Diagnostic

Cool thermoreceptors of the trigeminal nerve (TRPM8) play a critical role in the sensation of normal nasal airflow. It is hypothesized that defects in this receptor pathway contribute to the symptomology of ENS. Based on this relationship, the study evaluated nasal mucosal sensitivity to mechanical air-jet stimulation.

Two groups-ENS patients and septo-turbinate surgery patients without ENS symptoms—were presented with three stimuli using a custom device. Two stimuli were blanks with no airflow, and one was a positive airflow stimulus. Participants were asked to identify which of the three stimuli was positive (contained airflow).

Statistical analysis showed a significant difference in stimulation thresholds across locations in the ENS group, whereas no such differences were observed in the septo-turb group.

Significant correlations were found between the stimulation threshold and the SNOT score only at the opposing septum of the center of the inferior turbinate (not at other stimulation sites). These correlations were all positive, indicating that worse stimulation thresholds were associated with higher symptom scores. One possible explanation is that ENS patients may have experienced greater disruption or trauma to the septum after surgery.

Results demonstrate that nasal symptoms may be associated with lower regional mucosal sensitivity to airflow stimulation.

According to the authors, this was the first study to examine the microscopic changes associated with ENS. The study included 17 patients with ENS who underwent surgical treatment and completed the 1-year postoperative survey, along with 6 control patients with benign pituitary tumors undergoing transsphenoidal excision. Only ENS patients with a positive cotton test and no other sinonasal disease were included*.

All patients underwent a biopsy of no more than 0.5 cm³, taken from the midpoint of the remnant inferior turbinate, which represented the most atrophic region. Compared with the control group, the ENS group exhibited more pronounced squamous metaplasia, greater submucosal fibrosis, and significantly lower submucosal gland grading. Although the difference did not reach statistical significance, a unique histological feature - goblet cell metaplasia - was notably observed in six ENS patients. The epithelial layers in the ENS group were mostly intact, with preservation of ciliated and goblet cells, and there was no significant difference between groups in the presence of cilia or goblet cells**.

*Although the authors stated that patients had “no other sinonasal disease,” six of the participants were later noted to have allergic rhinitis. Further discussion can be found in the In Response to Distinct Histopathology Characteristics in Empty Nose Syndrome.

**It is important to acknowledge the limitations of this study, particularly the small sample size and the method used for patient selection.

A study describes a 50-year-old male with a previous medical history of maxillary osteomyelitis and multiple interventions resulting in a complex mediofacial resection. Nasal endoscopy and computed tomography revealed a large pathologic cavity with complete absence of the nasal septum and severe epithelial changes, including crusting, hemorrhage, and ulceration.

A biopsy showed severe, nonspecific changes in the nasal epithelium, including areas of minimal preserved respiratory epithelium, reserve cell hyperplasia, epithelial erosions and ulcers, squamous cell metaplasia with acanthosis, and extensive keratinization. Similar nonspecific changes were observed in the submucosa, with squamous metaplasia of submucosal glands sometimes leading to complete glandular replacement and formation of submucosal squamous cell nests without atypia. The interstitium exhibited abundant granulation tissue, fibrosis, and chronic inflammatory infiltrates of lymphocytes and plasma cells, while adjacent bones showed no active inflammation.

Although the case did not fit the current ENS classification, the diagnosis was accepted based on extensive but nonspecific clinical, endoscopic, radiologic, and histomorphologic findings; according to existing criteria, it was classified as ENS not elsewhere classified (NEC), since no specific category currently encompasses such presentations.

By the time of the study (2016), the most commonly used survey for ENS was the SNOT-25, an extension of the SNOT-20 with additional parameters for dryness, difficulty with nasal breathing, suffocation, nose feelling ‘too open’ and nasal crusting. However, a specific ENS questionnaire was needed because the SNOT-25 cannot reliably distinguish ENS from chronic rhinosinusitis (CRS) or other nasal conditions.

In this study, ENS was diagnosed in patients with nasal discomfort or paradoxical obstruction, a history of inferior turbinate reduction (confirmed by endoscopy or CT), and a positive cotton test. The ENS6Q was administered to three cohorts: 15 ENS patients, 30 patients with chronic rhinosinusitis without polyposis (CRSsNP), and 30 healthy controls with no prior nasal surgery. They rated six common ENS symptoms (suffocation, burning, openness, crusting, dryness, and lack of air sensation) on a 0–5 severity scale

ENS patients reported significantly higher ENS6Q scores at both the initial and follow-up evaluations. A score of 10.5 / 30 was identified as the optimal cut-off for predicting ENS. The symptoms most strongly associated with ENS were ‘nose feels too open’ and ‘lack of air sensation’.

Reliability was assessed through high internal consistency, meaning scores remained stable when a patient’s condition did not change. Patients completed the questionnaire again after 5 days.

ENS is a rare, poorly understood complication of turbinate surgery. It is divided into subtypes: ENS-IT (inferior turbinate removal, most common), ENS-MT (middle turbinate removal), and ENS-both (resection of both). A fourth subtype, “ENS-type,” has been proposed for patients with preserved turbinate structure but mucosal surface damage causing symptoms.

Diagnosing ENS is difficult due to the lack of objective tests, requiring reliance on patient-reported symptoms. It is largely a diagnosis of exclusion, as it must be distinguished from conditions such as chronic rhinosinusitis, autoimmune nasal diseases, and primary atrophic rhinitis. The condition may present months to years after surgery, and symptoms can sometimes improve spontaneously over time.

Numerous studies have documented the sensation of nasal obstruction without any anatomical blockage. This paradox is thought to arise because the sensation of nasal patency depends on activation of trigeminal “cool” thermoreceptors (TRPM8) by mucosal cooling. When these receptors are insufficiently stimulated, the brain perceives reduced airflow, leading to a sensation of congestion and shortness of breath.