1 2804 79 FETAL EPIGENETIC MECHANISMS AND INNATE IMMUNITY IN ASTHMA. ALLERGY AND ASTHMA ARE CHRONIC INFLAMMATORY DISEASES THAT RESULT FROM COMPLEX GENE-ENVIRONMENT INTERACTIONS. RECENT EVIDENCE POINTS TO THE IMPORTANCE OF PRENATAL AND POSTNATAL DEVELOPMENTAL PROCESSES IN THE MATURATION OF BALANCED IMMUNE RESPONSES. NOVEL DATA INDICATE THAT EPIGENETIC MECHANISMS CONTRIBUTE TO THE DEVELOPMENT OF T-HELPER-CELL FUNCTION. ENVIRONMENTAL FACTORS, INCLUDING DIESEL EXHAUST PARTICLES, VITAMINS, AND TOBACCO SMOKE, OPERATE THROUGH SUCH MECHANISMS. FURTHERMORE, THE ROLE OF ENVIRONMENTAL MICROBES PROVIDES ANOTHER-AND MAYBE AN EVEN MORE IMPORTANT-GROUP OF EXOGENOUS EXPOSURES THAT OPERATE IN THIS CRITICAL TIME FRAME. A BETTER UNDERSTANDING OF FETAL IMMUNO-MATURATION CONDITIONS WILL PROVIDE THE BASIS FOR THE DEVELOPMENT OF NOVEL ALLERGO-PROTECTIVE CLINICAL STRATEGIES. 2010 2 4094 64 MATERNAL SIGNALS FOR PROGENY PREVENTION AGAINST ALLERGY AND ASTHMA. ALLERGY AND ASTHMA ARE CHRONIC INFLAMMATORY DISEASES WHICH RESULT FROM COMPLEX GENE-ENVIRONMENT INTERACTIONS. RECENT EVIDENCE INDICATES THE IMPORTANCE OF PRENATAL AND POSTNATAL DEVELOPMENTAL PROCESSES IN TERMS OF MATURATION OF BALANCED IMMUNE RESPONSES. ACCORDING TO THE CURRENT VIEW, GENE-ENVIRONMENT INTERACTIONS DURING A RESTRICTED TIME FRAME ARE RESPONSIBLE FOR PROGRAMMING OF THE IMMUNE SYSTEM IN FAVOR OF ALLERGIC IMMUNE MECHANISMS LATER IN LIFE. THE INTERACTION BETWEEN GENES AND ENVIRONMENT IS COMPLEX AND ONLY PARTIALLY UNDERSTOOD; HOWEVER, HERITABLE EPIGENETIC MODIFICATIONS INCLUDING CHEMICAL ADDITIONS IN AND ALTERNATIVE PACKAGING OF THE DNA HAVE BEEN SHOWN TO PLAY A CRUCIAL ROLE IN THIS CONTEXT. NOVEL DATA INDICATE THAT EPIGENETIC MECHANISMS CONTRIBUTE TO THE DEVELOPMENT OF T-HELPER CELL FUNCTION. ENVIRONMENTAL FACTORS, INCLUDING DIESEL EXHAUST PARTICLES (DEP), VITAMINS AND TOBACCO SMOKE, OPERATE THROUGH SUCH MECHANISMS. FURTHERMORE, THE ROLE OF ENVIRONMENTAL MICROBES PROVIDES ANOTHER AND MAYBE EVEN MORE IMPORTANT GROUP OF EXOGENOUS EXPOSURES WHICH OPERATES IN THIS CRITICAL TIME FRAME. 2011 3 5552 28 ROLE OF EPIGENETICS IN THE PATHOGENESIS OF ASTHMA. ASTHMA IS A COMPLEX, HETEROGENEOUS AND CHRONIC AIRWAY INFLAMMATORY DISEASE WITH DIFFERENT CLINICAL PHENOTYPES CAUSED BY DIVERSE TRIGGERS AND PATHOPHYSIOLOGICAL MECHANISMS. ASTHMA HERITABILITY HAS BEEN ESTABLISHED IN MANY GENETIC STUDIES BUT IT IS EVIDENT THAT ONLY GENETIC ELEMENTS ARE NOT RESPONSIBLE FOR THE DEVELOPMENT OF ASTHMA. INCREASING RATE OF ASTHMA INCIDENCE DURING PAST DECADES HAS IMPLICATED THE ROLE OF EPIGENETICS IN DEVELOPMENT OF ASTHMA. ENVIRONMENTAL FACTORS PERFORM AS INITIATOR SIGNALS THROUGH EPIGENETIC MECHANISMS. THREE EPIGENETIC MECHANISMS HAVE BEEN IDENTIFIED, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND