1 5174 110 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 2 298 43 AIR POLLUTION AND AIRWAY DISEASE. EPIDEMIOLOGICAL AND TOXICOLOGICAL RESEARCH CONTINUES TO SUPPORT A LINK BETWEEN URBAN AIR POLLUTION AND AN INCREASED INCIDENCE AND/OR SEVERITY OF AIRWAY DISEASE. DETRIMENTAL EFFECTS OF OZONE (O(3)), NITROGEN DIOXIDE (NO(2)) AND PARTICULATE MATTER (PM), AS WELL AS TRAFFIC-RELATED POLLUTION AS A WHOLE, ON RESPIRATORY SYMPTOMS AND FUNCTION ARE WELL DOCUMENTED. NOT ONLY DO WE HAVE STRONG EPIDEMIOLOGICAL EVIDENCE OF A RELATIONSHIP BETWEEN AIR POLLUTION AND EXACERBATION OF ASTHMA AND RESPIRATORY MORBIDITY AND MORTALITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), BUT RECENT STUDIES, PARTICULARLY IN URBAN AREAS, HAVE SUGGESTED A ROLE FOR POLLUTANTS IN THE DEVELOPMENT OF BOTH ASTHMA AND COPD. SIMILARLY, WHILE PREVALENCE AND SEVERITY OF ATOPIC CONDITIONS APPEAR TO BE MORE COMMON IN URBAN COMPARED WITH RURAL COMMUNITIES, EVIDENCE IS EMERGING THAT TRAFFIC-RELATED POLLUTANTS MAY CONTRIBUTE TO THE DEVELOPMENT OF ALLERGY. FURTHERMORE, NUMEROUS EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES SUGGEST AN ASSOCIATION BETWEEN EXPOSURE TO NO(2) , O(3) , PM AND COMBUSTION PRODUCTS OF BIOMASS FUELS AND AN INCREASED SUSCEPTIBILITY TO AND MORBIDITY FROM RESPIRATORY INFECTION. GIVEN THE CONSIDERABLE CONTRIBUTION THAT TRAFFIC EMISSIONS MAKE TO URBAN AIR POLLUTION RESEARCHERS HAVE SOUGHT TO CHARACTERIZE THE RELATIVE TOXICITY OF TRAFFIC-RELATED PM POLLUTANTS. RECENT ADVANCES IN MECHANISMS IMPLICATED IN THE ASSOCIATION OF AIR POLLUTANTS AND AIRWAY DISEASE INCLUDE EPIGENETIC ALTERATION OF GENES BY COMBUSTION-RELATED POLLUTANTS AND HOW POLYMORPHISMS IN GENES INVOLVED IN ANTIOXIDANT PATHWAYS AND AIRWAY INFLAMMATION CAN MODIFY RESPONSES TO AIR POLLUTION EXPOSURES. OTHER INTERESTING EPIDEMIOLOGICAL OBSERVATIONS RELATED TO INCREASED HOST SUSCEPTIBILITY INCLUDE A POSSIBLE LINK BETWEEN CHRONIC PM EXPOSURE DURING CHILDHOOD AND VULNERABILITY TO COPD IN ADULTHOOD, AND THAT INFANTS SUBJECTED TO HIGHER PRENATAL LEVELS OF AIR POLLUTION MAY BE AT GREATER RISK OF DEVELOPING RESPIRATORY CONDITIONS. WHILE THE CHARACTERIZATION OF POLLUTANT COMPONENTS AND SOURCES PROMISE TO GUIDE POLLUTION CONTROL STRATEGIES, THE IDENTIFICATION OF SUSCEPTIBLE SUBPOPULATIONS WILL BE NECESSARY IF TARGETED THERAPY/PREVENTION OF POLLUTION-INDUCED RESPIRATORY DISEASES IS TO BE DEVELOPED. 2011 3 4954 27 PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. THE PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) ENCOMPASSES A NUMBER OF INJURIOUS PROCESSES, INCLUDING AN ABNORMAL INFLAMMATORY RESPONSE IN THE LUNGS TO INHALED PARTICLES AND GASES. OTHER PROCESSES, SUCH AS FAILURE TO RESOLVE INFLAMMATION, ABNORMAL CELL REPAIR, APOPTOSIS, ABNORMAL CELLULAR MAINTENANCE PROGRAMS, EXTRACELLULAR MATRIX DESTRUCTION (PROTEASE/ANTIPROTEASE IMBALANCE), AND OXIDATIVE STRESS (OXIDANT/ANTIOXIDANT IMBALANCE) ALSO HAVE A ROLE. THE INFLAMMATORY RESPONSES TO THE INHALATION OF ACTIVE AND PASSIVE TOBACCO SMOKE AND URBAN AND RURAL AIR POLLUTION ARE MODIFIED BY GENETIC AND EPIGENETIC FACTORS. THE SUBSEQUENT CHRONIC INFLAMMATORY RESPONSES LEAD TO MUCUS HYPERSECRETION, AIRWAY REMODELING, AND ALVEOLAR DESTRUCTION. THIS ARTICLE PROVIDES AN UPDATE ON THE CELLULAR AND MOLECULAR MECHANISMS OF THESE PROCESSES IN THE PATHOGENESIS OF COPD. 2007 4 6440 22 THERAPEUTIC APPROACHES FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) EXACERBATIONS. