Are There Neurophenotypes for Asthma? Functional Brain Imaging of the Interaction between Emotion and Inflammation in Asthma

Background: Asthma is a chronic inflammatory disease noteworthy for its vulnerability to stress and emotion-induced symptom intensification. The fact that psychological stress and mood and anxiety disorders appear to increase expression of asthma symptoms suggests that neural signaling between the brain and lung at least partially modulates the inflammatory response and lung function. However, the precise nature of the neural pathways implicated in modulating asthma symptoms is unknown. Moreover, the extent to which variations in neural signaling predict different phenotypes of disease expression has not been studied. Methods and Results: We used functional magnetic resonance imaging to measure neural signals in response to asthma-specific emotional cues, following allergen exposure, in asthmatics with a dual response to allergen challenge (significant inflammation), asthmatics with only an immediate response (minimal inflammation), and healthy controls. The anterior insular cortex was differentially activated by asthma-relevant cues, compared to general negative cues, during the development of the late phase of the dual response in asthmatics. Moreover, the degree of this differential activation predicted changes in airway inflammation. Conclusions: These findings indicate that neurophenotypes for asthma may be identifiable by neural reactivity of brain circuits known to be involved in processing emotional information. Those with greater activation in the anterior insula, in response to asthma-relevant psychological stimuli, exhibit greater inflammatory signals in the lung and increased severity of disease and may reflect a subset of asthmatics most vulnerable to the development of psychopathology. This approach offers an entirely new target for potential therapeutic intervention in asthma.