1 4954 76 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 2 1244 33 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 3 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 4 4953 38 PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) INDUCED BY CIGARETTE SMOKE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS A COMMON RESPIRATORY DISEASE THAT IS CHARACTERIZED BY FUNCTIONAL AND STRUCTURAL ALTERATIONS PRIMARILY CAUSED BY LONG-TERM INHALATION OF HARMFUL PARTICLES. CIGARETTE SMOKE (CS) INDUCES AIRWAY INFLAMMATION IN COPD, WHICH IS KNOWN TO PERSIST EVEN AFTER SMOKING CESSATION. THIS REVIEW DISCUSSES THE BASIC PATHOGENESIS OF COPD, WITH PARTICULAR FOCUS ON AN ENDOGENOUS PROTECTIVE MECHANISM AGAINST OXIDATIVE STRESS VIA NRF2, ALTERED IMMUNE RESPONSE OF THE AIRWAY INFLAMMATORY CELLS, EXAGGERATED CELLULAR SENESCENCE OF THE LUNG STRUCTURAL CELLS, AND CELL DEATH WITH EXPANDED INFLAMMATION. RECENTLY, CS-INDUCED MITOCHONDRIA AUTOPHAGY IS REPORTED TO INITIATE PROGRAMMED NECROSIS (NECROPTOSIS). NECROPTOSIS IS A NEW CONCEPT OF CELL DEATH WHICH IS DRIVEN BY A DEFINED MOLECULAR PATHWAY ALONG WITH EXAGGERATED INFLAMMATION. THIS NEW CELL DEATH MECHANISM IS OF IMPORTANCE DUE TO ITS ABILITY TO PRODUCE MORE INFLAMMATORY SUBSTANCES DURING THE PROCESS OF EPITHELIAL DEATH, CONTRIBUTING TO PERSISTENT AIRWAY INFLAMMATION THAT CANNOT BE EXPLAINED BY APOPTOSIS-DERIVED CELL DEATH. AUTOPHAGY IS AN AUTO-CELL COMPONENT DEGRADATION SYSTEM EXECUTED BY LYSOSOMES THAT CONTROLS PROTEIN AND ORGANELLE DEGRADATION FOR SUCCESSFUL HOMEOSTASIS. AS WELL AS IN THE PROCESS OF NECROPTOSIS, AUTOPHAGY IS ALSO OBSERVED DURING CELLULAR SENESCENCE. AGING OF THE LUNGS RESULTS IN THE ACQUISITION OF SENESCENCE-ASSOCIATED SECRETORY PHENOTYPES (SASP) THAT ARE KNOWN TO SECRETE INFLAMMATORY CYTOKINES, CHEMOKINES, GROWTH FACTORS, AND MATRIX METALLOPROTEINASES RESULTING IN CHRONIC LOW-GRADE INFLAMMATION. IN FUTURE RESEARCH, WE INTEND TO HIGHLIGHT THE GENETIC AND EPIGENETIC APPROACHES THAT CAN FACILITATE THE UNDERSTANDING OF DISEASE SUSCEPTIBILITY. THE GOAL OF PRECISION MEDICINE IS TO ESTABLISH MORE ACCURATE DIAGNOSIS AND TREATMENT METHODS BASED ON THE PATIENT-SPECIFIC PATHOGENIC CHARACTERISTICS. THIS REVIEW PROVIDES INSIGHTS INTO CS-INDUCED COPD PATHOGENESIS, WHICH CONTRIBUTES TO A VERY COMPLEX DISEASE. INVESTIGATING THE MECHANISM OF DEVELOPING COPD, ALONG WITH THE AVAILABILITY OF THE PARTICULAR INHIBITORS, WILL LEAD TO NEW THERAPEUTIC APPROACHES IN COPD TREATMENT. 