Allergic Rhinitis and House Dust Mite Sensitization Determine Persistence of Asthma in Children

Objective To specify clinical and immunological parameters of the mechanisms, which may lead to development of persistent asthma, or regression of the disease symptoms. Methods Eighty children with childhood asthma, diagnosed in the past by using the modifed Asthma Predicted Index (mAPI), were divided into two groups: remission group and persistent group. There were 3 study visits (baseline, at 6 mo, and at 12 mo). Clinical remission of asthma was defned as the absence of asthma symptoms for at least 12 mo without treatment. The patients could switch from one group to another during the 12 mo of follow-up. Clinical, infammatory, and immunoregulatory predictors of asthma remission/persistence were analyzed. Results The presence of mAPI criteria as well as house dust mite (HDM) allergy and allergic rhinitis at 7–10 y, were associated with a reduced prevalence of asthma remission. The increased eosinophil blood count in mAPI criteria was associated with a lower expression of CD25 positive cells. HDM allergy was associated with a higher fractional exhaled nitric oxide (FeNO) level (p=0.0061) and higher expression of CD25CD71 (p=0.0232). Allergic rhinitis was associated with a higher expression of PPAR (p=0.0493) and CD25CD71 (p=0.0198), and lower expression of glycoprotein A repetitions predominant (GARP). Conclusions Persistence of childhood asthma was largely determined by the presence of allergic rhinitis and sensitization to HDM. Additionally, API criteria but not immunoregulation processes, were related to asthma persistence.

Comparative study on establishing an immune tolerance model for allergic conjunctivitis in mice with different methods / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To establish an immune tolerance model for allergic conjunctivitis in newborn mice with different methods and observe the impact of environmental factors on allergic conjunctivitis in early life.METHOD: A total of 50 Balb/c newborn mice were randomly divided into blank control group, ovalbumin(OVA)+subcutaneous injection group, OVA+nebulized inhalation group, OVA+gastric group, ragweed pollen(RW)+subcutaneous injection group, RW+nebulized inhalation group, RW+gastric group, house dust mite(HDM)+subcutaneous injection group, HDM+nebulized inhalation group, HDM+intragastric group(n=5 animals/group). Except for the blank control group, mice in each group were individually exposed to the corresponding antigens to induce immune tolerance early in life and stimulated with the corresponding antigens in adulthood. The ocular surface was visualized by anterior segment photography. The relative expression level of conjunctival RANTES and IL-17 mRNA was measured by RT-qPCR and serum IL-17 concentration was measured by ELISA.RESULTS: Compared with the blank control group, the relative expression level of conjunctiva IL-17 mRNA in RW+gastric group was the highest, and it was the lowest in RW+subcutaneous group(all P<0.05). The relative expression level of conjunctiva RANTES mRNA was the highest in RW+gastric group(P<0.001). Compared with the blank control group, the serum concentration of IL-17 was increased in all treatment groups except OVA+nebulizer group and RW+subcutaneous group(P<0.05).CONCLUSION: The immune tolerance of allergic conjunctivitis induced by subcutaneous injection of antigen was the most suitable method in the early life of mice.

HSP90α exacerbates house dust mite-induced asthmatic airway inflammation by upregulating endoplasmic reticulum stress in bronchial epithelial cells / 南方医科大学学报

OBJECTIVE@#To explore the role of heat shock protein 90α (HSP90α) and endoplasmic reticulum (ER) stress pathway in allergic airway inflammation induced by house dust mite (HDM) in bronchial epithelial cells.@*METHODS@#A HDM- induced asthmatic cell model was established in human bronchial epithelial (HBE) cells by exposure to a concentration gradient (200, 400 and 800 U/mL) of HDM for 24 h. To test the effect of siHSP90α and HSP90 inhibitor 17-AAG on HDM-induced asthmatic inflammation, HBE cells were transfected with siHSP90α (50 nmol, 12 h) or pretreated with 17-AAG (900 nmol, 6 h) prior to HDM exposure (800 U/mL) for 24 h, and the changes in the expression of HSP90α and ER stress markers were assessed. We also tested the effect of nasal drip of 17-AAG, HDM, or their combination on airway inflammation and ER stress in C57BL/6 mice.@*RESULTS@#In HBE cells, HDM exposure significantly up-regulated the expression of HSP90α protein (P=0.011) and ER stress markers XBP-1 (P=0.044), ATF-6α (P=0.030) and GRP-78 (P=0.027). Knocking down HSP90α and treatment with 17-AAG both significantly inhibited HDM-induced upregulation of XBP-1 (P=0.008). In C57BL/6 mice, treatment with 17-AAG obviously improved HDM-induced airway inflammation and significantly reduced the number of inflammatory cells in the airway (P=0.014) and lowered the levels of IL-4 (P=0.030) and IL-5 (P=0.035) in alveolar lavage fluid. Immunohistochemical staining showed that the expressions of XBP-1 and GRP-78 in airway epithelial cells decreased significantly after the treatment of 17-AAG.@*CONCLUSIONS@#HSP90α promotes HDM-induced airway allergic inflammation possibly by upregulating ER stress pathway in bronchial epithelial cells.