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A PROGRESSIVE PULMONARY DISORDER UNDERPINNED BY POORLY REVERSIBLE AIRFLOW RESULTING FROM CHRONIC BRONCHITIS OR EMPHYSEMA. THE PREVALENCE AND MORTALITY OF COPD CONTINUE TO INCREASE. PHARMACOTHERAPY FOR PATIENTS WITH COPD HAS INCLUDED ANTIBIOTICS, BRONCHODILATORS, AND ANTI-INFLAMMATORY CORTICOSTEROIDS (BUT WITH LITTLE SUCCESS). ORAL DISEASES HAVE LONG BEEN ESTABLISHED AS CLINICAL RISK FACTORS FOR DEVELOPING RESPIRATORY DISEASES. THE ESTABLISHMENT OF A VERY SIMILAR MICROBIOME IN THE MOUTH AND THE LUNG CONFIRMS THE ORAL-LUNG CONNECTION. THE ASPIRATION OF PATHOGENIC MICROBES FROM THE ORAL CAVITY HAS BEEN IMPLICATED IN SEVERAL RESPIRATORY DISEASES, INCLUDING PNEUMONIA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). THIS REVIEW FOCUSES ON CURRENT AND FUTURE PHARMACOTHERAPEUTIC APPROACHES FOR COPD EXACERBATION INCLUDING ANTIMICROBIALS, MUCOREGULATORS, THE USE OF BRONCHODILATORS AND ANTI-INFLAMMATORY DRUGS, MODIFYING EPIGENETIC MARKS, AND MODULATING DYSBIOSIS OF THE MICROBIOME. 2022 5 360 33 AMBIENT AIR POLLUTION AND BIOMARKERS OF HEALTH EFFECT. RECENTLY, THE AIR POLLUTION SITUATION OF OUR COUNTRY IS VERY SERIOUS ALONG WITH THE DEVELOPMENT OF URBANIZATION AND INDUSTRIALIZATION. STUDIES INDICATE THAT THE EXPOSURE OF AIR POLLUTION CAN CAUSE A RISE OF INCIDENCE AND MORTALITY OF MANY DISEASES, SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), ASTHMA, MYOCARDIAL INFARCTION, AND SO ON. HOWEVER, THERE IS NOW GROWING EVIDENCE SHOWING THAT SIGNIFICANT AIR POLLUTION EXPOSURES ARE ASSOCIATED WITH EARLY BIOMARKERS IN VARIOUS SYSTEMS OF THE BODY. IN ORDER TO BETTER PREVENT AND CONTROL THE DAMAGE EFFECT OF AIR POLLUTION, THIS ARTICLE SUMMARIZES COMPREHENSIVELY EPIDEMIOLOGICAL STUDIES ABOUT THE BAD EFFECTS ON THE BIOMARKERS OF RESPIRATORY SYSTEM, CARDIOVASCULAR SYSTEM, AND GENETIC AND EPIGENETIC SYSTEM EXPOSURE TO AMBIENT AIR POLLUTION. 2017 6 5254 40 PROGRAMMING OF RESPIRATORY HEALTH IN CHILDHOOD: INFLUENCE OF OUTDOOR AIR POLLUTION. PURPOSE OF REVIEW: THIS OVERVIEW HIGHLIGHTS RECENT EXPERIMENTAL AND EPIDEMIOLOGICAL EVIDENCE FOR THE PROGRAMMING EFFECTS OF OUTDOOR AIR POLLUTION EXPOSURES DURING EARLY DEVELOPMENT ON LUNG FUNCTION AND CHRONIC RESPIRATORY DISORDERS, SUCH AS ASTHMA AND RELATED ALLERGIC DISORDERS. RECENT FINDINGS: AIR POLLUTANTS MAY IMPACT ANATOMY AND/OR PHYSIOLOGICAL FUNCTIONING OF THE LUNG AND INTERRELATED SYSTEMS. PROGRAMMING EFFECTS MAY RESULT FROM POLLUTANT-INDUCED SHIFTS IN A NUMBER OF MOLECULAR, CELLULAR, AND PHYSIOLOGICAL STATES AND THEIR INTERACTING SYSTEMS. SPECIFIC KEY REGULATORY SYSTEMS SUSCEPTIBLE TO PROGRAMMING MAY INFLUENCE LUNG DEVELOPMENT AND VULNERABILITY TO RESPIRATORY DISEASES, INCLUDING BOTH CENTRAL AND PERIPHERAL COMPONENTS OF NEUROENDOCRINE PATHWAYS AND AUTONOMIC NERVOUS SYSTEM (ANS) FUNCTIONING WHICH, IN TURN, INFLUENCE