© Global Initiative for Chronic Obstructive Lung Disease GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE...

© Global Initiative for Chronic Obstructive Lung Disease

GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE (GOLD): TEACHING SLIDE SET

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GOLD.

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© Global Initiative for Chronic Obstructive Lung Disease

GOLD StructureGOLD Structure

GOLD Board of DirectorsRoberto Rodriguez-Roisin, MD – Chair

Fernando Martinez, MD – Co-Chair

GOLD Board of DirectorsRoberto Rodriguez-Roisin, MD – Chair


Science Committee

Jorgen Vestbo, MD - Chair

Science Committee


Dissemination/ImplementationCommittee

Jean Bourbeau, MD - Chair

Dissemination/ImplementationCommittee


GOLD Board of Directors: 2011

GOLD Board of Directors: 2011

R. Rodriguez-Roisin, Chair, Spain

A. Anzueto, US [ATS]

J. Bourbeau, Canada

T. DeGuia, Philippines

D. Hui, Hong Kong PRC

F. Martinez, US

M. Mishima, Japan [APSR]

R. Rodriguez-Roisin, Chair, Spain

A. Anzueto, US [ATS]

J. Bourbeau, Canada

T. DeGuia, Philippines

D. Hui, Hong Kong PRC

F. Martinez, US

M. Mishima, Japan [APSR]

D. Nugmanova, Kazakhstan [WONCA]

A.Ramirez, Mexico [ALAT]

R. Stockley, UK

J. Vestbo, Denmark, UK

J. Wedzicha, UK [ERS]

GOLD Science Committee - 2011

GOLD Science Committee - 2011

J. Vestbo, Chair

A. Agusti,

A. Anzueto

P. Barnes

L. Fabbri

P. Jones

J. Vestbo, Chair

A. Agusti,

A. Anzueto

P. Barnes

L. Fabbri

P. Jones

F. Martinez

M. Nishimura

R. Rodriguez-

Roisin

D. Sin

R. Stockley

C. Vogelmeier

Evidence Category

Sources of Evidence

A Randomized controlled trials (RCTs). Rich body of data

B Randomized controlled trials(RCTs). Limited body of data

C Nonrandomized trialsObservational studies.

D Panel consensus judgment

Description of Levels of Evidence

GOLD StructureGOLD Structure

GOLD Executive CommitteeRoberto Rodriguez-Roisin, MD – Chair


GOLD Executive CommitteeRoberto Rodriguez-Roisin, MD – Chair


Science Committee


Science Committee


Dissemination/ImplementationTask Group


Dissemination/ImplementationTask Group


GOLD National Leaders - GNL

United StatesUnited States

United Kingdom

ArgentinaArgentina

AustraliaAustraliaBrazilBrazil

AustriaCanadaCanada

Chile

Belgium

ChinaChina

DenmarkDenmark

ColumbiaColumbia

CroatiaCroatia

EgyptEgypt

Germany

Greece

IrelandIreland

ItalyItaly

SyriaSyria

Hong Kong ROC

Japan

IcelandIndiaIndia

KoreaKorea

KyrgyzstanUruguayUruguay

MoldovaMoldova

NepalNepal

Macedonia

Malta

Netherlands

New Zealand

PolandPoland

NorwayNorway

Portugal

GeorgiaGeorgia

Romania

Russia

SingaporeSlovakia

Slovenia Saudi ArabiaSaudi Arabia

South AfricaSouth Africa

Spain

SwedenSweden

ThailandThailand

SwitzerlandSwitzerland

UkraineUkraine

United Arab EmiratesUnited Arab Emirates

Taiwan ROC

VenezuelaVenezuela

Vietnam

Peru

Yugoslavia

Albania

Bangladesh

France

Mexico

Turkey Czech Republic

Pakistan

Israel

GOLD National Leaders

PhilippinesYeman

Kazakhstan

GOLD Website Address

http://www.goldcopd.org


bstructive

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GOLD Objectives

Increase awareness of COPD among health professionals, health authorities, and the general public

Improve diagnosis, management and prevention

Decrease morbidity and mortality

Stimulate research

Global Strategy for Diagnosis, Management and Prevention of COPD


Definition, Classification

Burden of COPD Risk Factors Pathogenesis,

Pathology, Pathophysiology

Management of COPD

Primary Care Recommendations




Management of COPD

Primary Care Recommendations

Definition of COPD

COPD 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.

