1 1852 207 ELECTRONIC CIGARETTES: THEIR CONSTITUENTS AND POTENTIAL LINKS TO ASTHMA. PURPOSE OF REVIEW: VAPING IS GAINING POPULARITY IN THE USA, PARTICULARLY AMONG TEENS AND YOUNG ADULTS. WHILE E-CIGS ARE COMMONLY REPRESENTED AS SAFER ALTERNATIVES TO TOBACCO CIGARETTES, LITTLE IS KNOWN REGARDING THE HEALTH EFFECTS OF THEIR SHORT- OR LONG-TERM USE, ESPECIALLY IN INDIVIDUALS WITH PRE-EXISTING RESPIRATORY DISEASES SUCH AS ASTHMA. FLAVORED E-CIG LIQUIDS (E-LIQUIDS) AND E-CIG AEROSOLS CONTAIN AIRWAY IRRITANTS AND TOXICANTS THAT HAVE BEEN IMPLICATED IN THE PATHOGENESIS AND WORSENING OF LUNG DISEASES. IN THIS REVIEW, WE WILL SUMMARIZE EXISTING DATA ON POTENTIAL HEALTH EFFECTS OF COMPONENTS PRESENT IN E-CIG AEROSOLS, SUCH AS PROPYLENE GLYCOL, VEGETABLE GLYCERIN, NICOTINE, AND FLAVORINGS, AND DISCUSS THEIR RELEVANCE IN THE CONTEXT OF ASTHMA. RECENT FINDINGS: RECENT SURVEY DATA INDICATE THAT ADOLESCENTS WITH ASTHMA HAD A HIGHER PREVALENCE OF CURRENT E-CIG USE (12.4%) COMPARED TO THEIR NON-ASTHMATICS PEERS (10.2%) AND CONVEYED POSITIVE BELIEFS ABOUT TOBACCO PRODUCTS, ESPECIALLY E-CIGS. SIMILARLY, A STUDY CONDUCTED AMONG HIGH SCHOOL STUDENTS FROM ONTARIO, CANADA, INDICATED A GREATER LIKELIHOOD OF E-CIG USE IN ASTHMATICS AS COMPARED TO THEIR NON-ASTHMATIC PEERS. AVAILABILITY OF DIFFERENT FLAVORINGS IS OFTEN CITED AS THE MAIN REASON AMONG YOUTH/ADOLESCENTS FOR TRYING E-CIGS OR SWITCHING FROM CIGARETTES TO E-CIGS. OCCUPATIONAL INHALATION OF SOME COMMON FOOD-SAFE FLAVORING AGENTS IS REPORTED TO CAUSE OCCUPATIONAL ASTHMA AND WORSEN ASTHMATIC SYMPTOMS. MOREOVER, WORKPLACE INHALATION EXPOSURES TO THE FLAVORING AGENT DIACETYL HAVE CAUSED IRREVERSIBLE OBSTRUCTIVE AIRWAY DISEASE IN HEALTHY WORKERS. ADDITIONALLY, RECENT STUDIES REPORT THAT THERMAL DECOMPOSITION OF PROPYLENE GLYCOL (PG) AND VEGETABLE GLYCERIN (VG), THE BASE CONSTITUENTS OF E-LIQUIDS, PRODUCES REACTIVE CARBONYLS, INCLUDING ACROLEIN, FORMALDEHYDE, AND ACETALDEHYDE, WHICH HAVE KNOWN RESPIRATORY TOXICITIES. FURTHERMORE, RECENT NICOTINE STUDIES IN RODENTS REVEAL THAT PRENATAL NICOTINE EXPOSURES LEAD TO EPIGENETIC REPROGRAMMING IN THE OFFSPRING, ABNORMAL LUNG DEVELOPMENT, AND MULTIGENERATIONAL TRANSMISSION OF ASTHMATIC-LIKE SYMPTOMS. COMPARISONS OF THE TOXICITY AND HEALTH EFFECTS OF E-CIGS AND CONVENTIONAL CIGARETTES OFTEN FOCUS ON TOXICANTS KNOWN TO BE PRESENT IN CIGARETTE SMOKE (CS) (I.E., FORMALDEHYDE, NITROSAMINES, ETC.), AS WELL AS SMOKING-ASSOCIATED CLINICAL ENDPOINTS, SUCH AS CANCER, BRONCHITIS, AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). HOWEVER, THIS APPROACH DISREGARDS POTENTIAL TOXICITY OF COMPONENTS UNIQUE TO FLAVORED E-CIGS, SUCH AS PG, VG, AND THE MANY DIFFERENT FLAVORING CHEMICALS, WHICH LIKELY INDUCE RESPIRATORY EFFECTS NOT USUALLY OBSERVED IN CIGARETTE SMOKERS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
