08: Asthma

Question 1

3 major components of asthma

Answer 1

1. Bronchoconstriction
2. Airway inflammation
3. Airway hyperresponsiveness

All three lead to airflow obstruction

Question 2

Bronchoconstriction

Answer 2

• Narrowing of airways due to contraction of smooth muscle
• Partially reversible (distinguishes from chronic bronchitis and emphysema)
• Stimuli (allergens, irritants, viruses, cold air, exercise) activate ANS –> PNS/vagus releases acetylcholine –> acts on muscarinic receptors in airway smooth muscle –> contraction

Question 3

Airway inflammation

Answer 3

• Narrowed airway due to edema, cellular debris, increased mucus secretions
• Altered gas exchange and ventilation
  
  1. Severely obstructed airways
  2. Poorly ventilated areas of lung (↓V) with normal perfusion: V/Q mismatch
  3. Compensatory reduction in perfusion (↓Q) –> V/Q matching
  4. Fall in PaO2 reduced
  5. Low values of V/Q ratio (but less hypoxemia than with mismatch)
• Cells activated in airway inflammation:
  
  • Mast cells: release histamine (edema, mucus, SMC constriction)
  • Eosinophils: release Major Basic Protein (MBP) (edema, epithelial cell damage, airway hyperresponsiveness)
  • T helper-2 lymphocytes (TH2): release cytokines (stimulate movement of cells towards sites of inflammation)

Question 4

Airway hyperresponsiveness

Answer 4

• ↑sensitivity/irritability of airways in response to exposure to various allergens, viruses or other stimuli
  
  • Excessive airway narrowing due to exaggerated bronchoconstrictor response
  • ↑mast cells, eosinophils released
• Transient exposure: acute bronchoconstriction, inflammation –> variable (reversible) hyperresponsiveness –> reversible airflow obstruction
• Continuous, repeated exposure: prolonged bronchoconstriction, airway inflammation –> persistent hyperresponsiveness –> airflow obstruction with airway remodeling

Question 5

Asthma gross pathology

Answer 5

• Lungs hyperinflated: abnormal increase in volume of gas in lungs at end of tidal expiration
• Extensive mucus pluggin: cellular debris, mixture of inflammatory cells, mucin secreted by goblet cells
• Lung parenchyma intact

Question 6

Asthma histopathology

Answer 6

• Sloughing of ciliated columar epithelial cells
• Goblet cell metaplasia
• ↑thickness of subepithelial basement membrane
• full thickness inflammatory cell infiltrate of airways

Question 7

Metacholine challenge

Answer 7

• Administer methacholine to induce bronchoconstriction
• Objective measure of airway hyperresponsiveness
• Assess amount needed to decrease FEV1 by 20%
• Asthmatics will have low provocation tolerance

Question 8

Two classes of asthma medications

Answer 8

1. Rescue, quick-relief meds: reverse bronchoconstriction; best via inhaler/nebulizer
2. Long-term controller meds: reduce airway inflammation; can be delivered as tablets/liquids

Question 9

3 classes of rescue meds

Answer 9

1. Short-acting beta2 agonists (SABA)
   
   • ​Albuterol
   • Terbutaline
2. ​Short acting anti-cholinergic agents
   
   • Ipratropium bromide
3. ​Systemic corticosteroids
   
   • Prednisone​

Question 10

Long-term controller meds

Answer 10

1. Inhaled corticosteroids (ICS)
   
   • Budesonide
   • Fluticasone
2. Long-acting beta2 agonists (LABA)
   
   • Salmeterol
3. Leukotriene modifiers (LTRA)
   
   • Montelukast
   • Zafirlukast
4. Combo therapy (LABA/ICS)
   
   • Salmeterol/fluticasone (advair)
   • Formoterol/budesonide (symbicort)
5. Methylxanthines
   
   • Theophylline
6. Immunomodulators
   
   • Omalizumab

Question 11

Delivery devices

Answer 11

• Metered dose inhalers (asthma pumps): quick, portable, rescue/controller meds, require good coordination
• Dry poweder inhalers (discs, twisthalers): easy to use, no taste, moisture sensitive, can lose the dose
• Nebulizer (asthma machine): higher dose, more effective during exacerbation, require electricity, expensive, take longer time
• Valved holding chamber (spacer): inexpensive, good drug delivery, portable, require proper cleaning, dose differs by brand

Question 12

Intermittent asthma

Answer 12

• Daytime sx: < or = 2 days/wk
• Nighttime sx: < or = 2 nights/mo
• SABA use: < or = 2 days/wk
• No activity limitation
• Normal lung function
• Rx: SABA prn

Question 13

Persistent asthma

Answer 13

• Daytime sx > 2 days/wk
• Nighttime sx > 2 nights/mo
• SABA use > 2 days/wk
• Minor to extreme activity limitation
• Abnormal lung function
• Rx: Low to high dose ICS, LABA, oral corticosteroids