GRAND ROUNDS REVIEW

Asthma Phenotypes and Management:

A Precision Medicine Approach for the Practising Clinician

Dr Neeraj Manikath , claude.ai

I. Clinical Introduction

🏥 Clinical Vignette

The patient: A 34-year-old secondary school teacher presents to your respiratory clinic with a three-year history of recurrent breathlessness and wheeze. She has been on high-dose inhaled fluticasone-salmeterol for 18 months with minimal benefit. She has used her salbutamol inhaler up to eight times a day. She has had four courses of oral prednisolone in the past year. Blood tests reveal a peripheral eosinophil count of 680 cells/µL. Skin prick tests are negative. Her spirometry shows post-bronchodilator FEV1/FVC of 0.65 with 18% reversibility. Her FENO is 68 ppb.

The junior registrar increases her ICS dose. You pause. You know this patient does not simply need more of the same — she needs a fundamentally different approach.

Asthma affects over 350 million people globally, making it the most common chronic inflammatory airway disease in the world. Yet for all its prevalence, asthma remains profoundly misunderstood — not as a single disease, but as a clinical syndrome of remarkable heterogeneity. The one-size-fits-all approach that dominated asthma management for three decades is being replaced, rightly, by a precision medicine framework built around disease phenotypes and endotypes.

The stakes are high. Approximately 5–10% of patients have severe or difficult-to-treat asthma, yet this group accounts for over 50% of total asthma costs and the vast majority of asthma deaths. More troublingly, many of these patients are trapped in a cycle of escalating corticosteroids — accumulating significant steroid-related morbidity — when targeted biological therapies could transform their disease course.

This review is designed to equip you with the conceptual framework and practical tools to phenotype your patient at the bedside, choose investigations wisely, escalate therapy with precision, and know exactly when to reach for biologics — and which one.

II. Pathophysiology — The Clinically Relevant Framework

Modern asthma biology has converged on a central axis: the distinction between Type 2 (T2)-high and non-Type 2 (non-T2) asthma. This distinction is not academic — it is the single most therapeutically important dichotomy in asthma care today.

The T2 Inflammatory Cascade

In T2-high asthma, innate lymphoid cells type 2 (ILC2s) and CD4+ Th2 cells are activated by airway epithelial-derived cytokines — particularly TSLP (thymic stromal lymphopoietin), IL-25, and IL-33 — released in response to allergens, viruses, or particulate triggers. These cytokines drive a downstream cascade involving IL-4, IL-5, and IL-13, each of which is a current or emerging biologic target:

• IL-4: Drives IgE class switching and Th2 differentiation (target: dupilumab, which blocks the shared IL-4Rα subunit)

• IL-5: The master eosinophil survival and differentiation cytokine (targets: mepolizumab, reslizumab, benralizumab)

• IL-13: Mediates bronchial hyperresponsiveness, mucus hypersecretion, and subepithelial fibrosis (target: dupilumab, tralokinumab)

• IgE: Produced downstream of IL-4 signalling; binds high-affinity FcεRI receptors on mast cells, triggering degranulation (target: omalizumab)

Non-T2 Asthma: The Uncharted Territory

Approximately 30–50% of severe asthma is non-T2 in character, characterised by neutrophilic or paucigranulocytic airway inflammation. Triggers include obesity, smoking, occupational exposures, and chronic infection. The pathophysiology involves IL-17, IL-8, and NLRP3 inflammasome activation. This endotype is less steroid-responsive and currently lacks approved targeted biologics, making it a genuine clinical challenge. Macrolides (azithromycin) have emerged as an important adjunctive therapy in this group.

🔬 Endotype vs Phenotype — The Essential Distinction

Phenotype: The observable clinical characteristics — allergic asthma, exercise-induced asthma, late-onset asthma

Endotype: The underlying biological mechanism — T2-high eosinophilic, T2-high IgE-mediated, non-T2 neutrophilic

A patient can have overlapping phenotypes but usually one dominant endotype. Biomarkers help map phenotype to endotype and guide biologic selection.

