What are the Global Initiative of Asthma (GINA) 2025 guidelines for managing asthma?

Global Initiative for Asthma (GINA) 2025 Guidelines

Core Treatment Philosophy

All adults and adolescents with asthma must receive inhaled corticosteroid (ICS)-containing medication and should never be treated with short-acting beta-agonist (SABA) alone. 1 This represents a fundamental shift from historical practice where SABA monotherapy was acceptable for mild intermittent asthma.

Two-Track Treatment Approach

GINA 2025 divides asthma management into two distinct tracks 1:

Track 1 (Preferred)

• Reliever medication: As-needed combination low-dose ICS-formoterol for symptom relief 1
• This approach ensures anti-inflammatory treatment with every reliever use, reducing exacerbation risk even in mild asthma 2

Track 2 (Alternative)

• Reliever medication: SABA as needed 1
• Controller medication: Separate daily ICS inhaler 1
• This track requires strict adherence to daily ICS regardless of symptoms

Stepwise Pharmacological Management

Step 1-2: Mild Asthma

• Preferred: Low-dose ICS-formoterol as needed (Track 1) 3, 2
• Alternative: Daily low-dose ICS (fluticasone propionate 100-250 mcg/day or equivalent) plus as-needed SABA (Track 2) 3
• Approximately two-thirds of steroid-naive patients with mild asthma achieve control with ICS monotherapy within 4-8 weeks 4

Step 3: Moderate Persistent Asthma

• Preferred: Low-to-medium dose ICS-LABA combination (fluticasone/salmeterol 100-250/50 mcg twice daily) 3
• Alternative: Medium-dose ICS monotherapy 5
• The standard daily ICS dose of 200-250 mcg fluticasone propionate equivalent achieves 80-90% of maximum therapeutic benefit 6

Step 4: Moderate-to-Severe Asthma

• Preferred: Maintenance-and-reliever therapy (MART) with ICS-formoterol 2, 1
• This regimen uses the same ICS-formoterol inhaler for both daily maintenance and as-needed relief 7
• Alternative: Medium-dose ICS-LABA plus as-needed SABA 5

Step 5-6: Severe Persistent Asthma

• High-dose ICS-LABA combination 5
• Add long-acting muscarinic antagonist (LAMA) before considering phenotype-specific biologics 7, 8
• Consider omalizumab for patients with documented allergic triggers 5
• Oral corticosteroids may be necessary at Step 6, but minimize duration and dose due to systemic effects 5

Critical Dosing Guidance

The traditional "low-medium-high" ICS dose terminology is misleading and leads to excessive dosing. 6 The dose achieving 80-90% maximum benefit (200-250 mcg fluticasone propionate equivalent) is currently classified as "low dose," creating pressure to escalate unnecessarily 9, 6.

• Standard daily dose: 200-250 mcg fluticasone propionate equivalent 6
• Doses >500 mcg/day (traditional "high dose") carry significant systemic adverse effects including adrenal suppression equivalent to 5 mg oral prednisone daily 9
• In children, doses >400 mcg/day cause short-term reductions in tibial growth rate 9, 7

Acute Exacerbation Management

Severity Assessment

Assess objectively using these criteria 3, 5:

Severe Exacerbation:

• Cannot complete sentences in one breath 9
• Respiratory rate >25 breaths/min 9
• Heart rate >110 beats/min 9
• Peak expiratory flow (PEF) <50% predicted or personal best 9

Life-Threatening Features:

• PEF <33% predicted 9
• Silent chest, cyanosis, or feeble respiratory effort 9
• Bradycardia, hypotension, exhaustion, confusion, or coma 9
• Normal or elevated PaCO2 (5-6 kPa) in a breathless patient 9
• Severe hypoxia: PaO2 <8 kPa despite oxygen 9

Immediate Treatment Protocol

For all severe exacerbations, initiate simultaneously: 9, 3

• High-flow oxygen 40-60% 9, 5
• Nebulized salbutamol 5 mg or terbutaline 10 mg via oxygen-driven nebulizer 9, 3
• Prednisolone 30-60 mg orally OR intravenous hydrocortisone 200 mg 9, 3

If life-threatening features present, add: 9

• Ipratropium bromide 0.5 mg to each nebulization 9, 3
• Intravenous aminophylline 250 mg over 20 minutes (avoid if already on oral theophyllines) 9
• OR intravenous salbutamol/terbutaline 250 mcg over 10 minutes 9