THE IMMUNE SYSTEM. STARTING IN UTERO, ENVIRONMENTAL FACTORS, INCLUDING AIR POLLUTANTS, MAY PERMANENTLY ORGANIZE THESE SYSTEMS TOWARD TRAJECTORIES OF ENHANCED PEDIATRIC (E.G., ASTHMA, ALLERGY) AS WELL AS ADULT DISEASE RISK (E.G., CHRONIC OBSTRUCTIVE PULMONARY DISEASE). EVIDENCE SUPPORTS A CENTRAL ROLE OF OXIDATIVE STRESS IN THE TOXIC EFFECTS OF AIR POLLUTION. ADDITIONAL RESEARCH SUGGESTS XENOBIOTIC METABOLISM AND SUBCELLULAR COMPONENTS, SUCH AS MITOCHONDRIA ARE TARGETS OF AMBIENT AIR POLLUTION AND PLAY A ROLE IN ASTHMA AND ALLERGY PROGRAMMING. MECHANISMS OPERATING AT THE LEVEL OF THE PLACENTA ARE BEING ELUCIDATED. EPIGENETIC MECHANISMS MAY BE AT THE ROOTS OF ADAPTIVE DEVELOPMENTAL PROGRAMMING. SUMMARY: OPTIMAL COORDINATED FUNCTIONING OF MANY COMPLEX PROCESSES AND THEIR NETWORKS OF INTERACTION ARE NECESSARY FOR NORMAL LUNG DEVELOPMENT AND THE MAINTENANCE OF RESPIRATORY HEALTH. OUTDOOR AIR POLLUTION MAY PLAY AN IMPORTANT ROLE IN EARLY PROGRAMMING OF RESPIRATORY HEALTH AND IS POTENTIALLY AMENABLE TO INTERVENTION. 2013 7 2737 36 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 8 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 9 3698 31 INFLAMMATORY MECHANISMS LINKING MATERNAL AND CHILDHOOD ASTHMA. ASTHMA IS A CHRONIC INFLAMMATORY AIRWAY DISEASE CHARACTERIZED BY AIRWAY HYPERRESPONSIVENESS, INFLAMMATION, AND REMODELING. ASTHMA OFTEN DEVELOPS DURING CHILDHOOD AND CAUSES LIFELONG DECREMENTS IN LUNG FUNCTION AND QUALITY OF LIFE. RISK FACTORS FOR CHILDHOOD ASTHMA ARE NUMEROUS AND INCLUDE GENETIC, EPIGENETIC, DEVELOPMENTAL, AND ENVIRONMENTAL FACTORS. UNCONTROLLED MATERNAL ASTHMA DURING PREGNANCY EXPOSES THE DEVELOPING FETUS TO INFLAMMATORY INSULTS, WHICH FURTHER INCREASE THE RISK OF CHILDHOOD ASTHMA INDEPENDENT OF GENETIC PREDISPOSITION. THIS REVIEW FOCUSES ON THE ROLE OF MATERNAL ASTHMA IN THE DEVELOPMENT OF ASTHMA IN OFFSPRING. WE WILL PRESENT MATERNAL ASTHMA AS A TARGETABLE AND MODIFIABLE RISK FACTOR FOR CHILDHOOD ASTHMA AND DISCUSS THE MECHANISMS BY WHICH MATERNAL INFLAMMATION INCREASES CHILDHOOD ASTHMA RISK. TOPICS INCLUDE HOW EXPOSURE TO MATERNAL ASTHMA IN UTERO SHAPES STRUCTURAL LUNG DEVELOPMENT WITH A SPECIAL EMPHASIS ON AIRWAY NERVES, HOW MATERNAL TYPE-2 CYTOKINES SUCH AS IL-5 ACTIVATE THE FETAL IMMUNE SYSTEM, AND HOW CHANGES IN LUNG AND IMMUNE CELL DEVELOPMENT INFORM RESPONSES TO AERO-ALLERGENS LATER IN LIFE. FINALLY, WE HIGHLIGHT EMERGING EVIDENCE THAT MATERNAL ASTHMA ESTABLISHES A UNIQUE "ASTHMA SIGNATURE" IN THE AIRWAYS OF CHILDREN, LEADING TO NOVEL MECHANISMS OF AIRWAY HYPERREACTIVITY AND INFLAMMATORY CELL RESPONSES. 2020 10 363 39 AMBIENT AIR POLLUTION: HEALTH HAZARDS TO CHILDREN. AMBIENT AIR POLLUTION IS PRODUCED BY SOURCES INCLUDING VEHICULAR TRAFFIC, COAL-FIRED POWER PLANTS, HYDRAULIC FRACTURING, AGRICULTURAL PRODUCTION, AND FOREST FIRES. IT CONSISTS OF PRIMARY POLLUTANTS GENERATED BY COMBUSTION AND SECONDARY POLLUTANTS FORMED IN THE ATMOSPHERE FROM PRECURSOR GASES. AIR POLLUTION CAUSES AND EXACERBATES CLIMATE CHANGE, AND CLIMATE CHANGE WORSENS HEALTH EFFECTS OF AIR POLLUTION. INFANTS AND CHILDREN ARE UNIQUELY SENSITIVE TO AIR POLLUTION, BECAUSE THEIR ORGANS ARE