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OBJECTIVES/HYPOTHESIS The objective of this study was to determine the role of thrombin-activatable fibrinolysis inhibitor (TAFI) as a candidate biomarker for therapeutic efficacy of sublingual immunotherapy (SLIT) and to identify the role of TAFI in the pathogenesis of allergic rhinitis (AR). STUDY DESIGN Retrospective cohort study and laboratory study. METHODS Serum was collected from patients with allergies to Japanese cedar pollen before, during, and after treatment with SLIT. We measured the levels of immunoreactive TAFI, C3a, and C5a in serum by enzyme-linked immunosorbent assay (ELISA) and assessed their relative impact on a combined symptom-medication score. We also examined the impact of TAFI on mast cells and fibroblasts in experiments performed in vitro. RESULTS Serum levels of TAFI increased significantly in response to SLIT. By contrast, serum C3a levels decreased significantly over time; we observed a significant negative correlation between serum levels of TAFI versus C3a and symptom-medication score. Mast cell degranulation was inhibited in response to TAFI, as it was the expression of both CCL11 and CCL5 in cultured fibroblasts. CONCLUSIONS High serum levels of TAFI may be induced by SLIT. TAFI may play a critical protective role in pathogenesis of AR by inactivating C3a and by inhibiting mast cell degranulation and chemokines expression in fibroblasts. LEVEL OF EVIDENCE 4 Laryngoscope, 131:2413-2420, 2021.

Background The prevalence of allergic rhinitis (AR) is increasing worldwide, mainly due to an increase in antigen exposure. We conducted an epidemiological study involving the staff of the University of Fukui Hospital and its associated hospital in 2006. There were 1540 participants aged ≥20 years, and the rates of Japanese cedar (JC) pollinosis and mite-induced perennial allergic rhinitis (PAR) were 36.8% and 15.8%, respectively. In 2016, we conducted a second survey. Methods The rate of sensitization to JC pollen and mites and the prevalence of JC pollinosis and mite-induced PAR were analyzed based on data from questionnaires and antigen-specific immunoglobulin E (IgE) levels. Results In the present study, we analyzed data of 1472 participants aged between 20 and 59 years. Total sensitization to JC pollen and total prevalence of JC pollinosis were 57.8% (851/1472) and 40.8% (601/1472), respectively. Total sensitization to mites and total prevalence of mite-induced PAR were 41.4% (610/1472) and 18.8% (276/1472), respectively. Total prevalence of JC pollinosis and mite-induced PAR increased significantly over a decade. Among the 334 people who participated in the 2006 and 2016 cross-sectional studies, 13% of JC pollinosis and 36% of mite-induced PAR experienced remission. However, since the number of new onset cases was higher that the number of remission cases, a slight increase in prevalence was observed over a decade. Conclusions The prevalence of JC pollinosis and mite-induced PAR continues to show increasing trends, accompanied by an increase in antigen exposure. The remission rate of JC pollinosis was particularly low.

Background: Oral allergy syndrome (OAS) is an immediate allergy caused by a cross-reaction of highly homologous common antigens (pan-allergens) contained in fruits/vegetables and pollen. Methods: A questionnaire was provided to 6824 outpatient visitors and serum levels of specific IgEs against crude antigens and pan-allergen components were measured to study the relationship between the prevalence of OAS and pollinosis in the Fukui Prefecture where there is almost no dispersal of birch pollen. Results: The prevalence of OAS was 10.8%. The rate of pollinosis complication in the OAS group was 67.4%, and OAS was observed in 16.8% of pollinosis patients. Causative foods in order of frequency were melon, pineapple, kiwi fruit, peach, and apple. A significantly higher number of patients from the OAS group were positive for birch, alder, and timothy grass-specific IgE. The rate of positivity for anti-component IgE corresponding to pollen in OAS group was also significantly higher. Of 34 patients with OAS caused by eating apples, 28 (82.4%) were positive for Mal d1-specific IgE. Of the 52 patients with peach-induced OAS, 41 (78.8%) were positive for Pur p1-specific IgE. The concordance rates between crude antigen-specific IgE and anti-PR-10 component-specific IgE were 87.1% and 93.3% for apple and peach respectively. Conclusions: In regions where birch pollen is not dispersed, OAS patients have a significant association with the onset of Bet v1-associated allergy. Anti-PR-10 component IgE was useful in diagnosing OAS, and crude antigen-specific IgE was also associated with apple and peach allergies. Keywords: Allergen component, LTP, Oral allergy syndrome, Pollen-food allergy syndrome, PR-10

