Asthma Flashcards
How do you diagnose asthma?
1) Spirometry:
- FEV1/FVC <LLN or <75%, should be considered supportive of an asthma diagnosis and should prompt reversibility test
- Normal spiro does not rule out asthma
2) PEF:
- Should not be used as the primary test
- May be considered if no other lung function test is available
- Should be monitored over a two-week period - variation of >20% supportive of asthma. <20% variability does not rule out asthma
- useful to diagnosis occupational asthma
-
3) FeNO
- Cut-of: >40ppb
- <40 does not exclude asthma
- FeNO is lowered in smokers, impaired airway calibre, on ICS, on anti-IL4/IL13
- FeNO can be high in allergic rhinitis or chronic eosinophilic bronchitis
4) Bronchial challenge testing
- Asthma = Provocation concentration causing 20% fall in FEV1of methacholine (PC20-M) or histamine (PC20-H) <8mg/ml in steroid naïve & <16mg/ml in pts on regular ICS
- Indirect challenges (using mannitol or exercise) can be considered in pts which remain negative with direct constricting agents. PD mannitol <625mg suggestive of asthma
- Indirect challenges better correlated with the extent of airway inflammation
For pts already on maintenance ICS therapy:
- Do reversibility testing or bronchial challenge testing
- ICS gradually tapered and if Sx do not worsen or no significant decline in spiro/ PEF → bronchial challenge test
Reference: ERS 2022 Dx of asthma in adults
How do you manage asthma in general?
(Assess - Adjust - Review)
1) assess asthma control
- ACT score
- identify risk factors for poor control
- monitor spiro: before Rx, 3-6m post Rx, then annually
2) manage comorbidities
- look for:
allergic rhinitis
chronic rhinosinusitis
GORD
obesity
OSA
anxiety
depression
3) initiate treatment
Ax technique
provide written asthma plan
ask pt re goals & preference of Rx
- confirm Dx
- Mx comorbidities
- Ax Sx - ACT
- Asthma Action
Summary:
1) Assess
- Correct Dx
- Comorbidities (7)
- Sx (ACT)
- Asthma Action Plan
- Educate re technique & need for compliance
- Pt’s understanding/ goals
2) Adjust:
- based on ACT 3-6m post Rx
- ACT
- Ax technique/ compliance
3) Review:
- Spiro at baseline, 3-6m & annually
- ACT score
Phenotypes of asthma (5)
1) Allergic asthma - sputum is usu eosinophilic, assoc with other atopy (eczema, AR, drug/food allergy), childhood
2) Non-allergic asthma - sputum can be paucigranulocytic, neutrophilic or eosinophilic. not assoc with allergy
3) Adult-onset (late-onset) asthma - esp woman, usu non-allergic, needs high dose of ICS or relatively refractory to steroid. TRO occupational asthma
4) Asthma with persistent airflow limitation - in long standing asthma (persistent & incompletely reversible sec airway remodelling)
5) Asthma with obesity - min eosinophilic airway inflammation)
What is asthma?
What is the diagnostic criteria of asthma?
Resource: GINA 2023
Problem with bronchial challenge test: false positive in COPD, allergic rhinitis, CF & bronchopulmonary dysplasia
= A heterogenous disease,
- characterised by chronic airway inflammation,
- defined by the Hx of respiratory Sx e.g. wheeze, SOB, chest tightness & cough,
- that vary over time and in intensity,
- with variable expiratory airflow limitation.
3 diagnostic criteria of asthma:
1) Hx of typical variable resp Sx:
- wheeze/ SOB/ chest tightness/ cough
- variable over time & intensity
- worse at night or waking
- triggered by exercise, laughter, allergens, cold air
- worse with viral infections
2) Confirmed variable exp airflow limitation
- Options:
a) Spiro with reversibility test: Increase in FEV1 >12% and >200ml
b) Excessive variability in twice-daily PEF over 2 weeks: >10%
c) Increase lung function after 4 weeks of Rx: Increase FEV1 >12% and >200ml
d) Positive exercise challenge test: Decrease FEV1 >10% and >200ml
e) Positive bronchial challenge test: Decrease FEV1 ≥20% (with methacholine) or ≥15% (with hyperventilation, hypertonic saline or mannitol)
f) Excessive variation in lung function between visits: Decrease FEV1 >12% and >200ml
3) AND 2 documented exp airflow limitation
Conditions that increases and decreases FeNO
Conditions that increases FENO:
a) Type 2 airway inflammation asthma
b) Eosinophilic bronchitis
c) Atopy
d) Allergic rhinitis
e) Eczema
Conditions that decreases FENO:
a) Smokers
b) During bronchoconstriction
c) Early phase of allergic response
d) Neutrophilic asthma
Conditions that may increase or decrease FENO:
a) Viral resp infection
When is FeNO required in asthma setting?