DEVELOPING AND THEY HAVE HIGHER AIR PER BODY WEIGHT INTAKE. HEALTH EFFECTS LINKED TO AIR POLLUTION INCLUDE NOT ONLY EXACERBATIONS OF RESPIRATORY DISEASES BUT ALSO REDUCED LUNG FUNCTION DEVELOPMENT AND INCREASED ASTHMA INCIDENCE. ADDITIONAL OUTCOMES OF CONCERN INCLUDE PRETERM BIRTH, LOW BIRTH WEIGHT, NEURODEVELOPMENTAL DISORDERS, IQ LOSS, PEDIATRIC CANCERS, AND INCREASED RISKS FOR ADULT CHRONIC DISEASES. THESE EFFECTS ARE MEDIATED BY OXIDATIVE STRESS, CHRONIC INFLAMMATION, ENDOCRINE DISRUPTION, AND GENETIC AND EPIGENETIC MECHANISMS ACROSS THE LIFE SPAN. NATURAL EXPERIMENTS DEMONSTRATE THAT WITH INITIATIVES SUCH AS INCREASED USE OF PUBLIC TRANSPORTATION, BOTH AIR QUALITY AND COMMUNITY HEALTH IMPROVE. SIMILARLY, THE CLEAN AIR ACT HAS IMPROVED AIR QUALITY, ALTHOUGH EXPOSURE INEQUITIES PERSIST. OTHER EFFECTIVE STRATEGIES FOR REDUCING AIR POLLUTION INCLUDE ENDING RELIANCE ON COAL, OIL, AND GAS; REGULATING INDUSTRIAL EMISSIONS; REDUCING EXPOSURE WITH ATTENTION TO PROXIMITY OF RESIDENCES, SCHOOLS, AND CHILD CARE FACILITIES TO TRAFFIC; AND A GREATER AWARENESS OF THE AIR QUALITY INDEX. THIS POLICY REVIEWS BOTH SHORT- AND LONG-TERM HEALTH CONSEQUENCES OF AMBIENT AIR POLLUTION, ESPECIALLY IN RELATION TO DEVELOPMENTAL EXPOSURES. IT EXAMINES INDIVIDUAL, COMMUNITY, AND LEGISLATIVE STRATEGIES TO MITIGATE AIR POLLUTION. 2021 11 1143 31 CONCISE REVIEW: CLINICAL PROSPECTS FOR TREATING CHRONIC OBSTRUCTIVE PULMONARY DISEASE WITH REGENERATIVE APPROACHES. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS BECOMING A MAJOR CAUSE OF DEATH WORLDWIDE. COPD IS CHARACTERIZED BY A PROGRESSIVE AND NOT FULLY REVERSIBLE AIRFLOW LIMITATION CAUSED BY CHRONIC SMALL AIRWAY DISEASE AND LUNG PARENCHYMAL DESTRUCTION. CLINICALLY AVAILABLE DRUGS IMPROVE AIRFLOW OBSTRUCTION AND RESPIRATORY SYMPTOMS BUT CANNOT CURE THE DISEASE. SLOWING THE PROGRESSIVE LUNG DESTRUCTION OR REBUILDING THE DESTROYED LUNG STRUCTURE IS A PROMISING STRATEGY TO CURE COPD. IN CONTRAST TO SMALL ANIMAL MODELS, PHARMACOLOGICAL LUNG REGENERATION IS DIFFICULT IN HUMAN COPD. MATURATION, AGING, AND SENESCENCE IN COPD LUNG CELLS, INCLUDING ENDOGENOUS STEM CELLS, MAY AFFECT THE REGENERATIVE CAPACITY FOLLOWING PHARMACOLOGICAL THERAPY. THE LUNG IS A COMPLEX ORGAN COMPOSED OF MORE THAN 40 DIFFERENT CELL TYPES; THEREFORE, DETAILED ANALYSES, SUCH AS EPIGENETIC MODIFICATION ANALYSIS, IN EACH SPECIFIC CELL TYPE HAVE NOT BEEN PERFORMED IN LUNGS WITH COPD. RECENTLY, A METHOD FOR THE DIRECT ISOLATION OF INDIVIDUAL CELL TYPES FROM HUMAN LUNG HAS BEEN DEVELOPED, AND FINGERPRINTS OF EACH CELL TYPE IN COPD LUNGS CAN BE ANALYZED. RESEARCH USING THIS TECHNIQUE COMBINED WITH THE RECENTLY DISCOVERED LUNG ENDOGENOUS STEM-PROGENITOR POPULATIONS WILL GIVE A BETTER UNDERSTANDING ABOUT THE FATE OF COPD LUNG CELLS AND PROVIDE A FUTURE FOR CELL-BASED THERAPY TO TREAT THIS INTRACTABLE DISEASE. 