COPD Pathology with 3D Interactive Track I S Cerreta … · GOLD Standards COPD Pharmacotherapy 9 Manage Exacerbations: ... Global Initiative for Chronic Lung Disease, Pocket Guide

by

Scott Cerreta, BS, RRT

Director of Education

www.copdfoundation.org

COPD Pathology with3D Interactive

COPD: Change in Definition

• COPD used to include 5 disease processes1

1 Chronic Bronchitis

2 Emphysema

3 Asthma

4 Bronchiectasis

5 Cystic fibrosis & fibrosis from Tb

• Differential diagnosis separates 3 to 5

COPD: Definitions of 21st Century1

• Preventable and treatable

• Airflow limitation that is not fully reversible

• Progressive disease

• Abnormal inflammatory response of the lungs

• Subsets of patients

Chronic bronchitis Emphysema

Asthma

COPDCOPDDC

COPD Includes Chronic Bronchitis2

• Productive cough for 3 months in 2 consecutive years with intermittent wheezing and variable degrees of recurring dyspnea on exertion

• Inflammation of cells that line the bronchus resulting in excess sputum

• Mucous glands enlarge and bronchial walls thicken, resulting in a deformed and narrow airway lumen

COPD Includes Emphysema2

• Abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis.

• Destruction occurs in the alveoli and the orderly appearance of the acinus is disturbed.

• Normal elasticity is lost, air becomes trapped in over-inflated lungs.

COPD: Airway Effects7

Normal Emphysema

Structural changes of Emphysema10 Pathology, Pathogenesis, & Pathophysiology

• Pathology– Characteristics and effects of COPD

• Pathogenesis– Origin and cause of COPD

• Pathophysiology– Biologic and physical manifestations of COPD

• Processes within the body that result in signs and symptoms

COPD: Anatomy Review

Divisions of lower respiratory tract1. Trachea – cartilage; conducting airway

2. Mainstem bronchi – ß2 smooth muscle; conducting airway

3. Secondary bronchi – ß2 smooth muscle; conducting airway

4. Tertiary bronchi – ß2 smooth muscle; conducting airway

5. Bronchioles – ß2 smooth muscle; conducting airway

6. Terminal bronchioles – ß2 smooth muscle; conducting airway

7. Respiratory bronchioles – gas exchange starts here

8. Alveoli – gas exchange; septa are alveolar walls

COPD: Pathology

COPD Compromises Four Compartments of the Lung

1. Central airways – cartilaginous >2mm diameter

• Bronchial glands hypertrophy – increased sputum production

• Airway epithelium metaplasia changes – loss of cilia and cilliary

dysfunction, increased smooth muscle and connective tissue

• Inflammatory cells predominate – lymphocytes (CD8+),

neutrophils, and macrophages

COPD: Pathology


2. Peripheral airways – non-cartilaginous < 2mm diameter

• Bronchiolitis present in early stages of COPD

• Increased number of goblet cells and epethilial metaplasia

• Inflammatory cells predominate – lymphocytes (CD8+),

neutrophils, and macrophages

• Advanced disease reveals fibrosis and more collagen in walls

Cigarette smoke

(and other irritants)

PROTEASES Neutrophil elastaseCathepsinsMMPs

Alveolar wall destructionveolar wall destruct(Emphysema)

Mucus hypersecretion

CD8+

lymphocyte

Alveolar macrophageEpithelialcells

Fibrosis

(Obstructivebronchiolitis)

Fibroblast

MonocyteNeutrophil

Chemotactic factors

Source: Peter J. Barnes, MD

Inflammatory Cells Involved in COPD10

COPD: Pathology1


3. Lung parenchyma – respiratory bronchioles, alveoli, and

capillaries

• Emphysema – enlargement of air spaces distal to terminal

bronchioles, Two types

1. Centrolobular – dilation and destruction of respiratory bronchioles

2. Panlobular – destruction of entire acinus, Alpha1-antitrypisin

• Loss of alveolar attachments – airway collapse

• Inflammation similar to previous

• Development of bullae

Alveolar wall destruction

Loss of elasticity

Destruction of pulmonary

capillary bed

↑ Inflammatory cells

macrophages, CD8+ lymphocytes


Changes in the Lung Parenchyma in COPD Patients10

COPD: Pathology1


4. Pulmonary vasculature

• Begins early in disease

• Vessel wall thickening and endothelial dysfunction

• Increased vascular smooth muscle tone

• Infiltration of vessel wall with CD8+ and T lymphocytes

• Advanced stages – develop collagen deposition and capillary

bed destruction leading to pulmonary hypertension and cor-

pulmonale

Endothelial dysfunction

Intimal hyperplasia

Smooth muscle hyperplasia

↑ Inflammatory cells

(macrophages, CD8+ lymphocytes)


Changes in Pulmonary Arteries in COPD Patients10

COPD: Key Concept

Not everyone that smokes gets

COPD

Age (years)25 35 45 55 65

4

3

2

1

0

Disability

Death

Nonsmoker

Average

smoker

“Susceptible”

smoker

FE

V1 (

lite

rs)

