2.The role of neutrophils in asthma.
Wen HUA ; Huaqiong HUANG ; Yonghong ZHONG ; Min YU ; Fei CHEN
Journal of Zhejiang University. Medical sciences 2021;50(1):123-130
		                        		
		                        			
		                        			Bronchial asthma is a chronic respiratory disease,characterized by airway inflammation,airway hyperresponsiveness,reversible airway obstruction and airway remodeling,in which a variety of cells including airway inflammatory cells and structural cells are involved. Previous studies have shown that asthma is mainly driven by Th2 cytokines IL-4,IL-5,and IL-13,leading to airway eosinophil inflammation. With further research,however,it has been found that neutrophils are also closely related to asthma. Numbers of neutrophils are elevated in airway through increased chemotaxis and decreased apoptosis,which is earlier than eosinophils,leading to airway neutrophilic inflammation. Neutrophils can produce elastase,myeloperoxidase,neutrophil extra- cellular traps,chemokines and cytokines,participating in the occurrence and development of asthma. The antagonists against these molecules,such as anti-IL-8 receptor antibody,anti-IL-17 antibody,and DNase,have shown positive effects on neutrophilic asthma,but further studies are needed to support their clinical application. This article mainly reviews the role of neutrophils in asthma and related mechanisms.
		                        		
		                        		
		                        		
		                        			Asthma/immunology*
		                        			;
		                        		
		                        			Cytokines
		                        			;
		                        		
		                        			Eosinophils
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Inflammation
		                        			;
		                        		
		                        			Neutrophils/immunology*
		                        			
		                        		
		                        	
3.Asia Pacific Association of Allergy Asthma and Clinical Immunology White Paper 2020 on climate change, air pollution, and biodiversity in Asia-Pacific and impact on allergic diseases
Ruby PAWANKAR ; Jiu Yao WANG ; I Jen WANG ; Francis THIEN ; Yoon Seok CHANG ; Amir Hamzah Abdul LATIFF ; Takao FUJISAWA ; Luo ZHANG ; Bernard Yu Hor THONG ; Pantipa CHATCHATEE ; Ting Fan LEUNG ; Wasu KAMCHAISATIAN ; Iris RENGGANIS ; Ho Joo YOON ; Sonomjamts MUNKHBAYARLAKH ; Marysia T. RECTO ; Anne Goh Eng NEO ; Duy LE PHAM ; Le Thi Tuyet LAN ; Janet Mary DAVIES ; Jae Won OH
Asia Pacific Allergy 2020;10(1):11-
		                        		
		                        			
		                        			Air pollution, climate change, and reduced biodiversity are major threats to human health with detrimental effects on a variety of chronic noncommunicable diseases in particular respiratory and cardiovascular diseases. The extent of air pollution both outdoor and indoor air pollution and climate change including global warming is increasing-to alarming proportions particularly in the developing world especially rapidly industrializing countries worldwide. In recent years, Asia has experienced rapid economic growth and a deteriorating environment and increase in allergic diseases to epidemic proportions. Air pollutant levels in many Asian countries especially in China and India are substantially higher than are those in developed countries. Moreover, industrial, traffic-related, and household biomass combustion, indoor pollutants from chemicals and tobacco are major sources of air pollutants, with increasing burden on respiratory allergies. Here we highlight the major components of outdoor and indoor air pollutants and their impacts on respiratory allergies associated with asthma and allergic rhinitis in the Asia-Pacific region. With Asia-Pacific comprising more than half of the world's population there is an urgent need to increase public awareness, highlight targets for interventions, public advocacy and a call to action to policy makers to implement policy changes towards reducing air pollution with interventions at a population-based level.
		                        		
