Maintenance and Reliever Therapy (MART) in Pediatric Asthma

Asthma is a chronic inflammatory disorder of the lower airways characterized by variable airflow limitation and bronchial hyperresponsiveness.1 Inhaled therapy has long been the foundation of asthma management. Traditionally, children with persistent asthma have been treated using a dual-inhaler strategy: a daily inhaled corticosteroid (ICS) for maintenance and a short-acting β2-agonist (SABA) as needed for symptom relief.1 Despite its widespread use, this approach has important limitations. Poor adherence to daily ICS therapy, over-reliance on SABA, and fragmented symptom-based medication use frequently lead to suboptimal control and recurrent exacerbations in children. SABAs provide rapid bronchodilation but do not address airway inflammation, while ICS must be used consistently to maintain anti-inflammatory control—something often difficult to achieve in pediatric populations. Maintenance and reliever therapy (MART), also known as single MART (SMART), represents a paradigm shift in asthma management.2-4 MART utilizes a single inhaler containing both an ICS and a rapid-onset long-acting β2-agonist (LABA), most commonly formoterol, for both daily maintenance and symptom relief. This strategy aligns anti-inflammatory therapy with symptom occurrence, potentially improving adherence and reducing exacerbations. The development of MART was enabled by the unique pharmacodynamic profile of formoterol. Unlike salmeterol, which has a slower onset of action, formoterol produces bronchodilation within minutes while maintaining a prolonged effect. This rapid onset allows it to function effectively as a reliever medication. Combining formoterol with an ICS (such as budesonide) in a single inhaler permits simultaneous bronchodilation and escalation of anti-inflammatory therapy at times of worsening symptoms. This dynamic approach contrasts with traditional regimens in which SABA use may increase during exacerbations without a corresponding increase in anti-inflammatory treatment. Evidence from Clinical Trials Adult and Adolescent Trials: Initial large-scale trials evaluating MART were conducted in adults and adolescents with moderate to severe asthma. The SYGMA 1, SYGMA 2 and other studies demonstrated that as-needed budesonide-formoterol significantly reduced severe exacerbations compared with SABA-based strategies while maintaining acceptable symptom control.2-4 Meta-analyses have consistently shown that MART reduces severe exacerbations by approximately 30%–35% compared with fixed-dose ICS/LABA plus SABA regimens, while also lowering cumulative corticosteroid exposure. Pivotal Pediatric Trial: The first landmark pediatric trial evaluating MART was conducted by Bisgaard et al.5 This multicenter, randomized, double-blind study included children aged 4–11 years and compared: Budesonide/formoterol used as both maintenance and reliever (MART). Fixed-dose ICS/LABA plus SABA as needed. Higher-dose ICS plus SABA as needed. The study demonstrated a 70%–79% reduction in severe exacerbations in the MART group compared with comparator regimens. In addition, children receiving MART had a longer time to first exacerbation without a significant increase in adverse events. This trial remains the foundational pediatric evidence supporting MART therapy. However, compared to adults and adolescents, the pediatric evidence base remains more limited. Guideline Recommendations 1. Global Initiative for Asthma (GINA) (2024–2025)6 The GINA recommends MART as a preferred treatment option at steps 3 and 4 for children aged 6–11 years, using lower maintenance and maximum doses than in adults. For adolescents aged ≥12 years, MART is clearly recommended at steps 3 and 4, with formoterol as the only LABA suitable for reliever use. For children under 6 years of age, MART inhalers are not licensed, and evidence remains insufficient. 2. NICE/BTS/SIGN (UK, 2024)7 The UK guidelines recommend MART as a step-up option in children aged 5–11 years but clarify that this represents off-label use. They emphasize the importance of informed consent, specialist supervision, and careful monitoring. 3. National Asthma Education and Prevention Program (NAEPP) (United States, 2020+)8 The U.S. NAEPP supports ICS-formoterol as both controller and reliever therapy in children aged ≥4–5 years with inadequate control on ICS alone. However, regulatory approval from the U.S. FDA for this age group remains limited, creating implementation barriers. 4. Indian Pediatric National Respiratory Chapter (IAP-NRC) Guidelines (2025) The ICP-NRC recommendations broadly align with GINA, endorsing MART in moderate to severe asthma in children ≥6 years while highlighting the limited pediatric data and the need for further research. Clinical Advantages of MART in Children Reduction in severe exacerbations. Improved adherence due to single-inhaler strategy. Decreased SABA overuse. Lower cumulative systemic corticosteroid exposure. Simplified asthma action plans. By linking reliever use with ICS delivery, MART ensures that worsening symptoms automatically trigger increased anti-inflammatory therapy. Regulatory and Practical Challenges Despite strong clinical evidence, several barriers limit universal adoption in children: Off-label status in many regions for children <12 years. Regulatory discrepancies between guidelines and licensing authorities. Insurance coverage limitations. Need for careful inhaler technique training. Requirement for close specialist monitoring. These discrepancies between clinical recommendations and regulatory approval remain a major area of controversy. Safety Considerations Available pediatric data demonstrate no significant increase in serious adverse events compared to conventional therapy. Nevertheless, long-term safety data, particularly regarding growth and cumulative steroid exposure in younger children, require further evaluation. Conclusion MART therapy represents a major advancement in pediatric asthma management by integrating MART into a single, responsive treatment strategy. Robust evidence—including the pivotal Bisgaard pediatric trial showing substantial exacerbation reduction —supports its efficacy in children aged 6–11 years under specialist supervision. For adolescents ≥12 years, MART is now considered standard care in moderate to severe asthma. However, regulatory inconsistencies and limited data in children under 6 years necessitate cautious implementation and further research. The future of MART in pediatric care will depend on expanded clinical trials, harmonization of regulatory policies, improved inhaler technologies, and structured patient education to ensure safe and effective child-centered asthma management. Author contribution JJ: conceptualization, drafting, literature review, and final manuscript approval were performed by the author. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.