Asthma Flashcards
What percentage of asthma patients does spirometry confirm obstruction in?
16-39% of patients, only bronchodilator reversibility in 15-17% of patients.
In contrast those admitted to hospital with asthma attack 83% have obstructive lung function
What are the spirometric values that diagnose bronchodilator reversibility ?
Improvement in FEV1 >12% and 200ml (in response to Beta-Agonist / corticosteroid treatment
Improvement > 400 ml strongly suggestive of asthma
What makes a good peak flow assessment ?
3 forced expiratory blows with a maximum pause of 2 seconds before blowing and further blows should be done if peak flows not within 40 l/min of each other
During direct challenge tests what is considered a positive test ?
The provocation concentration (PC20) required to cause a 20 % fall in FEV1 .
A PC20 of ≤ 8mg/ml is considered a positive test
NB if patients have established air flow obstruction challenge tests have little value
What is the false -ve rate of metacholamine test ?
<10%
Who should be referred for challenge tests ?
Consider in adults where there is no evidence of obstruction in spirometry and objective tests are inconclusive but asthma diagnosis remains a possibility
Talk about indirect challenge tests
Indirect challenges such as exercise and inhaled mannitol. A positive response to these indirect stimuli such as fall in FEV1 > 15% is a specific marker of asthma but the tests are less sensitive than challenges using histamine and metacholine particularly in patients tested whilst on treatment
What does a positive FeNO test suggest ?
A positive FeNO test suggest eosinophilic inflammation and provides supportive but not conclusive evidence of asthma
What increases FeNO levels ?
- Allergic rhinitis (even if exposed to allergen without symptoms)
- Rhinovirus infection
- Men
- Tall ppl
- Intake of dietary nitrates
What decreases FeNO levels?
- Smoking
- Being a child
- Inhaled or oral corticosteroids
What is a positive FeNO?
In steroid naive adults > 40ppb considered positive
BUT
1 in 5 with positive FeNO won’t have asthma
1 in 5 with negative FeNO will have asthma
What are the components of an asthma review?
Current symptom control
Future risk of attack
Tests/Investigations
Management
Supported self management
What are the validated and non validated questionnaires in asthma ?
VALIDATED :
*ACQ (Asthma Control Questionnaire) - reviews last 1 week of sx
*ACT (Asthma Control Test) - reviews last 4 weeks of symptoms
*Mini Asthma quality of life Questionnaire
NON VALIDATED
RCP 3Qs - 1 Have you had difficulty sleeping bc of your asthma sx? 2. Have you had your usual asthma sx during day ? (Cough, wheeze , tightness of chest , breathlessness) 3. Has your asthma interfered with your usual actions ?
What greatly increases your risk of future asthma attacks ?
Previous asthma attacks
What moderately increases your risk of asthma attacks ?
Poor control (assess with ACT /ACQ)
Inappropriate or XS SABA use
What slightly increases your risk of asthma attack?
Old age, female , reduced lung function, obesity, smoking , depression
What do we classify as severe asthma?
More than 2 asthma attacks a year or persistent symptoms with SABA use more than twice a week despite specialist level therapy
What does the personalised asthma action plan do?
Reduced emergency use of healthcare resources including ED , hospital admissions and unscheduled visits
Improved markers of asthma control decreasing symptoms and days off work and improving QOL
What are the PAAPs suggested action points ?
PEFR <80% : Quadruple ICS
PEFR <60% : Commence oral steroids and get same day medical review
PEFR <50% : Urgent medical review
**NB with increasing the ICS , from studies may be that those who are fully adherent have little to gain and the perceived benefits are in the group who have poor usage prior to starting
What is the NICE-BTS asthma management recommendation for stable asthma
Regular Preventer (Low dose - ICS)
»>
Initial add on therapy (Add inhaled LABA to low dose ICS , fixed dose or MART)
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Additional controller therapies (Increasing ICS to medium dose or adding LTRA). If no response to LABA consider stopping
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Specialist therapies
What is the aim of asthma management ?
