Module 4 Section 5 (Asthma and COPD)

Question 1

What is asthma? What are the symptoms and subsequent consequences?

Answer 1

Asthma is an inflammatory respiratory syndrome characterized by narrowing of the bronchial airways and increased resistance to airflow.

Symptoms: shortness of breath, cough, chest tightness, and wheezing.

The consequences of asthma are largely regarded as preventable, since effective treatments for relief of acute attacks and prevention of attacks are available.

Question 2

What is COPD?

Answer 2

COPD results in a progressive decrease in lung function that is characterized by airflow limitation that is not fully reversible with treatment.

Question 3

Discuss the pathology of asthma.

Answer 3

The pathology of asthma includes inflammation of the bronchial walls, which leads to narrowing of the bronchial airways and increased resistance to airflow.

Question 4

How does the severity of asthma vary?

Answer 4

1) Mild asthma is characterized by occasional symptoms that occur during or after exposure to certain allergens, exercise, or viral upper respiratory infections.
2) Moderate asthma can flare up often and may last several days. This type of asthma will disrupt daily activities and may impact sleeping.
3) More severe forms of asthma are associated with frequent attacks of shortness of breath and wheezing, especially at night, or with chronic bronchial airway narrowing that causes chronic respiratory impairment.

Question 5

What are the 3 factors that increase bronchiolar airway narrowing in asthma attacks?

Answer 5

1) Bronchoconstriction: contraction of bronchial smooth muscles.
2) Mucosal edema: swelling that occurs as a result of irritation and inflammation of the bronchiolar epithelium.
3) Bronchiolar secretions: increased mucous secretion due to inflammation.

Question 6

The exact pathogenesis of asthma is not known, and has been attempted to be explained by a couple of different models. What are they?

Answer 6

1) Allergen-Induced Model

2) Nonspecific Bronchial Hyperreactivity Model

Question 7

What is the Allergen-Induced Model? What are the proposed mechanisms?

Answer 7

The classical model of asthma is an inflammatory respiratory disorder mediated by exposure to an allergen.

1) Allergens such as house dust mites, animal danders, moulds, and pollens cause the production of immune globulin (IgE) by mast cells and T lymphocytes (two types of white blood cells).

2) Once produced, IgE binds to mast cells in the airway mucosa. Then, on re-exposure to the allergen, the interaction of the allergen with IgE triggers the mast cells to release mediators stored in the cells, as well as cause the synthesis and release of other mediators.
- These released mediators include histamine, tryptase, leukotrienes (LTC), and prostaglandins (PGD).

3) The released mediators trigger contraction of the muscle in the bronchioles, narrowing the bronchiolar airways and eliciting an acute asthma attack.

4) Often, three to six hours after the allergen-induced acute asthma attack, a second, more sustained phase of bronchoconstriction is experienced, termed the “late asthmatic response.”
- This second phase of bronchoconstriction may last for several weeks after inhalation of an allergen, and is associated with inflammatory cell influx into the bronchial mucosa and increased bronchial reactivity.
- Allergic asthma has a genetic component, as it tends to cluster in families.

Question 8

What is wrong with the Allergen-Induced Model explanation?

Answer 8

The model of allergen-induced asthma is not complete, as it does not reproduce all features of asthma.

• For instance, many asthma attacks are not triggered by inhalation of allergens, but by viral respiratory infections.
• Some asthma is triggered by non-allergen stimuli such as exercise and cold air.
• The tendency to develop bronchospasm on encountering non-allergen stimuli is sometimes called “nonspecific bronchial hyper-reactivity” to distinguish it from allergen-induced asthma.

Question 9

What is the Nonspecific Bronchial Hyperreactivity Model? What are the proposed mechanisms?

Answer 9

The mechanisms underlying bronchial hyper-reactivity are not completely understood, but involve inflammation of the airway mucosa.

The hypothesis is that asthmatic bronchospasm results from a combination of both released mediators and exaggerated responsiveness to those mediators.
- In other words, the treatment of asthma is aimed not only at preventing or reversing acute bronchospasm, using bronchodilators, but also at reducing the overall amount of inflammation, using anti-inflammatory agents.

Question 10

What is the treatment of asthma?

