SM_177a: COPD

Question 1

COPD is a _____ and _____ disease

Answer 1

COPD is a preventable and treatable disease

(has extrapulmonary effects as well)

Question 2

The pulmonary component of COPD is _____ but rather is _____ and associated with _____

Answer 2

The pulmonary component of COPD is airflow limitation that is not fully reversible but rather is usually progressive and associated with an abnormal inflammatory response of lung to noxious particles or gases

Question 3

_____ is the major risk factor for COPD

Answer 3

Cumulative exposure to noxious particles is the major risk factor for COPD

(cigarette smoke, indoor air pollution, occupation dusts, outdoor air pollution)

Question 4

_____ deficiency is associated with COPD

Answer 4

Alpha-1-antitrypsin deficiency is associated with COPD

• PiZZ (homozygous) or PiMZ (heterozygote) + smoking
• Cigarette smoking remains most important risk factor for COPD in PiZZ individuals
• PiMZ is at increased risk for COPD vs PiMM (homozygous normal) especially in context of smoking

Question 5

The cells most heavily involved in COPD are _____, _____, and _____

Answer 5

The cells most heavily involved in COPD are alveolar macrophages, neutrophils, and CD8⁺ lymphocytes

Question 6

Describe the pathogenesis of COPD

Answer 6

1. Cigarette smoke or other irritants
2. Alveolar macrophages and epithelial cells activated
3. Alveolar macrophages active neutrophils, monocytes, fibroblasts, CD8⁺ lymphocytes, and proteases; epithelial cells activate fibroblasts and CD8⁺ lymphocytes
4. Neutrophils secrete proteases (neutrophil, elastase, cathepsins, MMPs), fibroblasts activated
5. Fibrosis (obstructive bronchiolitis), alveolar wall destruction (emphysema), and mucus hypersecretion

Question 7

The main pathological changes in COPD are _____, _____, and _____

Answer 7

The main pathological changes in COPD are fibrosis (obstructive bronchiolitis), alveolar wall destruction (emphysema), and mucus hypersecretion

Question 8

Describe the role of alveolar macrophages in COPD

Answer 8

Alveolar macrophages orchestrate much of inflammatory process underlying COPD and release elastolytic enzymes and ROS

(increased in COPD lungs)

Question 9

Describe the role of neutrophils in COPD

Answer 9

Neutrophils

• Critical effector cells: attracted by IL-8 and LTB4 from alveolar macrophages and PMNs, release ROS and MPO which contribute to ongoing inflammatory response
• Serine proteases like neutrophil elastase contribute to destruction of lung parenchyma

Question 10

Describe the role of CD8⁺ lymphocytes in COPD

Answer 10

CD8⁺ lymphocytes perpetuate inflammatory response by releasing chemoattractants and are found in the airway walls, vessels, and lymph nodes of smokers with COPD

Question 11

Describe the effects of inflammation in COPD

Answer 11

Inflammation leads to

• Small airway disease: airway inflammation, airway remodeling
• Parencymal destruction: loss of alveolar attachments, decrease of elastic recoil

Both lead to airflow limitation

Question 12

Changes occur in the _____ in the chronic bronchitis portion of COPD

Answer 12

Changes occur in the large airways in the chronic bronchitis portion of COPD

Question 13

_____ occurs in the small airways during COPD

Answer 13

Small airway remodeling occurs in the small airways during COPD

Question 14

Changes occur in the _____ in the emphysema portion of COPD

Answer 14

Changes occur in the lung parenchyma in the emphysema portion of COPD

Question 15

What changes occur in the large airways in the chronic bronchitis portion of COPD?

Answer 15

Large airways

• Mucus hypersecretion
• Goblet cell and mucus gland hyperplasia
• Squamous metaplasia of epithelium
• Increased macrophages and CD8⁺ lymphocytes
• Neutrophils in sputum

(note that there is no subepithelial basement membrane thickening or smooth muscle hypertrophy)

Question 16

What changes occur in the small airways in COPD?