Complete control of symptoms:
- no daytime sx
- no nighttime sx
- no need for rescue medication
- no asthma attacks
- no limitation on activity
- normal lung function
- minimal side effects for medications
Who should receive ICS?
Anyone who:
- has had asthma attack in last 2 years
- using B agonist X3 per week or more
- symptomatic x3 per week or more
- waking one night a week
*Start patients on steroid dose appropriate to their disease severity , mild to moderate confers no benefit giving higher dose
What dose regimen of ICS most effective ?
Twice a day
What does adding LABA therapy do?
Improves lung function, symptoms and decreases asthma attacks.
LABA should not be used without ICS
What is the benefit of MART?
Systematic reviews have shown MART can reduce risk of asthma attacks requiring oral steroids in patients who are not well controlled on ICS and have history of asthma attacks
(NICE guidance)
What formations is MART currently licensed for ?
Budesonide /Formoterol
Or
Beclomethasone/ Formoterol
What is the use for Tiotropium in asthma ?
In RCTs using Tiotropium in addition to ICS - LABA vs just ICS - LABA:
- fewer asthma exacerbations
- improved lung function
- some benefits relating to asthma control
BUT
- no improvement in QOL
What about adding theophylline ?
May improve lung function and symptoms but associated with increased adverse events
If asthma control inadequate on ICS - LABA what can you do?
- Incr ICS
- Add LTRA (if not already on it)
- Add Tiotropium
- Add theophylline
Who is at risk from steroid use ?
Those on longer term corticosteroids (ie longer than 3 months) or requiring frequent courses (3-4 per year)
What is the Anti IgE mAB?
OMALIZUMAB
- monoclonal antibody against IgE
- subcut injection every 2-4 weeks (dependent on IgE and weight) , can be administered at home
- reduces asthma exacerbation with moderate to severe asthma c/w placebo
- improve asthma symptoms
- improve QOL scores
- licensed for atopic individuals with difficult to control asthma
- IgE should be 30-700 with higher IgE acceptable at higher body weights
- Approved by NICE for severe persistent allergic asthma which is unstable despite optimised therapy
- Response is assessed at 16 weeks
So need:
- SENSITISATION to perennial aeroallergen (dust mite / mould)
AND
- have IgE in dosing range 30-700
AND
- ≥4 exacerbations in last twelve months or continuous steroids
What are the side effects of Anti IgE mAB OMALIZUMAB?
Local skin reactions
Anaphylaxis has occurred after first dose and after a year
Tell me about Mepolizumab
- Monoclonal antibody against IL5
- NICE approved for severe eosinophilic asthma (blood eosinophil count ≥ 0.3 ) with continuous OR frequent ≥ 4 oral corticosteroid courses in the last 12 months despite optimal standard therapy
- Subcut injection
- Reduces asthma exacerbations by 50% and reduces maintenance oral corticosteroid by 50 % compared with placebo
- Treatment response assessed at 12 months
Tell me about Benralizumab
- Monoclonal antibody against IL5 Receptor alpha
- NICE approved for eosinophils ≥ 0.3 OR continuous or frequent ≥ 4 corticosteroid courses in 12 months OR blood eosinophils ≥ 0.4 with continuous or frequent (≥ 3) oral corticosteroids in last 12 months
- 8 weekly after initial 3 doses are given 4 weekly
- 50% reduction in asthma exacerbation and 50% reduction in corticosteroid use c/w placebo
Tell me about Reslizumab
- Monoclonal antibody against IL5
- NICE approved for severe eosinophilic asthma (blood eosinophil count of ≥ 0.4) with continuous or frequent ≥ 3 corticosteroids in last 12 months
- IV infusion , 4 weekly
- Similar exacerbation reduction to Mepolizumab and Benralizumab
Tell me about Dupilumab
- Monoclonal antibody against IL4 receptor alpha
- Dupilumab blocks the action of IL4 and IL13
- Proven efficacy in moderate to severe type 2 asthma (as evidenced by blood eos and/ or FeNO) in reducing exacerbations and steroid reduction
- Licensed for use in asthma and also licensed for atopic dermatitis and nasal polyps (both conditions that co-exist with asthma)
- Undergoing NICE evaluation
What is the anti IgE mAB?
