What does the Global Initiative for Asthma (GINA) recommend as the stepwise treatment for persistent asthma in adults/adolescents, for children aged 5–11 years, and for mild intermittent asthma?

GINA Stepwise Treatment Recommendations for Asthma

Adults and Adolescents (≥12 years): Preferred Track 1

GINA recommends that all adults and adolescents with asthma receive ICS-containing medication at every treatment step, with low-dose ICS-formoterol as the preferred reliever therapy across all severity levels. 1, 2, 3

Step-by-Step Treatment Algorithm:

Step 1 (Mild Intermittent Asthma):

• Preferred: As-needed low-dose ICS-formoterol combination (taken only when symptomatic) 1, 2, 3
• Alternative: As-needed ICS plus SABA taken concomitantly 4, 1
• Never use SABA alone due to increased risk of severe exacerbations and asthma-related death 1, 2, 5

Step 2 (Mild Persistent Asthma):

• Preferred: As-needed low-dose ICS-formoterol (no daily maintenance required) 1, 2
• Alternative: Daily low-dose ICS plus as-needed SABA 4, 1
• This approach reduces severe exacerbations by ≥60% compared with SABA alone 2

Step 3 (Moderate Persistent Asthma):

• Preferred: Daily low-dose ICS-formoterol PLUS as-needed ICS-formoterol (MART/SMART therapy) 1, 2, 3
• Alternative: Low-to-medium dose ICS-LABA daily plus as-needed SABA 4, 1
• SMART therapy is superior to higher-dose ICS-LABA with SABA reliever for preventing exacerbations 4, 1

Step 4 (Moderate-to-Severe Persistent Asthma):

• Preferred: Medium-dose ICS-formoterol maintenance plus as-needed ICS-formoterol (MART) 1, 2
• Alternative: Medium-to-high dose ICS-LABA daily plus as-needed SABA 4, 1

Step 5 (Severe Persistent Asthma):

• Preferred: High-dose ICS-formoterol maintenance plus as-needed ICS-formoterol (MART) 1, 2
• Add-on options (in order): Long-acting muscarinic antagonist (LAMA), then consider phenotype-specific biologics 1, 2
• Oral corticosteroids only as last resort due to significant adverse effects 4, 2

Critical Safety Points:

• Formoterol is the ONLY LABA suitable for as-needed use due to rapid onset; salmeterol must never be used for SMART therapy 1, 6
• LABAs must NEVER be used as monotherapy as this increases asthma-related death risk 1, 6
• ICS doses >500 mcg/day carry significant systemic adverse effects including adrenal suppression 1

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Children Ages 5-11 Years

For children 5-11 years, GINA recommends a stepwise approach with ICS as the cornerstone, but SMART therapy is NOT recommended in this age group. 1, 2

Step-by-Step Treatment Algorithm:

Step 1 (Mild Intermittent):

• As-needed SABA alone may be acceptable if symptoms are truly infrequent (≤2 days/week) 4
• Consider low-dose ICS if symptoms occur >2 days/week 4

Step 2 (Mild Persistent):

• Preferred: Daily low-dose ICS 4, 1
• As-needed SABA for quick relief 4

Step 3 (Moderate Persistent):

• Preferred: Low-dose ICS-LABA combination daily 4, 2
• Alternative: Medium-dose ICS alone 4
• As-needed SABA for relief 4

Step 4 (Moderate-to-Severe Persistent):

• Preferred: Medium-dose ICS-LABA combination 4, 2
• As-needed SABA for relief 4

Step 5 (Severe Persistent):

• High-dose ICS-LABA combination 4
• Consider add-on LAMA or referral for biologic therapy 2
• Oral corticosteroids if necessary 4

Special Pediatric Considerations:

• ICS doses >400 mcg/day can cause short-term reductions in tibial growth rate (approximately 1 cm), though this effect is not progressive 4, 1
• Growth effects occur primarily in first several months of treatment 4
• The efficacy of ICS outweighs growth concerns, but titrate to lowest effective dose 4
• SMART therapy (ICS-formoterol as maintenance and reliever) is NOT recommended for children 6-11 years 1, 6

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Children Ages 0-4 Years

For infants and young children, initiate daily long-term controller therapy based on specific risk criteria, as diagnosis relies on symptoms rather than objective testing in this age group. 4, 1

Indications to Start Daily Controller Therapy:

Strong Recommendation (Start Daily Low-Dose ICS):

• ≥4 wheezing episodes in past year lasting >1 day AND affecting sleep 4
• PLUS positive Asthma Predictive Index: 4
  • Either: Parental history of asthma, physician-diagnosed atopic dermatitis, OR sensitization to aeroallergens
  • Or: ≥2 of following: sensitization to foods, >4% peripheral eosinophilia, wheezing apart from colds

Consider Starting Controller Therapy:

• Symptomatic treatment needed >2 days/week for >4 weeks 4
• ≥2 exacerbations requiring systemic corticosteroids within 6 months 4

Treatment Steps:

Step 1: As-needed SABA only 4

Step 2: Daily low-dose ICS (preferred controller) 4

Step 3: Medium-dose ICS 4

Step 4: Medium-dose ICS plus either LABA or leukotriene modifier 4

Critical Pediatric Caveats:

• Bronchodilator response is variable in this age group 1
• Consider seasonal controller therapy for children with symptoms only during specific periods 4
• Monitor response closely for 4-6 weeks; if no benefit, stop treatment and reconsider diagnosis 4
• GINA does not recommend ICS-formoterol as reliever therapy in children 0-5 years 1

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Universal Management Principles Across All Ages

Assessment and Monitoring:

• Well-controlled asthma requires ALL of the following over past 4 weeks: 1
  • Daytime symptoms ≤2 days/week
  • No nighttime awakenings
  • Reliever use ≤2 days/week
  • No activity limitation

When to Step Up Treatment:

• Asthma is partly controlled (1-2 criteria not met) or uncontrolled (≥3 criteria not met) 1
• ≥2 exacerbations requiring oral corticosteroids in past year 4, 1

When to Step Down Treatment:

• Asthma well-controlled for ≥3 months 4, 1
• Reduce ICS dose by 25-50% every 3 months to identify minimum effective dose 4
• Monitor closely for 2-6 weeks after reduction 4

Essential Non-Pharmacologic Management:

• Every patient must receive a written asthma action plan with specific thresholds for medication adjustment 1, 6
• Training on proper inhaler technique 1, 6
• Clear understanding of "relievers" versus "preventers" 1
• Identification and reduction of allergen/irritant exposure 1

When to Refer to Specialist:

• Difficulty achieving or maintaining control 1
• ≥2 bursts of oral corticosteroids in past year 1
• Any exacerbation requiring hospitalization 1
• Consideration for biologic therapy 1, 2