Session 8

Question 1

# Define asthma and describe the nature of the air flow obstruction in asthma LO 
1. Asthma is ?

2. What are the defining features of asthma?
3. What is a similarity and difference between asthma & COPD?
4. Describe, in outline, the pathophysiology of asthma LO
   Q. Aetiology/ risk factors for asthma

Answer 1

A. - heterogeneous disease

• chronic airway inflammation
• wheeze, shortness of breath, chest tightness & cough that vary over time and in intensity, together with variable expiratory airflow limitation

2. Susceptibility
   Airway hyper-responsiveness
   Chronic inflammatory process
   Reversibility
   Variable airflow obstruction

​3. Similarity: airways obstruction

Difference:
Airway obstruction in Asthma is often reversible – > 15% improvement either spontaneously or with bronchodilators (or steroids)

Airway obstruction in COPD is not fully reversible - < 15% improvement with treatment

4.

Question 2

Pathophysiology for asthma LO

1. Asthma is a chronic inflammatory process driven by what immune cell?
2. How are these cells activated? What do these cells do?
3. What response should they have?
4. What happens when they are exposed to the allergen for the first time?

Answer 2

1. T helper cells (TH2) (extracellular response)
2. Macrophages process & present antigens to TH2:

• release cytokines
• attract and activate mast cells, eosinophil etc
• activate B cells, which produce IgE

3. TH1 & produce IgG4 (intracellular)-> non harmful
4. Sensitised -> have memory B cells

Question 3

1. Typically, in a sensitized atopic asthmatic, exposure to antigen results in a 2 phase response:
2. Draw a diagram showing the first stage

Answer 3

1. Immediate response (reaching maximum in about 20 minutes) -> TYPE 1 HYPERSENSITIVITY

allergen & IgE antibodies = mast cells degranulation

• > histamine, tryptase, prostaglandin D2 and leukotriene
• > vascular perm, remodelling, airway remodelling ​

Late phase response (3 – 12 hours later) -> TYPE 4 HYPERSENSITIVITY

cell mediated, delayed, environmental infectious agents and self antigens

eosinophils, mast cells, lymphocytes, & neutrophils, which release mediators & cytokines, which cause airway inflammation. Macrophages

2.

Question 4

1. In the late phase which cell has the most effect. State its effect.
2. The air way inflammation causes reduced airway calibre (airway narrowing) due to: (5)
3. What would be seen on spirometry?
4. Describe the major precipitating factors for asthmatic attacks LO
   State Asthma Triggers

Answer 4

1. Eosinophils:
   - release Leukotriene C4 (bronchoconstriction)
2. Oedema (vascular leak - histamines)

Thickening of bronchial walls (infiltration of by inflammatory cells)

Mucous over production; thick, tenacious & slow moving -> usually unproductive cough

SM contraction

epithelium is shed and is incorporated into the thick mucus

3. Image
4. Allergens - pollen, animals (animal hair/dander), house dust mite faeces
5. Cold air
6. exercise
7. fumes - Car exhaust
8. cigarette smoke
9. perfumes
10. chemicals - Isocyanates and acid anhydrides (varnish/paint)
11. Drugs - NSAIDS and beta blockers emotional distress;

Question 5

1. How does it effect V/Q?
2. What is this type of respiratory failure?
3. Investigations for asthmatics?

Answer 5

1. Reduced ventilation (expiration)

V/Q < 1

2. Mild to moderate

Hyperventilation of better ventilated areas:

• cannot compensate for hypoxia
• can compensate for CO2 retention

Type 1 respiratory failure ​

Severe attacks

• extensive involvement of airways
• exhaustion (which limits respiratory effort)
• less CO2 removed -> increasing pCO2
• assisted ventilation

Question 6

Describe the typical clinical presentations of asthma including the symptoms reported by patients and their carers and signs on examination. LO

1. Increased probability that symptoms are due to asthma if:
2. Decreased probability that symptoms are due to asthma if:
3. Finding on examination & investigations
4. Wheezing is also found in other conditions, for example:

5.