Classification of COPD Severity

by SpirometryStage I: Mild FEV1/FVC < 0.70

FEV1 > 80% predicted

Stage II: Moderate FEV1/FVC < 0.70 50% < FEV1 < 80% predicted

Stage III: Severe FEV1/FVC < 0.70 30% < FEV1 < 50% predicted

Stage IV: Very Severe FEV1/FVC < 0.70 FEV1 < 30% predicted or

FEV1 < 50% predicted plus chronic respiratory failure

“At Risk” for COPD

COPD 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).






Management Primary Care

Recommendations





Recommendations

Burden 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.

Burden 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

COPD Prevalence Study in Latin America (Platino)

The prevalence of post-bronchodilator FEV1/FVC < 0.70 increases steeply with age in 5 Latin American Cities

Source: Menezes AM et al. Lancet 2005

Prevalence of GOLD Stage II & III in 12 Countries by Sex & Descending

Prevalence of Smoking

(Lancet,2007; 370: 741-50)

Burden 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.

Of the six leading causes of death in the United States, only COPD has been increasing steadily since 1970

Source: Jemal A. et al. JAMA 2005

COPD Mortality by GenderU.S., 1999-2006

Source: US Centers for Disease Control and Prevention, 2011

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.







Recommendations





Recommendations

Risk Factors for COPD

Lung growth and development

Oxidative stress

Gender

Age

Respiratory infections

Socioeconomic status

Nutrition

Comorbidities

Genes

Exposure to particles

●Tobacco smoke

●Occupational dusts, organic and inorganic

●Indoor air pollution from heating and cooking with biomass in poorly ventilated dwellings

●Outdoor air pollution

Risk Factors for COPD

NutritionNutrition

InfectionsInfections

Socio-economic Socio-economic statusstatus

Aging PopulationsAging Populations







Recommendations





Recommendations

LUNG INFLAMMATIONLUNG INFLAMMATION

COPD PATHOLOGYCOPD PATHOLOGY

OxidativeOxidativestressstress ProteinasesProteinases

Repair Repair mechanismsmechanisms

Anti-proteinasesAnti-proteinasesAnti-oxidantsAnti-oxidants

Host factorsAmplifying mechanisms

Cigarette smokeCigarette smokeBiomass particlesBiomass particles

ParticulatesParticulates

Source: Peter J. Barnes, MD

Pathogenesis of COPD

Alveolar wall destruction

Loss of elasticity

Destruction of pulmonarycapillary bed

↑ Inflammatory cells macrophages, CD8+ lymphocytes


Changes in Lung Parenchyma in COPD

Chronic hypoxiaChronic hypoxia

Pulmonary vasoconstrictionPulmonary vasoconstriction

MuscularizationMuscularization

Intimal Intimal hyperplasiahyperplasia

FibrosisFibrosis

ObliterationObliteration

Pulmonary hypertensionPulmonary hypertension

Cor pulmonaleCor pulmonale

Death

EdemaEdema

Pulmonary Hypertension in COPD


YYYYYY

Mast cellMast cell

CD4+ cellCD4+ cell(Th2)(Th2)

EosinophilEosinophil

AllergensAllergens

Ep cellsEp cells

ASTHMAASTHMA

BronchoconstrictionBronchoconstrictionAHRAHR

Alv macrophageAlv macrophage Ep cellsEp cells

CD8+ cellCD8+ cell(Tc1)(Tc1)

NeutrophilNeutrophil

Cigarette smokeCigarette smoke

Small airway narrowingSmall airway narrowingAlveolar destructionAlveolar destruction

COPDCOPD

Reversible IrreversibleAirflow LimitationAirflow Limitation








Recommendations





Recommendations

Four Components of COPD Management

Four Components of COPD Management

1. Assess and monitor disease

2. Reduce risk factors

3. Manage stable COPD Education Pharmacologic Non-pharmacologic

4. Manage exacerbations





• Relieve symptoms • Prevent disease progression• Improve exercise tolerance• Improve health status• Prevent and treat complications• Prevent and treat exacerbations• Reduce mortality

GOALS of COPD MANAGEMENTVARYING EMPHASIS WITH DIFFERING SEVERITY

Four Components of COPD ManagementFour Components of COPD Management









Management of Stable COPD

Assess and Monitor COPD: Key Points

A 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.