2 5380  57 RECENT UPDATES ON BIOMARKERS OF EXPOSURE AND SYSTEMIC TOXICITY IN E-CIGARETTE USERS AND EVALI. ELECTRONIC NICOTINE DELIVERY SYSTEMS (ENDS), OR E-CIGARETTES, ARE EMERGING TOBACCO PRODUCTS THAT PRODUCE AEROSOLS BY HEATING E-LIQUIDS, WHICH MOST OFTEN CONSIST OF PROPYLENE GLYCOL AND VEGETABLE GLYCERIN ALONG WITH VARIOUS FLAVORING COMPOUNDS, BYPASSING THE COMBUSTION THAT OCCURS IN THE USE OF TRADITIONAL TOBACCO CIGARETTES. THESE PRODUCTS HAVE SEEN A DRASTIC INCREASE IN POPULARITY IN RECENT YEARS BOTH AS SMOKING CESSATION DEVICES AS WELL AS AMONG YOUNGER GENERATIONS, DUE IN LARGE PART TO THE WIDESPREAD PERCEPTION AMONG CONSUMERS THAT E-CIGS ARE SIGNIFICANTLY LESS HARMFUL TO HEALTH THAN TRADITIONAL TOBACCO CIGARETTES. DUE TO THE NOVELTY OF ENDS AS WELL AS THEIR RAPIDLY INCREASING USE, RESEARCH INTO BIOMARKERS OF E-CIG EXPOSURE AND TOXICITY HAVE LAGGED BEHIND THEIR POPULARITY, LEAVING IMPORTANT QUESTIONS ABOUT THEIR POTENTIAL TOXICITY UNANSWERED. RESEARCH INTO POTENTIAL BIOMARKERS OF ACUTE AND CHRONIC E-CIG USE, AND E-CIGARETTE- OR VAPING-ASSOCIATED LUNG INJURY IS NECESSARY FOR INFORMING BOTH CLINICAL AND REGULATORY DECISION-MAKING. WE AIM TO PROVIDE AN UPDATED REVIEW OF RECENT RESEARCH INTO POTENTIAL CIRCULATING, GENOMIC, TRANSCRIPTOMIC, AND EPIGENETIC BIOMARKERS OF EXPOSURE TO AND TOXICITY OF E-CIGS. WE ADDITIONALLY HIGHLIGHT RESEARCH AREAS THAT WARRANT ADDITIONAL STUDY TO GAIN A BETTER UNDERSTANDING OF HEALTH RISKS ASSOCIATED WITH ENDS USE, AS WELL AS TO PROVIDE VALIDATION OF EXISTING DATA AND METHODS FOR MEASURING AND ANALYZING E-CIG-ASSOCIATED BIOMARKERS IN HUMAN AND ANIMAL BIOFLUIDS, TISSUES, AND CELLS. THIS REVIEW ALSO HIGHLIGHTS ONGOING EFFORTS WITHIN THE WNY CENTER FOR RESEARCH ON FLAVORED TOBACCO FOR RESEARCH INTO NOVEL BIOMARKERS IN EXTRACELLULAR VESICLES THAT MAY BE ASSOCIATED WITH SHORT- AND LONG-TERM ENDS USE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
3 2838  31 FORMALDEHYDE CARCINOGENICITY RESEARCH: 30 YEARS AND COUNTING FOR MODE OF ACTION, EPIDEMIOLOGY, AND CANCER RISK ASSESSMENT. FORMALDEHYDE IS A WIDELY USED HIGH PRODUCTION CHEMICAL THAT IS ALSO RELEASED AS A BYPRODUCT OF COMBUSTION, OFF-GASSING OF VARIOUS BUILDING PRODUCTS, AND AS A FIXATIVE FOR PATHOLOGISTS AND EMBALMERS. WHAT IS NOT OFTEN REALIZED IS THAT FORMALDEHYDE IS ALSO PRODUCED AS A NORMAL PHYSIOLOGIC CHEMICAL IN ALL LIVING CELLS. IN 1980, CHRONIC INHALATION OF HIGH CONCENTRATIONS OF FORMALDEHYDE WAS SHOWN TO BE CARCINOGENIC, INDUCING A HIGH INCIDENCE OF NASAL SQUAMOUS CELL CARCINOMAS IN