1 1259 103 CURRENT VIEWS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATHOGENESIS AND MANAGEMENT. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A PROGRESSIVE LUNG DYSFUNCTION CAUSED MAINLY BY INHALING TOXIC PARTICLES AND CIGARETTE SMOKING (CS). THE CONTINUOUS EXPOSURE TO RUINOUS MOLECULES CAN LEAD TO ABNORMAL INFLAMMATORY RESPONSES, PERMANENT DAMAGES TO THE RESPIRATORY SYSTEM, AND IRREVERSIBLE PATHOLOGICAL CHANGES. OTHER FACTORS, SUCH AS GENETICS AND AGING, INFLUENCE THE DEVELOPMENT OF COPD. IN THE LAST DECADE, ACCUMULATING EVIDENCE SUGGESTED THAT MITOCHONDRIAL ALTERATION, INCLUDING MITOCHONDRIAL DNA DAMAGE, INCREASED MITOCHONDRIAL REACTIVE OXYGEN SPECIES (ROS), ABNORMAL AUTOPHAGY, AND APOPTOSIS, HAVE BEEN IMPLICATED IN THE PATHOGENESIS OF COPD. THE ALTERATION CAN ALSO EXTEND TO EPIGENETICS, NAMELY DNA METHYLATION, HISTONE MODIFICATION, AND NON-CODING RNA. THIS REVIEW WILL DISCUSS THE RECENT PROGRESSIONS IN COPD PATHOLOGY, PATHOPHYSIOLOGY, AND MOLECULAR PATHWAYS. MORE FOCUS WILL BE SHED ON MITOCHONDRIAL AND EPIGENETIC VARIATIONS RELATED TO COPD DEVELOPMENT AND THE ROLE OF NANOMEDICINE AS A POTENTIAL TOOL FOR THE PREVENTION AND TREATMENT OF THIS DISEASE. 2021 2 6799 30 [EPIGENETIC AND CURRENT TREATMENT APPROACHES IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE]. EPIGENETICS MECHANISMS SUCH AS DNA METHYLATION, HISTONE ACETYLATION AND NON-CODING RNAS MAY PLAY ARE A ROLE IN THE PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). RESEARCHS WITH REGARD EPIGENETIC IN COPD CAN SHED LIGHT ON PATHOGENES AND MAY BE RELEVANT IN THE DEVELOPMENT OF NOVEL TARGETED THERAPIES. THE AIM OF THIS ARTICLE IS TO REVIEW EPIGENETIC MECHANISMS NEW TREATMENTS APPROACHES IN COPD. 2016 3 4026 28 LUNG CANCER AND ITS ASSOCIATION WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: UPDATE ON NEXUS OF EPIGENETICS. PURPOSE OF REVIEW: CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND LUNG CANCER ARE THE LEADING CAUSES OF MORBIDITY AND MORTALITY WORLDWIDE. THE CURRENT RESEARCH IS FOCUSED ON IDENTIFYING THE COMMON AND DISPARATE EVENTS INVOLVED IN EPIGENETIC MODIFICATIONS THAT CONCURRENTLY OCCUR DURING THE PATHOGENESIS OF COPD AND LUNG CANCER. THE PURPOSE OF THIS REVIEW IS TO DESCRIBE THE CURRENT KNOWLEDGE AND UNDERSTANDING OF EPIGENETIC MODIFICATIONS IN PATHOGENESIS OF COPD AND LUNG CANCER. RECENT FINDINGS: THIS REVIEW PROVIDES AN UPDATE ON ADVANCES OF HOW EPIGENETIC MODIFICATIONS ARE LINKED TO COPD AND LUNG CANCER, AND THEIR COMMONALITIES AND DISPARITIES. THE KEY EPIGENETIC MODIFICATION ENZYMES (E.G. DNA METHYLTRANSFERASES -- CPG METHYLATION, HISTONE ACETYLASES/DEACETYLASES AND HISTONE METHYLTRANSFERASES/DEMETHYLASES) THAT ARE IDENTIFIED TO PLAY AN IMPORTANT ROLE IN COPD AND