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ObjectiveTo investigate the therapeutic effects and difference in the effects of Arisaematis Rhizoma （AR） before and after processing （i.e.， Arisaematis Rhizoma Preparatum， ARP） with Zingiberis Rhizoma Recens-Alumen on allergic asthma in rats and to provide a basis for the theory of processing improving the efficacy. MethodA rat model of allergic asthma was established in 70 SD rats by intraperitoneal injection of ovalbumin （OVA）-aluminum hydroxide. The rats were administrated with the aqueous extracts of AR （1.2， 0.3 g∙kg-1） and ARP （1.2， 0.3 g∙kg-1） aqueous extracts by gavage， and montelukast sodium （0.001 g∙kg-1） was used as the positive drug. The T helper cell type 1/type 2 （Th1/Th2） ratio in the serum and bronchoalveolar lavage fluid （BALF） and percentages of inflammatory cells in BALF were determined. Polymerase chain reaction （PCR） was employed to determine the mRNA level of mucin 5AC （MUC5AC） in the lung tissue. The pathological changes in the lung tissue were observed by hematoxylin-eosin （HE） staining and PAS staining. Immunohistochemical assay was employed to measure the expression of c-Jun amino-terminal kinase （JNK）， extracellular signal regulated protein kinase （ERK）， and p38 mitogen-activated protein kinase （p38 MAPK） in rat lung tissue. Western blot was employed to determine the protein levels of ERK， p-ERK， JNK， p-JNK， p38， p-p38 in the lung tissue. The effects of AR and ARP were compared based on overall desirability. ResultCompared with the blank group， the levels of interleukin-12 （IL-12） and γ interferon （IFN-γ） in serum and BALF of rats in the model group were significantly lower （P<0.05， P<0.01）， and the levels of interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） were significantly higher （P<0.05， P<0.01）. Compared with the model group， the serum and BALF contents of IL-12 and IFN-γ in rats in the montelukast sodium group， high-dose AR group and high-dose ARP group were significantly higher （P<0.05， P<0.01）， and the contents of IL-4， IL-5 and IL-13 were significantly lower （P<0.05， P<0.01）， and the serum contents of IFN-γ in rats in the low-dose AR group and low-dose ARP group were in BALF was significantly higher （P<0.05） and IL-4 and IL-13 were significantly lower （P<0.05， P<0.01）， the percentages of macrophages， lymphocytes， neutrophils， and eosinophils were reduced in BALF， and the expression of JNK/ERK/p38 MAPK signaling pathway and MUC5AC protein was inhibited in lung tissues. Overall assessment of the normalized analysis revealed that the ARP group was slightly more potent than the AR group after administration of the same dose. ConclusionAR and ARP can effectively treat allergic asthma by inhibiting JNK/ERK/p38 MAPK signaling pathway， and the effect is better after concoction， which can provide data support for its "concoction efficiency".
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Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.
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Allergen immunotherapy(AIT)is considered the treatment capable of modifying the natural history of allergic respiratory disorders.The adverse reactions associated with AIT limit its clinical use in moderate to severe allergic asthma.Omalizumab is currently approved for the treatment of allergic asthma, chronic spontaneous urticaria, allergic rhinitis and other allergic diseases.A few trials have demonstrated the clinical efficacy of AIT and omalizumab combination therapy in children with moderate to severe allergic asthma.This review summarizes the research progress, mechanisma and application of omalizumab combined with AIT in children with moderate to severe allergic asthma.
