Ex. 3 - COPD

Question 1

COPD affects _% of the US adult population

Answer 1

10%

Question 2

_% if COPD patients are smokers

Answer 2

85

Question 3

COPD definition

Answer 3

Irreversible airflow obstruction due to
Emphysema
Chronic Bronchitis

Question 4

COPD symptoms

Answer 4

Chronic cough
Sputum (phlegm production)
Dyspnea
Barrel chest

Question 5

Emphysema

Answer 5

Permanent enlargement of bronchioles and alveoli due to destruction of their walls
Dyspnea-insufficient gas exchange
Cigarette smoking causes
Often asymptomatic until late stage

Question 6

Pathophysiology of emphysema

Answer 6

Tissue damage by proteases
cigarette smoke -> inflammation in alveoli
neutrophils and macrophages accumulate
^when activated, release proteases (resulting in tissue damage)
Oxidative injury by ROS
Ros in cigarette smoke deplete antioxidants in the lungs (superoxide dismutase, glutathione)
ROS inactive a1-antrypsin->responsible for suppressing protease activities
Activated neutrophils also release ROS

Question 7

Protease inhibitor produced in the liver (53kDa)
Inhibits neutrophil elastase
Limits lung tissue damage

Answer 7

a1-antitrypsin

Question 8

a1-antitrypsin deficiency

Answer 8

Rare genetic disorder
Increased neutrophil migration
Increased lung damage via inflammation and protease activity

Question 9

Chronic bronchitis

Answer 9

Chronic inflammation of bronchial tubes
-Mucus hypersecretion
-Fibrosis (makes tube thicker) and narrowing airways
Symptoms
-Producing cough
-Wheezing
-SOB/chest pain
Frequently coexists with emphysema
Smoking main cause

Question 10

Pathophysiology of chronic bronchitis

Answer 10

Initiated by the exposure to irritant (cigarette smoke/other air pollutants)
-Hypersecretion of the bronchial mucous glands
Hypertrophy of mucous glands
Metaplastic formation of mucin-secreting goblet cells
-Inflammation with infiltration of CD8+T cells, macrophages, and neutrophils (no involvement of eosinophils)
Microbial infection MAY PLAY secondary role in maintaining inflammation and exacerbating symptoms

Question 11

Tissue remodeling in COPD

Answer 11

-Fibrosis of small airways
-Hyperinflation of lungs:
Alveolar enlargement
Alveolar wall destruction
-Mucus hypersecretion

Question 12

Treatment of COPD

Answer 12

Nonpharmalogical therapy
Smoking cessation
Exercise
Immunization
Long-term oxygen therapy
Pharmacological therapy:
Bronchodilators
-B2 selective agonists
-Antimuscarinic agents
Methylxanthines
Corticosteroids for patients with exacerbations
a1-antitrypsin replacement therapy (rare)

Question 13

B2 selective Agonists (SABA)

Answer 13

Albuterol, levalbuterol
Rapid onset, but the response is less than seen in asthma

Question 14

B2 selective agonists - LABA

Answer 14

Salmeterol, formoterol
Every 12 hrs
Not for acute relief of symptoms

Question 15

B2 selective agonists: Ultra-LABA

Answer 15

Indacterol, olodaterol, vilanterol, bambuterol
Once daily
Can be used as monotherapy for COPD (not for asthma)

Question 16

B2 selective agonists - combination

Answer 16

Fluticasone furoate/vilanterol

Question 17

Antimuscarinic - SAMA

Answer 17

Ipratropium
As effective as albuterol in patients with COPD

Question 18

Antimuscarinic - LAMA

Answer 18

Tiortropium, aclidinium, umeclidinium
Once a day
Approved for maintenance therapy of COPD
Quaternary amine salt like ipratropium
Combination
-Fluticasone furoate/umeclidinium bromide/vilanterol

Question 19

Once considered first-line therapy for COPD
Mostly replaced by LABA and antimuscarinics
Theophylline
-Used in patients who are intolerant to/can’t use inhaled bronchodilators
-Bronchodilation AND anti-inflammatory action
-Systemic admin may be beneficial on peripheral airways

Answer 19

Methylxanthines

Question 20

Roflumilast
Increases the intracellular cAMP concentration as methylxanthines
Suppresses the release of cytokines and chemokines
Approved for COPD, but not for asthma

Answer 20

PDE4 inhibitor

Question 21

Corticosteroid use in COPD and MOA

Answer 21

Use:
-Short term systemic use for acute exacerbations
-Inhalation therapy for chronic stable COPD
Mechanism:
-Decrease mucus release by reducing capillary permeability
-Suppress protease release from immune cells
-Suppress prostaglandin production

Question 22

a1-antitrypsin replacement therapy

Answer 22

Products
-Derived from donated blood
-Prolastin, Aralast, Zemaira
Reduces lung tissue loss and destruction in patients with severe a1-Antitrypsin deficiency
Expensive (>$50k a year)