Case 9: John Fumer - COPD

COPD: Description

Lung condition with chronic resp symptoms and airflow obstruction from airway and alveoli abnormalities

COPD: Types

Chronic Bronchitis (Blue Bloater)

Emphysema (Pink Puffer)

Alpha-1 Antitrypsin Deficiency (AATD)

COPD: Chronic Bronchitis

Airway inflammation + occlusion from mucus

• Chronic productive cough

• Hypoxemia, hypercapnia, cor pulmonale (right ventricle failure from lung pathology)

COPD: Emphysema

Alveolar destruction decreasing elastic lung recoil

• Increase ventilation, normal PO2

COPD: AATD

Genetic predisposition to COPD

• AAT: Protein from liver inhibiting elastase in lungs

COPD: Epidemiology

Risk Factors:

• Particle exposure (smoking, pollution)

• Genetics and fam history

• Older age

• Low SES

• Infections

COPD: Etiology

Main: Exposure to smoke and pollution

Epigenetic factors

Exacerbations from infection 

COPD: Pathogenesis

1. Increase inflammatory cells in airways, lung parenchyma, and pulmonary vessels = Induce chemotaxis, inflammation, and structural changes

• Structural Changes:

  • Smooth muscle hyperplasia = Small airway + pulmonary vasculature narrowing

  • Proteases/elastases destroy elastin

  • ROS destroy alveolar attachments

2. Oxidative stress and proteases in lungs = Exacerbate inflammation

3. Impact lung function

• Airway narrowing = Decrease airflow

• Decrease elastic recoil = Lung hyperinflation

• Alveolar destruction + Blood vessel remodelling = Decrease gas exchange

• Pulmonary vasculature narrowing = Pulmonary hypertension

4. Progression

• Inflammatory mucus occlude small airways

• Inflammatory infiltrates in small airway walls (edema)

COPD: Investigations

Spirometry:

• FEV1/FVC < 70%

• Low FEV1

• Normal/low FVC

PFT:

• Body Plethysmography: High TLC, FRC, RV

• Diffusing Capacity: Low DLCO

Serum AAT Level: Screening

Resp failure tests

COPD: Clinical Manifestations

Chronic productive cough

Dyspnea

• Pursed lip breathing (emphysema)

Tachypnea

Long expiratory phase

Wheezing

Cyanosis (hypoxemia)

COPD: Treatment/Management

Decrease exposure to risk factors (smoking cessation)

Inhaled bronchodilators

• GOLD severity

• LABA, LABA + LAMA, + ICS

COPD Effects on Alveoli Physiology

Emphysema:

Alveolar wall destruction increases compliance (low elastic recoil) = Decrease expiratory force = Air trapping + hyperinflation

Supporting lung parenchyma destruction = Airway collapse

COPD Effects on Immune System

Innate:

• Increase alveolar macrophages and neutrophils

  • Decrease phagocytosis

  • Increase pro-inflammatory phenotype

• Epithelial and dendritic cells release cytokines and chemokines

Adaptive:

• Increase T-cells

• Increase B-cell production of autoantibodies against lung antigens

Gas Transfer

Gas movement/diffusion across alveolar-capillary membrane

Depend on:

• Pressure gradient (O2 and CO2 move high to low pressure)

• Membrane SA and thickness (Large SA and thin membrane = Easier)

• V/Q match

COPD Effects on Gas Transfer

Emphysema: Decrease membrane SA and increase thickness

• Alveolar wall and capillary destruction = Decrease SA

Chronic Bronchitis and Emphysema: V/Q mismatch

• Non-uniform decrease in ventilation (low and high V/Q in lungs = Heterogenous regions)

• Low V/Q (low V) from mucus plug and edema

• High V/Q (low Q) from capillary destruction

Dead Space

Ventilated air not participating in gas exchange (not reaching perfused alveoli)

Anatomic: Volume in conducting airways

Alveolar: Volume in alveoli ventilated but not perfused (embolism)