2012 12 3966 31 LONG NONCODING TRANSCRIPTOME IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC AIRWAY INFLAMMATION FROM RECURRING EXPOSURES TO NOXIOUS ENVIRONMENTAL STIMULI RESULTS IN A PROGRESSIVE AND IRREVERSIBLE AIRFLOW LIMITATION AND THE LUNG PARENCHYMAL DAMAGE THAT CHARACTERIZES CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). THE LARGE VARIABILITY OBSERVED IN THE ONSET AND PROGRESSION OF COPD IS PRIMARILY DRIVEN BY COMPLEX GENE-ENVIRONMENT INTERACTIONS. THE TRANSCRIPTOMIC AND EPIGENETIC MEMORY POTENTIAL OF LUNG EPITHELIAL AND INNATE IMMUNE CELLS DRIVE RESPONSES, SUCH AS MUCUS HYPERREACTIVITY AND AIRWAY REMODELING, THAT ARE TIGHTLY REGULATED BY VARIOUS MOLECULAR MECHANISMS, FOR WHICH SEVERAL CANDIDATE SUSCEPTIBILITY GENES HAVE BEEN DESCRIBED. HOWEVER, THE RECENTLY DESCRIBED NONCODING RNA SPECIES, IN PARTICULAR THE LONG NONCODING RNAS, MAY ALSO HAVE AN IMPORTANT ROLE IN MODULATING PULMONARY RESPONSES TO CHRONIC INHALATION OF TOXIC SUBSTANCES AND THE DEVELOPMENT OF COPD. THIS REVIEW OUTLINES THE FEATURES OF LONG NONCODING RNAS THAT HAVE BEEN IMPLICATED IN REGULATING THE AIRWAY INFLAMMATORY RESPONSES TO CIGARETTE SMOKE EXPOSURE AND THEIR POSSIBLE ASSOCIATION WITH COPD PATHOGENESIS. AS COPD CONTINUES TO DEBILITATE THE INCREASINGLY AGING POPULATION AND CONTRIBUTE TO HIGHER MORBIDITY AND MORTALITY RATES WORLDWIDE, THE SEARCH FOR BETTER BIOMARKERS AND ALTERNATIVE THERAPEUTIC OPTIONS IS PIVOTAL. 2019 13 4116 34 MECHANISMS OF AIRWAY EPITHELIAL INJURY AND ABNORMAL REPAIR IN ASTHMA AND COPD. THE AIRWAY EPITHELIUM COMPRISES OF DIFFERENT CELL TYPES AND ACTS AS A PHYSICAL BARRIER PREVENTING PATHOGENS, INCLUDING INHALED PARTICLES AND MICROBES, FROM ENTERING THE LUNGS. GOBLET CELLS AND SUBMUCOSAL GLANDS PRODUCE MUCUS THAT TRAPS PATHOGENS, WHICH ARE EXPELLED FROM THE RESPIRATORY TRACT BY CILIATED CELLS. BASAL CELLS ACT AS PROGENITOR CELLS, DIFFERENTIATING INTO DIFFERENT EPITHELIAL CELL TYPES, TO MAINTAIN HOMEOSTASIS FOLLOWING INJURY. ADHERENS AND TIGHT JUNCTIONS BETWEEN CELLS MAINTAIN THE EPITHELIAL BARRIER FUNCTION AND REGULATE THE MOVEMENT OF MOLECULES ACROSS IT. IN THIS REVIEW WE DISCUSS HOW ABNORMAL EPITHELIAL STRUCTURE AND FUNCTION, CAUSED BY CHRONIC INJURY AND ABNORMAL REPAIR, DRIVES AIRWAY DISEASE AND SPECIFICALLY ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). IN BOTH DISEASES, INHALED ALLERGENS, POLLUTANTS AND MICROBES DISRUPT JUNCTIONAL COMPLEXES AND PROMOTE CELL DEATH, IMPAIRING THE BARRIER FUNCTION AND LEADING TO INCREASED PENETRATION OF PATHOGENS AND A CONSTANT AIRWAY IMMUNE RESPONSE. IN ASTHMA, THE INFLAMMATORY RESPONSE PRECIPITATES THE EPITHELIAL INJURY AND DRIVES ABNORMAL BASAL CELL DIFFERENTIATION. THIS LEADS TO REDUCED CILIATED CELLS, GOBLET CELL HYPERPLASIA AND INCREASED EPITHELIAL MESENCHYMAL TRANSITION, WHICH CONTRIBUTE TO IMPAIRED MUCOCILIARY CLEARANCE AND AIRWAY REMODELLING. IN COPD, CHRONIC OXIDATIVE STRESS AND INFLAMMATION TRIGGER PREMATURE EPITHELIAL CELL SENESCENCE, WHICH CONTRIBUTES TO LOSS OF EPITHELIAL INTEGRITY AND AIRWAY INFLAMMATION AND REMODELLING. INCREASED NUMBERS OF BASAL CELLS SHOWING DEREGULATED DIFFERENTIATION, CONTRIBUTES TO CILIARY DYSFUNCTION AND MUCOUS HYPERPRODUCTION IN COPD AIRWAYS. DEFECTIVE ANTIOXIDANT, ANTIVIRAL AND DAMAGE REPAIR MECHANISMS, POSSIBLY DUE TO GENETIC OR EPIGENETIC FACTORS, MAY CONFER SUSCEPTIBILITY TO AIRWAY EPITHELIAL DYSFUNCTION IN THESE DISEASES. THE CURRENT EVIDENCE SUGGESTS THAT A CONSTANT CYCLE OF INJURY AND ABNORMAL REPAIR OF THE EPITHELIUM DRIVES CHRONIC AIRWAY INFLAMMATION AND REMODELLING IN ASTHMA AND COPD. MECHANISTIC UNDERSTANDING OF INJURY SUSCEPTIBILITY AND DAMAGE RESPONSE MAY LEAD TO IMPROVED THERAPIES FOR THESE DISEASES. 