Lecture 10: Asthma Flashcards

1
Q

Define asthma

A

An inflammatory process that leads to hyperresponsive airways and reversible airway obstruction

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2
Q

Causes of airflow obstruction (7 parts)

A

Bronchoconstriction, mucus plugging, bronchial wall edema, inflammatory infiltrate, airway remodeling (fibrosis), SM hypertrophy, uncoupling elastic recoil forces

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3
Q

Asthma represents an intra or extrathoracic obstruction. What does this mean for flow limitation during inspiration and expiration?

A

Intrathoracic: flow is decreased during expiration

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4
Q

How do we define obstruction (FEV1 / FVC)

A

FEV1 / FVC ratio of less than 0.7

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5
Q

Can you normalize obstruction with a bronchodilator in asthma?

A

Yes, you can completely normalize the FEV1 / FVC ratio

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6
Q

What is air trapping?

A

As aspect of asthma in which the alveolus cannot release air, leading to expanded alveolus

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7
Q

What does air trapping cause (in terms of RV/VC)?

A

Residual volume is greater, vital capacity is lower proportionally to TLC (which is fixed)

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8
Q

V/Q in asthma

A

Hypoxemia from V/Q mismatch (some airways more affected than others)

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9
Q

Mild asthma attack vs severe (in terms of PCO2)

A

PCO2 falls as functioning units can remove CO2; severe attacks can cause a rise in PCO2

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10
Q

Why does asthma increase pulsus paradoxus?

A

Large swings in intrapleural pressure due to battling increased pulmonary resistance increases pulsus paradoxus

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11
Q

Describe allergic asthma

A

Asthma exacerbated by exposure to various allergens

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12
Q

Allergic asthma pathophysiology (be sure to identify two phases)

A

An initial allergen causes an increase in Th2 CD4 cells, which release TH2 cytokines; re-exposure leads to IgE cross-linking on mast cells and histamine dumping + leukotrience production (early phase) –> bronchoconstriction and perpetuated inflammation via major basic protein (late phase)

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13
Q

Hygiene hypothesis

A

Exposure to infections early in life –> development of Th1-mediated response (protective immunity) and down regulation of Th2-mediated immune response (allergic diseases)

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14
Q

Th2 Cytokines

A

IL-4 –> B cells to synthesize IgE; IL-5 –> eosinophil maturation; IL-9 –> mast cell recruitment; IL-13 –> airway hyperresponsivneess and mucous secretion

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15
Q

Exercise-induced asthma pathophysiology

A

Exercise can provoke bronchoconstriction via cooling of air leading to fluid accumulation

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16
Q

Describe aspirin-exacerbated respiratory disease

A

Inhibition of cyclooxygenase pathway can shift pathway to production of bronchoconstrictor leukotrienes

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17
Q

Airway remodeling leads to…

A

Persistent airflow obstruction

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18
Q

Describe some features of airway remodeling (5)

A

Increase SM mass, increased mucous glands, inflammatory cells persist (ongoing inflammation), fibrosis/collagen deposition, elastolysis

19
Q

Symptoms of asthma

A

Cough, dyspnea, wheezing, chest tightness

20
Q

Signs of asthma

A

Wheezing, prolonged expiratory phase

21
Q

Why would you have no wheezing with severe asthma?

A

If asthma is so bad there is no airflow

22
Q

What is status asthmaticus?

A

Severe asthma attack refractory to treatment w/ bronchodilators that may require assisted ventilation

23
Q

What can be used during bronchoprovocation test?

A

Methacholine (stimulates SM receptors), mannitol (mast cell mediators), exercise, eucapnic voluntair hyperpnea

24
Q

If you give methacholine or mannitol, what do you measure?

A

PC20: conc of provacative med needed to cause fall in FEV1 by 20% (lower conc, higher chance of asthma)

25
How does eucapnic voluntair hyperpnea work?
Fast breathing causes cooling, which can lead to asthma attack
26
Asthma treatment (3)
Bronchodilators, anti-inflammatory agents, targeted therapy
27
Bronchodilators
Sympathomimetics, anticholinergics
28
Sympathomimetics should have what specificity? What is the chemical mediator?
Beta-2; cAMP --> SM relaxation
29
What are some beta-2 agonists used to treat asthma and time course
Short: albuterol, Long: salmeterol, formoterol
30
How do anticholinergics treat asthma? What are some drugs (4)?
Decrease bronchoconstrictor tone; ipratropium (short acting, M1, M2, M3), tioropium (long acting, blocks M1 and M3), umeclidinium/aclidinium (long acting, M3)
31
Why can't all anticholinergics be used to treat asthma?
Some do not cross into respiratory tract (scopolamine) and some cross BB barrier (atropine)
32
How do methylxanthines work?
Block adenosine receptors, inhibit PDE, which leads to inhibited degredation of cAMP (more cAMP = SM relaxation)
33
What are two methylxanthines? Are they used? Why?
Theophylline, aminophylline; NEVER USED; bad SEs (N, D, arrhythmias)
34
Corticosteroides do what? How are they delivered?
Decrease airway inflammation through various mechanisms; inhaled to deliver drugs locally (want LOW bioavailability)
35
What are some corticosteroids (note acute and chronic)
Belcomethoasone, fluticasone, mometasone; attacks: prednisone
36
Largely, leukotrienes cause..
Bronchoconstriction
37
What are medications that work on the leukotriene pathway?
Receptor antagonists: montelukast, zafirlukast, pranlukast; 5-LO inhibitor: zileuton
38
What is omalizumab?
Recombinant humaized monoclonal IgG that binds IgE --> down regulation of IgE receptor on mast cells/basophils; "heavier" medication
39
How does histamine lead to asthma?
Increased SM contraction, mucus production, etc...
40
Antihistamine drugs
H1 blockers; Fist generation: diphenhydramine, hydroxyzine (cause significant sedation because cross BBB); Second generation: ioratadine, fexofenadine, cetirizine
41
Does asthma respond to antihistamines?
No, not really
42
What is bronchial thermoplasty?
Treatment for very sever asthma that reduces hypertrophic bronchial SM
43
Asthma exacerbation meds
Short acting bronchodilators (albuterol + ipratropium)
44
Asthma controller meds
Inhaled corticosteroid (2x a day), longer acting sympathomimetic/anticholinergic medication