LUNG TUMORIGENESIS AND PROGRESSION ARE DESCRIBED IN THIS REVIEW. SUMMARY: DISTINCT DNA METHYLTRANSFERASES AND HISTONE MODIFICATION ENZYMES ARE DIFFERENTIALLY INVOLVED IN PATHOGENESIS OF LUNG CANCER AND COPD, ALTHOUGH SOME OF THE MODIFICATIONS ARE COMMON. UNDERSTANDING THE EPIGENETIC MODIFICATIONS INVOLVED IN PATHOGENESIS OF LUNG CANCER OR COPD WITH RESPECT TO COMMON AND DISPARATE MECHANISMS WILL LEAD TO TARGETING OF EPIGENETIC THERAPIES AGAINST THESE DISORDERS. 2011 4 1245 38 CURRENT CONCEPTS ON THE ROLE OF INFLAMMATION IN COPD AND LUNG CANCER. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND LUNG CANCER ARE LEADING CAUSE OF DEATH, AND BOTH ARE ASSOCIATED WITH CIGARETTE SMOKE EXPOSURE. IT HAS BEEN SHOWN THAT 50-70% OF PATIENTS DIAGNOSED WITH LUNG CANCER SUFFER FROM COPD, AND REDUCED LUNG FUNCTION IS AN IMPORTANT EVENT IN LUNG CANCER SUGGESTING AN ASSOCIATION BETWEEN COPD AND LUNG CANCER. HOWEVER, A CAUSAL RELATIONSHIP BETWEEN COPD AND LUNG TUMORIGENESIS IS NOT YET FULLY UNDERSTOOD. RECENT STUDIES HAVE SUGGESTED A CENTRAL ROLE OF CHRONIC INFLAMMATION IN THE PATHOGENESIS OF BOTH THE DISEASES. FOR EXAMPLE, IMMUNE DYSFUNCTION, ABNORMAL ACTIVATION OF NF-KAPPAB, EPITHELIAL-TO-MESENCHYMAL TRANSITION, ALTERED ADHESION SIGNALING PATHWAYS, AND EXTRACELLULAR MATRIX DEGRADATION/ALTERED SIGNALING ARE THE KEY UNDERLYING MECHANISMS IN BOTH COPD AND LUNG CANCER. THESE PARAMETERS ALONG WITH OTHER PROCESSES, SUCH AS CHROMATIN MODIFICATIONS/EPIGENETIC CHANGES, ANGIOGENESIS, AND AUTOPHAGY/APOPTOSIS ARE ALTERED BY CIGARETTE SMOKE, ARE CRUCIAL IN THE DEVELOPMENT OF COPD AND LUNG CANCER. UNDERSTANDING THE CELLULAR AND MOLECULAR MECHANISMS UNDERLYING THESE PROCESSES WILL PROVIDE NOVEL AVENUES FOR HALTING THE CHRONIC INFLAMMATION IN COPD AND DEVISING THERAPEUTIC STRATEGIES AGAINST LUNG CANCER. 2009 5 4901 26 OXIDATIVE, INFLAMMATORY, GENETIC, AND EPIGENETIC BIOMARKERS ASSOCIATED WITH CHRONIC OBSTRUCTIVE PULMONARY DISORDER. A LARGE BODY OF EVIDENCE INDICATES THAT CHRONIC OBSTRUCTIVE PULMONARY DISORDER (COPD) IS ACCOMPANIED BY OXIDATIVE STRESS AND INFLAMMATORY AND GENETIC PATHWAYS. EPIDEMIOLOGICAL STUDIES INDICATE THAT COPD IS A MAJOR CAUSE OF MORTALITY AND MORBIDITY IN THE WORLD. RECENT RESEARCH DEVELOPMENT IN COPD FOCUSES ON ACCELERATED AGING AND VARIOUS OXIDATIVE STRESS BIOMARKERS. IT INVOLVES THE CLINICAL MANIFESTATION OF THE DISEASE PROCESS AND MAY ALSO CONTAIN BIOCHEMICAL, IMMUNOLOGICAL, PHYSIOLOGICAL, MORPHOLOGICAL, AND GENETIC ASPECTS THAT ADD TO THE PROGRESSIVENESS OF THE DISEASE. HEREIN, WE SUMMARIZE FINDINGS THAT HIGHLIGHT THE ROLE OF DIMENSIONS OF COPD IN THE INVESTIGATION OF OXIDATIVE STRESS, INFLAMMATORY RESPONSES, GENETIC AND EPIGENETIC STUDIES, AND PHARMACOLOGICAL AND DIETARY ANTIOXIDANT INTERVENTION. 