2023 14 5916 25 TARGETING AGING PATHWAYS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) HAS BECOME A GLOBAL EPIDEMIC AND IS THE THIRD LEADING CAUSE OF DEATH WORLDWIDE. COPD IS CHARACTERIZED BY CHRONIC AIRWAY INFLAMMATION, LOSS OF ALVEOLAR-CAPILLARY UNITS, AND PROGRESSIVE DECLINE IN LUNG FUNCTION. MAJOR RISK FACTORS FOR COPD ARE CIGARETTE SMOKING AND AGING. COPD-ASSOCIATED PATHOMECHANISMS INCLUDE MULTIPLE AGING PATHWAYS SUCH AS TELOMERE ATTRITION, EPIGENETIC ALTERATIONS, ALTERED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELL SENESCENCE, STEM CELL EXHAUSTION AND CHRONIC INFLAMMATION. IN THIS REVIEW, WE WILL HIGHLIGHT THE CURRENT LITERATURE THAT FOCUSES ON THE ROLE OF AGE AND AGING-ASSOCIATED SIGNALING PATHWAYS AS WELL AS THEIR IMPACT ON CURRENT TREATMENT STRATEGIES IN THE PATHOGENESIS OF COPD. FURTHERMORE, WE WILL DISCUSS ESTABLISHED AND EXPERIMENTAL COPD TREATMENTS INCLUDING SENOLYTIC AND ANTI-AGING THERAPIES AND THEIR POTENTIAL USE AS NOVEL TREATMENT STRATEGIES IN COPD. 2020 15 6330 30 THE ROLE OF CIGARETTE SMOKE-INDUCED PULMONARY VASCULAR ENDOTHELIAL CELL APOPTOSIS IN COPD. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS ONE OF THE MOST COMMON CHRONIC RESPIRATORY DISEASES WITH HIGH MORBIDITY AND MORTALITY. IT HAS BECOME THE FIFTH MOST BURDENED AND THE THIRD MOST DEADLY DISEASE IN THE GLOBAL ECONOMY AND INCREASES YEAR BY YEAR. THE PREVENTION AND TREATMENT OF COPD ARE URGENT. SMOKING IS THE MAIN AND MOST COMMON RISK FACTOR FOR COPD. CIGARETTE SMOKE (CS) CONTAINS A LARGE NUMBER OF TOXIC SUBSTANCES, CAN CAUSE A SERIES OF CHANGES IN THE TRACHEA, LUNG TISSUE, PULMONARY BLOOD VESSELS, AND PROMOTES THE OCCURRENCE AND DEVELOPMENT OF COPD. IN RECENT YEARS, THE DEVELOPMENT OF EPIGENETICS AND MOLECULAR BIOLOGY HAVE PROVIDED NEW GUIDANCE FOR REVEALING THE PATHOGENESIS, DIAGNOSIS, AND TREATMENT OF DISEASES. THE LATEST RESEARCH INDICATES THAT PULMONARY VASCULAR ENDOTHELIAL CELL APOPTOSIS INITIATES AND PARTICIPATES IN THE PATHOGENESIS OF COPD. IN THIS REVIEW, WE SUMMARIZE THE CURRENT RESEARCH ON THE EPIGENETIC MECHANISMS AND MOLECULAR BIOLOGY OF CS-INDUCED PULMONARY VASCULAR ENDOTHELIAL CELL APOPTOSIS IN COPD, PROVIDING A NEW RESEARCH DIRECTION FOR PATHOGENESIS OF COPD AND A NEW TARGET FOR THE DIAGNOSIS, TREATMENT, AND PREVENTION OF COPD. 2021 16 4317 31 MICRORNAS AS REGULATORS OF AIRBORNE POLLUTION-INDUCED LUNG INFLAMMATION AND CARCINOGENESIS. THE INCREASING INCIDENCE OF PULMONARY INFLAMMATION AND LUNG CANCER, AS WELL AS EXACERBATION OF PRE-EXISTING CHRONIC LUNG DISEASES BY EXPOSURE TO AIRBORNE POLLUTANTS, E.G., PARTICULATE MATTER AND CIGARETTE SMOKE, IS BECOMING A MAJOR PUBLIC HEALTH CONCERN IN THE WORLD. HOWEVER, THE EXACT MECHANISMS OF PULMONARY INJURY FROM EXPOSURE TO THESE AIRBORNE INSULTS HAVE NOT BEEN FULLY ELUCIDATED. NEVERTHELESS, ACCUMULATING EVIDENCE SUGGESTS THAT MICRORNAS (MIRNAS) MAY PLAY A UNIQUE ROLE IN THE REGULATION OF