6Description of Levels of Evidence Evidence CategorySources of EvidenceARandomized controlled trials (RCTs). Rich body of dataBRandomized controlled trials(RCTs). Limited body of dataCNonrandomized trialsObservational studies.DPanel consensus judgment
8China GOLD National Leaders Israel Slovenia Germany Brazil Ireland BangladeshSaudi ArabiaSloveniaGermanyBrazilIrelandYugoslaviaCroatiaUnited StatesAustraliaCanadaAustriaTaiwan ROCPortugalPhilippinesThailandYemanNorwayMaltaMoldovaGreeceSyriaChinaSouth AfricaKazakhstanUnited KingdomHong Kong ROCItalyNew ZealandNepalChileIsraelArgentinaMexicoPakistanRussiaUnited Arab EmiratesJapanPeruGOLD National LeadersPolandKoreaNetherlandsEgyptSwitzerlandIndiaVenezuelaGeorgiaFranceMacedoniaIcelandCzech RepublicDenmarkTurkeySlovakiaBelgiumSingaporeSpainUkraineRomaniaColumbiaUruguaySwedenVietnamAlbaniaKyrgyzstan
10G O L Dlobal Initiative for Chronic bstructive ung isease
11GOLD ObjectivesIncrease awareness of COPD among health professionals, health authorities, and the general publicImprove diagnosis, management and preventionDecrease morbidity and mortalityStimulate research
12Global Strategy for Diagnosis, Management and Prevention of COPD Definition, ClassificationBurden of COPDRisk FactorsPathogenesis, Pathology, PathophysiologyManagement of COPDPrimary Care Recommendations
13Definition of COPDCOPD is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients.Its pulmonary component is characterized by airflow limitation that is not fully reversible.The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.
14Classification of COPD Severity by SpirometryStage I: Mild FEV1/FVC < 0.70FEV1 > 80% predictedStage II: Moderate FEV1/FVC < 0.7050% < FEV1 < 80% predictedStage III: Severe FEV1/FVC < 0.7030% < FEV1 < 50% predictedStage IV: Very Severe FEV1/FVC < 0.70FEV1 < 30% predicted orFEV1 < 50% predicted plus chronic respiratory failure
15“At Risk” for COPDCOPD includes four stages of severity classified by spirometry.A fifth category--Stage 0: At Risk--that appeared in the 2001 report is no longer included as a stage of COPD, as there is incomplete evidence that the individuals who meet the definition of “At Risk” (chronic cough and sputum production, normal spirometry) necessarily progress on to Stage I: Mild COPD.The public health message is that chronic cough and sputum are not normal remains important - their presence should trigger a search for underlying cause(s).
16Global Strategy for Diagnosis, Management and Prevention of COPD Definition, ClassificationBurden of COPDRisk FactorsPathogenesis, Pathology, PathophysiologyManagementPrimary Care Recommendations
17Burden of COPD: Key Points COPD is a leading cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing.COPD prevalence, morbidity, and mortality vary across countries and across different groups within countries.The burden of COPD is projected to increase in the coming decades due to continued exposure to COPD risk factors and the changing age structure of the world’s population.
18Burden of COPD: Prevalence Many sources of variation can affect estimates of COPD prevalence, including e.g., sampling methods, response rates and quality of spirometry.Data are emerging to provide evidence that prevalence of Stage I: Mild COPD and higher is appreciably higher in:- smokers and ex-smokers- people over 40 years of age- males
19in Latin America (Platino) COPD Prevalence Studyin Latin America (Platino)The prevalence of post-bronchodilator FEV1/FVC < 0.70 increases steeply with age in 5 Latin American CitiesSource: Menezes AM et al. Lancet 2005
20Prevalence of GOLD Stage II & III in 12 Countries by Sex & Descending Prevalence of Smoking (Lancet,2007; 370: )
21Burden of COPD: Mortality COPD is a leading cause of mortality worldwide and projected to increase in the next several decades.COPD mortality trends generally track several decades behind smoking trends.Between 1999 and 2006, death rates for COPD have declined among U.S. men; there has been no significant change among death rates among U.S. women.