Answer 6

1. • wheeze, shortness of breath, cough, chest tightness

- worse at night or in the early morning

- Symptoms vary over time and in intensity

• triggered by viral infections, exercise, allergen exposure, changes in weather,
  laughter, irritants such as car exhaust fumes, smoke, or strong smells

2. • Isolated cough

-Chronic production of sputum

• Shortness of breath associated with dizziness, light-headedness or peripheral tingling

- Chest pain

• Exercise-induced dyspnea with noisy inspiration (stridor)
  3. Auscultation: polyphonic wheeze on expiration

Percussion: hyper-resonant (More air)

PEFR:

Spirometry: scalloped - reversible with bronchodilator

FeNO Test

ABG?

4. - Respiratory infections

- COPD

(Upper airway dysfunction, Endobronchial obstruction, Inhaled foreign body)

5.

Question 7

Management/treatment LO

1. Treatment?
2. How does obstructive change the graph?
3. How does restructure disease change the graph?
4. Draw an asthmatics volume time curve

Answer 7

1. Check: adherence, inhaler technique, other co morbidities under control

SABA: salbutamol

Inhaled corticosteroid: budesonide, beclomethasone, fluticasone

LABA: Formoterol

Leukotriene Receptor Antagonists: Montelukast, Zafirlukast

Methylxanthines: theophylline, aminophylline (antagonise adenosine receptors)

LAMA (long acting anticholinergics): Tiotropium bromide (SPIRIVA)

Anti-IgE: Omalizumab ( preventing IgE binding to high affinity IgE receptor - no cross linking and activation of mast cells)

Anti-IL-5: Mepolizumab, Reslizumab

(Reduce peripheral blood and airway eosinophil numbers)

2. Airway narrowing
   difficulty in breathing out
   Increase in residual volume
   Decrease in vital capacity
3. Restrictive disease: problem in expanding lungs → less air inhaled → less available to exhale
   VC is also reduced
   IRV has decreased
4. Image

Question 8

1. Draw an asthmatics flow volume curve

Answer 8

Question 9

Describe in outline how to recognise and treat acute severe asthma and life threatening asthma. LO

Answer 9

Question 10

Life-threatening features LO (acute plus)

Answer 10

Question 11

Treatment for life threading asthma?

Answer 11

Question 12

Treatment of acute severe asthma

Answer 12

Question 13

1. Severity assessment of asthma
2. (1. What is asthma exacerbation?
3. Is it gradual or acute?
4. Often triggered by?
5. Other triggers:
6. Treatment)

Answer 13

1. Image
2. 1. Worsening of symptoms: cough, breathlessness, wheeze, chest tightness; some patients have chest pain
3. May be sudden onset or gradual
4. viral infection
5. allergen, pollution, chest infection
6. Symptoms not responding to usual inhalers
   • Need to assess severity

Question 14

1. What is the Aim of Asthma Management
2. What affects asthma control?

Answer 14

1. 1. Control
      – No daytime symptoms
      – No night-time awakening due to asthma
      – No need for rescue medication
      – No asthma attacks
      – No limitations on activity including exercise
      – Normal lung function (in practical terms FEV predicted or best) – Minimal side effects

SIMPLE
• Smoking Cessation
• Inhaler technique
• Monitoring
• Pharmacotherapy
• Lifestyle
• Education

2. Pharmacological Management
   Incorrect or suboptimal prescribing

Clinical factors

Environmental (triggers)
Medication (Beta blockers hypertension can cause bronchospams)

Co-existing condition

(anxiety, depression)

Behavioural Factors

Sub-optimal medication adherence
Poor inhaler technique
Smoking

Question 15

1. Define COPD LO
2. Causes of COPD? LO
3. What is alpha-1 antitrypsin?
4. Do all smokers get COPD?
5. Tests for COPD patients

Answer 15

1. airflow obstruction that is progressive and not fully reversible
2. • Smoking (in most cases) (90% of cases) (smoking can cause Alpha 1 antitrypsin deficiency)
     - Alpha-1-antitrypsin deficiency (less common)
     - Occupational exposure (eg coal dust)
     - Air pollution

Your SADO when you have COPD

3. Antiproteinase deficiency - less inhibition of elastase - breaks down elastin in alveoli - emphysema

4.