AIRBORNE AGENT-INDUCED LUNG INFLAMMATION AND CARCINOGENESIS. SINCE EPIGENETIC MODIFICATIONS ARE HERITABLE AND REVERSIBLE, THIS MAY PROVIDE A NEW INSIGHT INTO THE RELATIONSHIP OF MIRNAS AND ENVIRONMENTAL POLLUTION-RELATED LUNG DISORDERS. THE AIM OF THIS REVIEW WAS TO UPDATE OUR EXISTING KNOWLEDGE REGARDING THE MECHANISMS BY WHICH AIRBORNE POLLUTANTS ALTERING MIRNA PROFILES IN THE LUNG, SPECIFICALLY FOR CIGARETTE SMOKE AND AIRBORNE PARTICULATE MATTER, AND THE POTENTIAL BIOLOGICAL ROLES OF MIRNAS IN THE INITIATION OF PULMONARY INFLAMMATION AND LUNG CANCER, AS WELL AS THE REGULATION OF UNDERLYING GENETIC SUSCEPTIBILITY TO THESE ENVIRONMENTAL STRESSORS. 2015 17 299 41 AIR POLLUTION AND DNA METHYLATION: EFFECTS OF EXPOSURE IN HUMANS. AIR POLLUTION EXPOSURE IS ESTIMATED TO CONTRIBUTE TO APPROXIMATELY SEVEN MILLION EARLY DEATHS EVERY YEAR WORLDWIDE AND MORE THAN 3% OF DISABILITY-ADJUSTED LIFE YEARS LOST. AIR POLLUTION HAS NUMEROUS HARMFUL EFFECTS ON HEALTH AND CONTRIBUTES TO THE DEVELOPMENT AND MORBIDITY OF CARDIOVASCULAR DISEASE, METABOLIC DISORDERS, AND A NUMBER OF LUNG PATHOLOGIES, INCLUDING ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). EMERGING DATA INDICATE THAT AIR POLLUTION EXPOSURE MODULATES THE EPIGENETIC MARK, DNA METHYLATION (DNAM), AND THAT THESE CHANGES MIGHT IN TURN INFLUENCE INFLAMMATION, DISEASE DEVELOPMENT, AND EXACERBATION RISK. SEVERAL TRAFFIC-RELATED AIR POLLUTION (TRAP) COMPONENTS, INCLUDING PARTICULATE MATTER (PM), BLACK CARBON (BC), OZONE (O(3)), NITROGEN OXIDES (NO(X)), AND POLYAROMATIC HYDROCARBONS (PAHS), HAVE BEEN ASSOCIATED WITH CHANGES IN DNAM; TYPICALLY LOWERING DNAM AFTER EXPOSURE. EFFECTS OF AIR POLLUTION ON DNAM HAVE BEEN OBSERVED ACROSS THE HUMAN LIFESPAN, BUT IT IS NOT YET CLEAR WHETHER EARLY LIFE DEVELOPMENTAL SENSITIVITY OR THE ACCUMULATION OF EXPOSURES HAVE THE MOST SIGNIFICANT EFFECTS ON HEALTH. AIR POLLUTION EXPOSURE-ASSOCIATED DNAM PATTERNS ARE OFTEN CORRELATED WITH LONG-TERM NEGATIVE RESPIRATORY HEALTH OUTCOMES, INCLUDING THE DEVELOPMENT OF LUNG DISEASES, A FOCUS IN THIS REVIEW. RECENTLY, INTERVENTIONS SUCH AS EXERCISE AND B VITAMINS HAVE BEEN PROPOSED TO REDUCE THE IMPACT OF AIR POLLUTION ON DNAM AND HEALTH. ULTIMATELY, IMPROVED KNOWLEDGE OF HOW EXPOSURE-INDUCED CHANGE IN DNAM IMPACTS HEALTH, BOTH ACUTELY AND CHRONICALLY, MAY ENABLE PREVENTATIVE AND REMEDIAL STRATEGIES TO REDUCE MORBIDITY IN POLLUTED ENVIRONMENTS. 2019 18 5255 26 PROGRESS IN UNDERSTANDING THE PATHOGENESIS OF BPD USING THE BABOON AND SHEEP MODELS. BRONCHOPULMONARY DYSPLASIA (BPD) IS AMONG THE MOST COMMON CHRONIC LUNG DISEASES IN INFANTS IN THE US. IMPROVED SURVIVAL OF PRETERM INFANTS WHO DEVELOPED BPD IS BECOMING INCREASINGLY IMPORTANT BECAUSE OF THE HIGH RISK FOR PERSISTENT PULMONARY MORBIDITIES SUCH AS POOR RESPIRATORY GAS EXCHANGE, PULMONARY HYPERTENSION, AND EXCESS AIRWAY EXPIRATORY RESISTANCE LATER IN LIFE. THIS REVIEW FOCUSES ON UNIQUE INSIGHTS PROVIDED BY THE TWO LARGE-ANIMAL, PHYSIOLOGICAL MODELS OF NEONATAL CHRONIC LUNG DISEASE: PRETERM BABOONS AND PRETERM LAMBS. THE MODELS' ARE VALUABLE BECAUSE THEY CONTRIBUTE TO BETTER UNDERSTANDING OF THE UNDERLYING MOLECULAR PATHOGENIC MECHANISMS. AN EPIGENETIC HYPOTHESIS IS PROPOSED AS A PATHOGENIC MECHANISM FOR BPD AND ITS PERSISTENT PULMONARY MORBIDITIES. 