Assessing antiviral treatment efficacy and risk factors for severe COVID-19 in kidney transplant recipients during the Omicron subvariant-dominant period: a retrospective study.

BACKGROUND: Kidney transplant recipients (KTRs) are at risk of severe coronavirus disease 2019 (COVID-19), and even now that Omicron subvariants have become dominant, cases of severe disease are certain to occur. The aims of this retrospective study were to evaluate the efficacy of antiviral treatment for COVID-19 and to identify risk factors for severe disease in KTRs during Omicron subvariant-dominant periods. METHODS: A total of 65 KTRs diagnosed with COVID-19 who received antiviral treatment between July 2022 and September 2023 were analyzed. Mild cases received oral molnupiravir (MP) as outpatient therapy, while moderate or worse cases received intravenous remdesivir (RDV) as inpatient therapy. In principle, mycophenolate mofetil was withdrawn and switched to everolimus. We investigated the efficacy of antiviral treatment and compared the clinical parameters of mild/moderate and severe/critical cases to identify risk factors for severe COVID-19. RESULTS: Among 65 cases, 49 were mild, 6 were moderate, 9 were severe, and 1 was of critical severity. MP was administered to 57 cases; 49 (86%) improved and 8 (14%) progressed. RDV was administered to 16 cases; 14 (87%) improved and 2 (13%) progressed. Seventeen (26%) cases required hospitalization, and none died. Comparisons of the severe/critical group (n = 10) with the mild/moderate group (n = 55) demonstrated that the severe/critical group had a significantly higher median age (64 vs. 53 years, respectively; p = 0.0252), prevalence of diabetes (70% vs. 22%, respectively; p = 0.0047) and overweight/obesity (40% vs. 11%, respectively; p = 0.0393), as well as a significantly longer median time from symptom onset to initial antiviral therapy (3 days vs. 1 day, respectively; p = 0.0026). Multivariate analysis showed that a longer time from symptom onset to initial antiviral treatment was an independent risk factor for severe COVID-19 (p = 0.0196, odds ratio 1.625, 95% confidence interval 1.081-2.441). CONCLUSION: These findings suggest that a longer time from symptom onset to initial antiviral treatment is associated with a higher risk of severe COVID-19 in KTRs. Initiating antiviral treatment as early as possible is crucial for preventing severe outcomes; this represents a valuable insight into COVID-19 management in KTRs.

Long-term follow-up of a patient diagnosed with Crouzon syndrome who underwent Le Fort I and III distraction osteogenesis using a rigid external distractor system.

OBJECTIVE: This case report describes the successful treatment of a patient with Crouzon syndrome with severe midfacial deficiency and malocclusion, including reverse overjet. MATERIALS AND METHODS: In Phase I treatment, maxillary lateral expansion and protraction were performed. In Phase II treatment, after lateral expansion of the maxilla and leveling of the maxillary and mandibular dentition, an orthognathic approach including simultaneous Le Fort I and III osteotomies with distraction osteogenesis (DO) was used to improve the midfacial deficiency. RESULTS: After DO, 12.0 mm of the medial maxillary buttress and 9.0 mm of maxillary (point A) advancement were achieved, which resulted in a favorable facial profile and stable occlusion. CONCLUSION: Even after 8 years of retention, the patient's profile and occlusion were preserved without any significant relapse.

Craniofacial and dental characteristics of three Japanese individuals with genetically diagnosed SATB2-associated syndrome.

Craniofacial defects are one of the most frequent phenotypes in syndromic diseases. More than 30% of syndromic diseases are associated with craniofacial defects, which are important for the precise diagnosis of systemic diseases. Special AT-rich sequence-binding protein 2 (SATB2)-associated syndrome (SAS) is a rare syndromic disease associated with a wide variety of phenotypes, including intellectual disability and craniofacial defects. Among them, dental anomalies are the most frequently observed phenotype and thus becomes an important diagnostic criterion for SAS. In this report, we demonstrate three Japanese cases of genetically diagnosed SAS with detailed craniofacial phenotypes. The cases showed multiple dental problems, which have been previously reported to be linked to SAS, including abnormal crown morphologies and pulp stones. One case showed a characteristic enamel pearl at the root furcation. These phenotypes add new insights for differentiating SAS from other disorders.

