1  5875 130 SYMPTOMS OF ALLERGIC RHINITIS IN WOMEN DURING EARLY PREGNANCY ARE ASSOCIATED WITH HIGHER PREVALENCE OF ALLERGIC RHINITIS IN THEIR OFFSPRING. BACKGROUND: EPIGENETIC CONTROL OF GENE EXPRESSION PROFILES IS A UBIQUITOUS MECHANISM DURING CELL DIFFERENTIATION, ORGANOGENESIS AND CHRONIC INFLAMMATORY REACTIONS. RECENT STUDIES HAVE SHOWN THAT ALLERGEN EXPOSURE DURING VERY EARLY PREGNANCY INCREASES BRONCHIAL HYPERSENSITIVITY IN OFFSPRING IN A MURINE MODEL OF BRONCHIAL ASTHMA. HOWEVER, NO SUCH PHENOMENA WERE REPORTED IN HUMANS. IN THE PRESENT STUDY, THE ROLE OF EPIGENETIC CONTROL IN THE ONSET OF ALLERGIC DISEASES WAS INVESTIGATED. METHODS: A TOTAL OF 400 PAIRS OF MOTHERS WITH PHYSICIAN-DIAGNOSED ALLERGIC RHINITIS (AR) AND THEIR OFFSPRING (AGE 7-18 MONTHS) WHO PARTICIPATED IN A LARGE-SCALE MEDICAL CHECK-UP WERE ENROLLED IN THIS RETROSPECTIVE COHORT STUDY. FAMILY HISTORY OF ALLERGIC DISEASES AND THE PRESENCE OR ABSENCE OF AR SYMPTOMS DURING PREGNANCY WERE INQUIRED ABOUT USING A SELF-ANSWERED QUESTIONNAIRE. A LOGISTIC REGRESSION MODEL ADJUSTED FOR AGE, GENDER, BIRTH MONTH AND FATHER'S HISTORY OF ALLERGIC DISEASES WAS STATISTICALLY ANALYZED. RESULTS: OFFSPRING WHOSE MOTHERS HAD ANY AR SYMPTOMS DURING EARLY PREGNANCY SHOWED A SIGNIFICANTLY HIGHER ADJUSTED ODDS RATIO FOR THE ONSET OF AR IN OFFSPRING THAN THOSE WHOSE MOTHERS HAD NO SYMPTOMS DURING PREGNANCY (ADJUSTED ODDS RATIO: 6.26, P = 0.036). HOWEVER, THE SYMPTOMS OF AR DURING LATE PREGNANCY SHOWED NO EFFECTS ON THE ODDS RATIO. IN CONTRAST, THE PRESENCE OR ABSENCE OF AR SYMPTOMS DURING EARLY OR LATE PREGNANCY SHOWED NO ASSOCIATION WITH THE PREVALENCE OF FOOD ALLERGY, ATOPIC DERMATITIS OR ASTHMA IN OFFSPRING. CONCLUSIONS: OUR RESULTS SUGGEST THE PRESENCE OF POSSIBLE EPIGENETIC MECHANISMS REGULATING THE ONSET OF AR IN HUMANS PRESUMABLY THROUGH INCREASED ORGAN-SPECIFIC HYPERSENSITIVITY.	2007	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
2   846  37 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	
                                                                                                                                                         
3   300  30 AIR POLLUTION AND INDOOR SETTINGS. INDOOR ENVIRONMENTS CONTRIBUTE SIGNIFICANTLY TO TOTAL HUMAN EXPOSURE TO AIR POLLUTANTS, AS PEOPLE SPEND MOST OF THEIR TIME INDOORS. HOUSEHOLD AIR POLLUTION (HAP) RESULTING FROM COOKING WITH POLLUTING ("DIRTY") FUELS, WHICH INCLUDE COAL, KEROSENE, AND BIOMASS (WOOD, CHARCOAL, CROP RESIDUES, AND ANIMAL MANURE) IS A GLOBAL ENVIRONMENTAL HEALTH PROBLEM. INDOOR POLLUTANTS ARE GASES, PARTICULATES, TOXINS, AND MICROORGANISMS AMONG OTHERS, THAT CAN HAVE AN IMPACT ESPECIALLY ON THE HEALTH OF CHILDREN AND ADULTS THROUGH A COMBINATION OF DIFFERENT MECHANISMS ON OXIDATIVE STRESS AND GENE ACTIVATION, EPIGENETIC, CELLULAR, AND IMMUNOLOGICAL SYSTEMS. AIR POLLUTION IS A MAJOR RISK FACTOR AND CONTRIBUTOR TO MORBIDITY AND MORTALITY FROM MAJOR CHRONIC DISEASES. CHILDREN ARE SIGNIFICANTLY AFFECTED BY THE IMPACT OF THE ENVIRONMENT DUE TO BIOLOGICAL IMMATURITY, PRENATAL AND POSTNATAL LUNG DEVELOPMENT. POOR AIR QUALITY HAS BEEN RELATED TO AN INCREASED PREVALENCE OF CLINICAL MANIFESTATIONS OF ALLERGIC ASTHMA AND RHINITIS. HEALTH PROFESSIONALS SHOULD INCREASE THEIR ROLE IN MANAGING THE EXPOSURE OF CHILDREN AND ADULTS TO AIR POLLUTION WITH BETTER METHODS OF CARE, PREVENTION, AND COLLECTIVE ACTION. INTERVENTIONS TO REDUCE HOUSEHOLD POLLUTANTS MAY PROMOTE HEALTH AND CAN BE ACHIEVED WITH EDUCATION, COMMUNITY, AND HEALTH PROFESSIONAL INVOLVEMENT.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