III. Asthma Phenotypes — A Practical Classification

Six clinically meaningful phenotypes deserve the attention of every practicing internist and respiratory specialist:

1. Allergic (Atopic) Asthma

The most common phenotype, comprising 60–80% of childhood-onset and 40–60% of adult asthma. Characterised by elevated total and specific IgE, positive skin prick tests, frequently associated with allergic rhinitis, eczema, and food allergy. FENO is typically elevated (>25 ppb), reflecting eosinophilic airway inflammation driven by allergen-induced IL-4/IL-13 signalling. Responds well to ICS; omalizumab is the preferred biologic when inadequately controlled.

2. Eosinophilic (Late-onset) Asthma

Often presents in the 4th–6th decade; not atopic; blood eosinophils persistently ≥300 cells/µL. Frequently complicated by chronic rhinosinusitis with nasal polyps (CRSwNP). Frequently steroid-dependent. High FENO. The most biologic-responsive phenotype. Aspirin/NSAID sensitivity (AERD — aspirin-exacerbated respiratory disease) is present in ~10% of this group — a critical history pearl.

3. Obesity-Associated Asthma

Increasingly prevalent; mechanistically distinct. Adipose-derived mediators (leptin, adiponectin) promote airway inflammation through non-T2 pathways. Characterised by mechanical restriction, poor response to ICS, and frequent misdiagnosis. Weight loss is the most effective intervention. Blood eosinophils and FENO are often normal. Do not reflexively escalate ICS in these patients.

4. Exercise-Induced Bronchoconstriction (EIB)

EIB occurs in up to 90% of uncontrolled asthmatics but also exists as an isolated phenotype (EIB without asthma) in athletes. Triggered by exercise-related airway water loss and cooling. Diagnosed by post-exercise spirometry (>10–15% FEV1 fall). Short-acting beta2-agonists pre-exercise remain effective; regular ICS reduces EIB frequency. Montelukast has a niche role, particularly in aspirin-sensitive patients.

5. Occupational Asthma

Often missed for years. New-onset or significantly worsened asthma in an adult should always trigger a detailed occupational exposure history — isocyanates, flour dust, latex, wood dusts, and cleaning agents are common sensitisers. The hallmark: symptom improvement on days away from work. Early identification and removal from exposure is the only disease-modifying intervention; late diagnosis leads to permanent airway remodelling.

6. Non-T2 / Neutrophilic Asthma

The most therapeutically challenging phenotype. Steroid-resistant or steroid-refractory. Often associated with smoking, obesity, and recurrent respiratory infections. Induced sputum neutrophilia >61% confirms the diagnosis. Azithromycin 500 mg three times weekly (AMAZES trial) reduces exacerbations by 41% in this group. New IL-17 pathway inhibitors are in clinical trials.

Biomarker Reference Table

Biomarker	Threshold	Phenotype	Guides Biologic
Blood eosinophils	≥150 cells/µL (T2); ≥300 high	Eosinophilic	Mepolizumab, benralizumab, dupilumab
FENO (FeNO)	≥25 ppb (intermediate), ≥50 ppb (high)	Allergic/T2-high	Anti-IL4R (dupilumab)
Total IgE	>30 IU/mL (± specific IgE)	Allergic	Omalizumab
Periostin	Elevated (research use)	T2-high, eosinophilic	Dupilumab (emerging)
Sputum neutrophils	>61% (induced sputum)	Non-T2/neutrophilic	Macrolides (azithromycin)

IV. Clinical Pearls 🪙

🪙 Clinical Pearls — High-Yield Bedside Observations

Pearl 1 — The SABA Usage Rule: Any patient using salbutamol more than twice a week for symptom relief has uncontrolled asthma, irrespective of how well they 'feel' day to day. Excessive SABA use (>200 puffs/year) is independently associated with asthma death. It is a red flag, not a reassuring coping mechanism.