Orbital floor fracture, especially with constriction of orbital soft tissue, should be reconstructed surgically. Although various approaches to treat the orbital floor have been reported, procedures have not been unified among hospitals or surgeons. Since 2009, we have adopted a procedure combining a transorbital approach via subciliary incision with a transantral approach through upper gingival incision. The combined approach compensates for the shortcomings of each approach, leading to successful reconstruction. It is applicable safely for trapdoor fracture of the orbital floor in children, which more frequently constricts orbital soft tissue and which leaves permanent diplopia. This report retrospectively assessed clinical preoperative findings and postoperative outcomes of patients who received reconstruction of orbital floor fracture with the combined approach in our department from August 2009 through March 2021. Data of 21 patients with orbital floor fracture were analyzed, only one (4.8%) of whom had postoperative diplopia. Specifically, we describe children with trapdoor fracture treated with the combined approach, resulting in complete recovery. The combined approach stands as an excellent procedure for reconstruction of orbital floor fracture in adults and even in children.

Eosinophilic chronic rhinosinusitis (ECRS) is a subgroup of chronic rhinosinusitis with nasal polyps (CRSwNP), which is associated with severe eosinophilic infiltration and intractable. Its symptoms include dysosmia, nasal obstruction, and visous nasal discharge. The cause of ECRS is not clear, although it is thought that Staphylococcus aureus and its enterotoxins are involved in stimulating the Th2 system to promote IgE production and eosinophil infiltration through various pathways. While, the coagulation system is activated and the fibrinolytic system is suppressed, leading to deposition of fibrinous networks in nasal polyps. Therefore, a fibrin-degrading agent could be a new treatment for ECRS.Genetic analysis of nasal polyp cells using next-generation sequencing has identified some of the factors involved in ECRS, including periostin, which can be used as a biomarker of this condition. A protease inhibitor could be a therapeutic agent for ECRS. Regarding the role of eosinophils, many researchers have been interested in the mechanism of ETosis. However, the mechanism leading to development of nasal polyps is unknown.In Japan (as well as in East Asia), the incidence of non-ECRS is decreasing and that of ECRS is increasing, but the reason is also unknown. Thanks to the development of biologics therapy, it is thought that there will be a shift to precision medicine in the future. Keywords: Chronic rhinosinusitis with nasal polyp, CST-1, Eosinophilic chronic rhinosinusitis, JESREC study, Periostin

Submucous inferior turbinectomy (ST) can be combined with posterior nasal neurectomy (PNN) to treat intractable allergic rhinitis (AR) and vasomotor rhinitis (VR). This study assessed the long-term effects and complications of this surgical intervention. We enrolled 127 patients who had undergone combined ST and PNN. We mailed these patients card questionnaires. Of these questionnaires, we excluded the 5 patients with VR and 26 patients who had undergone concomitant endoscopic sinus surgery (ESS), because they had both AR or VR and sinusitis. Then, we assessed the questionnaire score of 31 patients with AR who had undergone combined ST and PNN. Postoperative bleeding was investigated in 127 subjects by medical records. Moreover, we compared the incidence of numbness in the palate, cheeks, or teeth between patients who had undergone PNN and those who had not. We found that 77.4% of the AR patients were satisfied with the improvement of their nasal symptoms after the operation. Although seven patients had been receiving medical treatment from an otolaryngology clinic every month before the operation, none needed any such treatment after the operation. One year postoperatively, all symptom scores were statistically decreased. However, the scores increased over time, although there was a significant improvement in nasal obstruction more than 3 years after the operation (P