		                        		
		                        		
		                        			Administrative Personnel
		                        			;
		                        		
		                        			Air Pollutants
		                        			;
		                        		
		                        			Air Pollution
		                        			;
		                        		
		                        			Air Pollution, Indoor
		                        			;
		                        		
		                        			Allergy and Immunology
		                        			;
		                        		
		                        			Asia
		                        			;
		                        		
		                        			Asian Continental Ancestry Group
		                        			;
		                        		
		                        			Asthma
		                        			;
		                        		
		                        			Biodiversity
		                        			;
		                        		
		                        			Biomass
		                        			;
		                        		
		                        			Cardiovascular Diseases
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Climate Change
		                        			;
		                        		
		                        			Climate
		                        			;
		                        		
		                        			Consumer Advocacy
		                        			;
		                        		
		                        			Developed Countries
		                        			;
		                        		
		                        			Economic Development
		                        			;
		                        		
		                        			Family Characteristics
		                        			;
		                        		
		                        			Global Warming
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypersensitivity
		                        			;
		                        		
		                        			India
		                        			;
		                        		
		                        			Rhinitis, Allergic
		                        			;
		                        		
		                        			Tobacco
		                        			
		                        		
		                        	
4.Metabolomic Analysis of Serum Glycerophospholipid Levels in Eosinophilic and Neutrophilic Asthma.
Xiao Yan GAI ; Li Jiao ZHANG ; Chun CHANG ; Cheng Lin GUO ; Mairipaiti ABULIKEMU ; Wen Xiong LI ; Juan WANG ; Wan Zhen YAO ; Xu ZHANG
Biomedical and Environmental Sciences 2019;32(2):96-106
		                        		
		                        			OBJECTIVE:
		                        			To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis.
		                        		
		                        			METHODS:
		                        			Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ⪖ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ⪖ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis.
		                        		
		                        			RESULTS:
		                        			The serum lysophosphatidylglycerol level was significantly higher in the group with ⪖ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ⪖ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ⪖ 71% and the group with sputum neutrophils < 71%.
		                        		
		                        			CONCLUSION
		                        			Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Asthma
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			Eosinophils
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Glycerophospholipids
		                        			;
		                        		
		                        			blood
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Metabolomics
		                        			;
		                        		
		                        			Middle Aged
		                        			;
		                        		
		                        			Neutrophils
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			Sputum
		                        			;
		                        		
		                        			cytology
		                        			;
		                        		
		                        			immunology
		                        			
		                        		
		                        	
5.Astragalus membranaceus improves therapeutic efficacy of asthmatic children by regulating the balance of Treg/Th17 cells.
Wei WANG ; Qing-Bin LIU ; Wei JING
Chinese Journal of Natural Medicines (English Ed.) 2019;17(4):252-263
		                        		
		                        			
		                        			Astragalus membranaceus may be a potential therapy for childhood asthma but its driving mechanism remains elusive. The main components of A. membranaceus were identified by HPLC. The children with asthma remission were divided into two combination group (control group, the combination of budesonide and terbutaline) and A. membranaceus group (treatment group, the combination of budesonide, terbutaline and A. membranaceus). The therapeutic results were compared between two groups after 3-month therapy. Porcine peripheral blood mononuclear cells (PBMCs) were isolated from venous blood by using density gradient centrifugation on percoll. The levels of FoxP3, EGF-β, IL-17 and IL-23 from PBMCs and serum IgE were measured. The relative percentage of Treg/Th17 cells was determined using flow cytometry. The main components of A. membranaceus were calycosin-7-O-glucoside, isoquercitrin, ononin, calycosin, quercetin, genistein, kaempferol, isorhamnetin and formononetin, all of which may contribute to asthma therapy. Lung function was significantly improved in the treatment group when compared with a control group (P < 0.05). The efficacy in preventing the occurrence of childhood asthma was higher in the treatment group than the control group (P < 0.05). The levels of IgE, IL-17 and IL-23 were reduced significantly in the treatment group when compared with the control group, while the levels of FoxP3 and TGF-β were increased in the treatment group when compared with the control group (P < 0.05). A. membranaceus increased the percentage of Treg cells and reduced the percentage of Th17 cells. A. membranaceus is potential natural product for improving the therapeutic efficacy of combination therapy of budesonide and terbutaline for the children with asthma remission by modulating the balance of Treg/Th17 cells.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Asthma
		                        			;
		                        		
		                        			drug therapy
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			Astragalus propinquus
		                        			;
		                        		
		                        			chemistry
		                        			;
		                        		
		                        			Budesonide
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Cells, Cultured
		                        			;
		                        		
		                        			Child
		                        			;
		                        		
		                        			Child, Preschool
		                        			;
		                        		
		                        			Cytokines
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Drugs, Chinese Herbal
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Immunologic Factors
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			pharmacology
		                        			;
		                        		