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Background Dibutyl phthalate (DBP) is a common plasticizer in daily life and has been proved to be related to the exacerbation of allergic asthma. Domestic and foreign studies have shown that lipid peroxidation is closely related to the severity of asthma, which can be used as a basis for the diagnosis and treatment of asthma. Whether DBP can induce lipid peroxidation in allergic asthma remains to be further studied. Objective To investigate whether DBP aggravates allergic asthma by inducing lipid peroxidation in allergic asthma mice. Methods Eighty male BALB/c mice were randomly divided into 4 groups, namely control group, DBP group (40 mg·kg−1), 50 μg ovalbumin (OVA) group (allergic asthma model group), and DBP+OVA group. The DBP group and the DBP+OVA group were given DBP by gavage from Day 1 to 28, and the OVA group and the DBP+OVA group were sensitized by intraperitoneal injection of OVA, once every 3 d, a total of 5 injections, from Day 9 to 21. From Day 29 to 35, the OVA group and the DBP+OVA group were challenged by OVA atomization. After the exposure, samples of blood and lung were collected. The airway hyperresponsiveness of mice was observed by lung function analysis. The serum contents of immunoglobulin E (IgE), OVA-specific immunoglobulin E (OVA-IgE), and lung homogenate levels of interleukin 4 (IL-4) were detected by enzyme-linked immunosorbent assay (ELISA) to evaluate airway allergic inflammation. The pathological changes of lung tissues were observed after hematoxylin-eosin (HE) staining and collagen fiber (Masson) staining. The contents of reactive oxygen species (ROS), lipid ROS, glutathione peroxidase 4 (GPX4), reduced glutathione (GSH), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) in lung homogenates were detected by ELISA to evaluate lipid peroxidation. Results The results of lung function analysis showed that compared with the control group, the inspiratory resistance (Ri) and expiratory resistance (Re) of the OVA group and the DBP+OVA group were increased, and the lung compliance (Cldyn) was decreased. The DBP + OVA group was more severe, and the difference between the OVA group and the DBP + OVA group was statistically significant (P<0.05 or P<0.01). Compared with the control group, the contents of IgE, OVA-IgE, and IL-4 in the OVA group and the DBP+OVA group were increased (P<0.05 or P<0.01), which indicated more severe allergic airway inflammation. The HE sections of the OVA group and the DBP+OVA group showed inflammatory cell infiltration around the airway, airway wall hyperplasia and thickening, and severe airway deformation, and the presentation of the DBP+OVA group was the most serious. After Masson staining, the OVA group and the DBP+OVA group showed depositions of a large number of collagen fibers, and the blue collagen fibrosis in the DBP+OVA group was even more serious. ROS, lipid ROS, MDA, and 4-HNE levels increased and GSH and GPX4 levels decreased in the OVA and DBP+OVA groups (P<0.05 or P<0.01), with the most severe effect in the DBP+OVA group. Conclusion DBP may induce lipid peroxidation in mice allergic asthma by producing excessive ROS which may aggravate the allergic asthma in mice.
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OBJECTIVE To study the pharmacological basis of Schisandra chinensis in the treatment of allergic asthma. METHODS The common components of 10 batches of S. chinensis from different habitats were analyzed by UPLC-Q-TOF-MS/MS. Furthermore， the allergic asthma model was established by intraperitoneal injection of ovalbumin （OVA） and aluminum hydroxide for stimulation combined with atomization exitation； general behavioral observation and the contents of interferon γ （IFN-γ）， interleukin-4 （IL-4） and immunoglobulin E （IgE） in serum were taken as criteria for evaluating the therapeutic effect of S. chinensis from different habitats in the treatment of allergic asthma. Correlation coefficients between common peak area and efficacy evaluation index of each batch of medicinal material were analyzed through grey correlation degree and Pearson correlation analysis. RESULTS A total of 21 common components were identified in 10 batches of S. chinensis from different habitats. After administration of S. chinensis， symptoms such as shortness of breath， sneezing and curling of rats were alleviated. In addition， the content of IFN-γ was significantly increased while the contents of IL-4 and IgE in serum were distinctly decreased （P＜0.01）. Grey correlation analysis showed that 11 common components had high correlation coefficients with IFN-γ， IL-4 and IgE （rˉ＞0.8）. Pearson correlation analysis showed that 8 components were significantly positively correlated with the content of IFN-γ （P＜ 0.05）， and 9， 8 components were significantly negatively correlated with the content of IL-4 and IgE （P＜0.05）. Based on the results of grey correlation degree and Pearson correlation analysis， 7 components such as peak 3， 4， 6， 7， 9， 19 and 20， were highly related to S. chinensis in the treatment of allergic asthma. CONCLUSIONS Schisandrol A， schisandrin B， schisandrin C， gomisin M2， gomisin J， pregomisin and angeloylgomisin H are the potential pharmacodynamic substance basis of S. chinensis in the treatment of allergic asthma.