BACKGROUND Paclitaxel-coated balloon angioplasty for de-novo coronary artery lesions causes late lumen enlargement (LLE), however, the mechanisms and predictors of LLE have not been elucidated. METHODS AND RESULTS We retrospectively analyzed 91 consecutive patients with 95 de-novo coronary lesions, who underwent paclitaxel-coated balloon angioplasty without stenting from August 2018 to July 2019 as well as follow-up coronary angiography and optical coherence tomography (OCT). The mean follow-up duration was 8.2 ± 2.9 months. The target lesion revascularization rate was 7.3%. OCT demonstrated LLE in 50.5% of lesions. The lesions with LLE had a higher incidence of vessel enlargement (76.6 vs. 29.2%, p

Murine models to elucidate the pathogenesis of pollen food allergy syndrome (PFAS), characterized by oral hypersensitivity symptoms induced by specific foods in patients previously sensitized with a pollen, are lacking. The study aimed to examine PFAS pathogenesis in a novel murine model. Birch pollen–immunized mice were orally administered apple extract, and oral symptoms were evaluated based on oral rubbing frequency following the challenge. The birch pollen–immunized mice orally challenged with apple extract exhibited PFAS-like symptoms, including oral rubbing and positive reaction of swelling by the prick test. The apple extract administered with a protease inhibitor reduced the oral rubbing frequency, which was also significantly reduced in the immunized Fcer1a−/− and mast cell–deficient mice compared with the immunized control mice. The oral rubbing frequency, serum IgE levels, and Th2-cytokine production by the cervical lymph node cells were significantly reduced in the immunized Il-33−/− and thymic stromal lymphopoietin receptor–deficient (Crlf2−/−) mice as compared with the immunized wild-type mice. IL-33 and thymic stromal lymphopoietin involve the pathogenesis of PFAS. The apple-extract stimulation did not lead to increased Th2-cytokine production in the oral mucosa or number of group 2 innate lymphoid cells or eosinophils. PFAS involves an early-phase response by mast cell degranulation via IgE signaling after the cross-reactivity of Bet v 1–specific IgE and the food allergen, and exacerbation of allergic symptom via proteases in food; PFAS does not involve a late phase with local Th2/eosinophilic inflammation in the oral mucosa. This novel murine model might be used for elucidating the pathogenesis and assessing new therapeutic strategies for PFAS.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is often comorbid with asthma and resistant to therapeutic interventions. We recently reported that excessive fibrin deposition caused by impairment of fibrinolysis might play pivotal role in forming nasal polyp. Nattokinase (NK), a serine protease produced by Bacillus subtilis , has been reported to be a strong fibrinolytic enzyme. NK could be a promising drug candidate for use in the treatment of both CRSwNP and asthma. The objective of this study was to investigate the effects of NK on nasal polyp tissues from patients with CRSwNP. The nasal discharge from patients with CRSwNP and sputum from subjects with asthma were also used to investigate whether NK influences the viscosity of mucus. Methods To examine the effects on NK on nasal polyp tissues, pieces of nasal polyps were incubated either with saline or NK (10–1000 FU/ml) at 37 °C for 24 h. We assessed the presence of fibrin in nasal polyp tissue incubated with NK by means of immunohistochemistry. To examine the effects of NK on nasal discharge and sputum from patients with CRSwNP and asthma, respectively, were incubated with NK solution at 37 °C for 1 h. Results NK effectively shrinks the nasal polyp tissue through fibrin degradation. We also found that the viscosity of the nasal discharge and sputum from patients with CRSwNP and asthma, respectively, was significantly reduced by incubation with NK solution. Conclusions NK may be an effective alternative therapeutic option in patients with CRSwNP and comorbid asthma by causing fibrin degradation.

