COPD: clinical trial of a novel drug

Question 1

What does COPD stand for?

Answer 1

Chronic Obstructive Pulmonary Disease

Question 2

What risk factors are associated with COPD?

Answer 2

Cigarette smoking

Smoke from cooking on open fires

Question 3

What sites are affected by asthma and COPD?

Answer 3

A- large and small airways
Always hyper-responsive, secrete mucus

C- Airways and lung
Very little AHR, secrete mucus

Question 4

What inflammatory cells are involved in asthma and COPD?

Answer 4

A- Eosinophils
Mast cells
Th2 lymphocytes

C-Neutrophils
Macrophages
Tc1 lymphocytes

Question 5

What mediators are involved in asthma and COPD?

Answer 5

A- IL-4, -5, cysLTs

C-TNFalpha, IL-8, LTB4

Question 6

How can asthma be treated?

Answer 6

Bronchodilators
Corticosteriods
Not effective with COPD

Question 7

What is chronic bronchitis?

Answer 7

Large disease
Excessive production of mucus
Occludes the airway
Greatly restricts airflow

Question 8

What is chronic bronchiolitis?

Answer 8

Small airways disease
Held open by alveolar attachments
Laying down of fibrotic tissue which closes the airway
Very few alveolar attachments

Question 9

What is emphysema/

Answer 9

Lung destruction

Disrupts alveolar attachments

Question 10

What three conditions comprise COPD?

Answer 10

Chronic bronchitis
Chronic bronchiolitis
Emphysema

Question 11

How can CB be treated?

Answer 11

Mucolytics

Thins mucous, easier to cough up

Question 12

What is the pathophysiology of emphysema and CB?

Answer 12

Incessant inhalation of cigarette smoke activates alveolar macrophages
MCP-1 brings in more macrophages
Secrete chemotactic factors recruiting neutrophils
Neutrophils produce an excess of proteases
Leads to emphysema

Question 13

What is a pack year?

Answer 13

A packet of cigarettes (20) every day for a year

Question 14

How could you measure annual decline lung function?

Answer 14

FEV1

Question 15

What happens to FEV1 in a smoker who stops smoking?

Answer 15

Rate of decline decreases to that of non-smoker but continues at low level

Question 16

Why does COPD assessment include a lung function test?

Answer 16

To assess how the drug affects the rate of decline of FEV1

Question 17

Why does COPD assessment include broncheolar lavage?

Answer 17

Look at protease activity in the lavage look for a decline protease activity if drug is successful

Question 18

Why does COPD assessment include a CT scan?

Answer 18

Look for a change in number and size of holes (calculate total surface area of holes)

SA will go up in placebo group

SA in successful treatment will stay the same

Question 19

Why do the small airways become obstructed?

Answer 19

Mucus

Question 20

Why do the small airways become stenosed?

Answer 20

Fibrous tissue

Question 21

Why do the small airways collapse?

Answer 21

Destruction of alveolar attachments holding the airways open

Question 22

What are the two types of emphysema?

Answer 22

Centri-acimar emphysema
associated with cigarette smoke

Pan-acinar emphysema
Genetic deficiency of alpha 1 anti-trypsin
Cannot break down neutrophil elastase

Question 23

Why don’t endogenous inhibitors work?

Answer 23

Balanced as been tipped

Too many proteases are being produced

Question 24

Why might you use a dual inhibitor?

Answer 24

To increase efficacy

Inhibit neutrophil elastase and MMPs