Answer 10

Treatment of asthma includes control of precipitating factors, such as allergens or viral respiratory infections, and use of anti-asthma agents, such as bronchodilators and anti-inflammatory agents.

Short-term relief from an acute asthma attack is most effectively achieved with bronchodilators, while long-term management of asthma is accomplished with both bronchodilators and anti-inflammatory agents.

Question 11

How do bronchodilators work?

Answer 11

A bronchodilator functions to dilate, or open, the airways in the lungs.

Bronchodilators are typically inhaled using a metered-dose inhaler (shown in image) or nebulizer.

Question 12

What are the 2 main classes of drugs used for bronchodilators?

Answer 12

1) Sympathomimetics, drugs that mimic the effects of endogenous agonists of the sympathetic nervous system.
2) Antimuscarinics, drugs that block the muscarinic receptor.

Question 13

What are sympathomimetics and how do they work?

Answer 13

Sympathomimetics selectively bind to and activate β2 receptors on the bronchial smooth muscles, leading to bronchodilation.
- β2 receptors are found predominantly in the lungs, blood vessels, GI muscle, and uterus, and that activation of these receptors results in muscle relaxation.

Question 14

Of the bronchodilators, β2 agonists are the most effective and the most widely used. What are they?

Answer 14

Short-acting drugs, such as salbutamol. For acute asthma attacks, short-acting β2 agonists are the first-line of treatment, and are inhaled as an aerosol or nebulised solution.

• Inhalation provides fast relaxation of the bronchiolar smooth muscle and minimal systemic toxicity.
• With metered-dose inhalers, bronchodilation is maximal within 15-30 minutes of inhalation, and persists for approximately three to four hours.

Long-acting drugs, such as salmeterol. Inhaled long-acting β2 agonists can be used in maintenance therapy of asthma, but only in combination with inhaled corticosteroids (anti-inflammatory agents that you will learn about later in this section).
- Long-acting β2agonists are not recommended to be used alone.

Question 15

What are antimuscarinics and how do they work? Provide an example.

Answer 15

Antimuscarinic drugs are antagonists at the muscarinic receptors in the lungs, blocking cholinergic mediated bronchoconstriction.

• Antimuscarinic drugs are administered via inhalation.
• They are not as effective as the β2 agonists, and are therefore only used as adjunct therapy, or when patients are intolerant of inhaled β2 agonists.

Ex: A common antimuscarinic is ipratropium.

• It is used to control and prevent symptoms caused by ongoing chronic obstructive pulmonary disease, such as wheezing and shortness of breath.
• It’s often administered with nebulized salbutamol (a β2 agonist), enhancing the bronchodilation produced in acute severe asthma.

Question 16

What are 3 anti-inflammatory agents commonly used in the chronic management of asthma.

Answer 16

Corticosteroids: a class of steroid hormones produced in the adrenal cortex that decreases the production of macrophages, eosinophils, and lymphocytes

Leukotriene receptor antagonists: a class of drugs that selectively block the action of leukotrienes on the respiratory tract.

Anti-IgE antibodies: a class of drugs that directly targets IgE, the protein responsible for initiating an allergic reaction.

Question 17

What are corticosteroids and how do they work? Provide an example. What are some adverse effects?

Answer 17

By blocking the production of immune cells in the respiratory tract, corticosteroids reduce bronchial reactivity, improving all indices of asthma control, including the severity of symptoms, bronchial reactivity, frequency of exacerbations, and quality of life.
- Inhaled corticosteroids are the first-line treatment for maintenance therapy of asthma.

Ex: Fluticasone is an inhaled synthetic corticosteroid commonly used to treat asthma.

Adverse effects:

• Oropharyngeal candidiasis (fungal infection of the mouth) and hoarseness (a direct local effect on the vocal cords).
• Inhaled corticosteroids may also increase the risks of osteoporosis and cataracts when used chronically.
• In children, inhaled corticosteroid therapy can slow the growth rate by about one centimetre in the first year of treatment, however the overall effect on adult height is minimal.
• Chronic systemic exposure to corticosteroids are associated with severe adverse effects.

Therefore, oral corticosteroids, such as prednisone, are reserved for treatment of severe or urgent asthma.