Dynamic changes in peripheral type Ⅱ innate lymphoid cell ( ILC2 ) subpopulation and its clinical significance in children with hay fever during the pollen season / 中华微生物学和免疫学杂志

Objective To analyze the dynamic changes in the expression and function of peripher-al typeⅡinnate lymphoid cell (ILC2) subpopulation and the activity of signal transducers and activators of transcription (STAT6) in children with hay fever during pollen season. Methods A total of 10 patients with hay fever, 10 patients with house dust mite ( HDM)-sensitized asthma and 12 healthy controls ( HC) were enrolled in this study. Changes in peripheral ILC2 and the intracellular expression of Th2-related cyto-kines were detected by flow cytometry during and outside the pollen season. Peripheral Lin- cell population was isolated from each group and cultured with the presence of IL-25 or IL-33 for 7 d. The concentrations of IL-5 and IL-13 in culture supernatants were measured by ELISA. Expression of phospho-STAT6 at protein level was quantified by Western blot. Results Within the pollen season, the percentage of peripheral ILC2 cells was significantly higher in children with hay fever [(23. 09±7. 86)％] than in children with HDM-sen-sitized asthma [(6. 84±3. 85)％, P<0. 05] and healthy children[(1. 69±0. 87)％, P<0. 05]. In the non-pollen season, the peripheral ILC2 cells in children with hay fever presented a decreasing trend [(11. 30±2. 45)％], but was still higher than that in HDM-sensitized asthmatics [(3. 76±1. 96)％, P<0. 05] and HC [(1. 32±0. 91)％, P<0. 05] at the same time point. Moreover, peripheral IL-13+ILC2 cells in children with hay fever [(6. 94±3. 16)％ vs(4. 17±1. 98)％, P<0. 05] and in HDM-sensitized asthmatics [(1. 89 ±0. 70)％ vs(1. 44±0. 55)％, P<0. 05] during the pollen season were significantly higher than those in the non-pollen season. After the in vitro stimulation with IL25 or IL-33, the levels of IL-5 and IL-13 in culture supernatants were both increased in children with hay fever and HDM-sensitized asthmatics, and a synergis-tic action was observed when IL25 and IL-33 were used in combination. Meanwhile, the protein level of phospho-STAT4 in Lin-cells was significantly up-regulated in the hay fever group after stimulation with IL25 and IL-33. Conclusions During the pollen season, the abnormal number and function of ILC2 subpopula-tion in children with hay fever might be another cause of the occurrence of clinical symptoms in a short period of time or acute exacerbation.

Dynamic changes in peripheral type Ⅱ innate lymphoid cell (ILC2) subpopulation and its clinical significance in children with hay fever during the pollen season / 中华微生物学和免疫学杂志