2019 6 1539 28 DNA METHYLATION IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A LUNG DISEASE AFFECTED BY BOTH GENETIC AND ENVIRONMENTAL FACTORS. THEREFORE, THE ROLE OF EPIGENETICS IN THE PATHOGENESIS OF COPD HAS ATTRACTED MUCH ATTENTION. AS ONE OF THE THREE EPIGENETIC MECHANISMS, DNA METHYLATION HAS BEEN EXTENSIVELY STUDIED IN COPD. THE PRESENT REVIEW AIMS AT OVERVIEWING THE EFFECT OF DNA METHYLATION ON ETIOLOGY, PATHOGENESIS, PATHOPHYSIOLOGICAL CHANGES, AND COMPLICATIONS OF COPD. THE CLARIFICATION OF ABERRANT METHYLATION OF TARGET GENES, WHICH PLAY IMPORTANT ROLES IN THE INITIATION AND PROGRESSION OF COPD, WILL PROVIDE NEW DISEASE-SPECIFIC BIOMARKER AND TARGETS FOR EARLY DIAGNOSIS AND THERAPY. 2020 7 2059 34 EPIGENETIC CONTROL OF GENE EXPRESSION IN THE LUNG. EPIGENETICS IS TRADITIONALLY DEFINED AS THE STUDY OF HERITABLE CHANGES IN GENE EXPRESSION CAUSED BY MECHANISMS OTHER THAN CHANGES IN THE UNDERLYING DNA SEQUENCE. THERE ARE THREE MAIN CLASSES OF EPIGENETIC MARKS--DNA METHYLATION, MODIFICATIONS OF HISTONE TAILS, AND NONCODING RNAS--EACH OF WHICH MAY BE INFLUENCED BY THE ENVIRONMENT, DIET, DISEASES, AND AGEING. IMPORTANTLY, EPIGENETIC MARKS HAVE BEEN SHOWN TO INFLUENCE IMMUNE CELL MATURATION AND ARE ASSOCIATED WITH THE RISK OF DEVELOPING VARIOUS FORMS OF CANCER, INCLUDING LUNG CANCER. MOREOVER, THERE IS EMERGING EVIDENCE THAT THESE EPIGENETIC MARKS AFFECT GENE EXPRESSION IN THE LUNG AND ARE ASSOCIATED WITH BENIGN LUNG DISEASES, SUCH AS ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, AND INTERSTITIAL LUNG DISEASE. TECHNOLOGICAL ADVANCES HAVE MADE IT FEASIBLE TO STUDY EPIGENETIC MARKS IN THE LUNG, AND IT IS ANTICIPATED THAT THIS KNOWLEDGE WILL ENHANCE OUR UNDERSTANDING OF THE DYNAMIC BIOLOGY IN THE LUNG AND LEAD TO THE DEVELOPMENT OF NOVEL DIAGNOSTIC AND THERAPEUTIC APPROACHES FOR OUR PATIENTS WITH LUNG DISEASE. 2011 8 1244 40 CURRENT CONCEPTS ON OXIDATIVE/CARBONYL STRESS, INFLAMMATION AND EPIGENETICS IN PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A GLOBAL HEALTH PROBLEM. THE CURRENT THERAPIES FOR COPD ARE POORLY EFFECTIVE AND THE MAINSTAYS OF PHARMACOTHERAPY ARE BRONCHODILATORS. A BETTER UNDERSTANDING OF THE PATHOBIOLOGY OF COPD IS CRITICAL FOR THE DEVELOPMENT OF NOVEL THERAPIES. IN THE PRESENT REVIEW, WE HAVE DISCUSSED THE ROLES OF OXIDATIVE/ALDEHYDE STRESS, INFLAMMATION/IMMUNITY, AND CHROMATIN REMODELING IN THE PATHOGENESIS OF COPD. AN IMBALANCE OF OXIDANTS/ANTIOXIDANTS CAUSED BY CIGARETTE SMOKE AND OTHER POLLUTANTS/BIOMASS FUELS PLAYS AN IMPORTANT ROLE IN THE PATHOGENESIS OF COPD BY REGULATING REDOX-SENSITIVE TRANSCRIPTION FACTORS (E.G., NF-KAPPAB), AUTOPHAGY AND UNFOLDED PROTEIN RESPONSE LEADING TO CHRONIC LUNG INFLAMMATORY