Inflammatory Comorbidity of Upper and Lower Airways: Epidemiology, Mechanism, and Therapeutic Advances of Rhinitis Combined with Asthma.

Abstract

Background: Asthma and rhinitis are the most common chronic inflammatory diseases of the lower and upper airways, respectively, and frequently coexist as inflammatory disorders of the same respiratory tract. However, the relationship between these two conditions is not simply unidirectional, and the underlying mechanisms remain incompletely understood.

Summary: Approximately 80% of asthma patients have comorbid rhinitis, whereas 30-40% of rhinitis patients develop asthma, with comorbidities associated with greater symptom burden, reduced quality of life, and higher healthcare costs. The underlying mechanisms involve shared type 2 inflammation, neural reflexes, and systemic inflammatory spread. However, emerging evidence reveals significant clinical and therapeutic discordance between the upper and lower airways: biologics targeting the same type 2 pathway show differential efficacy, and only a subset of rhinitis patients progress to asthma. These findings challenge the one airway, one disease model and support conceptualizing the relationship as an overlap syndrome with both shared and distinct components. Current management has evolved toward an integrated strategy, with combined nasal and inhaled glucocorticoids as the cornerstone, leukotriene receptor antagonists offering additional benefits, and biologic agents (anti-IgE, anti-IL-4Rα) together with allergen immunotherapy providing targeted or etiological options.

Key messages: The rhinitis-asthma comorbidity involves shared type 2 inflammation but also exhibits compartment-specific molecular and therapeutic differences. Biologic agents show discordant efficacy between upper and lower airways, underscoring the need for phenotype-driven endotyping rather than a one-size-fits-all approach. Future research should focus on compartment-specific biomarkers and precision management strategies to optimize outcomes for patients with airway comorbidities.