Pearl 2 — FENO Predicts Steroid Response, Not Disease Severity: A FENO >50 ppb tells you the patient will respond to ICS and/or anti-IL4/IL13 biologics. It does not tell you how severe the asthma is. A patient with low FENO but severe symptoms likely has non-T2 asthma — do not escalate ICS alone.

Pearl 3 — The Diurnal Variation Test at the Bedside: Ask the patient whether symptoms are worse on waking (early morning dipping of peak flow is classic asthma). Symptoms uniformly throughout the day with no diurnal pattern should make you reconsider the diagnosis — think dysfunctional breathing, VCD, or cardiac cause.

Pearl 4 — The 'Thunderclap' Blood Eosinophil Rule: A single blood eosinophil count during an OCS course will be suppressed. Always measure eosinophils when the patient is off steroids or stable. One count is insufficient — get at least two measurements to establish the true baseline, ideally ≥4 weeks apart.

Pearl 5 — Adherence Before Escalation: Studies consistently show that 30–50% of patients prescribed ICS use their inhalers incorrectly or not at all. Before escalating therapy, objectively assess adherence — check pharmacy refill records, perform a witnessed inhaler technique check, and measure blood eosinophils and FENO (which normalise with regular ICS if the drug is actually being taken).

V. Oysters 🦪 — Hidden Gems Most Clinicians Miss

🦪 Oysters — Underappreciated Clinical Insights

Oyster 1 — Vocal Cord Dysfunction (VCD) Masquerading as Asthma: Up to 30% of 'refractory asthma' referred to specialist centres has a significant component of VCD (now called inducible laryngeal obstruction, ILO). Key distinguishing features: inspiratory stridor rather than expiratory wheeze, symptom onset within seconds of trigger, symptom resolution within minutes, and a normal FENO. The diagnostic test of choice is laryngoscopy during a symptomatic episode. Speech therapy is the treatment, not steroids.

Oyster 2 — ABPA in Steroid-Dependent Asthma: Allergic bronchopulmonary aspergillosis is present in 2–15% of patients with corticosteroid-dependent asthma and up to 15% of those with cystic fibrosis-related lung disease. It is diagnosed by a combination of markedly elevated total IgE (>1000 IU/mL), specific Aspergillus IgE and IgG, peripheral eosinophilia, central bronchiectasis on CT, and skin test reactivity. Treating the underlying asthma without addressing ABPA guarantees failure.

Oyster 3 — ACE Inhibitor Cough Versus Asthma: ACE inhibitor-induced cough occurs in up to 20% of South Asian patients (compared to 5–10% in Caucasians) and may precipitate or worsen airway hyperresponsiveness. Always take a medication history — particularly ACEi, NSAIDs, and beta-blockers. NSAIDs can precipitate AERD in susceptible eosinophilic asthmatics with potentially life-threatening consequences.

Oyster 4 — The Spirometry Trap: A normal spirometry does not exclude asthma. In mild or well-controlled asthma, inter-bronchodilator spirometry is frequently normal. Bronchoprovocation testing (methacholine challenge) is the gold standard for confirming airway hyperresponsiveness when resting spirometry is normal. Conversely, an obstructive pattern that does not fully reverse post-bronchodilator should make you consider COPD-asthma overlap (ACO) — the 3-S-criteria: Significant smoking history, Significant reversibility, Senior age of onset.

Oyster 5 — Vitamin D and Asthma Control: There is growing epidemiological and mechanistic evidence linking vitamin D deficiency to increased asthma exacerbation frequency. Several randomised trials show that vitamin D supplementation in deficient patients reduces exacerbation rates. Check a 25-hydroxyvitamin D level in any asthmatic with frequent exacerbations — it is an inexpensive and easily correctable modifiable risk factor.