SYMPTOMScoughcough

sputumsputumshortness of breathshortness of breath

EXPOSURE TO RISKFACTORS

tobaccotobaccooccupationoccupation

indoor/outdoor pollutionindoor/outdoor pollution

SPIROMETRYSPIROMETRY

Diagnosis of COPDDiagnosis of COPD


Assess and Monitor COPD: Spirometry

Spirometry 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.

Spirometry: Normal and Patients with COPD

Differential Diagnosis: Differential Diagnosis: COPD and AsthmaCOPD and Asthma

COPD ASTHMA

• Onset in mid-life

• Symptoms slowly progressive

• Long smoking history

• Dyspnea during exercise

• Largely irreversible airflow limitation

• Onset early in life (often childhood)

• Symptoms vary from day to day

• Symptoms at night/early morning

• Allergy, rhinitis, and/or eczema also present

• Family history of asthma

• Largely reversible airflow limitation

COPD and Co-MorbiditiesCOPD and Co-Morbidities

COPD patients are at increased risk for: • Myocardial infarction, angina

• Osteoporosis

• Respiratory infection

• Depression

• Diabetes

• Lung cancer

COPD patients are at increased risk for: • Myocardial infarction, angina

• Osteoporosis

• Respiratory infection

• Depression

• Diabetes

• Lung cancer

COPD and Co-MorbiditiesCOPD and Co-Morbidities

COPD has significant extrapulmonary

(systemic) effects including:

• Weight loss

• Nutritional abnormalities

• Skeletal muscle dysfunction

COPD has significant extrapulmonary

(systemic) effects including:

• Weight loss

• Nutritional abnormalities

• Skeletal muscle dysfunction











Reduce Risk Factors: Key Points

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 in most people to reduce the risk of developing COPD and stop its progression (Evidence A).

Brief Strategies to Help the Patient Willing to Quit Smoking

• ASK Systematically identify all tobacco users at every visit

• ADVISE Strongly urge all tobacco users to quit

• ASSESS Determine willingness to make a quit attempt

• ASSIST Aid the patient in quitting

• ARRANGE Schedule follow-up contact.


Reduce Risk Factors: Smoking Cessation

Counseling 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.


Reduce Risk Factors: Indoor/Outdoor Air Pollution

Reducing 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.











Manage Stable COPD: Key Points

The 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.


Pharmacotherapy: Bronchodilators Bronchodilator 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).


Pharmacotherapy: Glucocorticosteroids

Regular 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.


Pharmacotherapy: Combination Therapy Glucocorticosteroids and Long-Acting ß2-agonist

An 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.


Pharmacotherapy: Systemic Glucocorticosteroids

Chronic treatment with systemic glucocorticosteroids should be avoided because of an unfavorable benefit-to-risk ratio (Evidence A).


Pharmacotherapy: Phosphodiesterase-4 Inhibitors

In 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.


Pharmacotherapy: Vaccines

In 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).


