What are the current Global Initiative for Asthma (GINA) guidelines for stepwise asthma management, including preferred reliever therapy with inhaled corticosteroid (ICS) plus short‑acting β2‑agonist (SABA) and maintenance options such as inhaled corticosteroid (ICS)‑long‑acting β2‑agonist (LABA) regimens?

GINA Guidelines for Asthma Management

Preferred Reliever Therapy: ICS-Formoterol Over SABA Alone

All adults and adolescents with asthma should receive ICS-containing therapy and should NOT be treated with SABA alone, as SABA-only treatment increases the risk of severe exacerbations and asthma-related mortality. 1, 2

The 2019-2024 GINA strategy represents a fundamental shift away from SABA monotherapy based on compelling evidence:

• As-needed low-dose ICS-formoterol reduces severe exacerbations by ≥60% in mild asthma compared with SABA alone, with equivalent symptom control, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA 1
• LABA must never be prescribed as monotherapy due to increased risk of asthma-related death; it should only be delivered in fixed-dose combination with ICS 3, 4

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GINA 2024 Two-Track Treatment Algorithm

GINA divides treatment into two distinct tracks across 5 steps 1, 2:

Track 1 (Preferred Track)

• Reliever at ALL steps: As-needed low-dose ICS-formoterol 5, 1, 2
• Step 1 (Mild Intermittent): As-needed low-dose ICS-formoterol only 5, 1
• Step 2 (Mild Persistent): As-needed low-dose ICS-formoterol only (no daily maintenance) 5, 1
• Step 3 (Moderate Persistent): Daily low-dose ICS-LABA + as-needed low-dose ICS-formoterol (MART regimen) 5, 1
• Step 4 (Severe Persistent): Daily medium-dose ICS-LABA + as-needed low-dose ICS-formoterol (MART regimen) 5, 1
• Step 5 (Very Severe): Daily high-dose ICS-LABA + as-needed low-dose ICS-formoterol, plus add-on therapies (tiotropium, biologics, or oral corticosteroids) 5, 1

Note: ICS-formoterol as reliever is currently off-label; data exist only for budesonide-formoterol or beclomethasone-formoterol 5

Track 2 (Alternative Track)

• Reliever at ALL steps: As-needed SABA 5, 1, 2
• Step 1: As-needed SABA only (though daily low-dose ICS is preferred to prevent exacerbations) 5
• Step 2: Daily low-dose ICS + as-needed SABA 5, 4, 6
• Step 3: Daily low-dose ICS-LABA + as-needed SABA 5, 3
• Step 4: Daily medium-dose ICS-LABA + as-needed SABA 5, 3
• Step 5: Daily high-dose ICS-LABA + as-needed SABA, plus add-on therapies 5, 3

Alternative controller options at Step 2-3 include leukotriene receptor antagonists (LTRA) or low-dose ICS taken whenever SABA is used (off-label), though these are less effective than preferred options 5, 4

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When to Step Up Therapy

Step up immediately if:

• SABA use for symptom relief exceeds 2 days/week (excluding pre-exercise use) 3, 4, 6
• Nighttime awakenings occur >2 nights/month 4
• Any activity limitation due to asthma 4
• FEV₁ or peak flow <80% predicted 3
• Any severe exacerbation in the past 12 months 5

Before stepping up, verify: medication adherence, correct inhaler technique, and control of environmental triggers 5, 3, 4

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Step 3-5: Add-On Therapies for Uncontrolled Asthma

Step 4 Add-Ons (After Medium-Dose ICS-LABA)

• Long-acting muscarinic antagonist (LAMA): Add tiotropium to ICS-LABA for patients ≥12 years with uncontrolled persistent asthma 5, 1
• Refer for phenotypic assessment to identify treatable traits 5

Step 5 Add-Ons (Severe Asthma)