RESPONSE. CIGARETTE SMOKE ALSO ACTIVATES CANONICAL/ALTERNATIVE NF-KAPPAB PATHWAYS AND THEIR UPSTREAM KINASES LEADING TO SUSTAINED INFLAMMATORY RESPONSE IN LUNGS. RECENTLY, EPIGENETIC REGULATION HAS BEEN SHOWN TO BE CRITICAL FOR THE DEVELOPMENT OF COPD BECAUSE THE EXPRESSION/ACTIVITY OF ENZYMES THAT REGULATE THESE EPIGENETIC MODIFICATIONS HAVE BEEN REPORTED TO BE ABNORMAL IN AIRWAYS OF COPD PATIENTS. HENCE, THE SIGNIFICANT ADVANCES MADE IN UNDERSTANDING THE PATHOPHYSIOLOGY OF COPD AS DESCRIBED HEREIN WILL IDENTIFY NOVEL THERAPEUTIC TARGETS FOR INTERVENTION IN COPD. 2011 9 629 31 BIOLOGICAL AND GENETIC MECHANISMS OF COPD, ITS DIAGNOSIS, TREATMENT, AND RELATIONSHIP WITH LUNG CANCER. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS ONE OF THE MOST PREVALENT CHRONIC ADULT DISEASES, WITH SIGNIFICANT WORLDWIDE MORBIDITY AND MORTALITY. ALTHOUGH LONG-TERM TOBACCO SMOKING IS A CRITICAL RISK FACTOR FOR THIS GLOBAL HEALTH PROBLEM, ITS MOLECULAR MECHANISMS REMAIN UNCLEAR. SEVERAL PHENOMENA ARE THOUGHT TO BE INVOLVED IN THE EVOLUTION OF EMPHYSEMA, INCLUDING AIRWAY INFLAMMATION, PROTEINASE/ANTI-PROTEINASE IMBALANCE, OXIDATIVE STRESS, AND GENETIC/EPIGENETIC MODIFICATIONS. FURTHERMORE, COPD IS ONE MAIN RISK FOR LUNG CANCER (LC), THE DEADLIEST FORM OF HUMAN TUMOR; FORMATION AND CHRONIC INFLAMMATION ACCOMPANYING COPD CAN BE A POTENTIAL DRIVER OF MALIGNANCY MATURATION (0.8-1.7% OF COPD CASES DEVELOP CANCER/PER YEAR). RECENTLY, THE DEVELOPMENT OF MORE RESEARCH BASED ON COPD AND LUNG CANCER MOLECULAR ANALYSIS HAS PROVIDED NEW LIGHT FOR UNDERSTANDING THEIR PATHOGENESIS, IMPROVING THE DIAGNOSIS AND TREATMENTS, AND ELUCIDATING MANY CONNECTIONS BETWEEN THESE DISEASES. OUR REVIEW EMPHASIZES THE BIOLOGICAL FACTORS INVOLVED IN COPD AND LUNG CANCER, THE ADVANCES IN THEIR MOLECULAR MECHANISMS' RESEARCH, AND THE STATE OF THE ART OF DIAGNOSIS AND TREATMENTS. THIS WORK COMBINES MANY BIOLOGICAL AND GENETIC ELEMENTS INTO A SINGLE WHOLE AND STRONGLY LINKS COPD WITH LUNG TUMOR FEATURES. 2023 10 970 34 CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND LUNG CANCER: COMMON PATHWAYS FOR PATHOGENESIS. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND LUNG CANCER COMPRISE THE LEADING CAUSES OF LUNG DISEASE-RELATED MORTALITY WORLDWIDE. EXPOSURE TO TOBACCO SMOKE IS A MUTUAL AETIOLOGY UNDERLYING THE TWO DISEASES, ACCOUNTING FOR ALMOST 90% OF CASES. THERE IS ACCUMULATING EVIDENCE SUPPORTING THE ROLE OF IMMUNE DYSFUNCTION, THE LUNG MICROBIOME, EXTRACELLULAR VESICLES AND UNDERLYING GENETIC SUSCEPTIBILITY IN THE DEVELOPMENT OF COPD AND LUNG CANCER. FURTHER, EPIGENETIC FACTORS, INVOLVING DNA METHYLATION AND MICRORNA EXPRESSION, HAVE BEEN IMPLICATED IN BOTH DISEASES. CHRONIC INFLAMMATION IS A KEY FEATURE OF