Comorbid functional dyspepsia reflects IL-33–mediated airway neuronal dysfunction in asthma - 13/07/24
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Graphical abstract |
Abstract |
Background |
Neuronal dysfunction is implicated in the pathophysiology of asthma and functional dyspepsia (FD). However, the relationship between these diseases remains unclear.
Objective |
This study aimed to clarify the clinical implications of comorbid FD in asthma and to explore the unified pathway between asthma and FD by focusing on airway neuronal dysfunction.
Methods |
Clinical indices and biomarkers, including capsaicin cough sensitivity (C-CS), were compared between patients with asthma with and without FD. C-CS was determined on the basis of capsaicin concentration that induced at least 2 coughs (C2) or 5 coughs (C5). Additionally, the associations of airway inflammation with airway innervation and gastrointestinal motility were evaluated in mouse models of type 2 airway inflammation.
Results |
Patients with asthma with FD had worse asthma control and cough severity and lower C2 and C5 thresholds than those without FD. The severity of FD symptoms was negatively correlated with C2 and C5 thresholds. FD and poor asthma control were predictors of heightened C-CS (defined as C5 ≤ 2.44 μmol) in asthma. A mouse model of papain-induced airway inflammation developed airway hyperinnervation and gastrointestinal dysmotility, and both pathologies were ameliorated by an anti–IL-33 antibody. Moreover, papain-induced gastrointestinal dysmotility was mitigated by silencing the airway sensory neurons using QX-314, a sodium channel blocker. Furthermore, sputum IL-33 levels were significantly elevated in patients with asthma with FD or heightened C-CS compared to their counterparts.
Conclusion |
FD is significantly associated with airway neuronal dysfunction in asthma. IL-33–mediated airway neuronal dysfunction may contribute to the interaction between asthma and FD.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, capsaicin, functional dyspepsia, interleukin-33, neuronal dysfunction
Abbreviations used : BALF, C2/5, C-CS, FD, Feno, FSSG, GERD, GI, GSRS, ICS, J-LCQ, OVA, PGP9.5, T2, TRPV1, VAS
Plan
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