Table 1.
Summary of the studies on the mechanisms of olfactory dysfunction in CRS.
| Study | Methodology | Measure of olfaction | Main outcomes |
|---|---|---|---|
| Histopathological study | |||
| Kern (28) | Olfactory epithelium | UPSIT | Infiltration of lymphocytes, macrophages, and eosinophils in the lamina propria of the olfactory epithelium in patients of CRS with olfactory dysfunction |
| Yee et al. (29) | Olfactory epithelium | Olfactory threshold task of phenylethyl alcohol | Increased erosion of the olfactory epithelium and eosinophils infiltrating the olfactory epithelium in patients of CRS with olfactory dysfunction |
| Hauser et al. (30) | Ethmoid mucosa | 40-item smell identification test | An association of tissue eosinophilia in the ethmoid sinuses and olfactory dysfunction |
| Lavin et al. (31) | Superior turbinate | UPSIT | An association of tissue eosinophilia in the superior turbinate and olfactory dysfunction |
| Wu et at. (32) | Superior turbinate | Sniffin' Sticks | An association of tissue eosinophilia in the superior turbinate and post-operative olfactory dysfunction |
| Association study | |||
| Schlosser et al. (33) | Measurement of biomarkers in collected olfactory cleft mucus | Sniffin' Sticks | A correlation of IL-5 levels and olfactory dysfunction in both CRSwNP and CRSsNP |
| Wu et al. (34) | Measurement of biomarkers in collected olfactory and middle meatal mucus | Smell Identification Test | Elevated levels of IL-2, IL-5, IL-6, IL-10, and IL-13 associated with reduced test scores for smell identification, especially in CRSwNP patients |
| Morse et al. (22) | Measurement of biomarkers in collected middle meatal mucus | Smell Identification Test | An association between IL-2, IL-5 and IL-13, and olfaction |
| Soler et al. (35) | Measurement of biomarkers in collected olfactory cleft mucus | Questionnaire of Olfactory Dysfunction | An association and elevations in TNF-α, IL-6, CCL2, CCL3, and CCL20 with lowest olfactory scores in clusters dominated by type 2 biomarkers |
| Animal study | |||
| Turner et al. (36) | Unilateral olfactory bulbectomy on IOI micea | IHC study of the olfactory epithelium | Suppression of olfactory regeneration by TNF-α |
| Sultan et al. (37) | Systemic corticosteroid treatment on IOI micea | IHC study of the olfactory epithelium; EOG | TNF-α causing physiologic dysfunction of olfactory neurons; prednisolone preventing neuronal loss and olfactory dysfunction by diminishing the subepithelial inflammation |
| Pozharskaya et al. (38) | TNFR2 knockout in IOI background micea | IHC study of the olfactory epithelium; EOG | TNFR2 mediating neuronal proliferation and death but not TNF-α-induced dysfunction of mature olfactory sensory neurons |
| Sousa Garcia et al. (39) | TNFR1 knockout in IOIa background and allergen-induced inflammation mice | IHC study of the olfactory epithelium; EOG | TNFR1 regulating TNF-α-induced inflammation and reduces allergen-induced inflammation |
a
Inducible olfactory inflammation mice is a genetic model of olfactory inflammation by temporally controlled induction of TNF-α by olfactory sustentabular cells.
CRS, chronic rhinosinusitis; UPSIT, University of Pennsylvania Smell Identification Test; IL, interleukin; CRSwNP, chronic rhinosinusitis with nasal polyps; CRSsNP, chronic rhinosinusitis without nasal polyps; TNF, tumor necrosis factor; CCL, C-C motif chemokine ligand; IOI, inducible olfactory inflammation; IHC, immunohistochemical; EOG, electro-olfactogram.