1 1225 101 CRITICAL ROLE OF EPIGENETIC MODIFICATION IN THE PATHOGENESIS OF ATOPIC DERMATITIS. ATOPIC DERMATITIS IS A CHRONIC INFLAMMATORY SKIN DISEASE CHARACTERISED BY RECURRENT ECZEMA-LIKE LESIONS AND SEVERE PRURITUS, ALONG WITH DRYING AND DECRUSTATION OF SKIN. CURRENT RESEARCH RELATES THE PATHOGENESIS OF ATOPIC DERMATITIS MAINLY TO GENETIC SUSCEPTIBILITY, ABNORMAL SKIN BARRIER FUNCTION, IMMUNE DISORDERS, STAPHYLOCOCCUS AUREUS COLONISATION, MICROBIOLOGICAL DYSFUNCTION AND VITAMIN D INSUFFICIENCY. EPIGENETIC MODIFICATIONS ARE DISTINCT GENETIC PHENOTYPES RESULTING FROM ENVIRONMENT-DRIVEN CHANGES IN CHROMOSOME FUNCTIONS IN THE ABSENCE OF NUCLEAR DNA SEQUENCE VARIATION. CLASSIC EPIGENETIC EVENTS INCLUDE DNA METHYLATION, HISTONE PROTEIN MODIFICATIONS AND NON-CODING RNA REGULATION. INCREASING EVIDENCE HAS INDICATED THAT EPIGENETIC EVENTS ARE INVOLVED IN THE PATHOGENESIS OF ATOPIC DERMATITIS BY THEIR EFFECTS ON MULTIPLE SIGNALLING PATHWAYS WHICH IN TURN INFLUENCE THE ABOVE FACTORS. THIS REVIEW PRIMARILY ANALYSES THE FUNCTION OF EPIGENETIC REGULATION IN THE PATHOGENESIS OF ATOPIC DERMATITIS. IN ADDITION, IT TRIES TO MAKE RECOMMENDATIONS FOR PERSONALISED EPIGENETIC TREATMENT STRATEGIES FOR ATOPIC DERMATITIS IN THE FUTURE. 2023 2 725 24 CAN THE BLOOD TRYPTASE BE AN INDICATOR OF THE SEVERITY OF ATOPIC DERMATITIS? ATOPIC DERMATITIS (AD - ATOPIC ECZEMA) IS A CHRONIC INFLAMMATORY DERMATOSIS RESULTING FROM COMPLEX GENETIC, EPIGENETIC AND ENVIRONMENTAL INTERACTIONS WITH AN OVERLAPPING DEFECT IN THE EPIDERMAL BARRIER.AD IS ONE OF THE MOST COMMON INFLAMMATORY DERMATOSES IN CHILDREN AND ADULTS. AIM: THE AIM OF THE STUDY WAS TO ASSESS THE RELATIONSHIP BETWEEN SERUM BASAL TRYPTASE (SBT) AND TOTAL IGE (TIGE) LEVEL IN BLOOD SERUM AND THE SEVERITY OF LESIONS (SCORAD; SCORING ATOPIC DERMATITIS). MATERIALS AND METHODS: THE STUDY WAS PERFORMED IN THE GROUP OF ADULT PATIENTS (57 PEOPLE, F/M: 30/27; AVERAGE AGE: 37.5 YEARS) AND IN THE CONTROL GROUP (10 PEOPLE, K/M: 6/4; AVERAGE AGE: 44 YEARS). DIAGNOSIS OF ATOPIC DERMATITIS WAS ESTABLISHED BY A DERMATOLOGIST-ALLERGIST SPECIALIST BASED ON THE CRITERIA OF HANIFIN AND RAJKA. THE SEVERITY OF LESIONS WAS DETERMINED ON THE SCORAD SCALE (SCORING ATOPIC DERMATITIS). RESULTS: THE DISTRIBUTION OF TRYPTASE CONCENTRATION DID NOT DIFFER STATISTICALLY SIGNIFICANTLY BETWEEN PATIENTS WITH VARIOUS DISEASE SEVERITY AND THE CONTROL GROUP ALSO THE SEVERITY OF SKIN LESIONS WAS SIGNIFICANTLY HIGHER (P<0.001) IN PATIENTS WHOSE TIGE LEVEL EXCEEDED 3500 IU / ML. CONCLUSION. SBT DID NOT PROVE TO BE A USEFUL BIOMARKER IN ASSESSING. CONCLUSIONS: SBT DID NOT PROVE TO BE A USEFUL BIOMARKER IN ASSESSING SEVERITY OF AD. THE PRESENT STUDY DEMONSTRATED THAT IN THE PATIENTS WITH ATOPIC DERMATITIS THE CONCENTRATION OF TOTAL IGE WAS CORRELATED WITH SEVERITY OF THE DISEASE SYMPTOMS. 2020 3 5454 31 REPURPOSING BELINOSTAT FOR ALLEVIATION OF ATOPIC DERMATITIS. ATOPIC DERMATITIS (AD) IS A HIGHLY PREVALENT CHRONIC INFLAMMATORY SKIN DISEASE THAT IS CHARACTERIZED BY INTENSE PRURITUS, SERIOUSLY AFFECTING PATIENTS' QUALITY OF LIFE. ITS PATHOPHYSIOLOGY, WHICH INVOLVES BOTH THE ADAPTIVE AND INNATE IMMUNE RESPONSES AS WELL AS SKIN BARRIER DEFECTS, IS STILL POORLY UNDERSTOOD. WE RECENTLY IDENTIFIED A MICRORNA, MIR-335, AS A KEY DRIVER OF KERATINOCYTE DIFFERENTIATION AND CORNIFICATION, WHICH IS ESSENTIAL FOR THE ESTABLISHMENT OF A HEALTHY SKIN BARRIER. HOWEVER, EXPRESSION OF MIR-335 IS LOST IN AD, LEADING TO BARRIER DEFECT. WE FURTHER DEMONSTRATED HOW BELINOSTAT, A HISTONE DEACETYLASE INHIBITOR, CAN EFFECTIVELY RESTORE MIR-335 AND RESOLVE THE BARRIER DEFECT IN A DRY SKIN MODEL. HERE, IN THIS COMMENTARY, WE HIGHLIGHT THE ROLE OF BELINOSTAT IN THE TREATMENT OF AD AND DISCUSS THE NEED FOR MORE RESEARCH INTO CROSSTALK BETWEEN EPIGENETIC AND NON-CODING RNA-BASED REGULATION, AS WELL AS POSSIBLE THERAPEUTIC STRATEGIES TARGETING THE EPIGENOME. 