Objective: Chronic rhinosinusitis with nasal polyps exhibits marked eosinophilic infiltration and its mucosal eosinophilia is associated with more severe symptoms. The Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis found that patients with nasal polyps required multiple surgeries when there were higher infiltrating eosinophils in the mucosa. In order to identify plasma biomarkers for local eosinophil infiltration in rhinosinusitis for surgery, we examined the levels of molecules in the plasma of patients and compared the number of infiltrating eosinophils in the nasal mucosa.Materials and Methods: Mucosal tissues from 97 patients with chronic rhinosinusitis (CRS) were obtained from the nasal polyps during surgery. Tissues were immediately fixed and sections were stained with hematoxylin-eosin. The number of eosinophils in the mucosa was counted at HPF (x 400). Blood samples were obtained and the plasma was stored at −80°C. We measured the plasma cytokine and chemokine levels using multiple assay systems according to the manufacturers' protocols. The tissues were divided into high- and low-eosinophil mucosal infiltration group for recurrence after endoscopic sinus surgery (ESS). We also observed chemokine secretion from nasal fibroblasts.Results: The plasma level of eotaxin-3/ CC chemokine ligand 26 (CCL26) was significantly higher in the high-eosinophil mucosal infiltration group (p < 0.005). The number of infiltrating eosinophils in the mucosa was significantly higher in the group with the higher eotaxin-3 level (p < 0.001), but there was no significant difference in the blood eosinophil numbers among two groups. A significant positive correlation was found between the mucosal eosinophil count and the plasma levels of eotaxin-3 (p < 0.005). The levels of interleukin 33 (IL-33) (p < 0.001) and thymic stromal-derived lymphopoietin (TSLP) (p < 0.005) were significantly higher in the high-level eotaxin-3 group. IL-13 strongly induced the secretion of eotaxin-3 from human nasal fibroblasts (p < 0.05).Conclusion: This is the first report suggesting eotaxin-3 as a plasma biomarker for mucosal eosinophil infiltration. Furthermore, the level of eotaxin-3 was found to be closely related to IL-33 and TSLP levels which indicate respiratory diseases.

Ethnopharmacological relevance The traditional Japanese herbal medicine Shin'iseihaito was reported to ameliorate the airway type 2 inflammatory response in clinical and experimental studies. Airway type 2 inflammatory diseases, including bronchial asthma and eosinophilic chronic rhinosinusitis (ECRS), often coexist and interact with each other. However, it is still unclear how Shin'iseihaito exerts its pharmacological effects on cells involved in airway mucosa. Aim of the study This study aims to examine the direct effect of baicalin, a representative bioactive compound of Shin'iseihaito, on type 2 immune responses in human airway epithelial cells and mast cells. Material and methods We measured the plasma pharmacokinetics of flavonoids derived from Shin'iseihaito and investigated the effects of baicalin on type 2 immune responses in human airway epithelial cells and human mast cells. Results Baicalin, wogonin, and wogonoside were detected in the plasma. The maximum plasma concentration of baicalin was highest at 1610 ng/ml (3.6 μM). In the normal human bronchial epithelial cells treated with baicalin, with or without stimulation by IFN-γ, the IL-33 expression was significantly downregulated. However, baicalin treatment did not affect the levels of thymic stromal lymphopoietin and IL-25. We noted that IL-33-dependent expression of tryptase mRNA in mast cells was significantly inhibited by baicalin. Also, the expression of IL-5 in mast cells enhanced by stimulation with TSLP plus IL-1β was significantly downregulated by baicalin treatment. Moreover, the enhancement of IL-13 expression in mast cells by IL-33 simulation was also significantly inhibited by baicalin. Conclusions Our results prove that by breaking off the vicious circle of mast cells and airway epithelial cells, baicalin may be an effective alternative therapeutic option for the treatment of type 2 inflammatory diseases, such as ECRS and comorbid asthma.

We experienced a case of Kounis syndrome with cardiopulmonary arrest and severe coronary spasm. A 70-year-old man with cardiac pacemaker and chronic dialysis was treated for angina pectoris of the right coronary artery. After diagnostic coronary angiography of the right coronary artery, optical coherence tomography was performed with contrast medium and low-molecular-weight dextran. The patient's blood pressure unexpectedly dropped to 40mmHg and erythema of the breast was noted. Electrocardiogram showed remarkable ST elevation in II, III, aVF leads. Coronary angiography showed total occlusion of the proximal right coronary artery. Although intracoronary infusion of sodium nitrate did not dilate the coronary artery promptly, coronary balloon angioplasty recovered the artery flow. Since severe anaphylaxis-related shock was contemplated, methyl prednisolone and epinephrine were administered intravenously. We could not introduce percutaneous cardiopulmonary support due to kinking of the vein. After 1 hour of cardiopulmonary resuscitation with frequent ventricular fibrillation and direct current shock, the sinus rhythm and blood pressure recovered. Following 2 months of intensive care treatment for other complications, including infection, the patient was discharged from hospital without any residual disability. Learning objective: An anaphylactic reaction is one of the causes of sudden deterioration of a patient's condition observed during interventional procedures. Kounis syndrome is a rare and not yet well known important concept that deals with the reaction. Therefore, we report a severe case of Kounis syndrome with cardiopulmonary arrest.