Question 18

What are leukotriene receptor antagonists and how do they work? Provide an example. What the main advantages?

Answer 18

By antagonizing leukotrienes in the respiratory tract, this class of drugs decreases mucous secretion and bronchoconstriction. 
- These drugs are administered orally as tablets, and can be used in the chronic management of asthma in combination with inhaled corticosteroids.

Ex: Montelukast, sold under the trade name Singulair, is a leukotriene receptor antagonist (LTRA) used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies.

Advantages

• Leukotriene receptor antagonists improve asthma control and reduce the frequency of asthma exacerbations.
• They are taken orally, which is beneficial to young children and to patients who comply poorly with inhaled therapies.

Question 19

What are Anti-IgE antibodies and how do they work? Provide an example. What the main advantages and disadvantages?

Answer 19

Anti-IgE antibodies specifically inhibit the binding of IgE to mast cells and other inflammatory cells, but also do not activate IgE that is already bound to mast cells.

• The result is that mast cell degranulation does not occur, stopping the cascade of events that leads to an acute asthma attack.
• After ten weeks of administration, IgE levels in the blood are lowered to undetectable levels and the magnitude of bronchoconstriction after antigen challenge is reduced.

Ex: Omalizumab is a type of anti-IgE monoclonal antibody medication that is used to try and control severe allergic asthma.

Advantages:
- Repeated administration of anti-IgE monoclonal antibodies reduces the frequency and severity of asthma exacerbations and decreases the requirement of corticosteroids.

Disadvantages:
- They are very expensive and have to be administered via injection. As such, they are generally only used in allergy-induced asthma that it is not managed with the other described therapies.

Question 20

Using the information provided, determine which drug would be the most applicable to prescribe to the patient for long-term management of asthma in conjunction with inhaled corticosteroids.

Patient Information:

• Age: 12
• Gender: Male
• Condition: Moderate Asthma
• Notes: Patient has poor compliance with inhaled therapies

Answer options:

a) Short-acting β2 Agonist
b) Leukotriene Receptor Antagonist
c) Anti-IgE antibodies
d) Long-acting β2 Agonist

Answer 20

b) Leukotriene Receptor Antagonist

A leukotriene receptor antagonist would be the best choice, as it is taken orally and is effective when combined with inhaled corticosteroids.

Short-acting β2 agonists are used to relieve acute asthma attacks, not long-term management.

Long-acting β2 agonists can be used for chronic maintenance, but may not be as effective, due to the patient’s poor compliance with inhaled therapies.

Anti-IgE antibodies are generally reserved for severe asthma that has an allergic component.

Question 21

How does one choose asthma therapy?

Answer 21

While some drugs are used in other conditions, the clinical use of leukotriene pathway inhibitors and monoclonal anti-IgE antibodies is almost exclusively for pulmonary diseases.

In the case of mild asthma, the occasional use of a bronchodilator, such as an inhaled short-acting β2 agonist, may be all that is required.

For more severe asthma and for long-term control of asthma, treatment with an anti-inflammatory agent, such as inhaled corticosteroids, is often necessary to relieve symptoms and restore function..

When monotherapy is not sufficient in relieving all symptoms of asthma, combinations of anti-asthma drugs may be used.

• Ex: treatment with long-acting β2 agonists and inhaled corticosteroids is effective in improving asthma control.
• Leukotriene pathway antagonists are less effective than corticosteroids, and are thus only used as adjuvants when symptoms are not adequately controlled with corticosteroids.
• Severe asthma can be treated with an anti-IgE antibody.

Question 22

Differentiate between chronic bronchitis and emphysema.

Answer 22

Chronic bronchitis is chronic inflammation of the bronchi and is defined clinically by a persistent cough.

Emphysema is characterized by an abnormal, permanent enlargement of air spaces in the peripheral lung, resulting from tissue destruction due to chemicals released during inflammation.
- Clinically, emphysema is characterized by shortness of breath.

Question 23

What is chronic obstructive pulmonary disease (COPD)?

Answer 23

The term chronic obstructive pulmonary disease (COPD) encompasses two co-existing diseases, that is, chronic bronchitis and emphysema.

