Lung Structure And Airway Disease

Question 0

What are the signs and symptoms of asthma?

Answer 0

Shortness of breath
Wheezing
Tight chest
Coughing

Question 1

What is asthma?

Answer 1

Asthma is a chronic inflammatory disease of the airways characterised by: bronchial obstruction and airflow limitation.

Question 2

What’s can cause asthma attacks?

Answer 2

Allergic reaction to house dust mite, grass, pollens, animals
Occupational
Exercise induced
Aspirin

Question 3

What are the 4 main features of asthma?

Answer 3

1. Bronchial obstruction
2. Airway hyperresponsiveness
3. Airway remodelling
4. Airflow limitation

Question 4

Define bronchial hyperresponsiveness?

Answer 4

Excess bronchial narrowing as a result of an exaggerated bronchoconstrictor response of the airways to various inhaled stimuli such as histamine, cold air and respiratory viruses.
Airway narrowing may be due to increase in airway smooth muscle force and/or mass as well as microvascular leakage.

Question 5

Possible mechanisms that contribute to bronchial hyperresponsiveness in asthma?

Answer 5

1. Resistance to airflow is inversely proportional to the radius if the lumen raised to power of 4. A small change in lumen causes a large change in resistance.
2. Increase in airway smooth muscle force and/or mass as well as microvascular leakage from post-capillary venules and resultant odema.

Question 6

What is the function of pulmonary arteries and veins?

Answer 6

Carry blood to arteries and from veins in the lungs.
Pulmonary veins carry O2 away from the lungs.
Pulmonary arteries carry CO2 towards the lungs.

Question 7

What is the function of the bronchial arteries and veins?

Answer 7

Supply blood to and drain from the airways.
Bronchial arteries carry O2 to tissues of lung.
Bronchial veins carry CO2 away from tissues of lung.
Bronchial oedema in asthma.

Question 8

Airway nerves - cholinergic (excitatory)

Answer 8

Dominant neural pathway in the airways.

Major role in regulating airway smooth muscle tone and mucus production.

Question 9

Airway nerves: excitatory = ?

Answer 9

Contraction.

Question 10

Airway nerves: inhibitory =?

Answer 10

Relaxation.

Question 11

Airway nerves: noradrenergic (inhibitory)

Answer 11

Noradrenaline decreases smooth muscle tone.
Relaxation due to b2 adrenoceptor.
Does not play a dominant role below main bronchi.

Question 12

Airway nerves - inhibitory noradrenergic noncholinergic (iNANC)

Answer 12

Release nitric oxide (NO)

Innervated smooth muscle directly to cause relaxation

Question 13

Excitatory noradrenergic noncholinergic (eNANC)

Answer 13

Release neuropeptides e.g. Substance p, neurokinin A.
Increases airway tone, secretion of mucus and microvascular leakage.
Used in pepper spray. Asthmatics are sensitive to this.

Question 14

Describe the allergic response in asthmatics?

Answer 14

Early phase response:
Decrease in FEV1 peak - 30-40 minutes, resolves 2-3 hours.
Mast cell-derived histamine and leukotrienes triggers.
Late phase response:
Release of inflammatory mediators cause submucosal oedema, airway wall swelling, secretion of mucus.
Epithelium remodelling, airway muscle hypertrophy/hyperplasia, subepithelial fibrosis.

Question 15

Describe bronchial obstruction in asthma?

Answer 15

Caused by a range of endogenous mediators. Involves:
Increased smooth muscle tone
Hyper secretion of mucus
Shedding of the epithelium and accumulation of debris in airway lumen
Oedema and swelling of submucosa
Airway smooth muscle hypertrophy (increase cell size) and hyperplasia (increase cell number)
Subepithelial fibrosis (makes cell wall thicker)

Question 16

What is airway remodelling in asthma?

Answer 16

Airway remodeling in asthma is what happens in response to long-term, unresolved airway inflammation. When airway inflammation is not adequately treated, it can result in permanent structural changes in the airways.
Increased wall thickening has repeatedly been associated with increased disease severity, including near fatal asthma. These changes are the result of epithelial cell alterations, subepithelial fibrosis, submucosal gland hyperplasia, increased airway smooth muscle mass, and increased airway vascularization

Question 17

Describe the airway mediator - histamines?

Answer 17

Stored in mast cells and basophils. They are released in response to an appropriate allergen and during early phase response.
It can cause bronchoconstriction and airway wall oedema which can lead to bronchial obstruction and airflow limitation.

Question 18

What are H1 receptor antagonists?

Answer 18

They are antihistamines used to treat seasonal allergies such as hay fever but are not useful in the treatment of asthma.

Question 19

What are H4 receptor antagonists?

Answer 19

Still in development but they are said to be used in the treatment of asthma, itching, chronic pain, autoimmune disease and cancer.

Question 20

Describe the airway mediator - leukotrienes?

Answer 20

Family of lipid mediators derived from arachidonic acid metabolism. Released in response to allergen exposure during the early and late phase responses.
LTB4 - chemoattractant for inflammatory cells
LTC4, LTD4, LTE4 - potent bronchoconstrictors, cause secretion of mucus, induce release of chemical mediators from inflammatory cells.

Question 21

What is chronic obstructive pulmonary disease? (COPD)

Answer 21

Caused by chronic bronchitis and emphysema.
It is a progressive degenerative disease causing death. It has debilitating symptoms and shortens the lifespan.
Primary causes are tobacco smoking and air pollution.
Currently the 4th leading cause of death according to WHO.

Question 22

What are the treatment options for COPD?