We report a case of Carney complex (CNC) with biatrial cardiac myxoma. The patient had left and right atrial myxomas which were resected in a surgery. She showed bilateral adrenal tumors and multiple mammary tumors. She had pigmentation on her lower lip. Previously, her daughter was also diagnosed with CNC with cardiac myxoma. Both of them showed mutations in the PRKAR1A gene.

Background: The pathological features of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) tissues include an eosinophilic infiltration pattern (eosinophilic CRS (ECRS)) or a less eosinophilic pattern (non-ECRS). Recently, it has been suggested that 15-lipoxygenase 1 (15-LOX-1) may have significant roles in allergic disease, however, the significance of 15-LOX-1 in CRS is not well understood. The objective of this study was to demonstrate the expression of 15-LOX-1 in CRS. Methods: The mRNA expression levels of 15-LOX-1 and periostin in nasal tissues were measured by quantitative real-time polymerase chain reaction. We also performed an immunofluorescence study of nasal tissues. Cells of the Eol-1 eosinophilic leukemic cell line were stimulated with interleukin-33 to test the induction of 15-LOX-1. Results: The expression level of 15-LOX-1 mRNA in nasal polyps (NPs) was significantly higher in ECRS patients than in non-ECRS patients. The immunofluorescence study revealed that both airway epithelial cells and eosinophils in NPs expressed 15-LOX-1. A significant correlation was seen between the number of eosinophils and the mRNA expression levels of 15-LOX-1 and periostin in nasal polyps. Moreover, interleukin-33 enhanced 15-LOX-1 expression in Eol-1 cells. Conclusions: 15-LOX-1 was shown to be a significant molecule that facilitates eosinophilic inflammation in ECRS.

Background Most patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD) suffer from recurrence of nasal polyps. However, little is known about the specific cellular and molecular mechanisms contributing to the pathogenesis of nasal polyp development in patients with NERD in particular, especially at baseline when cyclooxygenase 1 inhibitors are not present. The objectives of this study were to identify proteins involved in the pathogenesis of nasal polyps in patients with NERD. Methods We collected nasal polyp tissue from patients with NERD and from patients with aspirin-tolerant chronic rhinosinusitis with nasal polyps (CRSwNP). Protein profiles were analyzed by 2-dimensional electrophoresis and identified several proteins, including L-plastin, as highly expressed. We examined L-plastin and tissue factor (TF) expression by immunohistochemical and immunofluorescence analyses. To examine the role of L-plastin in eosinophils, we knocked down L-plastin expression in Eol-1 cells by using siRNA transfection. Results L-plastin protein levels in nasal polyp tissue were increased in patients with NERD relative to those in patients with aspirin tolerant CRSwNP. Immunofluorescence analysis revealed that L-plastin was dominantly expressed in eosinophils and L-plastin and TF were co-expressed in eosinophils in NERD nasal polyp tissue. Knockdown of L-plastin in Eol-1 cells disrupted the cell surface distribution of TF by stimulation with granulocyte macrophage colony-stimulating factor. Conclusion Increased expression of L-plastin by eosinophils may contribute to abnormal fibrin deposition through TF translocation to the eosinophil cell surface in NERD nasal polyp tissue, which in turn may contribute to the pathogenesis of NERD.