2021 4 541 40 ATOPIC DERMATITIS: THE FATE OF THE FAT. ATOPIC DERMATITIS (AD) IS A CHRONIC AND RELAPSING INFLAMMATORY SKIN DISEASE IN WHICH DRY AND ITCHY SKIN MAY DEVELOP INTO SKIN LESIONS. AD HAS A STRONG GENETIC COMPONENT, AS CHILDREN FROM PARENTS WITH AD HAVE A TWO-FOLD INCREASED CHANCE OF DEVELOPING THE DISEASE. GENETIC RISK LOCI AND EPIGENETIC MODIFICATIONS REPORTED IN AD MAINLY LOCATE TO GENES INVOLVED IN THE IMMUNE RESPONSE AND EPIDERMAL BARRIER FUNCTION. HOWEVER, AD PATHOGENESIS CANNOT BE FULLY EXPLAINED BY (EPI)GENETIC FACTORS SINCE ENVIRONMENTAL TRIGGERS SUCH AS STRESS, POLLUTION, MICROBIOTA, CLIMATE, AND ALLERGENS ALSO PLAY A CRUCIAL ROLE. ALTERATIONS OF THE EPIDERMAL BARRIER IN AD, OBSERVED AT ALL STAGES OF THE DISEASE AND WHICH PRECEDE THE DEVELOPMENT OF OVERT SKIN INFLAMMATION, MANIFEST AS: DRY SKIN; EPIDERMAL ULTRASTRUCTURAL ABNORMALITIES, NOTABLY ANOMALIES OF THE LAMELLAR BODY CARGO SYSTEM; AND ABNORMAL EPIDERMAL LIPID COMPOSITION, INCLUDING SHORTER FATTY ACID MOIETIES IN SEVERAL LIPID CLASSES, SUCH AS CERAMIDES AND FREE FATTY ACIDS. THUS, A COMPELLING QUESTION IS WHETHER AD IS PRIMARILY A LIPID DISORDER EVOLVING INTO A CHRONIC INFLAMMATORY DISEASE DUE TO GENETIC SUSCEPTIBILITY LOCI IN IMMUNOGENIC GENES. IN THIS REVIEW, WE FOCUS ON LIPID ABNORMALITIES OBSERVED IN THE EPIDERMIS AND BLOOD OF AD PATIENTS AND EVALUATE THEIR PRIMARY ROLE IN ELICITING AN INFLAMMATORY RESPONSE. 2022 5 2973 37 GENETIC AND EPIGENETIC STUDIES OF ATOPIC DERMATITIS. BACKGROUND: ATOPIC DERMATITIS (AD) IS A CHRONIC INFLAMMATORY DISEASE CAUSED BY THE COMPLEX INTERACTION OF GENETIC, IMMUNE AND ENVIRONMENTAL FACTORS. THERE HAVE MANY RECENT DISCOVERIES INVOLVING THE GENETIC AND EPIGENETIC STUDIES OF AD. METHODS: A RETROSPECTIVE PUBMED SEARCH WAS CARRIED OUT FROM JUNE 2009 TO JUNE 2016 USING THE TERMS "ATOPIC DERMATITIS", "ASSOCIATION", "ECZEMA", "GENE", "POLYMORPHISM", "MUTATION", "VARIANT", "GENOME WIDE ASSOCIATION STUDY", "MICROARRAY" "GENE PROFILING", "RNA SEQUENCING", "EPIGENETICS" AND "MICRORNA". A TOTAL OF 132 PUBLICATIONS IN ENGLISH WERE IDENTIFIED. RESULTS: TO ELUCIDATE THE GENETIC FACTORS FOR AD PATHOGENESIS, CANDIDATE GENE ASSOCIATION STUDIES, GENOME-WIDE ASSOCIATION STUDIES (GWAS) AND TRANSCRIPTOMIC PROFILING ASSAYS HAVE BEEN PERFORMED IN THIS PERIOD. EPIGENETIC MECHANISMS FOR AD DEVELOPMENT, INCLUDING GENOMIC DNA MODIFICATION AND MICRORNA POSTTRANSCRIPTIONAL REGULATION, HAVE BEEN EXPLORED. TO DATE, CANDIDATE GENE ASSOCIATION STUDIES INDICATE THAT FILAGGRIN (FLG) NULL GENE MUTATIONS ARE THE MOST SIGNIFICANT KNOWN RISK FACTOR FOR AD, AND GENES IN THE TYPE 2 T HELPER LYMPHOCYTE (TH2) SIGNALING PATHWAYS ARE THE SECOND REPLICATED GENETIC RISK FACTOR FOR AD. GWAS STUDIES IDENTIFIED 34 RISK LOCI FOR AD, THESE LOCI ALSO SUGGEST THAT GENES IN IMMUNE RESPONSES AND EPIDERMAL SKIN BARRIER FUNCTIONS ARE ASSOCIATED WITH AD. ADDITIONALLY, GENE PROFILING ASSAYS DEMONSTRATED AD IS ASSOCIATED WITH DECREASED GENE EXPRESSION OF EPIDERMAL DIFFERENTIATION COMPLEX GENES AND ELEVATED TH2 AND TH17 GENES. HYPOMETHYLATION OF TSLP AND FCER1G IN AD WERE REPORTED; AND MIR-155, WHICH TARGET THE IMMUNE SUPPRESSOR CTLA-4, WAS FOUND TO BE SIGNIFICANTLY OVER-EXPRESSED IN INFILTRATING T CELLS IN AD SKIN LESIONS. CONCLUSIONS: THE RESULTS SUGGEST THAT TWO MAJOR BIOLOGIC PATHWAYS ARE RESPONSIBLE FOR AD ETIOLOGY: SKIN EPITHELIAL FUNCTION AND INNATE/ADAPTIVE IMMUNE RESPONSES. THE DYSFUNCTIONAL EPIDERMAL BARRIER AND IMMUNE RESPONSES RECIPROCALLY AFFECT EACH OTHER, AND THEREBY DRIVE DEVELOPMENT OF AD. 2016 6 2064 29 EPIGENETIC CONTROL OF INFLAMMATION IN ATOPIC DERMATITIS. ATOPIC DERMATITIS (AD), ALSO KNOWN AS ATOPIC ECZEMA, IS A COMMON BUT ALSO COMPLEX CHRONIC, ITCHY SKIN CONDITION WITH UNDERLYING INFLAMMATION OF THE SKIN. THIS SKIN AILMENT IS PREVALENT WORLDWIDE AND AFFECTS PEOPLE OF ALL AGES, PARTICULARLY CHILDREN BELOW FIVE YEARS OF AGE. THE ITCHING AND RESULTING RASHES IN AD PATIENTS ARE OFTEN THE RESULT OF INFLAMMATORY SIGNALS, THUS NECESSITATING A CLOSER LOOK AT THE INFLAMMATION-REGULATING MECHANISMS FOR