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Objective:To investigate the sensitization characteristics of ragweed pollen in patients with allergic rhinitis（AR） and（or） allergic asthma in Beijing area, and to provide basis for the prevention and treatment of ragweed pollen sensitized population. Methods:Patients with allergic rhinitis and/or asthma from January 2017 to December 2019 in the outpatient department of Allergy Department of Beijing Shijitan Hospital were retrospectively analyzed in this study. Skin prick test（SPT） was performed with ragweed pollen allergen reagents to compare different ages, genders and respiratory diseases allergen distribution, and to observe the sensitization characteristics of its population. All of the analyses were performed using SAS software version 9.4. Results:A total of 9 727 patients were enrolled in the end. The total positive rate of ragweed pollen SPT was 45.50%（4 426/9 727）, the highest positive rate was 65.54% in 13-17 years old group; The positive rate of ragweed pollen SPT was 49.79% in allergic rhinitis combined with asthma patients, followed by 46.46% in allergic rhinitis patients, and the lowest rate was 19.42% in single allergic asthma patients. There were more females than males in both ragweed pollen sensitized and non-ragweed pollen sensitized groups（P<0.05）, and the proportion was higher in 30-39 years old than in other age groups（P<0.05）. Ragweed pollen sensitization was higher than non-ragweed pollen sensitization in the allergic rhinitis group（98.49% vs 94.76%, P<0.05）. Ragweed pollen with other summer and autumn pollen allergens in patients with positive SPT, the top three were Chenopodium pollen, Humulus pollen and Artemisia grandis pollen, with positive rates of 90.42%, 89.63% and 85.40%, respectively. Ragweed combined with other pollen sensitization accounted for 99.57%（4 407/4 426）. Allergic rhinitis was the main disease in patients sensitized with ragweed pollen alone or combined with other pollens, and there was no significant difference between the two groups（94.97% vs 98.50%, P>0.05）. Conclusion:Ragweed pollen is highly sensitized in Beijing area, single ragweed pollen sensitization is rare, often combined with multiple pollen sensitization, and allergic rhinitis is the main disease.
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Humans , Male , Female , Adolescent , Adult , Rhinitis, Allergic, Seasonal/epidemiology , Retrospective Studies , Allergens , Pollen , Rhinitis, Allergic , Asthma/epidemiology , Skin TestsABSTRACT
ObjectiveTo investigate the regulatory effects of Xuanfu Daizhetang on a mouse model of allergic asthma induced by ovalbumin （OVA）. MethodSixty female BALB/c mice （6-8 weeks old， SPF） were randomly divided into groups. Ten mice were assigned to the normal group and given 0.2 mL of saline， while the remaining groups received intraperitoneal injections of Al（OH）3 at 5 g·L-1 and OVA at 1 g·L-1. The mice were divided into normal group （10 mL·kg-1 saline）， OVA model group （10 mL·kg-1 saline）， dexamethasone group （OVA+DEX， 1 mg·kg-1）， OVA+ low-dose Xuanfu Daizhetang group （OVA+XL， 7.065 g·kg-1）， OVA+ medium-dose Xuanfu Daizhetang group （OVA+XM， 14.13 g·kg-1）， and OVA+ high-dose Xuanfu Daizhetang group （OVA+XH， 28.26 g·kg-1）. An OVA-induced asthma model was established in mice. Hematoxylin-eosin （HE） and periodic acid-Schiff （PAS） staining methods were used to observe bronchial tissue pathological changes. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of immunoglobulin E （IgE）， interleukin-4 （IL-4）， IL-5， IL-13， IL-17A， and γ interferon （IFN-γ） in bronchoalveolar lavage fluid. Western blot was used to detect the phosphorylation of extracellular signal-regulated kinase （ERK）， p38 mitogen-activated protein kinase （MAPK）， and c-Jun N-terminal kinase （JNK） proteins in lung tissue. ResultCompared with the normal group， the OVA model group showed increased inflammatory cell infiltration in mouse alveoli， elevated levels of IL-4， IL-5， IL-13， IL-17A， IFN-γ in bronchoalveolar lavage fluid， and IgE in serum （P<0.05， P<0.01）， and promoted phosphorylation of MAPK signaling pathway-related proteins. Compared with the model group， the OVA+XL， OVA+XM， and OVA+XH groups showed reduced inflammatory cell infiltration in mouse alveoli， decreased levels of IL-4， IL-5， IL-13， IL-17A， IFN-γ in bronchoalveolar lavage fluid， and IgE in serum （P<0.05， P<0.01）， and inhibited phosphorylation of MAPK signaling pathway-related proteins. ConclusionThe results of this study suggest that Xuanfu Daizhetang has potential anti-allergic asthma activity， providing a theoretical basis for its future clinical application.
