1 642 146 BIOMARKERS OF PARTICULATE MATTER EXPOSURE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A SYSTEMATIC REVIEW. BACKGROUND: IN RECENT YEARS, AMBIENT PARTICULATE MATTER (PM) EXPOSURE HAS BEEN STRONGLY LINKED WITH HEALTH EFFECTS. ELEVATED LEVELS OF PM IN POLLUTED AIR HAVE BEEN CORRELATED WITH THE ONSET AND DEVELOPMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). THIS SYSTEMATIC REVIEW WAS CONDUCTED TO EVALUATE BIOMARKERS THAT COULD REFLECT THE EFFECTS OF PM EXPOSURE IN PATIENTS WITH COPD. METHODS: WE PERFORMED A SYSTEMATIC REVIEW OF STUDIES PUBLISHED ON BIOMARKERS ASSOCIATED WITH PM EXPOSURE IN PATIENTS WITH COPD BETWEEN JANUARY 01, 2012 AND JUNE 30, 2022 IN PUBMED/MEDLINE, EMBASE, AND COCHRANE DATABASES. STUDIES THAT INCLUDED DATA ON BIOMARKERS WITH COPD EXPOSED PM WERE ELIGIBLE FOR INCLUSION. BIOMARKERS WERE CLASSIFIED INTO 4 GROUPS ACCORDING TO THEIR MECHANISMS. RESULTS: OF THE 105 STUDIES IDENTIFIED, 22 WERE INCLUDED IN THIS STUDY. NEARLY 50 BIOMARKERS HAVE BEEN PROPOSED IN THE STUDIES INCLUDED IN THIS REVIEW, AND THE MOST STUDIED IN RELATION TO PM ARE SEVERAL INTERLEUKINS. VARIOUS MECHANISMS HAVE BEEN REPORTED BY WHICH PM INDUCES AND AGGRAVATES COPD. SIX STUDIES RELATED TO OXIDATIVE STRESS, ONE RELATED TO DIRECT EFFECT OF INNATE AND ADAPTIVE IMMUNE SYSTEMS, 16 ASSOCIATED WITH GENETIC REGULATION OF INFLAMMATION, AND TWO RELATED TO EPIGENETIC REGULATION OF PHYSIOLOGY AND SUSCEPTIBILITY WERE FOUND. BIOMARKERS RELATED TO THESE MECHANISMS WERE DETECTED IN SERUM, SPUTUM, URINE, EXHALED BREATH CONCENTRATION (EBC), AND SHOWED VARIOUS CORRELATIONS WITH PM IN COPD. CONCLUSIONS: VARIOUS BIOMARKERS HAVE SHOWN POTENTIAL IN PREDICTING THE EXTENT OF PM EXPOSURE IN COPD PATIENTS. FUTURE STUDIES ARE NEEDED TO ESTABLISH RECOMMENDATIONS FOR REGULATION TO REDUCE AIRBORNE PM, WHICH COULD BE USED TO DEVELOP STRATEGIES FOR PREVENTION AND MANAGEMENT OF ENVIRONMENTAL RESPIRATORY DISEASES. 2023 2 3106 39 GENOMICS AND THE RESPIRATORY EFFECTS OF AIR POLLUTION EXPOSURE. ADVERSE HEALTH EFFECTS FROM AIR POLLUTANTS REMAIN IMPORTANT, DESPITE IMPROVEMENT IN AIR QUALITY IN THE PAST FEW DECADES. THE EXACT MECHANISMS OF LUNG INJURY FROM EXPOSURE TO AIR POLLUTANTS ARE NOT YET FULLY UNDERSTOOD. STUDYING THE GENOME (E.G. SINGLE-NUCLEOTIDE POLYMORPHISMS (SNP) ), EPIGENOME (E.G. METHYLATION OF GENES), TRANSCRIPTOME (MRNA EXPRESSION) AND MICRORNAOME (MICRORNA EXPRESSION) HAS THE POTENTIAL TO IMPROVE OUR UNDERSTANDING OF THE ADVERSE EFFECTS OF AIR POLLUTANTS. GENOME-WIDE ASSOCIATION STUDIES OF SNP HAVE DETECTED SNP ASSOCIATED WITH RESPIRATORY PHENOTYPES; HOWEVER, TO DATE, ONLY CANDIDATE GENE STUDIES OF AIR POLLUTION EXPOSURE HAVE BEEN PERFORMED. CHANGES IN EPIGENETIC PROCESSES, SUCH DNA METHYLATION THAT LEADS TO GENE SILENCING WITHOUT ALTERING THE DNA SEQUENCE, OCCUR WITH AIR POLLUTANT EXPOSURE, ESPECIALLY GLOBAL AND GENE-SPECIFIC METHYLATION CHANGES. RESPIRATORY CELL LINE AND ANIMAL MODELS DEMONSTRATE DISTINCT GENE EXPRESSION SIGNATURES IN THE TRANSCRIPTOME, ARISING FROM EXPOSURE TO PARTICULATE MATTER OR OZONE. PARTICULATE MATTER AND OTHER ENVIRONMENTAL TOXINS ALTER EXPRESSION OF MICRORNA, WHICH ARE SHORT NON-CODING RNA THAT REGULATE GENE EXPRESSION. WHILE IT IS CLEARLY IMPORTANT TO CONTAIN RISING LEVELS OF AIR POLLUTION, STRATEGIES ALSO NEED TO BE DEVELOPED TO MINIMIZE THE DAMAGING EFFECTS OF AIR POLLUTANT EXPOSURE ON THE LUNG, ESPECIALLY FOR PATIENTS WITH CHRONIC LUNG DISEASE AND FOR PEOPLE AT RISK OF FUTURE LUNG DISEASE. CAREFUL STUDY OF GENOMIC RESPONSES WILL IMPROVE OUR UNDERSTANDING OF MECHANISMS OF LUNG INJURY FROM AIR POLLUTION AND ENABLE FUTURE CLINICAL TESTING OF INTERVENTIONS AGAINST THE TOXIC EFFECTS OF AIR POLLUTANTS. 