Morphologic variations in the craniofacial structures in Japanese adults and their relationship with sex differences.

INTRODUCTION: The morphology of the human face varies broadly, with genetic and environmental factors determining these variations. Examining variations in the 3-dimensional (3D) craniomandibular morphology and identifying related factors (eg, sex differences) are important in orthodontic clinics. This study observed shape variations in the 3D facial morphology of Japanese adults showing skeletal Class 1 malocclusion and examined the association of sexual dimorphism with shape variations. METHODS: Sixty cone-beam computed tomography images of Japanese adults (30 males and 30 females) with skeletal Class I malocclusion were employed. In each cone-beam computed tomography image, wire mesh fitting was conducted as previously described. A principal component (PC) analysis after Procrustes registration and the PC clustering method was conducted to observe the shape variations. A PC regression analysis was conducted to determine the sexual morphologic characteristics. RESULTS: Nine PCs depicting 62% of the morphology were determined. Four typical phenotypes were found, mainly related to mandibular protrusion (PC1) and the vertical divergence of the face (PC2). PCs related to sex determination were PC3 (robustness of the mandibular angle in males), PC5 (greater size and shape of the coronoid and mastoid processes in males), and PC7 (greater maxillary width in males), accounting for 16% of total variations. CONCLUSIONS: The major shape variations in skeletal Class 1 subjects were related to nonsexual dimorphic characteristics (ie, mandibular protrusion and facial divergence). Sexual dimorphic characteristics were evaluated in detail and accounted for 16% of total morphologic variations.

Background factors involved in the epidemiology of functional constipation in the Japanese population: a cross-sectional study.

BACKGROUND: Functional constipation (FC), a functional bowel disorder with symptoms of constipation, has considerable impact on quality of life. As data regarding its prevalence and epidemiology are lacking, this study aimed to evaluate the prevalence, population composition, lifestyle, quality of life, and clinical characteristics of these individuals by comparing people with and without FC. These parameters were also compared among individuals with strong and weak awareness of constipation. METHODS: An internet survey was conducted among 10,000 individuals aged 20-69 years from the general Japanese population; they were registered with an internet survey company. The following data were obtained: age, sex, educational history, occupation, residence, history of other diseases, lifestyle (including smoking/drinking habits using the Japanese Health Practice Index, medication use, symptoms of constipation according to the Rome III criteria, stool types according to the Bristol stool scale, and use of laxatives, including the place of purchase and cost per month or acceptable cost per month. The 8-item Short Form Health Survey Questionnaire was also used; FC was diagnosed based on Rome III criteria. All respondents were classified according to their awareness of constipation (i.e. strong or weak), and their characteristic features were compared. RESULTS: The data of 3000 respondents were evaluated; 262 (8.7%) had FC, which was common among older adults, women, and homemakers. FC was associated with changes in the frequency of bowel movement, sensation of incomplete or scanty evacuation, and the use of manual maneuvers; these are consequential clinical symptoms of FC. These individuals frequently skipped breakfast, had insufficient sleep, had more severe constipation, and had purchased laxatives in pharmacies or online more often than those without FC. A strong awareness of constipation was significantly more prevalent among women and homemakers. A history of anemia and cardiovascular disease was significantly more frequent in the strong awareness group, whereas a history of hypertension was more frequent in the weak awareness group. CONCLUSIONS: Appropriate and comprehensive management should be provided for FC, based on the understanding of its characteristic features and considering the symptoms and lifestyle.

