Asthma

Question 1

What are obstructive lung diseases?

Answer 1

Lung disorders characterized by impaired airflow caused by an airway obstruction (partial or complete) at any level from the trachea to the bronchioles.

Includes:
1. asthma
2. COPD (emphysema and/or chronic bronchitis)
3. cystic fibrosis (also restrictive)

Question 2

What are the 4 mechanisms of airway obstruction?

Answer 2

1. increased thickness of airway walls.
2. Airway occlusion
3. Loss of elastic fibres
4. bronchoconstriction

Question 3

What are the effects of airway obstructive lung disease on ventilation?

Answer 3

During inhalation the airways are pulled open and air rushes past the obstruction.

During exhalation obstructed airways collapse before exhalation is complete (can’t get the air out).
- trapped air makes it difficult to take another breath
- increased work of breathing = accessory muscles are required
- air trapping causes lung hyperinflation

Question 4

What is FVC (forced vital capacity)?

Answer 4

Part of a pulmonary function test that measures the volume forcibly exhaled after a full inhalation.

Question 5

What is FEV1 (forced expiratory volume in 1 second)?

Answer 5

Part of a pulmonary function test that measures volume forcibly exhaled within 1 second.

Question 6

How is spirometry measured?

Answer 6

Expressed as a ratio (FEV1/FVC) or FEV1 as a percentage of a predicted value.

Question 7

What is asthma?

Answer 7

Chronic inflammatory disease of airways characterized by airway hyperresponsiveness (exaggerated tendancy to narrow in response to various triggers) resulting in airflow limitation.

Question 8

Asthma mainly affects which part of the lungs?

Answer 8

Bronchioles and small bronchi. The more airway inflammation present the more hyperresponsive the airways.

Question 9

What is the clinical presentation of asthma?

Answer 9

• variability of frequency, severity and triggers
• recurrent episodes of wheezing, chest tightness, cough an dyspnea
• airflow limitation is at least partially reversible (spontaneously or with treatment)
• treatment goals involve reducing the frequency of asthma episodes and severity of symptoms.
• poorly managed asthma results in airway remodeling (= permanent thickening of airway walls) and chronic obstruction

Question 10

Describe the etiology of asthma.

Answer 10

Genetic and environmental factors are proposed to play a role in the underlying airway inflammation and hyperresponsiveness.

1. genetic predispostion (> 100 genes identified in genome-wide studies associated with asthma)

Question 11

What are some proposed environmental factors across the lifespan that cause asthma?

Answer 11

• prenatal/perinatal: exposure to maternal smoking, maternal vitD deficiency, prematurity, c-section delivery
• childhood: exposure to allergens, microbiome dysbiosis (early abx exposure), childhood respiratory infections (RSV), exposure to air pollution and tobacco smoke
• adolescence/adult: exposure to chlorinated pools, active smoking, occupational exposures.

Question 12

What is the difference between allergic and non-allergic asthma?

Answer 12

1. Allergic (atopic) = initiated by exposure to an allergen.
2. non-allergic (non-atopic) = initiated by exposure to an airway irritant

Many asthmatics have a combination of both.

Question 13

Which kind of asthma accounts for most cases of childhood onset asthma?

Answer 13

Allergic asthma.

Question 14

Describe the genetic component to allergic asthma.

Answer 14

Individuals with allergic (atopic) asthma have a genetic predisposition to develop IgE in response to allergens (=atopy)

Question 15

What other atopic disorders are often present with allergic asthma?

Answer 15

• eczema, food allergies, allergic rhinitis
• tend to present with eczema from birth, food allergies around 1-2 years, rhinitis around 3 years and asthma around 7 years

Question 16

Describe the bodies initial immune response in allergic asthma.

Answer 16

With initial exposure to allergen:

• an abnormal immune response = large amounts of allergen specific-IgE in those genetically predisposed
• response involves an imbalance between Th1 and Th2 production (favouring Th2 cells and activation of B cells)
• IgE that isn’t exposed to the allergen, binds to airway mast cells = airway sensitization

Question 17

Describe the bodies subsequent response to an allergen in allergic asthma.

Answer 17

• The allergen cross-links IgE molecules bound to mast cells of sensitized airways
• Mast cell activation & degranulation cause the early phase of an acute asthma attack.

Question 18

What are triggers for non-allergic asthma?

Answer 18

Viral respiratory infections and exposure to bronchial irritants

Question 19

What percentage of asthmatics does non-allergic asthma account for?

Answer 19

30%

Question 20

When in the lifetime does non-allergic asthma typically evolve?

Answer 20

Adulthood

Question 21

How do respiratory infections lead to non-allergic asthma?