Answer 22

Involves a combination of 2 different drugs. 
Ipratropium bromide (muscarinic antagonist) and salbutamol (B2 adrenoceptor agonist)

Question 23

What is chronic bronchitis?

Answer 23

It is an inflammatory disease with irreversible airflow limitation.
It involves hypersecretion of bronchial mucus which leads to hypertrophy, hyperplasia, chronic coughs and excessive sputum.
It can also lead to second respiratory infections due to excessive mucus productions.

Question 24

What are the treatment options for chronic bronchitis?

Answer 24

Drugs may provide relief and may improve lung function such as: B2 adrenoceptor agonist, muscarinic antagonist, glucocorticoids, antibiotics.
Roflumilast is selective PDE IV inhibitor recently approved. It helps improve lung function, decrease frequency of exacerbations and may target underlying inflammation.

Question 25

What is emphysema?

Answer 25

It is a degenerative peripheral lung disease. It involves destruction of the alveolar membranes which causes severe impairment of oxygen delivery and CO2 clearance. It is commonly associated with smoking and chronic bronchitis.

Question 26

What are B2 adrenoceptor agonists?

Answer 26

Fast acting and effective relievers of airway obstruction. Causes relaxation of smooth muscle and reverse bronchoconstriction due to excitatory mediators such as histamine and leukotrienes. It inhibits mediator release from meat cells and stimulates cilia beat frequency which increases clearance of mucus.

Question 27

What does salbutamol (ventolin) and terbutaline (bricanyl) do?

Answer 27

They are short acting B2 adrenoceptor agonists. They provide about 6 hours of relief from bronchospasm.

Question 28

What does formoterol and salmeterol do?

Answer 28

They are long acting B2 adrenoceptor agonist drugs.

Provide up to 12 hours of relief from bronchospasm. Useful for those who are affected at night.

Question 29

What is methylxanthines - theophylline?

Answer 29

It is one of the oldest drug therapies doe asthma. It is administered orally.
Bronchodilator - decreases phosphodiesterase activity and increases cAMP levels.
Inhibition of all subtypes of PDE enzymes with severe side effects of nausea and arrhythmia. There is only a narrow therapeutic window.
Anti-inflammatory - decreases expression of inflammatory genes.

Question 30

What Ipratropium and tiotropium?

Answer 30

They are muscarinic receptor antagonists.
Effective bronchodilator in some asthmatics.
Decreases secretion of mucus.
No anti-inflammatory actions.
Administered via inhalation however not widely used as b2 agonist and glucocorticoids.

Question 31

Examples of short acting bronchodilators?

Answer 31

Airomir
Alupent
Asmol
Bricanyl
Respolin
Ventolin

Question 32

Examples of long acting bronchodilators?

Answer 32

Atrovent
Foradile
Oxis
Serevent

Question 33

What does glucocorticoids do in asthmatics?

Answer 33

Glucocorticoids is frontline therapy for asthma. The anti-inflammatory action makes them ideal for long term use. It can be used prophylactically to prevent, reduce and reverse airway inflammation.
It can be used in combination with B2 adrenoceptor agonists.

Question 34

What are beclomethasone and fluticasone?

Answer 34

Glucocorticoids administered via inhalation. This is an effective and direct method.

Question 35

What is prednisolone?

Answer 35

Glucocorticoid administered orally for severe asthmatics.

Question 36

Mechanism of action of glucocorticoids in asthmatics?

Answer 36

Inhibits phospholipidase A2 activity and cycloxygenase activity.
Prevents release of arachidonic acid. Reduces synthesis of leukotrienes and prostaglandins.
Reduces influx of inflammation cells.
Increases number of B2 adrenoceptors
Decrease microvascular permeability
Decrease mediator release from eosinophils.

Question 37

What are adverse effects of glucocorticoids on asthmatics?

Answer 37

Inhaled preparation - can cause oropharyngeal candidiasis (thrush). You can reduce this by using a spacer device.
Oral preparations - can cause suppression of hypothalamic-pituitary adrenal axis. This leads to adrenal insufficiency, reduced capacity to synthesise corticosteroids and osteoporosis.

Question 38

What is ciclesonide (Alvesco)?

Answer 38

Ciclesonide is a prodrug of glucocorticoids. It is converted to the active metabolite M1 in the lung. Affinity for the drug by the glucocorticoid receptor is 100x greater. Systemic bioavailability via inhalation is 50%. Oral systemic bioavailability is <1%.

Question 39

What is sodium cromoglycate (intal)?

Answer 39

It is glucocorticoid used for its anti-inflammatory action. It can be used prophylactically and mainly administered via inhalation.
Mechanism of action - inhibits mediator release from mast cells, inhibits infiltration and activation of inflammatory cells, suppresses the response of sensory nerves to irritants inhibits early and late phase responses to allergen.
Has been found to have fewer adverse effects to non-airway tissues.

Question 40

What is leukotriene receptor antagonist?

Answer 40

Drug that prevents leukotriene from acting. Both anti-inflammatory and bronchodilators.
Useful in elderly and young children where the use of spacer devices is difficult and they should avoid glucocorticoid use.

Question 41

What are montelukast and zafirlukast?

Answer 41

Leukotriene receptor antagonists that can be administered orally and have anti-inflammatory and bronchodilator effects.

Question 42

What is omalizumab (xolair)?

Answer 42

It is a recombinant DNA derived humanised monoclonal antibody that selectively binds to human immunoglobulin E (IgE)
It decreases the amount of circulating free IgE and decreases magnitude of clinical response when patients with known specific allergies are exposed to these allergens.
Usually administered by subcutaneous injection.