Day 2 :
Keynote Forum
Mona I Kidon
Keynote: Treatment of food allergies in preschool children: Minimizing the risks, enhancing the benefits
Time : 10:00-10:45
Biography:
Mona I Kidon is currently the Head of Pediatric Allergy at the Safra Children's Hospital in the Chaim Sheba Medical Center, Tel Hashomer and a Senior Lecturer with the Faculty of Pediatric Medicine, Sackler Medical School, Tel Aviv University in Israel. She is a long standing Member of the European Network of Drug Allergy (ENDA) and a Past Secretary of the EAACI's task force on NSAIDs hypersensitivity in children. She has published extensively on both drug allergy and food allergy in children. She has been a part of the allergy community in Singapore since the beginning of the century, when she established the Paediatric Allegy Clinic at KK Children's Hospital and collaborates extensively with researchers at the National University of Singapore.
Abstract:
Background: A majority of preschool children with Egg Allergy (EA), Cow's Milk Allergy (CMA) and sesame allergy, can tolerate Extensively Heated and Baked Forms of these foods (EHBF). Consumption of EHBF may promote faster resolution; however, no consensus exists as to the required amounts and treatment protocols. In the past few years we have conducted a series of studies evaluating the safety and efficacy and safety of a Structured Gradual Exposure Protocol (SGEP) with EHBF in promoting tolerance to allergenic foods in food allergic children.
Methods: In a series of case control studies, preschool children with Food Allergy (FA) to eggs, milk and sesame, treated with SGEP including EHBF were compared to children treated with strict avoidance. Data was collected from records and telephone questionnaires. Analysis was performed using non-parametric Kaplan-Meier and proportional hazard Cox regression model.
Results: The median age at resolution of FA in SGEP treated children was significantly lower in all treated groups compared to their matched controls. All treatment protocols were safe overall with few in treatment reactions, mostly during observed challenges.
Conclusion: A structured protocol with EHBF as practiced by a dedicated team of pediatric allergists in an appropriate setting appears to safely promote faster resolution of FA in preschool children.
Keynote Forum
Vincenzo Patella
Santa Maria della Speranza Hospital, Italy
Keynote: How air pollution and climate change impact on allergic and respiratory diseases
Biography:
Vincenzo Patella is the Professor of Post-doctoral Program in Allergy and Clinical Immunology, Department of Translational Medical Sciences, Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Italy. He is the Director of Allergy and Clinical Immunology Division, ASL SALERNO Battipaglia, Italy and also the Chairman of National Task Force for Climate and Environment Change, Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC).
Abstract:
The World Health Organization (WHO) reports that air pollution is associated with climate change and in particular with global warming. Moreover, the air pollution effects on airway and lung diseases were well documented in the past by a statement of the World Allergy Organization. Literatures were searched for the effects of interaction between air pollution and climate change on allergic and respiratory diseases. Since 1990 articles and reviews have been published on this topic and a large number of studies confirm that the warming of our planet is caused by the greenhouse effect, due to increased greenhouse gas emissions. However, air pollution is closely linked to global warming, the emissions of hydrocarbons combustion residues induce a growth also in the concentration of biological allergens such as pollen, generating a mixture of these micrometer particles, called PM. Understanding the mechanisms that make PM fraction a major cause of health problems is still a controversial issue. Several studies are trying to figure out the reasons of global warming. There is evidence that the raising of the concentration of pollen and air pollutants is able to activate the inflammatory mediators in the airways. Several studies underscore the major risks of global warming on human health due to increasing concentrations of air pollution. The impact of climate change on respiratory diseases appears well documented. Over the last decades, a rise in the concentration of pollen as well as air pollution has been registered. These phenomena are in parallel with an increasing number of people showing allergic symptoms (e.g. allergic rhinitis, conjunctivitis and asthma) which often lead to emergency medical care. Scientists of different disciplines should work together with institutions, pharmaceutical companies and lay organizations to limit the adverse health effects of air pollution and global warming.
