Asthma Flashcards
What is asthma?
Inflammatory condition in which there is recurrent reversible airways obstruction in response to irritant stimuli. Chemical mediators are released by mast cells in airways; bronchoconstriction, mucosal oedema, hypersecretion of mucus
What are the symptoms of asthma?
wheezing, tight chest, cough - especially at night
What is asthma cause by?
genetics
animal allergens
pollen
infections
chemicals
drugs - NSAIDs
smoking
emotions stress
exercise
cold weather
Describe the onset of asthma?
- Cases begin in childhood and can develop later in life
- Late onset: non-T2-type (absence of allergy) - such as NAIDs intolerance, rhino-sinusitis
What are the two onset sub-types?
T2 - allergy, exercise - induced, aspirin exacerbation.
Non-T2 - obesity associated, smoking related
What are the two phases of asthma?
Immediate
Late
What are the 3 features of airway hyper-responsiveness?
- Airway wall inflammation involving neutrophils, T cells (CD8+) alveolar dendritic cells and macrophages. Dendritic cell recruit T cells (CD4+) in the alveolar air spaces and eosinophils in bronchioles
- Luminal obstruction of the airways by mucus caused by hyper-secretion of bronchial mucous glands and infiltration by inflammatory cells.
- Vasodilation of bronchial microvasculature with increases vascular permeability and oedema.
What is hypersensitivity?
Bronchial hyper reactivity is abnormal sensitivity to a stumli - bronchoconstriction.
What is the 1st phase of Th2 response?
Attract inflammatory granulocytes (eosinophils) to the mucosal surface.
What is the 2nd phase of Th2 response?
IL-5 and granulocyte -macrophage colony stimulating factor prime eosinophils to produce cysteinyl leukotrienes to release granule proteins that damage the epithelium.
- This damage is a cause of bronchial hyper - responsiveness
What is the 3rd phase of Th2 response?
Promote IgE synthesis and responsiveness in some asthmatics.
- IL-4 and 13 switch B cells to IgE synthesis and cause expression of IgE receptors on mast cells and eosinophils - enhance adhesion of eosinophils to endothelium.
List the bronchodilators used in the treatment of asthma.
SABA
LABA
Anticholinergics
Methylxanthines
List the anti-inflammatories used in the treatment of asthma
- ICS
- LTRA
Describe the adrenergic receptors
All are typical G protein-coupled receptors
What are the 2 categories of adrenergic receptors?
- alpha - adrenergic receptors - 2 sub types
- beta - adrenergic receptors - 3 sub types
Where are beta1 receptors found?
mainly in the heart and responsible for effects of catecholamines
Where are beta2 receptors found?
mainly in the lungs and responsible for causing smooth muscle relaxation in many other tissues
Describe SABAs MOA and give examples.
MOA - activates B2-R which relaxes smooth muscle and widens airway to relieve symptoms.
- Patients with symptomatic asthma should be given SABA2A
- Well absorbed and does not cross BBB
Examples: Salbutamol, Terbutaline
Describe LABAs MOA
MOA: bind to 2 sites (exo & active) on R - longer duration of effect (12hours) - use x2 a day
- Patients with uncontrolled asthma by SABA alone
- Improve lung function and decreases asthma symptoms
- Must be used in combo with ICS
State examples of LABAs
Fostair - formoterol/ beclometasone
Duoresp - formoterol/ budesonide
Seretide - salmeterol/ fluticasone
Relvar - vilanterol/ fluticasone
Describe anticholinergics MOA and give examples.
MOA: block effects of acetylcholine and inhibit muscarinic GPCR leading to muscle relaxation.
- used in addition to SABA and LABA - rarely used in asthma
Examples:
SAMA - ipatropium
LAMA - tiotropium
Describe Methylxanthines MOA and give examples.
MOA:
- Relaxes smooth muscle of bronchial airways and pulmonary blood vessels which leads to low responsiveness to histamines, metchacholine, adenosine and allergens.
