What are the guidelines for using SMART therapy in pediatric patients with asthma?

SMART Therapy Guidelines for Pediatric Asthma

For children aged 5-11 years with moderate to severe persistent asthma (Steps 3-4), ICS-formoterol as single maintenance and reliever therapy (SMART) is recommended with age-appropriate ICS dosing, though this represents a conditional recommendation with moderate certainty of evidence. 1

Age-Specific Recommendations

Children Under 5 Years

• Do not use SMART therapy in children under 5 years of age. 1
• No evidence supports the safety or efficacy of ICS-formoterol as maintenance and reliever therapy in this age group 1
• Use conventional low-dose ICS with separate SABA reliever instead 1

Children Aged 5-11 Years

• ICS-formoterol is recommended as SMART at Steps 3 and 4 for moderate to severe persistent asthma 2, 1
• This is a conditional recommendation with moderate certainty of evidence 1
• Important caveat: The Global Initiative for Asthma (GINA) guidelines do NOT endorse SMART for this age group, creating a divergence between GINA and the National Asthma Education and Prevention Program (NAEPP) 2, 1
• Use age-appropriate ICS dosing in the formulation 2, 1

Adolescents Aged 12 Years and Older

• ICS-formoterol as SMART at Steps 3 and 4 is strongly recommended 1
• This carries a strong recommendation with high certainty of evidence 1
• For Step 3: One inhalation of budesonide-formoterol 160/4.5 μg once or twice daily for maintenance, plus additional inhalations as needed for symptom relief 3
• For Step 4: Two inhalations of budesonide-formoterol 160/4.5 μg twice daily for maintenance, plus additional inhalations as needed 3
• Maximum total daily dose: 12 inhalations in any single day (delivering 54 μg formoterol) 3

Evidence Supporting SMART in Pediatrics

Efficacy Data

• In children aged 4-11 years, SMART using budesonide-formoterol prolonged time to first exacerbation compared to both fixed-dose budesonide alone (p=0.02) and fixed-dose ICS-LABA combination (p<0.001) 4
• Exacerbation rates requiring medical intervention were reduced by 70-79% with SMART versus comparators (0.08/patient vs 0.28-0.40/patient; p<0.001) 4
• Meta-analysis shows SMART significantly decreases odds of severe exacerbations (OR 0.65; 95% CI 0.53-0.80) and exacerbations requiring hospitalization/ER treatment (OR 0.69; 95% CI 0.58-0.83) 5

Safety Considerations

• Growth velocity improved by 1.0 cm per year with SMART versus fixed-dose budesonide in children 4
• No increase in adverse events compared to traditional fixed-dose therapy 5
• ICS exposure is lower with SMART while maintaining superior exacerbation control 3
• Monitor growth in all pediatric patients on long-term ICS therapy 1

Specific Formulations Validated for SMART

Only budesonide-formoterol and beclometasone-formoterol have confirmed efficacy and safety for SMART 3

• Other ICS-LABA combinations have not been studied for SMART and should not be used in this manner 3
• The rapid onset of action of formoterol (similar to albuterol) is essential for the SMART approach 3

Implementation Algorithm

Step 1: Determine Eligibility

• Age ≥5 years 1
• Moderate to severe persistent asthma (Steps 3-4) 2, 1
• Patient/family capable of understanding dual role of inhaler (maintenance + reliever) 3

Step 2: Select Appropriate Dose

• Ages 5-11 years: Use lower ICS dose formulations appropriate for age 2, 1
• Ages ≥12 years:
  • Step 3: Budesonide-formoterol 160/4.5 μg, 1 inhalation once or twice daily 3
  • Step 4: Budesonide-formoterol 160/4.5 μg, 2 inhalations twice daily 3

Step 3: Patient Education

• Provide a customized written asthma action plan 3
• Explain the dual role: scheduled maintenance doses PLUS additional inhalations for symptom relief 3
• Emphasize maximum daily dose limits (12 total inhalations for adolescents/adults) 3
• Instruct to discontinue separate SABA use for symptom relief 6

Step 4: Monitoring

• Evaluate response within 4-6 weeks of initiation 1
• Track total daily inhaler use as a marker of asthma control 1
• Monitor growth velocity in pediatric patients 1
• Assess symptom control and exacerbation frequency at each visit 1

Step 5: Adjustment

• Once control is sustained for at least 3 months, consider step-down therapy 1
• Do not increase ICS dose during exacerbations in adherent patients 2, 1
• If using >8 reliever inhalations daily consistently, reassess control and consider step-up 3

Critical Pitfalls to Avoid

Device and Formulation Errors

• Never use SMART with ICS-LABA combinations other than budesonide-formoterol or beclometasone-formoterol 3
• Do not use salmeterol-containing products for SMART (salmeterol has slower onset than formoterol) 3
• Ensure single-device delivery; using separate inhalers negates the SMART approach 2

Prescribing Errors

• Do not prescribe SMART for children under 5 years 1
• Do not combine SMART with another LABA-containing medication 6
• Do not use SMART as rescue therapy alone without maintenance dosing 6

Monitoring Failures

• Do not ignore high reliever use (>8 inhalations/day suggests poor control) 3
• Do not increase ICS dose during exacerbations in patients adherent to maintenance therapy 2, 1
• Do not neglect growth monitoring in children on any ICS regimen 1, 6

Comparison with Alternative Strategies

SMART demonstrates superiority over fixed-dose ICS alone and fixed-dose ICS-LABA combination without increased adverse effects 5

• Fixed-dose combination (FDC) inhalers show small but significant benefit over separate ICS+LABA inhalers (adjusted OR 0.77; 95% CI 0.66-0.91) 7
• Adding LABA to ICS (non-SMART) does not significantly reduce exacerbations requiring oral steroids compared to ICS alone in children (RR 0.95; 95% CI 0.70-1.28) 8
• SMART provides the advantage of delivering additional ICS with each reliever dose, addressing inflammation during symptom worsening 3