Empty Nose Syndrome Pathophysiology: A Systematic Review

Otolaryngol Head Neck Surg. 2022 Sep;167(3):434-451. doi: 10.1177/01945998211052919. Epub 2021 Oct 19.


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.

Keywords: empty nose syndrome; nasal perception; neurogenic dysfunction; psychogenic comorbidity.

Publication types

  • Systematic Review

MeSH terms

  • Cross-Sectional Studies
  • Humans
  • Nasal Obstruction* / complications
  • Nose
  • Nose Diseases* / surgery
  • Syndrome
  • Turbinates / surgery