SMALL NONCODING RNAS. THESE MECHANISMS REGULATE THE IMMUNE RESPONSES AND INFLAMMATORY GENES EXPRESSION IN ASTHMA AND ALLERGY. THIS REVIEW EXPLAINS THE ROLE OF EPIGENETIC MODIFICATIONS IN CONTROLLING TH2 RESPONSE AND IGE PRODUCTION IN ASTHMA AND ALSO BRIEFLY OVERVIEWS THE ROLE OF ENVIRONMENTAL FACTORS SUCH AS POLLUTIONS, ALLERGENS, PRENATAL EXPOSURES AND DIET IN DEVELOPING ASTHMA. RECOGNIZING ENVIRONMENTAL RISK FACTORS AND THEIR EFFECTS ON EPIGENETIC MECHANISMS WOULD BE OF GREAT INTEREST FOR PROGNOSTIC AND PREVENTIVE ASPECT IN TREATMENT OF ASTHMA. 2017 4 6877 27 [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 5 6811 28 [EPIGENETICS, ENVIRONMENT AND ASTHMA]. ASTHMA IS A CHRONIC INFLAMMATORY DISEASE OF THE RESPIRATORY TRACT WITH A COMPLEX GENETIC BACKGROUND INFLUENCED BY THE EXPOSITION TO A SERIES OF ENVIRONMENTAL FACTORS. GENETIC STUDIES CAN ONLY ELUCIDATE PART OF THE HERITABILITY AND SUSCEPTIBILITY OF ASTHMA AND EVEN THOUGH SEVERAL DISEASES HAVE AN EVIDENT GENETIC ETIOLOGY, ONLY A FRACTION OF THE GENES INVOLVED IN THEIR PATHOGENICITY HAVE BEEN IDENTIFIED. THE EPIGENETIC REGULATION OF THE LATTER IS A FACT ONE SHOULD BEAR IN MIND IN ORDER TO EXPLAIN THE MAJOR TRIGGERS OF DISEASES WHOSE UNDERSTANDING IS COMPLICATED, SUCH AS ALLERGIES AND ASTHMA. EXTERNAL STIMULUS SUCH AS NOURISHMENT, STRESS, PHYSICAL ACTIVITY, ATMOSPHERIC POLLUTION, TOBACCO SMOKING AND ALCOHOL DRINKING CAN INDUCE EITHER GENE SILENCING OR GENE EXPRESSION. IN THIS REGARD, EPIGENETICS CAN EXPLAIN HOW THESE ENVIRONMENTAL FACTORS INFLUENCE OUR GENETIC INHERITANCE. THERE IS GROWING EVIDENCE THAT BACKS-UP THE FACT THAT DNA METHYLATION, HISTONE POST-TRANSLATIONAL MODIFICATION AND MICRORNA EXPRESSION ARE INFLUENCED BY THE ENVIRONMENT. THIS HELPS EXPLAINING HOW SEVERAL OF THE RISK FACTORS MENTIONED CONTRIBUTE TO THE DEVELOPMENT AND INHERITANCE OF ASTHMA. IN THIS REVIEW, DIFFERENT ENVIRONMENTAL FACTORS AND THEIR RELATION WITH THE MAIN EPIGENETIC REGULATORY MECHANISMS WILL BE ANALYZED, AS WELL AS THEIR POSSIBLE ROLE IN THE DEVELOPMENT OF ASTHMA. 2014 6 2049 22 EPIGENETIC CODE AND POTENTIAL EPIGENETIC-BASED THERAPIES AGAINST CHRONIC DISEASES IN DEVELOPMENTAL ORIGINS. ACCUMULATED FINDINGS HAVE DEMONSTRATED THAT THE EPIGENETIC CODE PROVIDES A POTENTIAL LINK BETWEEN PRENATAL STRESS AND CHANGES IN GENE EXPRESSION THAT COULD BE INVOLVED IN THE DEVELOPMENTAL PROGRAMMING OF VARIOUS CHRONIC DISEASES IN LATER LIFE. MEANWHILE, BASED ON THE FACT THAT EPIGENETIC MODIFICATIONS ARE REVERSIBLE AND CAN BE MANIPULATED, THIS PROVIDES A UNIQUE CHANCE TO DEVELOP MULTIPLE NOVEL EPIGENETIC-BASED THERAPEUTIC STRATEGIES AGAINST MANY CHRONIC DISEASES IN EARLY DEVELOPMENTAL PERIODS. THIS ARTICLE WILL GIVE A SHORT REVIEW OF RECENT FINDINGS OF PRENATAL INSULT-INDUCED EPIGENETIC CHANGES IN DEVELOPMENTAL ORIGINS OF SEVERAL CHRONIC DISEASES, AND WILL ATTEMPT TO PROVIDE AN OVERVIEW OF THE CURRENT EPIGENETIC-BASED STRATEGIES APPLIED IN THE EARLY PREVENTION, DIAGNOSIS AND POSSIBLE THERAPIES FOR HUMAN CHRONIC DISEASES. 