22Of the six leading causes of death in the United States, only COPD has been increasing steadily since 1970Source: Jemal A. et al. JAMA 2005
23COPD Mortality by Gender U.S., 1999-2006 Between 1999 and 2006, death rates for COPD have declined among U.S. men.There has been no significant change among death rates among U.S. women.Source: US Centers for Disease Control and Prevention, 2011
24Global Strategy for Diagnosis, Management and Prevention of COPD Definition, ClassificationBurden of COPDRisk FactorsPathogenesis, Pathology, PathophysiologyManagementPrimary Care Recommendations
25Risk Factors for COPD Genes Lung growth and development Exposure to particlesTobacco smokeOccupational dusts, organic and inorganicIndoor air pollution from heating and cooking with biomass in poorly ventilated dwellingsOutdoor air pollutionLung growth and developmentOxidative stressGenderAgeRespiratory infectionsSocioeconomic statusNutritionComorbidities
29Amplifying mechanisms Pathogenesis of COPDCigarette smokeBiomass particlesParticulatesHost factorsAmplifying mechanismsLUNG INFLAMMATIONAnti-oxidantsAnti-proteinasesOxidativestressProteinasesRepairmechanismsCOPD PATHOLOGYSource: Peter J. Barnes, MD
30Alveolar wall destruction Changes in Lung Parenchyma in COPDAlveolar wall destructionLoss of elasticityDestruction of pulmonarycapillary bed↑ Inflammatory cellsmacrophages, CD8+ lymphocytesSource: Peter J. Barnes, MD
31Pulmonary Hypertension in COPD Chronic hypoxiaPulmonary vasoconstrictionMuscularizationIntimalhyperplasiaFibrosisObliterationPulmonary hypertensionNewCor pulmonaleEdemaDeathSource: Peter J. Barnes, MD
32COPD ASTHMA Airflow Limitation Small airway narrowing Alv macrophageEp cellsCD8+ cell(Tc1)NeutrophilCigarette smokeSmall airway narrowingAlveolar destructionCOPDASTHMAAllergensYEp cellsMast cellCD4+ cell(Th2)EosinophilBronchoconstrictionAHRAirflow LimitationReversibleIrreversibleSource: Peter J. Barnes, MD
33Global Strategy for Diagnosis, Management and Prevention of COPD Definition, ClassificationBurden of COPDRisk FactorsPathogenesis, Pathology, PathophysiologyManagementPrimary Care Recommendations
34Four Components of COPD Management Assess and monitor diseaseReduce risk factorsManage stable COPDEducationPharmacologicNon-pharmacologicManage exacerbations
35GOALS of COPD MANAGEMENT VARYING EMPHASIS WITH DIFFERING SEVERITYRelieve symptomsPrevent disease progression• Improve exercise tolerance• Improve health status• Prevent and treat complications• Prevent and treat exacerbations• Reduce mortality
36Four Components of COPD Management Assess and monitor diseaseReduce risk factorsManage stable COPDEducationPharmacologicNon-pharmacologicManage exacerbations
37Assess and Monitor COPD: Key Points Management of Stable COPDAssess and Monitor COPD: Key PointsA clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough or sputum production, and/or a history of exposure to risk factors for the disease.The diagnosis should be confirmed by spirometry. A post-bronchodilator FEV1/FVC < 0.70 confirms the presence of airflow limitation that is not fully reversible.Comorbidities are common in COPD and should be actively identified.
38indoor/outdoor pollution Diagnosis of COPDEXPOSURE TO RISKFACTORSSYMPTOMScoughtobaccosputumoccupationshortness of breathindoor/outdoor pollutionA diagnosis of COPD should be considered in any patient who has cough, sputum production, or dyspnea and/or a history of exposure to risk factors. The diagnosis is confirmed by spirometry.To help identify individuals earlier in the course of disease, spirometry should be performed for patients who have chronic cough and sputum production even if they do not have dyspnea.Spirometry is the best way to diagnose COPD and to monitor its progression and health care workers to care for COPD patients should have assess to spirometry.èèèSPIROMETRY
39Assess and Monitor COPD: Spirometry Management of Stable COPDAssess and Monitor COPD: SpirometrySpirometry should be performed after the administration of an adequate dose of a short- acting inhaled bronchodilator to minimize variability.A post-bronchodilator FEV1/FVC < 0.70 confirms the presence of airflow limitation that is not fully reversible.Where possible, values should be compared to age-related normal values to avoid overdiagnosis of COPD in the elderly.