4  5099  34 PM2.5 EXPOSURE EXACERBATES ALLERGIC RHINITIS IN MICE BY INCREASING DNA METHYLATION IN THE IFN-GAMMA GENE PROMOTER IN CD4+T CELLS VIA THE ERK-DNMT PATHWAY. ALLERGIC RHINITIS (AR) IS A COMMON CHRONIC INFLAMMATORY DISEASE THAT HAS A SIGNIFICANT IMPACT ON THE QUALITY OF LIFE OF PATIENTS. OUR PREVIOUS STUDY SUGGESTED THAT PM2.5 MIGHT AFFECT PEDIATRIC AR THROUGH EPIGENETIC REGULATION, BUT THE UNDERLYING MECHANISMS REMAINED UNCLEAR. IN THIS STUDY, AN EXPERIMENTAL MURINE AR MODEL WAS CREATED, AND THE NASAL SYMPTOMS, PATHOLOGICAL CHANGES, THE DNA METHYLATION LEVEL OF THE IFN-GAMMA GENE PROMOTER AND ACTIVATION OF THE ERK-DNMT PATHWAY WERE EVALUATED AFTER TREATMENT WITH PM2.5. OUR RESULTS SHOWED THAT PM2.5 EXPOSURE LED TO MORE SEVERE SYMPTOMS OF AR IN MICE. IN ADDITION, PM2.5 EXPOSURE SIGNIFICANTLY DECREASED THE PERCENTAGE OF TH1 T CELLS IN THE AR GROUP, AND THIS CHANGE WAS CORRELATED WITH INCREASED DNA METHYLATION OF THE IFN-GAMMA GENE PROMOTER IN CD4 + T CELLS (R=-0.916, P = 0.029). IN ADDITION, PM2.5 EXPOSURE INCREASED THE ACTIVATION OF THE ERK-DNMT PATHWAY IN CD4+ T CELLS, AND INHIBITING THIS EFFECT RESCUED THE POLARIZATION OF THE TH1/TH2 BALANCE TOWARD TH2, THEREBY DECREASING THE RISK OF AR. OUR FINDINGS DEMONSTRATE THAT PM2.5 EXPOSURE COULD EXACERBATE AR BY INCREASING THE DNA METHYLATION OF THE IFN-GAMMA GENE PROMOTER IN CD4 + T CELLS VIA THE ERK-DNMT PATHWAY, AND THESE EFFECTS WERE RESCUED WHEN THE ERK-DNMT PATHWAY WAS INHIBITED.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
5  6382  43 THE ROLE OF PARTICULATE MATTERS ON METHYLATION OF IFN-GAMMA AND IL-4 PROMOTER GENES IN PEDIATRIC ALLERGIC RHINITIS. ALLERGIC RHINITIS (AR) IS A CHRONIC INFLAMMATORY DISORDER DRIVEN BY T CELL ACTIVATION. HOW PARTICULATE MATTER CONTRIBUTES TO EPIGENETIC CHANGES THAT IN TURN INFLUENCE CYTOKINE GENE EXPRESSION IN CD4(+)T CELLS REMAINS UNCLEAR. IN THIS STUDY, 105 CHILDREN DIAGNOSED WITH AR AND 90 HEALTHY CONTROLS WERE RECRUITED TO EXPLORE THE POSSIBLE MECHANISM OF PARTICULATE MATTER (PM) ON THE EPIGENETIC REGULATION OF CD4(+)T IFN-GAMMA AND IL-4 PROMOTER GENES. DAILY AVERAGE PM(10) AND PM(2.5) WERE OBTAINED FROM FIVE STATE-CONTROLLED MONITORING STATIONS, AND ACTIVITY-BASED DYNAMIC EXPOSURE AND PERSONAL EXPOSURE DATA WERE COLLECTED. DNA METHYLATION PATTERNS OF IFN-GAMMA AND IL-4 PROMOTER REGIONS WERE ANALYZED USING BISULFITE SEQUENCING. MRNA LEVELS WERE DETECTED BY REAL-TIME QUANTITATIVE REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION. WE FOUND THAT THE METHYLATION RATE IN IFN-GAMMA WAS HIGHER IN AR CD4(+)T CELLS THAN IN THE CONTROLS. IFN-GAMMA MRNA EXPRESSION WAS SIGNIFICANTLY DECREASED IN CD4(+)T CELLS, AND NEGATIVELY CORRELATED WITH THE MEAN METHYLATION LEVEL OF IFN-GAMMA. HOWEVER, NO CORRELATION BETWEEN IL-4 METHYLATION AND IL-4 MRNA EXPRESSION WAS FOUND. AFTER ADJUSTING FOR AGE, GENDER, EXCLUSIVE BREASTFEEDING WITHIN 4 MONTHS AFTER BIRTH AND PARENTAL HISTORY OF ALLERGIC DISEASE, OUT DATA SHOWED THAT PM(2.5) EXPOSURE LEVEL WAS POSITIVELY CORRELATED WITH METHYLATION LEVEL IN IFN-GAMMA PROMOTER REGION AND DECREASED CYTOKINE EXPRESSION. WE CONCLUDE THAT THE EFFECT OF PM(2.5) ON PEDIATRIC AR MAY BE MEDIATED THROUGH EPIGENETIC MODIFICATION OF IFN-GAMMA PROMOTER REGION.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