2014 7 2807 22 FETAL PROGRAMMING OF CHRONIC KIDNEY DISEASE: THE ROLE OF MATERNAL SMOKING, MITOCHONDRIAL DYSFUNCTION, AND EPIGENETIC MODFIFICATION. THE ROLE OF AN ADVERSE IN UTERO ENVIRONMENT IN THE PROGRAMMING OF CHRONIC KIDNEY DISEASE IN THE ADULT OFFSPRING IS INCREASINGLY RECOGNIZED. THE CELLULAR AND MOLECULAR MECHANISMS LINKING THE IN UTERO ENVIRONMENT AND FUTURE DISEASE SUSCEPTIBILITY REMAIN UNKNOWN. MATERNAL SMOKING IS A COMMON MODIFIABLE ADVERSE IN UTERO EXPOSURE, POTENTIALLY ASSOCIATED WITH BOTH MITOCHONDRIAL DYSFUNCTION AND EPIGENETIC MODIFICATION IN THE OFFSPRING. WHILE STUDIES ARE EMERGING THAT POINT TOWARD A KEY ROLE OF MITOCHONDRIAL DYSFUNCTION IN ACUTE AND CHRONIC KIDNEY DISEASE, IT MAY HAVE ITS ORIGIN IN EARLY DEVELOPMENT, BECOMING CLINICALLY APPARENT WHEN SECONDARY INSULTS OCCUR. ABERRANT EPIGENETIC PROGRAMMING MAY ADD AN ADDITIONAL LAYER OF COMPLEXITY TO ORCHESTRATE FIBROGENESIS IN THE KIDNEY AND SUSCEPTIBILITY TO CHRONIC KIDNEY DISEASE IN LATER LIFE. IN THIS REVIEW, WE EXPLORE THE EVIDENCE FOR MITOCHONDRIAL DYSFUNCTION AND EPIGENETIC MODIFICATION THROUGH ABERRANT DNA METHYLATION AS KEY MECHANISTIC ASPECTS OF FETAL PROGRAMMING OF CHRONIC KIDNEY DISEASE AND DISCUSS THEIR POTENTIAL USE IN DIAGNOSTICS AND TARGETS FOR THERAPY. 2015 8 1757 17 EARLY ORIGINS OF ASTHMA (AND ALLERGY). ASTHMA IS THE MOST COMMON CHRONIC DISEASE STARTING IN CHILDHOOD AND PERSISTING INTO ADULTHOOD IN MANY CASES. DURING CHILDHOOD, DIFFERENT FORMS OF ASTHMA AND WHEEZING DISORDERS EXIST THAT CAN BE DISCRIMINATED BY THE MECHANISMS THEY ARE CAUSED BY. SPECIFIC GENETIC CONSTELLATIONS AND EXPOSURE AGAINST ENVIRONMENTAL FACTORS DURING EARLY CHILDHOOD AND IN UTERO PLAY A DECISIVE ROLE IN THE EARLY DEVELOPMENT OF THE DISEASE. EPIGENETIC MECHANISMS WHICH ARE MASTER REGULATORS OF GENE TRANSCRIPTION AND THUS GOVERN THE ACCESSIBILITY AND USE OF GENOME INFORMATION, HAVE RECENTLY BEEN IDENTIFIED AS A "THIRD POWER" DETERMINING MANY FEATURES IN THE EARLY DEVELOPMENT OF ASTHMA AND ALLERGY. 2016 9 4126 26 MECHANISMS OF DISEASE: THE DEVELOPMENTAL ORIGINS OF DISEASE AND THE ROLE OF THE EPIGENOTYPE. THERE IS ACCUMULATING EVIDENCE THAT MANY CHRONIC DISEASES SUCH AS TYPE 2 DIABETES AND CORONARY HEART DISEASE MIGHT ORIGINATE DURING EARLY LIFE. THIS EVIDENCE GIVES RISE TO THE DEVELOPMENTAL ORIGINS OF DISEASE HYPOTHESIS, AND IS SUPPORTED BY EPIDEMIOLOGICAL DATA IN HUMANS AND EXPERIMENTAL ANIMAL MODELS. A PERTURBED ENVIRONMENT IN EARLY