- Asthma | Allergy and Immunology | Asthma Stages | Public Health Emergency Medicine
Location: Seletar Room 1, Level 3
Session Introduction
Nan Wang
Xi’an Jiaotong University, China
Title: The MRGPRX2 related pseudo-allergy was inhibited by several compounds from traditional Chinese medicine
Biography:
Nan Wang is an Associate Professor in Xi’an Jiaotong University. She has her expertise in allergic disease and anti-allergy drug discovery. She is currently focused on allergic asthma and mast cell related diseases.
Abstract:
Pseudo-allergic reactions; adverse, non-immunologic, anaphylaxis-like sudden onset reactions mediated through an IgE-independent pathway are activated by various basic compounds and occur at least as frequently as IgE-mediated reactions to drugs. A large family of G protein coupled receptors (Mas-related genes, MRGPRS) is closely related to pseudo-allergies. However, few therapies can directly target pseudo-allergies and related MRGPRS. Chinese herbal medicine has a long history in China and is still widely used owing to its specific therapeutic effect, broad indications, safety and convenience. Cell Membrane Chromatography (CMC) is an effective new method to directly screen and identify the target components from a complex system and has been widely used in recent years. Isoliquiritigenin (ISO) and Saikosaponin A (SSA) were screen from traditional Chinese medicine injection using a mast cell CMC system. We examined the effect of SSA and ISO on both IgE-independent and IgE-dependent responses using PCA and active systemic anaphylaxis models as well as in vitro cultured mast cells. We also evaluated whether the anti-allergy effect is related to MRGPRS by using in vitro MRGPRX2-expressing HEK293 cells. Both SSA and ISO could also dose-dependently inhibit C48/80-induced MRGPRX2-expressing HEK293 cell activation. This study provided a new sight on pseudo-allergy and its therapy.
Seung Heon Shin
Catholic University of Daegu, South Korea
Title: Effect of microencapsulated essential oil from Chamaecyparis obtusa on monocyte-derived dendritic cell activation and CD4+ T cell polarization
Biography:
Seung Heon Shin has graduated from Kyung Pook National University, School of Medicine, Daegu, South Korea. He is working as a Professor of Otorhinolaryngology, Catholic University of Daegu, School of Medicine, South Korea. He is a Member of Korean Society of Otorhinolaryngology Head & Neck Surgery, Korean Rhinology Society, International Rhinologic Society and Korean Society of Allergy & Asthma.
Abstract:
The essential oil of Chamaecyparis obtusa (C. obtusa) which is used in soap, toothpaste and aromatic agents has been known to have anti-inflammatory properties. In this study, we investigated the effects of microencapsulated C. obtusa essential oil on airborne fungus-induced Dendritic Cell (DC) activation and Th immune responses. We stimulated monocyte-derived DCs with Alternaria alternate and Lipopolysaccharide (LPS). To determine the anti-inflammatory effects, we pre-treated DCs with various concentrations of microencapsulated C. obtusa essential oil and collected the supernatants to measure Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-α) and we determined the expression of cell surface molecules. The effects of the essential oil on CD4+ T cells polarization was determine by culturing stimulated DCs and autologous CD4+ T cells. Alternaria enhanced the production of IL-6 and TNF-α from DCs, and pretreating DCs with 0.001, 0.01, and 0.05% of the essential oil significantly inhibited their production. Increased CD80 and CD86 expression by Alternaria was significantly inhibited with 0.05% of the essential oil. Alternaria-induced IL-5, IL-10, and interferon-gamma from CD4+ T cells were significantly inhibited with C. obtusa essential oil in a dose dependent manner. C. obtusa influenced both Alternaria- and LPS-induced Th1 and Th2 polarization of CD4+ T cells. These results suggest a novel pharmacological use for C. obtusa essential oil to treat inflammatory airway diseases.
Agata Wawrzyniak
Military Institute of Medicine, Poland
Title: The influence of Environmental Tobacco Smoke (ETS) on immune response in children with asthma
Biography:
Agata Wawrzyniak is a Physician at the Department of Pediatrics, Nephrology and Allergology, Military Institute of Medicine, Poland. She is currently pursuing specialization in Pediatrics. Her scientific interests are focused on the immunology of allergic diseases.