VI. Clinical Hacks & Tips ⚡

⚡ Clinical Hacks — Tools of the Master Clinician

Hack 1 — The '4-SABA' Rule for Urgent Review: Any patient using 4 or more canisters of SABA per year is at high risk of asthma death. Flag these patients in your clinic records and prioritise early review.

Hack 2 — The FENO-Eosinophil Quadrant: High FENO + high eosinophils = classic T2-high, IL-4/IL-5 driven — consider dupilumab or biologic targeting both pathways. High FENO + low eosinophils = mast cell/IgE driven — consider omalizumab. Low FENO + high eosinophils = late-onset eosinophilic — consider anti-IL5 therapy. Low FENO + low eosinophils = non-T2, consider macrolides, address modifiable triggers.

Hack 3 — The Step-Down Test for Over-Treatment: Not every patient on step 4 therapy needs to stay there. If a patient has been well-controlled for 3–6 months, attempt a supervised step-down. Start by reducing ICS dose by 25–50%. If control is maintained at 3 months, continue stepping down. Over-treatment with high-dose ICS carries significant risk — adrenal suppression, cataracts, osteoporosis, skin bruising.

Hack 4 — Treat the Nose to Treat the Lungs: The 'united airway' concept is clinically actionable. In patients with allergic rhinitis or CRSwNP alongside asthma, aggressive treatment of upper airway disease — intranasal corticosteroids, antihistamines, saline irrigation — significantly improves asthma control. Biologics like dupilumab now carry dual regulatory approval for both severe asthma and CRSwNP.

Hack 5 — The Biologic Trial Rule: No biologic works instantly. Set a formal review at 12–16 weeks for all newly initiated biologics. Use validated tools (ACQ-6, AQLQ) plus objective biomarker response (eosinophil count, FENO) to assess response. If no clinical benefit at 16 weeks, switch biologic class rather than increasing dose.

Hack 6 — As-Needed ICS-Formoterol (MART) in Mild Asthma: The 2024 GINA strategy now recommends as-needed low-dose budesonide-formoterol (rather than SABA alone) as the preferred reliever across all steps of asthma treatment. This is one of the most practice-changing recommendations of the past decade.

VII. State-of-the-Art Updates

1. MART (Maintenance and Reliever Therapy) — A Paradigm Shift

The SYGMA 1 and 2 trials (O'Byrne et al., NEJM 2018) established that as-needed budesonide-formoterol in mild asthma was non-inferior to maintenance ICS for preventing exacerbations and superior to SABA-only therapy. GINA 2022 incorporated this into a major strategic revision: the preferred reliever therapy at all steps is now low-dose ICS-formoterol, not salbutamol. This removes the concept of 'SABA-only' as a valid long-term treatment for any patient with asthma requiring regular symptom relief.

2. Tezepelumab — A Biologic for Non-T2 Asthma

Tezepelumab, an anti-TSLP monoclonal antibody, works upstream of the T2 cascade and reduces exacerbations across all asthma endotypes — including those with low eosinophils and low FENO. In the NAVIGATOR trial, tezepelumab reduced annualised exacerbation rates by 70% vs placebo in the overall population and by 70% even in the low-eosinophil subgroup. This positions tezepelumab as the first biologic option for non-T2 severe asthma — a previously unmet need.

3. Dupilumab — Dual-Pathway Biologic

Dupilumab (anti-IL-4Rα) simultaneously blocks IL-4 and IL-13 signalling. It reduces exacerbations, improves lung function, and allows OCS reduction in severe eosinophilic asthma with high FENO. Crucially, it is also approved for atopic dermatitis, CRSwNP, and eosinophilic oesophagitis — making it the preferred biologic for patients with multi-site T2 atopic disease. Expect a transient paradoxical eosinophilia in the first 2–4 weeks of therapy — do not discontinue.

4. The Death of Daily SABA Monotherapy

The GINA 2022 strategy represents perhaps the biggest clinical practice change in decades: no adult or adolescent with asthma should be prescribed SABA alone as sole therapy. Every patient who requires a reliever should be on at least an as-needed ICS-containing inhaler. This was supported by meta-analyses showing that SABA overuse increases asthma mortality through tolerance, rebound hyperresponsiveness, and delayed anti-inflammatory treatment.