Objective@#To analyze the dynamic changes in the expression and function of peripheral type Ⅱ innate lymphoid cell (ILC2) subpopulation and the activity of signal transducers and activators of transcription (STAT6) in children with hay fever during pollen season.@*Methods@#A total of 10 patients with hay fever, 10 patients with house dust mite (HDM)-sensitized asthma and 12 healthy controls (HC) were enrolled in this study. Changes in peripheral ILC2 and the intracellular expression of Th2-related cytokines were detected by flow cytometry during and outside the pollen season. Peripheral Lin- cell population was isolated from each group and cultured with the presence of IL-25 or IL-33 for 7 d. The concentrations of IL-5 and IL-13 in culture supernatants were measured by ELISA. Expression of phospho-STAT6 at protein level was quantified by Western blot.@*Results@#Within the pollen season, the percentage of peripheral ILC2 cells was significantly higher in children with hay fever [(23.09±7.86)%] than in children with HDM-sensitized asthma [(6.84±3.85)%, P<0.05] and healthy children[(1.69±0.87)%, P<0.05]. In the non-pollen season, the peripheral ILC2 cells in children with hay fever presented a decreasing trend [(11.30±2.45)%], but was still higher than that in HDM-sensitized asthmatics [(3.76±1.96)%, P<0.05] and HC [(1.32±0.91)%, P<0.05] at the same time point. Moreover, peripheral IL-13+ ILC2 cells in children with hay fever [(6.94±3.16)% vs(4.17±1.98)%, P<0.05] and in HDM-sensitized asthmatics [(1.89±0.70)% vs(1.44±0.55)%, P<0.05] during the pollen season were significantly higher than those in the non-pollen season. After the in vitro stimulation with IL25 or IL-33, the levels of IL-5 and IL-13 in culture supernatants were both increased in children with hay fever and HDM-sensitized asthmatics, and a synergistic action was observed when IL25 and IL-33 were used in combination. Meanwhile, the protein level of phospho-STAT4 in Lin- cells was significantly up-regulated in the hay fever group after stimulation with IL25 and IL-33.@*Conclusions@#During the pollen season, the abnormal number and function of ILC2 subpopulation in children with hay fever might be another cause of the occurrence of clinical symptoms in a short period of time or acute exacerbation.

Epithelial PI3K-δ Promotes House Dust Mite-Induced Allergic Asthma in NLRP3 Inflammasome-Dependent and -Independent Manners

PURPOSE: Phosphoinositide 3-kinase (PI3K)-δ-dependent Akt activation is known to play critical roles in various immune responses of white blood cells in which PI3K-δ isoform is mostly expressed in contrast to the classes IA PI3Ks p110α and p110β. However, the immunological role of PI3K-δ isoform is still controversial in airway epithelium under house dust mite (HDM)-induced allergic response. This study aimed to evaluate the role of PI3K-δ isoform in HDM-induced allergic responses, focusing on NLRP3 inflammasome activation in airway epithelium.METHODS: We used wild-type mice and PI3K-δ knock-out (KO) mice for HDM-induced asthma animal model and also performed in vitro experiments using primary cultured murine tracheal epithelial cells and human airway epithelial cells.RESULTS: PI3K-δ activated HDM-induced NLRP3 inflammasome and epithelial cell-derived cytokines in the lung including airway epithelial cells. PI3K-δ KO mice or knock-down of PI3K-δ using siRNA exhibited the significant reduction in allergic asthmatic features and the suppression of NLRP3 inflammasome assembly as well as epithelial cell-derived cytokines. Interestingly, significantly increased expression of PI3K-δ isoform was observed in stimulated airway epithelial cells and the increases in epithelial cell-derived cytokines were markedly suppressed by blocking PI3K-δ, while these cytokine levels were independent of NLRP3 inflammasome activation.CONCLUSIONS: The results of this study suggest that PI3K-δ-isoform can promote HDM-induced allergic airway inflammation via NLRP3 inflammasome-dependent response as well as via NLRP3 inflammasome-independent epithelial cell activation.

Comparison of Long-term Efficacy of Subcutaneous Immunotherapy in Pediatric and Adult Patients With Allergic Rhinitis

PURPOSE: Data comparing the long-term efficacy and safety of subcutaneous immunotherapy (SCIT) using house dust mite (HDM) in children and adults with allergic rhinitis (AR) are limited. This study aimed to compare the long-term effects of HDM-SCIT in a cohort of Chinese pediatric and adult patients with AR. METHODS: A total of 124 pediatric and adult AR patients received HDM-SCIT for 3 years, with 118 patients being followed-up for 2 years. Prior to treatment (baseline), at the end of the 3-year treatment periods (third year) and 2 years after the discontinuation of treatment (fifth year), all patients were evaluated for total nasal symptom scores (TNSS), daily medication score (DMS), total combined score (TCS; symptoms [nasal + ocular] + DMS) and quality of life (QoL). Safety was assessed according to adverse events reported. RESULTS: After 3-year treatment, HDM-SCIT significantly improved symptoms and QoL scores at the end of the third and fifth years in both groups. Better improvements were observed in the third and fifth years based on baseline, in children compared to adults (TNSSΔ3: 6.66 vs. 5.41, P = 0.011; TCSΔ3: 4.30 vs. 3.83, P = 0.027 and TNSSΔ5: 6.16 vs. 4.86, P = 0.037; TCSΔ5: 4.11 vs. 3.62, P = 0.044).Shorter duration of AR history before SCIT (<10 vs. ≥10 years) resulted in better improvements at the end of the third and fifth years (TCSΔ3: 4.12 vs. 3.13, P = 0.036; TCSΔ5: 3.90 vs. 3.09, P = 0.033). HDM-SCIT was safe and comparable in both children and adults with AR. CONCLUSIONS: Children with AR may achieve better long-term efficacy of HDM-SCIT than adults with AR.