Abstract:
Introduction: There has been an increase incidence of allergic diseases over the past several decades. For this reason, potentially modifiable factors that may influence the on immunological processes should be sought.
Aim: The aim of the study was to evaluate the influence of ETS on the immune response in asthma: Blood lymphocyte phenotype (CD3, CD4, CD8, CD19, CD16/56, CD3 anti HLA-DR), T-regulatory (Treg) percentage and cytokine profile (anti-inflammatory: IL-4, IL-10, TGF-β and proinflammatory: IL-1, IL-2, IL-6, IL-17A, IL-22, TNF and IFN).
Material & Methods: The study group consisted of 43 children with stable atopic asthma. The control group consisted of 37 children without atopic disease. ETS was assessed by measuring urinary cotinine concentration by ELISA. The phenotype of peripheral blood lymphocytes, percentage of Treg and interleukin concentration were determined by the cytometric method.
Results: The following results were obtained; higher levels of cytokine IL-1 and lower IL-4 were observed in children with asthma ETS (+) compared to children with asthma ETS (-) (respectively 0.40±0.58 pg/ml vs. 0.08±0.24 pg/ml, p=0.02; 1.19±0.72 pg/ml vs. 0.68±0.77 pg/ml, p=0.04). In the control group, higher levels of IL-4 were found in children ETS (+) compared to children ETS (-) (4.84±8.9 pg/ml vs. 1.53±0.8 pg/ml, p=0.05). Lower percentage of Treg were found in children with asthma ETS (+) compared to healthy children ETS (+) (0.68%±0.31 pg/ml vs. 1.02±0.43 pg/ml; p=0.03).
Conclusion: Exposure to tobacco smoke has immunomodulatory effects; exposure to tobacco smoke in children with asthma may be associated with the development of worse prognostic neutrophilic inflammation. Exposure to tobacco smoke of healthy children may be associated with the development of eosinophilic inflammation, which in the future may lead to allergies.
- Special Session
Location: Seletar Room 1, Level 3
Session Introduction
Hugo P S Van Bever
National University of Singapore, Singapore
Title: Approach to urticaria in children
Biography:
Hugo P S Van Bever has completed his medical studies at the State University of Ghent, Belgium (1971-1978) and did his training in Pediatrics at Children’s Hospital, State University of Ghent, Belgium (1978-1983). Following that he became Resident in Pediatric Allergy and Pulmonology, University of Antwerp, Belgium (1984-1993). He was the Associate Professor in Pediatric Allergy and Pulmonology, University of Antwerp, Belgium (1993-1997) and Professor in Pediatric Allergy and Pulmonology, University of Antwerp, Belgium (1997-2001). He was also the Head of the Department of Pediatrics, University of Antwerp, Belgium. He has joined the National University Singapore as Professor, Senior Consultant and Head of Pediatric Allergy and Immunology, the Department of Pediatrics in June 2002. He is currently an active Member of the Board of APAPARI, in which he is responsible for research and education in pediatric allergy, organizing APAPARI workshops in different Asian countries.
Abstract:
Studies in children have shown that urticaria occurs in about 5% to 7% of non-selected preschool children and in 17% of young children suffering from an underlying atopic disease. Acute urticaria (i.e. less than six weeks) is more frequently seen in young people and children and is usually linked to atopy, while chronic urticaria more frequently occurs in adults, mainly in middle-aged, non-allergic women. If chronic urticaria presents in children, an underlying immunologic or auto-immune disorder should be ruled out. A direct etiological cause can be suspected in >50% of acute urticaria, while this is only the case in about 20% in chronic urticaria. Acute urticaria in children can be caused by a number of triggers including allergens (food and inhalants), medication and infections (viral, bacterial and parasitic infections). There is still some confusion on the classification of urticaria. Most authors divide into three main types: Acute, chronic and physical but other classifications have been proposed. Children with chronic urticaria, in particular those having systemic symptoms (fever, weight loss, joint pain), deserve a diagnostic work-up. In these children it is important to rule out systemic diseases, malignancy, endocrine disorders and chronic infections. In children with persistent and severe painful lesions, without pruritus, urticarial vasculitis needs to be ruled out by skin biopsy. In older children suffering from (recurrent) angioedema without concomitant urticaria and sometimes presenting are recurrent attacks of abdominal pain, C1 esterase inhibitor deficiency should be excluded, even if the family history is negative (i.e. acquired deficiency). Except for the patients for whom an avoidable cause can be identified (such as food), treatment of urticaria is symptomatic. Treatment depends on the severity of symptoms. Scattered or mild hives are self-limited and usually require no treatment or at most a mild antihistamine as needed. In a number of comparative trials between the various non-sedating (2nd generation) agents, no significant difference in efficacy has been noted. All the agents have good safety profiles in children. Cetirizine has the most extensive safety profile in infants, showing efficacy in acute urticaria. In cases of severe urticaria immuno-modulatory treatments might be necessary such as systemic corticosteroids or anti-IgE.