5. Biologics and OCS Burden

Long-term OCS use confers significant morbidity: diabetes, osteoporosis, adrenal insufficiency, cataracts, and cardiovascular disease. A landmark real-world study (Price et al., 2018) showed that 50% of OCS-dependent severe asthmatics had developed at least one steroid-related comorbidity within 5 years. All biologic agents reduce OCS burden by 50–70% — their cost-effectiveness becomes compelling when compared to the long-term costs of OCS-induced organ damage.

VIII. Diagnostic Nuances

Diagnosis of asthma should never be assumed without objective confirmation. This is a discipline that separates good clinicians from great ones.

History

• Symptom variability is the cornerstone: wheeze, cough, chest tightness, and breathlessness that vary with time of day, season, and specific triggers (allergens, cold air, exercise, smoke).

• Trigger inventory: pets, house dust mite, moulds, exercise, cold air, NSAIDs, beta-blockers, occupational agents, menstrual cycle (perimenstrual asthma — an underrecognised phenotype)

• Red flags against asthma: monosymptomatic isolated cough, symptoms starting in childhood without clear adult onset, no diurnal variation, no trigger pattern, prominent gastrointestinal symptoms (think eosinophilic oesophagitis or GERD)

• Medication review: NSAIDs, ACEi, beta-blockers — all can trigger or worsen airways disease

Examination

• Expiratory polyphonic wheeze is classical; an inspiratory wheeze suggests upper airway obstruction (VCD, tracheal stenosis, epiglottitis)

• Normal examination does not exclude asthma — many patients are entirely asymptomatic between exacerbations

• Nasal polyps on anterior rhinoscopy strongly suggest eosinophilic phenotype ± AERD

• Signs of steroid toxicity: Cushingoid features, skin atrophy, bruising — quantify your patient's total OCS burden before prescribing another course

Investigations

• Spirometry with reversibility: Post-bronchodilator FEV1 increase of >200 mL AND >12% confirms significant reversibility (note: this is necessary but not sufficient to diagnose asthma)

• Serial peak flow monitoring (2 weeks, 4 times daily): Diurnal variability >10% supports asthma; >30% suggests severe or uncontrolled disease

• Methacholine challenge: PC20 <8 mg/mL confirms airway hyperresponsiveness (high sensitivity, lower specificity — false positives include COPD, rhinitis, recent URTI)

• FENO: Measured fasted, before spirometry, in a seated position — technical errors are common. A single low FENO does not exclude T2 disease if the patient is on ICS

• Full blood count: Blood eosinophils ≥150 cells/µL suggest T2 inflammation; always measure off OCS if possible

• Chest CT: Not routine but consider in atypical features — central bronchiectasis (ABPA), mosaic attenuation (hypersensitivity pneumonitis), air trapping (small airways disease)

IX. Management Intricacies

The GINA Step Approach — Updated

GINA 2024 retains a five-step framework but has substantially revised steps 1 and 2:

• Step 1 (Intermittent, mild): As-needed low-dose ICS-formoterol (budesonide-formoterol 200/6 µg) — NOT SABA alone

• Step 2 (Mild persistent): Daily low-dose ICS + as-needed SABA, OR as-needed ICS-formoterol (MART strategy)

• Step 3 (Moderate persistent): Low-dose ICS-LABA (preferred) OR medium-dose ICS; consider MART strategy

• Step 4 (Severe persistent): Medium-to-high dose ICS-LABA; consider LAMA (tiotropium) add-on; review phenotype and refer for biologic assessment

• Step 5 (Refractory/biologic): Add-on biologic therapy (omalizumab, mepolizumab, benralizumab, dupilumab, tezepelumab); low-dose OCS if no biologic alternative; referral to severe asthma centre

Biologic Selection Framework

Biologic choice should be guided by the patient's dominant biomarker profile:

• Omalizumab (anti-IgE): IgE 30–1500 IU/mL AND allergen sensitisation AND weight/IgE in dosing range. First approved biologic; reduces exacerbations by 25–50% in allergic asthma.

