Airflow limitation Flashcards
1
Q
Define airflow limitation?
A
Airflow limitation is defined by FEV1/FVC ratio less than the lower limit of normal (LLN) or less than 70%.
2
Q
Define asthma
A
- Asthma is a clinical diagnosis without a universally agreed definition
- Asthma is a chronic inflammatory disorder of the airways.
- It results in variable airflow limitation, airway hyperresponsiveness, and respiratory symptoms.
- Atopy, genetic, and environmental factors play a role.
- Inflammation involves Th2 cells, eosinophils, and mast cells. (See also [[Immunology B2 - Lecture 3]])
- Airway remodeling may lead to clinical features similar to COPD.
3
Q
Discuss the epidemiology of asthma
A
- Around 1 in 9 Australians have asthma (approximately 2.5 million).
- Higher prevalence among Indigenous Australians, especially older adults.
- Approximately 40,000 hospital admissions and over 400 deaths annually.
- SARS-CoV-2 has highlighted preventable presentations.
4
Q
Briefly describe asthma pathophysiology
A
- Atopy: IgE-antigen complexes
- Genetic and environmental factors
- Hygiene hypothesis
- Best thought of as chronic, mostly eosinophilic bronchitis or bronchiolitis
- Airway inflammation with infiltration by Th2 cells, eosinophils and mast cells
5
Q
Define COPD
A
- Characterized by symptomatic airflow limitation not fully reversible.
- Encompasses emphysema and chronic bronchitis.
- Tobacco is a major cause; occupational exposures contribute.
- Neonatal illnesses affecting lung development are relevant.
6
Q
Discuss the epidemiology of COPD
A
- About 7.5% of Australians aged 40 or older have symptomatic COPD, but half remain undiagnosed.
- COPD ranks second in avoidable hospital admissions in Australia.
- SARS-CoV-2 highlighted preventable cases.
- Globally, COPD is the third leading cause of death.
7
Q
Describe symptoms of asthma and COPD
A
Asthma Symptoms
- Wheeze
- Shortness of breath
- Chest tightness
- Cough
COPD Symptoms
- Wheeze
- Shortness of breath
- Chest tightness
- Cough
- Sputum
8
Q
HI
Describe how to distinguish between COPD and asthma
A
Diagnosis
- Not all that wheezes is asthma
- Asthma symptoms tend to be variable, intermittent, worse at night, and provoked by triggers.
- Note: cough variant asthma
- Diagnosis involves clinical evaluation via history, post-bronchodilator spirometry, and assessment of variability.
- post bronchodilator testing:
- PFR - Ideally for >3 days a week for two weeks
- ≥15% variability
- Minimum change of at least 60 l/min
- Reversibility of FEV1 or FVC (>12% change and at least 200 ml) – after short-acting beta2 agonist
- post bronchodilator testing:
- Reversibility testing, bronchoprovocation, and exhaled nitric oxide may also be used.
- Occasionally CT imaging may be required
- Always inquire about smoking, nasal symptoms, atopy, GORD, aspirin sensitivity, and occupation.
9
Q
Discuss spirometry in asthma and severe COPD
A
Asthma
- Reversible airflow limitation.
- Improve significantly after bronchodilator.
Severe COPD
- Irreversible airflow limitation.
- Minimal improvement after bronchodilator.
10
Q
Describe inhaled corticosteroids
A
- Mechanism of action
is complex, and includes although not limited to:- Reduced airway inflammation and bronchial hyper-reactivity.
- Reducedclonal proliferation of T-helper cells by reducing IL-2 and reduction in cytokines
- Inhibit allergen-induced influx of eosinophils
- Up regulation of beta receptors.
- Note dose?
- Used in asthma and some COPD patients.
- Adverse effects include mostly local effects (candidiasis, dysphonia) and potential systemic effects (at high doses for prolonged periods, especially in children)
- less likely to occur than with oral ICS e.g. imapired diabetic control, fractures, adrenal suppression, cataracts etc
- n.b. pneumonia in patients with COPD (local adverse effects)
11
Q
HI
Describe bronchodilators broadly
A
- β2 agonists and anticholinergics.
- β2 agonists act on β2 receptors to increase intracellular cAMP resulting in bronchodilation
- anticholinergics block muscarinic receptors, inhibiting bronchoconstriction, and inhibiting blocking of cAMP increase by β2 receptors
- Improve bronchomotor tone and reduce airway narrowing.
- Targeted therapy for symptom relief and bronchodilation.