- Pediatric Pulmonology | Internal Medicine | Pulmonary and Critical Care
Location: Seletar Room 1, Level 3
Session Introduction
Agnieszka Lipinska-Opalka
Military Institute of Medicine, Poland
Title: The influence of external factors: Vitamin D level and passive smoking on the severity of atopic dermatitis in children
Biography:
Agnieszka Lipinska-Opalka is a Physician in Allergology, Nephrology and Pediatric Department in the course of Pediatric Residency. She earned a Medical degree from the Medical University of Lublin, Poland. Her scientific interests include all aspects of allergic diseases with particular interests in immuno-pathogenesis of atopic dermatitis.
Abstract:
Background: Atopic Dermatitis (AD) is one of the most common inflammatory skin diseases in children and poses a significant burden on their quality of life. Due to these facts and worldwide rising in the prevalence of allergic diseases, there is an urgent need to look for new factors affecting the course of atopic dermatitis in children.
Aim: The aim was to assess, whether vitamin D level and Exposure to Tobacco Smoke (ETS) have an influence on the course of atopic dermatitis in children and their immune system (natural regulatory T cells, lymphocytes: CD3, CD4, CD8, CD4/CD8, CD19, CD16/56, CD3 anti-HLA-DR).
Methods: The study consisted of 49 children with atopic dermatitis. The course of disease was evaluated by SCORing Atopic Dermatitis (SCORAD) index. Vitamin D concentration was determined by chemiluminescent immunoassay technology, ETS was assessed by measuring urinary cotinine concentration by ELISA. The flow cytometry was used to evaluate the phenotype of lymphocytes.
Results: The vitamin D level was significantly lower in moderate and severe AD compared with mild (p=0.02). There was no significant correlation between ETS and the course of disease. A higher percentage of Natural killer T (NKT) cells was found in children with low concentration of vitamin D in serum compared to patients with optimal level (p=0.04). There were no significant differences in the course of atopic dermatitis between patients exposed to tobacco smoke and non-ETS group. A lower percentage of CD3 and CD4 lymphocytes was observed in patients with atopic dermatitis exposed to passive smoking compared to not exposed children (respectively p=0.04 and p=0.03).
Conclusion: The data suggest that vitamin D deficiency may be inversely associated with severity of atopic dermatitis in children. The study revealed that passive exposure to tobacco smoke may impair the number of CD3 and CD4 lymphocytes in children with atopic dermatitis.
Silvio Manfredo Vieira
Yale University, USA
Title: Spontaneous translocation of a gut pathobiont drives autoimmunity
Biography:
Silvio Manfredo Vieira is a creative and independent Scientist with a robust background in the field of immunology, pharmacology, therapeutics and autoimmunity. He has a strong experience in drug discovery projects and a proficiency in developing and implementing strategies to identify and validate novel biomarkers for investigational therapies in the application of disease understanding. He has expertise in human and translational research and a deep experience in cellular and molecular immunology.