COPD AND COULD BE A POTENTIAL DRIVER OF LUNG CANCER DEVELOPMENT. USING NEXT GENERATION TECHNOLOGIES, FURTHER STUDIES INVESTIGATING THE GENOMICS, EPIGENETICS AND GENE-ENVIRONMENT INTERACTION IN KEY MOLECULAR PATHWAYS WILL CONTINUE TO ELUCIDATE THE PATHOGENIC MECHANISMS UNDERLYING THE DEVELOPMENT OF COPD AND LUNG CANCER, AND CONTRIBUTE TO THE DEVELOPMENT OF NOVEL DIAGNOSTIC AND PROGNOSTIC TOOLS FOR EARLY INTERVENTION AND PERSONALISED THERAPEUTIC STRATEGIES. 2019 11 2162 42 EPIGENETIC MECHANISMS IN COPD: IMPLICATIONS FOR PATHOGENESIS AND DRUG DISCOVERY. INTRODUCTION: CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS THE FOURTH LEADING CAUSE OF DEATH WORLDWIDE. THE GROWING BURDEN OF COPD IS DUE TO CONTINUOUS TOBACCO USE, WHICH IS THE MOST IMPORTANT RISK FACTOR OF THE DISEASE, INDOOR FUMES, OCCUPATIONAL EXPOSURES AND ALSO AGING OF THE WORLD'S POPULATION. EPIGENETIC MECHANISMS SIGNIFICANTLY CONTRIBUTE TO COPD PATHOPHYSIOLOGY. AREAS COVERED: THIS REVIEW FOCUSES ON DISEASE-RELEVANT CHANGES IN DNA MODIFICATION, HISTONE MODIFICATION AND NON-CODING RNA EXPRESSION IN COPD, AND PROVIDES INSIGHT INTO NOVEL THERAPEUTIC APPROACHES MODULATING EPIGENETIC MECHANISMS. RECENT FINDINGS REVEALED, AMONG OTHERS, GLOBALLY CHANGED DNA METHYLATION PATTERNS, DECREASED LEVELS OF HISTONE DEACETYLASES AND REDUCED MICRORNAS LEVELS IN COPD. THE AUTHORS ALSO DISCUSS A POTENTIAL ROLE OF THE CHROMATIN SILENCING POLYCOMB GROUP OF PROTEINS IN COPD. EXPERT OPINION: COPD IS A HIGHLY COMPLEX DISEASE AND THERAPY DEVELOPMENT IS COMPLICATED BY THE FACT THAT MANY SMOKERS DEVELOP BOTH COPD AND LUNG CANCER. OF INTEREST, COMBINATION THERAPIES INVOLVING DNA METHYLTRANSFERASE INHIBITORS AND ANTI-INFLAMMATORY DRUGS PROVIDE A PROMISING APPROACH, AS THEY MIGHT BE THERAPEUTIC FOR BOTH COPD AND CANCER. ALTHOUGH THE FIELD OF EPIGENETIC RESEARCH HAS VIRTUALLY EXPLODED OVER THE LAST 10 YEARS, PARTICULAR EFFORTS ARE REQUIRED TO ENHANCE OUR KNOWLEDGE OF THE COPD EPIGENOME IN ORDER TO SUCCESSFULLY ESTABLISH EPIGENETIC-BASED THERAPIES FOR THIS WIDESPREAD DISEASE. 2014 12 6628 37 UNDERSTANDING THE GENETICS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE, ALPHA1-ANTITRYPSIN DEFICIENCY, AND IMPLICATIONS FOR CLINICAL PRACTICE. CIGARETTE SMOKING AND POOR AIR QUALITY ARE THE GREATEST RISK FACTORS FOR DEVELOPING CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), BUT GROWING EVIDENCE INDICATES THAT GENETIC FACTORS ALSO AFFECT PREDISPOSITION TO AND CLINICAL EXPRESSION OF DISEASE. WITH THE EXCEPTION OF ALPHA1-ANTITRYPSIN DEFICIENCY (AATD), A RARE AUTOSOMAL RECESSIVE DISORDER THAT IS PRESENT IN 1-3% OF INDIVIDUALS WITH COPD, NO SINGLE GENE IS ASSOCIATED WITH THE DEVELOPMENT OF OBSTRUCTIVE LUNG DISEASE. INSTEAD, A COMPLEX INTERPLAY