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The prevalence of allergic airway diseases has been increasing in recent years. Interleukin-18 (IL-18) plays an imperative role in allergic airway diseases by binding to IL-18Rα, thereby initiating the downstream proinflammatory pathway. IL-18 also binds to IL-18BP, thus inhibiting its binding to IL-18Rα. Therefore, further understanding of the role of IL-18 and its action mechanisms in allergic airway diseases is important for the treatment of allergic airway diseases, and for the development of IL-18-related biological agents.
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Objective:To explore the changes of T follicular regulatory (T FR) cells/T follicular helper (T FH) cells and their related cytokines in peripheral blood of children with dust mite allergic asthma, and their clinical significance. Methods:A total of 25 children with acute dust mite allergic asthma (the asthma group) in Affiliated Hospital of Jiangnan University from January to December 2021 and 16 age- and sex-matched healthy volunteers (the healthy control group) at the same time were enrolled in the retrospective study.The percentages of peripheral T FR cells and T FH cells of the 2 groups were measured by flow cytometry.The plasma levels of cytokines[interleukin (IL)-10, IL-21] of the 2 groups were assessed by the flow cytometric microsphere-based array technology.The specific IgE (sIgE) levels of dust mites in 2 groups were detected by fluorescence enzyme immunoassay.The percentage of eosinophils in peripheral blood detected by blood cell analyzer.Data between groups were compared by t-test, and the correlation among indicators was analyzed by Spearman rank correlation analysis. Results:The asthma group had evident T FR cells/T FH cells immune imbalance.Compared with the healthy control group, the asthma group had a significantly lower T FR cells level[(0.11±0.03)% vs.(0.13±0.03)%], a significantly higher T FH cells level[(5.07±1.75)% vs.(3.80 ± 1.60)%], and a significantly lower ratio of T FR cells /T FH cells(0.02±0.01 vs.0.05±0.03) ( t=2.29, 2.30, 3.71; all P<0.05). Compared with the healthy control group, the asthma group had a significantly higher IL-21 level[(547.85±195.13) ng/L vs.(404.94±110.41) ng/L], and a significantly lower IL-10 level[(10.18±3.49) ng/L vs.(14.79±5.65) ng/L] ( t=2.60, 3.15; all P<0.05). The ratio of T FR cells/T FH cells in asthma group was negatively correlated with sIgE ( r=-0.444 2, P=0.026 1), but not related to the eosinophil percentage ( r=-0.135 2, P=0.519 3). Conclusions:Children with dust mite allergic asthma suffer from T FR cells/T FH cells subset imbalance.The imbalanced T FR cells, T FH cells and their related cytokines IL-10 and IL-21 may play a role in regulating the production of asthma sIgE.
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Objective:To investigate the clinical efficacy of Omalizumab in the treatment of moderate-to-severe allergic asthma with allergic comorbidities in children.Methods:The clinical data of 50 children with moderate-to-severe allergic asthma and allergic comorbidities, who were treated with Omalizumab and completed 12-month follow-up in the Department of Pediatrics of Peking University First Hospital from July 2018 to March 2022, were retrospectively analyzed.A comparison was performed on the scale scores of childhood allergic asthma and allergic comorbidities including allergic rhinitis (AR) and chronic spontaneous urticaria (CSU), pulmonary function test indices and fractional exhaled nitric oxide (FeNO) concentration before and after treating with Omalizumab.The data were compared by ANOVA, paired t-test, chi- square test and rank sum test. Results:(1)Improvement of clinical symptoms: after 12 months of Omalizumab treatment, the childhood asthma control test score of 42 children aged ≤11 years increased from (20.98±5.03) points to (26.95±0.22) points ( F=18.189, P<0.001). The asthma control questionnaire 7 score of 50 children decreased from (0.89±0.11) points to (0.10±0.02) points ( F=5.662, P=0.006). The score of visual analogue scale of 47 children with AR decreased from (11.00±1.65) points to (0.2±0.14) points ( F=14.901, P<0.001), and the urticaria control test score of 13 children with CSU decreased from (4.82±0.88) points to (1.87±0.61) points ( F=4.329, P=0.018). (2)Improvement of quality of life: compared with those before treatment, the pediatric asthma quality of life questionnaire score in 50 children increased from (124.50±32.13) points to (159.40±6.21) points ( F=12.052, P<0.001), and global evaluation of asthma treatment effectiveness decreased from (2.23±0.70) points to (1.07±0.26) points ( F=68.865, P<0.001) after Omalizumab treatment for 12 months.(3)Improvement of pulmonary function results: after 12 months of Omalizumab treatment, the number of children with forced expiratory volume in one second/forced vital capacity< 80% decreased from 13 cases (26%) to 1 case (2%), and the values increased from (91.39±12.88)% to (96.96±8.54)%( χ2=11.960; t=2.486, all P<0.05). The peak expiratory flow of predicted value increased from (86.73±16.05)% to (94.01±13.11)% ( t=2.445, P<0.05). The number of children with two indicators among the forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled and maximal mid-expiratory flow lower than 65% decreased from 31 cases (62%) to 7 cases (14%) ( χ2=24.450, P<0.001). There was no significant difference in FeNO concentration before and after treatment ( P>0.05). Safety of Omalizumab: no obvious adverse reactions were found during treatment and follow-up. Conclusions:Omalizumab can significantly improve the clinical symptoms, small airway function and quality of life of children with allergic asthma and concomitant AR or CSU.It is a potential targeted drug for treating a variety of allergic diseases in children.