Efficacy and Safety of Sublingual Immunotherapy in Elderly Rhinitis Patients Sensitized to House Dust Mites

PURPOSE: This study aims to determine the efficacy and safety of house dust mite (HDM)-sublingual immunotherapy (SLIT) in elderly patients with AR. METHODS: A total of 45 patients aged ≥ 60 years with HDM-induced AR who had ≥ 3 A/H ratio on skin prick test and/or ≥ 0.35 IU/L to both Dermatophagoides farinae and Dermatophagoides pteronyssinus by ImmunoCAP were enrolled in 4 university hospitals. To evaluate additional effects of HDM-SLIT, they were randomized to the SLIT-treated group (n = 30) or control group (n = 15). Rhinoconjunctivitis total symptom score (RTSS), rhinoscopy score, Korean rhinoconjunctivitis quality of life questionnaire, rhinitis control assessment test, asthma control test scores, and adverse reactions, were assessed at the first visit (V1) and after 1 year of treatment (V5); for immunological evaluation, serum levels of HDM-specific immunoglobulin A/IgE/IgG1/IgG4 antibodies and basophil response to HDMs were compared between V1 and V5 in both groups. RESULTS: There were no significant differences in demographics, RTSS, skin reactivity to HDMs, or serum total/specific IgE levels to HDMs (P < 0.05, respectively) between the 2 groups. Nasal symptom score and RTSS decreased significantly at year 1 in the 2 groups (P < 0.05). There were no significant differences in percent decrease in nasal symptom score and RTSS at year 1 between the 2 groups (P < 0.05); however, rhinoscopic nasal symptom score decreased significantly in the SLIT-treated group (P < 0.05). Immunological studies showed that serum specific IgA levels (not specific IgE/IgG) and CD203c expression on basophils decreased significantly at V5 in the SLIT-treated group (P = 0.011 and P = 0.001, respectively), not in the control group. The control group required more medications compared to the treatment group, but there were no differences in adverse reactions. CONCLUSIONS: It is suggested that HDM-SLIT for 1 year could induce symptom improvement and may induce immunomodulation in elderly rhinitis patients.

Effect of Lyn on expression of MUC5AC in human bronchial epithelial cells induced by house dust mite and its mechanism / 吉林大学学报(医学版)

Objective:To investigate the effect of Lyn on the expression of MUC5AC in human bronchial epithelial cells induced by house dust mite(HDM),and to explore its possible mechanism.Methods:The human bronchial epithelial cells(16 HBE)were divided into PBS group and HDM group(1 μg·L-1HDM).The cells were transfected by liposome.The luciferase report gene of MUC5AC promoter was constructed.The relative luciferase unit(RLU)was detected by double luciferase report gene assay.The expression of MUC5AC in the cells was detected by immunofluorescence technique and observed by confocal microscope.The expression level of STAT6 in the 16HBE cells was detected by Western blotting method.Results:The results of double luciferase report gene assay showed that the RLU in HDM group was higher than that in PBS group(P<0.05).The RLU of cells in HDM group treated with LynsiRNA intervention was higher than that of the cells without LynsiRNA intervention(P<0.05).The immunofluorescence results demonstrated that the expression level of MUC5AC in HDM group was higher than that in PBS group(P<0.05),and the expression level of MUC5AC in HDM group was increased after LynsiRNA intervention(P<0.05).The Western blotting results indicated that the expression level of STAT6 was up-regulated in HDM group when the cells were intervened with LynsiRNA(P<0.05). Conclusion:Deficiencyof Lyn can increase the expression of MUC5AC in the human bronchial epithelial cells,and its mechanism may be related to regulating the STAT6 signal pathway by Lyn.