41Differential Diagnosis: COPD and Asthma Onset in mid-lifeSymptoms slowly progressiveLong smoking historyDyspnea during exerciseLargely irreversible airflowlimitationOnset early in life (often childhood)Symptoms vary from day to daySymptoms at night/early morningAllergy, rhinitis, and/or eczema also presentFamily history of asthmaLargely reversible airflow limitation
42COPD and Co-Morbidities COPD patients are at increased risk for:Myocardial infarction, anginaOsteoporosisRespiratory infectionDepressionDiabetesLung cancer
43COPD and Co-Morbidities COPD has significant extrapulmonary(systemic) effects including:Weight lossNutritional abnormalitiesSkeletal muscle dysfunction
44Four Components of COPD Management Assess and monitor diseaseReduce risk factorsManage stable COPDEducationPharmacologicNon-pharmacologicManage exacerbations
45Reduce Risk Factors: Key Points Management of Stable COPDReduce Risk Factors: Key PointsReduction of total personal exposure to tobacco smoke, occupational dusts and chemicals, and indoor and outdoor air pollutants are important goals to prevent the onset and progression of COPD.Smoking cessation is the single most effective — and cost effective — intervention in most people to reduce the risk of developing COPD and stop its progression (Evidence A).
46Brief Strategies to Help the Patient Willing to Quit Smoking ASK Systematically identify all tobacco users at every visitADVISE Strongly urge all tobacco users to quitASSESS Determine willingness to make a quit attemptASSIST Aid the patient in quittingARRANGE Schedule follow-up contact.Reduction of total personal exposure to tobacco smoke, occupational dusts and chemicals, and indoor and outdoor air pollutants are important goals to prevent the onset and progression of COPD.Smoking cessation is the single most effective - and cost effective - intervention to reduce the risk of developing COPD and stop its progression.Brief tobacco dependence treatment is effective, and every tobacco user should be offered at least this treatment at every visit to a health care provider.Three types of counseling are especially effective: practical counseling, social support as part of treatment, and social support arranged outside of treatment.
47Reduce Risk Factors: Smoking Cessation Management of Stable COPDReduce Risk Factors: Smoking CessationCounseling delivered by physicians and other health professionals significantly increases quit rates over self-initiated strategies. Even a brief(3-minute) period of counseling to urge a smoker to quit results in smoking cessation rates of 5-10%.Numerous effective pharmacotherapies for smoking cessation are available; pharmacotherapy is recommended when counseling is not sufficient to help patients quit smoking.
48Reduce Risk Factors: Indoor/Outdoor Air Pollution Management of Stable COPDReduce Risk Factors: Indoor/Outdoor Air PollutionReducing the risk from indoor and outdoor air pollution is feasible and requires a combination of public policy and protective steps taken by individual patients.Reduction of exposure to smoke from biomass fuel, particularly among women and children, is a crucial goal to reduce the prevalence of COPD worldwide.
49Four Components of COPD Management Assess and monitor diseaseReduce risk factorsManage stable COPDEducationPharmacologicNon-pharmacologicManage exacerbations
50Manage Stable COPD: Key Points Management of Stable COPDManage Stable COPD: Key PointsThe overall approach to managing stable COPD should be individualized to address symptoms and improve quality of life.For patients with COPD, health education plays an important role in smoking cessation (Evidence A) and can also play a role in improving skills, ability to cope with illness and health status.Most studies have shown that existing medications for COPD do not modify the long-term decline in lung function that is the hallmark of this disease (Evidence A). Therefore, pharmacotherapy for COPD is mainly used to decrease symptoms and/or complications.
51Pharmacotherapy: Bronchodilators Management of Stable COPDPharmacotherapy: BronchodilatorsBronchodilator medications are central to the symptomatic management of COPD (Evidence A).Bronchodilators are prescribed on an as-needed or on a regular basis to prevent or reduce symptoms.The principal bronchodilator treatments are ß2- agonists, anticholinergics, and methylxanthines used singly or in combination (Evidence A).Long-acting bronchodilators are more effective and convenient than treatment with short-acting bronchodilators (Evidence A).
52Pharmacotherapy: Glucocorticosteroids Management of Stable COPDPharmacotherapy: GlucocorticosteroidsRegular treatment with inhaled glucocorticosteroids reduces frequency of exacerbations for symptomatic COPD patients with an FEV1 < 50% predicted (Stage III: Severe COPD and Stage IV: Very Severe COPD) and repeated exacerbations.Treatment with inhaled glucocortciosteroids increases the likelihood of pneumonia and does not reduce overall mortality.
53Addition of a long-acting ß2-agonist /inhaled gluco- Management of Stable COPDPharmacotherapy: Combination Therapy Glucocorticosteroids and Long-Acting ß2-agonistAn inhaled glucocorticosteroid combined with a long-acting ß2-agonist is more effective than the individual components in reducing exacerbations and improving lung function (Evidence A).Combination therapy increases the likelihood of pneumonia and has no impact on mortality.Addition of a long-acting ß2-agonist /inhaled gluco-Corticosteroid comgination to an anticholinergic (tiotropium) appears to provide additional benefits.