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Abstract Protease-activated receptors (PARs) are metabotropic G-protein-coupled receptors that are activated via proteolytic cleavage of a specific sequence of amino acids in their N-terminal region. PAR2 has been implicated in mediating allergic airway inflammation. This study aims to study the effect of PAR2 antagonist ENMD1068in lung inflammation and airway remodeling in experimental asthma. Allergic lung inflammation was induced in sensitized BALB/c mice through intranasal instillations of ovalbumin (OVA), and mice were pretreated with ENMD1068 1 hour before each OVA challenge. Bronchoalveolar lavage fluid (BALF) was collected, and the lungs were removed at different time intervals after OVA challenge to analyze inflammation, airway remodeling and airway hyperresponsiveness. Ovalbumin promoted leukocyte infiltration into BALF in a PAR2-dependent manner. ENMD1068 impaired eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activity in the lung parenchyma into BALF and reduced the loss of dynamic pulmonary compliance, lung resistance in response to methacholine, mucus production, collagen deposition and chemokine (C-C motif) ligand 5 expression compared to those in OVA-challenged mice. We propose that proteases released after an allergen challenge may be crucial to the development of allergic asthma in mice, and PAR2 blockade may be useful as a new pharmacological approach for the treatment of airway allergic diseases.
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Animals , Female , Mice , Pneumonia/pathology , Receptor, PAR-2/antagonists & inhibitors , Receptors, Proteinase-Activated/antagonists & inhibitors , Airway Remodeling/drug effectsABSTRACT
Objective To explore the clinical efficacy and safety of the omalizumab treatment in children with high level IgE allergic asthma. Methods The clinical data of 2 children with allergic asthma treated with omalizumab in the Departemnt of Respiratory Medicine of Shanghai Children’s Hospital from August 2020 to May 2021 were retrospectively analyzed, and they had regular follow-up after end of treatment. The dosage and course of treatment, therapeutic effect and adverse drug reactions of omalizumab were analyzed. Results After receiving omalizumab treatment, asthma symptoms were well controlled, the dosage of inhaled corticosteroids during asthma treatment were reduced and nasal symptoms were relieved. 20 subcutaneous injections were received by 2 children, and no adverse reactions were found. After the treatment, regular pharmaceutical follow-up showed that the children were in good health. Conclusion Omalizumab is suitable for high level IgE allergic asthma and can improve asthma control symptoms with good long-term safety. However, the appropriate dosage and course of treatment still need further experience accumulation.
