Nasal Diagnostic Tests

Empty Nose Syndrome (ENS) is a highly complex iatrogenic condition resulting from the alteration or excessive resection of nasal turbinates [4][5]. Because ENS involves aerodynamic, neurosensory, and mucosal mechanisms, a multidisciplinary, objective diagnostic approach is required.

1. In-Office Clinical and Provocative Tests

  • Rigid Nasal Endoscopy: Direct visual inspection of the nasal cavity. While it is a standard part of the clinical evaluation, visual assessment of cavity width and nasal patency is inherently subjective and cannot predict or measure actual airflow dynamics or resistance. It is used to document a history of surgical turbinate tissue loss (e.g., surgical stumps) and rule out other structural obstructions. It is also used to assess mucosal health, identifying crusting, dryness, pallor, or the "Serpentine Sign"—a compensatory, undulating swelling of the central and posterior septal mucosa [6].
  • The Cotton Test: A vital provocative test used to confirm ENS and predict surgical success. A moistened cotton pledget is placed in the area of the missing turbinate (usually the inferior meatus) for 20–30 minutes. A "positive" test requires patients to report a reduction of at least 7 points on the ENS6Q score with the cotton in situ, which has been established as the Minimal Clinically Important Difference (MCID) [7].
  • Septal Patch Test (SPT) & Staged Cotton Testing: A concurrent Nasal Septal Perforation (NSP) can drastically alter anterior airflow and mask a patient's responsiveness to the standard cotton test (causing a false negative). A Septal Patch Test (SPT) is utilized to temporarily occlude the perforation. If the SPT is positive, clinical guidelines recommend a staged algorithm: surgically close the NSP first, allow it to heal, and then re-administer the cotton test to properly unmask and diagnose ENS [8].
  • Stepwise Empty Nose Syndrome Evaluation (SENSE) Test: An advanced, single-blinded, four-step modification of the traditional cotton test. Because ENS patients carry a heavy psychological burden, they are highly susceptible to the placebo effect. The SENSE test evaluates patients under four conditions while blindfolded: (1) a placebo maneuver, (2) complete cotton blockade of the nasal vestibule, (3) cotton placed medially against the septum, and (4) cotton placed laterally in the inferior meatus. It proves that genuine ENS patients can accurately discriminate minimal changes in nasal aerodynamics and typically experience the most relief when resistance is restored laterally [9].

2. Aerodynamic, Airflow, and Computational Tests

  • Rhinomanometry (RM) & Rhinoresistometry (RRM): Measures transnasal pressure and airflow. RRM specifically calculates the Friction Coefficient and Hydraulic Diameter to evaluate the tendency of the inner nasal walls to create pathological turbulence. ENS patients often show normal or low airway resistance despite severe feelings of obstruction, highlighting that these tools measure gross pressure/flow rather than the aerodynamic quality or neurosensory detection of the air [10].
  • Acoustic Rhinometry (AR): Uses reflected sound waves to objectively map the geometry, minimal cross-sectional area (MCA), and Nasal Diffuser Opening Angle of the nasal cavity.
  • Computational Fluid Dynamics (CFD): Utilizing 3D models derived from patient CT scans, CFD provides the most comprehensive simulation of invisible nasal airflow [11][12]. Advanced ENS parameters include:
    • Wall Shear Stress (WSS): Measures the friction generated when moving air contacts the mucosa, which provides the mechanical signal for breathing sensation. WSS is significantly reduced in ENS.
    • Airflow Partitioning: Detects abnormal aerodynamic shunting, often showing that air flows predominantly through the middle meatus, completely bypassing the inferior airway.
    • Heat Flux and Mucosal Cooling: Evaluates the temperature exchange between the air and mucosa, which directly activates thermoreceptors [13].
    • Nasal Air Conditioning & Particle Deposition: Evaluates the nose's ability to warm and humidify inspired air before it reaches the nasopharynx, as well as its ability to filter toxic inhaled aerosols—both of which are severely impaired in ENS [14].