LIFE IS THOUGHT TO ELICIT A RANGE OF PHYSIOLOGICAL AND CELLULAR ADAPTIVE RESPONSES IN KEY ORGAN SYSTEMS. THESE ADAPTIVE CHANGES RESULT IN PERMANENT ALTERATIONS AND MIGHT LEAD TO PATHOLOGY IN LATER LIFE. AGING ORGANS AND CELLS SEEM THEREFORE TO RETAIN A 'MEMORY' OF THEIR FETAL HISTORY AND ADAPTIVE RESPONSES. THE MECHANISMS UNDERLYING THE DEVELOPMENTAL ORIGINS OF DISEASE REMAIN POORLY DEFINED. EPIGENETIC TAGGING OF GENES, SUCH AS DNA METHYLATION AND HISTONE MODIFICATION, CONTROLS THE FUNCTION OF THE GENOME AT DIFFERENT LEVELS AND MAINTAINS CELLULAR MEMORY AFTER MANY CELLULAR DIVISIONS; IMPORTANTLY, TAGGING CAN BE MODULATED BY THE ENVIRONMENT AND IS INVOLVED IN ONSET OF DISEASES SUCH AS CANCER. HERE WE REVIEW THE EVIDENCE FOR THE DEVELOPMENTAL ORIGINS OF DISEASE AND DISCUSS THE ROLE OF THE EPIGENOTYPE AS A CONTRIBUTING MECHANISM. ENVIRONMENTALLY INDUCED CHANGES IN THE EPIGENOTYPE MIGHT BE KEY PRIMARY EVENTS IN THE DEVELOPMENTAL ORIGINS OF DISEASE, WITH IMPORTANT CLINICAL IMPLICATIONS. 2007 10 2160 20 EPIGENETIC MECHANISMS IN ASTHMA. ASTHMA AND ALLERGIC DISEASES ARE AMONG THE MOST PREVALENT CHRONIC NONCOMMUNICABLE DISEASES OF CHILDHOOD, BUT THE UNDERLYING PATHOGENETIC MECHANISMS ARE POORLY UNDERSTOOD. BECAUSE EPIGENETIC MECHANISMS LINK GENE REGULATION TO ENVIRONMENTAL CUES AND DEVELOPMENTAL TRAJECTORIES, THEIR CONTRIBUTION TO ASTHMA AND ALLERGY PATHOGENESIS IS UNDER ACTIVE INVESTIGATION. DNA METHYLATION SIGNATURES ASSOCIATED WITH CONCURRENT DISEASE AND WITH THE DEVELOPMENT OF ASTHMA DURING CHILDHOOD ASTHMA HAVE BEEN IDENTIFIED, BUT THEIR SIGNIFICANCE IS NOT EASILY INTERPRETABLE. ON THE OTHER HAND, THE CHARACTERIZATION OF EARLY EPIGENETIC PREDICTORS OF ASTHMA POINTS TO A POTENTIAL ROLE OF EPIGENETIC MECHANISMS IN REGULATING THE INCEPTION OF, AND THE SUSCEPTIBILITY TO, THIS DISEASE. 2016 11 6063 24 THE DEVELOPMENTAL ENVIRONMENT, EPIGENETIC BIOMARKERS AND LONG-TERM HEALTH. EVIDENCE FROM BOTH HUMAN AND ANIMAL STUDIES HAS SHOWN THAT THE PRENATAL AND EARLY POSTNATAL ENVIRONMENTS INFLUENCE SUSCEPTIBILITY TO CHRONIC DISEASE IN LATER LIFE AND SUGGESTS THAT EPIGENETIC PROCESSES ARE AN IMPORTANT MECHANISM BY WHICH THE ENVIRONMENT ALTERS LONG-TERM DISEASE RISK. EPIGENETIC PROCESSES, INCLUDING DNA METHYLATION, HISTONE MODIFICATION AND NON-CODING RNAS, PLAY A CENTRAL ROLE IN REGULATING GENE EXPRESSION. THE EPIGENOME IS HIGHLY SENSITIVE TO ENVIRONMENTAL FACTORS IN EARLY LIFE, SUCH AS NUTRITION, STRESS, ENDOCRINE DISRUPTION AND POLLUTION, AND CHANGES IN THE EPIGENOME CAN INDUCE LONG-TERM CHANGES IN GENE EXPRESSION AND PHENOTYPE. IN THIS REVIEW WE FOCUS ON HOW THE EARLY LIFE NUTRITIONAL ENVIRONMENT CAN ALTER THE EPIGENOME LEADING TO AN ALTERED SUSCEPTIBILITY TO DISEASE IN LATER LIFE. 2015 12 3698 28 