5. • The measurement of airflow obstruction -> spirometry FEV1 <80% predicted and FEV1/FVC ratio <70%
     - suggestive symptoms and signs together
     - CXR is not diagnostic in COPD but ismandatory to exclude other diagnoses
     - High-resolution computed tomography (HRCT) scanning provides a detailed assessment of the degree of macroscopic alveolar destruction in emphysema. This may be helpful if surgical intervention is contemplated or if the diagnosis is in doubt, but is not required for routine assessment of COPD.
     • Arterial Blood Gas to assess for respiratory failure
     • Alpha-1-antitrypsin blood test for younger patients

Question 16

Describe the pathophysiology of COPD including the causes and nature of air flow obstruction in COPD LO

1. COPD is an umbrella term for both:
2. Describe the pathological changes in emphysema
3. What is this image showing?

Answer 16

1. • Emphysema - Chronic Bronchitis

(Barrel chest -> incomplete expiration -> due to loss of elastin -> loss of balance of elastic forces of the chest wall, favouring outward expansion & elasticity and surface tension of the lung, favouring a smaller lung volume)

2. Emphysema:
   - Destruction of terminal bronchioles & distal airspaces

- Loss of alveolar SA (loss of elastin)

• Large redundant spaces -> bullae
• Destruction of the supporting tissue -> small airways collapse during expiration when the pressure outside the airways rises

Loss of elastic tissues -> hyperinflation because the lungs are unable to resist the natural tendency of the rib cage to expand outwards.

3. bullae -> alveolar combine/coalesce

Question 17

1. What are the pathological changes in chronic bronchitis
2. Difference between emphysema and bronchitis?
3. What is the MRC Dyspnoea Score. Describe it.

Answer 17

1. • Proliferation of mucus secreting cells due to inflammation (often due to smoke) –> chronic mucus hypersecretion

- chronic productive cough

• respiratory infections ( persists even after smoking has stopped)
• inflamed airways & mucus narrow the airways -> air way remodelling
• obstruction
  2. Image

3. Grade of breathlessness related to activities:
4. Not troubled by breathlessness except on strenuous exercise
5. Short of breath when hurrying or walking up a slight hill
6. Walks slower than contemporaries on level ground because of breathlessness, or has to stop for
   breath when walking at own pace
7. Stops for breath after walking about 100m or after a few minutes on level ground
8. Too breathless to leave the house, or breathless when dressing or undressing

Question 18

1. What will the results be from a flow volume curve?

Answer 18

1. spirometry FEV1 <80% predicted and FEV1/FVC ratio <70%

Question 19

1. Why is it a problem with expiration
2. Draw a flow volume curve for a COPD patient
3. Why does the COPD curve in the graph look like this?
4. Simple staging systems are used to categorise the severity of COPD according to the reduction in
   FEV1.
   The NICE guidelines suggest the following:
   ● Mild airflow obstruction - FEV1 ?% predicted
   ● Moderate airflow obstruction - FEV1 ?% predicted
   ● Severe airflow obstruction - FEV1 % predicted

Answer 19

1. Airway collapse and inability of elastin to recoil
2. Image
3. Due to the time scale

We know it is NOT RESTRICTIVE because the tangent is below the predictive line/normal as FEV1 is less

In restrictive the start is steep as the FEV1 is the same!

4. 50–80
   30–49
   30

Question 20

Outline the treatment of COPD LO

1. How do we treat patients with Stable COPD?
2. What is salbutamol? How does it work? ß-2- agonist (e.g. Salbutamol) MOA

Answer 20

1. Other LAMAs licensed for COPD only:

• Aclidinium (twice daily)
• Umeclidinium
• Glycopyrronium

LABA/LAMA combinations licensed for COPD only:

• Tiotropium/Olodaterol
• Aclidinium/formoterol (twice daily)
• Umeclidinium/vilanterol
• Glycopyrronium/indacaterol

Drug Therapy
• Bronchodilators
• Steroids – Inhaled
• Antimuscarinics
• Mucolytics
• Methylxanthines

2. MOA : Ligand binds to receptor activating adenyl cyclase, increasing cAMP and activating

Protein Kinase (PKA), leading to phosphorylation of downstream targets (Myosin light chain kinase - MLCK) leading to: relaxation of smooth muscle in 
airway → bronchodilation