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The present study investigated the effect of active components of Descurainia sophia on allergic asthma and explored the underlying mechanism. SD male rats were randomly divided into a normal group(NC), a model group(M), a D. sophia decoction group(DS), a D. sophia fatty oil group(FO), a D. sophia flavonoid glycoside group(FG), a D. sophia oligosaccharide group(Oli), and a positive drug dexamethasone group(Y). The allergic asthma model was induced in rats by intraperitoneal injection of ovalbumin(OVA) and aluminum hydroxide gel adjuvant(sensitization) and atomization of OVA solution(excitation). After modeling, asthma-related indicators, tracheal phenol red excretion, inflammatory cell levels in the peripheral blood, lung permeability index(LPI), and oxygenation index(OI) of rats were detected. The pathological changes of lung tissues were observed by HE staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect the content of inflammatory factors immunoglobulin E(IgE), interleukin-4(IL-4), and interferon-γ(IFN-γ) in the bronchoalveolar lavage fluid(BALF) and the content of endothelin-1(ET-1) and angiotensin-converting enzyme(ACE) in lung tissue homogenate. The serum content of nitric oxide(NO) was detected by colorimetry. Western blot was employed to determine the protein expression of Toll-like receptor 4(TLR4), nuclear factor κB-p65(NF-κB-p65), phosphorylated NF-κB-p65(p-NF-κB-p65), myosin light chain kinase(MLCK), vascular endothelial cadherin(VE cadherin), connexin 43, and claudin 5, and the mechanism of active components of D. sophia on allergic asthma was explored. As revealed by the results, the M group showed extensive infiltration of inflammatory cells around the bronchus of the lung tissues of the allergic asthma rats, thickened bronchial wall, severely deformed alveolar structure, increased number of wheezes, the content of IgE, IL-4, ET-1, and ACE, inflammatory cells, and LPI, and reduced latency of asthma, tracheal phenol red excretion, IFN-γ, NO content, and OI. After the intervention of the active components of D. sophia, the DS, FO, FG, Oli, and Y groups showed improved asthma-related indicators, tracheal phenol red excretion, and lung tissue lesions in allergic asthma rats, and the effects in the FO and Oli groups were superior. The content of inflammatory factors in BALF was recovered in the DS, FO, and Y groups and the FG and Oli groups. The number of inflammatory cells in rats was reduced in the DS and FO groups, and the FG, Oli, and Y groups to varying degrees, and the effect in the FO group was superior. DS, FO, Oli, and Y reduced ET-1, ACE, and LPI and increased NO and OI. FG recovered NO, ET-1, ACE, LPI, and OI to improve lung epithelial damage and permeability. Further investigation of inflammation-related TLR4/NF-κB pathways, MLCK, and related skeleton protein levels showed that TLR4, NF-κB-p65, p-NF-κB-p65, and MLCK levels were increased, and VE cadherin, connexin 43, and claudin 5 were reduced in the M group. DS, FO, FG, Oli, and Y could reduce the protein expression related to the TLR4 pathway to varying degrees, and regulate the protein expression of MLCK, VE cadherin, connexin 43, and claudin 5. It is inferred that the active components of D. sophia improve lung permeability in rats with allergic asthma presumedly by regulating the TLR4/NF-κB signaling pathway to improve airway inflammation, mediating MLCK and connexin, and regulating epithelial damage.
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Animals , Male , Rats , Asthma/drug therapy , Bronchoalveolar Lavage Fluid , Inflammation/metabolism , Lung , PermeabilityABSTRACT
Objective:To investigate the treatment of Omalizumab for allergic asthma (AS) combined with atopic dermatitis (AD) in children.Methods:Five children who were diagnosed with moderate-to-severe AS combined with AD were admitted in the Department of Respiratory, Children′s Hospital of Nanjing Medical University from November 2018 to August 2020.All children were treated with standardized treatment of AS and Omalizumab.The efficacy and adverse reactions of Omalizumab treated for AD were observed.The scoring atopic dermatitis index (SCORAD), eczema area and severity index (EASI), the children′s dermatology life quality index (CDLQI) and numerical rating scale (NRS) were selected, the scales were used to evaluate the severity, area, itching and quality of life of AD children.Results:The AD-related evaluation indexes were remarkably decreased through the treatment of Omalizumab for 4 months, including SCORAD, EASI, CDLQI, and NRS(60.80±10.79 vs.40.30±15.62; 13.93±6.81 vs.6.18±2.70; 18.80±6.26 vs.13.20±4.82; 8.60±0.89 vs.6.00±1.87), the differences were statistically significant ( t=7.833, 4.106, 5.199, 5.099, all P<0.05). Two children administered the combination of Omalizumab and allergen specific immunotherapy, and no adverse reactions were observed in the process of immunotherapy.Totally, 104 hypodermic injections were accepted in all children, without adverse reactions being observed. Conclusions:This study suggested that the Omalizumab treatment can significantly reduce the severity and area of AD, and improve the quality of life for children with moderate-to-severe AS combined with AD.The application of Omalizumab before the allergen specific immunotherapy can improve the immunotolerance and security.There were mild adverse reactions in the treatment with the long-term hypodermic injection of Omalizumab that has higher security.Being taken together, Omalizumab is a potential novel target drug for the treatment of AD in children, and perhaps it is an adjuvant administration for allergen specific immunotherapy.
