Asthma L18

Question 1

What are the 2 main pathological components of asthma?

Answer 1

• Smooth muscle contraction
• Airway inflammation

Question 2

IgE mast cell interaction

What is the mechanism here? (2)

Answer 2

1. IgE binds to mast cells
2. When in contact with the specific allergen causes mast cell degranulation

Question 3

Name the 2 targets for asthma treatment.

Answer 3

• Smooth muscle
• Inflammation

Question 4

Smooth muscle is under both sympathetic and parasympathetic control. ____1____ control (through the Vagus nerve) causes constriction, so blocking this is a target for muscle relaxation.

Another key controller of the smooth muscle is circulating ____2____ which binds to the B2 adrenergic receptors on the surface of the muscle cells. Both ____1____ and adrenergic control cause the release of cyclic AMP (cAMP) within the cell which causes relaxation of the smooth muscle.

Answer 4

1. Parasympathetic
2. Adrenaline

Question 5

Treatments based on targeting airway smooth muscle

Aim is to:

1. Increase cAMP levels in muscle cell
2. Decrease intracellular calcium
3. Muscle relaxation

What can we do to achieve this? (4)

Answer 5

• Block Vagus nerve
• Increase stimulation of B2 receptors
• Theophylline reduces break down of cAMP thus increasing intracellular levels
• Displace calcium with magnesium to lower calcium levels, leading to relaxation

Question 6

Asthma treatments

Describe the difference in effect between bronchodilators and anti-inflammatory agents.

Answer 6

Bronchodilators have an immediate effect. Anti-inflammatory agents have a less immediate effect due to the time it takes for the inflammatory response to die down. But the effects are more long lasting.

Question 7

BTS/SIGN guidelines for asthma management

Question 8

List the methods of diagnosing asthma. (6)

Answer 8

• Symptoms
• Presence of airflow obstruction
• Variability of airway calibre
• Response to bronchodilator
• Response to bronchoconstrictor
• Airway inflammation
  
  • Blood eosinophilia
  • Sputum eosinophilia
  • Exhaled air nitric oxide
  • Airway biopsy

Question 9

Read

One of the key features of asthma = variability of symptoms.

Exercise and cold air tend to dry out the airways. This drying out is a stimulus for contraction of the smooth muscle.

Important hormones = growth hormone, cortisol and adrenaline. All are bronchodilators and work by relaxing smooth muscles. There is little of the hormones circulating in the early hours of the morning which leads to asthma attacks being a distinct problem during sleep.

Question 10

Spirometry is an important tool in diagnosing and quantifying asthma.

Why is the reliability of spirometry dependent on when the measurement is taken though?

Answer 10

As most asthmatics breath normally throughout the day and would therefore be negatively diagnosed if they were tested at this time.

Question 11

If FEV1:FVC <__% = airway obstruction

Answer 11

70

Question 12

Define FEV1.

Answer 12

The volume of air that can forcibly be blown out in one second, after full inspiration.

Question 13

Define FVC.

Answer 13

Forced vital capacity (FVC) is the volume of air that can forcibly be blown out after full inspiration, measured in litres.

Question 14

Define peak expiratory flow.

Answer 14

A person’s maximum speed of expiration.

Question 15

Read

FEV1/FVC ratio (FEV1%)

FEV1/FVC (FEV1%) is the ratio of FEV1 to FVC. In healthy adults this should be approximately 70–85% (declining with age). In obstructive diseases (asthma, COPD, chronic bronchitis, emphysema) FEV1 is diminished because of increased airway resistance to expiratory flow; the FVC may be decreased as well, due to the premature closure of airway in expiration, just not in the same proportion as FEV1 (for instance, both FEV1 and FVC are reduced, but the former is more affected because of the increased airway resistance). This generates a reduced value.

Question 16

Define spirometry.

Answer 16

A set of tests to measure lung function, specifically the volume and/or speed (flow) of air that can be inhaled and exhaled.

Question 17

If you move from a country that is economically less developed to one that is more developed, you adopt the ___1___ of the allergy of your new home.

___2___ probably causes the change in sensitization.

Asthma is primarily an ___3___ disease.

Answer 17

1. Prevalence
2. Lifestyle
3. Environmental

Question 18

In the Barcelona epidemic people were sensitized to the ___1___ antibody to the ______ 2 ______ dust antigen.