		                        			Leukocytes, Mononuclear
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			metabolism
		                        			;
		                        		
		                        			Lung
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			physiology
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Swine
		                        			;
		                        		
		                        			T-Lymphocytes, Regulatory
		                        			;
		                        		
		                        			cytology
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Terbutaline
		                        			;
		                        		
		                        			administration & dosage
		                        			;
		                        		
		                        			Th17 Cells
		                        			;
		                        		
		                        			cytology
		                        			;
		                        		
		                        			drug effects
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
6.Research progress of mast cell activation-related receptors and their functions.
Yu-Cui JIANG ; Fan YE ; Ying DU ; Zong-Xiang TANG
Acta Physiologica Sinica 2019;71(4):645-656
		                        		
		                        			
		                        			Mast cells are widely distributed in various parts of the body, especially in the mucosal surface between the body and the external environment. Mast cell is one of the important immune cells and plays important roles in innate immunity, adaptive immunity and immune regulation. Previous researches have shown that excessive activation of mast cells is closely related to the development of allergic and inflammatory diseases such as asthma, allergic rhinitis, food allergies, acute and chronic itching. Mast cells infiltrate into the inflammation site and release various allergic mediators during the occurrence and development of these diseases. Therefore, termination of mast cell activation can be one of the effective methods for the treatment of allergic and inflammatory diseases, and receptors related to mast cell activation are potential targets for the development of anti-allergic drugs. There are many receptors related to mast cell activation, and the effects mediated by different receptors varied from each other. In the recent years, new mast cell receptors are being discovered, but there are not many literatures discussing the possible functions of these newly discovered receptors. This review aims to summarize the receptors involved in mast cell activation and classify related receptors according to their effects.
		                        		
		                        		
		                        		
		                        			Asthma
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypersensitivity
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			Immunity, Innate
		                        			;
		                        		
		                        			Inflammation
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			Mast Cells
		                        			;
		                        		
		                        			cytology
		                        			;
		                        		
		                        			immunology
		                        			
		                        		
		                        	
7.Therapeutic Effect of Glucosamine on an Atopic Dermatitis Animal Model
Hee Seong YOON ; Ji Won BYUN ; Jeonghyun SHIN ; Young Hyo KIM ; Gwang Seong CHOI
Annals of Dermatology 2019;31(5):538-544
		                        		
		                        			
		                        			BACKGROUND: Recent studies have reported that glucosamine (GlcN) showed therapeutic effects in allergic diseases such as asthma and rhinitis, and its mechanisms include the suppression of T helper type 2 immune responses and the nuclear factor-κB pathway. OBJECTIVE: We aimed to investigate the effect of GlcN on atopic dermatitis (AD) in an animal model. METHODS: Twenty-five BALB/c mice were divided into five groups (groups A~E). Group A was the phosphate-buffered saline (PBS)-treated group without AD induction. Group B was the PBS control group with AD induction. Groups C to E were the AD induction groups, which were treated with three different doses of GlcN (10 mg, 20 mg, and 40 mg, respectively). Histopathological examination was performed after GlcN administration. Interleukin (IL)-4, IL-13, and IL-17 cytokine levels were measured by enzyme-linked immunosorbent assay using skin biopsy specimens. Serum total immunoglobulin E (IgE) concentrations were measured before and after administration with GlcN or PBS. RESULTS: Clinical dermatitis scores decreased with increasing GlcN dose (p<0.001). Concentrations of tissue IL-13 and IL-17 decreased after GlcN administration (each group: p=0.002 and p<0.001, respectively), but the concentrations of tissue IL-4 did not show differences across groups. Serum IgE levels tended to be lower after GlcN administration (p=0.004). Histopathological scores were not significantly different among groups B~E (p=0.394). CONCLUSION: GlcN improved AD symptoms and decreased tissue IL-13, IL-17, and serum total IgE levels in an animal model.
		                        		
