Asthma Flashcards
How many generations in the respiratory tree?
23
Which generations of the respiratory tree are the:
Large airways >2mm?
Small airways <2mm?
Large = 0-7 Small = 8-23
At what generation does gas exchange begin?
Generation 17
What characterises asthma?
Allergic
Eosinophilic inflammation
Reversible
What are the generations of the respiratory tree for: Trachea? Bronchi? Bronchioles? Terminal bronchioles? Respiratory broonchioles? Alveolar ducts? Alveolar sacs?
Trachea = 0 Bronchi = 1 Bronchioles = 2-4 Terminal bronchioles = 5-16 Respiratory bronchioles = 17-19 Alveolar ducts =20-22 Alveolar sacs = 23
Asthma can be early or late onset?
True
Asthma can be atopic or non atopic?
True
Asthma can be extrinsic or intrinsic?
True
What is meant by extrinsic and intrinsic asthma?
Extrinsic- with an external trigger factor
Intrinsic- without an external trigger factor
What is in the asthma triangle?
Reversible airway obstruction
Airway inflammation
Airway hyperresponsiveness
What are the 3 stages to the dynamic evolution of asthma?
1) bronchoconstriction (brief symptoms)
2) chronic airway inflammation (exacerbations and airway hyperresponsiveness)
3) airway remoddeling (fixed airway obstruction due o collagen and scar tissue)
What are the hallmarks of remodelling in asthma?
1) Thickening of the basement membrane
2) Collagen deposition in the sub mucosa=> sub endothilial fibrosis)
3) Hypertrophy of smooth muscle cells
4) Epithilial damage exposing sensory nerve endings
Explain TH2 cytokine mediated inflammation?
1) Allergen present on airway epithilium
2) Allergen binds to TSLP
3) This complex is taken up by dendritic cells and translocates to a lymph node
4) Naive CD4+ T cells is activated and differentiates into a TH2 cell
5) TH2 cells activate B cells by binding to them and by the production of IL4
6) TH2 cells also release IL4 and IL13. TH2 cells and B cells leave the lymph node and enter the tissue
7) TH2 releases IL5 which acts as a chemotaxin to attract eosinophils
8) Eosinophils release histamine and CysLTs
9) B cells produce IgE which binds to mast cells causing then to release histamine. IgE also binds to basophils causing the release of LTD4
10) This causes the stimulation og goblet cells to produce mucus
11) MAst cells also secrete IL4 enhancing the TH2 response by positive feedback
Which cytokines are released by TH2 cells during an asthma attack?
IL4, IL13, IL5
What is the function of IL5?
To act as a chemotaxin to attract eosinophils
What do eosinophils release?
Histamine, CysLTs
What does IgE released by B cells bind to?
Mast cells and basophils
What do mast cells release?
Histamine and IL4 (which enhances the response)
What do basophils release?
LTD4
What histological changes can be seen due to eosinophillic asthma?
Entropy and disorder. Desquamation Thickening of the basement membrane Inflammation of the lamina propria Presence of eosinophils and inflammatory cells Mucus and epithilial plugging
Key symptoms in an asthma history
Episodic Diurnal variability Non productive cough and wheeze Trigger factors Associated atopy Family history Responsiveness to beta 2 agonist Blood eosinophilia >4%
How is air flow obstruction measured?
Spirometry
How is bronchial hyperresponsiveness measured?
Bronchial challenge testing
How is air way inflammation measured?
Using a bronchoscope and obtaining a biopsy.
Very invasive and uncommon
What would you expect the FEV1/FVC ratio to be in asthma?
<75%
What would you expect the FVC to be in asthma?
Maintained
What is neurogenic inflammation?
When sensory nerve endings are exposed and excited by allergens causing the release of inflammatory mediators- contributes to airway hyperresponsiveness
What is airway hyperresponsiveness?
The combination of the hypersensitivity and hyper reactivity of bronchioles
What type of hypersensitivity reaction is the immediate phase of an asthma attack and what does it involve?
Type 1
Involving bronchospasm and acute inflammation
What type of hypersensitivity reaction is the delayed phase of an asthma attack and what does it involve?
Type 4
Bronchospasm and delayed inflammation
When a non asthmatic is exposed to an allergen what immune response is generated?
Cell mediated immune response
Low levels of TH1 cells
When an asthmatic is exposed to an allergen what immune response is generated?
Antibody mediated immune response
High levels of TH2 cells
What classes of drug are releivers?
SABA
LABA
CysLT1 receptor antagonists
What classes of drug are preventers?
Glucocorticoids (steroids)
Cromoglicerate
Monoclonal IgE antibodies
What should preventative treatment be used?
If an individual has more than 2 episode of asthma in a week
What is the one class of drug that can be both a preventer and releiver?
Methylxanthines
Give 2 SABAs.
Salbutamol and Terbutaline
How long does it take for a SABA to act and when does it reach its most effective concentration?
5 mins
30 mins
Adverse effects of SABAs.
Beta agonist tremor, tachycardia, dysrythmia, hypokalemia
Give 2 LABAs
Salmoterol and Formoterol
When are LABAs most useful?
Noctural asthma as they act for 8 hours.
What must be given with a LABA?
ICS
Combination inhalers:
Symbicort?
Seratide?
Symbicort= Budesonide and formoterol Seratide = Fluticasone and salmeterol
LABAs used alone may worsen asthma. True or false?
True
What is the action of CysLT1 receptor antagonists?
Act competitively at the CysLT1 receptor which results in smooth muscle relaxation
Give 2 examples of CysLT1 receptor antagonists.
Montelukast and Zafirlukast
How are CysLT1 receptor agonists administered?
Orally
Give 2 examples of methylxanthines.
Aminophyline and theophylline
What is the action of methylxanthines?
Inhibit mediator release from mast cells and increase mucus clearance
Also increase diaphragmatic contractility and reduce fatigue which may improve lung ventilation
Why are methylxanthines not used so commonly?
Lots of drug interactions involving the cytokine P450
Narrow therapeutic index
Many unwanted side effects
How are methyxanthines administered?
Orally
How are glucorticiods administered?
Inhaled and orally
What are the signs of a severe asthma attack?
1) Unable to talk in complete sentences
2) FEV1/FVC ratio <50%
3) Respiratory rate >25
4) Heart rate >110bpm
What are the signs of a moderate asthma attack?
1) FEV1/FVC ratio <75%
2) increasing symptoms
What are the signs of a life threatening asthma attack?
1) Silent Chest/ reduced breath sounds
2) FEV1/FVC ratio <33%
3) Poor respiratory effort
4) Altered consciousness
How should acute asthma be treated?
1) Oxygen 60%
2) Salbutamol 5mg nebulised
3) Hydrocortisone 100mg IV
4) Ipratropium 0.5mg nebulised
5) Theophyline
6) Magnesium sulphate 1.2-2g IV over 20 minutes
7) Anaesthetist