OF GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS IS THE BASIS FOR PERSISTENT INFLAMMATORY RESPONSES, ACCELERATED CELL AGING, CELL DEATH, AND FIBROSIS, LEADING TO THE CLINICAL SYMPTOMS OF COPD AND DIFFERENT PHENOTYPIC PRESENTATIONS. IN THIS BRIEF REVIEW, WE DISCUSS CURRENT UNDERSTANDING OF THE GENETICS OF COPD, PATHOGENETICS OF AATD, EPIGENETIC INFLUENCES ON THE DEVELOPMENT OF OBSTRUCTIVE LUNG DISEASE, AND HOW CLASSIFYING COPD BY PHENOTYPE CAN INFLUENCE CLINICAL TREATMENT AND PATIENT OUTCOMES. 2021 13 2457 35 EPIGENETIC TARGETS FOR THERAPEUTIC APPROACHES IN COPD AND ASTHMA. NUTRIGENOMICS - POSSIBLE OR ILLUSIVE. OXIDATIVE STRESS GENERATED BY CIGARETTE SMOKING, ENVIRONMENTAL POLLUTION, OR OTHER NOXIOUS PARTICLES LEADS TO EPIGENETIC CHANGES IN THE CELLS OF THE RESPIRATORY TRACT. THEY REFLECT CELL ADAPTATION IN RESPONSE TO CHRONIC EXPOSURE TO EXTERNAL FACTORS. ALTHOUGH THERE IS NO CHANGE IN THE GENETIC CODE, EPIGENETIC CHANGES MAY BE HERITABLE AND TRANSLATED FROM ONE GENERATION TO ANOTHER, ACCUMULATING ABNORMALITIES AND RENDERING CELLS INTO ENTIRELY DIFFERENT PHENOTYPE, CAUSING DISEASE. DNA METHYLATION, POST-TRANSLATION HISTONE MODIFICATION, UBIQUITINATION, SUMOYLATION AND MIRNA TRANSCRIPTIONAL REGULATION ARE THE MAJOR PROCESSES THAT ARE RESPONSIBLE FOR THE EPIGENETIC CONTROL OF GENE EXPRESSION. ALL OF THEM ARE REVERSIBLE. THEY CAN BE REGULATED BY TARGETING SPECIFIC ENZYMES/PROTEINS INVOLVED IN THE PROCESS IN ORDER TO MITIGATE INFLAMMATION. CHRONIC RESPIRATORY DISEASES HAVE EPIGENETIC SIGNATURES THAT AFFECT GENE EXPRESSION IN THE LUNG. TARGETING THEM PROVIDES THE DEVELOPMENT OF NOVEL DIAGNOSTIC AND THERAPEUTIC APPROACHES IN RESPIRATORY MEDICINE. NUTRIGENOMICS REVEALS THE BENEFICIAL EFFECT OF NATURAL PHYTOCHEMICALS, AFFECTING KEY STEPS IN THE SIGNALING PATHWAYS OF CHRONIC RESPIRATORY DISEASES. 2019 14 971 35 CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND THE HALLMARKS OF AGING. AGING IS CHARACTERIZED BY PROGRESSIVE DETERIORATION OF PHYSIOLOGICAL INTEGRITY, DECLINE IN HOMEOSTASIS, AND DEGENERATION OF THE TISSUES THAT OCCURS AFTER THE REPRODUCTIVE PHASE OF LIFE IS COMPLETE, LEADING TO IMPAIRED FUNCTION. THIS DETERIORATION IS AN IMPORTANT RISK FACTOR FOR CHRONIC LUNG PATHOLOGIES SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). COPD IS A DISEASE THAT DEVELOPS GRADUALLY. EMPHYSEMATOUS CHANGES IN THE LUNG TAKE YEARS TO DEVELOP AFTER EXPOSURE TO CIGARETTE SMOKE; HENCE, THE VAST MAJORITY OF PATIENTS ARE ELDERLY. THERE HAS BEEN A DRAMATIC INCREASE IN THE LIFE EXPECTANCY OF THE GENERAL POPULATION, RESULTING IN AN INCREASED BURDEN OF CHRONIC LUNG DISEASES. THERE IS GROWING EVIDENCE THAT MOLECULAR MECHANISMS INVOLVED IN AGING MAY ALSO PLAY A ROLE IN COPD PATHOGENESIS. RECENTLY, THE NINE HALLMARKS OF AGING WERE IDENTIFIED. IN THIS ARTICLE, WE WILL REVIEW THE NINE HALLMARKS OF AGING AND HOW EACH HALLMARK CONTRIBUTES TO THE PATHOGENESIS OF COPD. 2018 15 3543 26 IMMUNOLOGY, GENETICS AND MICROBIOTA IN THE COPD PATHOPHYSIOLOGY: POTENTIAL SCOPE FOR PATIENT STRATIFICATION. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS CHARACTERIZED BY SUSTAINED INFLAMMATION OF THE AIRWAYS, LEADING TO DESTRUCTION OF LUNG TISSUE AND DECLINING PULMONARY FUNCTION. ALTHOUGH SMOKING IS THE MOST OBVIOUS RISK FACTOR FOR COPD, ONLY ABOUT 20% OF SMOKERS DEVELOP COPD AND SMOKING CESSATION DOES NOT REVERSE PROGRESSION OF COPD, INDICATING THAT WHILE SMOKING IS AN IMPORTANT CAUSE OR INITIATING FACTOR, IT IS NOT THE ONLY DRIVER OF ONGOING CHRONIC INFLAMMATION AND DISEASE PROGRESSION IN COPD PATIENTS. WE HYPOTHESIZE THAT SMOKING-INDUCED CHANGES IN LUNG MICROBIOTA, EPITHELIAL INTEGRITY AND EPIGENETIC CONTROL OF GENE EXPRESSION RESULT IN AUTOANTIGEN INDUCTION AND PERTURBED IMMUNE REGULATION IN GENETICALLY VUNERABLE INDIVIDUALS. IN OUR VIEW, COPD PATIENTS MAY BE STRATIFIED ACCORDING TO THEIR IMMUNOLOGICAL AND INFLAMMATORY STATUS RELATED TO SPECIFIC CHANGES IN THE LUNG MICROBIOTA (INNATE AND ADAPTIVE IMMUNITY), PRESENCE OF AUTOANTIGENS (ADAPTIVE IMMUNITY: TH1-B-CELL AXIS) AND EPIGENETIC MODIFICATIONS (INFLAMMATION AND STRUCTURAL CHANGES). 2015 16 3966 42 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 17 4445 34 MOLECULAR LINKS BETWEEN COPD AND LUNG CANCER: NEW TARGETS FOR DRUG DISCOVERY? COPD AND LUNG CANCER ARE LEADING CAUSES OF MORBIDITY AND MORTALITY WORLDWIDE, AND THEY SHARE A COMMON ENVIRONMENTAL RISK FACTOR IN CIGARETTE SMOKE EXPOSURE AND A GENETIC PREDISPOSITION REPRESENTED BY THEIR INCIDENCE IN ONLY A FRACTION OF SMOKERS. THIS REFLECTS THE ABILITY OF CIGARETTE SMOKE TO INDUCE AN INFLAMMATORY RESPONSE IN THE AIRWAYS OF SUSCEPTIBLE SMOKERS. MOREOVER, COPD COULD BE A DRIVING FACTOR IN LUNG CANCER, BY INCREASING OXIDATIVE STRESS AND THE RESULTING DNA DAMAGE AND REPRESSION OF THE DNA REPAIR MECHANISMS, CHRONIC EXPOSURE TO PRO-INFLAMMATORY CYTOKINES, REPRESSION OF INNATE IMMUNITY AND INCREASED CELLULAR PROLIFERATION. AREAS COVERED: WE HAVE FOCUSED OUR REVIEW ON THE POTENTIAL PATHOGENIC MOLECULAR LINKS BETWEEN TOBACCO SMOKING-RELATED COPD AND LUNG CANCER AND THE POTENTIAL MOLECULAR TARGETS FOR NEW DRUG DEVELOPMENT BY UNDERSTANDING THE COMMON SIGNALING PATHWAYS INVOLVED IN COPD AND LUNG CANCER. EXPERT COMMENTARY: RESEARCH IN THIS FIELD IS MOSTLY LIMITED TO ANIMAL MODELS OR SMALL CLINICAL TRIALS. LARGE CLINICAL TRIALS ARE NEEDED BUT MOSTLY COMBINED MODELS OF COPD AND LUNG CANCER ARE NECESSARY TO INVESTIGATE THE PROCESSES CAUSED BY CHRONIC INFLAMMATION, INCLUDING GENETIC AND EPIGENETIC ALTERATION, AND THE EXPRESSION OF INFLAMMATORY MEDIATORS THAT LINK COPD AND LUNG CANCER, TO IDENTIFY NEW MOLECULAR THERAPEUTIC TARGETS. 