Allergy in the Lung Flashcards
What is the term for failure to breathe out?
Ventilatory failure
Why is lung compensation an issue?
Because you can lose up to 70% of the capacity of your lungs without noticing or getting symptoms
How does the narrow inlet/exhaust make the lung vulnerble?
Because it is so narrow, it is easily occluded.
How does the enormous reserve surface area make the lung vulnerable?
Pathology is advanced before clinical deterioration is detected
- lost lung can’t be replaced like the liver
What is an allergy?
An immune system mediate intolerance.
- requires exposure to a trigger
- memory is a characteristic clinical feature
- dependent on which arm of the immune system
Allergies have two possible clinical reactions, what are they?
Acute and very sudden
Slow and progressive
What happens to lung tissue in a chronic allergy?
Tissue remodelling
- acute inflammation
- repair
What is the most common allergy of the airways?
Asthma
What is the most common allergy of the parenchyma?
Extrinsic allergic alveolitis
Which airways are not susceptible to intra-thoracic pressure?
Upper/Extra Thoracic airways
Give an example of extra-thoracic disease.
Laryngeal oedema
Which airways are susceptible to intra-thoracic pressure?
Bronchi
What are the clinical consequences of bronchial disease?
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)
What are the three types of definitions of asthma?
Clinical
Physiological
Pathological
What is the clinical definition of asthma?
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
What is the physiological definition of asthma?
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
What inflammatory cells would you expect to find in an asthmatic airway?
Neutrophils
Macrophages
Eosinophils
Lymphocytes
What are the inflammatory phenotypes of asthma?
Neutrophillic (61% neutrophils)
Eosinophilic (3% eosinophils)
Paucigranulocytic
Mixed
What is the pathophysiological definition of asthma?
Inflammation of the airways - has an inflammatory phenotype
Why does airway smooth muscle hypertrophy occur in asthmatic airways?
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
Why is hypertrophy of smooth muscle in the airways bad?
This decreases the size of the lumen of the airways - compression
What are the most important factors to consider when making a diagnosis of asthma?
Appropriate clinical history
Clinical signs at the times of symptoms
Supportive physiological tests
How can the causative allergen be found in asthma cases?
Scratch the patients skin with various common allergens and see which has a reaction
Briefly describe how an allergen can cause eosinophilic asthma?
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
What is corticosteriod responsive disease?
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
Which cytokines stimulate eosinophil release from bone?
Chemokines
- IL-5
- IL-13
- TSLP
Which cytokines stimulate airway remodelling in asthmatic airways?
TNF alpha
TGF beta
VEGF
IL-13
What happens during airway remodelling?
Angiogenesis
Epithelial cell damage
Fibrosis
Smooth muscle hypertrophy
What established therapies are available that target specific pathologies within asthma?
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
What future therapies are available that target specific pathologies within asthma?
Immunotherapy
Biological therapes
- TNF, IL-5, IL-13
Thermoplasty
How allergy of the parenchyma different from asthma?
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
What are the signs and symptoms of extrinsic allergic alveolitis?
Wheeze Cough Fever Chills Headache Myalgia Malaise Fatigue Lung consolidation Immune complex disease
What is the pathology of extrinsic allergic alveolitis?
Thickening of the spetae and filling of the alveolus with fluid
- fibrosis
- peribronchial granulomas
- honeycombing
How can EAA be identified?
Low oxygen levels Normal carbon dioxide levels - hypoxaemia - meaured by CO gas transfer Chest X-Ray - air space shadowing
What can happen in there is chronic exposure to an antigen that causes EAA?
Fibrosis
- interstitial scarring from chronic tissue remodelling/reapir pathways
Emphysema
- interstitial destruction from neutrophilic enzyme release
What ventilation/perfusion problems occur in EAA?
Reduced oxygen levels
Normal carbon dioxide levels
- emphysema (reduced surface area)
- pulmonary fibrosis (thicker membrane to travel through)
How does EAA effect spirometry?
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)
Describe acute extrinsic allergic alveolitis.
Acute illness is due to type 3 reaction
- serum sickness or immune complex disease
Describe sub-acute extrinsic allergic alveolitis.
Sub-acute can take days to weeks
- type IV T-cell mediated reaction
- like chronic dermatitis of lung
Describe chronic extrinsic allergic alveolitis.
Fibrosis and Emphysema
- final pathway of all chronic inflammatory conditions
How is extrinsic allergic alveolitis managed?
Allergy - avoid the trigger
Inflammation is controlled with corticosteriods
- neutrophils are modestly steriod responsive
- cytotoxics
Oxygen supplementation
