Airways Disease

Question 1

A 35-old patient with IgE-mediated asthma is poorly controlled on maximal dose inhaled therapy and has required 5 courses of oral steroids in the last year.

Which of the following medications would be indicated?

A Benralizumab (Fasenra)
B Dupilumab (Dupixent)
C Mepolizumab (Nucala)
D Omalizumab (Xolair)
E Resulizumab (Cinqaero)

Answer 1

D Omalizumab (Xolair)

Licensed for IgE mediated asthma. The others are licensed for eosinophilic asthma with the exception of dupilumab (Dupixent) which is licensed for allergic asthma with eosinophils >0.15 and no IgE indication.

Question 2

A 35-old patient with asthma which is poorly controlled on maximal dose inhaled therapy and has required 4 courses of oral steroids in the last year.

Eosinophil count 0.34

Which of the following medications should be commenced?

A Benralizumab (Fasenra)
B Mepolizumab (Nucala)
C Montelukast
D Omalizumab (Xolair)
E Theophylline

Answer 2

A Benralizumab (Fasenra)

Both benralizumab and mepolizumab could be offered here but benralizumab is more cost-effective.

Question 3

A patient with severe asthma is commenced on Omalizumab (Xolair).

Which best describes the mechanism of action of this drug?

A Anti IL-5 monoclonal antibody which reduces circulating eosinophils
B Binds to subunit of IL-4 receptor blocking IL-4 and IL-13 signalling
C Monoclonal antibody that binds to IgE
D Monoclonal antibody targeting IL-6 receptors
E Tumor necrosis factor (TNF)-alpha inhibitor

Answer 3

C Monoclonal antibody that binds to IgE

Anti IL-5 monoclonal antibody which reduces circulating eosinophils describes the action of mepolizumab, resulizumab and benralizumab

Binds to subunit of IL-4 receptor blocking IL-4 and IL-13 signalling describes the action of dupilumab.

Monoclonal antibody targeting IL-6 receptors describes the action of tocilizumab and sarulimab in treatment of COVID-19.

Tumor necrosis factor (TNF)-alpha inhibitors e.g. infliximab, etanercept and adalimumab are used in autoimmune conditions.

Question 4

Indication for Omalizumab (Xolair)

Answer 4

Severe persistent allergic IgE mediated asthma

Question 5

Clinical criteria for Omalizumab (Xolair)

Answer 5

IgE 30-1500

Positive skin test or in vitro reactivity to a perennial aeroallergen

FEV1 <80%

Frequent day symptoms or night waking

Frequent exacerbations despite daily high dose ICS+LABA

More than 4 courses of oral steroids in a year

Question 6

Mechanism of action of Mepolizumab (Nucala)

Answer 6

Anti IL-5 monoclonal antibody which reduces circulating eosinophils

Question 7

Clinical criteria for Mepolizumab (Nucala)

Answer 7

Blood eosinophils >0.30 in last 12 months

Optimised asthma management

4 or more exacerbations requiring systemic steroids in last 12 months or equivalent 5mg pred per day for 6 months

Question 8

Indication for Mepolizumab (Nucala)

Answer 8

Severe refractory eosinophilic asthma in adults

Question 9

A 25 year-old presents with intermittent shortness of breath and wheeze

She has a history of eczema and hayfever.

What is the most likely diagnosis?

A Allergic asthma
B Eosinophilic asthma
C Eosinophilic granulomatosis with polyangiitis
D Exercise-induced asthma
E Intermittent laryngeal obstruction

Question 10

Indication for Benralizumab (Fasenra)

Answer 10

Severe eosinophilic asthma inadequately controlled despite high dose maintenance ICS-LABA

Question 11

Mechanism of action of Benralizumab (Fasenra)

Answer 11

Anti IL-5 receptor monoclonal antibody which reduces circulating eosinophils

Question 12

Side effects of mAbs targeting eosinophils

Answer 12

Hypersensitivity reactions inc. anaphylaxis, skin reactions, fever, headache, nasal congestion, abdominal pain, back pain, eczema

Question 13

How to assess response to mAbs

Answer 13

Adequate response is clinically meaningful reduction in severe exacerbations needed OCS (~50% fewer) or

Clinically significant reduction in maintenance OCS use while maintaining or improving asthma control

Assess yearly and if no adequate response to treatment - stop, can continue if adequate response

Question 14

Mechanism of action of Dupilumab (Dupixent)

Answer 14

Severe asthma not controlled by high dose ICS plus another drug due to type 2 inflammation

Question 15

Clinical criteria for Dupilumab (Dupixent)

Answer 15

Blood eosinophil count of >0.15

FeNO of >20 parts

Sputum eosinophils of 2% or more

Asthma that is clinically allergen driven

The need for maintenance oral corticosteroids

(nb. also licensed for moderate to severe atopic dermatitis)

Question 16

A patient with severe asthma is commenced on Benralizumab (Fasenra).

Which best describes the mechanism of action of this drug?

A Anti IL-5 monoclonal antibody which reduces circulating eosinophils
B Binds to subunit of IL-4 receptor blocking IL-4 and IL-13 signalling
C Monoclonal antibody that binds to IgE
D Monoclonal antibody targeting IL-6 receptors
E Tumor necrosis factor (TNF)-alpha inhibitor

Answer 16

A Anti IL-5 monoclonal antibody which reduces circulating eosinophils. NB this is also the mechanism of action of mepolizumab and resilumumab.