6  6876  39 [PROLONGED EXPOSURE TO ATMOSPHERIC AIR POLLUTION AND MORTALITY FROM RESPIRATORY CAUSES]. DIFFERENT DESIGNS CAN BE USED TO ANALYZE THE RELATIONSHIPS BETWEEN RESPIRATORY MORTALITY AND LONG TERM EXPOSURE TO ATMOSPHERIC POLLUTION: EPIDEMIOLOGICAL STUDIES (COHORT, PREVALENCE STUDY) DEMONSTRATE THE REALITY OF THE RELATIONSHIP AND TOXICOLOGICAL STUDIES EXPLAIN IT. COHORT STUDIES HAVE THE ADVANTAGE OF BEING ABLE TO TAKE INTO ACCOUNT MANY CONFOUNDING FACTORS AND THUS AVOID BIASES (WHICH IS NOT THE CASE WITH PREVALENCE STUDIES), BUT REQUIRE SIGNIFICANT HUMAN AND FINANCIAL RESOURCES. THEY WERE FIRST ADOPTED IN THE US, BUT ARE NOW MORE OFTEN APPLIED IN EUROPE. THE RESULTS ARE RELATIVELY CONSISTENT, AS THEY ALL SHOW A STATISTICALLY SIGNIFICANT ASSOCIATION BETWEEN AN INCREASE IN PARTICULATE POLLUTION AND CARDIOPULMONARY MORTALITY. MORTALITY FROM LUNG CANCER IS ALSO ASSOCIATED WITH LONG TERM EXPOSITION TO PARTICLES AND SOMETIMES TO OZONE OR NITROGEN OXIDES. CEREBROVASCULAR DISEASES AND SUDDEN DEATH OF YOUNG CHILDREN HAVE ALSO BEEN ASSOCIATED WITH PARTICULATE POLLUTION. THE RELATIONSHIPS ARE MORE POWERFUL FOR LONG TERM THAN SHORT TERM EXPOSURE BUT ARE ALSO LINEAR AND WITHOUT THRESHOLD. IN ORDER TO EXPLAIN THESE EFFECTS (TODAY THE CAUSALITY OF THE RELATIONSHIP IS CERTAIN) THERE ARE MANY POSSIBLE FACTORS, PARTICULARLY REGARDING PARTICULATE EXPOSURES: AN INCREASE IN CARDIOVASCULAR RISK BIOMARKERS (FIBRINOGEN, WHITE BLOOD CELLS, AND PLATELETS), ATHEROSCLEROSIS, CHRONIC INFLAMMATION OF LUNG TISSUES INCREASED BY ACUTE EXPOSURE, ETC. MORE AND MORE STUDIES ADDRESS THE INTERACTION BETWEEN GENE AND ENVIRONMENT AND EVEN EPIGENETIC PHENOMENA WHICH COULD BE RESPONSIBLE OF THESE EFFECTS. PUBLIC HEALTH IMPACT COULD BE QUANTIFIED. THE EUROPEAN E&H SURVEILLANCE PROGRAM APHEIS, FOR EXAMPLE, ESTIMATED THAT IF PM2.5 LEVELS REMAINED BELOW 15 MICROG/M(3), A 30 YEAR OLD PERSON COULD SEE HIS LIFE EXPECTANCY INCREASED BY 1 MONTH TO 2 YEARS, DEPENDING ON THE STUDIED CITY. FINALLY, MORTALITY IS NOT THE ONLY RELEVANT INDICATOR FOR HEALTH EFFECTS OF AIR POLLUTION. ISAAC STUDIES ADDRESS ASTHMA, ALLERGIC RHINITIS AND ECZEMA AMONG CHILDREN.	2009	
                                                                                                                                                                                                                                     
7  2519  30 EPIGENETICS AND THE ENVIRONMENT IN AIRWAY DISEASE: ASTHMA AND ALLERGIC RHINITIS. ASTHMA AND RHINITIS ARE COMPLEX, HETEROGENEOUS DISEASES CHARACTERIZED BY CHRONIC INFLAMMATION OF THE UPPER AND LOWER AIRWAYS. WHILE GENOME-WIDE ASSOCIATION STUDIES (GWAS) HAVE IDENTIFIED A NUMBER OF SUSCEPTIBLE LOCI AND CANDIDATE GENES ASSOCIATED WITH THE PATHOGENESIS OF ASTHMA AND ALLERGIC RHINITIS (AR), THE RISK-ASSOCIATED ALLELES ACCOUNT FOR ONLY A VERY SMALL PERCENT OF THE GENETIC RISK. IN ALLERGIC AIRWAY AND OTHER COMPLEX DISEASES, IT IS THOUGHT THAT EPIGENETIC MODIFICATIONS, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND NON-CODING MICRORNAS, CAUSED BY COMPLEX INTERACTIONS BETWEEN THE UNDERLYING GENOME AND THE ENVIRONMENT MAY ACCOUNT FOR SOME OF THIS "MISSING HERITABILITY" AND MAY EXPLAIN THE HIGH DEGREE OF PLASTICITY IN IMMUNE RESPONSES. IN THIS CHAPTER, WE WILL FOCUS ON THE CURRENT KNOWLEDGE OF CLASSICAL EPIGENETIC MODIFICATIONS, DNA METHYLATION AND HISTONE MODIFICATIONS, AND THEIR POTENTIAL ROLE IN ASTHMA AND AR. IN PARTICULAR, WE WILL REVIEW EPIGENETIC VARIATIONS ASSOCIATED WITH MATERNAL AIRWAY DISEASE, DEMOGRAPHICS, ENVIRONMENT, AND NON-SPECIFIC ASSOCIATIONS. THE ROLE OF SPECIFIC GENETIC HAPLOTYPES IN ENVIRONMENTALLY INDUCED EPIGENETIC CHANGES ARE ALSO