Pathophys of Asthma

Question 1

3 classic signs and symptoms of asthma

Answer 1

Intermittent dyspnea
Cough
Wheezing

Question 2

Hygiene hypothesis

Answer 2

Exposure to infection early in life
Development of a predominately Th1 mediated immune response
Down regulation of a Th2 response

Question 3

Does Th1 or Th2 cells contribute to asthma?

Answer 3

Th2

Question 4

2 infections that decrease of incidence and 3 infections that increase the incidence

Answer 4

decrease: croup, otitis
increase: bronchiolitis, RSV, rhinovirus

Question 5

Atopy

Answer 5

Genetic predisposition to produce specific IgE following exposure to allergens

Question 6

How does obesity act as a risk factor for asthma?

Answer 6

Not sure, there are some hypotheses
Common genetic etiologies
Comorbidities (sleep disordered breathing and GERD)
Effect of obesity on lung mechanics (lung volume)
Inflammatory mediators secreted by adipose tissue

Question 7

4 host risk factors

Answer 7

Genetic (including predisposition to atopy)
Obesity
Sex
Preterm or small size for gestational age

Question 8

7 environmental factors

Answer 8

Allergens
Occupational sensitizers and allergens
Infections
Exposure to tobacco smoke
Outdoor or indoor air pollution
Diet
Stress

Question 9

Cells involved in asthma

Answer 9

Neutrophils
Basophils
Eosinophils
Mast cells
Macrophages
Structural cells

Question 10

2 core mechanisms of asthma

Answer 10

Airway inflammation

Airway remodelling

Question 11

3 main interleukins in airway inflammation

Answer 11

IL4, 5, 13

Question 12

Extrinsic vs intrinsic asthma

Answer 12

Ex: typically develops in childhood and is accompanied by IgE mediated allergic inflammation
In: typically develops later in life and is not associated with allergic sensitization

Question 13

Airway remodelling

Answer 13

Structural alteration of the airway

The degree of remodelling correlates with the severity of asthma

Question 14

4 major changes in airway remodelling

Answer 14

Proliferation and hyperplasia of goblet cells and submucosal glands
Increased deposition of subepithelial collagen
Airway smooth muscle hyperplasia
Microvascular changes

Question 15

How does the epithelium change with airway remodelling

Answer 15

Disruption of tight junctions (allows entry of allergens, activation of inflammatory cells, and propagation of inflammation)
Proliferation and hyperplasia of goblet cells (mucus hypersecretion)

Question 16

How does the epithelial basal lamina change in airway remodelling

Answer 16

Sub-basement membrane thickening (collagen deposition)

Increased number of myofibroblasts (producing matrix)

Question 17

How does airway smooth muscle change in remodelling

Answer 17

Increased smooth muscle mass (hypertrophy and hyperplasia)

Causes airway lumen narrowing, airway hyper-responsiveness, and promotes further airway remodelling)

Question 18

Microvascular changes in remodelling

Answer 18

Bronchial neovascularization
Dilated and tortuous mucosal blood vessels
Increased permeability
Associated with increased mucosal edema

Question 19

Airflow obstruction in asthma

Answer 19

Variable narrowing of the airway lumen causing variable airflow obstruction is a cardinal feature of asthma
Mechanisms: contraction of ASM (inflammation/bronchoconstriction), thickening of the airway (remodelling and edema), mucus plugging)