		                        		
		                        		
		                        			Allergy and Immunology
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Anti-Allergic Agents
		                        			;
		                        		
		                        			Asthma
		                        			;
		                        		
		                        			Biopsy
		                        			;
		                        		
		                        			Dermatitis
		                        			;
		                        		
		                        			Dermatitis, Atopic
		                        			;
		                        		
		                        			Enzyme-Linked Immunosorbent Assay
		                        			;
		                        		
		                        			Glucosamine
		                        			;
		                        		
		                        			Immunoglobulin E
		                        			;
		                        		
		                        			Immunoglobulins
		                        			;
		                        		
		                        			Interleukin-13
		                        			;
		                        		
		                        			Interleukin-17
		                        			;
		                        		
		                        			Interleukin-4
		                        			;
		                        		
		                        			Interleukins
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Models, Animal
		                        			;
		                        		
		                        			Rhinitis
		                        			;
		                        		
		                        			Skin
		                        			;
		                        		
		                        			Therapeutic Uses
		                        			
		                        		
		                        	
8.Characteristics of Adult Severe Refractory Asthma in Korea Analyzed From the Severe Asthma Registry.
Min Hye KIM ; Sang Heon KIM ; So Young PARK ; Ga Young BAN ; Joo Hee KIM ; Jae Woo JUNG ; Ji Yong MOON ; Woo Jung SONG ; Hyouk Soo KWON ; Jae Woo KWON ; Jae Hyun LEE ; Hye Ryun KANG ; Jong Sook PARK ; Tae Bum KIM ; Heung Woo PARK ; Kwang Ha YOO ; Yeon Mok OH ; Young Il KOH ; An Soo JANG ; Byung Jae LEE ; Young Joo CHO ; Sang Heon CHO ; Hae Sim PARK ; Choon Sik PARK ; Ho Joo YOON ; You Sook CHO
Allergy, Asthma & Immunology Research 2019;11(1):43-54
		                        		
		                        			
		                        			PURPOSE: Although mild to moderate asthma is much more common, the morbidity and mortality of severe asthma are much higher. This study was performed to identify and analyze the clinical characteristics of severe asthma in Korea. METHODS: We registered patients with severe refractory asthma into the Severe Asthma Registry supported by the Severe Asthma Work Group of the Korean Academy of Asthma, Allergy and Clinical Immunology. Patients were enrolled since 2010 from the 15 university hospitals nationwide in Korea. Severe asthma was defined according to modified European Respiratory Society/American Thoracic Society criteria. Information on demographics, medical history, pulmonary function tests and skin prick tests was collected; the clinical characteristics of severe asthmatics were analyzed from the collected data. RESULTS: A total of 489 patients were enrolled with a mean age of 62.3; 45% are male. Sixty percent of patients received Global Initiative for Asthma step 4 treatment, and 30% received step 5 treatment. The most common comorbidities were allergic rhinitis (58.7%). Aspirin hypersensitivity was observed in 14.0%. Approximately half (53.9%) are non-smokers. Atopy was proven in 38.5% of the patients. Regarding asthma medications, inhaled corticosteroids and long-acting β-agonist combination inhalers were most commonly prescribed (96.5%), followed by leukotriene antagonists (71.0%). A recombinant anti-immunoglobulin E monoclonal antibody (omalizumab) has been used in 1.8% of the patients. The mean forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and FEV1/FVC were 78.7%, 67.5% and 67.9% of predicted values, respectively. The mean Asthma Control Test and quality of life questionnaire scores were 16.5 out of 25 and 59.5 out of 85, respectively. CONCLUSIONS: The baseline characteristics of severe asthma patients in the Korea Severe Asthma Registry were analyzed and reported for the first time. With this cohort, further prospective studies should be performed to search for ways to improve management of severe refractory asthma.
		                        		
		                        		
		                        		
		                        			Adrenal Cortex Hormones
		                        			;
		                        		
		                        			Adult*
		                        			;
		                        		
		                        			Allergy and Immunology
		                        			;
		                        		
		                        			Aspirin
		                        			;
		                        		
		                        			Asthma*
		                        			;
		                        		
		                        			Cohort Studies
		                        			;
		                        		
		                        			Comorbidity
		                        			;
		                        		
		                        			Demography
		                        			;
		                        		
		                        			Forced Expiratory Volume
		                        			;
		                        		
		                        			Hospitals, University
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypersensitivity
		                        			;
		                        		
		                        			Korea*
		                        			;
		                        		
		                        			Leukotriene Antagonists
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Mortality
		                        			;
		                        		