RATS. SOME EPIDEMIOLOGIC STUDIES HAVE ALSO FOUND INCREASED NUMBERS OF NASOPHARYNGEAL CARCINOMA AND LEUKEMIA IN HUMANS EXPOSED TO FORMALDEHYDE THAT RESULTED IN FORMALDEHYDE BEING CONSIDERED A KNOWN HUMAN CARCINOGEN. THIS ARTICLE REVIEWS THE DATA FOR RODENT AND HUMAN CARCINOGENICITY, EARLY MODE OF ACTION STUDIES, MORE RECENT MOLECULAR STUDIES OF BOTH ENDOGENOUS AND EXOGENOUS DNA ADDUCTS, AND EPIGENETIC STUDIES. IT GOES ON TO DEMONSTRATE THE POWER OF THESE RESEARCH STUDIES TO PROVIDE CRITICAL DATA TO IMPROVE OUR ABILITY TO DEVELOP SCIENCE-BASED CANCER RISK ASSESSMENTS, INSTEAD OF DEFAULT APPROACHES. THE COMPLEXITY OF CONSTANT PHYSIOLOGIC EXPOSURE TO A KNOWN CARCINOGEN REQUIRES THAT NEW WAYS OF THINKING BE INCORPORATED INTO DETERMINATIONS OF CANCER RISK ASSESSMENT FOR FORMALDEHYDE, OTHER ENDOGENOUS CARCINOGENS, AND THE ROLE OF BACKGROUND ENDOGENOUS DNA DAMAGE AND MUTAGENESIS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
4 6783  35 [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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
5 5174  41 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
6 3631  37 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
7 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
8 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
9 1188  45 COPD: A MULTIFACTORIAL SYSTEMIC DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) HAS TRADITIONALLY BEEN CONSIDERED A DISEASE OF THE LUNGS SECONDARY TO CIGARETTE SMOKING AND CHARACTERIZED BY AIRFLOW OBSTRUCTION DUE TO ABNORMALITIES OF BOTH AIRWAY (BRONCHITIS) AND LUNG PARENCHYMA (EMPHYSEMA). IT IS NOW WELL KNOWN THAT COPD IS ASSOCIATED WITH SIGNIFICANT SYSTEMIC ABNORMALITIES, SUCH AS RENAL AND HORMONAL ABNORMALITIES, MALNUTRITION, MUSCLE WASTING, OSTEOPOROSIS, AND ANEMIA. HOWEVER, IT IS STILL UNCLEAR WHETHER THEY REPRESENT CONSEQUENCES OF THE PULMONARY DISORDER, OR WHETHER COPD SHOULD BE CONSIDERED AS A SYSTEMIC DISEASE. THESE SYSTEMIC ABNORMALITIES HAVE BEEN ATTRIBUTED TO AN INCREASED LEVEL OF SYSTEMIC INFLAMMATION. CHRONIC INFLAMMATION, HOWEVER, MAY NOT BE THE ONLY CAUSE OF THE SYSTEMIC EFFECTS OF COPD. RECENT DATA FROM HUMANS AND ANIMAL MODELS SUPPORT THE VIEW THAT EMPHYSEMA MAY BE A VASCULAR DISEASE. OTHER STUDIES HAVE HIGHLIGHTED THE ROLE OF REPAIR FAILURE, BONE MARROW ABNORMALITY, GENETIC AND EPIGENETIC FACTORS, IMMUNOLOGICAL DISORDERS AND INFECTIONS AS POTENTIAL CAUSES OF COPD SYSTEMIC MANIFESTATIONS. BASED ON THIS NEW EVIDENCE, IT IS REASONABLE TO CONSIDER COPD, AND EMPHYSEMA IN PARTICULAR, AS 'A DISEASE WITH A SIGNIFICANT SYSTEMIC COMPONENT' IF NOT A 'SYSTEMIC DISEASE' PER SE. THE AIM OF THIS REVIEW IS TO GIVE AN OVERVIEW OF THE MOST RELEVANT AND INNOVATIVE HYPOTHESIS ABOUT THE EXTRAPULMONARY MANIFESTATIONS OF COPD.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