2012 3 3631 44 INCORPORATING BIOMARKERS IN COPD MANAGEMENT: THE RESEARCH KEEPS GOING. GLOBALLY, CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) REMAINS A MAJOR CAUSE OF MORBIDITY AND MORTALITY, HAVING A SIGNIFICANT SOCIOECONOMIC EFFECT. SEVERAL MOLECULAR MECHANISMS HAVE BEEN RELATED TO COPD INCLUDING CHRONIC INFLAMMATION, TELOMERE SHORTENING, AND EPIGENETIC MODIFICATIONS. NOWADAYS, THERE IS AN INCREASING NEED FOR NOVEL THERAPEUTIC APPROACHES FOR THE MANAGEMENT OF COPD. THESE TREATMENT STRATEGIES SHOULD BE BASED ON FINDING THE SOURCE OF ACUTE EXACERBATION OF COPD EPISODES AND ESTIMATING THE PATIENT'S OWN RISK. THE USE OF BIOMARKERS AND THE MEASUREMENT OF THEIR LEVELS IN CONJUNCTION WITH COPD EXACERBATION RISK AND DISEASE PROGNOSIS IS CONSIDERED AN ENCOURAGING APPROACH. MANY TYPES OF COPD BIOMARKERS HAVE BEEN IDENTIFIED WHICH INCLUDE BLOOD PROTEIN BIOMARKERS, CELLULAR BIOMARKERS, AND PROTEASE ENZYMES. THEY HAVE BEEN ISOLATED FROM DIFFERENT SOURCES INCLUDING PERIPHERAL BLOOD, SPUTUM, BRONCHOALVEOLAR FLUID, EXHALED AIR, AND GENETIC MATERIAL. HOWEVER, THERE IS STILL NOT AN EXCLUSIVE BIOMARKER THAT IS USED FOR THE EVALUATION OF COPD BUT RATHER A COMBINATION OF THEM, AND THIS IS ATTRIBUTED TO DISEASE COMPLEXITY. IN THIS REVIEW, WE SUMMARIZE THE CLINICAL SIGNIFICANCE OF COPD-RELATED BIOMARKERS, THEIR ASSOCIATION WITH DISEASE OUTCOMES, AND COPD PATIENTS' MANAGEMENT. FINALLY, WE DEPICT THE VARIOUS SAMPLES THAT ARE USED FOR IDENTIFYING AND MEASURING THESE BIOMARKERS. 2022 4 228 46 ADAPTATION OF THE HUMAN POPULATION TO THE ENVIRONMENT: CURRENT KNOWLEDGE, CLUES FROM CZECH CYTOGENETIC AND "OMICS" BIOMONITORING STUDIES AND POSSIBLE MECHANISMS. THE HUMAN POPULATION IS CONTINUALLY EXPOSED TO NUMEROUS HARMFUL ENVIRONMENTAL STRESSORS, CAUSING NEGATIVE HEALTH EFFECTS AND/OR DEREGULATION OF BIOMARKER LEVELS. HOWEVER, STUDIES REPORTING NO OR EVEN POSITIVE IMPACTS OF SOME STRESSORS ON HUMANS ARE ALSO SOMETIMES PUBLISHED. THE MAIN AIM OF THIS REVIEW IS TO PROVIDE A COMPREHENSIVE OVERVIEW OF THE LAST DECADE OF CZECH BIOMONITORING RESEARCH, CONCERNING THE EFFECT OF VARIOUS LEVELS OF AIR POLLUTION (BENZO[A]PYRENE) AND RADIATION (URANIUM, X-RAY EXAMINATION AND NATURAL RADON BACKGROUND), ON THE DIFFERENTLY EXPOSED POPULATION GROUPS. BECAUSE SOME RESULTS OBTAINED FROM CYTOGENETIC STUDIES WERE OPPOSITE THAN HYPOTHESIZED, WE HAVE SEARCHED FOR A MEANINGFUL INTERPRETATION IN GENOMIC/EPIGENETIC STUDIES. A DETAILED ANALYSIS OF OUR DATA SUPPORTED BY THE STUDIES OF OTHERS AND CURRENT EPIGENETIC KNOWLEDGE, LEADS TO A HYPOTHESIS OF THE VERSATILE MECHANISM OF ADAPTATION TO ENVIRONMENTAL STRESSORS VIA DNA METHYLATION SETTINGS WHICH MAY EVEN ORIGINATE IN PRENATAL DEVELOPMENT, AND HELP TO REDUCE THE RESULTING DNA DAMAGE LEVELS. THIS HYPOTHESIS IS FULLY IN AGREEMENT WITH UNEXPECTED DATA FROM OUR STUDIES (E.G. LOWER LEVELS OF DNA DAMAGE IN SUBJECTS FROM HIGHLY POLLUTED REGIONS THAN IN CONTROLS OR IN SUBJECTS EXPOSED REPEATEDLY TO A POLLUTANT THAN IN THOSE WITHOUT PREVIOUS EXPOSURE), AND IS ALSO SUPPORTED BY DIFFERENCES IN DNA METHYLATION PATTERNS IN GROUPS FROM REGIONS WITH VARIOUS LEVELS OF POLLUTION. IN LIGHT OF THE ADAPTATION HYPOTHESIS, THE FOLLOWING POINTS MAY BE SUGGESTED FOR FUTURE RESEARCH: (I) THE CHRONIC AND ACUTE EXPOSURE OF STUDY SUBJECTS SHOULD BE DISTINGUISHED; (II) THE EXPOSURE HISTORY SHOULD BE MAPPED INCLUDING PLACE OF RESIDENCE DURING THE LIFE AND PRENATAL DEVELOPMENT; (III) CHANGES OF EPIGENETIC MARKERS SHOULD BE MONITORED OVER TIME. IN SUMMARY, INVESTIGATION OF HUMAN ADAPTATION TO THE ENVIRONMENT, ONE OF THE MOST IMPORTANT PROCESSES OF SURVIVAL, IS A NEW CHALLENGE FOR FUTURE RESEARCH IN THE FIELD OF HUMAN BIOMONITORING THAT MAY CHANGE OUR VIEW ON THE RESULTS OF BIOMARKER ANALYSES AND POTENTIAL NEGATIVE HEALTH IMPACTS OF THE ENVIRONMENT. 