70 75

Susceptible Smokers & COPD14

10-15ml/yr

15-25ml/yr

40-80ml/yr

0 1 2 3 4 5 6 7 8 10 119

2.8

2.6

2.4

2.2

2.0

FE

V1, lit

ers

3 4 5 6 7 8

Years of followup

Sustained quitters

Continuous smokers

Anthonisen et al, AJRCCM, 2002

COPD: Benefits of Smoking Cessation Lung Health Study

Age (years)25 35 45 55 65

4

3

2

1

0

Disability

Death

Nonsmoker

Average

smoker

“Susceptible”

smoker

FE

V1 (

lite

rs)

70 75

Susceptible Smokers & COPD14

COPD: Pathogenesis1

• Tobacco smoking is the main risk factor for COPD

• Some smokers display an exaggerated protected inflammatory response, which causes tissue destruction, impairs defense and repair mechanisms, thus leading to characteristics of COPD

COPD: Pathogenesis1

Three processes important to Pathogenesis

1. Inflammation cascade

• Differs from bronchial asthma cascade

2. Proteinase and antiprotease imbalance

• Released by inflammatory cells

3. Oxidative Stress

• Oxidizing biological molecules leads to cell

dysfunction and/or death

LUNG INFLAMMATION

COPD PATHOLOGY

Oxidative

stressProteinases

Repair

mechanisms

Anti-proteinasesAnti-oxidants

Host factors

Amplifying mechanisms

Cigarette smokeBiomass particles

Particulates


COPD: Pathogenesis10

COPD

Macrophages

PMNs

CD8 T cells

proteases

LTB4

IL-8, TNF-a

Asthma

Eosinophils

Mast cells

CD4 T cells

mediators

LTD4

IL-4, IL-5, Il-13

Inflammation in Asthma & COPD1

COPD: Pathophysiology1

Pathogenic mechanisms produce pathological changes, giving rise to four physiological abnormalities in COPD

1. Mucous hypersecretion and ciliary dysfunction

• First physiologic abnormality developed in COPD

• Enlarged mucous glands and epithelial cell metaplasia

Mucus gland hyperplasia

Goblet cell

hyperplasia

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 Patients10


2. Airflow limitation and hyperinflation

• Expiratory (largely irreversible) airflow limitation

– Physiologic hallmark of COPD

• Major site is smaller conducting airways <2mm

• Loss of elastic recoil due to alveolar wall destruction

• Destruction of alveolar attachments

• Accumulation of inflammatory cells, mucous and plasma exudate in the bronchi

• Smooth muscle contraction (tense vagal tone) and dynamic hyperinflation during exercise

– Major factor affecting exercise limitation in patients


3. Gas exchange abnormalities

• Occurs in advanced COPD characterized by hypoxemia with or without hypercapnia

• Abnormal gas exchange as a result of anatomical alterations as described previously

4. Pulmonary hypertension

• Occurs after severe gas exchange abnormalities

• Results from hypoxic vasoconstriction, endothelial dysfunction, remodeling of pulmonary arteries and destruction of capillary bed

• Leads to right sided heart failure – cor pulmonale

Chronic hypoxia

Pulmonary vasoconstriction

Muscularization

Intimal hyperplasia

Fibrosis

Obliteration

Pulmonary hypertension

Cor pulmonale

Death

Edema


Chronic hypoxia

Pulmonary Hypertension in COPD10 Only Two Things Clinically Proven to Prolong Life for COPD Patients

1. Quitting Tobacco

2. LTOT only for those who qualify

Pro-Active vs. Passive Referral

1-800

• Fax Referral System

• 50% enrollment rate

• 35-45% abstinence at 6mos

• 25-35% abstinence at 1 year

• Results = 20 @ 6mos / 15@yr

• Leaving it up to the individual

to call when ready

• According to research

conducted at San Diego State

University only 3% of clients

receiving literature containing

quit line information made a

call to the quit line

• Results = 1.2 @ 6mos / 1@yr

Pro-Active vs. Passive Referral

QuitFax Referral Form – Quick and Easy!

ASHLine 1-800-55-66-222

www.ashline.org

National Quit Line

1-800-Quit Now

COPD: Treatment & Management10

Four Components of Care

1. Assess and monitor disease• Spirometry is the tool

2. Reduce risk factors

3. Manage stable COPD• Pharmacologic and non-pharmacologic

4. Manage acute exacerbations• Steroids, antibiotics, ventilation support

FEV1 / FVC < 70%

I: MildFEV1>80% pred

II:ModerateFEV1 50-80% pred

III: SevereFEV1 30-50% pred

IV: Very SevereFEV1 < 30% pred

Avoidance of risk factor(s); influenza vaccination

Add short-acting bronchodilator when needed: ß2 agonists

Add regular treatment with one or more long-acting bronchodilators: ß2 agonists and anticholinergics