PUTATIVE RELIEF, CARE AND THERAPY. SEVERAL CHEMICAL- AS WELL AS GENETICALLY-INDUCED ANIMAL MODELS HAVE ESTABLISHED THE IMPORTANCE OF TARGETING PRO-INFLAMMATORY AD MICROENVIRONMENT. EPIGENETIC MECHANISMS ARE GAINING ATTENTION TOWARDS A BETTER UNDERSTANDING OF THE ONSET AS WELL AS THE PROGRESSION OF INFLAMMATION. SEVERAL PHYSIOLOGICAL PROCESSES WITH IMPLICATIONS IN PATHOPHYSIOLOGY OF AD, SUCH AS, BARRIER DYSFUNCTION EITHER DUE TO REDUCED FILAGGRIN / HUMAN BETA-DEFENSINS OR ALTERED MICROBIOME, REPROGRAMING OF FC RECEPTORS WITH RESULTING OVEREXPRESSION OF HIGH AFFINITY IGE RECEPTORS, ELEVATED EOSINOPHIL NUMBERS OR THE ELEVATED IL-22 PRODUCTION BY CD4 + T CELLS HAVE UNDERLYING EPIGENETIC MECHANISMS THAT INCLUDE DIFFERENTIAL PROMOTER METHYLATION AND/OR REGULATION BY NON-CODING RNAS. REVERSING THESE EPIGENETIC CHANGES HAS BEEN VERIFIED TO REDUCE INFLAMMATORY BURDEN THROUGH ALTERED SECRETION OF CYTOKINES IL-6, IL-4, IL-13, IL-17, IL-22 ETC, WITH BENEFIT AGAINST AD PROGRESSION IN EXPERIMENTAL MODELS. A THOROUGH UNDERSTANDING OF EPIGENETIC REMODELING OF INFLAMMATION IN AD HAS THE POTENTIAL OF OPENING AVENUES FOR NOVEL DIAGNOSTIC, PROGNOSTIC AND THERAPEUTIC OPTIONS. 2023 7 6643 36 UNRAVELLING THE COMPLEX GENETIC BACKGROUND OF ATOPIC DERMATITIS: FROM GENETIC ASSOCIATION RESULTS TOWARDS NOVEL THERAPEUTIC STRATEGIES. ATOPIC DERMATITIS (AD) IS A CHRONIC INFLAMMATORY SKIN DISEASE ARISING FROM COMPLEX INTERACTION BETWEEN GENETIC AND ENVIRONMENTAL FACTORS. AS THE STARTING POINT OF THE SO-CALLED "ATOPIC MARCH", E.G. THE PROGRESSION TOWARDS ALLERGIC ASTHMA IN SOME BUT NOT ALL AFFECTED CHILDREN, AD HAS COME INTO FOCUS FOR POTENTIAL DISEASE-MODIFYING STRATEGIES. TO ELUCIDATE THE GENETIC FACTORS INFLUENCING AD DEVELOPMENT, LINKAGE, ASSOCIATION AS WELL AS GENOME-WIDE ASSOCIATION STUDIES HAVE BEEN PERFORMED OVER THE LAST TWO DECADES. THE RESULTS SUGGEST THAT BESIDES VARIATION IN IMMUNE-MEDIATED PATHWAYS, AN INTACT SKIN BARRIER FUNCTION PLAYS A KEY ROLE IN AD DEVELOPMENT. MUTATIONS IN THE GENE ENCODING FILAGGRIN, A MAJOR STRUCTURAL PROTEIN IN THE EPIDERMIS, HAVE BEEN CONSISTENTLY ASSOCIATED WITH AD, ESPECIALLY THE EARLY-ONSET PERSISTENT FORM OF DISEASE, AND ARE REGARDED AS THE MOST SIGNIFICANT KNOWN RISK FACTOR FOR AD DEVELOPMENT TO DATE. ADDITIONALLY, VARIATION IN SOME OTHER GENES INVOLVED IN SKIN INTEGRITY AND BARRIER FUNCTION HAVE SHOWN ASSOCIATION WITH AD. HOWEVER, THE KNOWN GENETIC RISK FACTORS CAN ONLY EXPLAIN A SMALL PART OF THE HERITABILITY AT THE MOMENT. WHOLE-EXOME OR WHOLE-GENOME SEQUENCING STUDIES HAVE NOT BEEN REPORTED YET, BUT WILL PROBABLY SOON EVALUATE THE INFLUENCE OF RARE VARIATIONS FOR AD DEVELOPMENT. ADDITIONALLY, LARGE MULTI-CENTRE STUDIES COMPREHENSIVELY INCORPORATING GENE-GENE AND GENE-ENVIRONMENT INTERACTIONS AS WELL AS EPIGENETIC MECHANISMS MIGHT FURTHER ELUCIDATE THE GENETIC FACTORS UNDERLYING AD PATHOGENESIS AND, THUS, OPEN THE WAY FOR A MORE INDIVIDUALIZED TREATMENT IN THE FUTURE. 2015 8 3104 31 GENOMIC, EPIGENOMIC, TRANSCRIPTOMIC, PROTEOMIC AND METABOLOMIC APPROACHES IN ATOPIC DERMATITIS. ATOPIC DERMATITIS (AD) IS A CHRONIC INFLAMMATORY SKIN DISEASE WITH A HIGH PREVALENCE IN THE DEVELOPED COUNTRIES. IT IS ASSOCIATED WITH ATOPIC AND NON-ATOPIC DISEASES, AND ITS CLOSE CORRELATION WITH ATOPIC COMORBIDITIES HAS BEEN GENETICALLY DEMONSTRATED. ONE OF THE MAIN ROLES OF GENETIC STUDIES IS TO COMPREHEND THE DEFECTS OF THE CUTANEOUS BARRIER DUE TO FILAGGRIN DEFICIT AND EPIDERMAL SPONGIOSIS. RECENTLY, EPIGENETIC STUDIES STARTED TO ANALYZE THE INFLUENCE OF THE ENVIRONMENTAL FACTORS ON GENE EXPRESSION. THE EPIGENOME IS CONSIDERED TO BE A SUPERIOR SECOND CODE THAT CONTROLS THE GENOME, WHICH INCLUDES ALTERATIONS OF THE CHROMATIN. THE EPIGENETIC CHANGES DO NOT ALTER THE GENETIC CODE, HOWEVER, CHANGES IN THE CHROMATIN STRUCTURE COULD ACTIVATE OR INHIBIT THE TRANSCRIPTION PROCESS OF CERTAIN GENES AND CONSEQUENTLY, THE TRANSLATION PROCESS OF THE NEW MRNA INTO A POLYPEPTIDE CHAIN. IN-DEPTH ANALYSIS OF