3. Sensory, Trigeminal, and Chemosensory Tests

  • Menthol Lateralization Detection Thresholds (LDTs): Evaluates the function of the trigeminal nerve and TRPM8 (cool thermoreceptor) channels. ENS patients demonstrate significantly impaired (higher) detection thresholds compared to healthy controls, confirming a concurrent neurosensory loss alongside structural tissue loss.
  • Nasal Air-Jet Sensitivity Test: A highly specialized sensory test that uses a controlled device to deliver targeted air jets directly to the nasal mucosa to evaluate localized mechanosensitivity. Recent 2026 data validates that this test effectively and definitively differentiates true ENS patients (who have impaired air-jet detection) from asymptomatic patients who have undergone turbinate reductions [15].
  • Olfaction Testing: Uses standardized methods like the Sniffin' Sticks test (evaluating Threshold, Discrimination, and Identification). While the olfactory receptors themselves may be intact, ENS patients often experience functional hyposmia because the disorganized airflow fails to effectively transport odorant molecules to the olfactory cleft [16].

4. Imaging and Structural Tests

  • Computed Tomography (CT) Scans: Standard, Cone-Beam (CBCT), and Multi-slice CT scans are evaluated for ENS-specific morphological criteria. This includes measuring Inferior Turbinate Volume (ITV), anterior airspace diameter, and the mucosal thickness of the central and posterior septum (to identify compensatory hypertrophy/the Serpentine Sign) [17][6].
  • Functional Magnetic Resonance Imaging (fMRI): Observes real-time brain activity. In ENS patients, fMRI shows abnormal and heightened activation in the emotional processing areas (limbic system, amygdala, and prefrontal cortex) during respiration, directly linking their physical airway dysfunction to profound psychological distress [18].

5. Mucosal Function, Secretion, and Molecular Biomarkers

  • Nasal Secretions and Molecular Biomarkers: Analysis of glandular secretion markers (Mucin-5AC, Lactoferrin), neurogenic inflammation markers (Substance P, CGRP), and nonspecific inflammatory cytokines to objectively measure chronic mucosal inflammation.
  • Saccharine Test (Mucociliary Clearance): Measures mucociliary transport time. Poor clearance in ENS indicates severe disruption of epithelial health and ciliary function.
  • Nasal Nitric Oxide (nNO) Levels: Measured using a non-invasive electrochemical analyzer. nNO levels are often significantly lower in ENS patients.
  • Systemic Serum Biomarkers: Tests for systemic inflammatory markers, specifically High-Sensitivity C-Reactive Protein (hsCRP) and Interleukin-6 (IL-6). Elevated preoperative levels of these systemic inflammatory markers are highly associated with the severe postoperative psychiatric burden and suicidal ideation seen in ENS [19].

6. Advanced Histological Tests (Nasal Biopsy)

  • Tissue Biopsy (Light & Electron Microscopy): Direct sampling of the nasal tissue. In ENS, histopathology distinctly reveals squamous metaplasia, submucosal fibrosis (collagen scarring), glandular atrophy, and a unique finding called goblet cell metaplasia [20].
  • Immunohistochemical (IHC) Staining for TRPM8: A specific stain that quantifies the expression levels of TRPM8 cold receptors in the epithelium and submucosal vessels, which are significantly reduced in ENS [20].

7. Pulmonary, Systemic, and Autonomic Tests

  • Hyperventilation Provocation Test (HVPT) & End-Tidal CO2 (EpCO2): Abnormally low nasal airway resistance disrupts normal pulmonary mechanics and the nasopulmonary reflex, severely impairing alveolar gas exchange. To compensate for this mechanical failure and effectively inflate the lungs, patients are physically forced into a continuous hyperventilation cycle. The HVPT, combined with EpCO2 capnography, objectively assesses this physiological compensation by testing for Hyperventilation Syndrome (HVS) and hypocapnia (low blood CO2) [21].
  • Composite Autonomic Symptom Scale-31 (COMPASS 31): A validated, self-reported questionnaire utilized to assess the severity of systemic Autonomic Nervous System (ANS) dysfunction. ENS patients exhibit significantly higher COMPASS 31 scores compared to controls, correlating closely with ENS severity [22].
  • Spirometry and Cardiopulmonary Exercise Testing (CPET): Measures functional exercise capacity, maximum oxygen consumption (VO2 max), and the subjective Rating of Perceived Exertion (RPE) [23].