COPD is a progressive disease, leading to loss of pulmonary function over time, and is thought to reflect abnormal inflammation of the lung to noxious particles or gases.

Question 24

Who does COPD affect?

Answer 24

COPD occurs in older patients, and is characterized by a decrease in airflow that is not fully reversible with bronchodilators and is poorly responsive even to high-dose inhaled corticosteroids.

Question 25

What is the biggest risk factor for COPD?

Answer 25

Cigarette smoking is the single most important risk factor for COPD.

• Tar particles that are inhaled during smoking are small enough that they are easily deposited into the central and peripheral airways.
• This increases the recruitment of inflammatory cells, which will secrete a number of different components, including proteases and reactive oxygen species.
• These agents will damage epithelial cells and break down connective tissue airway structures.
• Oxidants and other substances found in tar particles directly injure lung cells.

While COPD is most often a consequence of cigarette smoking, about 15% of COPD cases occur in non-smokers.
- These cases are thought to be a result of industrial inhalations, such as that which occurs in mining.

Question 26

Discuss the pathogenesis of COPD.

Answer 26

In the progression of COPD, many changes occur to the airways that inhibit the function of the lungs. These changes occur in different locations within the respiratory system.

Bronchi (medium-sized airways of the lung):

• Decreased ciliary clearance: due to inhibition of activity and direct structural damage.
• Thickening of the wall: due to edema, direct toxic effects, effects of inflammatory cells provoked from cigarette smoke, mucous gland hyperplasia.
• Excess mucous: due to hypersecretion, hyperplasia, and decreased clearance.

Bronchioles (small-sized airways of the lung):

• Decreased airway diameter: due to increased wall thickness as a result of inflammation,edema, and fibrosis
• Increased mucous
• Bronchospasm

Question 27

True or false: while the pathogenesis of asthma and COPD are different, the approaches to treatment are similar.

Answer 27

True

However, the benefits of treating COPD are less than the benefits of treating asthma.

Question 28

What are the treatments for COPD?

Answer 28

1) Beta-2 agonists and antimuscarinics
2) Theophylline
3) Antibiotics

Question 29

How do beta-2 agonists and antimuscarinics work to treat COPD?

Answer 29

In general, the relief of acute symptoms of COPD is achieved by inhalation of a short-acting β2 agonist, an antimuscarinic drug, or a combination of the two.

Patients who have persistent symptoms of shortness of breath and limitation of activities will benefit from the regular use of a long-acting bronchodilator.

Longer-acting, selective antimuscarinic agent, tiotropium, is approved as a treatment for COPD only.
- This drug is taken daily by inhalation, and has been shown to improve the functional capacity of patients with COPD, and reduce the frequency of exacerbations.

Question 30

How does theophylline work to treat COPD?

Answer 30

The drug theophylline is sometimes used in severe cases of COPD, as it may improve contractile function of the diaphragm, improving long capacity.
- Theophylline is limited by its narrow therapeutic range and wide range of side effects, which include heart palpitations and dysrhythmias, tremors and convulsions, and abdominal pain and nausea.

Question 31

How do antibiotics work to treat COPD?

Answer 31

In COPD, antibiotics are routinely used, since exacerbations commonly involve bacterial infection of the lower airways.
- Bacterial infection of the lower airways does not commonly occur in asthma, and therefore antibiotics are not often used to manage asthma exacerbations.

Question 32

Which one of the following statements regarding asthma is correct?

a) Asthma is commonly treated with antibiotics
b) First-line treatment of acute asthma attacks are leukotriene receptor antagonists
c) Asthma is considered a chronic inflammatory disease
d) Anti-IgE monoclonal antibodies are commonly used and inexpensive

Answer 32

c) Asthma is considered a chronic inflammatory disease

Question 33

Which one of the following statements regarding chronic obstructive pulmonary disease (COPD) is correct?

a) COPD encompasses two co-existing diseases: asthma and chronic bronchitis
b) Cigarette smoking is the single most important risk factor for COPD
c) COPD leads to increased pulmonary function over time
d) Bacterial infections are uncommon with COPD

Answer 33

b) Cigarette smoking is the single most important risk factor for COPD