10 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
11  754  44 CARDIOVASCULAR ADAPTATIONS TO PARTICLE INHALATION EXPOSURE: MOLECULAR MECHANISMS OF THE TOXICOLOGY. AMBIENT AIR, OCCUPATIONAL SETTINGS, AND THE USE AND DISTRIBUTION OF CONSUMER PRODUCTS ALL SERVE AS CONDUITS FOR TOXICANT EXPOSURE THROUGH INHALATION. WHILE THE PULMONARY SYSTEM REMAINS A PRIMARY TARGET FOLLOWING INHALATION EXPOSURE, CARDIOVASCULAR IMPLICATIONS ARE EXCEPTIONALLY CULPABLE FOR INCREASED MORBIDITY AND MORTALITY. THE EPIDEMIOLOGICAL EVIDENCE FOR CARDIOVASCULAR DYSFUNCTION RESULTING FROM ACUTE OR CHRONIC INHALATION EXPOSURE TO PARTICULATE MATTER HAS BEEN WELL DOCUMENTED, BUT THE MECHANISMS DRIVING THE RESULTING DISTURBANCES REMAIN ELUSIVE. IN THE CURRENT REVIEW, WE AIM TO SUMMARIZE THE CELLULAR AND MOLECULAR MECHANISMS THAT ARE DIRECTLY LINKED TO CARDIOVASCULAR HEALTH FOLLOWING EXPOSURE TO A VARIETY OF INHALED TOXICANTS. THE PURPOSE OF THIS REVIEW IS TO PROVIDE A COMPREHENSIVE OVERVIEW OF THE BIOCHEMICAL CHANGES IN THE CARDIOVASCULAR SYSTEM FOLLOWING PARTICLE INHALATION EXPOSURE AND TO HIGHLIGHT POTENTIAL BIOMARKERS THAT EXIST ACROSS MULTIPLE EXPOSURE PARADIGMS. WE ATTEMPT TO INTEGRATE THESE MOLECULAR SIGNATURES IN AN EFFORT TO PROVIDE DIRECTION FOR FUTURE INVESTIGATIONS. THIS REVIEW ALSO CHARACTERIZES HOW MOLECULAR RESPONSES ARE MODIFIED IN AT-RISK POPULATIONS, SPECIFICALLY THE IMPACT OF ENVIRONMENTAL EXPOSURE DURING CRITICAL WINDOWS OF DEVELOPMENT. MATERNAL EXPOSURE TO PARTICULATE MATTER DURING GESTATION CAN LEAD TO FETAL EPIGENETIC REPROGRAMMING, RESULTING IN LONG-TERM DEFICITS TO THE CARDIOVASCULAR SYSTEM. IN BOTH DIRECT AND INDIRECT (GESTATIONAL) EXPOSURES, CONNECTING THE BIOCHEMICAL MECHANISMS WITH FUNCTIONAL DEFICITS OUTLINES PATHWAYS THAT CAN BE TARGETED FOR FUTURE THERAPEUTIC INTERVENTION. ULTIMATELY, FUTURE INVESTIGATIONS INTEGRATING "OMICS"-BASED APPROACHES WILL BETTER ELUCIDATE THE MECHANISMS THAT ARE ALTERED BY XENOBIOTIC INHALATION EXPOSURE, IDENTIFY BIOMARKERS, AND GUIDE IN CLINICAL DECISION MAKING.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
12 5400  34 REDUCING TOBACCO-RELATED DISABILITY IN CHRONIC SMOKERS. TOBACCO CONSUMPTION (PREDOMINANTLY CIGARETTES) IS THE LEADING PREVENTABLE CAUSE OF MORTALITY WORLDWIDE. ALTHOUGH THE MAJOR FOCUS OF STRATEGIES TO REDUCE MORTALITY FROM TOBACCO MUST INCLUDE PREVENTION OF FUTURE GENERATIONS FROM INITIALLY GAINING ACCESS, SOME SMOKERS ARE UNWILLING OR UNABLE TO QUIT. CAN THE HIGHER RISK CHRONIC SMOKER BE IDENTIFIED AND CAN THEIR RISK BE REDUCED? THE RISK OF