Housedustmite Allergy as the Cause of Eosinophilic Collitis: A Case Report

@#There are only few cases of Eosinophilic Collitis(EC) have been reported worldwide. The mechanism and aetiology of EC are still unclear. We describe a 35 years old man presented with chief complaints of gastrointestinal symptoms. In blood examination, his total IgE and specific IgE to house dust mites were very high. Colonoscopy was done and histological examination from biopsy specimens reported infiltration of lymphoplasmacytic cells and eosinophils, compatible with Eosinophilic colitis. The patient was treated with antihistamine and short course of antibiotics. He was been advised to avoid house dust mites. He was then remained asymptomatic. Our report suggests house dust mites allergy as the causes of EC. Combination of antihistamine, antibiotics and avoidance of house dust mites are helpful in treating EC in this particular case.

Changes in basophil activation during immunotherapy with house dust mite and mugwort in patients with allergic rhinitis

BACKGROUND: The basophil activation test (BAT) is a promising tool for monitoring allergen-specific immunotherapy responses. OBJECTIVE: We aimed to investigate the changes in basophil activation in response to the inhalant allergens of house dust mite (HDM) and mugwort pollen during immunotherapy in patients with allergic rhinitis. METHODS: We enrolled patients with allergic rhinitis who were to receive subcutaneous immunotherapy for the inhalant allergens HDM or mugwort. A BAT was performed to assess CD63 upregulation in response to allergen stimulation using peripheral blood collected from the patients prior to immunotherapy and at 3, 6, 12, and 24 months after beginning immunotherapy. Rhinitis symptoms were evaluated using the rhinitis quality of life questionnaire (RQLQ) at 1-year intervals. RESULTS: Seventeen patients (10 with HDM sensitivity, 3 with mugwort sensitivity, and 4 with sensitivity to both HDM and mugwort) were enrolled in the study. Basophil reactivity to HDM did not change significantly during 24 months of immunotherapy. However, a significant reduction in basophil reactivity to mugwort was observed at 24-month follow-up. There was no significant association between the change in clinical symptoms by RQLQ and the change in basophil reactivity to either allergen. The change in allergen-specific basophil reactivity to HDM was well correlated with the change in nonspecific basophil activation induced by anti-FcεRI antibody, although basophil reactivity to anti-FcεRI antibody was not significantly reduced during immunotherapy. CONCLUSION: Suppression of CD63 upregulation in the BAT was only observed with mugwort at 2-year follow-up. However, the basophil response did not reflect the clinical response to immunotherapy.

Comparison of Multiple Allergen Simultaneous Test and ImmunoCAP for the Diagnosis of Allergic Rhinitis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Specific IgE assays are important in the diagnosis and treatment of allergic rhinitis (AR). Among the diagnostic tests of AR, multiple allergen simultaneous test (MAST) and ImmunoCAP have been frequently used as simple, safe, and economical methods. In this study, we compared the diagnostic outcomes of MAST and ImmunoCAP in patients with AR. SUBJECTS AND METHOD: Seventy-eight patients (52 men, 26 women, mean age 34.5 years: range 6–80 years), who have nasal symptoms of allergy and no clinical factors to influence the test results, underwent routine skin prick test (SPT) and MAST, and ImmunoCAP for eight major allergens. The diagnosis of AR was based on the criteria of SPT. The class 1 responses or more were regarded as positive for both MAST and ImmunoCAP. The agreements, sensitivities, and specificities of MAST and ImmunoCAP were evaluated along with the correlation between the two tests. RESULTS: Total agreement rates of MAST and ImmunoCAP amounted to 91.5 and 92.1%, respectively. The overall sensitivity and specificity of MAST were 73.4 and 95.3%, respectively, and those of ImmunoCAP were 81.4 and 94.5%, respectively. The correlations between MAST and ImmunoCAP showed statistical significance for Dermatophagoides pteronyssinus/Dermatophagoides farinae. CONCLUSION: Our study demonstrated the diagnostic usefulness of both MAST and ImmunoCAP in AR, especially for the most prevalent allergens of house dust mites. Moreover, ImmunoCAP, which showed higher sensitivity than MAST, can be effectively used in rhinology clinics.