DISCUSSED. A MAJOR LIMITATION OF MANY OF THE CURRENT STUDIES OF ASTHMA EPIGENETICS IS THAT THEY EVALUATE EPIGENETIC MODIFICATIONS IN BOTH ALLERGIC AND NON-ALLERGIC ASTHMA, MAKING IT DIFFICULT TO DISTINGUISH THOSE EPIGENETIC MODIFICATIONS THAT MEDIATE ALLERGIC ASTHMA FROM THOSE THAT MEDIATE NON-ALLERGIC ASTHMA. ADDITIONALLY, MOST DNA METHYLATION STUDIES IN ASTHMA USE PERIPHERAL OR CORD BLOOD DUE TO POOR ACCESSIBILITY OF AIRWAY CELLS OR TISSUE. UNLIKE DNA SEQUENCES, EPIGENETIC ALTERATIONS ARE QUITE CELL- AND TISSUE-SPECIFIC, AND EPIGENETIC CHANGES FOUND IN AIRWAY TISSUE OR CELLS MAY BE DISCORDANT FROM THAT OF CIRCULATING BLOOD. THESE TWO CONFOUNDING FACTORS SHOULD BE CONSIDERED WHEN REVIEWING EPIGENETIC STUDIES IN ALLERGIC AIRWAY DISEASE.	2020	
                                                                                                                                                                                                                                                                                                                                                       
8  4872  30 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	
                                                                                                                                                                                                                                                                                                                                                                      
9   529  20 ASTHMA IN URBAN CHILDREN: EPIDEMIOLOGY, ENVIRONMENTAL RISK FACTORS, AND THE PUBLIC HEALTH DOMAIN. ASTHMA IS THE MOST COMMONLY REPORTED CHRONIC CONDITION OF CHILDHOOD IN DEVELOPED COUNTRIES, WITH 6.5 MILLION CHILDREN AFFECTED IN THE USA. A DISPARATE BURDEN OF CHILDHOOD ASTHMA IS SEEN AMONG SOCIOECONOMICALLY DISADVANTAGED YOUTH, OFTEN CONCENTRATED IN URBAN AREAS WITH HIGH POVERTY RATES. HOST FACTORS THAT PREDISPOSE A CHILD TO ASTHMA INCLUDE ATOPY, MALE GENDER, PARENTAL HISTORY OF ASTHMA, AND ALSO RACE, ETHNICITY, AND GENETIC AND EPIGENETIC SUSCEPTIBILITIES. ENVIRONMENTAL FACTORS, SUCH AS IMPROVED HYGIENE, AMBIENT AIR POLLUTION, AND EARLY LIFE EXPOSURES TO MICROBES AND AEROALLERGENS, ALSO INFLUENCE THE DEVELOPMENT OF ASTHMA. WITH GREATER THAN 90% OF TIME SPENT INDOORS, HOME EXPOSURES (SUCH AS COCKROACH, RODENT, AND INDOOR AIR POLLUTION) ARE HIGHLY RELEVANT FOR URBAN ASTHMA. MORBIDITY REDUCTION MAY REQUIRE FOCUSED PUBLIC HEALTH INITIATIVES FOR ENVIRONMENTAL INTERVENTION IN HIGH PRIORITY RISK GROUPS AND THE ADDITION OF IMMUNE MODULATORY AGENTS IN CHILDREN WITH POORLY CONTROLLED DISEASE.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
10  3580  38 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
11   298  35 AIR POLLUTION AND AIRWAY DISEASE. EPIDEMIOLOGICAL AND TOXICOLOGICAL RESEARCH CONTINUES TO SUPPORT A LINK BETWEEN URBAN AIR POLLUTION AND AN INCREASED INCIDENCE AND/OR SEVERITY OF AIRWAY DISEASE. DETRIMENTAL EFFECTS OF OZONE (O(3)), NITROGEN DIOXIDE (NO(2)) AND PARTICULATE MATTER (PM), AS WELL AS TRAFFIC-RELATED POLLUTION AS A WHOLE, ON RESPIRATORY SYMPTOMS AND FUNCTION ARE WELL DOCUMENTED. NOT ONLY DO WE HAVE STRONG EPIDEMIOLOGICAL EVIDENCE OF A RELATIONSHIP BETWEEN AIR POLLUTION AND EXACERBATION OF ASTHMA AND RESPIRATORY MORBIDITY AND MORTALITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), BUT RECENT STUDIES, PARTICULARLY IN URBAN AREAS, HAVE SUGGESTED A ROLE FOR POLLUTANTS IN THE DEVELOPMENT OF BOTH ASTHMA AND COPD. SIMILARLY, WHILE