Answer 18

1. IgE
2. Soya bean

Question 19

Inhaled allergens are thought to be processed by two mechanisms in asthmatic airways.

Allergens either:

1. Activate mast cells through ______-1-______ with IgE on their cell surfaces through the high-affinity type 1 IgE receptor (___2___) to release mediators that induce bronchoconstriction, such as histamine, cysteinyl leukotrienes, and prostaglandin D2 (PGD2)
2. Are processed by ___3___ cells, which are induced to secrete the CC chemokine ligand (CCL) 17 and CCL22 by thymic stromal lymphopoietin (TSLP). ___3___ cells then attract and activate ___4___ cells by the binding of CCL17 and CCL22 with CC chemokine receptor 4 (CCR4) on the ___4___ cell surface. IL-33 is produced by airway epithelial cells and activates dendritic cells and ___4___ by inducing the release of tumour necrosis factor-alpha from mast cells. ___4___ secretes cytokines, including IL-4 and IL-13, which switch B cells to produce IgE, IL-5, which promotes the development and survival of eosinophils, and IL-9, which activates mast cells. Once IL-13 is produced, it can increase the survival and migration of eosinophils, and it promotes activation of macrophages to create an M2, or an allergic cell phenotype. Airway epithelial cells are stimulated, and through mediators such as periostin and transforming growth factor β1 (TGF-β1), they can increase airway inflammation and lead to the increased permeability of airway epithelial cells and mucous hypersecretion. IL-13 also has direct effects on airway smooth muscle, leading to increased contraction to agonists such as acetylcholine and decreased relaxation with beta-agonists.

Answer 19

1. Cross-linking
2. FcɛR1
3. Dendritic
4. Th2

Question 20

Asthma is a ___1___ inflammatory condition of the airways characterized by airway hyperresponsiveness, inflammatory infiltrates in the bronchial wall including eosinophils, and elevated serum immunoglobulin-E (IgE) levels in allergic patients. T-helper type 2 (Th2) lymphocytes are thought to play a key role in the initiation and perpetuation of this airway inflammation in asthma.

For many years, asthma was considered a single disease. It is now becoming apparent that there is wide heterogeneity in the asthma phenotype, which may well explain the differential responses to established therapies such as inhaled ___2___ and long-acting beta2 agonists (LABA). Even with the introduction of new biological agents, there are still a large number of patients whose asthma remains uncontrolled. For example, up to 40% of patients with severe allergic asthma do not gain adequate disease control despite the addition of omalizumab, a monoclonal antibody that binds ___3___. Hence, there is still a need for new agents to treat asthma, and an even greater need for agents that are tailored to the individual phenotype of asthmatic patients.

Answer 20

1. Chronic
2. Corticosteroids
3. IgE

Question 21

Name the types (kind of) of bronchodilators. (4)

Answer 21

• Beta adrenergic agonists
• Anticholinergics
• Theophylline
• Magnesium

Question 22

___1___ have an immediate effect.

______-2-______ agents have a less immediate effect due to the time it takes for the inflammatory response to die down. But the effects are more long lasting.

Answer 22

1. Bronchodilators
2. Anti-inflammatory

Question 23

Name the types of anti-inflammatory agents. (3)

Answer 23

• Corticosteroids
• Leukotriene antagonists
• Anti IgE antibodies

Question 24

Features that increase the probability of asthma

Question 25

\_\_\_1\_\_\_ = air blown out in 1 second of exhale \_\_\_2\_\_\_ = air blown out in full exhale If FEV1:FVC \< 70% then the airways are \_\_\_3\_\_\_ as a healthy individual should be able to blow at least 70% of the air in their lungs out in 1 second.

Answer 25

1. FEV1 2. FVC 3. Constricted

Question 26

The diagnosis of asthma is a ______ one; there is no standardised definition of the type, severity or frequency of symptoms, nor of the findings on investigation. The absence of a gold standard definition means that it is not possible to make clear evidence based recommendations on how to make a diagnosis of asthma.

Answer 26

Clinical

Question 27

Define eosinophilia.

Answer 27

An increase in the number of eosinophils in the blood, occurring in response to some allergens, drugs, and parasites, and in some types of leukaemia.