The following is a summary of “Molecular pathways underlying lung-brain axis signaling in asthma: Relevance for psychopathology and neuroinflammation,” published in the January 2024 issue of Allergy & Immunology by Dill-McFarland, et al.

Growing evidence suggests that asthma has systemic effects and can influence brain function. While airway inflammation is proposed to initiate communication with the brain, the specific signaling pathways remain unclear. For a study, researchers sought to identify the cellular and molecular pathways involved in afferent lung-brain communication during airway inflammation in asthma.

Twenty-three adults with mild asthma underwent segmental bronchial provocation with an allergen (SBP-Ag) to induce airway inflammation. Bronchoalveolar lavage fluid was collected for targeted protein analysis and RNA sequencing to determine gene expression profiles. Neural responses to emotional cues in nodes of the salience network were assessed using functional magnetic resonance imaging (fMRI) at baseline and 48 hours after SBP-Ag.

Cell deconvolution and gene coexpression network analysis identified 11 cell-associated gene modules that changed in response to SBP-Ag. SBP-Ag increased bronchoalveolar lavage eosinophils and expression of an eosinophil-associated module enriched for genes related to T_H17-type inflammation (e.g., IL17A), as well as cell proliferation in the lung and brain (e.g., NOTCH1, VEGFA, and LIF). Increased expression of genes in this module and several T_H17-type inflammation–related proteins were associated with an increase in salience network reactivity compared to baseline.

The study findings identified a specific inflammatory pathway linking asthma-related airway inflammation and emotion-related neural function. T_H17-type inflammation, implicated in depression and neuroinflammation, appears to have systemic effects on long-term brain health. Thus, the data highlighted the potential for inflammation in the lung in asthma to impact areas outside of the lung, suggesting novel therapeutic targets may be warranted.

Reference: jacionline.org/article/S0091-6749(23)01183-1/fulltext