Lecture 20 - Airflow Limitation Flashcards
List some of the manifestations of atopy
- Allergic rhinitis (hay fever)
- Eczema
- Asthma
- Anaphylaxis
- Urticaria
What are the presentations of asthma?
Wheezing
Chest tightness
Dyspnoea
Cough
Describe the pathological features of the asthmatic airways
- Hypertrophy of smooth muscle in airways
- Mucous hyper secretion (from goblet cell metaplasia)
- Inflammatory cell infiltrate into submucosa
- Vasodilation
- Thickening of sub epithelial collagen layer
- Epithelial shedding
Characterise asthma
Chronic obstructive respiratory disease
although, individuals can be ‘healthy’ in between episodes
What are the clinical consequences of asthma?
Acute inflammation:
• Acute symptoms: bronchoconstriction
Chronic inflammation:
• Exacerbations, non-specific hyper reactivity
Airway remodelling:
• Persistent, fixed airway obstruction
• Significant limitation of airways, even between exacerbations
• Greatly increased work of breathing
Describe the respiratory function tests of individuals with asthma
FEV1: ↓↓
FVC: ↓
In obstructive disease, the airway is significantly narrowing, meaning flow through airways is likewise significantly reduced
What is dyspnoea?
Breathlessness
Recognition of inappropriate degree of respiratory work for body workload
Describe the pathogenesis of asthma
- Exposure to allergen
- Allergen cross-links on IgE bound to mast cells
- Activation of mast cells:
• Degranulation
• Metabolism of membrane phospholipids
• Transcription of cytokines
4.
• Recruitment of inflammatory cells
- Neutrophils, eosinophils, Th2
• Goblet cell metaplasia
• Epithelial shedding
• Vasodilation; angiogenesis
• Smooth muscle hypertrophy & hyperplasia
• Subepithelial fibrosis (Collagen deposition)
• Sensory nerve activation → bronchoconstriction (cholinergic reflex, parasympathetic)
What is the consequence of decreased airway diameter?
Increased airway resistance →
• Increased work of breathing
• Decreased FEV1
• Airflow limitation (obstruction)
Describe the worldwide burden of asthma
One of the commonest chronic diseases
Incidence increasing in developed countries
Which factors exacerbate asthma?
- Allergens
- Respiratory infections (particularly viral)
- Smoking
- Irritants
- Exercise and hyperventilation
- Weather
- Emotion
- Food, drugs
Describe the process of asthma diagnosis
Lung function tests: 1. Spirometry: • Look for airway obstruction: • Reduced FEV1 • FEV1/FVC ratio <70% 2. Peak flow
Bronchoprovocation test
• Measures airway hyperactivity (AHR)
• Reduction in FEV1 in response to irritants:
• Direct provocation (methacholine, histamine)
• Indirect provocation (exercise, mannitol, hypertonic saline)
Describe the effect of bronchodilators on spirometry in individuals with asthma
Bronchodilators can result in improvement in lung function, measured by:
• Increased FEV1
• Normalised FEV1/FVC ratio
Describe the therapeutic strategy for asthma
Therapy aims to minimise underlying pathophysiology:
1. Inflammation
• Preventer therapy
• Glucocorticoids:
- Inhaled (ICS)
- Oral (e.g. Prednisolone, only used in very severe cases)
2. Bronchoconstriction • Reliever therapy • β2-ADR agonists - SABAs: used in acute situations - LABAs: used continuously • Relieves symptoms (relaxes airway smooth muscle, improves latency)
Also:
• Combination inhalers (ICS/LABA)
• Leukotriene receptor antagonists
• Anti-IgE
Describe the balance between risk and reward of ICS therapy
Reward:
• Relatively low doses sufficient to achieve a considerable clinical improvement (i.e. reduction in inflammation)
Risk:
• Risk relatively low at low doses
• At high doses, infections (e.g. oral candidiasis, thrush) are seen
Thus, at low doses, the reward far outweighs the risk
To minimise the AEs, combination therapy is used:
• Low dose ICS/ LABA
List the commonest combination therapeutics for the control of asthma
Serotide
Spiriva
What are the main focuses of asthma therapy?
Death and severe exacerbations are not seen much any more, due to effective treatment
If day-to-day symptoms and impairment can be controlled, the more significant outcomes (death, severe exacerbations) can also be controlled
This is because control of symptoms is achieved through control of airway inflammation and remodelling
What is COPD?
Describe some clinical and epidemiological features
Chronic obstructive pulmonary disease
Two conditions:
• Emphysaema (destruction of lung tissue)
• Chronic bronchitis (inflammation and sputum production)
Group of heterogeneous conditions
Progressive, chronic condition
Abnormal inflammatory response to noxious stimuli
Third leading cause of morbidity in Australia (after heart disease and stroke)
Continues to increase in prevalence, unlike CVD, stroke etc.
