Lung-brain axis in asthma: linking type 2 inflammation, environmental triggers, and neuroinflammation

Asthma is a heterogeneous airway disease that may have systemic and neuroimmune effects in selected phenotypes and disease states. Central to this lung-brain link is airway epithelial barrier dysfunction. Injury induced by allergens and pollutants prolongs inflammatory signaling and promotes the release of type 2-associated alarmins, notably IL-33, TSLP, and IL-25, which initiate and sustain type 2 immune programs. These upstream epithelial cues drive hallmark pulmonary features, including eosinophilic inflammation and airway remodeling; however, their direct contribution to neurovascular or CNS immune changes in human asthma has not been established. Across clinical studies and neuroimaging datasets, asthma is associated with increased risk of anxiety, depression, sleep disruption, and cognitive impairment, alongside evidence of altered activity in brain networks involved in interoception, emotion regulation, and cognition. Experimental studies provide biological plausibility for brain-relevant immune responses following allergic airway inflammation, but do not establish an epithelial-alarmin-to-CNS causal pathway in human asthma. We integrate exposure-dependent epithelial responses with asthma endotypes and parallel humoral, neurovascular, and neural routes; distinguish associative human findings from experimental mechanisms; and identify testable interventions and evidence gaps without assuming proven CNS benefit.