All Stages of Disease Severity


All Stages of Disease Severity

Avoidance of risk factors

- smoking cessation

- reduction of indoor pollution

- reduction of occupational exposure

Influenza vaccination

Avoidance of risk factors

- smoking cessation

- reduction of indoor pollution

- reduction of occupational exposure

Influenza vaccination

IV: Very Severe III: Severe II: Moderate I: Mild

Therapy at Each Stage of COPD*

FEV1/FVC < 70%

FEV1 > 80% predicted

FEV1/FVC < 70%

50% < FEV1 < 80%

predicted

FEV1/FVC < 70%

30% < FEV1 < 50% predicted

FEV1/FVC < 70%

FEV1 < 30% predicted

or FEV1 < 50% predicted plus chronic respiratory failure

Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation

Add inhaled glucocorticosteroids if repeated exacerbations

Active reduction of risk factor(s); influenza vaccinationAdd short-acting bronchodilator (when needed)

Add long term oxygen if chronic respiratory failure. Consider surgical treatments

*Postbronchodilator FEV1 is recommended for the diagnosis

and assessment of severity of COPD


Other Pharmacologic Treatments

Antibiotics: Only used to treat infectious exacerbations of COPD

Antioxidant agents: No effect of n-acetyl-cysteine on frequency of exacerbations, except in patients not treated with inhaled glucocorticosteroids

Mucolytic agents, Antitussives, Vasodilators: Not recommended in stable COPD


Non-Pharmacologic Treatments

Rehabilitation: 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).










Management COPD Exacerbations

Key Points

An 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.”


Key Points

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).

Manage COPD Exacerbations

Key Points

Inhaled bronchodilators

(particularly inhaled ß2-agonists

with or without anticholinergics)

and oral glucocorticosteroids

are effective treatments for

exacerbations of COPD (Evidence

A).


Key Points

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.







Recommendations





Recommendations

Translating COPD Guidelines into Primary Care

KEY POINTS


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.

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.


KEY POINTS


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.

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.

Global Strategy for Diagnosis, Management and Prevention of

COPDSUMMARY

Global Strategy for Diagnosis, Management and Prevention of

COPDSUMMARY





Recommendations





Recommendations

Global Strategy for Diagnosis, Management and Prevention of COPD: Summary

COPD 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.

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.

Global Strategy for Diagnosis, Management and Prevention of COPD:

Summary

WORLD COPD DAYNovember 16, 2011

WORLD COPD DAYNovember 16, 2011

Raising COPD Awareness WorldwideRaising COPD Awareness Worldwide

United StatesUnited States

United Kingdom

ArgentinaArgentina

AustraliaAustraliaBrazilBrazil

AustriaCanadaCanada

Chile

Belgium

ChinaChina

DenmarkDenmark

ColumbiaColumbia

CroatiaCroatia

EgyptEgypt

Germany

Greece

IrelandIreland

ItalyItaly

SyriaSyria

Hong Kong ROC

Japan

IcelandIndiaIndia

KoreaKorea

KyrgyzstanUruguayUruguay

MoldovaMoldova

NepalNepal

Macedonia

Malta

Netherlands

New Zealand

PolandPoland

NorwayNorway

Portugal

GeorgiaGeorgia

Romania

Russia

SingaporeSlovakia

Slovenia Saudi ArabiaSaudi Arabia

South AfricaSouth Africa

Spain

SwedenSweden

ThailandThailand

SwitzerlandSwitzerland

UkraineUkraine

United Arab EmiratesUnited Arab Emirates

Taiwan ROC

VenezuelaVenezuela

Vietnam

Peru

Yugoslavia

Albania

Bangladesh

France

Mexico

Turkey Czech Republic

Pakistan

Israel

GOLD National Leaders

PhilippinesYeman

Kazakhstan

GOLD Website Address

http://www.goldcopd.org

ADDITIONAL SLIDES WITH NOTES

PREPARED BY:

PROFESSOR PETER J. BARNES, MD

NATIONAL HEART AND LUNG

INSTITUTE

LONDON, ENGLAND

Mucus gland hyperplasia

Goblet cellhyperplasia

Mucus hypersecretion Neutrophils in sputum

Squamous metaplasia of epithelium

↑ Macrophages

No basement membrane thickening

Little increase in airway smooth muscle

↑ CD8+ lymphocytes

Changes in Large Airways of COPD Patients

Changes in Large Airways of COPD Patients


Disrupted alveolar attachments

Inflammatory exudate in lumen

Peribronchial fibrosisLymphoid follicle

Thickened wall with inflammatory cells- macrophages, CD8+ cells, fibroblasts

Changes in Small Airways in COPD Patients


Alveolar wall destruction

Loss of elasticity

Destruction of pulmonarycapillary bed

↑ Inflammatory cells macrophages, CD8+ lymphocytes

Changes in the Lung Parenchyma in COPD Patients


Endothelial dysfunction

Intimal hyperplasia

Smooth muscle hyperplasia

↑ Inflammatory cells (macrophages, CD8+ lymphocytes)