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Airway epithelial barrier dysfunction has been observed in allergic asthma patients.Inhaled allergens have shown a disruptive effect on the airway epithelial barrier.Airway barrier related genetic variation and epigenetics are also involved in the airway epithelial barrier dysfunction.A lot of studies believe that airway epithelial barrier dysfunction underlie the development of asthma.The study of the relationship between allergic asthma and airway epithelial barrier function will be helpful to understand the pathogenesis of allergic asthma and provide new ideas for the treatment of allergic asthma.
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Introdução: a asma é uma doença heterogênea, caracterizada por inflamação crônica das vias aéreas inferiores, associada a diferentes fenótipos. O omalizumabe é utilizado em adição ao tratamento quando não se obtém o controle adequado da asma. Este estudo mostra o perfil epidemiológico e a adesão ao tratamento dos pacientes acompanhados no Ambulatório de Especialidades do Hospital Universitário da Universidade Estadual de Londrina (AEHU-UEL) em uso de omalizumabe em um período de 12 meses. Método: realizado um estudo transversal retrospectivo através de dados secundários de prontuário avaliando pacientes com diagnóstico de asma alérgica grave em uso de omalizumabe nos 12 meses prévios ao recrutamento. Resultados: foram selecionados 40 pacientes que preencheram os critérios de inclusão. A média de idade foi de 51,4 anos, com predomínio de mulheres (70%), brancos (48%), não tabagistas (90%), com sobrepeso ou obesidade (75%) e diagnóstico de asma na infância (45%). O tempo médio de tratamento foi de 8,1 anos (DP 0,8). Havia comorbidades em 85% dos pacientes, com predomínio de rinite (62,5%) e DRGE (40%). Houve exacerbação em 29 pacientes levando a 8 internações (27,5%); 93% dos exacerbadores apresentaram faltas. Conclusão: a amostra é comparável a outros estudos de vida real nos achados epidemiológicos (idade, sexo, fenótipo, tempo de diagnóstico, controle da doença e tabagismo). O elevado número de faltas, assim como frequência de DRGE e outras comorbidades e a baixa adesão à terapêutica, podem justificar o elevado número de exacerbações e maior dificuldade de controle.(AU)
Introduction: asthma is a hetereogeneous disease, characterized by chronic inflammation of the lower airways associated with different phenotypes. Omalizumab is used in addition to treatment when adequate asthma control is not achieved. This study shows the epidemiological profile and the adherence to the treatment of patients followed at the Medical Clinic of the State University Hospital of Londrina (AEHU-UEL) using omalizumab in the last 12 months. Methods: severe allergic asthma patients using omalizumab in the last 12 months were evaluated by means of secondary medical records. Results: forty patients were included and had complete medical record. The average age was 51.4 years mostly women (70%), white (48%), non-smoker (90%), overweight or obese (75%) and childhood asthma diagnosis (45%). The average treatment time was 8.1 years (SD0.8). There were co-morbidities in 85% of the patients, mainly rhinitis in 62.5% and GERD in 40%. There were exacerbations in 29 patients, leading to 8 hospitalizations (27.5%), 93% of exacerbators was missed at least one time. Strong association with rhinitis (p=0.07), and no disease control (p=0.22). Conclusion: the sample is comparable to other real-life studies in almost all epidemiological findings (age, sex, phenotype, time of diagnosis, disease control and smoking). The high number of absences and frequency of GERD and other comorbidities, and poor adhesion, may justify the high number of exacerbations and more difficulty to control the disease. (AU)
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Humans , Asthma , Disease , Omalizumab , Phenotype , Association , Diagnosis , Hospitalization , InflammationABSTRACT
OBJECTIVE：To provide reference for elucidating the anti-allergic asthma constituents in alkaloids-free part of Ephedrae Herba. METHODS ：Ephedrae Herba was extracted with 85％ ethanol and n-heptane，and then subjected to solid-phase extraction（filler AC 18）for pretreatment to enrich alkaloids-free part from the extract of Ephedrae Herba. HPLC method was adopted，and alkaloids-free fractions of Ephedrae Herba were performed on Unitary C 18 column and Eclipse XDB-C 18 column. Using high expression G protein coupled-receptor 35（GPR35 receptor）in HT- 29 cell as target ，GPR35 receptor agonist zaprinast （1 μmol/L）as positive control ，DMR response value as the detection index ，the agonistic and desensitizing activity of each fraction（100 μg/mL）on GPR 35 receptor was screened by label-free integrated pharmacological method ，so as to screen active anti-allergic asthma fraction. HPLC-Q-TOF-MS method was used to identify the chemical composition of the selected active fractions. RESULTS ：The alkaloids-free part of Ephedrae Herba was divided into two parts ，involving the precipitated part before solid phase extraction and the 95％ methanol elution part ；from them ，20 fractions were screened. Among them ，the precipitated fraction F 1.5-F1.10 and 95％ methanol eluted fraction F 2.5-F2.10 had a strong agonistic activity on GPR 35 receptor；at the same time，GPR35 receptor agonist zaprinast showed a relatively strong desensitization activity. The signal intensity of DMR induced by F1.5-F1.10 in the precipitated part of HT- 29 cells was even higher than that of reference drug zaprinast. By HPLC-Q-TOF-MS analysis，24 chemical components were identified from active fractions ，involving 14 flavonoids，2 volatile oils ，7 organic carboxylic acids ，1 anthraquinones. CONCLUSIONS ：The alkaloid-free part of Ephedrae Herba is mainly flavonoids and has anti-allergic asthma activity.