2017 5 1324 42 DEOXYRIBONUCLEIC ACID (DNA) METHYLATION IN CHILDREN EXPOSED TO AIR POLLUTION: A POSSIBLE MECHANISM UNDERLYING RESPIRATORY HEALTH EFFECTS DEVELOPMENT. AIR POLLUTION IS A SUBSTANTIAL ENVIRONMENTAL THREAT TO CHILDREN AND ACTS AS ACUTE AND CHRONIC DISEASE RISK FACTORS ALIKE. SEVERAL STUDIES HAVE PREVIOUSLY EVALUATED EPIGENETIC MODIFICATIONS CONCERNING ITS EXPOSURE ACROSS VARIOUS LIFE STAGES. HOWEVER, FINDINGS ON EPIGENETIC MODIFICATIONS AS THE CONSEQUENCES OF AIR POLLUTION DURING CHILDHOOD ARE RATHER MINIMAL. THIS REVIEW EVALUATED HIGHLY RELEVANT STUDIES IN THE FIELD TO ANALYZE THE EXISTING LITERATURE REGARDING EXPOSURE TO AIR POLLUTION, WITH A FOCUS ON EPIGENETIC ALTERATIONS DURING CHILDHOOD AND THEIR CONNECTIONS WITH RESPIRATORY HEALTH EFFECTS. THE SEARCH WAS CONDUCTED USING READILY AVAILABLE ELECTRONIC DATABASES (PUBMED AND SCIENCEDIRECT) TO SCREEN FOR CHILDREN'S STUDIES ON EPIGENETIC MECHANISMS FOLLOWING EITHER PRE- OR POST-NATAL EXPOSURE TO AIR POLLUTANTS. STUDIES RELEVANT ENOUGH AND MATCHED THE PREDETERMINED CRITERIA WERE CHOSEN TO BE REVIEWED. NON-ENGLISH ARTICLES AND STUDIES THAT DID NOT REPORT BOTH AIR MONITORING AND EPIGENETIC OUTCOMES IN THE SAME ARTICLE WERE EXCLUDED. THE REVIEW FOUND THAT EPIGENETIC CHANGES HAVE BEEN LINKED WITH EXPOSURE TO AIR POLLUTANTS DURING EARLY LIFE WITH EVIDENCE AND REPORTS OF HOW THEY MAY DEREGULATE THE EPIGENOME BALANCE, THUS INDUCING DISEASE PROGRESSION IN THE FUTURE. EPIGENETIC STUDIES EVOLVE AS A PROMISING NEW APPROACH IN DECIPHERING THE UNDERLYING IMPACTS OF AIR POLLUTION ON DEOXYRIBONUCLEIC ACID (DNA) DUE TO LINKS ESTABLISHED BETWEEN SOME OF THESE EPIGENETIC MECHANISMS AND ILLNESSES. 2021 6 5174 42 PREDICTIVE AND PROGNOSTIC BIOMARKERS OF RESPIRATORY DISEASES DUE TO PARTICULATE MATTER EXPOSURE. AIR POLLUTION IS GETTING SEVERE AND CONCERNS ABOUT ITS TOXICITY EFFECTS ON AIRWAY AND LUNG DISEASE ARE ALSO INCREASING. PARTICULATE MATTER (PM) IS MAJOR COMPONENT OF AIR POLLUTANT. IT CAUSES RESPIRATORY DISEASES, SUCH AS ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, LUNG CANCER, AND SO ON. PM PARTICLES ENTER THE AIRWAY AND LUNG BY INHALATION, CAUSING DAMAGES TO THEM. ESPECIALLY, PM(2.5) CAN PENETRATE INTO THE ALVEOLUS AND PASS TO THE SYSTEMIC CIRCULATION. IT CAN AFFECT THE CARDIOPULMONARY SYSTEM AND CAUSE CARDIOPULMONARY DISORDERS. IN THIS REVIEW, WE FOCUSED ON PM-INDUCING TOXICITY MECHANISMS IN THE FRAMEWORK OF OXIDATIVE STRESS, INFLAMMATION, AND EPIGENETIC CHANGES. WE ALSO REVIEWED ITS CORRELATION WITH RESPIRATORY DISEASES. IN ADDITION, WE REVIEWED BIOMARKERS RELATED TO PM-INDUCED RESPIRATORY DISEASES. THESE BIOMARKERS MIGHT BE USED FOR DISEASE PREDICTION AND EARLY DIAGNOSIS. WITH RECENT TREND OF USING GENOMIC ANALYSIS TOOLS IN THE FIELD OF TOXICOGENOMICS, RESPIRATORY DISEASE BIOMARKERS ASSOCIATED WITH PM WILL BE CONTINUOUSLY INVESTIGATED. EFFECTIVE BIOMARKERS DERIVED FROM EARLIER STUDIES AND FURTHER STUDIES MIGHT BE UTILIZED TO REDUCE RESPIRATORY DISEASES. 2017 7 2093 43 EPIGENETIC EFFECTS FOLLOWING ACUTE AND CHRONIC EXERCISE IN CARDIOVASCULAR DISEASE: A SYSTEMATIC REVIEW. INTRODUCTION: ACUTE EXERCISE AND EXERCISE TRAINING MAY CONFER EPIGENETIC MODIFICATIONS IN HEALTHY SUBJECTS. EPIGENETIC EFFECTS AFTER EXERCISE HAVE BEEN SHOWED IN PATIENTS WITH CARDIOVASCULAR DISEASE. THE AIM OF THIS SYSTEMATIC REVIEW WAS TO SUMMARIZE THE EVIDENCE FROM AVAILABLE CLINICAL TRIALS THAT STUDY EPIGENETIC ADAPTATIONS AFTER EXERCISE IN PATIENTS WITH CARDIOVASCULAR DISEASE. METHODS: THE SEARCH STRATEGY WAS PERFORMED IN PUBMED AND CENTRAL DATABASES ON ARTICLES PUBLISHED UNTIL SEPTEMBER 2020. STUDIES WITH TITLES AND ABSTRACTS RELEVANT TO EXERCISE EPIGENETIC MODIFICATION APPLIED TO CARDIOVASCULAR PATIENTS WERE FULLY EXAMINED. INCLUSION AND EXCLUSION CRITERIA WERE UTILIZED FOR STUDIES SCREENING. QUALITY ASSESSMENT WITH PEDRO SCALE AND EVALUATION BY TWO INDEPENDENT REVIEWERS WAS PERFORMED. RESULTS: OF THE 1714 ARTICLES RETRIEVED, 88 ARTICLES WERE ASSESSED FOR ELIGIBILITY CRITERIA AND 8 ARTICLES MATCHED OUR SEARCH CRITERIA AND FINALLY INCLUDED IN THE SYSTEMATIC ANALYSIS. THE ACUTE EXERCISE EPIGENETIC (MIRNAS) EFFECTS WERE ASSESSED IN THREE STUDIES AND THE CHRONIC EXERCISE TRAINING EFFECTS (MIRNAS AND DNA METHYLATION) IN SIX STUDIES. THE RESULTS HAVE SHOWN THAT THERE IS POSSIBLY AN ACUTE SIGNIFICANT EXERCISE EFFECT ON EPIGENETIC TARGETS WHICH IS MORE EVIDENT AFTER CHRONIC EXERCISE TRAINING. CONCLUSIONS: BY THE PRESENT SYSTEMATIC REVIEW, WE PROVIDE PRELIMINARY EVIDENCE OF BENEFICIAL EPIGENETIC ADAPTATIONS FOLLOWING ACUTE AND CHRONIC EXERCISE IN PATIENTS WITH CARDIOVASCULAR DISEASE. MORE CONTROLLED STUDIES ARE NEEDED TO CONFIRM SUCH EVIDENCE. 