• Mepolizumab (anti-IL5): Blood eos ≥150 on OCS or ≥300 cells/µL off OCS. 100 mg SC monthly. Reduces exacerbations by 47–53%.

• Benralizumab (anti-IL5Rα): Blood eos ≥300 cells/µL. 30 mg SC Q4W for 3 doses then Q8W. Advantage: faster eosinophil depletion, potentially superior OCS-sparing.

• Dupilumab (anti-IL4Rα): Eos ≥150 OR FENO ≥25 ppb. 200–300 mg SC Q2W. Best evidence for OCS reduction AND high FENO phenotype. Preferred in atopic multi-morbidity.

• Tezepelumab (anti-TSLP): All phenotypes, especially non-T2 severe asthma with low eosinophils. 210 mg SC monthly. The broadest-spectrum biologic available.

Inhaler Device Selection

The best inhaler is the one the patient can use correctly and consistently. Key considerations:

• Pressurised metered-dose inhalers (pMDI) require good hand-breath coordination — use with spacer in any patient who cannot coordinate

• Dry powder inhalers (DPI) require adequate inspiratory flow (>30 L/min minimum, ideally >60 L/min) — avoid in acute severe asthma and elderly patients with reduced inspiratory effort

• Soft mist inhalers (Respimat) have slower aerosol velocity and may suit patients who struggle with pMDI coordination

• Smart inhalers with digital sensors can detect, date-stamp, and log SABA use — invaluable for objective adherence monitoring in difficult asthma

Acute Severe Asthma — Management Pitfalls

Several management errors recur in acute severe asthma:

• Pitfall 1 — Underusing systemic corticosteroids: Prednisolone 40–50 mg daily for 5–7 days; there is no benefit to tapering over this duration — stop abruptly unless the patient is on long-term OCS

• Pitfall 2 — Overusing nebulised salbutamol without ipratropium: Combined ipratropium-salbutamol nebulisation in the first hour of acute severe asthma reduces hospitalisation by 30% compared to salbutamol alone

• Pitfall 3 — Missing the 'silent chest' danger sign: Reduced or absent breath sounds in a breathless asthmatic indicates critically reduced air entry — imminent respiratory arrest, not improvement

• Pitfall 4 — Overlooking magnesium sulphate: IV magnesium sulphate 2g over 20 minutes significantly reduces hospitalisation in acute severe asthma (life-threatening features or poor response to bronchodilators). It is underused.

• Pitfall 5 — Discharging too early: A 'discharge PEFR' >75% predicted AND ability to use inhaler correctly AND written action plan AND GP follow-up within 2 working days are all required before safe discharge from an acute episode

X. When to Escalate / When to Watch

🚨 Escalation Thresholds — Red Flags Requiring Urgent Action

Escalate immediately (same-day/emergency):

- PEFR or FEV1 <50% predicted despite bronchodilator therapy

- Respiratory rate >25/min, heart rate >110/min, inability to complete sentences

- Oxygen saturation <92% on room air

- Silent chest — no audible wheeze despite clear respiratory distress

- Exhaustion, altered consciousness, PaCO2 normal or rising (indicates impending respiratory failure)

- Previous near-fatal asthma (ICU admission, intubation) — any severe episode warrants hospital assessment

✅ Safe to Monitor — Criteria for Outpatient Management

PEFR >75% predicted after initial bronchodilator therapy

No risk factors for asthma death (young, no prior near-fatal episode, good adherence)

Symptom onset <24 hours with clear trigger identified and removed

Patient reliably able to self-monitor with peak flow meter and written action plan

Clear follow-up within 48–72 hours arranged with primary care or respiratory team

Risk Factors for Asthma Death — The GINA Fatal Five

• Previous severe exacerbation requiring intubation or ICU admission

• Hospitalisation or ED visit for asthma in the past 12 months

• Currently using or recently stopped OCS

• Not currently using ICS (or non-adherent to ICS)

• Over-reliance on SABA (>1 x 200-dose canister per month)

Any patient with two or more of these risk factors should be classified as high-risk and seen urgently in a dedicated severe asthma service. A written, individualised asthma action plan should be in place for every patient with asthma requiring regular treatment.

