Asthma and Severe Asthma — Viva

The scenario

A 49-year-old female veterinary nurse is referred to your severe asthma service. She has asthma since childhood, now with four to six exacerbations per year, two hospital admissions in the last 18 months (one to ICU), and daily symptoms despite high-dose budesonide-formoterol (MART), tiotropium, and maintenance prednisolone 10 mg daily. She has chronic rhinosinusitis with nasal polyps (two prior surgeries), allergic rhinitis, BMI 34, osteoporosis (T-score -2.9), and hypertension. Never-smoker. Bloods: eosinophils 520/microL, total IgE 310 IU/mL, FeNO 65 ppb. Spirometry: FEV1 64% predicted, fully reversible. Pharmacy data confirms adherence; technique is good on observation. [1]

Part A — Candidate opening statement (SASPOP)

Examiner: "Please present this patient." [1]

Candidate model answer: [1]

"This is Mrs K, a 49-year-old female veterinary nurse presenting with severe eosinophilic asthma. Her main problems are: (1) severe T2-high asthma uncontrolled despite high-dose inhaled corticosteroid-formoterol as MART, a long-acting muscarinic antagonist, and maintenance oral prednisolone; (2) chronic oral corticosteroid toxicity with established osteoporosis; (3) chronic rhinosinusitis with nasal polyps and allergic rhinitis; (4) obesity; and (5) hypertension. She is a never-smoker with confirmed adherence and correct technique. Her phenotype — eosinophils 520, FeNO 65, total IgE 310 on maximal therapy — defines her as T2-high and a candidate for biologic escalation. My integrated plan is to start dupilumab for its dual exacerbation-reduction and oral-steroid-sparing benefit and its effect on nasal polyps, to taper her prednisolone with bone protection, and to address her obesity and occupational exposures." [1]

Part B — Probing questions and model answers

Q1. "How do you know this is truly severe asthma and not difficult-to-treat asthma?"

"Before labelling her severe I confirmed four things. First, the diagnosis — she has variable airflow limitation with full reversibility on spirometry, so asthma is confirmed; I excluded COPD (never-smoker, fully reversible) and allergic bronchopulmonary aspergillosis (total IgE 310 is well below the ABPA threshold of above 1000, though I would send Aspergillus-specific IgE to be thorough). Second, adherence — pharmacy refill data shows full adherence and her technique is good on direct observation. Third, I addressed the raised FeNO: a high FeNO on high-dose ICS normally suggests non-adherence, but here adherence is objectively confirmed, so the high FeNO reflects active T2 inflammation despite therapy — consistent with true severe T2-high disease. Fourth, I treated her comorbidities — rhinitis, nasal polyps and obesity are already being addressed. Having excluded the modifiable causes of poor control, she meets the ERS/ATS 2014 definition of severe asthma." [1]

Q2. "Walk me through your biologic reasoning. Why dupilumab over an anti-IL-5 or omalizumab?"

"Her phenotype is T2-high with three converging signals: blood eosinophils above 300, FeNO above 50, and total IgE elevated with sensitisation. Three factors drive the choice. First, she is oral-steroid-dependent, and I want to stop the prednisolone to halt her osteoporosis — both dupilumab (VENTURE, Rabe 2018) and benralizumab (ZONDA) have oral-steroid-sparing evidence, while omalizumab and mepolizumab have weaker or absent steroid-sparing data. Second, she has chronic rhinosinusitis with nasal polyps, a Type 2 comorbidity that dupilumab is licensed to treat — an anti-IL-5 will not help her sinuses. Third, dupilumab blocks the IL-4 receptor alpha, inhibiting both IL-4 and IL-13, so it targets both the eosinophil arm (IL-5-driven) and the FeNO/mucus arm (IL-13-driven) of T2 inflammation; QUEST showed exacerbation reduction and FEV1 improvement across the T2-high population. So dupilumab gives me exacerbation control, steroid sparing, and sinus benefit in one drug. An anti-IL-5 like mepolizumab (MENSA) or benralizumab would be a reasonable second choice if dupilumab were contraindicated or unavailable; omalizumab is reserved for a purely allergic phenotype within the IgE/weight dosing window and is less compelling here." [1]

Q3. "She has been on prednisolone 10 mg daily for three years. How will you taper it?" [1]

"I will NOT stop it abruptly — she has hypothalamic-pituitary-adrenal axis suppression from three years of continuous prednisolone. My plan is to start dupilumab, allow 3-4 months to establish a response (defined as at least a 50% reduction in exacerbation rate and a fall in FeNO and eosinophils), then begin a slow taper: reduce by 1 mg every 2-4 weeks once stable, monitoring for adrenal insufficiency (fatigue, postural symptoms, nausea). For a prolonged course like hers I would involve endocrinology and consider a short synacthen test to assess adrenal recovery before completing the taper. Throughout, I maintain bone protection — calcium and vitamin D, a DEXA to monitor, and a bisphosphonate given her T-score of -2.9 — and screen for steroid-induced diabetes with an HbA1c. She should carry a steroid card and know to double the dose during severe illness until her adrenal axis recovers." [1]

Q4. "What is your occupational assessment, and could her work be driving this?"

