Asthma and Severe Asthma — DCE Clinical Case

LONG CASE

Patient brief (provided to candidate)

Mr D is a 52-year-old male carpenter referred for assessment after his third hospital admission for asthma in 12 months, the most recent requiring 48 hours in a high-dependency unit. He has had asthma since age 14. He is currently prescribed high-dose budesonide-formoterol as MART (maintenance and reliever therapy), tiotropium, and prednisolone 7.5 mg daily. He reports daily symptoms, nocturnal waking two to three times per week, and uses his reliever inhaler four to six times daily. He had three courses of oral prednisolone in the last six months for exacerbations, triggered mainly by viral colds. ^[1]

Past history: allergic rhinitis, chronic rhinosinusitis with nasal polyps (one polypectomy 3 years ago), osteoporosis (T-score -2.6 at lumbar spine, on alendronate), hypertension, diet-controlled type 2 diabetes (HbA1c 49 mmol/mol). He smoked 10 pack-years, quit 15 years ago. BMI 31. Family history of atopy (mother asthma, daughter eczema). He keeps a cat at home. ^[1]

Medications: budesonide-formoterol 200/6 (MART), tiotropium 5 mcg daily via Respimat (two 2.5 mcg puffs), prednisolone 7.5 mg daily, alendronate 70 mg weekly, perindopril 5 mg daily, intranasal mometasone, salbutamol PRN. ^{[1] [6]}

Examination: comfortable at rest, able to speak in full sentences. HR 92, BP 142/88, RR 18, SpO2 96% room air. Chest: bilateral expiratory wheeze, no accessory muscle use, no cyanosis. No clubbing. Nose: evidence of prior surgery, nasal airflow reduced. ^[1]

Investigations: FEV1 2.6 L (71% predicted), FVC 4.0 L, FEV1/FVC 0.65, 18% and 320 mL reversibility. Blood eosinophils 480/microL, total IgE 280 IU/mL, FeNO 60 ppb. CXR: hyperinflation, no focal lesion. Inhaler technique observed to be correct; pharmacy refill data confirms adherence. ^[1]

Candidate opening statement (SASPOP)

"This is Mr D, a 52-year-old male carpenter with a lifelong history of asthma presenting with severe, uncontrolled disease: frequent exacerbations requiring repeated hospital admission and oral corticosteroids despite high-dose inhaled corticosteroid-formoterol as MART, tiotropium, and maintenance oral prednisolone. His symptoms are daily wheeze, nocturnal waking, and frequent reliever use. He has a cluster of Type 2 comorbidities — allergic rhinitis, nasal polyps, atopy — and steroid toxicity with established osteoporosis. He is a former smoker. His phenotype is T2-high eosinophilic asthma (eosinophils 480, FeNO 60, IgE 280 on maximal therapy) with confirmed adherence and correct technique. My priorities are to confirm he has true severe asthma, to escalate to a biologic — I favour dupilumab for its exacerbation-reduction, oral-steroid-sparing and nasal-polyp benefits — to taper his prednisolone with bone and metabolic protection, and to address his environmental exposures." ^[1]

Structured problem list

1. Severe T2-high eosinophilic asthma, uncontrolled on high-dose ICS-LABA (MART) + LAMA + maintenance OCS — recurrent exacerbations, hospital admissions, nocturnal symptoms, frequent reliever use.
2. Chronic oral corticosteroid therapy with established osteoporosis (T-score -2.6) — steroid-sparing strategy and bone protection required.
3. Chronic rhinosinusitis with nasal polyps and allergic rhinitis — Type 2 upper-airway comorbidity; prior polypectomy.
4. Type 2 diabetes (HbA1c 49) — exacerbated by corticosteroids.
5. Hypertension — on perindopril.
6. Obesity (BMI 31) — contributes to inflammation and steroid resistance.
7. Environmental exposures — cat at home (animal dander allergen), former smoker (10 pack-years). ^[1]

Integrated management plan

1. Confirm severe asthma and exclude mimics (defence of the diagnosis):

• Asthma confirmed by variable airflow limitation (18%, 320 mL reversibility).
• Asthma-COPD overlap excluded: former light smoker (10 pack-years), fully reversible obstruction, T2-high phenotype — overlap is not the primary picture.
• Allergic bronchopulmonary aspergillosis: total IgE 280 is below the ABPA threshold (typically above 1000 IU/mL); send Aspergillus-specific IgE and precipitins to exclude, given refractory disease.
• Adherence and technique confirmed (pharmacy refill data + observed technique); high FeNO on high-dose ICS here reflects active T2 inflammation despite therapy (not non-adherence, which is objectively excluded). ^[1]