OMALIZUMAB
What are the anti IL5 mAB
Mepolizumab (IL5)
Reslizumab (IL5)
Benralizumab (IL5 Recoetor alpha)
What is the anti IL4 receptor alpha mAB
Dupilumab (blocks IL4 and IL13)
What is bronchial thermoplasty?
Aim to reduce bronchial smooth muscle mass reducing the capacity for bronchoconstriction
(Following procedure in short term , increased adverse resp events)
If have to use MDI what is the preferred propellant?
HFA 134a (1,1,1,2 - tetrafluoroethane)
MDIs contribute to 3.5% of NHS carbon footprint
Who are the patients at risk of developing near fatal or fatal asthma?
COMBINATION OF SEVERE ASTHMA RECOGNISED AS:
- Previous near fatal asthma (ie previous ventilation or respiratory acidosis)
- Previous admission for asthma (esp in last year)
- Requiring 3 or more classes of asthma medication
- Heavy B2 agonist
- Repeated attendances at ED for asthma care particularly in last 1 year
AND adverse behavioral/ psychosocial features recognised by one or more of :
- non adherence with treatment or monitoring
- failure to attend appts
- fewer GP contacts
- frequent home visits
- self discharge from hospital
- psychosis, depression, other psych illness and deliberate self harm
- current or recent major tranquilizer use
- denial
- alcohol or drug abuse
- obesity
- LD
- employment problems / income problems
- social isolation
- childhood abuse
- severe domestic marital or legal stress
What is a moderate asthma exacerbation?
Increasing symptoms
Peak Flow 50-75 % best or predicted
No features of acute severe asthma
What are the feature of Acute severe asthma ?
Any one of :
- Peak flow 33-50%
- RR ≥ 25
- HR ≥ 110
- Inability to complete sentences in one breath
What are the features of life threatening asthma ?
Severe asthma PLUS:
Clinical signs
- Altered consciousness level
- Exhaustion
- Hypotension
- Arrythmia
- Silent chest
- Cyanosis
- Poor respiratory effort
Measurements
PEFR <33%
SpO2 < 92%
PaO2 < 8kPa
Normal paCO2 (4.6-6)
What is near fatal asthma?
Raised PaCO2 and/or requiring mechanical ventilation with raised inflation pressures
What is the seasonal variation demonstrated in asthma deaths?
July and August in younger ppl upto 44 years
And
December to January in older people
Who needs admission with asthma exacerbation?
Adult patients with features of life threatening or near fatal or severe asthma that does not resolve after initial treatment should be admitted
Admission may also be appropriate when PEFR has improved to >75% best or predicted after initial tx but concerns about sx, previous hx or psychosocial issues:
- still having significant symptoms
- concerns about adherence
- living alone / socially isolated
- psych issues
- previous near fatal asthma
- asthma attach despite adequate corticosteroids
- presentation at night
- pregnancy
What do steroids do in acute asthma exacerbation?
Reduce : Mortality, relapse, subsequent hospital admission and requirement of beta agonist therapy
What dose of steroids ?
40mg Prednisone OD
100mg QDS Hydrocortisone
For minimum of 5 days
Who gets MgSO4?
Acute severe asthma and beyond
Single dose may improve lung function, reduce intubation rates and may reduce admission
What are the criteria for discharge ?
PEFR ≥ 75%, 24 hours off nebulisers
ALSO - ensure education done
Evidence suggests that those with PEFR ≤75 % or PEFR diurnal variability >25% more likely to have early relapse and remission
What is difficult asthma?