Question 21

ß-2 agonists (e.g. Salbutamol) Adverse Effects:

Answer 21

• Tachycardia (atrial ß-2 receptors)
• Tremor (skeletal ß-2 receptors)
• Anxiety
• Palpitations
• Hypokalaemia (skeletal muscle uptake K+)

​

Question 22

Generally, if on less than 800mcg inhaled steroid/day, unlikely to get significant systemic effects If above this dose or oral steroids:

Q. Why do we have pulmonary rehabilitation?
A. Many patients with COPD avoid exercise and physical activity because of breathlessness resulting
in Deconditioning -> increasing social isolation and inactivity leading to worsening of symptoms
Pulmonary Rehabilitation aims to break this cycle of Deconditioning
– a 6-12 week MDT programme of supervised exercise, unsupervised home
exercise, nutritional advice, and disease education
Q. Long Term Oxygen Therapy (LTOT)
• Extended periods of hypoxia cause renal and cardiac damage – can be prevented by LTOT
• Continuous oxygen therapy for most of the day – at least 16 hours/day for a survival benefit
• LTOT offered if pO2 consistently below 7.3 kPa, or below 8 kPa with cor pulmonale
• Patients must be non-smokers and not retain high levels of CO
• Safety – Home Fire Risk Assessment
Q. What surgical options are available and who are they offered to?
A. • Lung Volume Reduction - The reduction of hyperinflation is the principal aim of surgical
techniques in the treatment of appropriately selected COPD patients
• Lung Transplant may be an option for younger patients

Answer 22

A. - skin atrophy

• cataracts/ Cushing’s/
• avascular necrosis
• peptic ulcers
• hypertension
• osteoporosis
• increased infections/ impair growth

Question 23

Cystic fibrosis LO

1. Pathophysiology
2. How to diagnose
3. CF Presentations – main ways

Answer 23

1. Autosomal recessive, chromosome 7 CFTR
2. Image
3. Meconium ileus: newborn CF infants the bowel is blocked by sticky secretions - bilious vomiting, abdominal distension & delay in passing meconium.

Intestinal malabsorption: > 90% of CF individuals, evident in infancy -> failure to thrive - deficiency of pancreatic enzymes (acute pancreatitis)

3. Chest infections - pseudomonas, haemophilus influenza,
4. Newborn screening

Question 24

Describe, in outline, the pathophysiology, clinical features and principles of treatment of
bronchiectasis LO

1. Definition?
2. Investigations and why?
3. Symptoms

Answer 24

1. • chronic dilatation of bronchi
     - poor mucusm clearance
     - recurrent bacterial infection
2. CT (specifically High Resolution CT) - bronchial dilatation bigger than the adjacent blood vessel, bronchial wall thickening

Signet Ring Sign

3. Very Common:

• Chronic cough

• Daily sputum production – can vary in quantity, colour and consistency (differentiate from COPD)

Common:

• Breathlessness on exertion
• Intermittent haemoptysis
• Nasal symptoms
• Chest Pain
• Fatigue Less Common:
• Wheeze

Question 25

1. Bronchiectasis causes
2. Management?

Answer 25

1. Haemophilus influenza - a Gram-negative, coccobacillary -> pneumonia
2. • stopping smoking (if you smoke)
     - having the flu vaccine every year -> pneumococcal vaccine to protect against pneumonia
     - physiotherapy /airways clearance
     - exclude autoimmunity
     - Pulmonary Rehabilitation if MRC dyspnoea score > 3

(• Patient labelled as “asthma” without any great objective evidence, particularly lifelong

• History of severe chest infection earlier in life (bacterial, viral or atypical)
• Lifelong chest infections ?genetic cause
• Nasal and ear symptoms or admitted to SCBU at birth
• Recurrent chest infections ?immunodeficiency
• Sputum culture positive for common organisms such as haemophilus or pseudomonas
• Inflammatory bowel disease, rheumatoid arthritis)

Question 26

1. CF Complications
2. CF Lifestyle advice

Answer 26

1. Image
2. • influenza vaccination

• No smoking

• Avoid other CF patients

• Avoid friends / relatives with colds / infections
• Avoid jacuzzis (pseudomonas)

REPLACE PANCREATIC ENZYMES