Asthma pathophysiology Flashcards
Outline the effects of LABA’s
Reduced bronchoconstriction Reduced bronchohyperactivity Reduced hyperplasia Reduced inflammatory mediator release Reduced mucousal oedema and tissue remodeling
Outline the effects of inhaled steroids
Reduced bronchohyperactivity Reduced inflammatory cell conc. Reduced oedema Reduced epithelial damage Reduced tissue remodeling Reduced cell proliferation
Why is asthma still such a problem?
Under diagnosed and undertreated
Misdiagnosed and mistreated
Patient compliance with treatment is poor
What factors indicate a high probability of asthma?
Cough + wheeze Cough is worse at night Exercise induced Family history of asthma Evidence of airway narrowing
In the asthma control test, what do the scores mean?
Out of 25:
25: Perfectly controlled asthma
20-24: Well controlled asthma
<20: Further treatment necessary
Steps of asthma therapy
- SABA alone
- SABA + ICS (low) (if need for maintenance is shown)
3.SABA + ICS (low)+ LRTA - SABA+ ICS (low)+ LRTA + LABA (review LRTA effectiveness)
- MART (with low ICS) +/- LRTA
- MART (with moderate ICS) +/- LRTA
- MART +/- LRTA (Or high ICS on fixed dose therapy)
Consider also LAMA and additional advice for step 7
What does it mean to have well controlled disease?
The patient should suffer from no symptoms during the day and should be able to carry out their regular activities without hindrance
What lifestyle messages should you aim to get across to asthma patients?
Understand the risks of uncontrolled asthma
Encourage to stay active and lose weight
They should know of their lung health and personal health plan
Recommend taking vaccines
Share info with each other about meds and devices
BTS/SIGN vs NICE guidance
Main difference are the tests done and the order of the drugs given
NICE is more cost effective
Assessing an acute exacerbation
ID the trigger factor
ID the type and duration of symptoms
ID the treatment started and if its working
Assess severity of exacerbation
Ask about depression, alcohol misuse, poor compliance, previous exacerbation.
Use these as a basis for deciding whether to admit to hospital
Assessing the severity of an exacerbation
Check for signs of exhaustion: cyanosis, SOB
Examine patient chest and record respiratory rate, pulse an BP
Check peak expiratory flow rate:
->50-75%=moderate
-33-50%=severe
-<33%=life threatening
Measure O2 sat. if possible
How can you manage acute exacerbations?
Give high O2 to maintain O2 sat at 94-98%
High dose SABA+ICS
IV Beta agonists for patient where inhalation not possible
Oral steroids in doses suitable for severity
IV magnesium sulfate for patients unresponsive to beta agonists
The 5 steps of the BTS/SIGN guidelines
- Low dose ICS
- LABA + ICS (usually as MART)
- -If LABA doesn’t work then stop LABA and increase ICS
- If LABA works but inadequate then increase LABA + continue ICS OR continue LABA+ICS and add LRTA - Increase to high dose ICS or add 4th drug eg LAMA
- Add in oral steroids at lowest adequate dose
What is difficult asthma?
Asthma patients suffering from symptoms even on steps 4/5 of BTS/SIGN guidelines and one of:
- life threatening exacerbation requiring invasive ventilation in the last 10 years
- daily dose of oral steroids >7.5mg daily
- 2 hospitilisations in last 12 months on high dose ICS
- FEV1 <70% of normal
Questions you should ask of difficult asthma patients?
Do they actually have asthma?
Are there conditions that are making the asthma worse?
These include:
Bronchostasis- abnormal widening of airways causing build up of sputum and causes infection
Dysfunctional breathing
Severe COPD
Vocal chord dysfunction
How should asthma be diagnosed in the future?
Objective tests such as FeNOand spirometry
These are necessary due to over diagnosis based on signs and symptoms
This will take time however to build up the infrastructure necessary
Alternative treatments for difficult asthma?
Anti eosinophils
Anti immunoglobulin E
Steroid sparing agents: Gold, methtrexate, ciclosporin and Terbutaline (not recommended as can be hard to stop treatment, also monitor heart rate)
Anti-IgE (Omalizumab) indications
For difficult patient with: FEV1 <80% of normal
>2 severe excerabtions
+ve prick or RAST test
IgE>50 and <700 IU/ml
People outside of the weight limit and/or serum conc. for IgE should not be given Omalizumab. Usually administered to arm or thigh
How does Omalizumab work?
Binds to IgE preventing binding to Mast cells
Reduces IgE bearing bronchial cells
Reduces density of IgE receptors on basophils, mast cells and APC’s
Reduces conc. of sub mucousal eosinophils
T cell profiling
Patient with a higher ratio of Th2 to Th1 which is associated with higher levels of interleukins
One particular group have higher eosinophil counts and more frequent exacerbations less controlled asthma
These patients have eosinophilia promoted by IL-5. Can be treated with anti-IL-5 Mepolizumab
Mepolizumab
Binds to IL-5 an interleukin which promotes eosinophil growth and activation
Reduces clinically significant exacerbations and halves no. of exacerbations requiring hospitilisations
Indication for mepolizumab
For severe eosinophilic
Eosinophil count >300 cells/mcl in last 12 months
>4 exacerbations requiring oral steroids
Maintenance oral steroid dose >5mg prednisolone/day
Company provides drug at discount for patient access
Indications for Resulizumab
For severe eosinphilic asthma
Eosinophil count >400 cells/mcl in last 12 months
>3 exacerbations requiring systemic steroids
Company discounts drug for patient access
Steroid sparing agents
Usually immunosuppressant
Reduces the need for steroids but have significant side effects
Should be done by specialist
Only given after other treatments have proven unsuccessful
Terbutaline Infusion
2.5mg/day via PICC (Peripherally inserted central catheter)
Consequences of long term oral steroid use
Endocrine: Cushings syndrome, adrenal suppression
Eye: cataracts, glaucoma and papilloedema (optic disk swelling)
GI: Ulceration, pancreatitis and candidiasis
Immune: Increased chance of infection
Musculoskeletal: Myopathy, osteoporosis, fractures, growth suppression
Neurological: Makes epilepsy worse
Psychiatric: Psychosis, behavioural and cognitive disorders