2013 19 927 30 CHRONIC INFLAMMATION, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, AND LUNG CANCER. PURPOSE OF REVIEW: SMOKING IS A MAJOR RISK FACTOR FOR LUNG CANCER, WHICH IS THE LEADING CAUSE OF CANCER-RELATED DEATHS BOTH IN THE USA AND WORLDWIDE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND EMPHYSEMA ARE COMORBID CONDITIONS OFTEN FOUND IN LUNG CANCER PATIENTS. THE INFLAMMATORY PATHWAYS THAT LINK CHRONIC OBSTRUCTIVE PULMONARY DISEASE, EMPHYSEMA, AND LUNG CANCER LIKELY INVOLVE GENETIC AND EPIGENETIC MODULATIONS DUE TO CHRONIC TISSUE INJURY AND ABNORMAL TUMOR IMMUNITY IN SUSCEPTIBLE HOSTS. RECENT FINDINGS: CHRONIC AIRWAY INFLAMMATION CONTRIBUTES TO ALTERATIONS IN THE BRONCHIAL EPITHELIUM AND LUNG MICROENVIRONMENT, PROVOKING A MILIEU CONDUCIVE TO PULMONARY CARCINOGENESIS. FOR EXAMPLE, INFLAMMATION-INDUCIBLE CYCLOOXYGENASE-2 IS UPREGULATED IN NONSMALL CELL LUNG CANCER AND ALSO PLAYS AN IMPORTANT ROLE IN PROMOTING EPITHELIAL-TO-MESENCHYMAL TRANSITION. GENETIC CHANGES IN THE AIRWAY EPITHELIUM OF SMOKERS MAY HELP PREDICT OR IDENTIFY INDIVIDUALS AT RISK FOR LUNG CANCER. FINALLY, RADIOGRAPHIC FINDINGS OF EMPHYSEMA HAVE BEEN ESTABLISHED AS INDEPENDENT RISK FACTORS FOR LUNG CANCER. SUMMARY: THE RELATIONSHIPS BETWEEN INFLAMMATION, AIRFLOW OBSTRUCTION, AND LUNG CANCER ARE COMPLEX. DEREGULATED INFLAMMATION IS COMPLICIT IN THE PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND LUNG CANCER, BUT THE OVERLAP OF SIGNALING EVENTS IS NOT YET FULLY UNDERSTOOD. TOBACCO EXPOSURE IS AN IMPORTANT RISK FACTOR THAT CONFERS LONG-TERM RISK OF LUNG DISEASE. DIAGNOSTIC SENSITIVITY OF DETECTING LUNG CANCER MAY IMPROVE WITH THE UTILIZATION OF GENETIC PROFILING IN COMBINATION WITH PATHOLOGIC EVALUATION OF AIRWAY EPITHELIUM. ADDITIONAL RESEARCH IS REQUIRED TO UNDERSTAND THE ROLE OF EPITHELIAL-TO-MESENCHYMAL TRANSITION IN CHRONIC INFLAMMATORY LUNG DISEASES AND LUNG CARCINOGENESIS. 2009 20 973 27 CHRONIC OBSTRUCTIVE PULMONARY DISEASE: AN UPDATE ON NUCLEAR SIGNALING RELATED TO INFLAMMATION AND ANTI-INFLAMMATORY TREATMENT. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS ONE OF THE MOST FREQUENT DISEASES WORLDWIDE. CIGARETTE SMOKE IS CONSIDERED THE MAIN PATHOLOGICAL CAUSE OF THE DISORDER, ALTHOUGH EVIDENCE IS GROWING CONCERNING OTHER ETIOLOGICAL FACTORS, SUCH AS ENVIRONMENTAL POLLUTION, BIOMASS COMBUSTION, INFECTIONS, GENETIC PREDISPOSITION, WHICH MAY EXPLAIN WHY SOME INDIVIDUALS DEVELOP COPD WITH NO HISTORY OF SMOKING. CHRONIC INFLAMMATION AND REMODELING OF THE SMALL AIRWAYS CHARACTERIZE THE DISEASE AT THE CELLULAR LEVEL, AND OXIDATIVE STRESS IS CONSIDERED THE MAIN DRIVING FORCE THAT STANDS BEHIND COPD INFLAMMATION. RECENTLY, CHROMATIN REMODELING AND EPIGENETIC CHANGES HAVE BEEN FOUND TO UNDERLIE DISEASE PATHOLOGY AND PROGRESSION. IN THIS REVIEW, THE AUTHORS GAVE A SHORT UPDATE ON THE RECENT HYPOTHESIS AND FINDINGS THAT MAY IMPLY NOVEL APPROACH TO PHARMACOTHERAPY OF THE DISEASE, FOCUSING ON THE ROLE OF GLUCOCORTICOSTEROIDS, THEOPHYLLINE, AND ANTIOXIDANTS. 2008