"As a veterinary nurse she is exposed to animal dander, saliva and latex — all recognised causes of occupational asthma and sustained T2 sensitisation. I would take a detailed exposure history, send specific IgE to relevant animal allergens (cat, dog, horse dander) and latex, and arrange serial peak expiratory flow monitoring at and away from work for at least 2 weeks to look for work-related variability. If occupational asthma is confirmed, allergen avoidance — workplace modification, respiratory protective equipment, or in some cases a change of role — can be the single most effective intervention and may dramatically reduce her exacerbation rate. I would involve an occupational physician." [1]

Q5. "How will you monitor the biologic and decide whether to continue it?"

"I trial the biologic for 3-4 months. At each visit I record the exacerbation rate, oral corticosteroid dose, FEV1, ACQ-5 and AQLQ scores, and the eosinophil and FeNO trend. A clinically meaningful response is at least a 50% reduction in exacerbations and/or a successful prednisolone taper with improved quality of life. If she responds, I continue and taper the steroid. If there is no response after 4 doses, I withdraw the biologic and reconsider — in particular I re-examine whether she might have a non-T2 component, persistent exposure (occupational or untreated rhinitis), or an alternative diagnosis. I do not continue an ineffective biologic indefinitely." [1]

Q6. "She has a severe asthma attack while on dupilumab. Does the biologic change your acute management?"

"No. The acute severe asthma algorithm is unchanged by background biologic therapy. I grade severity, give high-flow oxygen to target SpO2 93-95%, nebulised salbutamol 5 mg with ipratropium 500 mcg driven by oxygen (repeated), systemic corticosteroid early (prednisolone 40-50 mg orally or hydrocortisone 100 mg IV), and IV magnesium sulfate 2 g over 20 minutes if she is not responding. The biologic is a preventive, not a rescue, therapy. The one consideration is that she is on maintenance prednisolone and may have adrenal suppression, so during a severe physiological stress I would give a stress-dose hydrocortisone (e.g. 100 mg IV) rather than rely on her oral prednisolone." [1]

Part C — Short-case discussion: the respiratory examination in asthma

Examiner: "You are asked to examine the respiratory system of a 26-year-old woman with known asthma in the short-case station. Talk me through what you are looking for and what you might find." [1]

Candidate model answer: [1]

"I begin at the end of the bed: is she distressed, using accessory muscles, able to speak in full sentences? In a well-controlled asthmatic the examination is frequently NORMAL — and I would state that explicitly, because the absence of signs is itself an important finding. I look for atopic stigmata — eczema, allergic shiners, a transverse nasal crease and nasal speech suggesting allergic rhinitis or polyps. On the hands I check for clubbing (its absence supports asthma; its presence argues for bronchiectasis or alternative diagnosis) and cyanosis. I assess the pulse and respiratory rate, and look for the paradoxical (in-drawing) abdominal movement of fatiguing respiratory muscles.

On chest inspection I look for hyperinflation and symmetrical movement. Percussion is resonant (dullness suggests consolidation or effusion). Auscultation may reveal expiratory polyphonic wheeze — but a silent chest in a breathless patient is a life-threatening sign, indicating airflow too low to generate wheeze. I listen for the inspiratory-to-expiratory ratio (prolonged expiration in obstruction). I complete the examination by checking for features of severity — pulsus paradoxus, ability to count to ten in one breath, and SpO2 — and I would offer to perform a peak flow measurement." [1]

Examiner: "She has expiratory wheeze but is otherwise well. What is your differential for wheeze?" [1]

"Wheeze is a musical sound from narrowed airways. The differentials are asthma (variable, reversible, with atopy), COPD (older smoker, partially reversible), bronchiectasis (chronic productive cough, clubbing), cardiac failure ('cardiac asthma' from pulmonary oedema — look for raised JVP, basal crackles, S3), pulmonary embolism (sudden dyspnoea, pleuritic pain), vocal cord dysfunction (stridorous inspiratory noise, normal spirometry and FeNO, laryngeal tightness), anaphylaxis (acute, urticaria, hypotension), and in a child, foreign body aspiration. The keys to discrimination are the history (variability, triggers, reversibility), spirometry with bronchodilator response, FeNO, and the chest X-ray." [1]

Part D — Examiner's high-yield traps

"The candidate who tells me SABA monotherapy is acceptable for mild asthma fails. GINA abolished it in 2019 — the answer is as-needed low-dose ICS-formoterol." [1]

"The candidate who reaches for a biologic before confirming adherence, technique and comorbidity control has misdiagnosed 'severe' asthma. The workup comes first." [1]

"The candidate who is reassured by a 'normal' PaCO2 in a tachypnoeic asthmatic does not understand ventilatory failure. A normal CO2 at RR 30 is abnormal and life-threatening." [1]

"The candidate who cannot name the intubation criteria — rising CO2, exhaustion, silent chest, bradycardia, altered consciousness — is not safe to manage an acute severe attack." [1]