THE TRANSCRIPTOMIC, METABOLOMIC AND PROTEOMIC STUDIES ALLOW TO UNRAVEL DETAILED MECHANISMS THAT CAUSE AD. THE EXTRACELLULAR SPACE AND LIPID METABOLISM ARE ASSOCIATED WITH AD THAT IS INDEPENDENT OF THE FILAGGRIN EXPRESSION. ON THE OTHER HAND, AROUND 45 PROTEINS ARE CONSIDERED AS THE PRINCIPAL COMPONENTS IN THE ATOPIC SKIN. MOREOVER, GENETIC STUDIES BASED ON THE DISRUPTED CUTANEOUS BARRIER CAN LEAD TO THE DEVELOPMENT OF NEW TREATMENTS TARGETING THE CUTANEOUS BARRIER OR CUTANEOUS INFLAMMATION. UNFORTUNATELY, AT PRESENT, THERE ARE NO TARGET THERAPIES THAT FOCUS ON THE EPIGENETIC PROCESS OF AD. HOWEVER, IN THE FUTURE, MIR-143 COULD BE AN IMPORTANT OBJECTIVE FOR NEW THERAPIES, AS IT TARGETS THE MIR-335:SOX AXIS, THEREBY RESTORING THE MIR-335 EXPRESSION, AND REPAIRING THE CUTANEOUS BARRIER DEFECTS. 2023 9 6158 37 THE GENETICS AND EPIGENETICS OF ATOPIC DERMATITIS-FILAGGRIN AND OTHER POLYMORPHISMS. ATOPIC DERMATITIS (AD) IS A CHRONIC INFLAMMATORY SKIN DISEASE CAUSED BY A COMBINATION OF GENETIC AND ENVIRONMENTAL FACTORS. GENETIC EVIDENCES DEPICT A COMPLEX NETWORK COMPRISING BY EPIDERMAL BARRIER DYSFUNCTIONS AND DYSREGULATION OF INNATE AND ADAPTIVE IMMUNITY IN THE PATHOGENESIS OF AD. MUTATIONS IN THE HUMAN FILAGGRIN GENE (FLG) ARE THE MOST SIGNIFICANT AND WELL-REPLICATED GENETIC MUTATION ASSOCIATED WITH AD, AND OTHER MUTATIONS ASSOCIATED WITH EPIDERMAL BARRIERS SUCH AS SPINK5, FLG-2, SPRR3, AND CLDN1 HAVE ALL BEEN LINKED TO AD. GENE VARIANTS MAY ALSO CONTRIBUTE TO THE ABNORMAL INNATE AND ADAPTIVE RESPONSES FOUND IN AD, INCLUDING MUTATIONS IN PRRS AND AMPS, TSLP AND TSLPR, IL-1 FAMILY CYTOKINES AND RECEPTORS GENES, VITAMIN D PATHWAY GENES, FCER1A, AND TH2 AND OTHER CYTOKINES GENES. GWAS AND IMMUNOCHIP ANALYSIS HAVE IDENTIFIED A TOTAL OF 19 SUSCEPTIBILITY LOCI FOR AD. CANDIDATE GENES AT THESE SUSCEPTIBILITY LOCI IDENTIFIED BY GWAS AND IMMUNOCHIP ANALYSIS ALSO SUGGEST ROLES FOR EPIDERMAL BARRIER FUNCTIONS, INNATE AND ADAPTIVE IMMUNITY, INTERLEUKIN-1 FAMILY SIGNALING, REGULATORY T CELLS, THE VITAMIN D PATHWAY, AND THE NERVE GROWTH FACTOR PATHWAY IN THE PATHOGENESIS OF AD. INCREASING EVIDENCES SHOW THE MODERN LIFESTYLE (I.E., THE HYGIENE HYPOTHESIS, WESTERN DIET) AND OTHER ENVIRONMENTAL FACTORS SUCH AS POLLUTION AND ENVIRONMENTAL TOBACCO SMOKE (ETS) LEAD TO THE INCREASING PREVALENCE OF AD WITH THE DEVELOPMENT OF INDUSTRIALIZATION. EPIGENETIC ALTERATIONS IN RESPONSE TO THESE ENVIRONMENTAL FACTORS, INCLUDING DNA METHYLATION AND MICRORNA RELATED TO IMMUNE SYSTEM AND SKIN BARRIERS, HAVE BEEN FOUND TO CONTRIBUTE TO THE PATHOGENESIS OF AD. GENETIC VARIANTS AND EPIGENETIC ALTERATION MIGHT BE THE KEY TOOLS FOR THE MOLECULAR TAXONOMY OF AD AND PROVIDE THE BACKGROUND FOR THE PERSONALIZED MANAGEMENT. 2016 10 4872 40 OUTSIDE-IN HYPOTHESIS REVISITED: THE ROLE OF MICROBIAL, EPITHELIAL, AND IMMUNE INTERACTIONS. OBJECTIVE: OUR UNDERSTANDING OF THE ORIGIN OF ALLERGIC DISEASES HAS INCREASED IN RECENT YEARS, HIGHLIGHTING THE IMPORTANCE OF MICROBIAL DYSBIOSIS AND EPITHELIAL BARRIER DYSFUNCTION IN AFFECTED TISSUES. EXPLORING THE MICROBIAL-EPITHELIAL-IMMUNE CROSSTALK UNDERLYING THE MECHANISMS OF ALLERGIC DISEASES WILL ALLOW THE DEVELOPMENT OF NOVEL PREVENTION AND TREATMENT STRATEGIES FOR ALLERGIC DISEASES. DATA SOURCES: THIS REVIEW SUMMARIZES THE RECENT ADVANCES IN MICROBIAL, EPITHELIAL, AND IMMUNE INTERACTIONS IN ATOPIC DERMATITIS, ALLERGIC RHINITIS, CHRONIC RHINOSINUSITIS, AND ASTHMA. STUDY SELECTIONS: WE PERFORMED A LITERATURE SEARCH, IDENTIFYING RELEVANT RECENT PRIMARY ARTICLES AND REVIEW ARTICLES. RESULTS: DYNAMIC CROSSTALK BETWEEN THE ENVIRONMENTAL FACTORS AND MICROBIAL, EPITHELIAL, AND IMMUNE CELLS IN THE DEVELOPMENT OF ATOPIC DERMATITIS, ALLERGIC RHINITIS, CHRONIC RHINOSINUSITIS, AND ASTHMA UNDERLIES THE PATHOGENESIS OF THESE DISEASES. THERE IS SUBSTANTIAL EVIDENCE IN THE LITERATURE SUGGESTING THAT ENVIRONMENTAL FACTORS DIRECTLY AFFECT BARRIER FUNCTION OF THE EPITHELIUM. IN ADDITION, T-HELPER 2 (T(H)2) CELLS, TYPE 