Allergy in the Lung

Question 1

What is the term for failure to breathe out?

Answer 1

Ventilatory failure

Question 2

Why is lung compensation an issue?

Answer 2

Because you can lose up to 70% of the capacity of your lungs without noticing or getting symptoms

Question 3

How does the narrow inlet/exhaust make the lung vulnerble?

Answer 3

Because it is so narrow, it is easily occluded.

Question 4

How does the enormous reserve surface area make the lung vulnerable?

Answer 4

Pathology is advanced before clinical deterioration is detected
- lost lung can’t be replaced like the liver

Question 5

What is an allergy?

Answer 5

An immune system mediate intolerance.

• requires exposure to a trigger
• memory is a characteristic clinical feature
• dependent on which arm of the immune system

Question 6

Allergies have two possible clinical reactions, what are they?

Answer 6

Acute and very sudden

Slow and progressive

Question 7

What happens to lung tissue in a chronic allergy?

Answer 7

Tissue remodelling

• acute inflammation
• repair

Question 8

What is the most common allergy of the airways?

Answer 8

Asthma

Question 9

What is the most common allergy of the parenchyma?

Answer 9

Extrinsic allergic alveolitis

Question 10

Which airways are not susceptible to intra-thoracic pressure?

Answer 10

Upper/Extra Thoracic airways

Question 11

Give an example of extra-thoracic disease.

Answer 11

Laryngeal oedema

Question 12

Which airways are susceptible to intra-thoracic pressure?

Answer 12

Bronchi

Question 13

What are the clinical consequences of bronchial disease?

Answer 13

Medium to small airways have flaccid walls that aren’t protected by cartilage to hold them open

• narrowing occurs during the expiatory phase (causes wheeze)
• Impairs muco-ciliary clearance (sputum build up)

Question 14

What are the three types of definitions of asthma?

Answer 14

Clinical
Physiological
Pathological

Question 15

What is the clinical definition of asthma?

Answer 15

Appropriate symptoms with signs
- wheeze, cough, yellow/clear sputum 
- breathlessness, exercise intolerant
Episodic, triggered, variable (paroxysmal)
- exercise, cats, chemicals
- diurnal 
Responds to asthma therapies
- 20% of asthma cases don't respond to treatment

Question 16

What is the physiological definition of asthma?

Answer 16

Reversible airflow obstruction - spirometry before and after a nebuliser
Variable airflow obstruction
Airways are hyper-responsive
- histamine causes airway narrowing at lower concentrations in asthmatics

Question 17

What inflammatory cells would you expect to find in an asthmatic airway?

Answer 17

Neutrophils
Macrophages
Eosinophils
Lymphocytes

Question 18

What are the inflammatory phenotypes of asthma?

Answer 18

Neutrophillic (61% neutrophils)
Eosinophilic (3% eosinophils)
Paucigranulocytic
Mixed

Question 19

What is the pathophysiological definition of asthma?

Answer 19

Inflammation of the airways - has an inflammatory phenotype

Question 20

Why does airway smooth muscle hypertrophy occur in asthmatic airways?

Answer 20

Remodelling occurs in the airways due to inflammation

• the body is trying to regrow the lung (isn’t possible)
• enters a cycle or repair and regrowth, leading to increased muscle in the airway wall

Question 21

Why is hypertrophy of smooth muscle in the airways bad?

Answer 21

This decreases the size of the lumen of the airways - compression

Question 22

What are the most important factors to consider when making a diagnosis of asthma?

Answer 22

Appropriate clinical history
Clinical signs at the times of symptoms
Supportive physiological tests

Question 23

How can the causative allergen be found in asthma cases?

Answer 23

Scratch the patients skin with various common allergens and see which has a reaction

Question 24

Briefly describe how an allergen can cause eosinophilic asthma?

Answer 24

The pathogen binds to IgE antibodies

• the body recognises this as a pathogen and the mast cell is activated, producing histamine and cytokines
• histamine activates smooth muscle and causes inflammation
• this is when the airway becomes swollen and narrow
• cytokines attract eosinophils to the area and also drive inflammation and remodelling

Question 25

What is corticosteriod responsive disease?

Answer 25

A disease which is commonly found in asthma airways and if stimulated, will drive an asthma phenotype - stimulated by late allergic reactions and viral infections

Question 26

Which cytokines stimulate eosinophil release from bone?

Answer 26

Chemokines - IL-5 - IL-13 - TSLP

Question 27

Which cytokines stimulate airway remodelling in asthmatic airways?

Answer 27

TNF alpha TGF beta VEGF IL-13

Question 28

What happens during airway remodelling?

Answer 28

Angiogenesis Epithelial cell damage Fibrosis Smooth muscle hypertrophy

Question 29

What established therapies are available that target specific pathologies within asthma?

Answer 29

Anti-IgE biological therapy Corticosteriods - affects mast cells and smooth muscle Anti-leukotriene receptor drugs - affects macrophages and smooth muscle Bronchodilators - affect smooth muscle and autonomic nerves controlling bronchial closing

Question 30

What future therapies are available that target specific pathologies within asthma?

Answer 30

Immunotherapy Biological therapes - TNF, IL-5, IL-13 Thermoplasty

Question 31

How allergy of the parenchyma different from asthma?

Answer 31

T-mediated inflammatory pathway that causes IgG production in the lung - delayed allergic response - 4/6 hours after the exposure - may last for several days - chronic exposure leads to fibrosis

Question 32

What are the signs and symptoms of extrinsic allergic alveolitis?

Answer 32

``` Wheeze Cough Fever Chills Headache Myalgia Malaise Fatigue Lung consolidation Immune complex disease ```

Question 33

What is the pathology of extrinsic allergic alveolitis?

Answer 33

Thickening of the spetae and filling of the alveolus with fluid - fibrosis - peribronchial granulomas - honeycombing

Question 34

How can EAA be identified?

Answer 34

``` Low oxygen levels Normal carbon dioxide levels - hypoxaemia - meaured by CO gas transfer Chest X-Ray - air space shadowing ```

Question 35

What can happen in there is chronic exposure to an antigen that causes EAA?

Answer 35

Fibrosis - interstitial scarring from chronic tissue remodelling/reapir pathways Emphysema - interstitial destruction from neutrophilic enzyme release

Question 36

What ventilation/perfusion problems occur in EAA?

Answer 36

Reduced oxygen levels Normal carbon dioxide levels - emphysema (reduced surface area) - pulmonary fibrosis (thicker membrane to travel through)

Question 37

How does EAA effect spirometry?

Answer 37

Pulmonary fibrosis is a resitrictive lung defect - flow/volume loop shows reduced lung capacity and reduced flow during exhalation and inspiration (no change in the size of airspaces)

Question 38

Describe acute extrinsic allergic alveolitis.

Answer 38

Acute illness is due to type 3 reaction | - serum sickness or immune complex disease

Question 39

Describe sub-acute extrinsic allergic alveolitis.

Answer 39

Sub-acute can take days to weeks - type IV T-cell mediated reaction - like chronic dermatitis of lung

Question 40

Describe chronic extrinsic allergic alveolitis.

Answer 40

Fibrosis and Emphysema | - final pathway of all chronic inflammatory conditions

Question 41

How is extrinsic allergic alveolitis managed?

Answer 41

Allergy - avoid the trigger Inflammation is controlled with corticosteriods - neutrophils are modestly steriod responsive - cytotoxics Oxygen supplementation