Answer 16

Small airway remodeling

• Inflammatory exudate in lumen
• Disrupted alveolar attachments
• Thickened wall with macrophages, CD8⁺ cells, fibroblasts
• Peribronchial fibrosis
• Lymphoid follicles

Question 17

What changes occur in the lung parenchyma in the emphysema portion of COPD?

Answer 17

Lung parenchyma

• Alveolar wall destruction
• Loss of elasticity
• Destruction of pulmonary capillary bed
• Increased macrophages and CD8⁺ lymphocytes

Question 18

This pathology represents the ______ portion of COPD

Answer 18

This pathology represents the chronic bronchitis portion of COPD

Question 19

This pathology represents the ______ portion of COPD

Answer 19

This pathology represents the small airway remodeling portion of COPD

Question 20

Emphysema leads to permanent ________

Answer 20

Emphysema leads to permanent distal acinar enlargement

Question 21

This pathology represents the ______ portion of COPD

Which side is normal? Which is COPD?

Answer 21

This pathology represents the emphysema portion of COPD

Left is normal, right is emphysema

Question 22

Diagnosis of COPD is made by ______

Answer 22

Diagnosis of COPD made by spirometry after looking at symptoms and exposure to risk factors

(FEV₁ / FVC < 0.70 and not reversible)

• Symptoms: cough, sputum, dyspnea
• Exposure to risk factors: tobacco, occupation, indoor / outdoor pollution

(misdiagnosed in women)

Question 23

Describe the flow-volume and volume-time curves in COPD

Answer 23

• Flow-volume curve: scooped out / concave
• Volume-time curve: less steep than normal and takes much longer to achieve FVC

Question 24

Mechanisms of airflow limitation in COPD are _____, _____, and _____

Answer 24

Mechanisms of airflow limitation in COPD are mucus hypersecretion (luminal obstruction), disrupted alveolar attachments (emphysema), and mucosal and peribronchial inflammation and fibrosis (obliterative bronchiolitis)

Question 25

FEV₁ does not correlate well with _____ or _____ in COPD while ____ is inextricably linked to these two

Answer 25

FEV₁​ does not correlate well with quality of life or exercise capacity in COPD while hyperinflation is inextricably linked to these two

Question 26

Describe the respiratory response to exercise in COPD

Answer 26

In people with COPD, with exercise ERV increases so IC decreases, which becomes inefficient in increasing minute ventilation, causing people to experience breathlessness

Question 27

Describe the clinical manifestations of COPD

Answer 27

• Breathlessness: with or without strenuous exercise, can cause person to walk more slowly or stop to catch their breathe, or can cause person to not engage in daily activities
• History of exacerbations

(for COPD evaluation, look at symptoms and risk for exacerbations)

Question 28

_____ are the treatment for COPD if the patient does not have exacerbation because they _____

Answer 28

Bronchodilators are the treatment for COPD if the patient does not have exacerbation because they reduce hyperinflation

(bronchodilators cannot fix the fact that patient is out of shape, so tell patient to increase activity level or attend pulmonary rehabilitation)

Question 29

Add _____ to the regimen of bronchodilators if a COPD patient has exacerbations

Answer 29

Add an inhaled corticosteroid to the regimen of bronchodilators if a COPD patient has exacerbations

Question 30

If the patient has elevated eosinophils, treat the patient using _____ and _____

Answer 30

If the patient has elevated eosinophils, treat the patient using bronchodilators and inhaled corticosteroids

(basically treating both COPD and asthma at the same time)

Question 31

Describe the pathobiology of COPD exacerbations

Answer 31

Greater airway inflammation has multiple effects leading to symptoms of exacerbations

Question 32

Compare and contrast the pathophysiology of asthma and COPD

Answer 32

Question 33

Etiology of breathlessness in COPD is ______

Answer 33

Etiology of breathlessness in COPD is hyperinflation

Question 34

The major risk factor for COPD is ______

Answer 34

The major risk factor for COPD is cigarette smoking

Question 35

COPD is characterized by three distinct but concurrent pathologic changes: ______, ______, and ______

Answer 35

COPD is characterized by three distinct but concurrent pathologic changes: chronic bronchitis in central airways, small airway remodeling, and emphysema