2 INNATE LYMPHOID CELLS, AND THEIR CYTOKINE INTERLEUKIN 13 (IL-13) DAMAGE SKIN AND LUNG BARRIERS. THE EFFECTS OF ENVIRONMENTAL FACTORS MAY AT LEAST IN PART BE MEDIATED BY EPIGENETIC MECHANISMS. HISTONE DEACETYLASE ACTIVATION BY TYPE 2 IMMUNE RESPONSE HAS A MAJOR EFFECT ON LEAKY BARRIERS AND BLOCKING OF HISTONE DEACETYLASE ACTIVITY CORRECTS THE DEFECTIVE BARRIER IN HUMAN AIR-LIQUID INTERFACE CULTURES AND MOUSE MODELS OF ALLERGIC ASTHMA WITH RHINITIS. WE ALSO PRESENT AND DISCUSS A NOVEL DEVICE TO DETECT AND MONITOR SKIN BARRIER DYSFUNCTION, WHICH PROVIDES AN OPPORTUNITY TO RAPIDLY AND ROBUSTLY ASSESS DISEASE SEVERITY. CONCLUSION: A COMPLEX INTERPLAY BETWEEN ENVIRONMENTAL FACTORS, EPITHELIUM, AND THE IMMUNE SYSTEM IS INVOLVED IN THE DEVELOPMENT OF SYSTEMIC ALLERGIC DISEASES. 2020 11 3518 29 IGE SENSITIZATION PROFILES DIFFER BETWEEN ADULT PATIENTS WITH SEVERE AND MODERATE ATOPIC DERMATITIS. BACKGROUND: ATOPIC DERMATITIS (AD) IS A COMPLEX CHRONIC INFLAMMATORY DISEASE WHERE ALLERGENS CAN ACT AS SPECIFIC TRIGGERING FACTORS. AIM: TO CHARACTERIZE THE SPECIFICITIES OF IGE-REACTIVITY IN PATIENTS WITH AD TO A BROAD PANEL OF EXOGENOUS ALLERGENS INCLUDING MICROBIAL AND HUMAN ANTIGENS. METHODOLOGY: ADULT PATIENTS WITH AD WERE GROUPED ACCORDING TO THE SCORAD INDEX, INTO SEVERE (N = 53) AND MODERATE AD (N = 126). AS CONTROLS 43 PATIENTS WERE INCLUDED WITH SEBORRHOEIC ECZEMA AND 97 INDIVIDUALS WITHOUT HISTORY OF ALLERGY OR SKIN DISEASES. SPECIFIC IGE REACTIVITY WAS ASSESSED IN PLASMA USING PHADIATOP(R), IMMUNOCAP, MICRO-ARRAYED ALLERGENS, DOT-BLOTTED RECOMBINANT MALASSEZIA SYMPODIALIS ALLERGENS, AND IMMUNE-BLOTTED MICROBIAL AND HUMAN PROTEINS. RESULTS: IGE REACTIVITY WAS DETECTED IN 92% OF PATIENTS WITH SEVERE AND 83% OF PATIENTS WITH MODERATE AD. SENSITIZATION TO CAT ALLERGENS OCCURRED MOST FREQUENTLY, FOLLOWED BY SENSITIZATION TO BIRCH POLLEN, GRASS POLLEN, AND TO THE SKIN COMMENSAL YEAST M. SYMPODIALIS. PATIENTS WITH SEVERE AD SHOWED A SIGNIFICANTLY HIGHER FREQUENCY OF IGE REACTIVITY TO ALLERGENS LIKE CAT (RFEL D 1) AND HOUSE DUST MITE (RDER P 4 AND 10), TO STAPHYLOCOCCUS AUREUS, M. SYMPODIALIS, AND TO HUMAN ANTIGENS. IN CONTRAST, THERE WERE NO SIGNIFICANT DIFFERENCES IN THE FREQUENCIES OF IGE REACTIVITY TO THE GRASS POLLEN ALLERGENS RPHL P 1, 2, 5B, AND 6 BETWEEN THE TWO AD GROUPS. FURTHERMORE THE IGE REACTIVITY PROFILE OF PATIENTS WITH SEVERE AD WAS MORE SPREAD TOWARDS SEVERAL DIFFERENT ALLERGEN MOLECULES AS COMPARED TO PATIENTS WITH MODERATE AD. CONCLUSION: WE HAVE REVEALED A HITHERTO UNKNOWN DIFFERENCE REGARDING THE MOLECULAR SENSITIZATION PROFILE IN PATIENTS WITH SEVERE AND MODERATE AD. MOLECULAR PROFILING TOWARDS ALLERGEN COMPONENTS MAY PROVIDE A BASIS FOR FUTURE INVESTIGATIONS AIMING TO EXPLORE THE ENVIRONMENTAL, GENETIC AND EPIGENETIC FACTORS WHICH COULD BE RESPONSIBLE FOR THE DIFFERENT APPEARANCE AND SEVERITY OF DISEASE PHENOTYPES IN AD. 2016 12 845 30 CHILDHOOD ATOPIC DERMATITIS: CURRENT DEVELOPMENTS, TREATMENT APPROACHES, AND FUTURE EXPECTATIONS. ATOPIC DERMATITIS (AD) IS THE MOST COMMON CHRONIC INFLAMMATORY SKIN DISORDER OF CHILDHOOD. UNDERLYING FACTORS THAT CONTRIBUTE TO AD ARE IMPAIRED EPITHELIAL BARRIER, ALTERATIONS IN THE LIPID COMPOSITION OF THE SKIN, IMMUNOLOGICAL IMBALANCE INCLUDING INCREASED TH2/TH1 RATIO, PROINFLAMMATORY CYTOKINES, DECREASED T REGULATORY CELLS, GENETIC MUTATIONS, AND EPIGENETIC ALTERATIONS. ATOPIC DERMATITIS IS A MULTIFACTORIAL DISEASE WITH A PARTICULARLY COMPLICATED PATHOPHYSIOLOGY. DISCOVERIES TO DATE MAY BE CONSIDERED THE TIP OF THE ICEBERG, AND THE INCREASING NUMBER OF STUDIES IN THIS FIELD INDICATE THAT THERE ARE MANY POINTS TO BE ELUCIDATED IN AD PATHOPHYSIOLOGY. IN THIS REVIEW, WE AIMED TO ILLUSTRATE THE CURRENT UNDERSTANDING OF THE UNDERLYING PATHOGENIC MECHANISMS IN AD, TO EVALUATE AVAILABLE TREATMENT OPTIONS WITH A FOCUS ON RECENTLY DISCOVERED THERAPEUTIC AGENTS, AND TO DETERMINE THE PERSONAL, FAMILIAL, AND ECONOMIC BURDENS OF THE DISEASE, WHICH ARE FREQUENTLY NEGLECTED ISSUES IN AD. CURRENTLY AVAILABLE THERAPIES ONLY PROVIDE TRANSIENT SOLUTIONS AND CANNOT FULLY CURE THE DISEASE. HOWEVER, ADVANCES IN THE UNDERSTANDING OF THE PATHOGENIC MECHANISMS OF THE DISEASE HAVE LED TO THE PRODUCTION OF NEW TREATMENT OPTIONS, WHILE ONGOING DRUG TRIALS ALSO HAVE HAD PROMISING RESULTS. 