Effect of Lyn on expression of MUC5AC in human bronchial epithelial cells induced by house dust mite and its mechanism / 吉林大学学报(医学版)

Objective: To investigate the effect of Lyn on the expression of MUC5AC in human bronchial epithelial cells induced by house dust mite (HDM), and to explore its possible mechanism. Methods: The human bronchial epithelial cells 16HBE) were divided into PBS group and HDM group 1 μg · L-1 HDM). The cells were transfected by liposome. The luciferase report gene of MUC5AC promoter was constructed. The relative luciferase unit (RLU) was detected by double luciferase report gene assay. The expression of MUC5AC in the cells was detected by immunofluorescence technique and observed by confocal microscope. The expression level of STAT6 in the 16HBE cells was detected by Western blotting method. Results: The results of double luciferase report gene assay showed that the RLU in HDM group was higher than that in PBS group (P<0.05). The RLU of cells in HDM group treated with LynsiRNA intervention was higher than that of the cells without LynsiRNA intervention (P<0.05). The immunofluorescence results demonstrated that the expression level of MUC5AC in HDM group was higher than that in PBS group (P<0.05), and the expression level of MUC5AC in HDM group was increased after LynsiRNA intervention (P<0.05). The Western blotting results indicated that the expression level of STAT6 was up-regulated in HDM group when the cells were intervened with LynsiRNA (P<0.05). Conclusion: Deficiency of Lyn can increase the expression of MUC5AC in the human bronchial epithelial cells, and its mechanism may be related to regulating the STAT6 signal pathway by Lyn.

Changes in percentage and function of CD4+CD25+regulatory T cells in peripheral blood of patients with hay fever / 中华微生物学和免疫学杂志

Objective To investigate the changes in percentage and function of CD4+CD25+regu-latory T cells ( Tregs) in peripheral blood of patients with hay fever. Methods A total of 20 patients with hay fever, 20 patients with house dust mite-induced allergic asthma and 20 healthy subjects were enrolled in this study. Peripheral blood samples were collected from all subjects to isolate PBMCs. Percentages of Tregs in PBMCs were measured by flow cytometry. CD4+CD25+ Tregs and CD4+CD25-T cells ( Teffs) were isola-ted by immunomagnetic cell sorting. Effects of CD4+CD25+Tregs on the proliferation of Teffs were evaluated by MTT assay. Expression of Foxp3 and TGF-β1 at mRNA level was analyzed by RT-PCR. Results During the pollen season, the percentage of circulating Tregs in patients with hay fever [(1. 82+0. 82)％] was sig-nificantly lower than that in patients with house dust mite-induced allergic asthma [(2. 96±1. 34)％] and health subjects [(5. 78±2. 29)％] (both P<0. 05). Expression of Foxp3 at mRNA level was significantly reduced in patients with hay fever (0. 46±0. 25) as compared with that of the house dust mite-induced aller-gic asthma (0. 64±0. 31) and healthy control (1. 04±0. 21) groups (both P<0. 05). Expression of TGF-β1 at mRNA level in both hay fever (0. 34±0. 27) and house dust mite-induced allergic asthma (0. 43±0. 31) groups was lower than that of the healthy control group (0. 99±0. 34). Treg-mediated suppression of Teff proliferation was significantly decreased in patients with hay fever [(17. 1±8. 4)％] as compared with that in patients with house dust mite-induced allergic asthma [(21. 4±9. 1)％]) and healthy subjects [(36. 0± 13. 9)％] (P<0. 05). Conclusion Decreased percentage and defective function of Tregs might be one of the major causes for the occurrence and development of hay fever in children during the pollen season.

Dynamic changes in Th17/Treg balance among children with seasonal allergic rhinitis / 中华微生物学和免疫学杂志

Objective To investigate the levels and significance of Th17 cells and regulatory T cells (Treg) in peripheral blood of children with allergic rhinitis during pollen and non-pollen seasons.Methods Thirteen children with hay fever, 10 children with house dust mite(HDM)-allergic asthma and 10 healthy children were recruited into this study.Percentages of Th17 and Treg cells were detected by flow cytometry.Levels of IL-17, IL-10 and TGF-β in cell culture supernatants were measured by ELISA.Results (1) The percentages of Th17 cells in children with allergic rhinitis [(3.4±2.4)%] were significantly higher than those in HDM-allergic asthmatics [(2.1±1.6)%] and those in healthy children [(0.5±0.3)%] during pollen season (both P<0.05).The levels of Treg cells in allergic rhinitis group [(2.1±1.3)%] and in HDM-allergic asthma group [(3.6±1.9)%] were significantly lower than those in healthy control group [(5.5±2.8)%] (both P<0.05).The levels of Th17 cells [(3.0±1.9)% vs (3.4±2.4)%, P<0.05] and ratios of Th17/Treg cells [(1.4±1.0)% vs (1.7±1.5)%, P<0.05] in children with allergic rhinitis were significantly decreased during non-pollen season as compared with those during pollen season, but the levels of Treg cells were up-regulated [(2.4±1.6)% vs (2.1±1.3)%, P<0.05].(2) Correlation analysis revealed that the ratios of Th17/Treg cells were positively correlated with the concentrations of FeNO (fractional concentration of exhaled NO) (r=0.321, P<0.05) and the counts of circulating eosinophils (r=0.198, P<0.05) in children with allergic rhinitis during pollen season.Conclusion The imbalanced Th17 and Treg cells in children with allergic rhinitis during pollen season might play a vital role in the regulation of allergic airway inflammation.