ADVERSE EVENTS IN CIGARETTE SMOKERS IS INFLUENCED BY THE INTENSITY AND DURATION OF CIGARETTE SMOKING OR SECONDHAND EXPOSURE, ASSOCIATED CONVENTIONAL RISK FACTORS, ENVIRONMENTAL STRESSORS, AND CERTAIN GENETIC VARIANTS AND EPIGENETIC MODIFIERS. RECENT DATA SUGGEST THAT INFLAMMATORY MARKERS SUCH AS HIGH-SENSITIVITY C-REACTIVE PROTEIN (HS CRP) AND TARGETED IMAGING CAN IDENTIFY SOME SMOKERS AT HIGHER RISK. AS SMOKING IS PROTHROMBOTIC, ASPIRIN INITIATION AND EXPANDED STATIN USE MIGHT REDUCE CARDIOVASCULAR RISK IN THOSE WHO DO NOT PRESENTLY MEET CRITERIA FOR THESE THERAPIES, BUT FURTHER STUDY IS REQUIRED. THUS, ALTHOUGH ADVOCACY FOR SMOKING CESSATION SHOULD ALWAYS BE THE PRIMARY APPROACH, INCREASED EFFORTS ARE NEEDED TO IDENTIFY AND POTENTIALLY TREAT THOSE WHO ARE UNABLE OR UNWILLING TO QUIT.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
13  642  39 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
14 6633  43 UNHEALTHY SMOKERS: SCOPES FOR PROPHYLACTIC INTERVENTION AND CLINICAL TREATMENT. BACKGROUND: GLOBALLY, TOBACCO USE CAUSES APPROXIMATELY 6 MILLION DEATHS PER YEAR, AND PREDICTIONS REPORT THAT WITH CURRENT TRENDS; MORE THAN 8 MILLION DEATHS ARE EXPECTED ANNUALLY BY 2030. CIGARETTE SMOKINGS IS CURRENTLY ACCOUNTABLE FOR MORE THAN 480,000 DEATHS EACH YEAR IN UNITED STATES (US) AND IS THE LEADING CAUSE OF PREVENTABLE DEATH IN THE US. ON AVERAGE, SMOKERS DIE 10 YEARS EARLIER THAN NONSMOKERS AND IF SMOKING CONTINUES AT ITS CURRENT PROPORTION AMONG ADOLESCENTS, ONE IN EVERY 13 AMERICANS AGED 17 YEARS OR YOUNGER IS EXPECTED TO DIE PREMATURELY FROM A SMOKING-RELATED ILLNESS. EVEN THOUGH THERE HAS BEEN A MARGINAL SMOKING DECLINE OF AROUND 5% IN RECENT YEARS (2005 VS 2015), SMOKERS STILL ACCOUNT FOR 15% OF THE US ADULT POPULATION. WHAT IS ALSO CONCERNING IS THAT 41,000 OUT OF 480,000 DEATHS RESULTS FROM SECONDHAND SMOKE (SHS) EXPOSURE. HEREIN, WE PROVIDE A DETAILED REVIEW OF HEALTH COMPLICATIONS AND MAJOR PATHOLOGICAL MECHANISMS INCLUDING MUTATION, INFLAMMATION, OXIDATIVE STRESS, AND HEMODYNAMIC AND PLASMA PROTEIN CHANGES ASSOCIATED WITH CHRONIC SMOKING. FURTHER, WE DISCUSS PROPHYLACTIC INTERVENTIONS AND ASSOCIATED BENEFITS AND PROVIDE A RATIONALE FOR THE SCOPE OF CLINICAL TREATMENT. CONCLUSIONS: CONSIDERING THESE PREMISES, IT IS EVIDENT THAT MUCH DETAILED TRANSLATIONAL AND CLINICAL STUDIES ARE NEEDED. FACTORS SUCH AS THE LENGTH OF SMOKING CESSATION FOR EX-SMOKERS, THE LEVEL OF SMOKE EXPOSURE IN CASE OF SHS, PRE-ESTABLISHED HEALTH CONDITIONS, GENETICS (AND EPIGENETICS MODIFICATION CAUSED BY CHRONIC SMOKING) ARE FEW OF THE CRITERIA THAT NEED TO BE EVALUATED TO BEGIN ASSESSING THE PROPHYLACTIC AND/OR THERAPEUTIC IMPACT OF TREATMENTS