Physiological: Anatomic + alveolar

• Bohr Enghoff equation

Dead Space: Bohr Enghoff Equation

Calculate physiological dead space (VD) relative to tidal volume (VT)

PECO2: CO2 in expired air

COPD Effects on Dead Space

Decrease expiration (air trapping) = Increase dead space = Less perfusion (no gas exchange) = High V/Q

Emphysema:

• Alveolar-capillary unit and small airway destruction = Ventilated air not perfused (no capillaries) = Increase dead space

Chronic Bronchitis:

• Airway narrowing + destruction = Air trapping + uneven ventilation = Increase dead space

Venous Admixture

Deoxygenated blood mixing with oxygenated blood in pulmonary circulation to decrease arterial PO2

CO passing through lungs without gas exchange (shunt)

• Increase A-a ratio

• Low V/Q

Cause hypoxemia

COPD Effects on Venous Admixture

Increased from V/Q mismatch

Airway + vascular changes = Poor ventilation, normal perfusion = Physiological shunt

Spirometry

Measure exhaled volume vs time during forced exhalation

Spirometry: FEV1

Forced expiratory volume in 1 sec

Spirometry: FVC

Forced vital capacity

Spirometry in COPD

Decreased expiratory force = Low FEV1/FVC < 0.7

Lung Volumes

Measure volume in lungs before and after expiration

Lung Volumes: VC

Vital capacity

Measured with spirometry

Lung Volumes: TLC, RV, FRC

Total lung capacity, residual volume, functional residual capacity

Measured with dilution tests and body plethysmography

Lung Volumes: Dilution Tests

1. Known volume + conc of inert gas inhaled

2. Inert gas diluted by gas in lungs

3. Conc of exhaled gas = Initial volume in lungs

Lung Volumes: Body Plethysmography

Compress and expand gas in thorax in airtight box

Boyle’s law calculates gas volumes

Lung Volumes in COPD

Gas trapping + Hyperinflation = Increase RV and FRC (+ TLC in emphysema), Decrease VC

Diffusing Capacity (DLCO)

Measure gas exchange rate from alveolus to Hb in capillary

Small [CO] inhaled → Measure [CO] during expiration

DLCO in COPD

Emphysema:

• Decrease gas exchange units = Decrease DLCO

Chronic Bronchitis:

• Airway changes (no gas exchange unit changes) = Normal DLCO

Resp Muscle Strength Tests

Measure inspiratory and expiratory pressures

Max inspiratory pressure (MIP)

Max expiratory pressure (MEP)

Resp Muscle Strength: MIP

Inspiratory muscle strength

1. Exhale to RV and suck on tube at max effort

2. Record greatest neg pressure

Resp Muscle Strength: MEP

Expiratory muscle strength

1. Max inspiration and exhale in tube at max effort

2. Record greatest pos pressure

Resp Muscle Strength in COPD

Hyperinflation pushes muscles into suboptimal force-generating positions = Decrease muscle contraction force

Ex: Chronic diaphragm depression

Smoking Pack-Year

Measure lifetime smoking exposure

# packs per day x # years smoked

Smoking Health Effects

Impair resp ciliary function

• Shorten cilia + decrease beating frequency

• Mucus buildup

Increase bronchial mucus glands (size + number)

• Excess number

• Decrease airway lumen diameter

Impair resp immune system

• Increase inflammatory cells and mediators

• Inhibit macrophages

Inhibit anti-protease/elastase

Release ROS

• Oxidative stress damage tissues

Increase CO

• High Hb affinity = Shift dissociation curve left = Prevent O2 delivery

Smoking Cessation (5 A’s)

Help up to 67%

1. Ask: About tobacco use

2. Advise: Encourage to quit

3. Assess: Willingness to quit + dependence

4. Assist: Help users quit (plan, pharm, behaviour support)

5. Arrange: Follow-up care and support