INFLAMMATORY MECHANISMS LINKING MATERNAL AND CHILDHOOD ASTHMA. ASTHMA IS A CHRONIC INFLAMMATORY AIRWAY DISEASE CHARACTERIZED BY AIRWAY HYPERRESPONSIVENESS, INFLAMMATION, AND REMODELING. ASTHMA OFTEN DEVELOPS DURING CHILDHOOD AND CAUSES LIFELONG DECREMENTS IN LUNG FUNCTION AND QUALITY OF LIFE. RISK FACTORS FOR CHILDHOOD ASTHMA ARE NUMEROUS AND INCLUDE GENETIC, EPIGENETIC, DEVELOPMENTAL, AND ENVIRONMENTAL FACTORS. UNCONTROLLED MATERNAL ASTHMA DURING PREGNANCY EXPOSES THE DEVELOPING FETUS TO INFLAMMATORY INSULTS, WHICH FURTHER INCREASE THE RISK OF CHILDHOOD ASTHMA INDEPENDENT OF GENETIC PREDISPOSITION. THIS REVIEW FOCUSES ON THE ROLE OF MATERNAL ASTHMA IN THE DEVELOPMENT OF ASTHMA IN OFFSPRING. WE WILL PRESENT MATERNAL ASTHMA AS A TARGETABLE AND MODIFIABLE RISK FACTOR FOR CHILDHOOD ASTHMA AND DISCUSS THE MECHANISMS BY WHICH MATERNAL INFLAMMATION INCREASES CHILDHOOD ASTHMA RISK. TOPICS INCLUDE HOW EXPOSURE TO MATERNAL ASTHMA IN UTERO SHAPES STRUCTURAL LUNG DEVELOPMENT WITH A SPECIAL EMPHASIS ON AIRWAY NERVES, HOW MATERNAL TYPE-2 CYTOKINES SUCH AS IL-5 ACTIVATE THE FETAL IMMUNE SYSTEM, AND HOW CHANGES IN LUNG AND IMMUNE CELL DEVELOPMENT INFORM RESPONSES TO AERO-ALLERGENS LATER IN LIFE. FINALLY, WE HIGHLIGHT EMERGING EVIDENCE THAT MATERNAL ASTHMA ESTABLISHES A UNIQUE "ASTHMA SIGNATURE" IN THE AIRWAYS OF CHILDREN, LEADING TO NOVEL MECHANISMS OF AIRWAY HYPERREACTIVITY AND INFLAMMATORY CELL RESPONSES. 2020 13 3421 31 HUMAN MATTERS IN ASTHMA: CONSIDERING THE MICROBIOME IN PULMONARY HEALTH. MICROBIAL COMMUNITIES FORM AN IMPORTANT SYMBIOTIC ECOSYSTEM WITHIN HUMANS AND HAVE DIRECT EFFECTS ON HEALTH AND WELL-BEING. NUMEROUS EXOGENOUS FACTORS INCLUDING AIRBORNE TRIGGERS, DIET, AND DRUGS IMPACT THESE ESTABLISHED, BUT FRAGILE COMMUNITIES ACROSS THE HUMAN LIFESPAN. CROSSTALK BETWEEN THE MUCOSAL MICROBIOTA AND THE IMMUNE SYSTEM AS WELL AS THE GUT-LUNG AXIS HAVE DIRECT CORRELATIONS TO IMMUNE BIAS THAT MAY PROMOTE CHRONIC DISEASES LIKE ASTHMA. ASTHMA INITIATION AND PATHOGENESIS ARE MULTIFACETED AND COMPLEX WITH INPUT FROM GENETIC, EPIGENETIC, AND ENVIRONMENTAL COMPONENTS. IN THIS REVIEW, WE SUMMARIZE AND DISCUSS THE ROLE OF THE AIRWAY MICROBIOME IN ASTHMA, AND HOW THE ENVIRONMENT, DIET AND THERAPEUTICS IMPACT THIS LOW BIOMASS COMMUNITY OF MICROORGANISMS. WE ALSO FOCUS THIS REVIEW ON THE PEDIATRIC AND BLACK POPULATIONS AS HIGH-RISK GROUPS REQUIRING SPECIAL ATTENTION, EMPHASIZING THAT THE WHOLE PATIENT MUST BE CONSIDERED DURING TREATMENT. ALTHOUGH NEW CULTURE-INDEPENDENT TECHNIQUES HAVE BEEN DEVELOPED AND ARE MORE ACCESSIBLE TO RESEARCHERS, THE EXACT CONTRIBUTION THE AIRWAY MICROBIOME MAKES IN ASTHMA PATHOGENESIS IS NOT WELL UNDERSTOOD. UNDERSTANDING HOW THE AIRWAY MICROBIOME, AS A LIVING ENTITY IN THE RESPIRATORY TRACT, PARTICIPATES IN LUNG IMMUNITY DURING THE DEVELOPMENT AND PROGRESSION OF ASTHMA MAY LEAD TO CRITICAL NEW TREATMENTS FOR ASTHMA, INCLUDING POPULATION-TARGETED INTERVENTIONS, OR EVEN MORE EFFECTIVE ADMINISTRATION OF CURRENTLY AVAILABLE THERAPEUTICS. 