An Integrated Framework for Olfactory Cleft-Related Olfactory Dysfunction:Anatomy, Immunity, and Microbiota
Olfactory dysfunction affects 10%–20% of the general population and up to 80% of patients with chronic rhinosinusitis, yet it frequently remains refractory to single-modality therapy. This issue's cover illustrates an integrated "Anatomy–Immunity–Microbiota" framework that positions obstruction of the olfactory cleft—the narrow corridor through which odorants reach the olfactory epithelium—as the initiating event in a self-amplifying cascade, in which obstruction, inflammation, and dysbiosis reinforce one another. Drawing on a comprehensive synthesis of the current literature, the authors propose a framework in which anatomical obstruction as the trigger factor, type 2 inflammation the amplifier, and microbiota dysbiosis the modulator. This model helps explain why anti-inflammatory or antimicrobial therapy alone often yields partial and transient benefit, and it reframes the management protocol around endotype-driven, multi-modality intervention. The review maps a multidimensional diagnostic approach—encompassing psychophysical testing, the Olfactory Cleft Endoscopy Scale, imaging, and olfactory cleft mucus biomarkers such as eosinophil-derived neurotoxin (EDN) and galectin-10—and recommended therapies based on evidence quality, from local drug delivery and biologics (dupilumab, tezepelumab) to regenerative platelet-rich plasma. Its central anatomical insight is a mechanism-based surgical dichotomy: hyposmia from structural blockage indicates olfactory cleft dilatation, whereas parosmia from aberrant peripheral signaling may require cleft blocking, the same structure demanding opposite interventions. This work highlights that anatomy-driven reasoning can clarify the refractory nature of olfactory cleft-related smell loss, offering a practical framework for mechanism-based clinical decision-making.
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