- FENO is indicated in spiro which is above normal, instead of bronchodilator challenge
- FENO is to be done before spirometry
DDx of asthma
CCC-II-B-H-M
Age 12-39:
Chronic upper airway cough syndrome
Inducible laryngeal obstruction
Bronchiectasis
Cystic fibrosis
Congenital heart disease
AATD
Inhaled foreign body
Age 40+:
Inducible laryngeal obstruction
Hyperventilation, dysfunctional breathing
COPD
Bronchiectasis
Cardiac failure
Medication-related cough
Parenchymal lung disease
PE
CAO
All ages:
TB
Pertussis
Comorbidities that affect asthma control
a) AR
b) Rhinosinusitis
c) GORD
d) Obesity
e) OSA
f) Depression
g) Anxiety
Drugs that can affect asthma control
1) Cytochrome P450 inhibitors
- e.g. ketoconazolem ritonavir, itraconazole, erythromycin, clarithromycin
- effect:
a) increase systemic ICS SE (e.g adrenal insuff)
b) increase CVD adverse effects with LABA Salmeterol and Vilanterol
2) Paxlovid (nirmatrelvir + ritonavir)
- used in prevention to severe covid-19 infection
- effects:
a) Interacts with salmeterol & vilanterol –> need to swap to different LABA as these LABAs increases cardiac toxicity in combination with Paxlovid.
- Duration of swap is upon starting Paxlovid until 5d after stopping Paxlovid
Factors that contribute to difficult asthma control
a) poor technique
b) poor compliance
c) over-use of SABA
d) comorbidities: GORD, obesity, rhinosinusitis, OSA, allergic rhinitis
e) persistent environmental exposures: triggers at home/ work, smoking, allergen exposure, meds (NSAIDs, beta-blocker)
f) psychosocial factors: anxiety, depression, social difficulties
Controller options in Step 3 of asthma Mx
a) Sublingual allergen immunotherapy (SLIT): in AR & sensitised to house dust mites & FEV1 >70%
b) Add LAMA
c) Add LTRA (e.g. montelukast)
d) Add Theophylline MR
Controller options in Step 5 of asthma Mx
a) Add on Azithromycin
- Consider after high-dose of ICS/LABA
- Dose: 500mg 3x/week
- Things to do before initiating it: check sputum for NTM, ECG for prolonged QTc, risk of microbial resistance
- Duration of Rx is 6m at least (studies have not shown significant improvement in 3m)
b) Add on biologic
c) Add on bronchial thermoplasty: long term effects on lung function is not known
d) Add on OCS (last resort)
Asthma treatment according to the steps
Steps:
1: Sx <2/month
2: Sx <4-5d/week
3: Sx most days, OR waking up at night >1d/week
4: Daily Sx, OR waking up at night >1day/week, AND low lung function
Rx:
Preferred pathway:
Step 1-2: PRN ICS-formoterol
Step 3: Low dose ICS-formoterol
Step 4: Medium dose ICS-formoterol
Step 5: Add on LAMA +/- biologic. Consider high dose ICS-formoterol
Reliever: PRN ICS-formoterol (lower risk of exac compared to SABA as PRN)
** Alternative pathway**:
Step 1: ICS whenever SABA is taken
Step 2: Low dose ICS
Step 3: Low dose ICS-LABA
Step 4: Medium/ high dose ICS-LABA
Step 5: Add on LAMA.
Consider biologic
Other controller options:
Step 2: Low dose ICS whenever SABA taken, OR daily LTRA, OR HDLM SLIT
Step 3: Medium dose ICS, OR add LTRA, or add HDM SLIT
Step 4: Add LAMA OR LTRA OR HDM SLIT or switch to high dose ICS
Step 5: Add azithromycin (adults only) or LTRA.
