NLRP3 inflammasome expression in pediatric asthma: sputum-based insights, inflammatory mechanisms, and targeted therapeutic strategies

Abstract Asthma is a common chronic inflammatory disease in children. Pediatric asthma has a wide range of immunologic phenotypes and different treatment responses. Recent data from various studies suggest that the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a cytosolic multiprotein complex, has a central role in innate immunity, may be implicated in pediatric asthma pathogenesis, especially in the neutrophilic corticosteroid-resistant type. This review article investigates the mechanism of NLRP3 inflammasome activation as well as its role in airway inflammation and its expression in pediatric asthma based on sputum studies. The findings emphasize an association between elevated NLRP3 levels and poor asthma control. The need for novel treatments is important because Current using therapies such as corticosteroids and biologics demonstrate variable efficacy. According to data, their efficacy heavily depends on the underlying inflammatory phenotype. Biologics such as mepolizumab, benralizumab, and dupilumab are well known for their corticosteroid-sparing effects especially in cases of severe eosinophilic asthma. even though, their therapeutic benefits are limited when it comes to neutrophilic or steroid-resistant phenotypes. NLRP3 inhibitors are new, promising treatments which emerged recently and show potential capability in reducing airway inflammation in animal models. Furthermore, NLRP3-driven inflammation appears to play a role not only in asthma but also in inflammatory bowel disease and juvenile idiopathic arthritis, indicating a wider relevance for therapies that target the inflammasome pathway. Although promising data, application of this data in clinical practice is still challenging due to many causes, including diagnostic challenges, ethical considerations in trials involving children, and the lack of approved NLRP3 inhibitors for use in children. More research is required and essential to confirm that NLRP3 could be used as a biomarker or therapeutic target in pediatric asthma. Graphical abstract