several kinases, including platelet-derived growth factor receptor (PDGFR)β, SRC kinase family (Lck, Src, and Yes), and extracellular signal-regulated kinase (ERK), was upregulated. Further, CCR5, PDGFRβ, and/or Src kinase inhibition partially restored CCL4-induced CD69 upregulation. Thus, CCL4, which is derived from airway epithelial cells, plays a role in the accumulation and activation of eosinophils at inflammatory sites. These findings may provide a novel therapeutic target for eosinophilic airway inflammation, such as ECRS.

Eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic rhinosinusitis with nasal polyps, is recognized as a refractory eosinophilic disorder characterized by both upper and lower airway inflammation. In some severe cases, disease control is poor, likely due to local steroid insensitivity. In this study, we focused on protein phosphatase 2A (PP2A), a key factor regulating glucocorticoid receptor (GR) nuclear translocation, and examined its association with local responses to corticosteroids in eosinophilic airway inflammation. Our results indicated reduced responses to corticosteroids in nasal epithelial cells from ECRS patients with asthma, which were also associated with decreased PP2A mRNA expression. Eosinophil peroxidase stimulates elevated PP2A phosphorylation levels, reducing PP2A protein expression and activity. In addition, mRNA levels of inflammatory mediators (TSLP, IL-25, IL-33, CCL4, CCL5, CCL11, and CCL26) associated with eosinophilic airway inflammation in epithelial cells were increased in nasal polyps (eosinophil-rich areas) compared with those in uncinate process tissues (eosinophil-poor areas) from the same patients. PP2A reduction by siRNA reduced GR nuclear translocation, whereas PP2A overexpression by plasmid transfection, or PP2A activation by formoterol, enhanced GR nuclear translocation. Collectively, our findings indicate that PP2A may represent a promising therapeutic target in refractory eosinophilic airway inflammation characterized by local steroid insensitivity.

Eosinophilic airway inflammatory disease is associated with bronchial asthma, with eosinophilic chronic rhinosinusitis (ECRS) typical of refractory type 2 airway inflammation. CCL4 produced at local inflammatory sites is involved in them via the accumulation and activation of type 2 inflammatory cells, including eosinophils. The detailed mechanism of CCL4 production remains unclear, and also the possibility it could function as a biomarker of type 2 airway inflammation remains unresolved. In this study, we evaluated CCL4 mRNA expression and production via the TSLP receptor (TSLPR) and toll-like receptors (TLRs) or proteinase-activated receptor-2 (PAR2) in BEAS-2B bronchial epithelial cells co-incubated with purified eosinophils or eosinophil peroxidase (EPX). We examined serum chemokine (CCL4, CCL11, CCL26, and CCL17) and total IgE serum levels, fractionated exhaled nitrogen oxide (FENO), and CCL4 expression in nasal polyps in patients with severe ECRS and asthma. CCL4 was induced by TSLP under eosinophilic inflammation. Furthermore, CCL4 was released via TLR3 signaling, which was enhanced by TSLP. CCL4 was mainly located in nasal polyp epithelial cells, while serum CCL4 levels were reduced after dupilumab treatment. Serum CCL4 levels were positively correlated with FENO, serum IgE, and CCL17 levels. Thus, CCL4 released from epithelial cells via the innate immune system during type 2 airway inflammation may function as a useful biomarker for the condition.