The next frontier: From clinical remission to structural remission-rethinking airway remodeling in asthma

The concept of remission in asthma has gained increasing prominence with the expanding use of biologic therapies. However, a central conceptual and clinical question remains unresolved: does clinical remission represent true disease resolution, or does it reflect suppression of the most visible manifestations of a still-active airway-wall disease? This review critically examines airway remodeling as a major determinant of asthma chronicity, severity, and incomplete reversibility, while evaluating the extent to which current therapeutic strategies are moving the field toward meaningful structural remission. Contemporary evidence indicates that asthma is not simply a disorder of variable bronchoconstriction, but a complex airway-wall disease characterized by persistent interactions among epithelial dysfunction, type 2 and non-type 2 inflammation, mucus dysregulation, extracellular matrix remodeling, vascular alterations, and airway smooth muscle expansion. These abnormalities may arise early, involve both large and small airways, and persist despite apparent clinical stability. Inhaled corticosteroids remain essential for controlling inflammatory activity and can attenuate selected remodeling features, particularly when introduced early, although their capacity to reverse established structural disease appears limited. Importantly, biologics have major disease-modifying potential, including exacerbation reduction, corticosteroid sparing, lung-function improvement, and possible prevention of further decline or remodeling-related damage. Evidence from bronchial biopsies, computed tomography, physiological studies, and biomarker analyses increasingly suggests that biologics can modify specific remodeling domains. Although complete structural normalization remains unproven, current data indicate that meaningful steps toward disease modification are already being achieved, making structural remission a more realistic long-term goal than previously believed.