		                        			Nebulizers and Vaporizers
		                        			;
		                        		
		                        			Prospective Studies
		                        			;
		                        		
		                        			Quality of Life
		                        			;
		                        		
		                        			Respiratory Function Tests
		                        			;
		                        		
		                        			Rhinitis, Allergic
		                        			;
		                        		
		                        			Skin
		                        			;
		                        		
		                        			Vital Capacity
		                        			
		                        		
		                        	
9.Transcriptomic microarray profiling of peripheral CD4+ T cells from asthmatic patients.
Min ZHU ; Min HE ; Yarong HE ; Yulin JI
Chinese Journal of Medical Genetics 2018;35(6):828-831
		                        		
		                        			OBJECTIVE:
		                        			To identify differentially expressed genes in peripheral blood mononuclear cells between patients with continuous mild-to-moderate asthma and healthy controls using mRNA microarray in order to explore the underlying signaling pathways and clarify the roles of CD4+ T cells in the pathogenesis of asthma.
		                        		
		                        			METHODS:
		                        			Global transcriptomic profiles of the CD4+ T cells were defined by using Agilent Sure Print G3 Human GE 8×60K microarray. Enrichment pathways were analyzed with Ingenuity Pathway Analysis (IPA) software.
		                        		
		                        			RESULTS:
		                        			Compared with controls, 805 genes were up-regulated, 192 were down-regulated in asthma patients. Among these, the expression of 38 annotated genes have varied by 4 times or more. Expression of CD300A was inversely proportional to the absolute value of eosinophils (r=-0.89, P=0.02) as well as the proportion of eosinophils (r=-0.94, P=0.004), while CSF1R was inversely proportional to PD20 (r=-0.83, P=0.04) and AQLQ (r=-0.88, P=0.02) by correlation analysis.
		                        		
		                        			CONCLUSION
		                        			Numerous pathophysiological pathways may be involved in the pathogenesis of asthma. Above findings have provided a basis for the delineation the pathogenesis of asthma.
		                        		
		                        		
		                        		
		                        			Antigens, CD
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Asthma
		                        			;
		                        		
		                        			immunology
		                        			;
		                        		
		                        			CD4-Positive T-Lymphocytes
		                        			;
		                        		
		                        			cytology
		                        			;
		                        		
		                        			Case-Control Studies
		                        			;
		                        		
		                        			Eosinophils
		                        			;
		                        		
		                        			Gene Expression Profiling
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Leukocytes, Mononuclear
		                        			;
		                        		
		                        			Oligonucleotide Array Sequence Analysis
		                        			;
		                        		
		                        			Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Receptors, Immunologic
		                        			;
		                        		
		                        			genetics
		                        			;
		                        		
		                        			Transcriptome
		                        			
		                        		
		                        	
10.Regulatory T cells and asthma.
Sheng-Tao ZHAO ; Chang-Zheng WANG
Journal of Zhejiang University. Science. B 2018;19(9):663-673
		                        		
		                        			
		                        			Asthma is a chronic disease of airway inflammation due to excessive T helper cell type 2 (Th2) response. Present treatment based on inhalation of synthetic glucocorticoids can only control Th2-driven chronic eosinophilic inflammation, but cannot change the immune tolerance of the body to external allergens. Regulatory T cells (Tregs) are the main negative regulatory cells of the immune response. Tregs play a great role in regulating allergic, autoimmune, graft-versus-host responses, and other immune responses. In this review, we will discuss the classification and biological characteristics, the established immunomodulatory mechanisms, and the characteristics of induced differentiation of Tregs. We will also discuss the progress of Tregs in the field of asthma. We believe that further studies on the regulatory mechanisms of Tregs will provide better treatments and control strategies for asthma.
		                        		
		                        		
		                        		
		                        			Antigens, CD/analysis*
		                        			;
		                        		
		                        			Apyrase/analysis*
		                        			;
		                        		
		                        			Asthma/immunology*
		                        			;
		                        		
		                        			Cell Differentiation
		                        			;
		                        		
		                        			Cytokines/metabolism*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lymphocyte Transfusion
		                        			;
		                        		
		                        			T-Lymphocytes, Regulatory/immunology*
		                        			
		                        		
		                        	
            
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