2021 8 5882 45 SYSTEMATIC REVIEW OF LUNG FUNCTION AND COPD WITH PERIPHERAL BLOOD DNA METHYLATION IN POPULATION BASED STUDIES. BACKGROUND: EPIGENETIC VARIATIONS IN PERIPHERAL BLOOD HAVE POTENTIAL AS BIOMARKERS FOR DISEASE. THIS SYSTEMATIC REVIEW ASSESSES THE ASSOCIATION OF LUNG FUNCTION AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) WITH DNA METHYLATION PROFILES IN PERIPHERAL BLOOD FROM POPULATION-BASED STUDIES. METHODS: ONLINE DATABASES MEDLINE, EMBASE, AND WEB OF SCIENCE WERE SEARCHED. GOOGLE SCHOLAR WAS SEARCHED TO IDENTIFY GREY LITERATURE. AFTER REMOVING DUPLICATE ARTICLES, 1155 ARTICLES WERE INDEPENDENTLY SCREENED BY TWO INVESTIGATORS. PEER REVIEWED REPORTS ON POPULATION-BASED STUDIES THAT EXAMINED PERIPHERAL BLOOD DNA METHYLATION IN PARTICIPANTS WITH MEASURED LUNG FUNCTION (FEV1, FEV1/FVC RATIO) OR KNOWN COPD STATUS WERE SELECTED FOR FULL-TEXT REVIEW. SIX ARTICLES WERE SUITABLE FOR INCLUSION. INFORMATION REGARDING STUDY CHARACTERISTICS, DESIGNS, METHODOLOGIES AND CONCLUSIONS WAS EXTRACTED. A NARRATIVE SYNTHESIS WAS PERFORMED BASED ON PUBLISHED RESULTS. RESULTS: THREE OF THE SIX ARTICLES ASSESSED THE ASSOCIATION OF COPD WITH DNA METHYLATION, AND TWO OF THESE ALSO INCLUDED ASSOCIATIONS WITH LUNG FUNCTION. OVERALL, FIVE REPORTS EXAMINED THE ASSOCIATION OF LUNG FUNCTION WITH DNA METHYLATION PROFILES. FIVE OF THE SIX ARTICLES REPORTED 'SIGNIFICANT' RESULTS. HOWEVER, NO CONSISTENT CPG SITES WERE IDENTIFIED ACROSS STUDIES FOR COPD STATUS OR LUNG FUNCTION VALUES. CONCLUSIONS: DNA METHYLATION PATTERNS IN PERIPHERAL BLOOD FROM INDIVIDUALS WITH REDUCED LUNG FUNCTION OR COPD MAY BE DIFFERENT TO THOSE IN PEOPLE WITH NORMAL LUNG FUNCTION. HOWEVER, THIS SYSTEMATIC REVIEW DID NOT FIND ANY CONSISTENT ASSOCIATIONS OF LUNG FUNCTION OR COPD WITH DIFFERENTIALLY METHYLATED CPG SITES. LARGE STUDIES WITH A LONGITUDINAL DESIGN TO ADDRESS REVERSE CAUSALITY MAY PROVE A MORE FRUITFUL AREA OF RESEARCH. TRIAL REGISTRATION: PROSPERO 2016: CRD42016037352 . 2017 9 247 40 ADULTHOOD ASTHMA AS A CONSEQUENCE OF CHILDHOOD ADVERSITY: A SYSTEMATIC REVIEW OF EPIGENETICALLY AFFECTED GENES. THERE IS AN ACCUMULATING DATA THAT SHOWS RELATION BETWEEN CHILDHOOD ADVERSITY AND VULNERABILITY TO CHRONIC DISEASES AS WELL AS EPIGENETIC INFLUENCES THAT IN TURN GIVE RISE TO THESE DISEASES. ASTHMA IS ONE OF THE CHRONIC DISEASES THAT IS INFLUENCED FROM GENETIC REGULATION OF THE INFLAMMATORY BIOMOLECULES AND THEREFORE THE HYPOTHESIS IN THIS RESEARCH WAS CHILDHOOD ADVERSITY MIGHT HAVE CAUSED EPIGENETIC DIFFERENTIATION IN THE ASTHMA-RELATED GENES IN THE POPULATION WHO HAD CHILDHOOD TRAUMA. TO TEST THIS HYPOTHESIS, THE LITERATURE WAS SYSTEMATICALLY REVIEWED TO EXTRACT EPIGENETICALLY MODIFIED GENE DATA OF THE ADULTS WHO HAD CHILDHOOD ADVERSITY, AND AFFECTED GENES WERE FURTHER EVALUATED FOR THEIR ASSOCIATION WITH ASTHMA. PRISMA GUIDELINES WERE ADOPTED AND PUBMED AND GOOGLE SCHOLAR WERE INCLUDED IN THE SEARCHED DATABASES, TO EVALUATE EPIGENETIC MODIFICATIONS IN ASTHMA-RELATED GENES OF PHYSICALLY, EMOTIONALLY OR SEXUALLY ABUSED CHILDREN. AFTER RETRIEVING A TOTAL OF 5245 ARTICLES, 36 OF THEM WERE INCLUDED IN THE STUDY. SEVERAL GENES AND PATHWAYS THAT MAY CONTRIBUTE TO PATHOGENESIS OF ASTHMA DEVELOPMENT, INCREASED INFLAMMATION, OR RESPONSE TO ASTHMA TREATMENT WERE FOUND EPIGENETICALLY AFFECTED BY CHILDHOOD TRAUMAS. CHILDHOOD ADVERSITY, CAUSING EPIGENETIC CHANGES IN DNA, MAY LEAD TO ASTHMA DEVELOPMENT OR INFLUENCE THE COURSE OF THE DISEASE AND THEREFORE SHOULD BE TAKEN INTO ACCOUNT FOR THE PROLONGED HEALTH CONSEQUENCES. 