Diagnosis of asthma and asthma like sx and exacerbations persist despite prescription of high dose asthma therapy
Factors contributing : poor adherence , psychological, dysfunctional breathing , allergy
What happens to asthma in pregnancy?
1/3 improve , 1/3 worsen , 1/3 stay the same
Severe asthma more likely to worsen in pregnancy than mild asthma
What is the physiological effect of pregnancy?
Progesterone driven increase in minute ventilation which may lead to hypocapnia and resp alkalosis and increase Pa02 but remember sats are unaltered
What is the best question for occupational asthma?
Do symptoms improve on days away from work?
Are you same / better / worse on holiday?
Optimal PEFR for occupational asthma?
At least 3/7 in each consecutive work period and at least 4 evenly spaced readings per day
Ideally sustained period away from work also (usually 3 weeks)
How useful is IgE with occupational asthma?
Can be used for high molecular weight agents but less useful for low molecular weight agents
What is gold standard test for occupational asthma?
Specific Bronchial Provocation testing
You see a patient in clinic with asthma and do an assessment of asthma control , see answers below , given these please state asthma control
- Daytime symptoms more than twice per week? YES
- Any night waking due to asthma ? YES
- SABA reliever needed more than twice a week (NB SABA pre exercise not included) YES
- Any limitation in activity due to asthma ? YES
Uncontrolled
(A score of 3-4 is indicative of uncontrolled asthma )
You see a patient in clinic with asthma and do an assessment of asthma control , see answers below , given these please state asthma control
- Daytime symptoms more than twice per week? NO
- Any night waking due to asthma ? NO
- SABA reliever needed more than twice a week (NB SABA pre exercise not included) YES
- Any limitation in activity due to asthma ? NO
Partially controlled
(A score of 1-2 is indicative of partially controlled asthma)
You see a patient in clinic with asthma and do an assessment of asthma control , see answers below , given these please state asthma control
- Daytime symptoms more than twice per week? NO
- Any night waking due to asthma ? NO
- SABA reliever needed more than twice a week (NB SABA pre exercise not included) NO
- Any limitation in activity due to asthma ? NO
Well Controlled
(Score of 0 indicative well controlled)
What are the risk factors for poor asthma control as per GINA guidelines ?
MEDICATION
- SABA overuse (≥3 x 200 dose canisters per year; if > 1 canister per month mortality significantly increases
- Inadequate ICS (not px, poor adherence, poor technique)
CO-MORBIDITIES
-Obesity / GERD / Chronic Rhinosinustitis/ Confirmed food allergy / anxiety / depression
EXPOSURE
- Smoking /E-Cigarette / Allergens / Pollution
SETTING
- Major socio-economic issues
LUNG FUNCTION
- <FEV1 especially if <60% predicted
- high bronchodilator responsiveness
TYPE 2 INFLAMMATIOn
- High blood eosinophils
- High FeNO despite tx
Independent risk factors :
- ever been intubated or required ICU
- having ≥ 1 severe exacerbation in last 12 months
Who is eligible for bronchial thermoplasty?
High dose ICS
Non smokers for > 1 year
FEV1 >60%
No life threatening exacerbation
<3 hospitalizations
Willingness to accept risk of asthma exacerbation post procedure
What is needed to diagnose eosinophilic granulomatosis with polyangitis ?
Need 4 out of the following 6 criteria:
Asthma
Peripheral eosinophilia >10%
Paranasal sinus abnormality
Pulmonary Infiltrates
Neuropathy
Extravascular eosinophils on histology
What is atopy?
The tendency to produce IgE against innocuous antigens (allergens)
What is allergic sensitization ?
Presence of IgE to a specific allergic as measured by +ve skin test or specific IgE test
Largely genetically determined but environment factors are relevant - think hygeine hypothesis
Remember allergic sensistisation does not imply allergy , more over the potential for allergy
What produces IgE?