DNA methyldtion and asthma: Recent progress / 第二军医大学学报

DNA methylation is one of the most common forms of epigenetic modification, and t is closely related to the development of bronchial asthma, but its mechanism is unclear. Without altering the sequences of genes, DNA methylation can transfer the cytosine on the 5 end of CpG dinucleotide into methyl cytosine by DNA methyltransferase. Hence, DNA methylation can regulate gene expression, leading to the development and progression of diseases. In this review, we summarized the roles of DNA methylation in bronchial asthma, including related predisposing factors and mechanisms of action.

Efficacy of Nasal Cellulose Powder in the Symptomatic Treatment of Allergic Rhinitis: A Randomized, Double-Blind, Placebo-Controlled Trial

PURPOSE: Nasal Cellulose Powder (NCP), which can prevent from binding an allergen to nasal mucosa, may reduce allergic rhinitis (AR) symptoms in dust mite-sensitized children. This study was conducted to assess the efficacy of NCP in improving clinical symptoms of a nasal airflow limitation and the response of nasal inflammatory cells. METHODS: Children with dust mite-sensitized AR aged 6–18 years were recruited. After a 4-week run-in period, NCP or a placebo was administered, 1 puff per nostril 3 times daily for 4 weeks. The nasal provocation test (NPT) with Dermatophagoides pteronyssinus (Der p) was performed before and after treatment. The daily symptom scores (DSS), daily medication scores (DMS), the peak nasal inspiratory flows (PNIF), nasal airway resistance (NAR), as well as the maximum tolerated dose of NPT and eosinophil counts in nasal scraping, were evaluated. RESULTS: Sixty children (30 NCP and 30 placebos) were enrolled. Before treatment, there were no significant differences in age, dust mite control measures, DSS, DMS, PNIF, NAR, the maximum tolerated dose of NPT, or nasal eosinophil scores between children receiving NCP and placebos. After treatment, there were no significant differences between the NCP and placebo groups in the median (range) of the outcomes—DSS: 2.06 (0.18–3.77) vs. 1.79 (0.08–7.79), P=0.756; DMS: 1.60 (0–5.13) vs. 0.56 (0–4.84), P=0.239; PNIF (L/min): 110 (60–160) vs. 100 (50–180), P=0.870; NAR (Pa/cm³/s): 0.40 (0.20–0.97) vs. 0.39 (0.24–1.32), P=0.690; the maximum tolerated dose of NPT and the nasal eosinophil scores: 1 (0–4) vs. 1 (0–4), P=0.861. CONCLUSIONS: NCP treatment may not be more effective than placebo treatment in dust mite-sensitized AR children.

Changes in percentage and function of CD4+CD25+regulatory T cells in peripheral blood of patients with hay fever / 中华微生物学和免疫学杂志