PREVALENCE AND SEVERITY OF ATOPIC CONDITIONS APPEAR TO BE MORE COMMON IN URBAN COMPARED WITH RURAL COMMUNITIES, EVIDENCE IS EMERGING THAT TRAFFIC-RELATED POLLUTANTS MAY CONTRIBUTE TO THE DEVELOPMENT OF ALLERGY. FURTHERMORE, NUMEROUS EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES SUGGEST AN ASSOCIATION BETWEEN EXPOSURE TO NO(2) , O(3) , PM AND COMBUSTION PRODUCTS OF BIOMASS FUELS AND AN INCREASED SUSCEPTIBILITY TO AND MORBIDITY FROM RESPIRATORY INFECTION. GIVEN THE CONSIDERABLE CONTRIBUTION THAT TRAFFIC EMISSIONS MAKE TO URBAN AIR POLLUTION RESEARCHERS HAVE SOUGHT TO CHARACTERIZE THE RELATIVE TOXICITY OF TRAFFIC-RELATED PM POLLUTANTS. RECENT ADVANCES IN MECHANISMS IMPLICATED IN THE ASSOCIATION OF AIR POLLUTANTS AND AIRWAY DISEASE INCLUDE EPIGENETIC ALTERATION OF GENES BY COMBUSTION-RELATED POLLUTANTS AND HOW POLYMORPHISMS IN GENES INVOLVED IN ANTIOXIDANT PATHWAYS AND AIRWAY INFLAMMATION CAN MODIFY RESPONSES TO AIR POLLUTION EXPOSURES. OTHER INTERESTING EPIDEMIOLOGICAL OBSERVATIONS RELATED TO INCREASED HOST SUSCEPTIBILITY INCLUDE A POSSIBLE LINK BETWEEN CHRONIC PM EXPOSURE DURING CHILDHOOD AND VULNERABILITY TO COPD IN ADULTHOOD, AND THAT INFANTS SUBJECTED TO HIGHER PRENATAL LEVELS OF AIR POLLUTION MAY BE AT GREATER RISK OF DEVELOPING RESPIRATORY CONDITIONS. WHILE THE CHARACTERIZATION OF POLLUTANT COMPONENTS AND SOURCES PROMISE TO GUIDE POLLUTION CONTROL STRATEGIES, THE IDENTIFICATION OF SUSCEPTIBLE SUBPOPULATIONS WILL BE NECESSARY IF TARGETED THERAPY/PREVENTION OF POLLUTION-INDUCED RESPIRATORY DISEASES IS TO BE DEVELOPED.	2011	
                                                         
12   363  27 AMBIENT AIR POLLUTION: HEALTH HAZARDS TO CHILDREN. AMBIENT AIR POLLUTION IS PRODUCED BY SOURCES INCLUDING VEHICULAR TRAFFIC, COAL-FIRED POWER PLANTS, HYDRAULIC FRACTURING, AGRICULTURAL PRODUCTION, AND FOREST FIRES. IT CONSISTS OF PRIMARY POLLUTANTS GENERATED BY COMBUSTION AND SECONDARY POLLUTANTS FORMED IN THE ATMOSPHERE FROM PRECURSOR GASES. AIR POLLUTION CAUSES AND EXACERBATES CLIMATE CHANGE, AND CLIMATE CHANGE WORSENS HEALTH EFFECTS OF AIR POLLUTION. INFANTS AND CHILDREN ARE UNIQUELY SENSITIVE TO AIR POLLUTION, BECAUSE THEIR ORGANS ARE DEVELOPING AND THEY HAVE HIGHER AIR PER BODY WEIGHT INTAKE. HEALTH EFFECTS LINKED TO AIR POLLUTION INCLUDE NOT ONLY EXACERBATIONS OF RESPIRATORY DISEASES BUT ALSO REDUCED LUNG FUNCTION DEVELOPMENT AND INCREASED ASTHMA INCIDENCE. ADDITIONAL OUTCOMES OF CONCERN INCLUDE PRETERM BIRTH, LOW BIRTH WEIGHT, NEURODEVELOPMENTAL DISORDERS, IQ LOSS, PEDIATRIC CANCERS, AND INCREASED RISKS FOR ADULT CHRONIC DISEASES. THESE EFFECTS ARE MEDIATED BY OXIDATIVE STRESS, CHRONIC INFLAMMATION, ENDOCRINE DISRUPTION, AND GENETIC AND EPIGENETIC MECHANISMS ACROSS THE LIFE SPAN. NATURAL EXPERIMENTS DEMONSTRATE THAT WITH INITIATIVES SUCH AS INCREASED USE OF PUBLIC TRANSPORTATION, BOTH AIR QUALITY AND COMMUNITY HEALTH IMPROVE. SIMILARLY, THE CLEAN AIR ACT HAS IMPROVED AIR QUALITY, ALTHOUGH EXPOSURE INEQUITIES PERSIST. OTHER EFFECTIVE STRATEGIES FOR REDUCING AIR POLLUTION INCLUDE ENDING RELIANCE ON COAL, OIL, AND GAS; REGULATING INDUSTRIAL EMISSIONS; REDUCING EXPOSURE WITH ATTENTION TO PROXIMITY OF RESIDENCES, SCHOOLS, AND CHILD CARE FACILITIES TO TRAFFIC; AND A GREATER AWARENESS OF THE AIR QUALITY INDEX. THIS POLICY REVIEWS BOTH SHORT- AND LONG-TERM HEALTH CONSEQUENCES OF AMBIENT AIR POLLUTION, ESPECIALLY IN RELATION TO DEVELOPMENTAL EXPOSURES. IT EXAMINES INDIVIDUAL, COMMUNITY, AND LEGISLATIVE STRATEGIES TO MITIGATE AIR POLLUTION.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