Last resort: add low dose OCS
ICS doses according to strength, and triple therapy inhalers
Budesonide (DPI or MDI)
Low: 200mcg
Mod: >400mcg
High: >800mcg
Beclomethasone (extrafine)
Low: 100mcg
Mod: >200
High: >400
Beclomethasone (std particle)
Low: 200mcg
Mod: >500
High: >1000
When should we consider stepping down asthma treatment?
a) When asthma Sx have been very well controlled and lung function has been stable for ≥3m, with close supervision
b) Choose appropriate time: not travelling/ pregnant/ resp infection
c) Engage the pt with the process, provide clear instructions and pt has sufficient med to resume previous dose if needed.
d) Step down ICS by 25-50% at 3m interval
Vaccination advice in asthma
a) Annual fluvax in mod-severe asthma
b) Insufficient data for pneumococcal or pertussis vax
c) Covid-19 vax
Covid-19 vax & fluvax can be given on same day
Non-pharmacological intervention in asthma
i. Avoid meds that make asthma worse: e.g NSAIDs, ophthalmic or oral B-blocker – not absolute contraindication but need to monitor closely
ii. Healthy diet: high fruits & vege for general wellbeing
iii. Avoid indoor/ outdoor allergens/ weather condition: e.g. smoking, vaping, mold, pollen, pets, very cold weather/ haze
iv. Weight reduction: weight reduction + 2x/w aerobic & strength exercises more effective
v. Emotional stress Mx: mental health Ax, breathing exercise
vi. Address social risk
vii. Food avoidance: only recommended when it is confirmed by supervised oral challenge
viii. Asthma education
ix. Ensure correct technique
x. Vaccination – influenza & Covid-19
Aspirin-Exacerbated Respiratory Disease (AERD)
A) Clinical course:
- Nasal congestion and anosmia –> chronic rhinosinusitis and nasal polyps (regrow rapidly after surgery) –> asthma & aspirin/NSAIDs hypersensitivity
- After exposure to aspirin/NSAIDs –> acute asthma develops within 1-2h, often assoc with rhinorrhea, nasal obstruction, conjunctival irritation, flushing of head & neck –> severe bronchospasm, shock, LOC & resp arrest
- Prevalence 7% of adult asthmatics & 15% in severe asthma
B) Ix:
- Aspirin challenge (oral/ bronchial/ nasal) – gold std
- No in vitro test
C) Mx:
- Avoidance of COX-1
- Consider COX-2 (e.g. celecoxib), PCM
- ICS, LTRA
- Aspirin desensitization, followed by daily aspirin
What is the definition of uncontrolled asthma?
Either 1 or both of the following:
i. Poor Sx control – frequent Sx or reliever use, activity limited by asthma, night waking due to asthma)
ii. Frequent exacerbations - ≥2/year requiring OCS or ≥1 requiring hospitalisation
What is the definition of difficult-to-treat asthma?
i. Asthma that is uncontrolled
ii. despite prescribing medium or high-dose ICS-LABA Rx, or
iii. that requires high-dose ICS-LABA Rx
iv. to maintain good Sx control and reduce exacerbation.
v. It does not mean ‘difficult pt’.
vi. Often due to modifiable factors e.g. incorrect inhaler technique, poor adherence, smoking, comorbidities, incorrect Dx
What is the definition of severe asthma?
i. Asthma that is uncontrolled
ii. despite adherence with optimised high-dose ICS-LABA therapy
iii. and Rx of contributory factors,
iv. or that worsens when high-dose Rx is decreased.
v. 3-10% of asthmatics have severe asthma.