Internet Survey of Japanese Patients With Chronic Constipation: Focus on Correlations Between Sleep Quality, Symptom Severity, and Quality of Life.

BACKGROUND/AIMS: Chronic constipation and lifestyle factors can affect sleep quality. We evaluated the relationship between chronic constipation and sleep in the Japanese population. METHODS: This cross-sectional internet-based survey included 3000 subjects with constipation, classified according to sleep status (good/poor). Primary endpoints were Bristol stool form scale (BSFS) score and correlations between sleep disorder criteria of the Pittsburgh Sleep Quality Index (PSQI) and sleep status (good/poor sleep). Secondary endpoints included correlations between quality of life (QOL) and mood, medical, lifestyle, and sleep factors. RESULTS: The proportion of participants with BSFS category 4 (normal stool) was significantly higher in the good sleep group (P < 0.001). Sleep disturbance (P < 0.05), sleep quality, and duration, use of hypnotic medication, and daytime dysfunction of PSQI (all P < 0.001) significantly correlated with poor sleep. In the poor sleep group, QOL was significantly worse and anxiety and depression levels were significantly higher (all P < 0.001) compared with the good sleep group. Anemia and smoking (both P < 0.05), recent body weight increases, and poor eating habits (all P < 0.001) were significantly higher in the poor sleep group. Male sex, onset associated with change in frequency of stools, sensation of incomplete evacuation for at least 25% of defecations, and manual maneuvers to facilitate at least 25% of defecations correlated with poor sleep. CONCLUSIONS: Subjects with constipation and poor sleep experienced severe symptoms and had poor QOL. These data support the need for a multifocal treatment approach, including lifestyle advice and pharmacotherapy.

Synergistic role of retinoic acid signaling and Gata3 during primitive choanae formation.

Developmental defects of primitive choanae, an anatomical path to connect the embryonic nasal and oral cavity, result in disorders called choanal atresia (CA), which are associated with many congenital diseases and require immediate clinical intervention after birth. Previous studies revealed that reduced retinoid signaling underlies the etiology of CA. In the present study, by using multiple mouse models which conditionally deleted Rdh10 and Gata3 during embryogenesis, we showed that Gata3 expression is regulated by retinoid signaling during embryonic craniofacial development and plays crucial roles for development of the primitive choanae. Interestingly, Gata3 loss of function is known to cause hypoparathyroidism, sensorineural deafness and renal disease (HDR) syndrome, which exhibits CA as one of the phenotypes in humans. Our model partially phenocopies HDR syndrome with CA, and is thus a useful tool for investigating the molecular and cellular mechanisms of HDR syndrome. We further uncovered critical synergy of Gata3 and retinoid signaling during embryonic development, which will shed light on novel molecular and cellular etiology of congenital defects in primitive choanae formation.

Observation of the Epithelial Cell Behavior in the Nasal Septum During Primary Palate Closure in Mice.

Epithelial fusion is critical in palatogenesis, and incomplete fusion results in various type of facial cleft, depending on the region that fails to fuse. In mammalian palatogenesis, the bilateral secondary palatal processes fuse in the middle of the face to form the secondary palate. Later, the dorsal side of the secondary palatal shelves fuses with the nasal septum to complete palatogenesis. Importantly, the anterior border of the secondary palatal shelf fuses with the primary palate, which is located at the anterior and ventral border of the nasal septum. While numerous studies have investigated the mechanism of fusion between secondary palatal shelves, very little is known about how the primary palate touches and fuses with the secondary palatal shelves. In this study, we investigate the possible epithelial cell behaviors on the surface of the primary palate using palatal explant cultures of K14-GFP mice. A time-lapse observation of the GFP-labeled epithelium and an SEM analysis revealed that the extrusion epithelium appeared at the region corresponding to the fusing area and expanded rostrally on the nasal septum surface in the absence of the secondary palatal processes. Unlike on the secondary palate surface, cellular migration and subsequent autonomous mesenchymal exposure were not evident on the nasal septum or the primary palate. TUNEL staining revealed that these extrusion epithelia were undergoing apoptosis. These findings indicated that extrusion with apoptosis was autonomously initiated at the presumptive region of the fusion without contact with the opposing secondary palate.