2022 14 2279 29 EPIGENETIC REGULATION IN ALLERGIC DISEASES AND RELATED STUDIES. ASTHMA, A CHRONIC INFLAMMATORY DISORDER OF THE AIRWAY, HAS FEATURES OF BOTH HERITABILITY AS WELL AS ENVIRONMENTAL INFLUENCES WHICH CAN BE INTRODUCED IN UTERO EXPOSURES AND MODIFIED THROUGH AGING, AND THE FEATURES MAY ATTRIBUTE TO EPIGENETIC REGULATION. EPIGENETIC REGULATION EXPLAINS THE ASSOCIATION BETWEEN EARLY PRENATAL MATERNAL SMOKING AND LATER ASTHMA-RELATED OUTCOMES. EPIGENETIC MARKS (DNA METHYLATION, MODIFICATIONS OF HISTONE TAILS OR NONCODING RNAS) WORK WITH OTHER COMPONENTS OF THE CELLULAR REGULATORY MACHINERY TO CONTROL THE LEVELS OF EXPRESSED GENES, AND SEVERAL ALLERGY- AND ASTHMA-RELATED GENES HAVE BEEN FOUND TO BE SUSCEPTIBLE TO EPIGENETIC REGULATION, INCLUDING GENES IMPORTANT TO T-EFFECTOR PATHWAYS (IFN-GAMMA, INTERLEUKIN [IL] 4, IL-13, IL-17) AND T-REGULATORY PATHWAYS (FOXP3). THEREFORE, THE MECHANISM BY WHICH EPIGENETIC REGULATION CONTRIBUTES TO ALLERGIC DISEASES IS A CRITICAL ISSUE. IN THE PAST MOST PUBLISHED EXPERIMENTAL WORK, WITH FEW EXCEPTIONS, HAS ONLY COMPRISED SMALL OBSERVATIONAL STUDIES AND MODELS IN CELL SYSTEMS AND ANIMALS. HOWEVER, VERY RECENTLY EXCITING AND ELEGANT EXPERIMENTAL STUDIES AND NOVEL TRANSLATIONAL RESEARCH WORKS WERE PUBLISHED WITH NEW AND ADVANCED TECHNOLOGIES INVESTIGATING EPIGENETIC MARK ON A GENOMIC SCALE AND COMPREHENSIVE APPROACHES TO DATA ANALYSIS. INTERESTINGLY, A POTENTIAL LINK BETWEEN EXPOSURE TO ENVIRONMENTAL POLLUTANTS AND THE OCCURRENCE OF ALLERGIC DISEASES IS REVEALED RECENTLY, PARTICULAR IN DEVELOPED AND INDUSTRIALIZED COUNTRIES, AND ENDOCRINE DISRUPTING CHEMICALS (EDCS) AS ENVIRONMENTAL HORMONE MAY PLAY A KEY ROLE. THIS REVIEW ADDRESSES THE IMPORTANT QUESTION OF HOW EDCS (NONYLPHENOL, 4 OCTYLPHENOL, AND PHTHALATES) INFLUENCES ON ASTHMA-RELATED GENE EXPRESSION VIA EPIGENETIC REGULATION IN IMMUNE CELLS, AND HOW ANTI-ASTHMATIC AGENTS PROHIBIT EXPRESSION OF INFLAMMATORY GENES VIA EPIGENETIC MODIFICATION. THE DISCOVERY AND VALIDATION OF EPIGENETIC BIOMARKERS LINKING EXPOSURE TO ALLERGIC DISEASES MIGHT LEAD TO BETTER EPIGENOTYPING OF RISK, PROGNOSIS, TREATMENT PREDICTION, AND DEVELOPMENT OF NOVEL THERAPIES. 