2. Biologic escalation — start dupilumab:

• Rationale: T2-high phenotype (eosinophils at least 300, FeNO at least 50) + oral-steroid-dependent + nasal polyps. Dupilumab (anti-IL-4 receptor alpha, 300 mg SC every 2 weeks after a loading dose) offers exacerbation reduction (QUEST) ^[2], oral-steroid-sparing (VENTURE) ^[3], and treatment of nasal polyps — addressing his three biggest problems in one agent.
• Alternative considered: an anti-IL-5 pathway agent (mepolizumab 100 mg SC every 4 weeks — exacerbation reduction shown in MENSA ^[4] — or benralizumab 30 mg SC at weeks 0, 4 then every 8 weeks), but neither treats nasal polyps as a primary indication. Omalizumab is anti-IgE and appropriate for allergic asthma but is less consistently steroid-sparing.
• Trial for 3-4 months; define response as at least 50% reduction in exacerbations and/or successful prednisolone taper with improved ACQ-5/AQLQ. ^[1]

3. Oral corticosteroid taper and steroid-toxicity management:

• Do NOT stop abruptly — he has HPA axis suppression from long-term prednisolone. Taper by 1 mg every 2-4 weeks once the biologic response is established; involve endocrinology and consider a short synacthen test before completing the taper.
• Bone protection: continue alendronate and calcium/vitamin D; repeat DEXA to monitor; reassure that steroid tapering is the most effective bone intervention.
• Screen: HbA1c (diabetes already present — optimize), blood pressure, ophthalmic review (cataract risk), and consider bone and skin surveillance with very long courses. ^[1]

4. Comorbidity management:

• Nasal polyps/rhinitis: continue intranasal mometasone and saline; dupilumab will address polyps; ENT input if obstructive symptoms persist.
• Diabetes and hypertension: monitor and optimize; the corticosteroid taper will improve both.
• Obesity: weight-management referral; reinforce that weight loss improves both inflammation and steroid responsiveness. ^[1]

5. Environmental exposure reduction:

• Cat at home: advise on allergen reduction (bedroom exclusion, HEPA filtration); consider specific IgE to cat dander; in severe allergic disease, omalizumab (if dupilumab fails) or allergen immunotherapy (selected cases) may be considered.
• Smoking: reinforce ex-smoker status; avoid second-hand smoke. ^[1]

6. Acute-care preparedness, action plan, and follow-up:

• Written asthma action plan with traffic-light zones (green: maintenance; yellow: increase reliever, start oral prednisolone 40-50 mg at PEF 50-80% of best; red: call ambulance at PEF below 50% or life-threatening features).
• Oral corticosteroid starter pack at home.
• Asthma education: reinforce the danger of overusing reliever (more than two canisters per year predicts severe attacks); teach PEF self-monitoring (give him a peak flow meter; his best is recorded).
• Follow-up: severe asthma service for biologic administration and 3-4 monthly review; primary care review within 2 weeks of discharge. ^[1]

Probing questions and model answers

Q: "How do you interpret his FeNO of 60 ppb on high-dose ICS given confirmed adherence?"

"A high FeNO normally signals non-adherence with ICS, because ICS suppresses IL-13-driven FeNO within days. Here adherence is objectively confirmed by pharmacy refill data and his technique is correct, so the persistently high FeNO reflects ACTIVE Type 2 inflammation despite maximal inhaled therapy — it confirms he has true severe T2-high asthma that has outstripped conventional therapy, and it strengthens the case for a biologic rather than signalling a behaviour problem." ^[1]

Q: "He is a former smoker. Does this change your phenotype or your biologic choice?"

"It raises asthma-COPD overlap as a consideration, but the picture is predominantly T2-high asthma: fully reversible obstruction, eosinophils and FeNO markedly elevated, atopy, and a relatively modest (10 pack-year) smoking history. Smoking does reduce the response to ICS and biases towards a neutrophilic phenotype, but his biomarkers are squarely T2-high, so my biologic reasoning is unchanged. I would monitor his FEV1 trend over time for an emerging fixed component, and if overlap develops I would add GOLD-style bronchodilation reasoning to his care." ^[1]

Q: "He presents acutely during your clinic wait. Walk me through your immediate actions if he has PEF 35% of best, RR 30, SpO2 91%, and cannot complete sentences."

"He has an acute severe attack with a life-threatening feature (SpO2 below 92%). I would manage him in a high-acuity area with continuous monitoring, take an ABG to assess PaCO2, and give: high-flow oxygen to target SpO2 94-98%; nebulised salbutamol 5 mg with ipratropium 500 mcg driven by oxygen, repeated every 15-20 minutes for the first hour; systemic corticosteroid early (hydrocortisone 100 mg IV, with a stress-dose given his maintenance prednisolone and likely adrenal suppression). If he has not responded after the first hour, I give IV magnesium sulfate 2 g over 20 minutes (Cochrane Kew 2014: 25% admission reduction). ^[5] I would escalate to ICU if he develops a rising PaCO2, exhaustion, a silent chest, bradycardia, or altered consciousness — these are intubation criteria. Ketamine is my induction agent of choice; I ventilate slowly with a long expiratory time to avoid breath-stacking." ^[1]