2019 5 1245 30 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 6 4658 19 NEW ANTI-INFLAMMATORY TARGETS FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE. CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IS ASSOCIATED WITH CHRONIC INFLAMMATION OF THE PERIPHERAL AIRWAYS AND LUNG PARENCHYMA, WHICH LEADS TO PROGRESSIVE OBSTRUCTION OF THE AIRWAYS. CURRENT MANAGEMENT WITH LONG-ACTING BRONCHODILATORS DOES NOT REDUCE DISEASE PROGRESSION, AND THERE ARE NO TREATMENTS THAT EFFECTIVELY SUPPRESS CHRONIC INFLAMMATION IN COPD. AN INCREASED UNDERSTANDING OF THE INFLAMMATORY PROCESSES THAT ARE INVOLVED IN THE PATHOPHYSIOLOGY OF COPD HAS IDENTIFIED SEVERAL NEW THERAPEUTIC TARGETS. THIS REVIEW DISCUSSES SOME OF THE MOST PROMISING OF THESE TARGETS, INCLUDING NEW ANTIOXIDANTS, KINASE INHIBITORS AND DRUGS THAT TARGET CELLULAR SENESCENCE, MICROBIAL COLONIZATION, EPIGENETIC REGULATION OF INFLAMMATORY GENE EXPRESSION AND CORTICOSTEROID RESISTANCE. 2013 7 4901 21 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 8 973 30 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 9 4445 29 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 10 1188 30 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 11 970 23 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 12 927 25 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 13 971 24 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 14 3535 26 IMMUNE AND GENETIC MECHANISMS IN COPD: POSSIBLE TARGETS FOR THERAPEUTIC INTERVENTIONS. GENETIC, IMMUNE AND ENVIRONMENTAL INTERACTIONS ARE KEY ELEMENTS FOR THE DEVELOPMENT OF COPD. CIGARETTE SMOKING IS CONSIDERED THE PRIMARY RISK FACTOR INITIATING INFLAMMATORY CASCADES IN GENETICALLY SUSCEPTIBLE INDIVIDUALS. THE "DANGER SIGNALS" ELICITED BY THE INJURED CELLS OF NON-SPECIFIC IMMUNITY INDUCE THE DOWNSTREAM ACTIVATION OF PROINFLAMMATORY CASCADES AND ANTIGEN-SPECIFIC ADAPTIVE IMMUNE RESPONSES. THE PRODUCED OXIDATIVE STRESS FURTHER DAMAGES THE LUNG LEADING TO ACQUIRED GENETIC CHANGES (HISTONE DEACETYLATION, MICROSATELLITE DNA INSTABILITY, DNA METHYLATION, TELOMERE SHORTENING, MIRNA ALTERATIONS) DUE TO AN INEFFICIENT DNA REPAIR MACHINERY. ON THE OTHER HAND, AUGMENTED APOPTOSIS, IMPAIRED EFFEROCYTOSIS AND ABNORMAL TISSUE REMODELING CONTRIBUTE TO THE CHRONIC INFLAMMATORY RESPONSE AND TISSUE DESTRUCTION IN COPD. THIS REVIEW FOCUSES ON THE ROLE OF GENETIC, EPIGENETIC AND IMMUNE MECHANISMS IN THE DEVELOPMENT OF COPD IN ORDER TO PUT FORWARD POSSIBLE PROGNOSTIC AND THERAPEUTIC TARGETS. 