2014 15 6735 26 WHAT HAVE MECHANISTIC STUDIES TAUGHT US ABOUT CHILDHOOD ASTHMA? CHILDHOOD ASTHMA IS A CHRONIC HETEROGENEOUS SYNDROME CONSISTING OF DIFFERENT DISEASE ENTITIES OR PHENOTYPES. THE IMMUNOLOGIC AND CELLULAR PROCESSES THAT OCCUR DURING ASTHMA DEVELOPMENT ARE STILL NOT FULLY UNDERSTOOD BUT REPRESENT DISTINCT ENDOTYPES. MECHANISTIC STUDIES HAVE EXAMINED THE ROLE OF GENE EXPRESSION, PROTEIN LEVELS, AND CELL TYPES IN EARLY LIFE DEVELOPMENT AND THE MANIFESTATION OF ASTHMA, MANY UNDER THE INFLUENCE OF ENVIRONMENTAL STIMULI, WHICH CAN BE BOTH PROTECTIVE AND RISK FACTORS FOR ASTHMA. GENETIC VARIANTS CAN REGULATE GENE EXPRESSION, CONTROLLED PARTLY BY DIFFERENT EPIGENETIC MECHANISMS. IN ADDITION, ENVIRONMENTAL FACTORS, SUCH AS LIVING SPACE, NUTRITION, AND SMOKING, CAN CONTRIBUTE TO THESE MECHANISMS. ALL OF THESE FACTORS PRODUCE MODIFICATIONS IN GENE EXPRESSION THAT CAN ALTER THE DEVELOPMENT AND FUNCTION OF IMMUNE AND EPITHELIAL CELLS AND SUBSEQUENTLY DIFFERENT TRAJECTORIES OF CHILDHOOD ASTHMA. THESE EARLY CHANGES IN A PARTIALLY IMMATURE IMMUNE SYSTEM CAN HAVE DRAMATIC EFFECTS (E.G., CAUSING DYSREGULATION), WHICH IN TURN CONTRIBUTE TO DIFFERENT DISEASE ENDOTYPES AND MAY HELP TO EXPLAIN DIFFERENTIAL RESPONSIVENESS TO ASTHMA TREATMENT. IN THIS REVIEW, WE SUMMARIZE PUBLISHED STUDIES THAT HAVE AIMED TO UNCOVER DISTINCT MECHANISMS IN CHILDHOOD ASTHMA, CONSIDERING GENETICS, EPIGENETICS, AND ENVIRONMENT. MOREOVER, A DISCUSSION OF NEW, POWERFUL TOOLS FOR SINGLE-CELL IMMUNOLOGIC ASSAYS FOR PHENOTYPIC AND FUNCTIONAL ANALYSIS IS INCLUDED, WHICH PROMISE NEW MECHANISTIC INSIGHTS INTO CHILDHOOD ASTHMA DEVELOPMENT AND THERAPEUTIC AND PREVENTIVE STRATEGIES. 2023 16 3580 28 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 17 602 26 BETTER UNDERSTANDING OF CHILDHOOD ASTHMA, TOWARDS PRIMARY PREVENTION - ARE WE THERE YET? CONSIDERATION OF PERTINENT LITERATURE. ASTHMA IS A CHRONIC DISEASE, CHARACTERIZED BY REVERSIBLE AIRWAY OBSTRUCTION, AIRWAY INFLAMMATION AND HYPER-REACTIVITY. THE PREVALENCE OF ASTHMA HAS RISEN DRAMATICALLY OVER THE PAST DECADE, AFFECTING AROUND 300,000,000 PEOPLE. THE ETIOLOGY IS MULTIFACTORIAL, WITH GENETIC, EPIGENETIC, DEVELOPMENTAL AND ENVIRONMENTAL FACTORS PLAYING A ROLE. A COMPLEX INTERACTION BETWEEN THE INTRAUTERINE ENVIRONMENT, THE DEVELOPING IMMUNE SYSTEM, THE INFANT'S MICROBIOME AND INFECTIOUS ORGANISMS MAY LEAD TO THE DEVELOPMENT OF ALLERGIC SENSITIZATION AND ASTHMA. THUS, A LARGE NUMBER OF STUDIES HAVE INVESTIGATED THE RISK FACTORS FOR CHILDHOOD ASTHMA, WITH A METICULOUS SEARCH OF MODIFIABLE FACTORS THAT COULD AID IN PRIMARY PREVENTION. WE PRESENT A CURRENT LITERATURE REVIEW FROM 2014-2017, AS WELL AS OLDER CLASSIC PUBLICATIONS, ON THE PATHOGENESIS AND THE POTENTIAL MODIFIABLE FACTORS FOR PRIMARY PREVENTION OF ASTHMA. NO IDEAL PREVENTIVE MEASURE HAS YET BEEN FOUND. RATHER, CREATING FAVORABLE PRENATAL AND POSTNATAL ENVIRONMENTS, MINIMAL EXPOSURE TO HOSTILE ENVIRONMENTAL FACTORS, PREVENTION OF INFECTIONS IN EARLY LIFE, ALLERGIC DESENSITIZATION AND NUTRITIONAL MODIFICATIONS COULD POSSIBLY REDUCE ASTHMA INCEPTION. IN THE ERA OF PERSONALIZED MEDICINE, IDENTIFYING INDIVIDUAL RISK FACTORS AND TAILORING SPECIFIC PREVENTIVE MEASURES IS WARRANTED. 