Objective To investigate the changes in percentage and function of CD4+CD25+regu-latory T cells ( Tregs) in peripheral blood of patients with hay fever. Methods A total of 20 patients with hay fever, 20 patients with house dust mite-induced allergic asthma and 20 healthy subjects were enrolled in this study. Peripheral blood samples were collected from all subjects to isolate PBMCs. Percentages of Tregs in PBMCs were measured by flow cytometry. CD4+CD25+ Tregs and CD4+CD25-T cells ( Teffs) were isola-ted by immunomagnetic cell sorting. Effects of CD4+CD25+Tregs on the proliferation of Teffs were evaluated by MTT assay. Expression of Foxp3 and TGF-β1 at mRNA level was analyzed by RT-PCR. Results During the pollen season, the percentage of circulating Tregs in patients with hay fever [(1. 82+0. 82)％] was sig-nificantly lower than that in patients with house dust mite-induced allergic asthma [(2. 96±1. 34)％] and health subjects [(5. 78±2. 29)％] (both P<0. 05). Expression of Foxp3 at mRNA level was significantly reduced in patients with hay fever (0. 46±0. 25) as compared with that of the house dust mite-induced aller-gic asthma (0. 64±0. 31) and healthy control (1. 04±0. 21) groups (both P<0. 05). Expression of TGF-β1 at mRNA level in both hay fever (0. 34±0. 27) and house dust mite-induced allergic asthma (0. 43±0. 31) groups was lower than that of the healthy control group (0. 99±0. 34). Treg-mediated suppression of Teff proliferation was significantly decreased in patients with hay fever [(17. 1±8. 4)％] as compared with that in patients with house dust mite-induced allergic asthma [(21. 4±9. 1)％]) and healthy subjects [(36. 0± 13. 9)％] (P<0. 05). Conclusion Decreased percentage and defective function of Tregs might be one of the major causes for the occurrence and development of hay fever in children during the pollen season.

Efficacy of Sublingual Immunotherapy for House Dust Mite-Induced Allergic Rhinitis: A Meta-Analysis of Randomized Controlled Trials

PURPOSE: Allergic rhinitis (AR) has become a global issue for a large part of the general population. Sublingual immunotherapy (SLIT) has been used extensively to treat persistent allergic rhinitis (PAR). Although systematic reviews have confirmed the effectiveness of SLIT for the treatment of AR, a considerable number of studies using extracts of house dust mites (HDMs) for immunotherapy found no consensus on basic treatment parameters and questioned the efficacy of SLIT. METHODS: In this study, we evaluated SLIT for PAR by a meta-analysis of randomized controlled trials (RCTs). Medline, Embase, and Cochrane Library database searches were performed for RCTs on the treatment of PAR by SLIT that assessed clinical outcomes related to efficacy through May 2016. Descriptive and quantitative information was abstracted. An analysis was performed with standardized mean differences (SMDs) under a fixed or random effects model. Subgroup analyses were performed. Heterogeneity was assessed using the I2 metric. RESULTS: In total, 25 studies were eligible for inclusion in the meta-analysis for symptom scores and 15 studies for medication scores. SLIT was significantly different from the controls for symptom scores (SMD=1.23; 95% confidence interval [CI]=1.74 to 0.73; P<0.001). For medication scores, significant differences for SLIT were also observed versus the controls (SMD=-1.39; 95% CI=-1.90 to -0.88; P<0.001). CONCLUSIONS: Our meta-analysis indicates that SLIT provided significant symptom relief and reduced the need for medications in PAR. In this study, significant evidence was obtained despite heterogeneity with regard to the use of mite extract. Specifically, the mite extract used was provided by the patients with PAR. Furthermore, to confirm both the objective outcomes and the effective doses of HDM allergen extracts, experimental data should be obtained from large high-quality population-based studies.

Prevalence and Clinical Characteristics of Local Allergic Rhinitis to House Dust Mites

Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy. The aim of this study was to evaluate the prevalence and clinical characteristics of LAR in Korean rhinitis patients compared to allergic rhinitis (AR) and non-allergic rhinitis (NAR). A total of 304 rhinitis patients were enrolled from November 2014 to March 2016. A skin prick test, serum total and specific immunoglobulin E, and a nasal provocation test (NPT) with house dust mite (HDM) were performed on all patients. Subjects also documented changes in rhinitis symptoms before and after NPT. Seventy-four patients with nasal hyper-reactivity and 80 patients with subclinical allergy were excluded. AR was diagnosed in 69 (46.0%) patients, NAR in 75 (50.0%) patients, and LAR to HDM in 6 (4.0%) patients. The average medication score and disease duration of each group were 14.5 points and 77.6 months in AR, 12.1 point and 51.1 months in NAR, and 17.7 point and 106.0 months in LAR, respectively. There were no significant differences in the baseline nasal symptom score of the three groups. However, after NPT with HDM, the score of rhinitis, itching, and obstructive were 4.83±1.47 vs. 1.95±2.53, 3.00±2.10 vs. 1.45±2.06, and 5.50±1.38 vs. 2.57±2.84 in LAR and NAR, respectively (p<0.05). LAR patients had longer duration of disease and tended to be older and have higher medication score than other rhinitis patients.