How to manage pt with difficult to treat or severe asthma?
i. Confirm the Dx of asthma
ii. Provide asthma self-management education (written or electronic). Refer to asthma educator.
iii. Identify and manage contributing factors to Sx/ poor QoL or exacerbations
iv. Assess the clinical or inflammatory phenotype to decide on add-on Rx
v. Depending on the phenotype, consider LAMA, LTRA, low dose azithromycin and biologic agents
vi. Low dose OCS as maintenance should only be considered as last resort if other options are not available due to its long term side effects
vii. Stop ineffective Rx
viii. Multidisciplinary team care
ix. Collaborate with primary care clinician for pt’s social and emotional needs
x. Invite pt to enroll in registry or clinical trial if available & relevant
Side effects of long-term OCS use are?
i. OP & fragility fracture
ii. DM
iii. Obesity
iv. Cataract
v. HTN
vi. Adrenal insuff
vii. Depression/ anxiety
viii. Sleep disturbance
ix. Increased risk of infection
x. Thromboembolism
What are the tests that need to be done in severe asthma cases?
Bloods:
i. CBC – eosinophil count
ii. CRP
iii. Total Ig: IgG, IgA, IgM, IgE, specific IgE
iv. Fungal precipitins
v. If Eos ≥300 → stool ova, cyst & culture + Strongyloides serology
vi. If Eos ≥500 →TRO EGPA, so send ANCA
vii. BNP if concern re CCF
Imaging:
i. CXR/ HRCT
ii. CT sinuses
iii. DEXA scan, adrenal insufficiency test for pt on OCS or high dose ICS
iv. Echocardiogram
Others:
i. FENO
ii. DLCO
iii. Bronchoscopy – TRO tracheobronchomalacia, sub-glottic stenosis, inducible laryngeal obstruction
What are the Type 2 inflammation criteria? (only 1 is required to fulfil Type 2 inflam criteria)
i. Eosinophils ≥150/microL
ii. FeNO ≥20ppb
iii. Sputum eosinophils ≥2%
iv. Asthma is clinically allergen driven
(Repeat eosinophils & FeNO up to 3x, at least 1-2w after OCS or on lowest OCS dose)
How do you manage asthma with Type 2 inflammation vs those without Type 2?
In Type 2 inflammation:
i. FeNO to check adherence
ii. Increase ICS for 3-6m
iii. Consider add-on non-biologic: LTRA, aspirin desensitisation, treat comorbidities
iv. Add on non-biologic Rx e.g. ABPA, rhinosinusitis, nasal polyposis, atopic dermatitis Rx
v. If biologic agents not an option:
a) High dose ICS
b) Add-on LAMA, LTRA, low dose azithro
c) Low dose OCS with Rx to prevent SE
d) Stop ineffective therapies
vi. Biologic agents – consider checking & treating parasite infection first
- Funding for biologic in Msia: self-funding, application from JPA
In non-type 2 airway inflammation:
i. Review DDx, inhaler technique, adherence, comorbidities, med side-effects
ii. Avoid exposure: smoking, allergen, irritants (at home & work)
iii. Other Ix that has not been done e.g. bronch (TRO tracheobronchomalacia, subglottic stenosis), HRCT
iv. Trial of add-on Rx: LAMA, low dose azithromycin (check sputum for NT, do ECG and recheck after 1m) & consider Abx resistance
v. Anti-IL4R (Dupilumab) if taking OCS
vi. Anti-TSLP (Tezepelumab)
vii. Low dose OCS + Rx to prevent SE
viii. Bronchial thermoplasty
ix. Stop ineffective therapies
Which biologic agents to use in asthma?
Anti-IgE:
a) eos ≥260/microL
b) FeNO ≥20ppn
c) Allergen-driven
d) Childhood-onset
Anti-IL5/ Anti-IL5R:
a) Eos ++ (≥150 /microL or ≥300/microL)
b) more exac in previous year
c) Adult-onset
d) Nasal polyposis
Anti-IL4R:
a) Eos ++ (≥150 and ≤1500/microL)
b) High FeNO ≥25ppb
c) taking OCS
Anti-TSLP:
a) Eos ++
b) High FeNO
How to initiate and continue on biologics?
i. Choose the most appropriate biologic
ii. Trial of at least 4m and reassess response
iii. If good response, re-evaluate every 3-6m
- Consider reducing OCS (check for adrenal insuff. If unwell, need to get OCS for 6m post cessation of OCS), then stop other add ons. Continue mod dose ICS-LABA
- Consider stopping biologic after 12m if Sx well controlled on mod dose ICS-LABA & no further exposure to allergic trigger. Some pts may relapse.
iv. If unclear response, extend trial to 6 to 12m
v. If no good response, consider switching to different biologic.
vi. If still no good response, stop biologic. Do Mx as per non-Type2
– continue to optimise inhaler technique, adherence, non-pharmacological strategies, social/emo needs, communication with GP
Response review by looking at:
i. Asthma Sx, exac & lung function
ii. Other Type 2 comorbids – nasal polyposis, atopic dermatitis
iii. Meds: treatment side effects, affordability
iv. Pt satisfaction
What is the definition of asthma-COPD overlap?
