Dichapong KanjanawaseeRaewyn G. CampbellJanet RimmerRaquel AlvaradoJesada KanjanaumpornKornkiat SnidvongsLarry KalishRichard J. HarveyRaymond SacksSiriraj HospitalUNSW SydneyChulalongkorn UniversityThe University of SydneyMacquarie UniversityRoyal Prince Alfred HospitalFaculty of Medicine and HealthNotre Dame University2022-08-042022-08-042021-01-01Otolaryngology - Head and Neck Surgery (United States). (2021)10976817019459982-s2.0-85117478958https://repository.li.mahidol.ac.th/handle/20.500.14594/78585Objective: The pathophysiology of empty nose syndrome (ENS) remains unclear despite significant research. The pathophysiologic mechanism of ENS was systematically reviewed. Data Sources: MEDLINE and Embase. Review Methods: Data were systematically reviewed for studies that provided original data on pathophysiology. Results: A total of 2476 studies were screened, and 19 met the inclusion criteria: 13 case-control and 6 cross-sectional. Nine pathophysiologic themes were identified. • Demographics: ENS symptoms had no relationship with climatic factors. • Symptomatology: ENS patients demonstrated high symptom severity. • Mental health: Anxiety and depression including hyperventilation were reported in >50% of ENS patients and correlated with ENS symptom severity. • Anatomic features: Structural changes in response to turbinate surgery were similar between ENS and non-ENS patients. • Airflow analysis: Airflow parameters were similar between ENS and non-ENS patients after turbinate surgery. On computational fluid dynamic analysis, differences were found on multiple outcomes. • Diagnostic testing: The menthol detection test was impaired in ENS, and cotton placement in the airway improved ENS symptoms. • Cognitive function: Functional magnetic resonance imaging showed activation in emotional processing area during breathing. • Olfactory function: Subjective impairment was reported in ENS, but quantitative measures were similar to non-ENS patients. • Mucosal physiology/innate immunity: Turbinate histopathology in ENS showed a tissue-remodeling pattern. Nasal nitric oxide level was lower in ENS patients. Conclusion: There is evidence of high comorbid mental health disorders in ENS patients. An abnormal trigeminal-thermoreceptor response may be present in some patients. The influence of altered airflow and the evidence of surgery as the cause for ENS are unclear.Mahidol UniversityMedicineReviewSCOPUS10.1177/01945998211052919