Recovery Over Time and Prognostic Factors in Treated Patients with Post-Infectious Olfactory Dysfunction: A Retrospective Study.

OBJECTIVES: The aims of the present study were to clarify the time-course of olfactory recovery and the prognostic factors in PIOD patients treated with Toki-shakuyaku-san (TSS). METHODS: A retrospective cohort study of patients with PIOD was conducted by reviewing patients' medical records. This study included patients who received TSS or a combination of TSS and zinc sulfate. Olfactory function was examined by T&T olfactometer at each 3-monthly follow-up visit. Patients with normal and mild olfactory dysfunction were excluded. Gender, age, treatment, duration of disease until the first visit and olfactory function scores of the T&T olfactometer at the first visit were analyzed as candidate clinical predictors of recovery. RESULTS: A total of 82 PIOD patients with ages ranging from 16 to 79 years were included. The mean duration of follow-up was 14.5 months (range 3-45 months). The number of patients with olfactory recovery increased for 24 months and the cumulative recovery rate was 77.3%. In about 60% of patients, olfactory recovery occurred within 6 months. Multivariate analysis showed that younger age (<65 years) and residual olfactory function were significantly associated with good olfactory recovery. CONCLUSIONS: We revealed recovery rates over time in patients with PIOD. The recovery of olfactory function often occurred during the early period (≤6 months). However, the number of patients with olfactory recovery increased for a long-term of 24 months after the first visit. Residual olfactory function and younger age were prognostic factors exactly. TSS may be a useful therapeutic agent for patients with PIOD. We believe that these results provide important information that is useful for counseling patients with PIOD.

The association among enterobacterial flora, dietary factors, and prognosis in patients with ulcerative colitis.

The role of enterobacterial flora in the onset and progression of inflammatory bowel diseases is a topic of considerable interest. Here, we assessed the association among enterobacterial flora, dietary factors, and ulcerative colitis (UC) progression. Forty-six patients with UC who were diagnosed as being in remission were enrolled. We collected each patient's stool sample one or two days before diagnostic colonoscopy. After colonoscopy, we observed the patients for one year and then retrospectively divided them into two groups: remission (n = 39) and relapse (n = 7) groups, depending on whether the relapse occurred during the follow-up period, and analyzed the relationship among patient characteristics, dietary factors, enterobacterial flora, and UC relapse. Overall, there were no significant differences in bacterial community populations between the remission and relapse groups, except that the order Lactobacillales was detected at a significantly higher rate in the relapse than in the remission group (100% vs 71.4%, p<0.05). Vitamin C intake was significantly higher in the remission than in the relapse group (p<0.05). Although there were no obvious differences in enterobacterial flora between the remission and relapse groups, there was a relationship among enterobacterial flora, diet, and UC progression. Given that the enterobacterial flora was only analyzed at the initiation of the study, we conclude that in future analyses, enterobacterial flora should be sampled at numerous time points to examine its role in UC progression. Further long-term longitudinal studies examining enterobacterial flora, dietary factors, and UC progression are also required.

Endoscopic resection of gangliocytic paraganglioma of the duodenum: a case report.

Duodenal gangliocytic paragangliomas are extremely rare. A 79-year-old woman underwent gastrointestinal endoscopy for screening prior to resection of gallbladder carcinoma. Gastrointestinal endoscopy revealed a 5-mm submucosal tumor in the second portion of the duodenum. Contrast-enhanced computed tomography revealed no tumor or metastasis. Endoscopic ultrasonography revealed low echo pattern of the tumor. Histopathological examination of the biopsy specimen revealed proliferation of three types of cells (epithelioid cells, spindle cells, and ganglion cells). Immunohistochemical examination revealed that the tumor was positive for S-100 and synaptophysin. The preoperative diagnosis was gangliocytic paraganglioma. The tumor was completely resected by endoscopic mucosal resection (EMR). In conclusion, an early stage of gangliocytic paraganglioma of the duodenum could be resected using EMR.