AIMED AT CHRONIC AND FORMER SMOKERS (ESPECIALLY EARLY STAGE EX-SMOKERS) INCLUDING THOSE FREQUENTLY SUBJECTED TO SECOND HAND TOBACCO SMOKE EXPOSURE. HEREIN, WE PROVIDE A DETAILED REVIEW OF HEALTH COMPLICATIONS AND MAJOR PATHOLOGICAL MECHANISMS INCLUDING MUTATION, INFLAMMATION, OXIDATIVE STRESS, AND HEMODYNAMIC AND PLASMA PROTEIN CHANGES ASSOCIATED WITH CHRONIC SMOKING. FURTHER, WE DISCUSS ABOUT PROPHYLACTIC INTERVENTIONS AND ASSOCIATED BENEFITS AND PROVIDE A RATIONALE AND SCOPE FOR CLINICAL TREATMENT.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
15 4767  38 NUCLEAR AND MITOCHONDRIAL DNA ALTERATIONS IN NEWBORNS WITH PRENATAL EXPOSURE TO CIGARETTE SMOKE. NEWBORNS EXPOSED TO MATERNAL CIGARETTE SMOKE (CS) IN UTERO HAVE AN INCREASED RISK OF DEVELOPING CHRONIC DISEASES, CANCER, AND ACQUIRING DECREASED COGNITIVE FUNCTION IN ADULTHOOD. ALTHOUGH THE LITERATURE REPORTS MANY DELETERIOUS EFFECTS ASSOCIATED WITH MATERNAL CIGARETTE SMOKING ON THE FETUS, THE MOLECULAR ALTERATIONS AND MECHANISMS OF ACTION ARE NOT YET CLEAR. SMOKING MAY ACT DIRECTLY ON NUCLEAR DNA BY INDUCING MUTATIONS OR EPIGENETIC MODIFICATIONS. RECENT STUDIES ALSO INDICATE THAT SMOKING MAY ACT ON MITOCHONDRIAL DNA BY INDUCING A CHANGE IN THE NUMBER OF COPIES TO MAKE UP FOR THE DAMAGE CAUSED BY SMOKING ON THE RESPIRATORY CHAIN AND LACK OF ENERGY. IN ADDITION, INDIVIDUAL GENETIC SUSCEPTIBILITY PLAYS A SIGNIFICANT ROLE IN DETERMINING THE EFFECTS OF SMOKING DURING DEVELOPMENT. FURTHERMORE, PRIOR EXPOSURE OF PATERNAL AND MATERNAL GAMETES TO CIGARETTE SMOKE MAY AFFECT THE HEALTH OF THE DEVELOPING INDIVIDUAL, NOT ONLY THE IN UTERO EXPOSURE. THIS REVIEW EXAMINES THE GENETIC AND EPIGENETIC ALTERATIONS IN NUCLEAR AND MITOCHONDRIAL DNA ASSOCIATED WITH SMOKE EXPOSURE DURING THE MOST SENSITIVE PERIODS OF DEVELOPMENT (PRIOR TO CONCEPTION, PRENATAL AND EARLY POSTNATAL) AND ASSESSES HOW SUCH CHANGES MAY HAVE CONSEQUENCES FOR BOTH FETAL GROWTH AND DEVELOPMENT.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
16 2737  38 EXPOSING A DEADLY ALLIANCE: NOVEL INSIGHTS INTO THE BIOLOGICAL LINKS BETWEEN COPD AND LUNG CANCER. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AFFECTS MORE THAN 200 MILLION PEOPLE WORLDWIDE AND IS EXPECTED TO BECOME THE THIRD LEADING CAUSE OF DEATH IN 2020. COPD IS CHARACTERIZED BY PROGRESSIVE AIRFLOW LIMITATION, DUE TO A COMBINATION OF CHRONIC INFLAMMATION AND REMODELING OF THE SMALL AIRWAYS (BRONCHIOLITIS) AND LOSS OF ELASTIC RECOIL CAUSED BY DESTRUCTION OF THE ALVEOLAR WALLS (EMPHYSEMA). LUNG CANCER IS THE MOST IMPORTANT CAUSE OF CANCER-RELATED DEATH IN THE WORLD. (CIGARETTE) SMOKING IS THE PRINCIPAL CULPRIT CAUSING BOTH COPD AND LUNG CANCER; IN