Week 2: Asthma

Question 1

Definition of asthma

Answer 1

Chronic lung disease that includes the following characteristics:

• airway narrowing: wheezing, breathlessness, cough, chest tightness
• reversibility
• hyperreactivity
• inflammation leading to remodeling

Question 2

Pathophysiology of asthma

Answer 2

1. Genetics: complex pattern
   - polymorphisms at B2-receptor gene
   - Arg/Arg at position 16: more likely to experience decline in lung function and more exacerbations. Compared to Gly/Gly and Arg/Gly
2. Environment: less asthma in rural societies (hygiene hypothesis)
   - mediated by Th2 phenotype: Il-4, Il-5, Il-13
3. NSAID sensitive asthma
   - pathway shunted into LTC4+LTD4, which are potent bronchoconstrictors (since COX1/2 blocks prostaglandin synthesis )and LTB4 (chemoattractant for PMNs)

Question 3

Cellular mechanisms of asthma

Answer 3

• hyperresponsive airways, react to allergens, leads to inflammation
• IgE release of inflammatory mediators
• Immediate: mostly histamine-sneeing, congesting, itchy, runny nose, watery eyes
• minutes: Leukotrienes and Pgs (bronchoconstriction and chemoattractant)– wheezing
• hours: cytokines Il-4, Il-5, Il-13 –mucus and Eosinophils

Question 4

Assessment of asthma severity

Answer 4

• frequency of acute episodes
• episodic nature- day/night variations
• frequency of medication use
• spirometry

Question 5

Clinical features of asthma

Answer 5

Signs
-wheezing
-diminished breath sounds
-prolonged expiration
-accessory muscle use
-tachypnea, tachycardia
-pulsus paradoxus
SYmptoms
-cough
-shortness of breath
-chest tightness

Question 6

PFTs in asthma

Answer 6

• flows are reduced
• flows improve with inhaled bronchodilator
• evidence of hyperinflation (increased lung volumes)
• inhalation challenge: methacholine, exercise, allergen challenge
• flow-volume: more concave as disease worsens
• FEV1/FVC>70 in mild disease

Question 7

Asthma lab findings

Answer 7

1. PFTs-see other card
2. Chest X-ray: normal usually
3. CBC: eosinophilia
4. Sputa
   - eosinophils
   - Curschmann’s spirals: casts of mucus
   - Charcot-Leyden crystals: breakdown products of eosinophils
5. IgE usually elevated
6. inhalation challenge -positive indicates hyperresponsiveness
7. eNO- elevated in asthma and COPD, indicator of inflammation

Question 8

Asthma classification

Answer 8

1. Intermittent
   - symptoms less than 2days/week
   - nighttime symptoms less than 2/month
   - SABA use less than 2 days/week
   - asymp with normal activity
   - FEV1>80%, FEV/FVC normal
2. Mild persistent
   - symptoms>2days/week but not daily
   - nighttime symptoms 3-4x/month
   - SABA use>2days/week but >1x/day
   - FEV1/week but not nightly
   - daily use of SABA
   - FEV1>60 but <60% predicted

Question 9

Asthma Medications

Answer 9

RELIEVERS
-inhaled short acting b2-agonists (SABA)
-inhaled cholinergics
CONTROLLERS
-inhaled or systemic glucocoids
-leukotriene modifiers
-long acting b2-agonists
-sustained release theophylline
-oral antiallergics

Question 10

Approach to managing asthma

Answer 10

-start with SABA
-add ICS
-then add ICS+long acting beta agonists (LABA)
-increase dosage of before
-then add Omalizumab (monoclonal antibodies)
NEVER use long acting beta agonists without inhaled corticosteroids–higher mortality

Question 11

Why do some asthmatics not respond to b2-agonist?

Answer 11

Genetic polymorphisms at b2-receptor

• Arg/Arg16 patients using regular daily albuterol more likely to have decline in lung function and less control over asthma
• Gly/gly 16 and Arg/Gly 16 have better control with regular albuterol use

Question 12

Airway remodeling in asthma

Answer 12

• alteration of tissue structural components in response to inflammation and/or inflammation
• airway thickening: subepithelial fibrosis, increase of smooth muscle, mucus metaplasia, angiogenesis
• goblet cell hyperplasia
• narrowing lumen causing obstruction