54Pharmacotherapy: Systemic Glucocorticosteroids Management of Stable COPDPharmacotherapy: Systemic GlucocorticosteroidsChronic treatment with systemic glucocorticosteroids should be avoided because of an unfavorable benefit-to-risk ratio (Evidence A).
55Pharmacotherapy: Phosphodiesterase-4 Inhibitors Management of Stable COPDPharmacotherapy: Phosphodiesterase-4 InhibitorsIn patients with Stage III: Severe COPD or Stage IV: Very Severe COPD and a history of exacerbations and chronic bronchitis, the phospodiesterase-4 inhibitor, roflumilast, reduces exacerbations treated with oral glucocorticosteroids.
56Pharmacotherapy: Vaccines Management of Stable COPDPharmacotherapy: VaccinesIn COPD patients influenza vaccines can reduce serious illness (Evidence A).Pneumococcal polysaccharide vaccine is recommended for COPD patients 65 years and older and for COPD patients younger than age 65 with an FEV1 < 40% predicted (Evidence B).Influenza, not pneumococcal vaccination is associated with reduced risk of all-cause mortality in COPD (Evidence B).
57Management of Stable COPD All Stages of Disease Severity Avoidance of risk factors- smoking cessation- reduction of indoor pollution- reduction of occupational exposureInfluenza vaccination
58Therapy at Each Stage of COPD* I: MildII: ModerateIII: SevereIV: Very SevereFEV1/FVC < 70%FEV1 < 30% predictedor FEV1 < 50% predicted plus chronic respiratory failureFEV1/FVC < 70%30% < FEV1 < 50% predictedFEV1/FVC < 70%50% < FEV1 < 80%predictedFEV1/FVC < 70%FEV1 > 80% predictedActive reduction of risk factor(s); influenza vaccinationAdd short-acting bronchodilator (when needed)Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitationAdd inhaled glucocorticosteroids if repeated exacerbationsAdd long term oxygen if chronic respiratory failure. Consider surgical treatments*Postbronchodilator FEV1 is recommended for the diagnosisand assessment of severity of COPD
59Other Pharmacologic Treatments Management of Stable COPDOther Pharmacologic TreatmentsAntibiotics: Only used to treat infectious exacerbations of COPDAntioxidant agents: No effect of n-acetyl-cysteine on frequency of exacerbations, except in patients not treated with inhaled glucocorticosteroidsMucolytic agents, Antitussives, Vasodilators: Not recommended in stable COPD
60Non-Pharmacologic Treatments Management of Stable COPDNon-Pharmacologic TreatmentsRehabilitation: All COPD patients benefit from exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A).Oxygen Therapy: The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival (Evidence A).
61Four Components of COPD Management Assess and monitor diseaseReduce risk factorsManage stable COPDEducationPharmacologicNon-pharmacologicManage exacerbations
62Key Points An exacerbation of COPD is defined as: Management COPD ExacerbationsKey PointsAn exacerbation of COPD is defined as:“An event in the natural course of the disease characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD.”
63Key Points Management COPD Exacerbations The most common causes of an exacerbation are infection of the tracheobronchial tree and air pollution, but the cause of about one-third of severe exacerbations cannot be identified (Evidence B).Patients experiencing COPD exacerbations with clinical signs of airway infection (e.g., increased sputum purulence) may benefit from antibiotic treatment (Evidence B).
64Key Points Manage COPD Exacerbations Inhaled bronchodilators (particularly inhaled ß2-agonists with or without anticholinergics) and oral glucocortico- steroids are effective treatments for exacerbations of COPD (Evidence A).
65Key Points Management COPD Exacerbations Noninvasive mechanical ventilation in exacerbations improves respiratory acidosis, increases pH, decreases the need for endotracheal intubation, and reduces PaCO2, respiratory rate, severity of breathlessness, the length of hospital stay, and mortality (Evidence A).Medications and education to help prevent future exacerbations should be considered as part of follow-up, as exacerbations affect the quality of life and prognosis of patients with COPD.
66Global Strategy for Diagnosis, Management and Prevention of COPD Definition, ClassificationBurden of COPDRisk FactorsPathogenesis, Pathology, PathophysiologyManagementPrimary Care Recommendations
67Translating COPD Guidelines into Primary Care KEY POINTS Better dissemination of COPD guidelines and their effective implementation in a variety of health care settings is urgently required.In many countries, primary care practitioners treat the vast majority of patients with COPD and may be actively involved in public health campaigns and in bringing messages about reducing exposure to risk factors to both patients and the public.