Changes in Pulmonary Arteries in COPD Patients


LUNG INFLAMMATIONLUNG INFLAMMATION

COPD PATHOLOGYCOPD PATHOLOGY

OxidativeOxidativestressstress ProteinasesProteinases

Repair Repair mechanismsmechanisms

Anti-proteinasesAnti-proteinasesAnti-oxidantsAnti-oxidants

Host factorsAmplifying mechanisms

Cigarette smokeCigarette smokeBiomass particlesBiomass particles

ParticulatesParticulates

Pathogenesis of COPD


Cigarette smoke Cigarette smoke (and other irritants)(and other irritants)

PROTEASES PROTEASES Neutrophil elastaseNeutrophil elastaseCathepsinsCathepsinsMMPsMMPs

Alveolar wall destructionAlveolar wall destruction(Emphysema)(Emphysema)

Mucus hypersecretionMucus hypersecretion

CD8CD8+ +

lymphocytelymphocyte

Alveolar Alveolar macrophagemacrophage

EpithelialEpithelialcellscells

FibrosisFibrosis(Obstructive(Obstructivebronchiolitis)bronchiolitis)

FibroblastFibroblast

MonocyteMonocyteNeutrophilNeutrophil

Chemotactic factorsChemotactic factors

Inflammatory Cells Involved in COPD


Anti-proteases

SLPI 1-AT

Proteolysis

OO22--, H, H220022

OHOH.., ONOO, ONOO--

Mucus secretion

Plasma leak Bronchoconstriction

NF-NF-BB

IL-8IL-8

NeutrophilNeutrophilrecruitmentrecruitment

TNF-TNF-

IsoprostanesIsoprostanes

↓ ↓ HDAC2HDAC2

↑↑InflammationInflammationSteroidSteroid

resistanceresistance

Macrophage NeutrophilOxidative Stress in COPD


Differences in Inflammation and its Consequences: Asthma and COPD

YYYYYY

Mast cellMast cell

CD4+ cellCD4+ cell(Th2)(Th2)

EosinophilEosinophil

AllergensAllergens

Ep cellsEp cells

ASTHMAASTHMA

BronchoconstrictiBronchoconstrictionon

AHRAHR

Alv macrophageAlv macrophage Ep cellsEp cells

CD8+ cellCD8+ cell(Tc1)(Tc1)

NeutrophilNeutrophil

Cigarette smokeCigarette smoke

Small airway narrowingSmall airway narrowingAlveolar destructionAlveolar destruction

COPDCOPD

Reversible IrreversibleAirflow LimitationAirflow Limitation


NormalNormalInspiration

Expiration

alveolar attachments

Mild/moderateMild/moderateCOPD COPD

loss of elasticity

Severe Severe COPD COPD

loss of alveolar attachments

closure

small small airwayairway

Dyspnea↓ Exercise capacity

Air trappingAir trappingHyperinflationHyperinflation

↓ ↓ HealthHealthstatusstatus

Air Trapping in COPD


Chronic hypoxiaChronic hypoxia

Pulmonary vasoconstrictionPulmonary vasoconstriction

MuscularizationMuscularization

Intimal Intimal hyperplasiahyperplasia

FibrosisFibrosis

ObliterationObliteration

Pulmonary hypertensionPulmonary hypertension

Cor pulmonaleCor pulmonale

Death

EdemaEdema

Pulmonary Hypertension in COPD


Macrophages

TNF- IL-8 IL-6

Bacteria Viruses Non-infective Pollutants

Epithelial cells

Oxidative stressOxidative stress

Neutrophils

Inflammation in COPD Exacerbations


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