BackgroundNasal polyps (NP) are characterized by pseudocysts derived from stromal tissue edema and cause persistent infections in patients with chronic rhinosinusitis (CRS). A low level of tissue-type plasminogen activator (gene name PLAT) is considered a cause of stromal tissue edema because of insufficient plasmin activation in NP; however, the mechanism regulating PLAT gene expression levels is still unclear. The epigenetic mechanism regulating the PLAT gene expression has been studied in other tissues.ObjectiveWe aimed to investigate the methylation levels in the proximal PLAT promoter and their effects on gene expression in NP tissue.MethodsWe investigated the methylation levels at 3 CpG sites in the proximal PLAT promoter regions (−618, −121, and −105 with respect to the transcription initiation site) by bisulfite pyrosequencing and their effects on the gene expression by quantitative real-time polymerase chain reaction (qPCR) in 20 paired samples of NP and inferior turbinate tissue (IT) from patients with CRS.ResultsThe DNA methylation levels at all CpG sites were higher ( P ConclusionsHypermethylation of PLAT promoter may downregulate the gene expression in NP, leading to excessive fibrin deposition by aberrant coagulation cascade. DNA methylation of proximal PLAT promoter may contribute to NP growth and have a potential as a new therapeutic target.

To develop an immunotherapeutic vaccine for treatment of allergic rhinitis, we developed a controlled release formulation of Cryj1, a major Japanese cedar pollen allergen, with immunostimulatory potency. Two sets of hexapod-like structured DNA (hexapodna) were prepared using six oligodeoxynucleotides (ODNs) each, including ODNs with an unmethylated cytosine–phosphate–guanine (CpG) sequence (CpG motif), to obtain an immunostimulatory DNA hydrogel (sDNA hydrogel). A non-immunostimulatory DNA hydrogel (nsDNA hydrogel) was also prepared using ODNs with no CpG motifs. The sDNA hydrogel was more effective than its components or the nsDNA hydrogel for production of interleukin (IL)-12 after addition to murine macrophage-like RAW264.7 cells or after intranasal administration to mice. Then, a Cryj1-loaded sDNA hydrogel (Cryj1/sDNA hydrogel) formulation was prepared by mixing solutions containing both Cryj1 and hexapodna. Cryj1 was slowly released from the sDNA hydrogel in phosphate-buffed saline. After intranasal administration of the fluorescein isothiocyanate (FITC)-labeled Cryj1/sDNA hydrogel in mice, FITC-Cryj1 was retained in the nasal cavity for a longer period than FITC-Cryj1 mixed with hexapodna in solution. Intranasal immunization of mice with the Cryj1/sDNA hydrogel resulted in high levels of Cryj1-specific IgG in nasal lavage fluid (NFL), IL-12 and interferon-γ release from spleen cells after re-stimulation with Cryj1 when compared with intranasal immunization with the other formulations examined. These results indicate that the self-gelling immunostimulatory DNA hydrogel is an effective formulation for controlled induction of allergen-specific immune responses.

A 72-year-old male was treated. First percutaneous coronary intervention (PCI) for chronic total occlusion of proximal left anterior descending artery was performed after rotational atherectomy with 1.5-mm burr. Focal underexpansion of Promus stent occurred due to the heavily calcified plaque. After first restenosis, OCT-guided PCI was performed with 26 atm balloon dilatation. After second restenosis, Resolute Integrity was implanted. After third restenosis, rotational atherectomy with 1.5-, 1.75- and 2.15-mm burrs was performed. All stent struts disappeared at the lesion and Promus Element was implanted. No restenosis occurred after 6 months. Cautious rotational atherectomy could ablate double layer drug-eluting stents effectively.

In this study, we found Cystatin SN (CST1), a type 2 cystatin subfamily member, to be highly expressed in nasal polyps from patients with intractable chronic rhinosinusitis (CRS) with nasal polyps, using a whole-transcript analysis with next-generation sequencing. Eosinophilic CRS (ECRS) involves nasal polyps that are refractory and recur immediately after endoscopic sinus surgery. We hypothesized that CST1 may contribute to the pathogenesis of ECRS. We examined the expression of CST1 in nasal polyps from patients with ECRS by assessing mRNA expression levels using real-time PCR and immunohistochemistry. CST1 showed significantly greater expression in the epithelial cells of nasal polyps from patients with ECRS than in those from patients who did not have ECRS (non-ECRS). In particular, CST1 showed very strong expression in patients with severe ECRS. The expression of CST1 may be correlated with the recurrent and refractory nature of ECRS. We examined the function of CST1 using nasal epithelial cells and nasal fibroblasts. Stimulation by a combination of IL-4 plus double-stranded RNA plus CST1 significantly elevated mRNA expression levels and protein levels of TSLP in nasal epithelial cells. Stimulation by TSLP or IL-33 significantly elevated mRNA expression levels of CST1 in nasal epithelial cells. Stimulation of CST1 significantly elevated mRNA expression levels of CCL11 and POSTN in nasal fibroblasts. CST1 could amplify eosinophilic infiltration and T-helper cell type 2 inflammation by interacting with epithelial-derived cytokines and fibroblasts on nasal polyps. CST1 may be involved in the pathogenesis of ECRS, and may contribute to the severity and recurrence of CRS with nasal polyps after endoscopic sinus surgery.

