Comorbid functional dyspepsia reflects IL-33-mediated airway neuronal dysfunction in asthma

Area of Science:

• Neuroscience
• Immunology
• Pulmonology
• Gastroenterology

Background:

• Neuronal dysfunction is a key factor in asthma and functional dyspepsia (FD).
• The link between asthma and FD, particularly concerning neuronal pathways, is not well understood.

Purpose of the Study:

• To investigate the clinical impact of co-occurring FD in asthma patients.
• To explore a shared pathway between asthma and FD, focusing on airway neuronal dysfunction.

Main Methods:

• Compared capsaicin cough sensitivity (C-CS) in asthma patients with and without FD.
• Assessed airway inflammation, innervation, and gastrointestinal motility in mouse models.
• Measured sputum interleukin-33 (IL-33) levels.

Main Results:

• Asthma patients with FD exhibited poorer asthma control, increased cough severity, and reduced C-CS thresholds.
• FD symptom severity correlated negatively with C-CS thresholds.
• Airway inflammation in mice led to hyperinnervation and gastrointestinal dysmotility, both improved by anti-IL-33 therapy and sensory neuron silencing.
• Elevated sputum IL-33 levels were observed in asthma patients with FD or heightened C-CS.

Conclusions:

• Functional dyspepsia is significantly associated with airway neuronal dysfunction in asthma patients.
• Interleukin-33 (IL-33)-mediated airway neuronal dysfunction is a potential mechanism underlying the interaction between asthma and FD.