13  1760  30 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
14  2605  22 EPIGENETICS-A POTENTIAL MEDIATOR BETWEEN AIR POLLUTION AND PRETERM BIRTH. PRETERM BIRTH IS A MAJOR CAUSE OF INFANT MORBIDITY AND MORTALITY AND A POTENTIAL RISK FACTOR FOR ADULT CHRONIC DISEASE. WITH OVER 15 MILLION INFANTS BORN PRETERM WORLDWIDE EACH YEAR, PRETERM BIRTH POSES A GLOBAL HEALTH CONCERN. THERE IS A POSSIBLE ASSOCIATION BETWEEN AIR POLLUTION AND PRETERM BIRTH, THOUGH STUDIES HAVE BEEN INCONSISTENT, LIKELY DUE TO VARIATION IN STUDY DESIGN. HOW AIR POLLUTION INDUCES HEALTH EFFECTS IS UNCERTAIN; HOWEVER, STUDIES HAVE REPEATEDLY DEMONSTRATED THE EFFECTS OF AIR POLLUTION ON EPIGENETIC MODIFICATIONS. MORE RECENT EVIDENCE SUGGESTS THAT EPIGENETICS MAY, IN TURN, BE LINKED TO PRETERM BIRTH. DISCOVERY OF ENVIRONMENTALLY MODIFIABLE EPIGENETIC PROCESSES CONNECTED TO PRETERM BIRTH MAY HELP TO IDENTIFY WOMEN AT RISK OF PRETERM BIRTH, AND ULTIMATELY LEAD TO DEVELOPMENT OF NEW PRETERM BIRTH PREVENTION MEASURES.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
15  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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
16   360  27 AMBIENT AIR POLLUTION AND BIOMARKERS OF HEALTH EFFECT. RECENTLY, THE AIR POLLUTION SITUATION OF OUR COUNTRY IS VERY SERIOUS ALONG WITH THE DEVELOPMENT OF URBANIZATION AND INDUSTRIALIZATION. STUDIES INDICATE THAT THE EXPOSURE OF AIR POLLUTION CAN CAUSE A RISE OF INCIDENCE AND MORTALITY OF MANY DISEASES, SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), ASTHMA, MYOCARDIAL INFARCTION, AND SO ON. HOWEVER, THERE IS NOW GROWING EVIDENCE SHOWING THAT SIGNIFICANT AIR POLLUTION EXPOSURES ARE ASSOCIATED WITH EARLY BIOMARKERS IN VARIOUS SYSTEMS OF THE BODY. IN ORDER TO BETTER PREVENT AND CONTROL THE DAMAGE EFFECT OF AIR POLLUTION, THIS ARTICLE SUMMARIZES COMPREHENSIVELY EPIDEMIOLOGICAL STUDIES ABOUT THE BAD EFFECTS ON THE BIOMARKERS OF RESPIRATORY SYSTEM, CARDIOVASCULAR SYSTEM, AND GENETIC AND EPIGENETIC SYSTEM EXPOSURE TO AMBIENT AIR POLLUTION.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
17   362  33 AMBIENT AIR POLLUTION IMPAIRS REGULATORY T-CELL FUNCTION IN ASTHMA. BACKGROUND: ASTHMA IS THE MOST FREQUENT CHRONIC DISEASE IN CHILDREN, AND CHILDREN ARE AT HIGH RISK FOR ADVERSE HEALTH CONSEQUENCES ASSOCIATED WITH AMBIENT AIR POLLUTION (AAP) EXPOSURE. REGULATORY T (TREG) CELLS ARE SUPPRESSORS OF IMMUNE RESPONSES INVOLVED IN ASTHMA PATHOGENESIS. TREG-CELL IMPAIRMENT IS ASSOCIATED WITH INCREASED DNA METHYLATION OF FORKHEAD BOX TRANSCRIPTION FACTOR 3 (FOXP3), A KEY TRANSCRIPTION FACTOR IN TREG-CELL ACTIVITY. BECAUSE AAP EXPOSURE CAN INDUCE EPIGENETIC CHANGES, WE HYPOTHESIZED THAT TREG-CELL FUNCTION WOULD BE IMPAIRED BY AAP, ALLOWING AMPLIFICATION OF AN INFLAMMATORY RESPONSE. OBJECTIVES: TO ASSESS WHETHER EXPOSURE TO AAP LED TO HYPERMETHYLATION OF THE FOXP3 GENE, CAUSING IMPAIRED TREG-CELL SUPPRESSION AND WORSENED ASTHMA SYMPTOM SCORES. METHODS: CHILDREN WITH AND WITHOUT ASTHMA FROM FRESNO, CALIF (HIGH POLLUTION, FRESNO ASTHMA GROUP [FA], N = 71, AND FRESNO NON ASTHMATIC GROUP, N = 30, RESPECTIVELY), AND FROM STANFORD, CALIF (LOW POLLUTION, STANFORD ASTHMA GROUP, N = 40, AND STANFORD NON ASTHMATIC GROUP, N = 40), WERE ENROLLED IN A CROSS-SECTIONAL STUDY. PERIPHERAL BLOOD TREG CELLS WERE USED IN FUNCTIONAL AND EPIGENETIC STUDIES. ASTHMA OUTCOMES WERE ASSESSED BY GLOBAL INITIATIVE IN ASTHMA SCORE. RESULTS: FRESNO ASTHMA GROUP TREG-CELL SUPPRESSION