Reassessment and Disposition

Monitor response 15-30 minutes after initial treatment: 9, 3

• If PEF >75% predicted: Step up usual treatment, arrange follow-up within 48 hours 9
• If PEF 50-75% predicted: Give prednisolone 30-60 mg, step up treatment, follow-up within 24-48 hours 9, 5
• If PEF <50% or any life-threatening features persist: Immediate hospital admission 9, 3

Lower threshold for admission if: 9

• Attack occurs in afternoon/evening 9
• Recent nocturnal symptoms or previous severe attacks 9
• Recent hospital admission 9
• Patient unable to assess own condition or poor social circumstances 9

Mandatory Patient Education Components

Every patient must receive: 9, 7, 5

• Written asthma action plan with specific PEF or symptom thresholds for medication adjustment 9, 7, 1
• Inhaler technique training verified and documented 9, 7, 5
• Clear distinction between "relievers" and "preventers": Patients must understand that bronchodilators (SABA, formoterol) provide immediate symptom relief while ICS medications prevent inflammation and exacerbations 9, 7, 5
• Recognition of worsening symptoms: Emphasize importance of nocturnal awakenings, increased SABA use, and declining PEF 9, 7
• Self-initiation protocols: Patients with prior exacerbations requiring oral corticosteroids should be empowered to self-initiate prednisolone when PEF falls below predetermined threshold (typically <60% personal best) 9

Assessment of Asthma Control

Well-controlled asthma requires ALL of the following over the past 4 weeks: 9

• Daytime symptoms ≤2 days/week 9
• No nighttime awakenings due to asthma 9
• Reliever use ≤2 days/week 9
• No activity limitation due to asthma 9

Before escalating treatment, verify: 9

• Correct inhaler technique 9
• Medication adherence 9
• Identification and management of triggers (allergens, irritants, occupational exposures) 7
• Assessment for comorbidities: gastroesophageal reflux, rhinosinusitis, obesity, obstructive sleep apnea 9

This "treatable traits" approach prevents unnecessary escalation of ICS doses when symptoms arise from alternative causes 9.

Special Population Considerations

Children 0-4 Years

• Diagnosis relies on symptoms rather than objective testing 9, 7
• Bronchodilator response is variable in the first year of life but should still be attempted 9
• Consider alternative diagnoses: gastroesophageal reflux, cystic fibrosis, chronic lung disease of prematurity 9
• Start Step 2 with low-dose ICS, reassess in 4-6 weeks 3

Children 5-11 Years

• Maximum dose: fluticasone/salmeterol 100/50 mcg twice daily 3
• Monitor growth velocity with prolonged ICS use 3, 7
• Use lowest effective ICS dose providing acceptable control 9, 7

Pregnant Women

• Worsening asthma requires specialist referral 9, 7
• Continue ICS therapy as uncontrolled asthma poses greater fetal risk than ICS 9

Patients with Comorbid Asthma and Allergen Immunotherapy

• Evaluate for asthma before initiating allergen immunotherapy (AIT) 9
• Assess asthma control before each subcutaneous immunotherapy (SCIT) injection using validated tools (Asthma Control Test, Asthma Control Questionnaire) 9
• Do not administer SCIT in patients with severe or uncontrolled asthma 9
• Withhold SCIT temporarily if asthma control deteriorates 9
• Patients with eosinophilic esophagitis should not receive sublingual immunotherapy (SLIT) but may receive SCIT 9

Follow-Up and Monitoring

Post-exacerbation: 3, 5

• Primary care follow-up within 24-48 hours 3, 5
• Respiratory specialist within 4 weeks 3
• Do not discharge from hospital until PEF >75% predicted/personal best and stable on discharge medications for 24 hours 9, 5

Stable asthma: 7

• Assess control every 2-6 weeks initially 7
• Once stable, assess every 1-6 months 7
• Consider step-down therapy when well-controlled for ≥3 months 7, 5

Critical Pitfalls to Avoid

• Never prescribe LABA monotherapy: This increases risk of asthma-related death 7
• Do not underestimate exacerbation severity: Many asthma deaths result from failure to appreciate severity by patients, relatives, and physicians 9
• Avoid delayed corticosteroid administration: Systemic corticosteroids must be given immediately in severe exacerbations 9, 5
• Do not sedate patients during acute asthma: This masks deterioration and increases mortality risk 5
• Recognize that symptom control does not eliminate exacerbation risk: Patients may feel well-controlled while remaining at high risk for severe exacerbations, particularly in severe asthma 7