Pts who have persistent airflow limitation together with clinical features that are consistent with both asthma and COPD
Content of asthma action plan
i. All pts should receive written, electronic or pictorial asthma action plan
ii. Details of the best PEF, current regimen
iii. Details of signs of worsening Sxs & next step.
iv. When to increase the dose/ present to hosp
What are the triple therapy inhalers available?
Management of severe asthma exacerbation
What is the content of ‘Asthma Action Plan’?
Asthma Action Plan
i. All pts should receive written, electronic or pictorial asthma action plan
ii. Details of the best PEF, current regimen
iii. Details of signs of worsening Sxs & next step.
iv. When to increase the dose/ present to hosp
Sites of where specific biologics work
How to manage asthma exac in primary care setting
Mx of exac of asthma in primary care:
A) Determine severity
Mild-mod features:
- Talk in phrases
- Prefers sitting (to lying)
- Not agitated
- RR increased
- No accessory muscle use
- HR 100-120
- SpO2 90-95%
- PEF >50% predicted
Severe features:
- Talks in words
- Sits hunched forward
- Agitated
- RR >30
- Accessory muscle use
- HR >120
- SpO2 <90%
- PEF ≤50% predicted
Life-threatening features:
- Drowsy
- Confused
- Silent chest
B) Treatment:
1) ABC
2) SABA 4-10p, every 20mins for 1h, then every 1-4h PRN
3) Pred 40-50mg (1mg/kg)
4) O2 – aim SpO2 93-95%
5) Ax for d/c in mild-mod, or transfer to hosp in life-threatening
- D/c if:
i) Sx improved not needing SABA, ii) PEF >60-80%,
iii) SpO2 >94%,
iv) resources at home adequate
6) If d/c: Cont reliever, start or step up controller, pred for 5-7d, f/up 2-7d. Abx only if with infection evidence
7) F/up:
- check whether exac resolving,
- reduce reliever,
- cont controller higher dose for 1-2w or 3m (depend on exact),
- check risk factors inc technique & adherence.
- Refer if >1-2 exac/year.
- Ax whether action plan needs to be modified
What are the effects of SABA overuse and OCS short term/ long term use
SABA overuse:
Regular use of SABA in 1-2w –> beta-receptor downregulation –> increased airway hyperresponsiveness and increased eosinophilic inflammation –> reduce bronchodilator response
SE: hypoK, hyperlactatemia, hyperglycemia, tachycardia, tremors
OCS:
Short term SE:
- sleep disturbance,
- increased appetite,
- reflux,
- mood change,
- sepsis,
- VTE
#Use of ICS 4-5 lifetime courses assoc with osteoporosis, fractures, DM, CCF, cataract
Rx of asthma exac in ED
Treatment of asthma exac in ED:
1) ABC – if drowsy/ confused/ silent chest → refer ICU, SABA & prepare intubation
2) Ax severity features
Mild-mod features:
- Talk in phrases
- Prefers sitting (to lying)
- Not agitated
- RR increased
- No accessory muscle use
- HR 100-120
- SpO2 90-95%
- PEF >50% predicted
Severe features:
- Talks in words
- Sits hunched forward
- Agitated
- RR >30
- Accessory muscle use
- HR >120
- SpO2 <90%
- PEF ≤50% predicted
3) Mild-mod Mx: SABA, consider ipratropium, O2 supp (aim 93-95%), OCS
4) Severe Mx: SABA, ipratropium, O2 supp, OCS or iv steroid, consider IV Mg, consider high dose ICS
5) Ax frequently with lung function to be Ax in 1h after Rx
6) Monitor K level with high dose of SABA
7) D/c if FEV1 or PEF 60-80% predicted or personal best