12
Q
Describe SABA
A
SABA
- Examples – salbutamol, terbutaline
- Onset of action rapid and maximum effect in 30 mins
- Duration of effect 3 – 5 hours
- All β2 agonists may also stimulate β1- receptors leading to tachycardia, tachyarrhythmias, tremor, etc
- In high doses, all β2 agonists can cause hypokalaemia and hyperglycaemia
13
Q
Describe LABA
A
- Examples – salmeterol, eformoterol, vilanterol
- Onset of action depends on agent can be within 10 mins
- Duration of action 8 – 24 hours
- Always given in combination with inhaled corticosteroids in asthma (and often in COPD)
- Similar adverse effect profile to SABA
14
Q
Describe anticholinergics
A
- Examples ipratropium bromide (short- acting anticholinergic drug), umeclidinium, aclidinium and tiotropium (long-acting anticholinergic drugs)
- LAMA can be given once a day
- Consistent with their anticholinergic activity, S/LAMAs should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia or
bladder-neck obstruction
15
Q
Compare and contrast beta agonists and anticholinergics
A
- mechanism of action different
- end result same
- both saba and lama
- beta agonists quicker
- beta: exacerbations, reduced responsiveness, risk of ED presentation and death with increased use
- Ma: reduce exacerbations, local (candidiadis) and systemic – less likely with oral (hyperglyc, hypoK)
16
Q
Describe some less commonly used drugs: methylxanthines
A
Methylxanthines
- Controversy exists regarding the effects of xanthine derivatives (Theophylline and Aminophylline).
- They might act as non-selective phosphodiesterase inhibitors.
- Their mechanism of action isn’t well understood.
- Bronchodilator effects of theophylline generally offer no advantage over β2 agonists.
- These drugs are challenging to use due to their narrow therapeutic ratio and potential for toxicity.
17
Q
Describe cromoglycates
A
- Examples include nedocromil sodium and sodium cromoglycate.
- Administered via inhalation (dry powder device, nebulizer, or metered dose inhaler).
- They are thought to stabilize mast cells, inhibiting histamine and leukotriene release.
- These drugs are prophylactic and not used for acute relief.
- Generally well-tolerated, adverse effects are rare.
18
Q
Describe leukotriene antagonists
A
- Examples: montelukast, zafirlukast.
- Orally administered selective antagonists of leukotrienes.
- Act by preventing leukotriene release or blocking leukotriene receptors on bronchial tissues.
- Useful in preventing bronchoconstriction, mucus secretion, and edema.
- Not all asthmatics will respond to them.
19
Q
Describe monoclonal antibodies
A
- Target specific immune mediators.
- Omalizumab: Binds circulating IgE, reducing exacerbation rate and steroid use. SC infusion with an elevated srum Ige AND CONTINOUS OR frequent treatmetn with oral CS
- Anti-IL5: Targets cytokine IL-5, reducing eosinophil-related inflammatio, improve health related quality of life, exacerbations and lung function
- Dupilumab: Blocks IL-4 and IL-13 signal transduction, targeting alpha subunit of IL-4R, signficantly fewer severe exacerbations, btter lung function and asthma control
- greater benefirs with higer baseline basophils
20
Q
List possible future therapies
A
- Research into novel treatments continues, including agents targeting Thymic Stromal Lymphopoietin (TSLP).
- These therapies aim to provide more options for managing severe asthma.
21
Q
List the aims of asthma treatment
A
- No daytime symptoms
- No nighttime awakenings due to asthma
- No need for rescue medication
- No exacerbations
- No limitations on activity, including exercise
- Normal lung function
- Minimal side effects from medication
22
Q
Describe non-medical management of asthma
A
- Smoking cessation, including avoiding secondhand smoke
- Steroid resistance consideration for smokers/ex-smokers, LRAs?
- Allergen avoidance
- Dietary modifications (food avoidance/supplementation)
- Probiotics, air ionizers, mist, salt caves, acupuncture, homeopathy, Buteyko breathing technique
23
Q
Describe the risks of ‘mild asthma’
A
- Inhaled SABA (Short-Acting Beta-Agonists) was the primary treatment for asthma for 50 years.
- This era associated asthma with bronchoconstriction.
- Patients with seemingly mild asthma are at risk of serious adverse events.
- 30–37% of adults with acute asthma
- 16% of patients with near-fatal asthma
- 15–20% of adults dying of asthma
24
Q
Describe risks of regular or frequent SABA use
A
- β-receptor downregulation
- Increased allergic response and eosinophilic airway inflammation
- Higher SABA use is linked to adverse clinical outcomes:
- Using ≥3 canisters per year is associated with a higher risk of ED presentations
- Dispensing ≥12 canisters per year is associated with a higher risk of death
25
# Hi
List and describe the steps of asthma treatment
Track1
1. asneeded low dose ICS formoterol
2. as bove
3. low dose maintenane ICS- formoter
4. medium dose maintenance ICS-formoterol
5. add on LAMA, phenotypic assessment, pplus minus anti IgE, IL5/R, 4R. Consider high dose ICS-formoterol
with releiver low dose ICS formoterol as needed
Track 2
1. ICS with SABA
2. Low dose maintenecane ICS
3. ld maintenance ICS and LABA
4. Medium/high dose maintenance ICS LBA
5. as above, consider high dose ICS-LABA
WITH: as needed SABA reliever, add additional controller options from step 2
**Inhaled Corticosteroids (ICS)**
- Step 3 and 4 ICS/LABA dose equivalence:
- FF/VIL 92/22 once daily = FP/SAL 250/50 twice daily = 400 BUD twice daily = 200 BDP twice daily (as Qvar) = 500 BDP twice daily (as Clenil)
**Step 4 (and 5) Tiotropium**
- Tiotropium's role is shifting, potentially helpful in asthma.