Gut Environment and Dietary Habits in Healthy Japanese Adults and their Association with Bowel Movement.

INTRODUCTION: Constipation is a common symptom that impairs the quality of life (QOL). This study aimed to investigate the relationship between bowel movement and gut microbiota and dietary intake. METHODS: To investigate correlations among bowel movement, food intake, and gut environment, 60 healthy Japanese participants were recruited. Bowel movement was assessed using the Bristol stool form scale (BSFS) and constipation scoring system (CSS). Dietary habit was assessed with a self-administered questionnaire wherein the food intake frequency was classified into 8 categories for 72 food/food groups. Gut microbiota was analyzed using terminal restriction fragment length polymorphism analysis. RESULTS: The constipation rate was significantly higher in females than in males. The QOL was significantly impaired in the constipated group. The fecal count of Bacteroides was decreased and that of Clostridium cluster IV was increased in participants with constipation. The BSFS score was negatively associated with the fecal count of Clostridium cluster XI and positively associated with the fecal count of Clostridium cluster XVIII and consumption of green tea. The total CSS score was positively associated with the fecal Prevotella count and negatively associated with fecal acetate levels and consumption of vegetables. Discriminant analysis estimated that constipation could be predicted correctly in 83% (p < 0.001) of the participants based on fecal microbiota and fecal short-chain fatty acids. DISCUSSION/CONCLUSION: Bowel movement was strongly affected by gut environment and food intake in Japanese participants. Improvement in dietary habits could promote bowel movement through the improvement of the environment in the gut, resulting in ameliorated QOL issues in healthy adults.

Internet survey on the actual situation of constipation in the Japanese population under 70 years old: focus on functional constipation and constipation-predominant irritable bowel syndrome.

BACKGROUND: In Japan, the prevalence of constipation-predominant irritable bowel syndrome (IBS-C) and functional constipation (FC) diagnosed by the Rome III criteria is unclear, as are the demographic profile, quality of life (QOL), and habits of persons with IBS-C or FC. METHODS: We performed an internet survey of constipation. After extracting 3000 persons fitting the composition of the general Japanese population, we investigated demographic factors, lifestyle, defecation, and laxatives. IBS-C and FC were diagnosed by Rome III criteria. Respondents also completed the Japanese IBS severity index (IBS-SI-J), Japanese IBS QOL scale (IBS-QOL-J), SF-8, Hospital Anxiety and Depression Scale (HADS), and Japanese Health Practice Index (JHPI). RESULTS: There were 262 respondents with FC (8.73%) [73 men and 189 women; mean age: 49.8 ± 13.1 years; mean body mass index (BMI): 21.0 ± 3.3 g/m2] and 149 respondents with IBS-C (4.97%) (76 men and 73 women; mean age; 41.6 ± 13.7 years; mean BMI: 20.8 ± 3.0 kg/m2). Total IBS-QOL-J score were significantly lower in the IBS-C group than the FC group. With regard to SF-8, score of mental component summary (MCS) was significantly lower in the IBS-C group. The total IBS-SI-J score and item scores, except for satisfactory defecation, were significantly higher in the IBS-C group than the FC group. HADS showed a significant increase of anxiety and depression in both the groups, and the JHPI revealed insufficient sleep. CONCLUSIONS: In Japan, among the population of under 70 years old, the prevalence of IBS-C and FC (Rome III criteria) was 4.97% and 8.76%, respectively. IBS-C caused more severe symptoms than FC, resulting in impairment of QOL.