8) If required ICU, below are other Mx in refractory bronchospasm;
- NIV/ IMV
- Bronch for mucous plugging
- Sedative/ muscle relaxant (e.g. Ketamine, propofol)
- Inhaled anaesthetics (e.g. isoflurane)
- ECMO, ECCO2-R
Doses for meds use in asthma exacerbation
Dosing of meds:
a) Salbutamol neb:
- Salbutamol 0.5% inhalation solution
- Dose: 2.5-5mg, repeat every 20mins for 1 hour
b) Salbutamol infusion:
- Salbutamol 5mg/5ml
- Dose:
Loading dose 0.25mg over 10mins
Dilute 0.5mls (0.5mg) of salbutamol in 20mls N/saline
Use syringe pump. Rate: 60mls/hr (20mls over 20mins)
Infusion dose: 5-20mcg/min
Dilute 3mls (3mg) of salbutamol in 50mls N/saline or D5%
1ml /hr = 1mcg/min
Run 5-20mls/hr
c) Ipratropium bromide
- Ipratropium bromide 0.025% inhalation solution (250mcg/ml)
- Dose: 0.5mg, repeat every 4-6h
d) MgSo4
- Dose: 2g over 20mins
e) Hydrocortisone
- Dose: 200mg stat, and 100mg TDS
f) Pred
- Dose: 1mg/kg (max 50mg) OD 5-7d
g) Adrenaline
- Use in angioedema/ allergy
- Adrenaline 1:1000 (1mg/ml)
- Dose:
IM: 0.5mg every 20mins (max 3 doses)
S/cut: (same as IM)
IV: 0.1mcg/kg/min
h) Aminophylline
- Not recommended due to adverse & cardiac effects
- Dose: iv 6mg/kg over 30mins, then IVI 0.5mg/kg/h. Check serum level with aim 8-12 mcg/ml
i) Ketamine
- Dose: 0.1-0.5mg/h
j) Propofol
- Dose: 5-50mcg/kg/min
Criteria for D/c from ED and risk factors for readmission
Criteria for hospitalisation vs D/c from ED
1) Pre-Rx FEV1 or PEF <25%, or post-Rx FEV1 or PEF <40% → admit
2) Post-Rx 40-60%, d/c possible after Ax pt’s risk & availability of f/up
3) Post-Rx >60% → d/c
Other risk factors for admission:
1) Female, older, non-white
2) ≥8x SABA in past 24h
3) Severe exac
4) PHx of severe exac (intubation, admission)
5) Previous OCS use
6) Social circumstance
D/c planning following asthma exac
D/c planning post exac:
1) F/up 2-7d
2) Use MART or AIR (to reduce severe exac & OCS use) compared to SABA reliever
3) Review pt’s understanding of triggers, modifiable risk factors (i.e. smoking), technique, actions needed if deteriorated
4) Optimise pt’s Rx
Biologics dosing & SE
How to Dx Asthma (GINA 2023 guideline)
a) Spiro with reversibility test: Increase in FEV1 >12% and >200ml
b) Excessive variability in twice-daily PEF over 2 weeks: >10%
c) Increase lung function after 4 weeks of Rx: Increase FEV1 >12% and >200ml
d) Positive exercise challenge test: Decrease FEV1 >10% and >200ml
e) Positive bronchial challenge test: Decrease FEV1 ≥20% (with methacholine) or ≥15% (with hyperventilation, hypertonic saline or mannitol)
f) Excessive variation in lung function between visits: Decrease FEV1 >12% and >200ml
Biologics
- their phase 3 trials
- special points
Phase 3 trials for specific biologics:
Mepolizumab: MENSA, SIRIUS
Benralizumab: CALIMA, SIROCCO, ZONDA
Dupilumab: QUEST, VENTURE
Omalizumab: EXTRA
Special points:
- Anti-IL5/5R does not look at FENO - so FENO is not applicable in deciding for it
- Dupilumab has specific advantages:
a) better FEV1 improvement (QUEST study)
b) biggest reduction in OCS use (SINUS 24 study)
c) biggest reduction in nasal polyposis (SINUS 24 study)
- Dupilumab can unmask EGPA
Factors to be considered in choosing biologics
1) OCS regular use
2) EOS
3) FENO
4) Allergy driven
5) CRSwNP
