Reference: GOLD 20131

COPDBasic

Reference for Year 3 and Final Year Students

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Module Year 3 / Final Year

Title COPD

Lecturer Dr. Hla MyintAims and Objectives Aims

Getting the correct diagnosis of COPD is the crucial step in the management of COPD ObjectivesExpected to know:(1) Definition (2) Risk Factors (3) Mechanisms underlying airflow limitation(4) Diagnosis (5) Differential diagnosis(6) Commonly Used Drugs (7) Assess and monitoring disease(8) Management of stable and acute exacerbationSpecial emphasis on no 8 for Year 4 (MBS 362)

Assumed Knowledge The concept of physiology and pathology in accordance with the knowledge obtained from BCS module in Phase I B/2nd

yearLecture Contents 1. Definition

2. Pathophysiology3. Diagnosis4. Assessment of disease5. Medications6. Management of Stable COPD and COPD exacerbations

Clinical Relevance Diagnosis and management based on the knowledge learned from this seminar

References The Global Initiative for Chronic Obstructive Lung Disease (GOLD)". 2014.

Seminar Outline

Global Initiative for Chronic Obstructive Lung Disease (GOLD)

♗ COPD is a common preventable and treatable disease

♗ Characterized by persistent airflow limitation that is

usually progressive and associated with an enhanced

chronic inflammatory response in the airways and the

lung to noxious particles and gases.

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COPD

♗ Exacerbations and comorbidities contribute to the

overall severity in individual patients.

This definition does not use the terms chronic bronchitis and emphysema and

excludes asthma (reversible airflow limitation).

♗ The chronic airflow limitation characteristic of COPD

is caused by a mixture of small airway disease

(obstructive bronchiolitis) and parenchymal destruction

(emphysema), the relative contributions of which vary

from person to person.

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EMPHYSEMA

A - Centriacinar emphysema

It usually involves upper lobes and superior segments of

lower lobes and is the most common type of emphysema.

Associated with smoking and coal dust.

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EMPHYSEMA

B - Panacinar emphysema

In panacinar (panlobular) emphysema, there is

involvement of the complete respiratory lobule .

Typically involves the lower zones.

Associated with alpha 1-antitrypsin deficiency

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α1 ANTITRYPSIN DEFICIENCY

Protease inhibitor (PI or SERPINA1) locus that encodes α1AT

1. M allele: normal α1AT levels

2. S allele: slightly reduced α1AT levels

3. Z allele: markedly reduced α1AT levels (>1% in most Caucasian

populations)

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α 1 ANTITRYPSIN DEFICIENCY

4. Rare individuals inherit null alleles absence of any

α1AT production

The most common form of severe α1AT deficiency:

Individuals with two Z alleles or one Z and one null allele

are referred to as PiZ

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Airflow Limitation in COPD

A mixture of small airway disease (obstructive bronchiolitis) and parenchymal destruction

(emphysema)

1. Chronic inflammation structural changes and narrowing of

the small airways

2. Destruction of the lung parenchyma loss of alveolar

attachments to the small airways decreases lung elastic recoil

diminished ability of the airways to remain open during expiration

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Small airway disease Parenchymal destruction

Airway inflammation Loss of alveolar attachments

Airway fibrosis; luminal plugs Decrease of elastic recall

Increased airway resistance

AIRFLOW LIMITATION

Mechanisms Underlying Airflow Limitation in COPD

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Disease development and progression

1. Genes (alpha-1 antitrypsin, rare recessive trait disorder,

leading cause of panlobular emphysema); suspect age

< 45

2. Age (cumulative exposure) and Gender (now F=M)

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Risk Factors for COPD

3. Lung Growth and Development

Any factor that affects lung growth during gestation

and childhood has the potential for increasing an

individuals risk of developing COPD.

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Risk Factors for COPD

4. Exposure to particles

• Tobacco smoke

• Occupational organic and inorganic dusts and chemical

agents and fumes

• Wood, animal dung, crop residues and coal burned in open

fires or poorly functioning stoves

• Outdoor air pollution (Mechanism unknown)

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Risk Factors for COPD

5. Respiratory infections

A history of severe childhood respiratory infection has

been associated with reduced lung function and

increased respiratory symptoms in adulthood.

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Risk Factors for COPD

6. Socioeconomic status

7. Asthma may be risk factor for the development of

COPD, although the evidence is not conclusive.

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Pathological changes characteristic of COPD

• Airways

• Lung parenchyma

• Pulmonary vasculature

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Physiological changes characteristic of the disease

• Airflow limitation and air trapping

• Gas exchange abnormalities

• Mucus hypersecretion

• Pulmonary hypertension

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Systemic features of COPD

Skeletal muscle wasting and cachexia

IHD & HF

Anemia

Osteoporosis

Diabetes and metabolic syndrome

Depression

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Differences in Pulmonary Inflammation Between Asthma and COPD

COPD Asthma Severe asthma

Cells Neutrophils ++Macrophages +++CD8+ T cells (Tc1)

Eosinophils ++Macrophages +CD4+ T cells (Th2)

Neutrophils +MacrophagesCD4+ T cells (Th2), CD8+ T cells (Tc1)

Key mediators IL-8TNF-⍺, IL-1β, IL-6NO +

EotaxinIL-4, IL-5, IL-13NO +++

IL-8IL-5, IL-13NO ++

Oxidative stress Peripheral airwaysLung parenchymaPulmonary vessels

Proximal airways Proximal airwaysPeripheral airways

Site of disease +++ + +++

Consequences Squamous metaplasiaMucous metaplasiaSmall airway fibrosisParenchymal destructionPulmonary vascularremodeling

Fragile epitheliumMucous metaplasia↑Basement membraneBronchoconstriction

Response to therapy Small b/d responsePoor response to steroids

Large b/d responseGood response to steroids

Smaller b/d responseReduced response to steroids

NO = nitric oxide, b/d = bronchodilator