Immunological effects of sublingual immunotherapy with Japanese cedar pollen extract in patients with combined Japanese cedar and Japanese cypress pollinosis.

Sublingual immunotherapy (SLIT) with Japanese cedar (JCe) pollinosis was expected to be effective for Japanese cypress (JCy) pollinosis. However, only a half of JCy pollinosis patients clinically improved. Therefore, we examined the immunological effect of SLIT for JCy pollinosis. Peripheral blood mononuclear cells (PBMCs) from patients with JCe and JCy pollinosis who did and did not receive SLIT were incubated with Cry j 1, Cha o 1 and Cha o 3 antigens. Basophil activation test (BAT) were performed. Production of IL-5 and IL-17 induced by antigens was inhibited in the SLIT group. Cry j 1-specific production of IL-10 was increased, and serum Cry j 1-specific IgE and -IgG4 were elevated. However, Cha o 1- or Cha o 3-specific production of IL-10 and specific IgG4 was not increased. Antigens-specific BAT did not decrease after SLIT. New SLIT with JCe and JCy is needed for patients with combined JCe and JCy pollinosis.

[Internet survey of the actual situation of constipation in Japanese general population REACTION-J:Research for Actual Situation of Constipation in the Japanese].

Although chronic constipation is highly prevalent, its definition remains unclear. Therefore, the prevalence varies depending on reports, and the understanding of actual situations is unclear. Hence, we performed an internet survey on constipation among the Japanese general population to study the background factors and actual situations. Preliminary study on the awareness of constipation was conducted among 10000 people in which 9523 of them was asked if they had constipation at the time of the survey. In this population, 51.5% realized that they had constipation. Multivariate analysis showed the significant association of constipation to age, sex, and past histories or complications of diabetes, hemorrhoids, and cerebrovascular diseases. In a main research composed of 3000 general Japanese population, approximately 30.9% of the subjects reported the use of laxatives to treat constipation, and 43.8% of them were found to use irritant laxatives. Moreover, 67.5% of the subjects purchased laxatives at a pharmacy. The frequency of bowel movement less than 3 times per week was manifested in 36.3% of the subjects, and more than once per week in 21.4%. The percentage of hard (Bristol Stool Form Scale [BSFS] Type 1-2), normal (BSFS Type 3-5), and diarrhea stools (BSFS Type 6-7) was 33.1%, 60.0%, and 6.9%, respectively. The quality of life (QOL) of the subjects with hard and diarrhea stools evaluated by SF-8 was significantly lower than that of those with normal stools. Furthermore, the actual monthly cost for the therapeutic drugs used for treating constipation was less than 1000 yen in 75% of the subjects. Analysis of the IBS-QOL-J indicated that the ≥5000 yen payable group had the lowest satisfaction of defecation among the study groups. At present, many Japanese patients with constipation have not been receiving enough treatment for constipation. Therefore, appropriate medication by physicians as well as instruction to patients is required.

Endoscopic Resection of a Pedunculated Cavernous Hemangioma of the Sigmoid Colon: A Case Report.

Hemangiomas are common benign tumors that usually occur on the head and neck in children. However, colonic hemangiomas are rare in clinical practice. Approximately 80% of colonic hemangiomas are of the cavernous type, and morphologically, ≥80% of colonic hemangiomas are sessile and semi-pedunculated. Notably, pedunculated colonic hemangiomas are rare. A 69-year-old woman presented with hematochezia and underwent colonoscopy, which revealed a soft pedunculated submucosal tumor (SMT) measuring 1.5 cm in diameter, in the sigmoid colon. The surface of the SMT resembled the surrounding normal colonic mucosa with regard to color and appearance, with multiple red patches. Narrow-band imaging revealed a few telangiectasias on the surface of the SMT. The lesion could not be definitively diagnosed based on endoscopic findings. Therefore, for more accurate diagnosis, the SMT was removed by snare polypectomy with electrocautery after clipping the basal portion of the tumor stalk for prophylactic hemostasis. Histopathological examination of the specimen revealed a cavernous hemangioma with a negative resection margin. We report a case of a pedunculated cavernous hemangioma of the sigmoid colon removed by snare polypectomy with electrocautery after clipping the basal portion of the tumor stalk for prophylactic hemostasis.