2013 15 1259 31 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 16 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 17 4026 22 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 18 2357 29 EPIGENETIC REGULATION OF PULMONARY INFLAMMATION. PULMONARY DISEASE SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), ASTHMA, PULMONARY FIBROSIS AND PULMONARY HYPERTENSION ARE THE LEADING CAUSE OF DEATHS. MORE IMPORTANTLY, LUNG DISEASES ARE ON THE RISE AND ENVIRONMENTAL FACTORS INDUCED EPIGENETIC MODIFICATIONS ARE MAJOR PLAYERS ON THIS INCREASED PREVALENCE. IT HAS BEEN REPORTED THAT DYSREGULATION OF GENES INVOLVED IN EPIGENETIC REGULATION SUCH AS THE HISTONE DEACETYLASE (HDACS) AND HISTONE ACETYLTRANSFERASE (HATS) PLAY IMPORTANT ROLE IN LUNG HEALTH AND PULMONARY DISEASE PATHOGENESIS. INFLAMMATION IS AN ESSENTIAL COMPONENT OF RESPIRATORY DISEASES. INJURY AND INFLAMMATION TRIGGER RELEASE OF EXTRACELLULAR VESICLES THAT CAN ACT AS EPIGENETIC MODIFIERS THROUGH TRANSFER OF EPIGENETIC REGULATORS SUCH AS MICRORNAS (MIRNAS), LONG NON-CODING RNAS (LNCRNAS), PROTEINS AND LIPIDS, FROM ONE CELL TO ANOTHER. THE IMMUNE DYSREGULATIONS CAUSED BY THE CARGO CONTENTS ARE IMPORTANT CONTRIBUTORS OF RESPIRATORY DISEASE PATHOGENESIS. N6 METHYLATION OF RNA IS ALSO EMERGING TO BE A CRITICAL MECHANISM OF EPIGENETIC ALTERATION AND UPREGULATION OF IMMUNE RESPONSES TO ENVIRONMENTAL STRESSORS. EPIGENETIC CHANGES SUCH AS DNA METHYLATION ARE STABLE AND OFTEN LONG TERM AND CAUSE ONSET OF CHRONIC LUNG CONDITIONS. THESE EPIGENETIC PATHWAYS ARE ALSO BEING UTILIZED FOR THERAPEUTIC INTERVENTION IN SEVERAL LUNG CONDITIONS. 2023 19 6834 25 [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 6005 26 THE AIRWAY EPITHELIUM-A CENTRAL PLAYER IN ASTHMA PATHOGENESIS. ASTHMA IS A CHRONIC INFLAMMATORY AIRWAY DISEASE CHARACTERIZED BY VARIABLE AIRFLOW OBSTRUCTION IN RESPONSE TO A WIDE RANGE OF EXOGENOUS STIMULI. THE AIRWAY EPITHELIUM IS THE FIRST LINE OF DEFENSE AND PLAYS AN IMPORTANT ROLE IN INITIATING HOST DEFENSE AND CONTROLLING IMMUNE RESPONSES. INDEED, INCREASING EVIDENCE INDICATES A RANGE OF ABNORMALITIES IN VARIOUS ASPECTS OF EPITHELIAL BARRIER FUNCTION IN ASTHMA. A CENTRAL PART OF THIS IMPAIRMENT IS A DISRUPTION OF THE AIRWAY EPITHELIAL LAYER, ALLOWING INHALED SUBSTANCES TO PASS MORE EASILY INTO THE SUBMUCOSA WHERE THEY MAY INTERACT WITH IMMUNE CELLS. FURTHERMORE, MANY OF THE IDENTIFIED SUSCEPTIBILITY GENES FOR ASTHMA ARE EXPRESSED IN THE AIRWAY EPITHELIUM. THIS REVIEW FOCUSES ON THE BIOLOGY OF THE AIRWAY EPITHELIUM IN HEALTH AND ITS PATHOBIOLOGY IN ASTHMA. WE WILL SPECIFICALLY DISCUSS EXTERNAL TRIGGERS SUCH AS ALLERGENS, VIRUSES AND ALARMINS AND THE EFFECT OF TYPE 2 INFLAMMATORY RESPONSES ON AIRWAY EPITHELIAL FUNCTION IN ASTHMA. WE WILL ALSO DISCUSS EPIGENETIC MECHANISMS RESPONDING TO EXTERNAL STIMULI ON THE LEVEL OF TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL REGULATION OF GENE EXPRESSION, AS WELL THE AIRWAY EPITHELIUM AS A POTENTIAL TREATMENT TARGET IN ASTHMA. 2020