Novel olfactory cleft computed tomography staging system reveals a trizone anatomic model and biphasic progression in central compartment atopic disease.

Central compartment atopic disease (CCAD) is an early stage of type 2 chronic rhinosinusitis characterized by type 2 inflammation and frequent olfactory dysfunction, primarily due to olfactory cleft (OC) obstruction. A novel OC computed tomographic scoring system was developed to evaluate multisectional obstruction patterns in CCAD, identify key regions of OC obstruction, and examine their associations with olfactory function and eosinophilic inflammation. A prospective cross-sectional study enrolled 257 adults with primary bilateral chronic rhinosinusitis. Participants were divided into a development cohort (n = 177) and a validation cohort (n = 80), with 75 allergic rhinitis patients as controls. A Multisection Olfactory Cleft Opacity Staging System (MOCOS) was developed to assess apical and middle-lower opacification by evaluating 6 coronal sections. Peripheral blood was analyzed for inflammatory endotypes. Risk factors were identified for CCAD and the relative importance of variables associated with olfactory dysfunction analyzed. Scores fell into 3 distinct zones according to OC subtype: a disease signature zone, which is predictive of CCAD diagnosis; an olfactory functional zone, which correlates with smell loss severity; and an eosinophilic inflammation zone, which is linked to systemic type 2 inflammation. Opacification progression from the disese signature zone to the olfactory function zone drives both the onset and progressive worsening of the olfactory dysfunction. MOCOS permitted us to identify a trizone OC model in CCAD, revealing a biphasic opacification progression that drives olfactory dysfunction onset and progression, thereby refining disease classification and elucidating its underlying pathogenesis to inform targeted therapy.