Abstract:
Regardless of the multiple associations between microbiota and immune mediate diseases, its contribution to the pathogenesis of autoimmunity is largely unknown. Here we show that a gut commensal, E. gallinarum reaches lymphocytes beyond the gut barrier, as well as liver and spleen, in the (NZWxBXSB) F1 model of autoimmunity. Oral vancomycin treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, lowered pathogenic autoantibodies, Th17 and Tfh cells. Hepatocyte-commensal co-cultures revealed induction of IFN-, TNF-, IL-1, AhR, CYP1A1 and CYP1A2. E. gallinarum monocolonization in C57BL/6 germ-free animals also led to translocation and induction of autoantibodies as well as increase Plasmacytoid Dendritic Cells (pDCs) and Th17 responses in small intestinal lamina propria. Additionally E. gallinarum altered ileal molecules related to barrier function (occludin, claudins, PLVAP, Axin2), the mucus layer (mucin, FUT2), antimicrobial defense (REG3B, DEFA2) and inflammation (CXCR2, AhR/CYP1A1, ENPP3). Species-specific PCR of liver biopsies from Autoimmune Hepatitis (AIH) and Systemic lupus erythematosus (SLE) patients also revealed E. gallinarum, suggesting similar processes in humans. Outstandingly, human hepatocyte-commensal co-culture demonstrated production of autoimmune-promoting factors. Consistent with enhanced adaptive immune responses to E. gallinarum, AIH and SLE patients showed increased serum titers against its RNA, which may act as a potential TLR7/8 stimulus. Collectively, these data indicate that a human pathobiont translocates spontaneously to promote autoimmunity in genetically predisposed hosts, broadening our understanding of autoimmune host-microbiota interactions.
Biography:
Abstract:
Interferon gamma (IFN)-γ confers crucial immune surveillance positively for immunomodulation (such as macrophage activation, antigen presentation and T cell differentiation), antimicrobial [such as antiviral replication, microbial killing and Major Histocompatibility Complex (MHC) induction] and anticancer activity (such as growth inhibition, cytotoxicity and immune priming). Patients with adult-onset immunodeficiency, negative in Human Immunodeficiency Virus (HIV) infection, show defects in IFN-γ signaling and immune surveillance against mycobacterial infection. In addition to genetic defects, the presence of neutralizing anti-IFN-γ autoantibody (autoAb) is speculated. In the first part, detection of anti-IFN-γ autoAb and characterization of its neutralizing activity were carried out. First, Enzyme-linked Immunosorbent Assay (ELISA)-based colorimetric assays and immunoblotting was utilized for detecting autoAbs. Antibody-antigen reactivity and epitope clarification showed different patterns among these patients. Results showed the blockade of IFN-γ-activated Signal Transducer and Activator of Transcription (STAT)-1 activation and Interferon Regulatory Factor (IRF1) transactivation by patient serum containing autoAbs. Furthermore, IFN-γ-regulated inflammation, chemokine production and cytokine production after T cell activation were also blocked. These results provide potential methods for detecting anti-IFN-γ autoAb and for characterizing the blockade effects of autoAbs on IFN-γ signaling and bioactivity. For the second part, the blockade effect of that antibody on IFN-γ-regulated antimicrobial activity will be detected. We will perform a model of monocyte-derived type-1 macrophage by using Phorbol-12-Myristate-13-Acetate (PMA) and IFN-γ induction. Furthermore, blockade effect of type-1 macrophage differentiation and bacterial phagocytosis/killing by anti-IFN-γ autoAbs will be performed by detection of inhibition on cell marker expression, attachment/engulfment phase and Reactive Oxygen Species (ROS)/Nitric oxide (NO) production. The results provide evidence of blockade effects of IFN-γ against antimicrobial activity by anti-IFN-γ autoAbs.
Sharipova О Ð
Samarkand State Medical Institute, Uzbekistan
Title: Evaluation of sexual development in patients with chronic bronchitis
Biography:
Sharipova O A has completed her PhD from Tashkent Pediatric Medical Institute, Uzbekistan. She is working as an Associate Professor of the Department of Pediatrics and Medical Genetics. She has published more than 30 papers in Uzbekistan and international reputed journals.