2022 10 6790 34 [DNA METHYLATION ANALYSIS IN ENVIRONMENTAL AND OCCUPATIONAL CANCER RESEARCH]. THE PRESENT PAPER REVIEWS RECENT LABORATORY METHODS AND EXPERIMENTAL EVIDENCE CONCERNING EPIGENETIC BIOMARKERS INVOLVED IN CARCINOGENESIS MECHANISMS. WE INTRODUCE DNA METHYLATION AND ITS ROLE IN GENE EXPRESSION CONTROL. DNA METHYLATION ANALYSIS MAY ALLOW TO IDENTIFY EARLY CHANGES LEADING TO CANCER AND OTHER CHRONIC DISEASES. WE DESCRIBE HERE STRATEGIES FOR LABORATORY ANALYSES AND THEIR POSSIBLE APPLICATIONS. WE EXAMINE RESULTS FROM RECENT EXPERIMENTAL STUDIES SUGGESTING THAT THE EFFECTS OF CERTAIN OCCUPATIONAL AGENTS ARE MEDIATED BY ALTERATIONS IN DNA METHYLATION. PLANNING AND CONDUCTING INVESTIGATIONS ON EXPOSED HUMAN SUBJECTS WILL ALLOW TO VERIFY WHETHER DNA METHYLATION CHANGES IDENTIFIED IN ANIMAL AND IN-VITRO STUDIES MAY BE USED AS EARLY-EFFECT AND SUSCEPTIBILITY BIOMARKERS. DNA METHYLATION ANALYSIS HAS THE POTENTIAL FOR FUTURE APPLICATIONS IN RISK ASSESSMENT AND PREVENTION PROGRAMS CONDUCTED ON SUBJECTS EXPOSED TO HUMAN CARCINOGENS. 2005 11 396 40 AN UPDATE ON EPIGENETICS AND CHILDHOOD RESPIRATORY DISEASES. EPIGENETIC MECHANISMS, DEFINED AS CHANGES IN PHENOTYPE OR GENE EXPRESSION CAUSED BY MECHANISMS OTHER THAN CHANGES IN THE UNDERLYING DNA SEQUENCE, HAVE BEEN PROPOSED TO CONSTITUTE A LINK BETWEEN GENETIC AND ENVIRONMENTAL FACTORS THAT AFFECT COMPLEX DISEASES. RECENT STUDIES SHOW THAT DNA METHYLATION, ONE OF THE KEY EPIGENETIC MECHANISMS, IS ALTERED IN CHILDREN EXPOSED TO AIR POLLUTANTS AND ENVIRONMENTAL TOBACCO SMOKE EARLY IN LIFE. SEVERAL CANDIDATE GENE STUDIES ON EPIGENETICS HAVE BEEN PUBLISHED TO DATE, BUT IT IS ONLY RECENTLY THAT GLOBAL METHYLATION ANALYSES HAVE BEEN PERFORMED FOR RESPIRATORY DISORDERS SUCH AS ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE. HOWEVER, LARGE-SCALE STUDIES WITH ADEQUATE POWER ARE YET TO BE PRESENTED IN CHILDREN, AND IMPLICATIONS FOR CLINICAL USE REMAIN TO BE EVALUATED. IN THIS REVIEW, WE SUMMARIZE THE RECENT ADVANCES IN EPIGENETICS AND RESPIRATORY DISORDERS IN CHILDREN, WITH A MAIN FOCUS ON METHODOLOGICAL CHALLENGES AND ANALYSES RELATED TO PHENOTYPE AND EXPOSURE USING GLOBAL METHYLATION APPROACHES. 2014 12 6783 27 [CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN WOMEN]. FOR THE PAST SEVERAL YEARS THE NUMBER OF WOMEN SUFFERING FROM CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) HAS BEEN STEADILY INCREASING. THIS FACT PROMPTS THE DEBATE WHICH FACTORS, IN ADDITION TO CONSIDERABLY INCREASING PREVALENCE OF CIGARETTE SMOKING AMONG YOUNG WOMEN, ARE RESPONSIBLE FOR THESE EPIDEMIOLOGIC CHANGES. DIFFERENCES IN THE NATURAL HISTORY AND PROGNOSIS OF COPD IN FEMALES AND MALES ARE PRESENTED IN THE PAPER, AS WELL AS THE NUMBER OF POTENTIAL ETHIOPATHOGENETIC AND PATHOPHYSIOLOGIC FACTORS INFLUENCING THESE VARIATIONS. AMONG THEM, DIFFERENCES IN THE COPD RISK FACTORS SPECTRUM IN BOTH GENDERS AND IN AIRWAYS ANATOMY ARE POINTED OUT, AND THE MECHANISMS RESPONSIBLE FOR GREATER WOMEN'S SUSCEPTIBILITY TO COMPONENTS OF CIGARETTE SMOKE, WHICH REFLECT GENETIC (ENZYME POLYMORPHISMS), EPIGENETIC (DIMINISHED DNA METHYLATION) AND HORMONAL (ESTROGENS) INFLUENCES ON XENOBIOTICS METABOLISM. FURTHER, SEX-RELATED DIFFERENCES REGARDING COPD PHENOTYPES (CHRONIC BRONCHITIS VS. EMPHYSEMA), IMMUNOLOGICAL MARKERS AND CLINICAL MANIFESTATION OF DISEASE ARE UNDERLINED IN THE PAPER. MORE FREQUENT COEXISTENCE OF ANXIETY AND DEPRESSION, COPD EXACERBATIONS AND WORSE QUALITY OF LIFE IN WOMEN ARE ALSO EMPHASIZED. OTHER DIFFERENCES, POINTED OUT BY AUTHORS INCLUDE AUTOIMMUNOLOGICAL CONCEPTION OF PATHOGENESIS OF COPD (GREATER FEMALE SUSCEPTIBILITY TO PRODUCE AUTOANTIBODIES), RISK FACTORS OF DISEASE EXACERBATION AND, AT LAST, RESPONSE TO CERTAIN FORMS OF COPD TREATMENT (NICOTINE REPLACEMENT THERAPY, LONG-TERM OXYGEN THERAPY). 2012 13 6834 36 [IMMUNOPATHOLOGY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE]. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A COMMON, PREVENTABLE AND TREATABLE CONDITION THAT HAS A COMPLEX PATHOPHYSIOLOGY AND AN EVEN MORE COMPLEX IMMUNOPATHOLOGICAL PROCESS. THE PURPOSE OF THIS REVIEW WAS TO ANALYZE COPD IMMUNOPATHOLOGICAL ASPECTS, WHICH WAS ADDRESSED BY UNDERTAKING A LITERATURE SEARCH FOR THE MOST RELEVANT DOCUMENTS INDEXED IN THE PUBMED DATABASE OVER THE LAST 10 YEARS. DIFFERENT CONCLUSIONS COULD BE DRAWN: IN COPD IMMUNOPATHOLOGY THERE ARE IMMUNE AND NON-IMMUNE INFLAMMATORY CHANGES WITH OXIDATIVE STRESS IMBALANCE, THERE ARE ALTERATIONS IN THE PROTEASE/ANTI-PROTEASE RATIO CAUSED BY DIRECT AND INDIRECT GENETIC AND EPIGENETIC-ENVIRONMENTAL DEFECTS; COPD PRODUCES IRREVERSIBLE TISSUE DAMAGE AND CHRONIC INFLAMMATION WITH TISSUE REPAIR ALTERATION, WHICH INDUCES CHRONIC OBSTRUCTION OF THE AIRWAY, BRONCHITIS AND SYSTEMIC DAMAGE. MOST COMMON RESULTING COMORBIDITIES INCLUDE CARDIOVASCULAR DISEASE, METABOLIC SYNDROME, OSTEOPOROSIS, DEPRESSION, MUSCULOSKELETAL DYSFUNCTION, INCREASED BIOLOGICAL AGE, LUNG CANCER AND OTHER TYPES OF MALIGNANCIES. IN THE CONCEPTION OF COPD, RECOGNIZING THAT IT IS A NON-TRANSMITTABLE AND PREVENTABLE DISEASE IS INDISPENSABLE. 2017 14 2075 35 EPIGENETIC DIFFERENCES IN INFLAMMATION GENES OF MONOZYGOTIC TWINS ARE RELATED TO PARENT-CHILD EMOTIONAL AVAILABILITY AND HEALTH. THE INFLAMMATORY RESPONSE IS AN IMMUNE DEFENSE ENGAGED IMMEDIATELY AFTER INJURY OR INFECTION. CHRONIC INFLAMMATION CAN BE DELETERIOUS FOR VARIOUS HEALTH OUTCOMES AND IS CHARACTERIZED BY HIGH LEVELS OF PRO-INFLAMMATORY MARKERS SUCH AS C-REACTIVE PROTEIN (CRP), INTERLEUKIN 6 (IL-6), AND TUMOR NECROSIS FACTOR ALPHA (TNF-ALPHA). A LARGE BODY OF RESEARCH DEMONSTRATES THESE INFLAMMATORY MARKERS ARE RESPONSIVE TO STRESS AND QUALITY OF SOCIAL RELATIONSHIPS THROUGHOUT THE LIFESPAN. FOR EXAMPLE, THE QUALITY OF THE EARLY PARENTAL BOND PREDICTS VARIOUS HEALTH OUTCOMES AND MAY BE DRIVEN BY CHANGES IN IMMUNE FUNCTION. EPIGENETIC PROCESSES, SUCH AS DNA METHYLATION, MAY BE ONE MECHANISM BY WHICH EARLY SOCIAL EXPERIENCES SHAPE IMMUNE FUNCTIONING. THE PRESENT STUDY USED A MONOZYGOTIC TWIN DIFFERENCE DESIGN TO ASSESS IF MOTHER-REPORTED EMOTIONAL AVAILABILITY AT 1 YEAR AND 2.5 YEARS PREDICTED IMMUNE GENE METHYLATION AT 8 YEARS OF AGE. FURTHER, WE ASSESSED IF INFLAMMATION GENE METHYLATION WAS RELATED TO GENERAL HEALTH PROBLEMS (E.G. INFECTIONS, ALLERGIES, ETC.). WE FOUND THAT MOTHER-REPORTED EMOTIONAL AVAILABILITY AT 1 YEAR, BUT NOT 2.5 YEARS, WAS RELATED TO METHYLATION OF VARIOUS IMMUNE GENES IN MONOZYGOTIC TWINS. FURTHERMORE, TWIN PAIRS DISCORDANT IN HEALTH PROBLEMS HAVE MORE DIFFERENCE IN IMMUNE GENE METHYLATION COMPARED TO TWIN PAIRS CONCORDANT FOR HEALTH PROBLEMS, SUGGESTING THAT METHYLATION OF IMMUNE GENES MAY HAVE FUNCTIONAL CONSEQUENCES FOR GENERAL HEALTH. THESE RESULTS SUGGEST THAT THE EMOTIONAL COMPONENT OF ATTACHMENT QUALITY DURING INFANCY CONTRIBUTES TO IMMUNE EPIGENETIC PROFILES IN CHILDHOOD, WHICH MAY INFLUENCE GENERAL HEALTH. 2020 15 4112 44 MECHANISMS CONTRIBUTING TO THE COMORBIDITY OF COPD AND LUNG CANCER. LUNG CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) OFTEN CO-OCCUR, AND INDIVIDUALS WITH COPD ARE AT A HIGHER RISK OF DEVELOPING LUNG CANCER. WHILE THE UNDERLYING MECHANISM FOR THIS RISK IS NOT WELL UNDERSTOOD, ITS MAJOR CONTRIBUTING FACTORS HAVE BEEN PROPOSED TO INCLUDE GENOMIC, IMMUNE, AND MICROENVIRONMENT DYSREGULATION. HERE, WE REVIEW THE EVIDENCE AND SIGNIFICANT STUDIES THAT EXPLORE THE MECHANISMS UNDERLYING THE HEIGHTENED LUNG CANCER RISK IN PEOPLE WITH COPD. GENETIC AND EPIGENETIC CHANGES, AS WELL AS THE ABERRANT EXPRESSION OF NON-CODING RNAS, PREDISPOSE THE LUNG EPITHELIUM TO CARCINOGENESIS BY ALTERING THE EXPRESSION OF CANCER- AND IMMUNE-RELATED GENES. OXIDATIVE STRESS GENERATED BY TOBACCO SMOKING PLAYS A ROLE IN REDUCING GENOMIC INTEGRITY, PROMOTING EPITHELIAL-MESENCHYMAL-TRANSITION, AND GENERATING A CHRONIC INFLAMMATORY ENVIRONMENT. THIS LEADS TO ABNORMAL IMMUNE RESPONSES THAT PROMOTE CANCER DEVELOPMENT, THOUGH NOT ALL SMOKERS DEVELOP