Asthma

Question 1

Does asthma improve with age?

Answer 1

Yes, 30-70% of children are markedly improved or asymptomatic by early adulthood

Question 2

Causes of airflow obstruction in asthma

Answer 2

Acute bronchoconstriction, mucus plugging of airways, bronchial wall edema, inflammatory cell infiltration, airways wall remodeling (fibrosis), smooth muscle hypertrophy

Question 3

Flow euqation

Answer 3

Q=(Change in P * πr^4)/ 8nL

Question 4

How does radial traction keep airways open?

Answer 4

On inflation, lung parenchyma pulls open airways like spokes on a wheel.

Question 5

Do airways stay open or do they close on inspiration?

Answer 5

They close slightly because of positive pleural pressure

Question 6

What FEV/FVC ratio defines obstruction?

Answer 6

<0.7, Can reverse with bronchodilator

Question 7

What is air trapping and what are the consequences?

Answer 7

Because of bronchoconstriction, some air remains trapped in alveoli. Therefore, residual volume grows and vital capacity shrinks.

Question 8

Is increased airway resistance uniformly distributed in the lung?

Answer 8

No, some airways affected more than others

Question 9

Effect of asthma on V/Q

Answer 9

V/q mismatch causes hypoxemia. Perfusion does decrease due to hypoxia-induced vasoconstriction, but it doesnt happen perfectly.

Question 10

What happens to pACO2 during a mild asthma attack?

Answer 10

It actually falls, the reason why is unclear

Question 11

What happens to PACO2 during a severe asthma attack?

Answer 11

It increases, made worse by respiratory muscle fatigue

Question 12

Pulsus paradoxus in asthma

Answer 12

Systemic arterial pressure falls by more than 10mmHg during inspiration due to large swings in pleural pressure. Increased RV return causes decreased LV preload, also increased pulmonary capacitance reduces LV preload. Increased LV afterload because negative thoracic pressure.

Question 13

Asthma phenotypes

Answer 13

Allergic (atopic) asthma
Non-allergic (nonatopic) asthma
Aspirin-exacerbated respiratory disease
Exercise-induced asthma

Or by pathology:
Eosinophilic
Neutrophilic
Pauci-granulocytic

Question 14

Does allergic asthma have a genetic component?

Answer 14

yes. Strong family history correlation

Question 15

How does an allergic asthma reaction happen?

Answer 15

Allergen inhalation, causes eosinophil reaction and TH2 response, which causes the production of IgE. IgE’s cross link on mast cells then degranulate next time the antigen is encountered.

Question 16

Late phase of allergic asthma reaction?

Answer 16

Occurs due to the recruitment of additional inflammatory cells like basophils and neutrophils.

Question 17

Asthma pathology

Answer 17

Cellular infiltrates and edema within the bronchial wall. Epithelial damage. Smooth muscle layer hypertrophy and hyperplasia. Basement membrane thickening. Increased number of goblet cells and mucous gland hypertrophy

Question 18

Hygiene hypothesis

Answer 18

Exposure to infections early in like causes the development of TH1 mediated response and shifts the balance away from TH2.

Question 19

TH2 Cytokines

Answer 19

IL4 cause IgE synthesis in B cells
IL5 causes eosinophil maturation
IL-9 mediated mast cell recruitment and function
IL-13 causes airway hyperresponsiveness and mucous hypersecretion

Question 20

Exercise induced asthma

Answer 20

Pathogenesis seems to involve cooling of the airway. High energy water molecules evaporate and lead to cooling. This causes bronchoconstriction.

Question 21

Aspirin-Exacerbated respiratory disease

Answer 21

Aspirin inhibits COX, which shifts the pathway to the production of Leukotrienes in the lipoxygenase pathway. Leukotrienes C4/D4/E4 cause bronchospasm/congestion/mucous plugging.

Question 22

Samter’s triad

Answer 22

Asthma
Aspirin sensitivity
Nasal polyps

Question 23

Airway remodeling

Answer 23

Consists of smooth muscle mass increase, mucous secretion increase, persistence of inflammatory cells, collegen depositon, reduced elasticity of airway wall.

Question 24

Signs of asthma

Answer 24

Wheezing, prolonged expiratory phase

Question 25

Can severe asthma occur without wheezing?

Answer 25

Yes!

Question 26

Status asthmaticus

Answer 26

Severe attack that is refractory to treatment with bronchodilators. Must be ventilated

Question 27

Tests to check airway reactivity

Answer 27

Bronchoprovocation tests - where agents are delivered by nebulizer device

Question 28

What is measured in bronchoprovocation tests?

Answer 28

PC20 (the provocative concentration for a fall in FEV1 by 20%.

Question 29

Methacholine

Answer 29

Derivative of acetylcholine, directly stimulates smooth muscle receptors to cause bronchoconstriction

Question 30

Mannitol

Answer 30

Increases osmolarity of airway surface, resulting in release of mast cell mediators to cause bronchoconstriction

Question 31

Albuterol

Answer 31

Short acting B2 agonist that increases cAMP, which activates PKA which bronchodilates

Question 32

Salmeterol, formoterol

Answer 32

Beta 2 agonists that are long lasting ~12 hours.

Question 33

Ipratropium

Answer 33

Anticholinergic agent that decreases bronchoconstrictive tone to airways. Blocks M1 (constrictive), M2 (autoreceptor so dilatory), and M3 receptor. Lasts 6 hours

Question 34

Tiotropium

Answer 34

Anticholinergic agent that decreases bronchoconstriction. Blocks M1 and M3 but not M2(which is bronchodilatory).

Question 35

Theophylline/aminophylline

Answer 35

PDE inhibitors, increases cAMP so causes vasodilation. Decreased mediator release from mast cells as well.

Also inhibit adenosine receptors.

Many side effects that include nausea/diarrhea, arrhytmias, CNS excitation

Question 36

Use of corticosteroids in asthma

Answer 36

Decrease airway inflammation through numerous mechanisms.

Question 37

Omalizumab

Answer 37

Prevents IgE from binding to mast cells and cross linking. Can’t bind antigen and degranulate. The MAB binds IgE and prevents it from being stuck onto mast cells.

Question 38

H1 receptor mediated actions

Answer 38

Increased vascular permeability. Bronchial and intestinal smooth muscle contraction. Increased nasal mucus production. Increased chronotropy and inotropy. Vasodilation. Flushing.