WAS IMPAIRED AND FA TREG-CELL CHEMOTAXIS WERE REDUCED COMPARED WITH OTHER GROUPS (P </= .05). TREG-CELL DYSFUNCTION WAS ASSOCIATED WITH MORE PRONOUNCED DECREASES IN ASTHMA GLOBAL INITIATIVE IN ASTHMA SCORE IN FA VERSUS THE STANFORD ASTHMA GROUP. FOXP3 WAS DECREASED IN FA COMPARED WITH THE FRESNO NON ASTHMATIC GROUP (P </= .05). FA ALSO CONTAINED SIGNIFICANTLY HIGHER LEVELS OF METHYLATION AT THE FOXP3 LOCUS (P </= .05). CONCLUSION: INCREASED EXPOSURE TO AAP IS ASSOCIATED WITH HYPERMETHYLATION OF THE FOXP3 LOCUS, IMPAIRING TREG-CELL FUNCTION AND INCREASING ASTHMA MORBIDITY. AAP COULD PLAY A ROLE IN MEDIATING EPIGENETIC CHANGES IN TREG CELLS, WHICH MAY WORSEN ASTHMA BY AN IMMUNE MECHANISM.	2010	
                                                                                                                                                                                                                                                                                                          
18   299  27 AIR POLLUTION AND DNA METHYLATION: EFFECTS OF EXPOSURE IN HUMANS. AIR POLLUTION EXPOSURE IS ESTIMATED TO CONTRIBUTE TO APPROXIMATELY SEVEN MILLION EARLY DEATHS EVERY YEAR WORLDWIDE AND MORE THAN 3% OF DISABILITY-ADJUSTED LIFE YEARS LOST. AIR POLLUTION HAS NUMEROUS HARMFUL EFFECTS ON HEALTH AND CONTRIBUTES TO THE DEVELOPMENT AND MORBIDITY OF CARDIOVASCULAR DISEASE, METABOLIC DISORDERS, AND A NUMBER OF LUNG PATHOLOGIES, INCLUDING ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). EMERGING DATA INDICATE THAT AIR POLLUTION EXPOSURE MODULATES THE EPIGENETIC MARK, DNA METHYLATION (DNAM), AND THAT THESE CHANGES MIGHT IN TURN INFLUENCE INFLAMMATION, DISEASE DEVELOPMENT, AND EXACERBATION RISK. SEVERAL TRAFFIC-RELATED AIR POLLUTION (TRAP) COMPONENTS, INCLUDING PARTICULATE MATTER (PM), BLACK CARBON (BC), OZONE (O(3)), NITROGEN OXIDES (NO(X)), AND POLYAROMATIC HYDROCARBONS (PAHS), HAVE BEEN ASSOCIATED WITH CHANGES IN DNAM; TYPICALLY LOWERING DNAM AFTER EXPOSURE. EFFECTS OF AIR POLLUTION ON DNAM HAVE BEEN OBSERVED ACROSS THE HUMAN LIFESPAN, BUT IT IS NOT YET CLEAR WHETHER EARLY LIFE DEVELOPMENTAL SENSITIVITY OR THE ACCUMULATION OF EXPOSURES HAVE THE MOST SIGNIFICANT EFFECTS ON HEALTH. AIR POLLUTION EXPOSURE-ASSOCIATED DNAM PATTERNS ARE OFTEN CORRELATED WITH LONG-TERM NEGATIVE RESPIRATORY HEALTH OUTCOMES, INCLUDING THE DEVELOPMENT OF LUNG DISEASES, A FOCUS IN THIS REVIEW. RECENTLY, INTERVENTIONS SUCH AS EXERCISE AND B VITAMINS HAVE BEEN PROPOSED TO REDUCE THE IMPACT OF AIR POLLUTION ON DNAM AND HEALTH. ULTIMATELY, IMPROVED KNOWLEDGE OF HOW EXPOSURE-INDUCED CHANGE IN DNAM IMPACTS HEALTH, BOTH ACUTELY AND CHRONICALLY, MAY ENABLE PREVENTATIVE AND REMEDIAL STRATEGIES TO REDUCE MORBIDITY IN POLLUTED ENVIRONMENTS.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
19  1553  36 DNA METHYLATION LEVELS ASSOCIATED WITH RACE AND CHILDHOOD ASTHMA SEVERITY. OBJECTIVE: ASTHMA IS A COMMON CHRONIC CHILDHOOD DISEASE WORLDWIDE. SOCIOECONOMIC STATUS, GENETIC PREDISPOSITION AND ENVIRONMENTAL FACTORS CONTRIBUTE TO ITS INCIDENCE AND SEVERITY. A DISPROPORTIONATE NUMBER OF CHILDREN WITH ASTHMA ARE ECONOMICALLY DISADVANTAGED AND LIVE IN SUBSTANDARD HOUSING WITH POTENTIAL INDOOR ENVIRONMENTAL EXPOSURES SUCH AS COCKROACHES, DUST MITES, RODENTS AND MOLDS. THESE EXPOSURES MAY MANIFEST THROUGH EPIGENETIC MECHANISMS THAT CAN LEAD TO CHANGES IN RELEVANT GENE EXPRESSION. WE EXAMINED THE ASSOCIATION OF GLOBAL DNA METHYLATION LEVELS WITH SOCIOECONOMIC STATUS, ASTHMA SEVERITY AND RACE/ETHNICITY. METHODS: WE MEASURED GLOBAL DNA METHYLATION IN PERIPHERAL BLOOD OF CHILDREN WITH ASTHMA ENROLLED IN THE KANSAS CITY SAFE AND HEALTHY HOMES PROGRAM. INCLUSION CRITERIA INCLUDED RESIDING IN THE SAME HOME FOR A MINIMUM OF 4 DAYS PER WEEK AND TOTAL FAMILY INCOME OF LESS THAN 80% OF THE KANSAS CITY MEDIAN FAMILY INCOME. DNA METHYLATION LEVELS WERE QUANTIFIED BY AN IMMUNOASSAY THAT ASSESSED THE PERCENTAGE OF 5-METHYLCYTOSINE. RESULTS: OUR RESULTS INDICATE THAT OVERALL, AFRICAN AMERICAN CHILDREN HAD HIGHER LEVELS OF GLOBAL DNA METHYLATION THAN CHILDREN OF OTHER RACES/ETHNICITIES (P = 0.029). THIS DIFFERENCE WAS MORE PRONOUNCED WHEN SOCIOECONOMIC STATUS AND ASTHMA SEVERITY WERE COUPLED WITH RACE/ETHNICITY (P = 0.042) WHERE LOW-INCOME, AFRICAN AMERICAN CHILDREN WITH PERSISTENT ASTHMA HAD SIGNIFICANTLY ELEVATED METHYLATION LEVELS RELATIVE TO OTHER RACES/ETHNICITIES IN THE SAME CONTEXT (P = 0.006, HEDGES G = 1.14). CONCLUSION: OUR STUDY DEMONSTRATES A SIGNIFICANT INTERACTION EFFECT AMONG GLOBAL DNA METHYLATION LEVELS, ASTHMA SEVERITY, RACE/ETHNICITY, AND SOCIOECONOMIC STATUS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
20   327  24 ALLERGIC INFLAMMATORY MEMORY IN HUMAN RESPIRATORY EPITHELIAL PROGENITOR CELLS. BARRIER TISSUE DYSFUNCTION IS A FUNDAMENTAL FEATURE OF CHRONIC HUMAN INFLAMMATORY DISEASES(1). SPECIALIZED SUBSETS OF EPITHELIAL CELLS-INCLUDING SECRETORY AND CILIATED CELLS-DIFFERENTIATE FROM BASAL STEM CELLS TO COLLECTIVELY PROTECT THE UPPER AIRWAY(2-4). ALLERGIC INFLAMMATION CAN DEVELOP FROM PERSISTENT ACTIVATION(5) OF TYPE 2 IMMUNITY(6) IN THE UPPER AIRWAY, RESULTING IN CHRONIC RHINOSINUSITIS, WHICH RANGES IN SEVERITY FROM RHINITIS TO SEVERE NASAL POLYPS(7). BASAL CELL HYPERPLASIA IS A HALLMARK OF SEVERE DISEASE(7-9), BUT IT IS NOT KNOWN HOW THESE PROGENITOR CELLS(2,10,11) CONTRIBUTE TO CLINICAL PRESENTATION AND BARRIER TISSUE DYSFUNCTION IN HUMANS. HERE WE PROFILE PRIMARY HUMAN SURGICAL CHRONIC RHINOSINUSITIS SAMPLES (18,036 CELLS, N = 12) THAT SPAN THE DISEASE SPECTRUM USING SEQ-WELL FOR MASSIVELY PARALLEL SINGLE-CELL RNA SEQUENCING(12), REPORT TRANSCRIPTOMES FOR HUMAN RESPIRATORY EPITHELIAL, IMMUNE AND STROMAL CELL TYPES AND SUBSETS FROM A TYPE 2 INFLAMMATORY DISEASE, AND MAP KEY MEDIATORS. BY COMPARISON WITH NASAL SCRAPINGS (18,704 CELLS, N = 9), WE DEFINE SIGNATURES OF CORE, HEALTHY, INFLAMED AND POLYP SECRETORY CELLS. WE REVEAL MARKED DIFFERENCES BETWEEN THE EPITHELIAL COMPARTMENTS OF THE NON-POLYP AND POLYP CELLULAR ECOSYSTEMS, IDENTIFYING AND VALIDATING A GLOBAL REDUCTION IN CELLULAR DIVERSITY OF POLYPS CHARACTERIZED BY BASAL CELL HYPERPLASIA, CONCOMITANT DECREASES IN GLANDULAR CELLS, AND PHENOTYPIC SHIFTS IN SECRETORY CELL ANTIMICROBIAL EXPRESSION. WE DETECT AN ABERRANT BASAL PROGENITOR DIFFERENTIATION TRAJECTORY IN POLYPS, AND PROPOSE CELL-INTRINSIC(13), EPIGENETIC(14,15) AND EXTRINSIC FACTORS(11,16,17) THAT LOCK POLYP BASAL CELLS INTO THIS UNCOMMITTED STATE. FINALLY, WE FUNCTIONALLY DEMONSTRATE THAT EX VIVO CULTURED BASAL CELLS RETAIN INTRINSIC MEMORY OF IL-4/IL-13 EXPOSURE, AND TEST THE POTENTIAL FOR CLINICAL BLOCKADE OF THE IL-4 RECEPTOR ALPHA-SUBUNIT TO MODIFY BASAL AND SECRETORY CELL STATES IN VIVO. OVERALL, WE FIND THAT REDUCED EPITHELIAL DIVERSITY STEMMING FROM FUNCTIONAL SHIFTS IN BASAL CELLS IS A KEY CHARACTERISTIC OF TYPE 2 IMMUNE-MEDIATED BARRIER TISSUE DYSFUNCTION. OUR RESULTS DEMONSTRATE THAT EPITHELIAL STEM CELLS MAY CONTRIBUTE TO THE PERSISTENCE OF HUMAN DISEASE BY SERVING AS REPOSITORIES FOR ALLERGIC MEMORIES.	2018