Monoclonal antibody that binds to IgE describes the action of omalizumab.

Binds to subunit of IL-4 receptor blocking IL-4 and IL-13 signalling describes the action of dupilumab.

Monoclonal antibody targeting IL-6 receptors describes the action of tocilizumab and sarulimab in treatment of COVID-19.

Tumor necrosis factor (TNF)-alpha inhibitors e.g. infliximab, etanercept and adalimumab are used in autoimmune conditions.

Question 17

A patient with severe asthma is commenced on dupilumab (Dupixent).

Which best describes the mechanism of action of this drug?

A Anti IL-5 monoclonal antibody which reduces circulating eosinophils
B Binds to subunit of IL-4 receptor blocking IL-4 and IL-13 signalling
C Monoclonal antibody that binds to IgE
D Monoclonal antibody targeting IL-6 receptors
E Tumor necrosis factor (TNF)-alpha inhibitor

Answer 17

B Binds to subunit of IL-4 receptor blocking IL-4 and IL-13 signalling

Question 18

A 22-year-old with asthma complains of intermittent breathlessness. She has persistent nasal discharge and frequent bouts of sinusitis.

Eosinophils are 0.44. IgE is normal.

What is the most likely diagnosis?

A Allergic asthma
B Eosinophilic asthma
C Eosinophilic granulomatosis with polyangiitis
D Exercise-induced asthma
E Intermittent laryngeal obstruction

Answer 18

B Eosinophilic asthma

Question 19

A 38-year-old male presents with worsening asthma not controlled on high-dose inhaled steroids. It was diagnosed aged 30 and he also has a history of rhinitis and nasal polyps.

Eosinophils are 1.25. pANCA is negative.

What is the most likely diagnosis?

A Allergic asthma
B Eosinophilic asthma
C Eosinophilic granulomatosis with polyangiitis
D Exercise-induced asthma
E Intermittent laryngeal obstruction

Answer 19

C Eosinophilic granulomatosis with polyangiitis

NB pANCA is only positive in 35-75% of cases. Clinical features here are typical. Blood eosinophils >10%.

Question 20

A 24-year-old student presents with frequent bouts of sudden onset wheeze following a suspected chest infection a few weeks prior.

Bloods are normal.

What is the most likely diagnosis?

A Allergic asthma
B Eosinophilic asthma
C Exercise-induced asthma
D Intermittent laryngeal obstruction
E Viral-induced wheeze

Answer 20

D Intermittent laryngeal obstruction

Question 21

A 54 year old man attends your clinic with a 6-month history of dry cough and worsening exertional dyspnoea. He is a smoker with a history of longstanding rheumatoid arthritis (RA), not currently on treatment. Pulmonary function testing demonstrates forced expiratory volume in 1 second (FEV 1) 40% predicted, forced vital capacity (FVC) 35% predicted, FEV 1:FVC ratio 75%, total lung capacity (TLC) 42% predicted, and transfer factor corrected for alveolar volume (KCO) 15% predicted.

Which of the following would be consistent with these findings?

A Caplan’s syndrome
B Pulmonary arterial hypertension
C Rheumatoid arthritis-associated interstitial lung disease (RA-ILD)
D Rheumatoid arthritis-associated pleural effusion
E Shrinking lung syndrome

Answer 21

C RA-ILD

The combination of restrictive spirometry with reduced lung volumes and transfer factor suggest a pulmonary parenchymal pathology. In this scenario, RA-ILD is the most likely diagnosis. ILD is the most common pulmonary manifestation of RA and may onset before joint symptoms.
Prevalence is up to 40 % with peak age 50–60 years, males > females. RA-associated lung disease may also manifest as rheumatoid nodules (solitary or multiple, can cavitate), pleural effusions (exudative, pH <7.2, glucose <1.6, LDH > 700, raised cholesterol), pneumothoraces, and rarely
bronchiectasis and bronchiolitis obliterans. RA-ILD may mimic IPF (UIP) or NSIP. Treatment with anti-infl ammatory agents (prednisone) and immunomodulators (azathioprine/cyclophosphamide) is recommended. Avoid anti-TNF agents (cause accelerated death from ILD) and methotrexate. Caplan’s syndrome, the combination of pneumoconiosis with rheumatoid factor positivity, is associated with exposure to mining dust. Shrinking lung syndrome is associated with SLE, the features being reduced lung volumes due to diaphragmatic weakness but preserved KCO. Pulmonary arterial hypertension typically manifests as an isolated reduction in TLCO/KCO.

Question 22

A 53 year old woman presents with an 8-week history of cough, fever, and sweats. Her blood eosinophil count is 1.0 ×10 9 /L (normal range 0.0–0.4 × 10 9 /L), immunoglobulin E (IgE) is normal. CXR shows bilateral peripheral dense opacifi cation with an inverse pulmonary oedema appearance. Sputum eosinophil count is mildly elevated.

What is the most likely diagnosis?

A Acute eosinophilic pneumonia
B Chronic eosinophilic pneumonia
C Churg–Strauss syndrome
D Hypereosinophilic syndrome
E Loeffler’s syndrome (simple pulmonary eosinophilia)