- Studies show adding tiotropium to selected patients' treatment can significantly improve morning peak flows, similar to salmeterol's effect.
**Step 5 and Severe COPD**
- Rarely, continuous oral steroids are beneficial but come with common adverse effects.
- Monitor patients on oral steroids for various health parameters.
- Severe COPD requires onward referral for hospital assessment.
## Footnote
Note: - Up to 60% of patients struggle with inhaler use.
- Proper technique is crucial for optimal treatment outcomes.
26
Bronchial thermosplasty
treat with heat
reduced smooth muscle ?hyperplasia?
27
Describe how to step down
- Titrate inhaled steroid doses to the lowest effective control dose.
- Attempt to halve inhaled steroid doses every three months for stable patients.
28
Describe the treatment aims for COPD
- Relieve symptoms
- Prevent exacerbations
- Maximize exercise capacity
- Limit further damage
- Minimize treatment adverse effects
29
Describe some measures taken to improve COPD outcomes
- Smoking cessation significantly improves COPD outcomes.
- Vaccines can also provide benefits to COPD patients.
30
Breakdown COPD classification
- 4 grades: GOLD 1-4
- spirometrically confirmed diagnosis, assessment of airflow limitation, assessment of symptoms/risk of exacerbations
- post-bronchodilator <0.7
- A and B, C and D to assess symptoms and risk of exacerbations: C and D habe moderate or severe exacerbation historu. greater 2 or 1 leading to hospital admission
31
Describe goals of pulmonary rehab
- Pulmonary rehab improves quality of life and exercise tolerance.
- It reduces hospital admissions and mortality.
## Footnote
* Minimum length of an effective
rehabilitation program is 6 weeks
* The longer the program continues, the
more effective the results
* Offer to all patients following hospitalised
AECOPD and to those with mMRC ≥ 2
* Effects wear off over time
32
Describe non-medical COPD management
Management – non medical
- smoking cessation
pulmonary rehab
surgery
bullectomy
NIV
rndobroncial approach
33
Describe the use of long term oxygen
Oxygen only helpful if hypoxic pO2 ≤55mmHg to get mortality
benefit or pO2 between 55-60mmHg with evidence of
downstream effects (polycythaemia, HF, lower limb oedema,
etc.
34
Describe the use of long-term macrolides
e.g. Azythromycin, clazithromycin
• Antibiotics with anticillary anti-inflammatory effects
• Side effects
• Cardiovascular events (affect QT)
• Hearing
• Emergence of resistant bacteria and non-tuberculous
mycobacteria
35
DESCRIBE THE USE of roflumilast and mucolytics
* Phosphodiesterase-4 inhibitor
* Not available in Australia
* Cannot be used with theophylline
* SE GI upset, weight loss
* Improves lung function and decreases the
rate of moderate or severe exacerbations
in patients with FEV 1 <50%, chronic
productive cough and a history of
exacerbations.
- mucolytics not currently in use in Au
36
Describe surgical approaches to treat
**Lung Volume Reduction Surgery**
Because ULs have higher VQ ratio, pathology more likely to affect
Lower part lo VQ- pathology in blood more likely to affect
Emphysema causes dilation and bullae, cannot expand upwards due to clavicles so push down on relatively normal lower tloves -- cut off upper lobe to reduce lower lobe damage
**Endobronchial approach**
insert valves, air comes out of upper lobes rather than coming back in, UL collapse, does not push on lower lobes
**Other surgical procedures**
- bullectomy
- lung transplant
37
Describe indications for ventilatory support
* Consider NIV when PaCO2 <53 mmHg
(7kPa)
* Bring CO2 down (high pressures and back
up rate) this may well require hospital
admission
* ?initiate immediately after AECOPD
* Early studies suggest may worsen QoL
* Always look for (and treat) OSA
38
Describe acute asthma in adults management
- bronchodilators - use 2 if not improving
- steroids take time
- go to hospital
- Magnesium IV may provide additional benefit in acute severe asthma treatment.
* iv magnesium may provide additional
benefit in acute severe asthma when used
with steroids and bronchodilators.
* Unclear mode of action
* ?smooth muscle relaxation by interacting
with intracellular calcium
* May stabilize T cells and inhibit mast cell
degranulation, leading to a reduction in
inflammatory mediators.