68Translating COPD Guidelines into Primary Care KEY POINTS Spirometric confirmation is a key component of the diagnosis of COPD and primary care practitioners should have access to high quality spirometry.Older patients frequently have multiple chronic health conditions. Comorbidities can magnify the impact of COPD on a patient’s health status, and can complicate the management of COPD.
69Global Strategy for Diagnosis, Management and Prevention of COPD SUMMARY Definition, ClassificationBurden of COPDRisk FactorsPathogenesis, Pathology, PathophysiologyManagementPrimary Care Recommendations
70COPD is increasing in prevalence in many countries of the world. Global Strategy for Diagnosis, Management and Prevention of COPD: SummaryCOPD is increasing in prevalence in many countries of the world.COPD is treatable and preventable.The GOLD program offers a strategy to identify patients and to treat them according to the best medications available.
71Global Strategy for Diagnosis, Management and Prevention of COPD: Summary COPD can be prevented by avoidance of risk factors, the most notable being tobacco smoke.Patients with COPD have multiple other conditions (comorbidities) that must be taken into consideration.GOLD has developed a global network to raise awareness of COPD and disseminate information on diagnosis and treatment.
73China GOLD National Leaders Israel Slovenia Germany Brazil Ireland BangladeshSaudi ArabiaSloveniaGermanyBrazilIrelandYugoslaviaCroatiaUnited StatesAustraliaCanadaAustriaTaiwan ROCPortugalPhilippinesThailandYemanNorwayMaltaMoldovaGreeceSyriaChinaSouth AfricaKazakhstanUnited KingdomHong Kong ROCItalyNew ZealandNepalChileIsraelArgentinaMexicoPakistanRussiaUnited Arab EmiratesJapanPeruGOLD National LeadersPolandKoreaNetherlandsEgyptSwitzerlandIndiaVenezuelaGeorgiaFranceMacedoniaIcelandCzech RepublicDenmarkTurkeySlovakiaBelgiumSingaporeSpainUkraineRomaniaColumbiaUruguaySwedenVietnamAlbaniaKyrgyzstan
75ADDITIONAL SLIDES WITH NOTES PREPARED BY: PROFESSOR PETER J. BARNES, MDNATIONAL HEART AND LUNG INSTITUTELONDON, ENGLAND
76Squamous metaplasia of epithelium No basement membrane thickening Changes in Large Airways of COPD PatientsMucus hypersecretionNeutrophils in sputumSquamous metaplasia of epitheliumNo basement membrane thickeningGoblet cellhyperplasia↑ Macrophages↑ CD8+ lymphocytesChanges in large airways of COPD patients. The epithelium often shows squamous metaplasia and there is goblet cell and submucosal gland hyperplasia, resulting in mucus hypersecretion. The airway wall is infiltrated with macrophages and CD8+ lymphocytes, whereas neutrophils predominate in the airway lumen and around submucosal glands. Airway smooth muscle and basement membrane are minimally increased compared to the findings in asthma.Mucus gland hyperplasiaLittle increase inairway smooth muscleSource: Peter J. Barnes, MD
77Changes in Small Airways in COPD Patients Inflammatory exudate in lumenDisrupted alveolar attachmentsChanges in small airways in COPD patients. The airway wall is thickened and infiltrated with inflammatory cells, predominately macrophages and CD8+ lymphocytes, with increased numbers of fibroblasts. In severe COPD there are also lymphoid follicles. The lumen is often filled with an inflammatory exudate and mucus. There is peribronchial fibrosis and airway smooth muscle may be increased, resulting in narrowing of the airway.Thickened wall with inflammatory cells- macrophages, CD8+ cells, fibroblastsPeribronchial fibrosisLymphoid follicleSource: Peter J. Barnes, MD
78Alveolar wall destruction Changes in the Lung Parenchyma in COPD PatientsAlveolar wall destructionLoss of elasticityChanges in the lung parenchyma in COPD patients. There is loss of elasticity and alveolar wall destruction, and accumulation of inflammatory cells, predominantly macrophages and CD8+ lymphocytes. The destructive changes reduce the pulmonary capillary bed. The left panel shows a scanning electron micrograph of a patient with emphysema demonstrating the enlargement of alveoli and destruction of the alveolar walls.Destruction of pulmonarycapillary bed↑ Inflammatory cellsmacrophages, CD8+ lymphocytesSource: Peter J. Barnes, MD