- Competitively inhibits PDE which is the enzyme responsible for breakdown of cAMP in smooth muscle resulting in bronchodilation.
Examples; theophylline
Describe the MOA of ICS and give an example
- Restrain clonal proliferation of the Th cell by decreasing transcription of the IL-2 gene and decreases cytokine formation. Th2 cytokines recruit and activate eosinophils. They are responsible for promoting production of IgE and expression of IgE-R.
- Glucocorticoids inhibit the generation of vasodilators PGE2 and PGI2 by inhibiting COX-2.
- Activate GR & inhibit inflammatory stimuli to decrease inflammation.
Example: beclometasone diproprionate by brand - QVAR or Clenil
Describe the MOA of LTRA and give and examples
- CysLT (LTC4,LTD4,LTE4) are eicosanoids released by mast cells and eosinophils.
- CysLT bind to CysLT type 1 receptor on respiratory airway smooth muscle cells, airway macrophages & pro-inflammatory cells e.g. eosinophils
- Decreases sputum eosinophilia
Examples: montelukast, zafirlukast
Why are corticosteroids used in asthma?
Inhibit mediators involved in airway inflammation
Oral - predisnolone for severe attack
What is the MART regime?
Maintenance And Reliever Therapy - one inhaler used as reliever and preventer ICS/LABA - LABA must be rapid acting.
What are the requirements for MART regime?
- 18+
- Pt prefers one inhaler
- Continued poor control after regular, preventative therapies.
How is the MART regime used?
- Twice a day - am and pm
- Reliever dose throughout the day
- up to 6 puffs a day MAX 8 a day
What are the licensed MART products?
- Fostair 100/6
- Duoresp 160/4.5
- Symbicort 100/6 or 200/6
What are the benefits of MART?
- Decreases airway inflammation
- Relives symptoms - breathlessness, tight chest
- Quickly manages symptoms - decreases risk of asthma attack and decreases hospital admission.
- Freq use will decrease due to extra anti inflammatory effects of ICS providing LT control.
What are the different types of asthma?
Moderate - PEF >50-75%
Acute - PEF 33-50%
Life-threatening - PEF <33%
Describe the spirometry test
- Positive results : improvement in FEV1 of more than or equal to 12% and increase in vol of 200mL
- Improvement in FEV1 of more than or equal to 400mL this suggest asthma
Describe Peak Low test
Estimate in variability of airflow
- repeat 2x a day fir 2 weeks
- take an average of best readings am and pm
- take highest and lowest readings & express as a % - 20% difference suggest asthma
How is PF test performed?
- deep breath in
- hold for 2s
- rapidly breath out
- record value
- repeat 3x am and pm, records best from each
What are examples from reliever?
bronchodilators
SABAs
SAMAs
Theophylline
What are examples of preventers?
Anti-inflammatory drugs - ICS
What suggests poor control?
- Asthma attack in last 2 years
- Using SABA 3 times a week
- Symptomatic 3x a week +
- Waking 1 night a week
- Asthma affecting daily activities
What to you check in an asthma review?
- Adherence
- Technique - ask Pt to show you
- Symptoms - daytime, night time, activities
- Asthma control questionnaire
- PEF
- Triggers/ smoking status
- Does Pt have a personal asthma action plan (PAAP)
What shows high probability of asthma?
wheeze heard by HCP
history
How do you confirm an asthma diagnosis
- Code Pt as ‘suspected asthma’
- 6 weeks treatment trail of ICS & SABA
- Assess response; asthma control questionnaire, LFTs - spirometry and PEF
- Improvement following 6 wk treatment strongly suggests asthma.
How is asthma diagnosed?
- Investigations - spirometry - compare results when pt is symptomatic or asymptomatic.
- Structured clinical assessment: episodic symptoms, atopic history, confirmed wheeze by HCP on auscultation, diurnal variability.