XI. Summary — The ASTHMA Mnemonic

Letter	Principle
A	Assess phenotype (T2-high vs non-T2), adherence, and allergen triggers
S	Spirometry: confirm variable obstruction; exclude mimics (VCD, ABPA, cardiac)
T	T2 biomarkers: FENO, blood eosinophils, total IgE — guide biologic choice
H	Hierarchy: SABA → low ICS → medium ICS+LABA → high ICS+LABA → add-on → biologic
M	Minimise: OCS dependence, SABA overuse, exposure to triggers and irritants
A	Action plan: written, individualised — increases adherence and reduces hospitalisations

Phenotype-to-Management Summary Table

Phenotype	T2 High?	Key Biomarker	Preferred Add-on	Avoid
Allergic	Yes	IgE, FENO	Anti-IgE (omalizumab)	Over-reliance on SABA
Eosinophilic	Yes	Blood eos, FENO	Anti-IL5/5R, Anti-IL4R	OCS long-term
Late-onset eosinophilic	Yes	Blood eos ≥300	Benralizumab, mepolizumab	NSAIDs (if AERD)
Non-T2 / Neutrophilic	No	Sputum neutrophils	Macrolides (adjunct)	High-dose ICS escalation
Obesity-associated	Variable	BMI, leptin	Weight loss, LABA/LAMA	ICS dose escalation alone
Exercise-induced	Variable	Spirometry post-exercise	SABA pre-exercise, ICS	Chronic SABA without ICS

References

1. 1. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. Updated 2024. Available from: https://ginasthma.org

2. 2. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med. 2012;18(5):716-25.

3. 3. Fahy JV. Type 2 inflammation in asthma — present in most, absent in many. Nat Rev Immunol. 2015;15(1):57-65.

4. 4. Bel EH, Wenzel SE, Thompson PJ, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371(13):1189-97.

5. 5. Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378(26):2486-96.

6. 6. Pavord ID, Chanez P, Criner GJ, et al. Mepolizumab for eosinophilic chronic obstructive pulmonary disease. N Engl J Med. 2017;377(17):1613-29.

7. 7. Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO). Lancet. 2016;388(10056):2115-27.

8. 8. O'Byrne PM, FitzGerald JM, Bateman ED, et al. Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med. 2018;378(20):1865-76.

9. 9. Bateman ED, Reddel HK, O'Byrne PM, et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med. 2018;378(20):1877-87.

10. 10. Dusser D, Montani D, Chanez P, et al. Mild asthma: an expert review on epidemiology, clinical characteristics and treatment. Allergy. 2007;62(6):591-604.

11. 11. Bourdin A, Husereau D, Molinari N, et al. Matching the right biologic to the right patient: a systematic review from a clinician's perspective. Eur Respir J. 2018;52(5):1801393.

12. 12. Price DB, Trudo F, Voorham J, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy. 2018;11:193-204.

13. 13. Reddel HK, Bacharier LB, Bateman ED, et al. Global Initiative for Asthma Strategy 2021: executive summary and rationale for key changes. Eur Respir J. 2022;59(1):2102730.

14. 14. Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376(25):2448-58.

15. 15. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES). Lancet. 2017;390(10095):659-68.

This article is intended for educational purposes for postgraduate medical trainees and practicing clinicians. Clinical decisions should always be individualised to the patient context and aligned with current institutional guidelines.

Asthma Phenotypes and Management