2019 13 429 27 ANTI-INFLAMMATORY TOPICAL MEDICATION - NEW DEVELOPMENTS IN THE TREATMENT OF ATOPIC DERMATITIS. ATOPIC DERMATITIS IS A CHRONIC INFLAMMATORY DISEASE THAT ARISES FROM POLYGENIC DISPOSITION, A DYSFUNCTION OF THE PHYSICOCHEMICAL EPITHELIAL BARRIER, A CUTANEOUS DYSBIOSIS, AND A FAULTY NEUROSENSORY ACTIVITY AND SHOWS A HIGHLY INDIVIDUAL ACUITY DUE TO EPIGENETIC FACTORS. AN ESSENTIAL COMPONENT OF THERAPEUTIC MANAGEMENT IS THE APPLICATION OF ANTI-INFLAMMATORY TOPICAL MEDICATION. CURRENTLY, TOPICAL GLUCOCORTICOIDS AND TOPICAL CALCINEURIN INHIBITORS ARE ROUTINELY USED IN REACTIVE AND PROACTIVE THERAPY. IN RECENT YEARS, THE DEVELOPMENT OF MOLECULAR MEDICINE HAS IDENTIFIED SEVERAL NEW THERAPEUTIC TARGETS THAT HAVE ENABLED THE DEVELOPMENT OF INNOVATIVE THERAPEUTIC APPROACHES. IN ADDITION TO PHOSPHODIESTERASE-4 INHIBITORS AND ARYL HYDROCARBON RECEPTOR MODULATORS, IT IS MAINLY JANUS KINASE INHIBITORS WITH DIFFERENT SELECTIVITY THAT ARE EMERGING AS NEW EFFECTIVE AND SAFE OPTIONS FOR TOPICAL THERAPY. THE CURRENT DATA SUGGESTS THAT IN THE COMING MONTHS AND YEARS REPRESENTATIVES OF THE ABOVE-MENTIONED SUBSTANCE CLASSES WILL BE APPROVED FOR TOPICAL USE. 2021 14 5087 29 PIMECROLIMUS FOR THE TREATMENT OF ATOPIC DERMATITIS IN INFANTS: AN ASIAN PERSPECTIVE. ATOPIC DERMATITIS (AD) IS A COMMON CHRONIC, MULTISYSTEM INFLAMMATORY SKIN DISEASE IN PEDIATRIC PATIENTS. THERE HAS BEEN AN INCREASE IN THE INCIDENCE OF AD IN THE PEDIATRIC POPULATION OF THE ASIA-PACIFIC REGION. STUDIES HAVE SHOWN THAT GENETIC, EPIGENETIC, ENVIRONMENTAL AND CULTURAL FACTORS MAY LEAD TO DIFFERENCES IN THE CLINICAL MANIFESTATION AND PREVALENCE OF AD BETWEEN RACES. EARLY TREATMENT OF AD IS NECESSARY TO PREVENT THE ATOPIC MARCH LEADING TO COMORBIDITIES SUCH AS ASTHMA AND ALLERGIC RHINITIS. TOPICAL CORTICOSTEROIDS (TCS) ARE USED AS FIRST-LINE THERAPY FOR THE TREATMENT OF AD, BUT THEIR LONG-TERM USAGE POSES A RISK TO THE PATIENT'S HEALTH. PIMECROLIMUS (1%) IS A TOPICAL CALCINEURIN INHIBITOR (TCI) THAT IS INDICATED FOR THE TREATMENT OF MILD TO MODERATE AD. PIMECROLIMUS HAS NO APPARENT INCREASE IN ADVERSE EVENTS COMPARED TO TCS, AND IT CAUSES LESS OF A BURNING SENSATION THAN TACROLIMUS. THE SAFETY AND EFFICACY OF PIMECROLIMUS HAS BEEN ESTABLISHED THROUGH VARIOUS CLINICAL TRIALS; YET, IN MANY ASIAN COUNTRIES, THE USE OF PIMECROLIMUS IN INFANTS IS STILL RESTRICTED DUE TO SAFETY CONCERNS. BASED ON THE AVAILABLE EVIDENCE, THE EXPERT PANEL RECOMMENDS PIMECROLIMUS IN INFANTS BETWEEN 3 MONTHS AND 2 YEARS OF AGE IN THE ASIAN POPULATION. 2023 15 6877 28 [REASONS FOR THE DEVELOPMENT OF ALLERGIES IN CHILDREN]. ALLERGIES ARE ONE OF THE MOST COMMON CHRONIC DISEASES IN CHILDHOOD, CONTRIBUTING TO A TREMENDOUS MEDICAL AND ECONOMICAL BURDEN IN HEALTH CARE SYSTEMS OF MOST INDUSTRIALIZED COUNTRIES. THE DEVELOPMENT OF ALLERGIES IS DEPENDENT ON A COMPLEX INTERACTION OF-AMONG OTHERS-ENVIRONMENTAL FACTORS, NUTRITION, GENETIC AND EPIGENETIC MECHANISMS AS WELL AS THE MICROBIOME. THESE DIVERSE FACTORS CAN INFLUENCE EARLY LIFE IMMUNE REGULATION INCLUDING INNATE AND ADAPTIVE IMMUNE MECHANISMS IN A COMPLEX FASHION. IN CASE OF ANY CHILDHOOD ALLERGIES HAVE INCREASED SIGNIFICANTLY IN PAST DECADES. IN ADDITION TO ENVIRONMENTAL FACTORS AND NUTRITION, GENETIC AND EPIGENETIC MECHANISMS AS WELL AS THE MICROBIOME OF CHILDREN PLAY AN IMPORTANT ROLE. OF RELEVANCE IS THE WAY IN WHICH THESE DIVERSE FACTORS INFLUENCE EARLY IMMUNE DEVELOPMENT OF THE INNATE AND ADAPTIVE IMMUNE SYSTEMS OF CHILDREN. THEIR COMPLEX REGULATION IS DECISIVE FOR WHETHER OR NOT A CHILD DEVELOPS AN ALLERGY THAT MANIFESTS IN MOST CASES AS ATOPIC DERMATITIS, BRONCHIAL ASTHMA, OR ALLERGIC RHINO CONJUNCTIVITIS, OR WHETHER A CHILD DEVELOPS AN IMMUNE TOLERANCE. THESE INFLUENCES CAN BEGIN PRENATALLY, ALREADY SETTING THE COURSE FOR LATER IMMUNE SYSTEM DEVELOPMENT AND OCCURRENCE OF DISEASE. 