- Under-recognised
- Under-diagnosed (even when respiration is severely impaired)
- Under-treated
What is the major risk factor for COPD?
Smoking
In Australia, COPD is almost completely caused by smoking
This is despite the reducing prevalence of smoking in Australia.
The population respiratory effects of smoking and lung cancer take a few years to be realised (20 years)
Other causes are seen in other countries (smoke from stoves)
Describe the pathogenesis of COPD
- Exposure to noxious agent
- Inflammation
3a. Small airway disease
• Inflammation
• Remodelling
3b. Parenchymal destruction
• Loss of alveolar attachments
• Loss of elastic recoil
- Airway limitation (restrictive lung disease)
What is the significance of loss of elastic recoil in COPD?
Elastic recoil is endowed by ECM components in the lung parenchyma
This functions to elastically pull on the airways, maintaining airway patency
When the lung tissue is destroyed, the airways tend to collapse
What is Dynamic hyper-inflation?
Trapping of air in the lungs that cannot be exhaled
Much more common in COPD than asthma
Compare the inflammation and consequences thereof in asthma and COPD
Asthma:
• Triggered by allergens
• Mast cells and epithelial cells respond
• Eosinophils and Th2 recruited and cause damage
• Results in bronchoconstriction
• Leads to reversible airway restriction
COPD:
• Triggered by chronic exposure to noxious agent (cigarette smoke)
• Epithelial cells and alveolar macrophages response
• Neutrophils and CD8 T cells recruited and cause damage
• Results in destruction of lung parenchyma and small airway narrowing
• Leads to irreversible airway restriction
Why is COPD a risk factor for lung cancer?
There is shared genetic predisposition for these two things
So, smoking cessation, and thus mitigation of COPD can decrease risk for lung cancer
Are asthma and COPD fully reversible?
Asthma:
• Yes, through therapy
• Reversible airway limitation
COPD:
• No
• Irreversible airway limitation
If one smokes, what is the risk of COPD?
Up to 50% of long term smokers will develop COPD
Which is the core feature of COPD leading to mortality?
Inflammation
List the various components of COPD
• Airway inflammation (core component) • Airway restriction • Mucociliary dysfunction • Destruction of lung parenchyma (alveolar tissue) • Systemic component: - Leukocytosis - Inflammation
Describe exacerbations in COPD
Present quite similarly to those in asthma
Aetiology:
• Infection (viral, bacterial)
• Air pollution
Describe the process of diagnosis of COPD
Evaluation of risk factors: • Any past / current smoker • Dyspnoea • Chronic cough • Productive cough • Recreational drugs (marijuana, esp. bongs) • α-1 antitrypsin (autosomal recessive) • Passive smoking etc.
Describe the therapeutic strategy for COPD
Smoking cessation is the most important feature
• Biggest factor in prevention
• Leads to most dramatic slowing in acceleration in lung function decline therapeutically
How?
- Non-pharmacological
- Pharmacological:
Other pharmacological therapy:
1. β2-ADR agonists
- Anticholinergics
- Inhaled corticosteroids (ICS)
- Combination therapy
Other strategies:
• Vaccination (esp. influenza)
• Long term antibiotics
What benefit can smoking cessation bring?
Before 50 years:
• Resolution of accelerated decline in lung function
• Lost lung function can not be regained
• Most likely won’t progress to ‘disability’ stage
After onset of ‘disability’:
• Slows the rate of decline
If smoking isn’t stopped:
• Onset of ‘disability’ around age 65
• Most likely die due to lung failure at age 70
What is classed as lung function ‘disability’?
FEV1 <25% value at 25 yrs
Describe the use of β2-ADR agonists for COPD therapy
- LABAs for regular use
- SABAs for symptomatic use
- Higher doses can lead to reduced QOL (AE: tremor, tachycardia)
Describe the use of anticholinergics for COPD therapy
• Long-acting, for regular use
Achieves: • ↓ Dyspnoea • ↑ Exercise tolerance • Fewer exacerbations • ↓ Mortality • AE: dry mouth
Describe the use of ICS for COPD therapy
- Inflammation is not such a concern in COPD compared to asthma
- Neutrophilic inflammation (as in COPD) is ‘steroid-resistant’
- Benefit demonstrated in severe COPD
Describe combination therapy for COPD
May achieve:
• Fewer exacerbations
• ↑ QOL
• Improved FEV1
Seretide:
• Fluticase / Salmeterol
Symbicort:
• Budesonide / Formoterol
Describe how smoking cessation can be achieved
1. Non-pharmacological • Eduction • Will power • Counselling etc. • Useful in combination with pharmacological therapy, but rarely works in isolation
- Pharmacological:
• Nicotine replacement therapy:
• Varenicline (Champix)
• Bupropion
• These are partial agonists at the nicotine receptor in the brain
• When one is one these drugs, nicotine does not have its effect in the brain, even if taken
