Abstract
Long-acting muscarinic antagonists (LAMAs) are a class of bronchodilators that work by blocking the muscarinic receptors in the airway smooth muscle, leading to bronchodilation and reduced mucus secretion. They are primarily used in the management of chronic obstructive pulmonary disease, but their use in asthma, including in pediatric patients, has been increasing, especially in cases where asthma is not well-controlled by standard therapies. The Global Initiative for Asthma includes LAMAs as add-on therapy for children with severe asthma who are not adequately controlled with inhaled corticosteroid and long-acting beta-agonists. They are not recommended as a first-line treatment for children with mild asthma. The most commonly used LAMA in children with asthma is tiotropium, which has been studied for its efficacy and safety in this population. In this updated review, we have discussed the pharmacology, efficacy, and safety of LAMAs in children with recurrent wheezing and asthma.
Key Points:
- Mechanism of Action: LAMAs block muscarinic receptors in airway smooth muscle, leading to bronchodilation and reduced mucus secretion. They exhibit selectivity for M1 and M3 receptors while sparing M2 autoreceptors.
- Approved Use: Tiotropium is FDA-approved for children ≥6 years with asthma uncontrolled by ICS and LABAs, emphasizing its role in severe cases.
- Efficacy: Clinical trials show significant improvement in lung function (FEV1), reduced use of rescue medications, and lower exacerbation rates in children treated with tiotropium compared to placebo.
- Safety Profile: LAMAs are well-tolerated in pediatric populations, with adverse events comparable to placebo and other controller therapies like LABAs and leukotriene receptor antagonists (LTRAs).
- Combination Therapy: LAMAs are often used alongside ICS or as part of triple inhaler combinations for comprehensive asthma management.
- Formulations: Tiotropium is available in various inhaler forms, including dry powder (DPI), metered dose inhaler (MDI), and soft mist inhalers, facilitating individualized delivery.
- Clinical Limitations: Evidence for LAMAs in children <6 years remains limited, and their use in mild asthma is not recommended due to insufficient data.
- Research Gaps: Studies evaluating long-term safety, high-dose efficacy, and real-world application in diverse populations are needed to refine guidelines.
- Global Guidelines: The 2023 Global Initiative for Asthma (GINA) endorses LAMAs as step-up therapy for severe asthma but highlights the need for monitoring and specialist consultation.
- Potential Benefits Beyond Bronchodilation: Emerging evidence suggests anti-inflammatory and airway remodeling inhibition properties of LAMAs, warranting further exploration.