2017 18 6808 16 [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 19 1453 19 DISCOVERING HOW ENVIRONMENTAL EXPOSURES ALTER GENES COULD LEAD TO NEW TREATMENTS FOR CHRONIC ILLNESSES. EMERGING RESEARCH DEMONSTRATES THAT DIET, POLLUTION, AND OTHER ENVIRONMENTAL TRIGGERS CAN ALTER BOTH THE FUNCTION AND EXPRESSION OF HUMAN GENES AND LEAD TO A HEIGHTENED DISEASE RISK. THESE ENVIRONMENT-GENE INTERACTIONS CAN CAUSE SO-CALLED EPIGENETIC CHANGES IN GENE EXPRESSION-PATTERNS OF WHICH GENES ARE SWITCHED "ON" OR "OFF"-THAT MAY ACCOUNT FOR THE RISING MORTALITY FROM CHRONIC DISEASES IN INDUSTRIALIZED NATIONS. IN THIS PAPER, WE CALL FOR A NEW TRANSDISCIPLINARY APPROACH TO PUBLIC HEALTH THAT WOULD EXAMINE HOW ENVIRONMENTAL EXPOSURES, BOTH PHYSICAL AND SOCIAL, INFLUENCE GENE EXPRESSION AND A PERSON'S SUSCEPTIBILITY TO CHRONIC DISEASE. THIS INITIATIVE COULD LEAD TO NEW WAYS TO PREVENT AND TREAT SUCH ILLNESSES. 2011 20 1926 30 ENVIRONMENTAL EPIGENETICS OF ASTHMA: AN UPDATE. ASTHMA, A CHRONIC INFLAMMATORY DISORDER OF THE AIRWAY, IS INFLUENCED BY INTERPLAY BETWEEN GENETIC AND ENVIRONMENTAL FACTORS NOW KNOWN TO BE MEDIATED BY EPIGENETICS. ABERRANT DNA METHYLATION, ALTERED HISTONE MODIFICATIONS, SPECIFIC MICRORNA EXPRESSION, AND OTHER CHROMATIN ALTERATIONS ORCHESTRATE A COMPLEX EARLY-LIFE REPROGRAMMING OF IMMUNE T-CELL RESPONSE, DENDRITIC CELL FUNCTION, MACROPHAGE ACTIVATION, AND A BREACH OF AIRWAY EPITHELIAL BARRIER THAT DICTATES ASTHMA RISK AND SEVERITY IN LATER LIFE. ADULT-ONSET ASTHMA IS UNDER ANALOGOUS REGULATION. THE SHARP INCREASE IN ASTHMA PREVALENCE OVER THE PAST 2 OR 3 DECADES AND THE LARGE VARIATIONS AMONG POPULATIONS OF SIMILAR RACIAL/ETHNIC BACKGROUND BUT DIFFERENT ENVIRONMENTAL EXPOSURES FAVORS A STRONG CONTRIBUTION OF ENVIRONMENTAL FACTORS. THIS REVIEW ADDRESSES THE FUNDAMENTAL QUESTION OF WHETHER ENVIRONMENTAL INFLUENCES ON ASTHMA RISK, SEVERITY, AND STEROID RESISTANCE ARE PARTLY DUE TO DIFFERENTIAL EPIGENETIC MODULATIONS. CURRENT KNOWLEDGE ON THE EPIGENETIC EFFECTS OF TOBACCO SMOKE, MICROBIAL ALLERGENS, OXIDANTS, AIRBORNE PARTICULATE MATTER, DIESEL EXHAUST PARTICLES, POLYCYCLIC AROMATIC HYDROCARBONS, DIETARY METHYL DONORS AND OTHER NUTRITIONAL FACTORS, AND DUST MITES IS DISCUSSED. EXCITING FINDINGS HAVE BEEN GENERATED BY RAPID TECHNOLOGICAL ADVANCES AND WELL-DESIGNED EXPERIMENTAL AND POPULATION STUDIES. THE DISCOVERY AND VALIDATION OF EPIGENETIC BIOMARKERS LINKED TO EXPOSURE, ASTHMA, OR BOTH MIGHT LEAD TO BETTER EPIGENOTYPING OF RISK, PROGNOSIS, TREATMENT PREDICTION, AND DEVELOPMENT OF NOVEL THERAPIES. 2010