Abstract:
The study included 84 children with chronic bronchitis in the age from 11 to 16 years. Of these, 37 (35.7%) were girls and 47 (64.3%) were boys. To check the status of sexual development in boys we carried out genitometric analysis and evaluation of the stages of sexual development by J.M. Tanner (1967). It has been revealed that the boys with chronic bronchitis have reliable lessening in size of penis and testicles. When evaluating the sexual development of girls we paid attention to the pubis and axillary hair distribution, the growth of the mammary glands, for a period of menarche. It is revealed that by the age of 16 in 8 (25%) patients with chronic bronchitis mammary glands were at Ma3 stage and in 24 (75%) did not exceed Tanner II degree. By the age of 16 the sexual body hair was in P2Ax2 stage in 26 (81.3%) and in P3Ax2 stage was only in 6 (18.7%) sick girls. Only 5 (15.6%) girls aged 14-16 had steady menstrual cycle. Thus, our findings allow us to draw a conclusion about the negative impact of chronic bronchitis on sexual development, which requires the development of purposeful practical measures in this direction. In general, all patients maintained a sequence of development of secondary sexual characteristics, but the rates of development of secondary sexual characteristics in comparison with healthy peers are different, i.e. in patients with chronic bronchitis process of puberty occur gradually and does not complete until the end of puberty.
- Asthma Pharmacology | Asthma Triggers | Asthma Medications | Allergy Medication | Allergens and Allergies | Occupational Asthma | COPD
Location: Seletar Room 1, Level 3
Session Introduction
Qian Zhang
Nanjing Medical University, China
Title: Epigenetic regulation on the gene expression signature in bronchial asthma with rhinitis syndrome by RNA sequence
Biography:
Qian Zhang has pursued his PhD degree in Pulmonary Medicine from Nanjing Medical University, Nanjing, China. In 2010, he has worked as a Visiting Scholar in the Department of Internal Medicine at Far Eastern Memorial Hospital, Taiwan. From 2011 to 2016, he has worked as a Post-Doctor in Nanjing General Hospital of Nanjing Military Command, Nanjing, China. Currently, he is working as a Chief Physician, Associate Professor and Director in the Department of Respiratory Medicine at Changzhou No.2 People’s Hospital affiliated to Nanjing Medical University. He is interested in pulmonary medicine, critical care medicine, molecular biology, allergy and immunology.
Abstract:
Background: Bronchial asthma with rhinitis syndrome is the global health problem that affects numbers of patients. This study was intended to identify the signature genes, which was helpful in understanding the potential molecule mechanism of bronchial asthma with rhinitis syndrome.
Methods: The blood samples of three patients with bronchial asthma (accompanied with rhinitis syndrome), three patients with rhinitis and three normal controls were obtained for the RNA sequence. Differentially expressed genes (DEGs) and miRNAs were identified by different software. MiRNA-gene target analysis was performed through prediction tools and the regulatory network was also constructed. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the biological function of differentially expressed genes.
Results: A total of 353 differentially expressed genes and 59 differentially expressed miRNAs were obtained in bronchial asthma compared with that in rhinitis. And 4650 differentially expressed genes and 88 differentially expressed miRNAs were screened in rhinitis compared with that in the control. After targeting correlation analysis, 159 differentially expressed genes were not only the target genes but also negatively correlated with 39 differentially expressed miRNAs in bronchial asthma compared with that in rhinitis. And 2685 differentially expressed genes were not only the target genes but also negatively correlated with 88 differentially expressed miRNAs in rhinitis compared with that in control. Finally, 52 differentially expressed genes and 16 differentially expressed miRNAs were identified after merging the data in above three groups. Among which, five genes including SLC14A1, SNCA, TNS1, KAT2B, PARP1 were target genes of differentially expressed miRNAs (hsa-miR-93-5p, hsa-miR-92a-3p, hsa-miR-21-5p) and were significantly associated with bronchial asthma with rhinitis syndrome. Additionally, functional analysis showed that phagosome was the significantly enriched signal pathway involving three important genes (HLA-DOA, TUBB2A and MRC2).