2019 18 5916 39 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 19 5456 34 RESEARCH ADVANCES ON DNA METHYLATION IN IDIOPATHIC PULMONARY FIBROSIS. IDIOPATHIC PULMONARY FIBROSIS (IPF) IS A CHRONIC COMPLEX LUNG DISEASE WITH NO SPECIFIC TREATMENT AND POOR PROGNOSIS, CHARACTERIZED BY THE PULMONARY PROGRESSIVE FIBROSIS AND DYSFUNCTIONS THAT LEAD TO RESPIRATORY FAILURE. SEVERAL FACTORS MAY IMPACT THE PROGRESS OF IPF, INCLUDING AGE, CIGARETTE SMOKING, AND DUSTS, OF WHICH GENETIC AND EPIGENETIC FACTORS MAINLY CONTRIBUTE TO LUNG TISSUE FIBROSIS. DNA METHYLATION IS ONE OF EPIGENETIC PROCESSES THAT OCCUR IN MANY DISEASES AND REGULATE CHROMOSOMAL AND EXTRACHROMOSOMAL DNA FUNCTIONS IN RESPONSE TO ENVIRONMENTAL EXPOSURES. THE METHYLATION PLAYS PIVOTAL ROLES IN REGULATION OF GENE EXPRESSION TO FACILITATE THE FORMATION OF FIBROBLASTIC FOCI AND LUNG FIBROSIS. THIS CHAPTER WILL DESCRIBE ALTERATIONS AND EFFECTS OF THE DNA METHYLATION ON GENE EXPRESSION, THE POTENTIAL APPLICATION OF DNA METHYLATION AS A BIOMARKER, AND SIGNIFICANCE AS THERAPEUTIC TARGETS. THOSE UNDERSTANDING WILL PROVIDE US NEW INSIGHT INTO THE TREATMENT AND PROGNOSIS OF IPF. 2020 20 6880 36 [RESEARCH PROGRESS OF LUNG AGING IN CHRONIC RESPIRATORY DISEASES]. CELL AGING IS AN EXTREMELY COMPLEX PROCESS, WHICH IS CHARACTERIZED BY MITOCHONDRIAL STRUCTURAL DYSFUNCTION, TELOMERE SHORTENING, INFLAMMATORY MICROENVIRONMENT, PROTEIN HOMEOSTASIS IMBALANCE, EPIGENETIC CHANGES, ABNORMAL DNA DAMAGE AND REPAIR, ETC. AGING IS USUALLY ACCOMPANIED BY STRUCTURAL AND FUNCTIONAL DAMAGE OF TISSUES AND ORGANS WHICH FURTHER INDUCES THE OCCURRENCE AND DEVELOPMENT OF AGING-RELATED DISEASES. AGING INCLUDES PHYSIOLOGICAL AGING CAUSED BY INCREASED AGE AND PATHOLOGICAL AGING INDUCED BY A VARIETY OF FACTORS. NOTEWORTHY, AS A TARGET ORGAN DIRECTLY CONTACTING WITH THE OUTSIDE AIR, LUNG IS MORE PRONE TO VARIOUS STIMULI, CAUSING PATHOLOGICAL PREMATURE AGING WHICH IS LUNG AGING. STUDIES HAVE FOUND THAT THERE IS A CERTAIN PROPORTION OF SENESCENT CELLS IN THE LUNGS OF MOST CHRONIC RESPIRATORY DISEASES. HOWEVER, THE UNDERLYING MECHANISM BY WHICH THESE SENESCENT CELLS INDUCE LUNG SENESCENCE AND THEIR ROLE IN CHRONIC RESPIRATORY DISEASES IS STILL OBSCURE. THIS PAPER FOCUSES ON THE CAUSES AND CLASSIFICATION OF LUNG AGING, THE INTERNAL MECHANISM OF LUNG AGING INVOLVED IN CHRONIC RESPIRATORY DISEASES, AND THE APPLICATION OF ANTI-AGING TREATMENTS IN CHRONIC RESPIRATORY DISEASES. WE HOPE TO PROVIDE NEW RESEARCH IDEAS AND THEORETICAL BASIS FOR THE CLINICAL PREVENTION AND TREATMENT IN CHRONIC RESPIRATORY DISEASES. 2022