2019 16 3580 30 IMPACT OF PERINATAL ENVIRONMENTAL TOBACCO SMOKE ON THE DEVELOPMENT OF CHILDHOOD ALLERGIC DISEASES. ALLERGIC DISEASES SUCH AS ASTHMA, ALLERGIC RHINITIS, ATOPIC DERMATITIS, AND FOOD ALLERGY, ARE MOST COMMON CHRONIC, NONCOMMUNICABLE DISEASES IN CHILDHOOD. IN THE PAST FEW DECADES, THE PREVALENCE HAS INCREASED ABRUPTLY WORLDWIDE. THERE ARE 2 POSSIBLE EXPLANATIONS FOR THE RISING PREVALENCE OF ALLERGIC DISEASES WORLDWIDE, THAT AN INCREASED DISEASE-AWARENESS OF PHYSICIAN, PATIENT, OR CAREGIVERS, AND AN ABRUPT EXPOSURE TO UNKNOWN HAZARDS. UNFORTUNATELY, THE UNDERLYING MECHANISMS REMAIN LARGELY UNKNOWN. DESPITE THE CONTINUING EFFORTS WORLDWIDE, THE ETIOLOGIES AND RISING PREVALENCE REMAIN UNCLEAR. THUS, IT IS IMPORTANT TO IDENTIFY AND CONTROL RISK FACTORS IN THE SUSCEPTIBLE INDIVIDUAL FOR THE BEST PREVENTION AND MANAGEMENT. GENETIC SUSCEPTIBILITY OR ENVIRONMENTS MAY BE A POTENTIAL BACKGROUND FOR THE DEVELOPMENT OF ALLERGIC DISEASE, HOWEVER THEY ALONE CANNOT EXPLAIN THE RISING PREVALENCE WORLDWIDE. THERE IS GROWING EVIDENCE THAT EPIGENETIC CHANGE DEPENDS ON THE GENE, ENVIRONMENT, AND THEIR INTERACTIONS, MAY INDUCE A LONG-LASTING ALTERED GENE EXPRESSION AND THE CONSEQUENT DEVELOPMENT OF ALLERGIC DISEASES. IN EPIGENETIC MECHANISMS, ENVIRONMENTAL TOBACCO SMOKE (ETS) EXPOSURE DURING CRITICAL PERIOD (I.E., DURING PREGNANCY AND EARLY LIFE) ARE CONSIDERED AS A POTENTIAL CAUSE OF THE DEVELOPMENT OF CHILDHOOD ALLERGIC DISEASES. HOWEVER, THE CAUSAL RELATIONSHIP IS STILL UNCLEAR. THIS REVIEW AIMED TO HIGHLIGHT THE IMPACT OF ETS EXPOSURE DURING THE PERINATAL PERIOD ON THE DEVELOPMENT OF CHILDHOOD ALLERGIC DISEASES AND TO PROPOSE A FUTURE RESEARCH DIRECTION. 2016 17 6808 19 [EPIGENETICS IN ALLERGIC DISEASES AND ASTHMA]. ALLERGIC DISEASES AND ASTHMA ARE THE RESULT OF COMPLEX INTERACTIONS BETWEEN GENETIC PREDISPOSITION AND ENVIRONMENTAL FACTORS. ASTHMA IS ONE OF THE MOST PREVALENT CHRONIC DISEASE AMONG CHILDREN. IN THIS ARTICLE WE REVIEW SOME ENVIRONMENTAL FACTORS LIKE: ALLERGEN EXPOSITION, TOBACCO, BACTERIA, MICROBIAL COMPONENTS, DIET, OBESITY AND STRESS, WHICH INFLUENCES DURING INTRAUTERINE AND INFANCY LIFE IN THE EPIGENETIC REGULATION OF ASTHMA AND ALLERGIC DISEASES. THE REVIEW HAS BEEN DONE IN THREE MODELS: IN-VITRO, ANIMAL AND HUMAN. 2016 18 846 31 CHILDHOOD EXPOSURE TO AMBIENT POLYCYCLIC AROMATIC HYDROCARBONS IS LINKED TO EPIGENETIC MODIFICATIONS AND IMPAIRED SYSTEMIC IMMUNITY IN T CELLS. BACKGROUND: EVIDENCE SUGGESTS THAT EXPOSURE TO POLYCYCLIC AROMATIC HYDROCARBONS (PAHS) INCREASES ATOPY; IT IS UNCLEAR HOW PAH EXPOSURE IS LINKED TO INCREASED SEVERITY OF ATOPIC DISEASES. OBJECTIVE: WE HYPOTHESIZED THAT AMBIENT PAH EXPOSURE IS LINKED TO IMPAIRMENT OF IMMUNITY IN ATOPIC CHILDREN (DEFINED AS CHILDREN WITH ASTHMA AND/OR ALLERGIC RHINITIS) FROM FRESNO, CALIFORNIA, AN AREA WITH ELEVATED AMBIENT PAHS. METHODS: WE RECRUITED 256 SUBJECTS FROM FRESNO, CA. AMBIENT PAH CONCENTRATIONS (NG/M(3) ) WERE MEASURED USING A SPATIAL-TEMPORAL REGRESSION MODEL OVER MULTIPLE TIME PERIODS. ASTHMA DIAGNOSIS WAS DETERMINED BY CURRENT NHLBI CRITERIA. PHENOTYPING AND FUNCTIONAL IMMUNE MEASUREMENTS WERE PERFORMED FROM ISOLATED CELLS. FOR EPIGENETIC MEASUREMENTS, DNA WAS ISOLATED AND PYROSEQUENCED. RESULTS: WE SHOW THAT HIGHER AVERAGE PAH EXPOSURE WAS SIGNIFICANTLY ASSOCIATED WITH IMPAIRED TREG FUNCTION AND INCREASED METHYLATION IN THE FORKHEAD BOX PROTEIN 3 (FOXP3) LOCUS (P < 0.05), CONDITIONAL ON ATOPIC STATUS. THESE EPIGENETIC MODIFICATIONS WERE SIGNIFICANTLY LINKED TO DIFFERENTIAL PROTEIN EXPRESSION OF FOXP3 (P < 0.001). METHYLATION WAS ASSOCIATED WITH CELLULAR FUNCTIONAL CHANGES, SPECIFICALLY TREG DYSFUNCTION, AND AN INCREASE IN TOTAL PLASMA IGE LEVELS. PROTEIN EXPRESSION OF IL-10 DECREASED AND IFN-GAMMA INCREASED AS