Empty nose syndrome pathophysiology: a systematic review

Dichapong Kanjanawasee*, Raewyn G. Campbell, Janet Rimmer, Raquel Alvarado, Jesada Kanjanaumporn, Kornkiat Snidvongs, Larry Kalish, Richard J. Harvey, Raymond Sacks

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Objective: 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.

Original languageEnglish
Number of pages18
JournalOtolaryngology - Head and Neck Surgery (United States)
Early online date19 Oct 2021
Publication statusE-pub ahead of print - 19 Oct 2021


  • empty nose syndrome
  • nasal perception
  • neurogenic dysfunction
  • psychogenic comorbidity


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