• Biologics for allergic asthma: Omalizumab (anti-IgE) for patients ≥12 years with documented allergic asthma and elevated IgE; reduces exacerbations by ≈15% absolute risk reduction (NNT=6) 3, 1
• Biologics for eosinophilic asthma: Anti-IL5/5R (mepolizumab, benralizumab) or anti-IL4R (dupilumab) for patients with elevated blood eosinophils 5, 1
• Azithromycin: Consider for non-eosinophilic severe asthma 1
• Oral corticosteroids: Last resort due to significant side effects; consider only after exhausting all other options 5, 3

Specialist consultation (pulmonology or allergy) is mandatory at Step 4 or higher 3

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Assessment of Asthma Control

Reassess control every 2-6 weeks after initiating or changing therapy 3, 4, 6

Well-Controlled Asthma Criteria:

• Daytime symptoms ≤2 days/week 5, 4
• No nighttime awakenings 5
• SABA use ≤2 days/week (excluding pre-exercise) 5, 4
• No activity limitation 5
• FEV₁ or peak flow ≥80% predicted 5, 3

Very Poorly Controlled Asthma:

• Daily symptoms 5
• FEV₁ or peak flow <60% predicted 5
• Frequent nighttime awakenings 5

Step down therapy only after ≥3 consecutive months of well-controlled asthma 3, 4, 6

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Risk Factors Requiring Ongoing Assessment

Assess at diagnosis and at least every 1-2 years 5:

• Medication-related risks: ICS not prescribed, poor adherence, incorrect inhaler technique, high SABA use (>1×200-dose canister/month associated with increased mortality) 5
• Comorbidities: Obesity, chronic rhinosinusitis, GERD, confirmed food allergy, anxiety, depression 5
• Exposures: Smoking, allergen exposure if sensitized, air pollution 5
• Lung function: Low FEV₁ (especially <60% predicted), high reversibility 5
• Inflammatory markers: Sputum/blood eosinophilia, elevated FeNO in allergic adults on ICS 5
• History: Ever intubated or in ICU for asthma, ≥1 severe exacerbation in past 12 months 5

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Pediatric Considerations (Ages 6-11 Years)

• Step 2: Daily low-dose ICS is preferred; LTRA is an alternative if adherence is problematic 3, 1
• Step 3: Low-dose ICS-LABA is preferred for children ≥4 years; medium-dose ICS monotherapy is preferred for children <4 years due to lack of LABA safety data 3
• Step 4-5: Medium-to-high-dose ICS-LABA with specialist consultation 3, 1

As-needed ICS-formoterol is NOT recommended for children <12 years due to insufficient evidence 1

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Critical Pitfalls to Avoid

• Never prescribe LABA as monotherapy—this increases asthma-related deaths 3, 4, 6
• Never ignore SABA overuse (>2 days/week)—this signals inadequate control and mandates stepping up therapy 3, 4, 6
• Do not delay ICS initiation in patients with mild persistent asthma; even "mild" asthma carries exacerbation and mortality risk 7, 8
• Verify inhaler technique at every visit—poor technique is a major cause of treatment failure 5, 3
• Provide a written asthma action plan to all patients 3, 2

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Nuance: Controversy Regarding As-Needed ICS-Formoterol

While GINA 2019-2024 strongly endorses as-needed ICS-formoterol for mild asthma, critics argue that regular daily ICS administration was actually more effective for multiple asthma control endpoints in the pivotal trials 8. Concerns include:

• Patient-driven treatment relies on accurate perception of airway narrowing, which is often impaired in asthma 8
• Intermittent ICS regimens are inferior to regular treatment for some patients 8
• Not all asthmatics respond to the same ICS dose 8

Despite this critique, the GINA recommendation stands based on the ≥60% reduction in severe exacerbations with as-needed ICS-formoterol versus SABA alone, which prioritizes the most critical outcome: preventing life-threatening exacerbations 1. For patients with poor symptom perception or adherence concerns, Track 2 (daily ICS + as-needed SABA) remains a valid alternative 5, 1.