THE EXTENT OF PAH EXPOSURE INCREASED. THE STRENGTH OF THE ASSOCIATIONS GENERALLY INCREASED AS THE TIME WINDOW FOR AVERAGE PAH EXPOSURE INCREASED FROM 24 HR TO 1 YEAR, SUGGESTING MORE OF A CHRONIC RESPONSE. SIGNIFICANT ASSOCIATIONS WITH CHRONIC PAH EXPOSURE AND IMMUNE OUTCOMES WERE ALSO OBSERVED IN SUBJECTS WITH ALLERGIC RHINITIS. CONCLUSIONS AND CLINICAL RELEVANCE: COLLECTIVELY, THESE RESULTS DEMONSTRATE THAT INCREASED AMBIENT PAH EXPOSURE IS ASSOCIATED WITH IMPAIRED SYSTEMIC IMMUNITY AND EPIGENETIC MODIFICATIONS IN A KEY LOCUS INVOLVED IN ATOPY: FOXP3, WITH A HIGHER IMPACT ON ATOPIC CHILDREN. THE RESULTS SUGGEST THAT INCREASED ATOPIC CLINICAL SYMPTOMS IN CHILDREN COULD BE LINKED TO INCREASED PAH EXPOSURE IN AIR POLLUTION. 2015 19 5208 31 PRENATAL STRESS, PREMATURITY, AND ASTHMA. ASTHMA IS THE MOST COMMON CHRONIC DISEASE OF CHILDHOOD, AFFECTING MILLIONS OF CHILDREN IN THE UNITED STATES AND WORLDWIDE. PREMATURITY IS A RISK FACTOR FOR ASTHMA, AND CERTAIN ETHNIC OR RACIAL MINORITIES SUCH AS PUERTO RICANS AND NON-HISPANIC BLACKS ARE DISPROPORTIONATELY AFFECTED BY BOTH PREMATURITY AND ASTHMA. IN THIS REVIEW, WE EXAMINE CURRENT EVIDENCE TO SUPPORT MATERNAL PSYCHOSOCIAL STRESS AS A PUTATIVE LINK BETWEEN PREMATURITY AND ASTHMA, WHILE ALSO FOCUSING ON DISRUPTION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS AND IMMUNE RESPONSES AS POTENTIAL UNDERLYING MECHANISMS FOR STRESS-INDUCED "PREMATURE ASTHMA." PRENATAL STRESS MAY CAUSE NOT ONLY ABNORMALITIES IN THE HPA AXIS BUT ALSO EPIGENETIC CHANGES IN THE FETAL GLUCOCORTICOID RECEPTOR GENE (NR3C1), LEADING TO IMPAIRED GLUCOCORTICOID METABOLISM. MOREOVER, MATERNAL STRESS CAN ALTER FETAL CYTOKINE BALANCE, FAVORING TH2 (ALLERGIC) IMMUNE RESPONSES CHARACTERISTIC OF ATOPIC ASTHMA: INTERLEUKIN 6 (IL-6), WHICH HAS BEEN ASSOCIATED WITH PREMATURE LABOR, CAN PROMOTE TH2 RESPONSES BY STIMULATING PRODUCTION OF IL-4 AND IL-13. GIVEN A LINK AMONG STRESS, PREMATURITY, AND ASTHMA, FUTURE RESEARCH SHOULD INCLUDE BIRTH COHORTS AIMED AT CONFIRMING AND BETTER CHARACTERIZING "PREMATURE ASTHMA." IF CONFIRMED, CLINICAL TRIALS OF PRENATAL MATERNAL STRESS REDUCTION WOULD BE WARRANTED TO REDUCE THE BURDEN OF THESE COMMON COMORBIDITIES. WHILE AWAITING THE RESULTS OF SUCH STUDIES, SOUND POLICIES TO PREVENT DOMESTIC AND COMMUNITY VIOLENCE (EG, FROM FIREARMS) ARE JUSTIFIED, NOT ONLY BY PUBLIC SAFETY BUT ALSO BY GROWING EVIDENCE OF DETRIMENTAL EFFECTS OF VIOLENCE-INDUCED STRESS ON PSYCHIATRIC AND SOMATIC HEALTH. 2015 20 1760 25 EARLY PREDICTORS OF ASTHMA AND ALLERGY IN CHILDREN: THE ROLE OF EPIGENETICS. PURPOSE OF REVIEW: ASTHMA AND ALLERGIC DISEASES ARE AMONG THE MOST PREVALENT CHRONIC NONCOMMUNICABLE DISEASES OF CHILDHOOD. ALTHOUGH EPIDEMIOLOGIC STUDIES SUGGEST THAT ASTHMA BEGINS IN THE PRESCHOOL YEARS, THE LACK OF FIRM DIAGNOSTIC CRITERIA TO DISTINGUISH CHILDREN WHO WILL WHEEZE ONLY TRANSIENTLY DURING EARLY-LIFE LOWER RESPIRATORY ILLNESSES FROM CHILDREN WHO WILL WHEEZE PERSISTENTLY AND DEVELOP ASTHMA PREVENTS PINPOINTING THE TIME AT WHICH DISEASE TRULY BEGINS. EPIGENETIC MECHANISMS LINK GENE REGULATION TO ENVIRONMENTAL CUES AND DEVELOPMENTAL TRAJECTORIES. THIS ARTICLE REVIEWS, THE SEARCH FOR EPIGENETIC PREDICTORS OF ASTHMA AND/OR ALLERGY THAT CAN BE IDENTIFIED ALREADY AT BIRTH AND/OR IN EARLY LIFE. RECENT FINDINGS: DNA METHYLATION SIGNATURES ASSOCIATED WITH ASTHMA AND/OR ALLERGY AT BIRTH, AND TIME-DEPENDENT DNA METHYLATION SIGNATURES ASSOCIATED WITH ALLERGIC DISEASE PHENOTYPES IN EARLY LIFE HAVE BEEN IDENTIFIED. SUMMARY: THE IDENTIFICATION OF EARLY EPIGENETIC PREDICTORS OF ALLERGIC DISEASES POINTS TO A POTENTIAL ROLE OF EPIGENETIC MECHANISMS IN REGULATING THE INCEPTION OF AND THE SUSCEPTIBILITY TO THESE DISEASES. PREDICTIVE SIGNATURES TO MORE ACCURATELY ESTIMATE A CHILD'S RISK FOR ASTHMA AND ALLERGY MAY IMPROVE CHILDHOOD ASTHMA DIAGNOSIS. MOREOVER, UNDERSTANDING THE BIOLOGICAL IMPLICATIONS OF THESE SIGNATURES MAY HELP ELUCIDATE NOVEL DISEASE PATHWAYS AND ENDOTYPES. 2015