B cells following class switching driven by IL4
What causes allergic early phase response ?
Mast cell degranulation due to IgE cross linking by antigens
What causes allergic late phase response ?
Mediated through Th2 cells and ILC2 and accumulation of eosinophils
What affects allergic response ?
Exercise
EtOH
Sleep
NSAIDs
What are the 4 types of hypersensitivity ?
Type I - IgE Mediated <1 hour occasionally longer - Anaphylaxis , rhinitis, bronchospasm, Urticaria, angioedema , pruritis
Type II- IgG Mediated (cytotoxicity) - Hours to days - Cytopenia , Haemolytic anaemia
Type III - Immune Complex mediated (IgAg) - Hours to days - Serum sickness w rash malaise , fever , arthralgia , myalgia , renal impairment
Type IV - T cell mediated - Days - dermatitis/eczema flare , maculopapular eruptions , severe cutaneous drug reaction , contact hypersensitivity
Drug reactions - Type IV usually
Reacruons that not technically reactions - NSAIDs
What is anaphylaxis ?
Sudden release of mast cell mediators into systemic circulation leading to potentially life threatening acute multi system syndrome
If allergic reaction is skin and mucosa alone, what is it ?
Angioedema
What is the treatment of anaphylaxis ?
Remove trigger
Lie flat, raise legs
IM Adrenaline 500micrograms
What is the lifetime prevalence of anaphylaxis ?
1 in 300 , rarely fatal 20-30 per year
Should we sent Tryptase levels in anaphylaxis ?
Yes , can give biochemical confirmation but not required for diagnosis
Levels rise very rapidly and has a half life of 2.5 hours
Take 3 samples - ASAP, 1-2 hours (<4 hours) and 24 hours (can be 3 weeks later)
What are the fatalities from anaphylaxis in teens vs adults ?
Teens/ 20s - food anaphylaxis
Older age (50s) - iatrogenic
What is the threshold for tryptase?
≥ 1.2 x baseline + 2
(Sufficient to confirm but don’t have to have)
What are important differentials of anaphylaxis?
Major : Urticaria +/- Angioedema
Isolated angioedema (check ACEi)
Laryngospasm
Anxiety/Panic
Vasovagal attack
Acute asthma
Scomboid poisoning - intake of fish not stored at Cold temp - increased histamine level
What is rhinitis?
2 or more of:
- Running nose
- Blocking of nose
- Sneezing / Itching
For more than 2 hour per day
50-70% will have rhinoconjuctivitis
Considered allergic when IgE mediated (70-80%)
How do we treat rhinitis ?
Intranasal steroids , can add histamine but no evidence of benefit
2nd line combined steroid and nasal antihistamine - dymista
Consider immunotherapy
What are the different types of chronic rhinosinusitis ?
CRSsNP - often assoc with bronchiectasis
CRSwNP- often assoc w asthma , high FeNO , check ANCA/ aspergillus , ask about NSAIDs
What is a positive skin test ?
≥3mm (assuming negative control of 0mm)
Pretty good negative predictive value
What are the pitfalls of skin testing ?
- antihistamines or drugs affecting - TCAs
- test only as good as the extract
- some allergens not accessible (sesame)
- cross reaction with pollen allergy
What makes a positive IgE?
≥ 0.35
What does desensitization mean in allergy?
Temporary reduced or non reaction to allergen , usually relies on ongoing or very recent exposure to high does of the allergen
(Aspirin , Penicillin, Peanuts , Chemo drugs)
What does tolerance mean ?
Immunological state of long lasting hypo/non reactivity that persists even without ongoing exposure
Which allergens can we give allergen immunotherapy to?
Grass Pollen, Silver Birch Pollen , House dust mite, cat dander , Ragweed
What is the latency with occupational asthma?
6-24 months