LUNG CANCER. SEX DIFFERENCES IN THE METABOLISM OF TOBACCO SMOKE PREDISPOSE FEMALES TO DEVELOPING COPD AND ACCUMULATING DAMAGE FROM OXIDATIVE STRESS THAT POSES A RISK FOR THE DEVELOPMENT OF LUNG CANCER. DYSREGULATION OF THE LUNG MICROENVIRONMENT AND MICROBIOME CONTRIBUTES TO CHRONIC INFLAMMATION, WHICH IS OBSERVED IN COPD AND KNOWN TO FACILITATE CANCER INITIATION IN VARIOUS TUMOR TYPES. FURTHER, THERE IS A NEED TO BETTER CHARACTERIZE AND IDENTIFY THE PROPORTION OF INDIVIDUALS WITH COPD WHO ARE AT A HIGH RISK FOR DEVELOPING LUNG CANCER. WE EVALUATE POSSIBLE NOVEL AND INDIVIDUALIZED SCREENING STRATEGIES, INCLUDING BIOMARKERS IDENTIFIED IN GENETIC STUDIES AND EXHALED BREATH CONDENSATE ANALYSIS. WE ALSO DISCUSS THE USE OF CORTICOSTEROIDS AND STATINS AS CHEMOPREVENTIVE AGENTS TO PREVENT LUNG CANCER. IT IS CRUCIAL THAT WE OPTIMIZE THE CURRENT METHODS FOR THE EARLY DETECTION AND MANAGEMENT OF LUNG CANCER AND COPD IN ORDER TO IMPROVE THE HEALTH OUTCOMES FOR A LARGE AFFECTED POPULATION. 2023 16 4025 38 LUNG CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE: NEEDS AND OPPORTUNITIES FOR INTEGRATED RESEARCH. LUNG CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) ARE LEADING CAUSES OF MORBIDITY AND MORTALITY IN THE UNITED STATES AND WORLDWIDE. THEY SHARE A COMMON ENVIRONMENTAL RISK FACTOR IN CIGARETTE SMOKE EXPOSURE AND A GENETIC PREDISPOSITION REPRESENTED BY THE INCIDENCE OF THESE DISEASES IN ONLY A FRACTION OF SMOKERS. THE PRESENCE OF COPD INCREASES THE RISK OF LUNG CANCER UP TO 4.5-FOLD. TO INVESTIGATE COMMONALITIES IN DISEASE MECHANISMS AND PERSPECTIVES FOR DISEASE CHEMOPREVENTION, THE NATIONAL HEART, LUNG, AND BLOOD INSTITUTE (NHLBI) AND THE NATIONAL CANCER INSTITUTE (NCI) HELD A WORKSHOP. THE PARTICIPANTS IDENTIFIED FOUR RESEARCH OBJECTIVES: 1) CLARIFY COMMON EPIDEMIOLOGICAL CHARACTERISTICS OF LUNG CANCER AND COPD; 2) IDENTIFY SHARED GENETIC AND EPIGENETIC RISK FACTORS; 3) IDENTIFY AND VALIDATE BIOMARKERS, MOLECULAR SIGNATURES, AND IMAGING-DERIVED MEASUREMENTS OF EACH DISEASE; AND 4) DETERMINE COMMON AND DISPARATE PATHOGENETIC MECHANISMS. THESE OBJECTIVES SHOULD BE REACHED VIA FOUR RESEARCH APPROACHES: 1) IDENTIFY, PUBLICIZE, AND ENABLE THE EVALUATION AND ANALYSIS OF EXISTING DATASETS AND REPOSITORIES OF BIOSPECIMENS; 2) OBTAIN PHENOTYPIC AND OUTCOME DATA AND BIOSPECIMENS FROM LARGE STUDIES OF SUBJECTS WITH AND/OR AT RISK FOR COPD AND LUNG CANCER; 3) DEVELOP AND USE ANIMAL AND OTHER PRECLINICAL MODELS TO INVESTIGATE PATHOGENETIC LINKS BETWEEN THE DISEASES; AND 4) CONDUCT EARLY-PHASE CLINICAL TRIALS OF POTENTIAL CHEMOPREVENTIVE AGENTS. TO FOSTER MUCH NEEDED RESEARCH INTERACTIONS, TWO FINAL RECOMMENDATIONS WERE MADE BY THE PARTICIPANTS: 1) INCORPORATE BASELINE PHENOTYPING AND OUTCOME MEASURES FOR BOTH DISEASES IN FUTURE LONGITUDINAL STUDIES OF EACH DISEASE AND 2) EXPAND COLLABORATIVE EFFORTS BETWEEN THE NCI AND NHLBI. 2009 17 311 37 ALCOHOL AND THE METHYLOME: DESIGN AND ANALYSIS CONSIDERATIONS FOR RESEARCH USING HUMAN SAMPLES. BACKGROUND: A GROWING NUMBER OF STUDIES IN HUMAN SAMPLES HAVE SOUGHT TO DETERMINE WHETHER CHRONIC ALCOHOL USE AND ALCOHOL USE DISORDERS (AUDS) MAY BE ASSOCIATED WITH EPIGENETIC FACTORS, SUCH AS DNA METHYLATION. WE REVIEW THE EXTANT LITERATURE IN LIGHT OF SOME OF THE CHALLENGES THAT CURRENTLY AFFECT THE DESIGN AND INTERPRETATION OF EPIGENETIC RESEARCH IN HUMAN SAMPLES. METHOD: A LITERATURE SEARCH WAS USED TO IDENTIFY STUDIES THAT HAVE EXAMINED DNA METHYLATION IN RELATION TO ALCOHOL USE OR AUDS IN HUMAN SAMPLES (THROUGH JULY 2013). A TOTAL OF 22 STUDIES WERE IDENTIFIED. RESULTS: ASSOCIATIONS WITH QUANTITATIVE OR DIAGNOSTIC PHENOTYPES OF ALCOHOL USE OR AUDS HAVE BEEN REPORTED FOR SEVERAL GENES. HOWEVER, ALL STUDIES TO DATE HAVE RELIED ON RELATIVELY SMALL SAMPLES AND CROSS-SECTIONAL STUDY DESIGNS. ADDITIONALLY, ATTEMPTS TO REPLICATE RESULTS HAVE BEEN RARE. MORE GENERALLY, RESEARCH PROGRESS IS HAMPERED BY SEVERAL ISSUES, INCLUDING