ADDITION, EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE, BIOMASS FUEL SMOKE, COAL SMOKE AND OUTDOOR AIR POLLUTION HAVE ALSO BEEN ASSOCIATED WITH AN INCREASED INCIDENCE OF BOTH DISEASES. IMPORTANTLY, SMOKERS WITH COPD--DEFINED AS EITHER NOT FULLY REVERSIBLE AIRFLOW LIMITATION OR EMPHYSEMA--HAVE A TWO- TO FOUR-FOLD INCREASED RISK TO DEVELOP LUNG CANCER. IN THIS REVIEW, WE HIGHLIGHT SEVERAL OF THE GENETIC, EPIGENETIC AND INFLAMMATORY MECHANISMS, WHICH LINK COPD AND CARCINOGENESIS IN THE LUNGS. ELUCIDATING THE BIOLOGICAL PATHWAYS AND NETWORKS, WHICH UNDERLIE THE INCREASED SUSCEPTIBILITY OF LUNG CANCER IN PATIENTS WITH COPD, HAS IMPORTANT IMPLICATIONS FOR SCREENING, PREVENTION, DIAGNOSIS AND TREATMENT OF THESE TWO DEVASTATING PULMONARY DISEASES.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
17 6915  23 [VULNERABILITY OF WOMEN TO TOBACCO: THE BRONCHO-PULMONARY CONSEQUENCES (ASTHMA, COPD)]. SMOKING REMAINS COMMON, WITH AN EXPOSURE THAT BEGINS EARLY DURING PREGNANCY. IT INDUCES EPIGENETIC CHANGES, WITH A TRANS-GENERATIONAL TRANSMISSION. SMOKING INCREASES THE RISK OF UNCONTROLLED ASTHMA DURING CHILDHOOD AND ADULT LIFE. ASTHMA IS ALSO ASSOCIATED WITH INCREASED RISK OF A DECLINE OF LUNG FUNCTION AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). WOMEN ARE MORE AT RISK OF DEVELOPING EARLY AND SEVERE COPD. THE MECHANISMS ARE CURRENTLY POORLY KNOWN.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
18 6781  51 [BREATHING: AMBIENT AIR POLLUTION AND HEALTH - PART III]. THE THIRD PART OF THE DGP STATEMENT INTRODUCES THE CURRENT BODY OF KNOWLEDGE ON LESS STUDIED HEALTH OUTCOMES ASSOCIATED WITH EXPOSURE TO AMBIENT AIR POLLUTION: THE NEGATIVE IMPACT ON METABOLISM LEADING TO IMPAIRED GLUCOSE TOLERANCE AND DIABETES AS WELL AS CONTRIBUTION TO THE DEVELOPMENT OF NEURODEGENERATIVE DISORDERS AND DELAYED COGNITIVE FUNCTION IN CHILDREN. FURTHERMORE, PRENATAL EXPOSURE AND ADVERSE EFFECTS ON MOTHER AND CHILD ARE ADDRESSED. FINALLY, THE CURRENTLY DISCUSSED BIOLOGICAL MECHANISMS UNDERLYING VARIOUS HEALTH EFFECTS ASSOCIATED WITH EXPOSURE TO AIR POLLUTION ARE DESCRIBED.DIFFERING, BUT OFTEN COMPLEMENTARY BIOLOGICAL MECHANISMS CREATE THE BASIS FOR THE DIVERSE HEALTH OUTCOMES CAUSED BY AIR POLLUTION. OXIDATIVE STRESS AND A SUBCLINICAL INFLAMMATORY RESPONSE IN THE LUNGS AND ON A SYSTEMIC LEVEL ("LOW-GRADE SYSTEMIC INFLAMMATION") ARE CONSIDERED TO BE KEY MECHANISMS. THEY PROMOTE SECONDARY ALTERATIONS IN THE BODY, SUCH AS VASCULAR OR METABOLIC PROCESSES, AND MAY ALSO RESULT IN THE CURRENTLY STUDIED EPIGENETIC PHENOMENA OR NEUROINFLAMMATION. IN THIS CONTEXT, THE HEALTH SIGNIFICANCE OF SOLUBLE PARTICULATE MATTER AND THE ROLE OF ULTRAFINE PARTICLES TRANSLOCATED