Continuous positive airway pressure (CPAP) is effective for patients with SAS. CPAP therapy requires long-term usage to prevent recurrence of symptoms. It is, thus, important to examine the level of long-term CPAP use and the factors influencing compliance with CPAP therapy for SAS. Compliance with CPAP therapy was examined in 204 patients in whom such therapy was started between 2003 and 2009. The median follow-up duration was 19 months (IQR = 6.8-37.5). Although the subjective and objective curative effects were significant, 18 patients (8.9%) refused CPAP therapy. Survival analysis showed that the patients' adherence to CPAP after 5 years was 89.8%. Multivariate analysis, including gender, age, BMI, AHI, arousal index, minSpO₂, ESS, sleep stage, and LMI, indicated that the degree of improvement of AHI, percentage of deep sleep stage, and LMI were clinical variables independently associated with long-term adherence to CPAP. Furthermore, use of appropriate drugs for the patients with nasal congestion resulted in better satisfaction and adherence to CPAP therapy. We have shown that the rate of compliance and the subjective and objective curative effects of CPAP therapy were high, and detected the independent clinical factors associated with continued CPAP therapy.

Background The number of patients with eosinophilic chronic rhinosinusitis (ECRS) has been increasing in recent years in Japan. In ECRS, nasal polyps recur immediately after endoscopic sinus surgery. The molecular biological mechanism underlying the refractoriness of ECRS is unclear. Methods Whole-transcriptome analysis with next-generation sequencing (RNA-seq) was conducted to investigate the molecular biological mechanism of ECRS. Real-time PCR, immunohistochemical staining, and immunofluorescence staining were performed to validate the results of RNA-seq. Results RNA-seq analysis revealed that in the nasal polyps of ECRS, the levels of 3 transcripts were elevated significantly and those of 7 transcripts were diminished significantly. Among the genes encoding these transcripts, TRPV3 (transient receptor potential cation channel, subfamily V, member 3) was identified as the only gene that is highly expressed in ECRS nasal polyps but this gene's expression was not previously detected using DNA microarray analysis in peripheral blood eosinophils. TRPV3 is newly identified here as a gene transcribed in ECRS. Our analysis also revealed that TRPV3 was highly expressed in the infiltrating eosinophils and mucosal epithelium of the nasal polyps of ECRS, and further that the more severe the refractoriness was after surgery, the higher the TRPV3 expression was in nasal polyps. Conclusions TRPV3 might play a role in the refractoriness of ECRS. Additional studies are required to evaluate the function of TRPV3 in ECRS.

Atresia of the anterior nares is a rare disease caused by a congenital or acquired disorder. Car accidents, burns, postoperative scar, iatrogenic damage, and so on reportedly induce acquired atresia of the anterior nares. This report describes a rare case of nasal alar deformity and anterior nasal atresia caused by scar tissue formation following zona facialis. An 80-year-old woman was infected with herpes zoster at the right trigeminal nerve second division and intravenous acyclovir was administered. After treatment, increasing deformity of the right ala was gradually noted. The right nostril had closed completely in 10 months. She was treated with surgical enlargement of the stenosis using a nasolabial skin flap. Stenosis has not recurred during the six months since the nasolabial skin flap reconstruction. Various techniques have been used for reconstruction related to anterior nasal atresia: scar excision, skin graft, Z-plasty, V-Y advancement flap, composite graft, nasolabial skin flap, and others. It is important to choose an appropriate operative method for prevention of postoperative recurrence.