Novel insights into asthma pathophysiology and pharmacological interventions: spiral of respiratory symptoms and psychiatric episodes.

backgroundAsthma is the most common respiratory disorder with airway inflammation and alterations. Included among comorbidities with asthma are psychiatric conditions; however, it is unclear how these disorders engaging with each other.

findingsIn type-2-high asthma, allergens cause airway type-2 immune responses with respiratory symptoms. When the patients experience high blood levels of pro-inflammatory cytokines, they can promote reactive glial cell-induced neuroinflammation and hyperactivation of the thalamus, insula, and cingulate cortex, responsible for interoceptive states, as well as those of the hippocampus/amygdala, contributing to emotions, via the blood-cerebrospinal fluid barrier structure and cerebrospinal fluid system. The prefrontal cortex controls these brain regions to maintain cognitive responses in harmony with interoception and emotion, while over time, dysregulation of the prefrontal cortex is induced. This likely prompts cognitive-perceptual bias-related cognitive distortion or catastrophic thinking of respiratory symptoms and asthma-dependent emotions, which, rather than airway sensory hyperinnervation, may mediate uncontrollable respiratory sensory perception, leading to a spiral along with asthma symptoms.

conclusionCollectively, it is hypothesized that type-2 immune responses initiate airway abnormalities, while neuroinflammation and neuronal hyperactivation can induce brain neural network disruption with psychiatric episodes, presumably enhancing the progression of asthma. The notion predicts novel therapeutics for type-2-high asthma comorbid with psychiatric disorders.