ACROSS BIOLOGICAL MEMBRANES INTO BLOOD VESSEL AND TRANSPORTED VIA THE CIRCULATION TO SECONDARY TARGET ORGANS, SUCH AS LIVER, BRAIN OR THE FETUS, ARE INTENSIVELY DISCUSSED.DIABETES IS ONE OF THE LEADING CHRONIC DISEASES WORLDWIDE, WITH A PREVALENCE OF ALMOST 14 % IN GERMANY. ALTHOUGH LIFESTYLE FACTORS ARE THE MAIN CAUSES, CURRENT EVIDENCE SUGGESTS THAT LONG-TERM EXPOSURE TO AIR POLLUTION MAY ADDITIONALLY INCREASE THE RISK FOR TYPE 2 DIABETES. SUPPORTING EVIDENCE FOR A CAUSAL ROLE OF AIR POLLUTION IS PROVIDED BY STUDIES ADDRESSING THE REGULATION OF THE BLOOD GLUCOSE LEVELS IN METABOLICALLY HEALTHY PARTICIPANTS, INSULIN SENSITIVITY, OR PREGNANCY-RELATED DIABETES. EXPERIMENTAL STUDIES PROVIDE FURTHER SUPPORT FOR PLAUSIBLE BIOLOGICAL MECHANISMS. HOWEVER, PROSPECTIVE STUDIES ARE NEEDED TO GAIN MORE EVIDENCE, TAKING MULTIPLE LIFESTYLE AND ENVIRONMENTAL FACTORS, SUCH AS GREEN SPACE AND NOISE, AND AN IMPROVED INDIVIDUAL EXPOSURE ASSESSMENT INTO ACCOUNT.THE AGING POPULATION HAS AN INCREASED RISK OF NEURODEGENERATIVE DISEASES. FIRST STUDIES POINT TOWARDS A CONTRIBUTION OF CHRONIC EXPOSURE TO AIR POLLUTION, SPECIFICALLY BY PARTICULATE MATTER. SEVERAL STUDIES REPORT ITS ASSOCIATION WITH DECREASED NEUROCOGNITIVE CAPACITY OR AN INCREASED PREVALENCE OF DEMENTIA OR ALZHEIMER'S DISEASE IN ADULTS. HOWEVER, THE STUDIES ARE INHOMOGENEOUS REGARDING DESIGN, EXPOSURE AND OUTCOME, LEADING TO INCONSISTENT RESULTS. WITH RESPECT TO THE INFLUENCE ON NEUROCOGNITIVE DEVELOPMENT OF CHILDREN, FIRST STUDIES SUGGEST AN ASSOCIATION BETWEEN THE LEVEL OF AIR POLLUTION, E. G. AT SCHOOL, AND DELAYED COGNITIVE DEVELOPMENT.EVEN THOUGH THE EVIDENCE FOR THE DIFFERENT BIOLOGICAL ENDPOINTS DURING PREGNANCY IS STILL HETEROGENEOUS, THE STUDIES GENERALLY POINT TOWARDS AN ADVERSE IMPACT OF AIR POLLUTION ON THE MATERNAL AND FETAL ORGANISMS. THE STRONGEST EVIDENCE EXISTS FOR LOW BIRTH WEIGHT, WITH SMALL EFFECT SIZES OF ONLY SOME GRAMS, AND FOR A HIGHER INCIDENCE OF REDUCED BIRTH WEIGHT (< 2500 G). AN INCREASED RISK FOR GESTATIONAL HYPERTENSION AND PREECLAMPSIA UNDERSCORES THE POSSIBLE IMPACT OF EXPOSURE TO AIR POLLUTION ON THE MATERNAL ORGANISM. HOWEVER, THE CURRENT BODY OF EVIDENCE DOES NOT YET ALLOW A FINAL CONCLUSION ON THE INFLUENCE OF INTRAUTERINE EXPOSURE TO AIR POLLUTION REGARDING EARLY CHILDHOOD LUNG FUNCTION AND DEVELOPMENT OF ALLERGIES, PARTICULARLY IN LIGHT OF THE FACT THAT IT IS HARD TO DISTINGUISH IN EPIDEMIOLOGICAL STUDIES BETWEEN THE EFFECTS OF PRE- AND POSTNATAL EXPOSURE.	2019	

19 6834  32 [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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
20 4112  48 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