Observational Study on Knowledge and Eating Habits with Respect to Low- and High-FODMAP Foods in Medical Checkup Populations in Japan.

BACKGROUND: There has been an increasing interest in low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diets for irritable bowel syndrome. The aims of the present study were (1) to survey knowledge and eating habits with respect to low- and high-FODMAP foods in a general population, and (2) to analyze the relationship between lower gastrointestinal problems (LGIP, pain and irregular stool habits) and habits/foods for prevention. METHODS: The present study was carried out with medical examinees (n = 1024) at a clinic in Japan using self-administrated questionnaires. The subjects were asked whether they knew each FODMAP food, eating habit, and cooking habit. Chi-squared tests were used for analyzing the characteristics of LGIP-related factors. Logistic regression models were utilized to select foods which predict LGIP. RESULTS: Women cooking by themselves and who were younger indicated less LGIP (Chai-square for trend). More than 60% reported that they often ate rice, coffee, eggs, pork, chicken, breads, noodles, and onions, which are solely classified as high-FODMAP foods. LGIP was related to age and self-cooking habits in women. Soybeans had the least significant relationship with LGIP (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.32-0.73), followed by seaweed, shellfish, wheat, cow's milk, green beans, and cauliflower. In contrast, artificial sweeteners were most significantly related with LGIP (OR 1.54, 95% CI 1.16-2.03), followed by margarine and tomato paste. CONCLUSIONS: The associations between FODMAP foods and LGPI appeared to be different from the Western results. Furthermore, some diets related to LGIP are suggested.

Evidence for the induction of Th2 inflammation by group 2 innate lymphoid cells in response to prostaglandin D2 and cysteinyl leukotrienes in allergic rhinitis.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) play important roles in allergic inflammation. However, their roles in the pathophysiology of allergic rhinitis (AR) are poorly understood. OBJECTIVE: Prevalence of ILC2s in the inferior nasal turbinate (INT) tissues and the activating mechanisms of ILC2s were examined in patients with house dust mite (HDM)-induced AR. METHODS: Eighteen patients with HDM-induced AR and 13 control subjects were recruited. Fresh INT tissues and peripheral blood mononuclear cells (PBMCs) were analysed using flow cytometry. Nasal lavage fluids (NLF) were collected at 10 minutes after the nasal provocation test (NPT) with HDM disc, and released mediators were measured by ELISA. Sorted ILC2s were cultured and stimulated with mediators associated with AR. RESULTS: The prevalence of ILC2s was significantly increased in nasal mucosa of patients with HDM-induced AR, and it was positively correlated with the number of infiltrating eosinophils. ILC2s in the INT tissues expressed a prostaglandin D2 (PGD2 ) receptor, chemoattractant receptor-homologous molecule-expressed TH2 cells (CRTH2) and a cysteinyl leukotriene (cysLTs) receptor, CysLT1. After NPT, the number of eosinophils and concentrations of PGD2 and cysLTs were significantly increased in the NLF from AR patients. PGD2 and cysLTs significantly induced IL-5 production from cultured PBMC-derived ILC2s dose-dependently. PGD2 -induced and cysLTs-induced productions of IL-5 and IL-13 from ILC2s were completely inhibited by ramatroban, a dual CRTH2 and thromboxane receptor antagonist, and montelukast, a CysLT1 antagonist, respectively. CONCLUSIONS: PGD2 -CRTH2 and cysLTs-CysLT1 axes may activate tissue-resident ILC2s to produce Th2 cytokines, IL-5 and IL-13, leading to the development of allergic inflammation in AR.