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Objective: In this study our main aim is to evaluate impact ofSerum Total IgE and Disease Severity in Patients with AllergicAsthma.Method: This cross-sectional study was conducted at NIDCH,Mohakhali, Dhaka from one year (July 2012 - June2013).Among 150 asthma patients, 50 mild asthma patients, 50moderate and 50 severe asthma were selected in this study.Result: In our study among 150 patients, patients with midasthma belong to 15-19 years age group, where as patientswith moderate asthma and severe asthma belong to 25-29years and 35-39 years age group.21% patients with mildasthma unusually visit for regular checkup to doctor whereas48% patients with moderate asthma unusually visit regularly todoctor.47% patients with severe asthma level had >400 IU/mLserum level where as 19% patients with moderate asthma had>400 IU/mL serum level.Conclusion: From our study we can conclude that, serum totalIgE levels in adult patients with persistent allergic asthma fromBangladesh were high (two-thirds with levels >150 IU/mL) andvaried significantly. Further study is highly appreciated forbetter outcome.
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Introduction: Immunoglobulin E dependent mechanisms play an important role in the development of airway inflammation in allergic asthma. Atopic patients with severe asthma frequently have poorly controlled disease. Many have poor asthma control despite intensive treatment. Severe allergic asthma patients frequently treated with oral corticosteroids and therefore may develop serious side-effects. Anti-IgE antibody had been used in severe persistent allergic asthma in Western countries. However, its long-term efficacy in patients in India has not been reported. Objective: To assess the efficacy of anti IgE therapy in patients with severe allergic asthma. Method: 30 (16 male and 14 female) patients, with mean age of 49 having severe persistent allergic asthma, with recurrent exacerbations and on oral/IV steroids, received Omalizumab 150mg/300mg/450 mg for 1 year. Total dose of oral Steroids, use of rescue medications, changes in lung function (FEV1) were recorded at the baseline, 16 weeks & at end of the treatment (52 weeks) and then analyzed. Results: Significant reduction observed in total oral steroid use at 16 week & at 52 weeks. -10.5mg (p<0.003) & 22.5mg respectively. Use of rescue medications decreased by -7.90 puffs(p- <0.001) at 16 weeks and by -13.67 puffs (13.67 (p -<0.001) at 52 weeks. Improvements in lung Function (FEV1) observed with a tune of 700 ml. from Baseline after 52 weeks therapy. Conclusion: Use of anti-IgE antibody for 1 year is well tolerated and led to an overall significant improvement in patients with severe persistent allergic asthma.
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Hookworm infection remains a global health concern, which threatens human health. Hookworm infection is widely prevalent across the world, notably in tropical and subtropical areas. Recently, with the in-depth study of the immunity of parasitic infections, the“bidirectional effect”of host immune responses induced by helminth infections (including hookworm infections) has become increasingly prominent. On one hand, an immune response is induced in the host to kill the infected worms; on the other hand, the host produces a series of immunological changes that are conducive to the maintenance of parasite survival. The immune state of the host is regulated by various complicated mechanisms, and this may lead to the reduction in the incidence of allergic and autoimmune diseases or alleviation of the disease symptoms, which provide new insights into the management of these allergic and autoimmune diseases. The present article reviewed the advances of host immune responses induced by hook-worm infection and its potential values in the treatment of allergic asthma, inflammatory bowel disease and rheumatoid arthritis.