Upper and lower airway crosstalk in acute exacerbations of COPD: a clinical and biological overview

Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are acute worsening events characterized by increased dyspnea, cough, and sputum production. Although traditionally viewed as lower airway events, growing evidence suggests that AE-COPD may reflect broader pan-airway dysfunction involving both upper and lower respiratory compartments.

This overview examines upper - lower airway crosstalk in AE-COPD across three domains: pan-airway inflammation, epithelial alarmin/cytokine networks, and the continuous airway microbiome. We discuss the coexistence of COPD with sinonasal inflammation, chronic rhinitis, and chronic rhinosinusitis, and their possible contribution to symptom burden, impaired quality of life, and exacerbation risk. We also review mechanisms linking upper and lower airways, including epithelial barrier dysfunction, impaired antiviral responses, innate immune activation, alarmin release, and microbiome-driven dysbiosis.

Recognizing AE-COPD as a manifestation of pan-airway dysfunction may have relevant clinical implications. Systematic assessment of upper airway symptoms and comorbidities could improve phenotyping, risk stratification, and therapeutic targeting, particularly in frequent exacerbators. Future longitudinal and multi-omic studies are needed to validate upper airway biomarkers and determine whether targeted treatment of upper airway disease can modify COPD outcomes.