8. Validated Psychometric and Patient-Reported Outcome Measures (PROMs)

  • Empty Nose Syndrome 6-Item Questionnaire (ENS6Q): The gold-standard diagnostic questionnaire scoring six items: dryness, diminished airflow, suffocation, nose feeling too open, crusting, and burning. A score of ≥11 strongly suggests ENS (or ≥12 to specifically differentiate ENS from other mechanical nasal obstructions) [7].
  • Sino-Nasal Outcome Test (SNOT-25): Adds the five core ENS symptoms (dryness, difficulty with nasal breathing, suffocation, excessively open nose, and crusting) to the foundational SNOT-20 tool. It is comprehensive, covering rhinologic, sleep, ear/facial, and psychological domains [24].
  • Symptom Cluster Analysis Profiling: A prognostic analytical tool that utilizes hierarchical dendrograms and heatmaps to group a patient's preoperative symptoms across domains (rhinogenic, extra-nasal, eye/facial, sleep, and psychological). This clustering helps determine the Positive Predictive Value (PPV) for surgical success and flags patients at high risk for persistent postoperative ENS symptoms [25].
  • Mental Health Assessments: Formal psychiatric evaluations, including the Beck Depression Inventory (BDI-II), Beck Anxiety Inventory (BAI), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7) [26].
  • Sleep Assessments (EpSS, PSQI, & PSG): Sleep dysfunction is a hallmark of ENS. Testing includes the Epworth Sleepiness Scale (EpSS), the Pittsburgh Sleep Quality Index (PSQI), and formal Polysomnography (PSG) to evaluate the Apnea-Hypopnea Index (AHI) and arousal index.
  • Functional Impairment and Quality of Life Indices: Used to quantify the severe disabling nature of the disease. These include the Work Productivity and Impairment (WPAI) questionnaire, the EuroQol General Health State Survey (EQ-5D-5L), and the Rhinosinusitis Disability Index (RSDI).

References

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  2. Borchard, N. A., Dholakia, S. S., Yan, C. H., Zarabanda, D., Thamboo, A., & Nayak, J. V. (2019). Use of intranasal submucosal fillers as a transient implant to alter upper airway aerodynamics: implications for the assessment of empty nose syndrome. International Forum of Allergy & Rhinology, 9(6), 681-687.
  3. Chang, F.-Y., Fu, C.-H., & Lee, T.-J. (2021). Outcomes of olfaction in patients with empty nose syndrome after submucosal implantation. American Journal of Otolaryngology, 42(6), 103131.
  4. Fu, C.-H., Chen, C.-C., Huang, C.-C., Chang, P.-H., & Lee, T.-J. (2021). Serum high-sensitivity C-reactive protein is associated with postoperative psychiatric status in patients with empty nose syndrome. Diagnostics, 11(12), 2388.
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  6. Huang, C.-C., Wu, P.-W., Fu, C.-H., Huang, C.-C., Chang, P.-H., Wu, C.-L., & Lee, T.-J. (2019). What drives depression in empty nose syndrome? A sinonasal outcome test-25 subdomain analysis. Rhinology, 57(6), 469-476.
  7. Huang, C.-C., Sun, P.-H., Wu, P.-W., Fu, C.-H., Huang, C.-C., Chang, P.-H., ... & Lee, T.-J. (2023). Computed tomographic evaluations in patients with empty nose syndrome. The Laryngoscope, 134(5), 2087-2092.
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  10. Lee, D. W., Kim, J. Y., & Kwon, J. H. (2024). Functional exercise capacity and perceived exertion in patients with empty nose syndrome. Diagnostics, 14(9), 885.
  11. Malik, J., Dholakia, S., Spector, B. M., Yang, A., Kim, D., Borchard, N. A., ... & Nayak, J. V. (2021). Inferior meatus augmentation procedure (IMAP) normalizes nasal airflow patterns in empty nose syndrome patients via computational fluid dynamics (CFD) modeling. International Forum of Allergy & Rhinology, 11(5), 902-909.
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  14. Nayak, J. V., Borchard, N. A., & Thamboo, A. (2024). Stepwise empty nose syndrome evaluation (SENSE) test: A modified cotton test for reduced bias in office diagnosis of ENS. International Forum of Allergy & Rhinology, 14(6), 1140-1144.
  15. Radulesco, T., Meister, L., Bouchet, G., et al. (2019). Functional relevance of computational fluid dynamics in the field of nasal obstruction: A literature review. Clinical Otolaryngology, 44(5), 801-809.
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