Answer 21

• viral infections harm the epithelium, causing airway inflammation
• increases airway sensitivity, including to other triggers

Question 22

What is exercise-induced bronchoconstriction?

Answer 22

Loss of heat and water from airways causes irritation and inflammation (worse in cool, dry weather)

Attacks often occur when exercise stops and airways are less dilated (within 3 mins)

Tend to resolve within 60 mins

Question 23

How do aspirin, NSAIDs cause to non-allergic asthma?

Answer 23

• block the COX enzyme and PG synthesis and a relative increase in leukotrines = bronchoconstriction
• attacks occur within minutes to hours (up to 12 hours) of ingestion

Question 24

How do inhaled irritants cause non-allergic asthma?

Answer 24

• cigarette smoke, air pollutants, strong odours = stimulate irritant receptors in airway walls causing reflex bronchoconstriction

Question 25

What happens in the acute asthmatic response phase?

Answer 25

- allergens activate mast cells and Th2 cells within airway walls - mast cell activation = release of preformed inflammatory mediators such as histamine and chemotactic factors - Th2 cells produce cytokines that contribute to B cell activation and IgE synthesis Airway changes: - bronchoconstriction - airway swelling (edema) - mucous production

Question 26

How does a bronchodilater work?

Answer 26

relaxes bronchial smooth muscle and typically increases airflow within 5 mins

Question 27

What happens in the late asthmatic response?

Answer 27

1. the effects of slower acting cytokines, prostaglandins, and leukotrines 2. epithelial injury by recruited eosinophils 3. the activation of parasympathetic reflexes

Question 28

What the slower acting prostaglandins and leukotrines do in asthma?

Answer 28

Contribute to inflammation, bronchoconstriction, and mucus production.

Question 29

What role to eosinophils play in asthma?

Answer 29

Eosinophils are recruited by chemotactic factors released by Th2 cells (IL-5) and mast cells. They release damaging proteins (e.g. major basic protein) - normally toxic to parasites - cause airway epithelial damage (along with tryptase from mast cells) and inflammation

Question 30

What are creola bodies?

Answer 30

Shed epithelial cells found in the sputum of symptomatic asthmatics.

Question 31

Describe the activation of parasympathetic reflexes in late asthmatic response?

Answer 31

Epithelial damage exposes subendothelial sensory nerve endings. - activates the parasympathetic (vagal) reflexes causing further bronchoconstriction and mucus secretion

Question 32

What are the effects of partial obstruction on lung function?

Answer 32

- air trapping and hyperinflation - increased work of breathing

Question 33

What are the effects of total obstruction of airways?

Answer 33

- obstructive atelectasis = collapse of alveoli

Question 34

What is airway remodelling?

Answer 34

Occurs with frequent asthma attacks and persistent inflammation and is irreversible. 1. epithelial cell damage stimulates collagen deposition and subepithelial fibrosis 2. airway smooth muscle layer thickens

Question 35

Why do attacks occur at night or upon waking?

Answer 35

- muscle relax during sleep and tend to narrow - reclining position causes secretions to accumulate - low epinephrine (especially at 4am) which normally causes bronchodilation

Question 36

Describe 6 steps in diagnosing asthma.

Answer 36

1. patient history 2. physical exam 3. spirometry (pre and post bronchodilator), peak flow monitoring (PFM), methacholine challenge 4. lab tests (CBC (elevated eosinophils, serum IgE) 5. chest x-ray (r/o other causes, may show lung hyperinflation during an attack) 6. allergy testing

Question 36

What do FEV1 and FVC stand for in spirometry?

Answer 36

FEV1 = forced expiratory volume in 1 second, or the amount of air you can exhale in the first second after a deep breath. FVC = Forced vital capacity, or the total amount of air you can exhale forcefully in one breath

Question 37

Describe 4 steps to manage asthma.

Answer 37

1. Prevention: - removal of triggers (#1 preventative measure) - vaccinations 2. Develop an asthma action plan/ regular follow up care - educate patient on how to self-manage worsening symptoms and when to seek medical help 3. Quick relief of acute attacks e.g. short-acting beta-2 agonist (SABAs) or budesonide/formeterol (symbicort) - goal is to minimize use (>2 uses/week is a sign of poorly controlled asthma) 4. Long-term management (controller meds) - used on a regular basis - treat underlying inflammation, maintain asthma control, and prevent attacks - e.g. inhaled corticosteroids, long-acting beta-2 agonists (LABAs), leukotrine receptor antagonists.

Question 38

What is 'good control' of asthma defined as?

Answer 38

- daytime asthma symptoms < or equal to 2 days/week and no nighttime symptoms - little to no need for reliever meds (< or equal to 2 days/week) - no limitations to physical activity or absence from school/work - normal or near normal lung function