Airflow limitation Flashcards
Define airflow limitation?
Airflow limitation is defined by FEV1/FVC ratio less than the lower limit of normal (LLN) or less than 70%.
Define asthma
- 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.
Discuss the epidemiology of asthma
- 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.
Briefly describe asthma pathophysiology
- 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
Define COPD
- 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.
Discuss the epidemiology of COPD
- 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.
Describe symptoms of asthma and COPD
Asthma Symptoms
- Wheeze
- Shortness of breath
- Chest tightness
- Cough
COPD Symptoms
- Wheeze
- Shortness of breath
- Chest tightness
- Cough
- Sputum
HI
Describe how to distinguish between COPD and asthma
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.
Discuss spirometry in asthma and severe COPD
Asthma
- Reversible airflow limitation.
- Improve significantly after bronchodilator.
Severe COPD
- Irreversible airflow limitation.
- Minimal improvement after bronchodilator.
Describe inhaled corticosteroids
- 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)
HI
Describe bronchodilators broadly
- 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.
Describe SABA
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
Describe LABA
- 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
Describe anticholinergics
- 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
Compare and contrast beta agonists and anticholinergics
- 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)
Describe some less commonly used drugs: methylxanthines
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.
Describe cromoglycates
- 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.
Describe leukotriene antagonists
- 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.
Describe monoclonal antibodies
- 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
List possible future therapies
- Research into novel treatments continues, including agents targeting Thymic Stromal Lymphopoietin (TSLP).
- These therapies aim to provide more options for managing severe asthma.
List the aims of asthma treatment
- 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
Describe non-medical management of asthma
- 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
Describe the risks of ‘mild asthma’
- 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
Describe risks of regular or frequent SABA use
- 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
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.
Note: - Up to 60% of patients struggle with inhaler use.
- Proper technique is crucial for optimal treatment outcomes.
Bronchial thermosplasty
treat with heat
reduced smooth muscle ?hyperplasia?
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.
Describe the treatment aims for COPD
- Relieve symptoms
- Prevent exacerbations
- Maximize exercise capacity
- Limit further damage
- Minimize treatment adverse effects
Describe some measures taken to improve COPD outcomes
- Smoking cessation significantly improves COPD outcomes.
- Vaccines can also provide benefits to COPD patients.
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
Describe goals of pulmonary rehab
- Pulmonary rehab improves quality of life and exercise tolerance.
- It reduces hospital admissions and mortality.
- 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
Describe non-medical COPD management
Management – non medical
- smoking cessation
pulmonary rehab
surgery
bullectomy
NIV
rndobroncial approach
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.
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
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
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
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
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.