Add rehabilitation

Add ICS for repeated exacerbations

Add LTOT

Surgical interventions

GOLD Standards COPD Pharmacotherapy9 Manage Exacerbations: Introduction1

• An exacerbation of COPD is an event in the natural course of the disease characterized by a sudden change in the patients baseline symptoms: dyspnea, cough, and/or sputum that is beyond normal day-to-day variations

• May warrant a change in regular medication usage

COPD Exacerbations: Epidemiology

• Exacerbations play a role in decline of FEV1

– Decline in FEV1 of 46.1 ml/yr with frequent (>1.5) exacerbations per year

– Decline in FEV1 of 25.3 ml/yr with infrequent (<1.5) exacerbations per year

– Greater lung function decline value observed in COPD exacerbations amongst current smokers

Donaldson et al, Thorax 2002;57;847-52)

COPD Exacerbations: Epidemiology1

• Seasonality

– 50% more likely in the winter

• Recurrent Exacerbations

– 30% of those hospitalized have another

exacerbation within 8 weeks

COPD Exacerbations: Epidemiology8

• The most common causes are:– Infection of the tracheobronchial tree

– Air pollution

• Cause of 1/3 of severe exacerbations unknown

• Conditions that mimic exacerbations: pneumonia, CHF, PE, pneumothorax, pleural effusions, arrhythmia– Important to Differential Diagnosis

WORLD COPD DAYNovember 16, 2011

Raising COPD Awareness Worldwide

Interactive COPD Education System

Click to Launch the

COPD Active Learning Module

This interactive module is provided by Syandus, Inc.

References

1. American Thoracic Society – European Respiratory Society: Standards for the Diagnosis and Management of Patients with COPD, 2004. download manual:

http://www.thoracic.org/sections/copd

2. Arizona Department of Health Services: Arizona Comprehensive Lung Disease Control Plan, download manual: http://www.azdhs.gov/phs/tepp/pdf/lungdiseaseplan.pdf

3. National Heart Lung and Blood Institute, COPD Learn More Breathe Better: COPD: It has a Name, 2007. download provider edition:

http://www.nhlbi.nih.gov/health/public/lung/copd/campaign-materials/index.htm

4. National Heart Lung and Blood Institute, COPD Learn More Breathe Better: COPD: It has a Name, 2007. download consumer edition:


5. National Heart Lung and Blood Institute, COPD Learn More Breathe Better: COPD: Are You at Risk, 2007. download handout:


6. National Heart Lung and Blood Institute, COPD Learn More Breathe Better: Breathing Better with a COPD Diagnosis, 2007. download handout:


References

7. National Lung Health Education Program: Prevent COPD Now! Information for Patients Who May Be Developing COPD, 2007. download Save Your Breath, America!:

http://www.nlhep.org/pdfs/saveyourbreath.pdf

8. Global Initiative for Chronic Lung Disease, Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: Executive Summary, 2006. download manual: http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=996

9. Global Initiative for Chronic Lung Disease, Pocket Guide to COPD Diagnosis, Management, and Prevention: A Guide for Health Care Professionals, 2006. download manual:

http://www.goldcopd.org/Guidelineitem.asp?l1=2&l2=1&intId=1116

10. Global Initiative for Chronic Lung Disease, Power Point Presentation with NHLBI diagrams by: Peter J. Barnes, M.D., 2006. download manual:

http://www.goldcopd.com/OtherResourcesItem.asp?l1=2&l2=2&intId=969

11. National Lung Health Education Program and AlphaMedia, Inc., Simple Office Spirometry, Thomas L. Petty, M.D., and Paul L. Enright, M.D., download manual:

http://www.ndd.ch/Downloads/Docs/Petty-Enright-SimpleOfficeSpirometryForPrimaryCarePractitioners.pdf

12. American Thoracic Society – European Respiratory Society: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency, 2006. download manual:

http://www.thoracic.org/sections/publications/statements/pages/respiratory-disease-adults/alpha1.html

References

13. Rau JL: Respiratory Care Pharmacology, Mosby, 2002.

14. American Lung Association of Minnesota, COPD Educator Course, 2006. Cheryl Sasse; Jeff Rubins, MD; Kathy Schultz, RRT; Charles McArthur, RRT, RPFT; Janet Malkiewicz, RN, PHN; Lynn Sieben, RRT; Dick Stenholz LSW; Bob McVoy, RRT, FAARC; Charlene McEvoy, MD

15. Arizona Department of Health Services, Tobacco Education & Prevention Program, University of Arizona HealthCare Partnership, Basic Tobacco Intervention Skills Certification Guidebook, 2006.

Medical Reviewer: Dr. David R. Sanderson, M.D., Professor of Medicine: Emeritus Mayo Clinic College of Medicine

Documents

COPD Pathology with 3D Interactive Track I S Cerreta … · GOLD Standards COPD Pharmacotherapy 9 Manage Exacerbations: ... Global Initiative for Chronic Lung Disease, Pocket Guide