Asthma

Question 1

What are some parts of the definition for asthma

Answer 1

chronic inflammatory disorder with mast cells, eosinophils, CD4 t lymphocytes. causes wheezes, breathlessness, chest tightness, and cough but not really chest pain.

Question 2

3 critical components of asthma

Answer 2

1. Episodic cough, wheeze, SOB, chest tightness
2. Variable airflow obstruction that reverses sponatenously or with treatment
3. Increased bronchial hyperreactivity

Question 3

2 critical measures of asthma severity

Answer 3

impairment of activities because of symptoms

2. risk of exacerpabation

Question 4

Difference btw first presentation of asthma in adults and kids

Answer 4

kids: atopic march of eczema, food allergies, rhinitis, and asthma. Occasionally preceded by RSV infection.
adults: may not require allergic history. Often preceded by a hx of recent infection that settled in the chest. For adults, rule out occupational/environmental exposures.

Question 5

What is the definition of severe asthma? Important sequelae/considerations?

Answer 5

Severe: attacks and symptoms every day despite medications. Increased risk of acute decompensation and death. the biggest risk for fatal astham is prior hospitalization or ICU admission for asthma. may be because these people’s bodies don’t recognize signs of hypoxia and hypercarbia as well as other people’s

Question 6

One cause of fatal asthma in kids

Answer 6

mucus plugs

Question 7

Airflow obstruction: What is happening physically?

Answer 7

symptoms: wheezing and other expiratory limitation from smooth muscle constriction, mucus production, and airway collapse. segment of the airway collapses with high upstream pressure and low downstream pressure.

Question 8

Aiflow obstruction tests

Answer 8

FEV1/FVC ratio below 70%. reverses with bronchodilators: increase of FEV1 greater than or equal to 12% and 200 mL in volume.

Question 9

How do you test for bronchial hyper responsiveness? Agents used?

Answer 9

broncho provocation studies.  inhale something that is irritating and do serial FEV1 measurements.  
Use methacholine (direct smooth muscle constrictor) or mannitol (indirect irritant).  
Normal people should be ok, but asthmatics tend to show a decrease in FEV1 as you give more irritant.
test is 85% sensitive.  may get false negatives with medication use; hyperreactivity may also wax and wane

Question 10

What is airway remodeling

Answer 10

structural change to the airway that occurs after long-term chronic asthma. see subepithelial collagen deposition, more smooth muscle mass, thickened epithelium. this is basically a form of irreversible obstruction, as in COPD

Question 11

What factors are made by TH2 lymphocytes. Which ones casuse similar effects?

Answer 11

IL4, IL5, and IL13. IL4 and IL13 grouped together.

Question 12

Effects of IL5

Answer 12

increased eosinophils –> incr. leukotrienes (from arachidonic acid) and increased granules. Ultimately, this causes vascular leak/edema, mucus secretion, and smooth muscle contraction.

Question 13

Effects of IL4 and IL13

Answer 13

two systems:

1. epithelium –> increased mucus chemokines and inducible nitric oxide synthetase. Leads to increased mucus and increased nitric oxide
2. B cells –> IgE –> activated mast cells –> mast cell degranulation in presence of an allergen –> bronchospasm, edema, air flow constriction, and hyper-responsiveness.

Question 14

Exhaled NO

Answer 14

because IL4 and IL13 stimulate the epithelium to make inducible nitric oxide synthetase, many asthmatics have elevated exhaled NO. may reflect airway inflammation. not very sensitive, but quite specific. exhaled NO >50 ppm usually means asthma. Good for monitoring therapy

Question 15

Short term pharmacological therapies for asthma. goals and classes.

Answer 15

relieve bronchospasm. include inhaled beta agonists, epinepherine derivatives, and anti-cholinergis.

Question 16

Long term pharmacologic therapies for asthma. goals and classes

Answer 16

to treat inflammation. inhaled corticosteroids, systemic steroids, lekuotriene modifiers, and anti-IgE antibodies

Question 17

Inhaled beta agonists: types, duration, examples

Answer 17

usually dry powder inhalers
may be short or long acting
short lasts 4-6 hrs: albuterol and levobuterol
long: 12-24 hrs. lipid part for membrane insertion. think salmeterol.
Beta 2 G protein coupled receptor (7 membrane pass) relaxes bronchial smooth muscle through PKA activation.

Question 18

What is the first drug for mild intermittent asthma

Answer 18

short acting beta agonist

Question 19

What should I know about long acting beta agonists?

Answer 19

based on SMART study, may cause increased problems, esp. in African Americans, when compared with other drugs. Therefore, long acting beta agonists are NOT used as monotherapy. May be used in combination with inhaled steroids for moderate asthma

Question 20

Inhaled steroids: when use, effects.

Answer 20

first line therapy for persistent asthma. may even reduce remodeling but we don’t know for sure.
cause decreased mucus chemokines, decr. IgE production, decreased IL5, and decreased eosinophils.
increase neutrophils.

Question 21

Drawbacks of corticosteroids.

Answer 21

decr. bone mass, decr. height, cataracts.

also, very expensive. none are generic.

Question 22

Name of an inhaled corticosteroid

Answer 22

symbicot, advair

Question 23

Leukotriene antagonists.

Answer 23

singular and zyflo

Question 24

Targets for antibody asthma treatments. Other new treatments?

Answer 24

1. Xolair targets IgE and is already on the market
   in future:
   targets against IL5 and IL13.
   also, things that zap unnecessary bronchiole smooth muscle.