LIMITATIONS OF THE TECHNOLOGIES USED TO ASSESS DNA METHYLATION, TISSUE- AND CELL-SPECIFICITY OF METHYLATION PATTERNS, THE DIFFICULTIES OF RELATING OBSERVED METHYLATION DIFFERENCES AT A GIVEN LOCUS TO A FUNCTIONAL EFFECT, AND LIMITED KNOWLEDGE ABOUT THE MOLECULAR MECHANISMS UNDERLYING THE EFFECTS OF ALCOHOL ON DNA METHYLATION. CONCLUSIONS: ALTHOUGH WE SHARE THE OPTIMISM THAT EPIGENETICS MAY LEAD TO NEW INSIGHTS INTO THE ETIOLOGY AND PATHOPHYSIOLOGY OF AUDS, THE METHODOLOGICAL AND SCIENTIFIC CHALLENGES ASSOCIATED WITH CONDUCTING METHYLOMIC RESEARCH IN HUMAN SAMPLES NEED TO BE CAREFULLY CONSIDERED WHEN DESIGNING AND EVALUATING SUCH STUDIES. 2013 18 540 41 ATMOSPHERIC FINE PARTICULATE MATTER AND EPITHELIAL MESENCHYMAL TRANSITION IN PULMONARY CELLS: STATE OF THE ART AND CRITICAL REVIEW OF THE IN VITRO STUDIES. EXPOSURE TO FINE PARTICULATE MATTER (PM(2.5)) HAS BEEN ASSOCIATED WITH SEVERAL DISEASES INCLUDING ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND LUNG CANCER. MECHANISMS SUCH AS OXIDATIVE STRESS AND INFLAMMATION ARE WELL-DOCUMENTED AND ARE CONSIDERED AS THE STARTING POINT OF SOME OF THE PATHOLOGICAL RESPONSES. HOWEVER, A NUMBER OF STUDIES ALSO FOCUSED ON EPITHELIAL-MESENCHYMAL TRANSITION (EMT), WHICH IS A BIOLOGICAL PROCESS INVOLVED IN FIBROTIC DISEASES AND CANCER PROGRESSION NOTABLY VIA METASTASIS INDUCTION. UP UNTIL NOW, EMT WAS WIDELY REPORTED IN VIVO AND IN VITRO IN VARIOUS CELL TYPES BUT INVESTIGATIONS DEALING WITH IN VITRO STUDIES OF PM(2.5) INDUCED EMT IN PULMONARY CELLS ARE LIMITED. FURTHER, FEW INVESTIGATIONS COMBINED THE NECESSARY ENDPOINTS FOR VALIDATION OF THE EMT STATE IN CELLS: SUCH AS EXPRESSION OF SEVERAL SURFACE, CYTOSKELETON OR EXTRACELLULAR MATRIX BIOMARKERS AND ACTIVATION OF TRANSCRIPTION MARKERS AND EPIGENETIC FACTORS. STUDIES EXPLORED VARIOUS CELL TYPES, CULTURED UNDER DIFFERING CONDITIONS AND EXPOSED FOR VARIOUS DURATIONS TO DIFFERENT DOSES. SUCH UNHARMONIZED PROTOCOLS (1) MIGHT INTRODUCE BIAS, (2) MAKE DIFFICULT COMPARISON OF RESULTS AND (3) PRECLUDE REACHING A DEFINITIVE CONCLUSION REGARDING THE ABILITY OF AIRBORNE PM(2.5) TO INDUCE EMT IN PULMONARY CELLS. SOME QUESTIONS REMAIN, IN PARTICULAR THE SPECIFIC PM(2.5) COMPONENTS RESPONSIBLE FOR EMT TRIGGERING. THE AIM OF THIS REVIEW IS TO EXAMINE THE AVAILABLE PM(2.5) INDUCED EMT IN VITRO STUDIES ON PULMONARY CELLS WITH SPECIAL EMPHASIS ON THE CRITICAL PARAMETERS CONSIDERED TO CARRY OUT FUTURE RESEARCH IN THIS FIELD. THIS CLARIFICATION APPEARS NECESSARY FOR PRODUCTION OF RELIABLE AND COMPARABLE RESULTS. 2020 19 3027 43 GENETICS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A COMPLEX DISEASE WITH MULTIFACTORIAL BACKGROUND, BASED ON THE INTERACTION OF ENVIRONMENTAL AND GENETIC FACTORS. ENVIRONMENTAL FACTORS ARE CLEARLY RELATED TO THE DEVELOPMENT OF THE DISEASE. HOWEVER, FAMILY AND TWIN STUDIES SUGGESTED GENETICS FACTORS TO BE ONE OF THE IMPORTANT DETERMINANTS FOR THE DEVELOPMENT OF COPD. DIFFERENT APPROACHES HAVE BEEN USED TO IDENTIFY GENES OF INTEREST. GENOMEWIDE LINKAGE ANALYSIS FOUND AREAS OF INTEREST ON DIFFERENT CHROMOSOMES, WITH SOME GENES LOCATED IN THIS REGIONS BEING IDENTIFIED AND REPLICATED AS SUSCEPTIBILITY GENES. NUMEROUS OF CANDIDATE GENES THAT COULD BE LINKED TO DISEASE PATHOGENESIS HAVE BEEN IMPLICATED IN COPD GENETICS. HOWEVER, THE CANDIDATE GENE APPROACH IS OFTEN LIMITED BY INCONSISTENT RESULTS IN OTHER STUDY POPULATIONS. RECENTLY, A COMBINATION OF DIFFERENT METHODS IS USED GIVING MORE EVIDENCE FOR SOME CANDIDATE GENES, INCLUDING TGFBETA-1, SURFACTANT, SERPINE2 AND MICROSOMAL EPOXIDE HYDROLASE. IN THE FUTURE ONGOING EXACT PHENOTYPE DEFINITION, COMBINATION OF SEVERAL APPROACHES, GENOME-WIDE ASSOCIATION STUDIES AND ANIMAL MODEL GENETICS WILL LEAD TO NEW INSIGHTS INTO THE GENETICS OF COPD, WITH EPIGENETIC FACTORS NEEDS TO BE FURTHER INVESTIGATED AND CONSIDERED IN CONCERT WITH GENETIC FINDINGS. 2007 20 6876 44 [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