Conclusion: Taken together, eight genes including TLR2, ICAM1, C1QB, HLA-DOA, ABL1, CASP3, CAV1, CD55, RPS26 and TUBB2A under the regulation of miRNAs played significant roles in the process of bronchial asthma with rhinitis syndrome.
Tae Young Jang
Inha University, South Korea
Title: Nasal provocation test: Allergen provocation and cold air provocation test
Biography:
Tae Young Jang is a Professor at the Department of ORL-HNS, Inha University Hospital, Former President of Korean Rhinoloy Society, President of Korean Society of Aerospace Medicine, Board Member of PAFPRS and Board Member of ARSR.
Abstract:
Nasal Provocation Test (NPT) is an ideal test for diagnosing Allergic Rhinitis (AR), since the target organ, the nasal cavity itself, is directly provoked by the causative allergen. In spite of its usefulness, NPT has not been widely accepted in clinical practice, because of its lack of standardized method and diagnostic criteria. The nonspecific Nasal Hyper-Reactivity (NHR) could be defined as hyper-responsiveness of the nasal cavity induced by nonspecific, non-allergenic stimuli. Cold Dry Air (CDA) provocation test is one of the provocative protocols designed to detect and evaluate this NHR. It has been accepted that CDA provocation is superior to other protocols in detecting NHR. However, there had been still very few studies about its clinical application. This lecture will introduce our method of NPT using intranasal spray of house dust mite allergen extract. This lecture will also discuss the association between NPT and skin prick test, and the proposed diagnostic criteria of AR using acoustic rhinometry in our large-population based study. This lecture will introduce CDA machinery we developed, and discuss its usefulness in detecting and evaluating NHR. This lecture will also cover the diagnostic criteria of NHR using CDA provocation and acoustic rhinometry. Finally, our Subjective Cold Hyper-responsiveness (SCH) grade would be introduced, which was proved to correlate well with the actual result of CDA provocation test.
Jue Wang
Xi’an Jiaotong University, China
Title: Several drugs induce mast cell degranulation and pseudo-allergic reactions via MRGPRX2
Biography:
Jue Wang has her expertise in pseudo-allergic reactions and the possible mechanisms underlying anaphylactoid reactions. She currently focused on allergic asthma and mast cell related diseases.
Abstract:
Mast cells are unique immunocytes that function as sentinel cells in host defense reactions such as immediate hypersensitivity responses and anaphylactic responses. The mast cell specific receptor MRGPRX2 (Mas-related G protein-coupled receptor X2) triggers mast cell degranulation; a key process in anaphylactic reactions. In 2014, McNeil, et al. reported that MRGPRX2 was crucial for drug-induced pseudoallergic reactions. It is widely observed that antimicrobials, opioid receptor and muscle relaxant agonists can induce pseudo-allergic reactions (i.e. IgE-independent mechanism) with symptoms ranging from skin inflammation to life-threatening systemic anaphylaxis. But the allergy effects of these drugs and the possible mechanisms underlying anaphylactoid reactions have not been demonstrated.
Several drugs were screened by Ca2+ imaging using MRGPRX2 overexpressing HEK293 cells. MRGPRX2 related anaphylactoid reactions induced by these components were investigated using skin swelling and extravasation assays in vivo and mast cell degranulation assay in vitro. We showed that MRGPRX2 is involved in allergic-like reactions to three types of antimicrobials(antifungal agents, aminoglycosides and sulfonamides) and muscle relaxant agonists (Mivacurium and Cisatracurium). These drugs caused pseudo-allergic reactions in wild-type mice by inducing mast cells to release histamine. However, it did not induce a similar phenomenon in KitW-sh/W-sh mice. Furthermore, MrgprB2-knockout(MrgprB2 is the murine homologue of MRGPRX2) mice displayed no inflammatory response to them. They induced LAD2 cell degranulation in a dose-dependent manner. They stimulated intracellular calcium ion (Ca2+) influx in MRGPRX2-HEK293 cells but not in NC-HEK293 cells. The results of this study suggest that many clinicians should pay more attention to the possible pseudo-allergic reactions caused by these drugs and reduce the risk of allergic reactions.