79Endothelial dysfunction Smooth muscle hyperplasia Changes in Pulmonary Arteries in COPD PatientsEndothelial dysfunctionIntimal hyperplasiaSmooth muscle hyperplasiaChanges in pulmonary arteries in COPD patients. There is dysfunction of endothelial cells (reduced vasodilator release), intimal thickening, hyperplasia of smooth muscle and infiltration with inflammatory cells, predominantly macrophages and CD8+ lymphocytes.↑ Inflammatory cells(macrophages, CD8+ lymphocytes)Source: Peter J. Barnes, MD
80Amplifying mechanisms Pathogenesis of COPDCigarette smokeBiomass particlesParticulatesHost factorsAmplifying mechanismsLUNG INFLAMMATIONAnti-oxidantsAnti-proteinasesOxidativestressPathogenesis of COPD, illustrating the central role of inflammationProteinasesRepairmechanismsCOPD PATHOLOGYSource: Peter J. Barnes, MD
81PROTEASES Fibrosis Inflammatory Cells Involved in COPD CD8+ Neutrophil Cigarette smoke(and other irritants)EpithelialcellsAlveolar macrophageChemotactic factorsCD8+lymphocyteFibroblastNeutrophilMonocyteInflammatory cells involved in COPD. Cigarette smoke activates macrophages and epithelial cells to release chemotactic factors that recruit neutrophils, monocytes and CD8+ T-lymphocytes from the circulation. They also release factors that activate fibroblasts leading to small airway obstruction (obstructive bronchiolitis). Proteases released from neutrophils and macrophages may cause mucus hypersecretion and emphysema.Neutrophil elastaseCathepsinsMMPsPROTEASESFibrosis(Obstructivebronchiolitis)Alveolar wall destructionMucus hypersecretion(Emphysema)Source: Peter J. Barnes, MD
82↓ HDAC2 ↑Inflammation Steroid resistance Oxidative Stress in COPDMacrophageNeutrophilAnti-proteasesSLPI1-ATNF-BProteolysisIL-8TNF-↓ HDAC2↑InflammationSteroidresistanceO2-, H202OH., ONOO-NeutrophilrecruitmentOxidative stress in COPD has several detrimental consequences, including activation of the transcription factor nuclear factor-κB (NF-κB), reduction in antiproteases, plasma leakage and mucus hypersecretion. In addition it reduces histone deacetylase-2, resulting in amplified inflammation and reduced anti-inflammatory response to corticosteroids.IsoprostanesBronchoconstrictionPlasma leak Mucus secretionSource: Peter J. Barnes, MD
83COPD ASTHMA Airflow Limitation Differences in Inflammation and its Consequences: Asthma and COPDAlv macrophageEp cellsCD8+ cell(Tc1)NeutrophilCigarette smokeSmall airway narrowingAlveolar destructionCOPDASTHMAAllergensYEp cellsMast cellCD4+ cell(Th2)EosinophilBronchoconstrictionAHRAirflow LimitationIrreversibleReversibleSource: Peter J. Barnes, MD
84Air Trapping in COPD Mild/moderate COPD Normal Severe COPD ↓ Health Inspirationsmallairwayalveolar attachmentsloss of elasticityloss of alveolar attachmentsExpirationclosureAir trapping in COPD. During expiration small airways narrow but closure is prevented by the elasticity of alveolar attachments. In COPD patients there is a loss of elasticity with greater narrowing in small airways, which may close completely when there is loss of alveolar attachments as a result of emphysema. This results in air trapping and hyperinflation, leading to dyspnea and reduced exercise capacity.↓ HealthstatusDyspnea↓ Exercise capacityAir trappingHyperinflationSource: Peter J. Barnes, MD
85Pulmonary Hypertension in COPD Chronic hypoxiaPulmonary vasoconstrictionMuscularizationIntimalhyperplasiaFibrosisObliterationPulmonary hypertensionCor pulmonaleEdemaDeathSource: Peter J. Barnes, MD
86Inflammation in COPD Exacerbations Bacteria Viruses Non-infectivePollutantsMacrophagesEpithelial cellsTNF-IL-8IL-6Inflammation in COPD exacerbations induced by several causal mechanisms. Increased numbers of inflammatory cells, particularly neutrophils, are seen with increased concentrations of inflammatory mediators and oxidative stress.NeutrophilsOxidative stressSource: Peter J. Barnes, MD