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BACKGROUND Empty nose syndrome (ENS) remains a controversial disease primarily associated with inferior turbinate tissue loss. Cotton placement into the inferior meatus often alleviates ENS symptoms within minutes, but the physiologic explanation for this phenomenon is unknown. Computational fluid dynamics (CFD) was employed to evaluate the mechanisms of altered nasal airflow conferred by cotton testing. METHODS Six ENS patients (12 sides) with pre-existing sinus computed tomography (CT) imaging were enrolled after marked symptomatic improvement (decrease in score on the Empty Nose Syndrome 6-Item Questionnaire [ENS6Q] of >7 points) with office-based cotton testing. The fashioned cotton plug was labeled in situ with iohexol contrast spray, and sinus CT was immediately obtained to detect cotton contouring in the inferior meatus. CT imaging from pre- and post-cotton placement was analyzed using comparative CFD techniques. RESULTS After cotton placement, significant symptomatic improvement and reduced ENS6Q scores (16.8 ± 4.1 to 3.1 ± 2.4; p < 0.001) were recorded. Using CFD, cotton placement produced an expected 21% increase in upper airway resistance (p < 0.05). However, a significant shift in the nasal airflow distribution was also detected, with a transition of airflow vectors away from a middle meatus jetstream (-41%; p < 0.002). CONCLUSION Objective CFD assessment confirmed that the cotton test not only increases nasal resistance, but also restores airflow distribution to the inferior meatus in symptomatic ENS patients. These results highlight the potential efficacy of cotton test in ENS patients and further bolster the utility of this tool in identifying appropriate candidates for the inferior meatus augmentation procedure.

Our understanding of empty nose syndrome (ENS) continues to evolve. Prior studies evaluating airway augmentation to treat ENS did not use validated disease-specific questionnaires, making the true impact of these surgeries unclear. We present a case series of 10 patients with ENS (11 procedures) who underwent the inferior meatus augmentation procedure (IMAP) between September 2014 and May 2017. Subjective outcomes of IMAP included comparisons of preoperative and postoperative assessments (1 week, 1 month, 3 months, 6 months) using the Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item Scale (GAD-7), and Sino-Nasal Outcome Test-22 (SNOT-22). The decrement in ENS6Q scores observed maintained statistical significance at 6 months (P ≤ .001). Similar results were achieved with PHQ-9, GAD-7, and SNOT-22 (P ≤ .01, P ≤ .01, P ≤ .001, respectively). IMAP can dramatically improve the quality of life of ENS patients regarding both ENS-specific symptoms and psychological well-being.

Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from coronavirus disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little is known about the extent to which distinct tissue sites in the human head and neck region and proximal respiratory tract selectively permit SARS-CoV-2 infection and replication. In this translational study, we discover key variabilities in expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential SARS-CoV-2 entry factors, among the mucosal tissues of the human proximal airways. We show that SARS-CoV-2 infection is present in all examined head and neck tissues, with a notable tropism for the nasal cavity and tracheal mucosa. Finally, we uncover an association between smoking and higher SARS-CoV-2 viral infection in the human proximal airway, which may explain the increased susceptibility of smokers to developing severe COVID-19. This is at least partially explained by differences in interferon (IFN)-β1 levels between smokers and non-smokers., Graphical Abstract, Nakayama et al. discover key variabilities in expression of SARS-CoV-2 entry factors among human head and neck mucosal tissues. They demonstrate that SARS-CoV-2 preferentially infects the nasal cavity and trachea. They uncover an association between smoking and higher SARS-CoV-2 in the human proximal airway, in part because of differences in IFN-β1 expression.

The patient is a 68-year-old male who reported a history of excellent health until 10 years ago, when he developed a cardiac/thromboembolic condition that required use of aspirin and clopidogrel for anticoagulation. In his first year of treatment, he unfortunately developed recurrent right-sided epistaxis. He recalled presenting to his local emergency department (ED) on multiple occasions to manage the nosebleeds, which led to multiple right-sided nasal cautery procedures. On his last ED visit, given profuse recurrent epistaxis, additional cautery of the nasal septum and right-sided nasal packing were pursued. Upon aggressive placement and advancement of the nasal packing into his right nasal cavity by the ED treatment team, the patient recalls experiencing an “unbearable, tearing sensation” and “excruciating, blistering pain” to his right face. Because of this traumatic experience, the patient was admitted and taken to the OR the following day by an otolaryngologist for additional surgical control of epistaxis. After this procedure, he learned that a large nasal septum perforation was found, and that “there was damage to his nasal turbinate” but that nothing further could be offered.

Empty nose syndrome (ENS) is a debilitating condition associated with inferior turbinate tissue loss. Surgical augmentation of the inferior meatus has been proposed to treat ENS, although efficacy data with validated, disease-specific questionnaires is limited. Instead we evaluated submucosal injection of a transient, resorbable filler into the inferior meatus to favorably alter nasal aerodynamics in ENS patients.Patients with a history of inferior turbinate reduction, diagnosed with ENS via Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) and cotton testing, were enrolled and underwent submucosal injection of carboxymethylcellulose/glycerin gel (Prolaryn®) into the inferior meatuses between July 2014 and May 2018. This material likely resorbs over several months. Outcomes included comparisons of preinjection and postinjection symptoms at 1 week, 1 month, and 3 months using the ENS6Q, 22-item Sino-Nasal Outcome Test (SNOT-22), Generalized Anxiety Disorder 7-item scale (GAD-7), and Patient Health Questionnaire-9 (PHQ-9).Fourteen patients underwent injections. Mean ENS6Q scores significantly decreased from baseline at 1 week (20.8 vs 10.5; p0.0001), and remained reduced but upward-trending at 1 month (13.7, p = 0.002) and 3 months (15.5, p0.05) following injections. Mean SNOT-22 scores significantly decreased at 1 week (p = 0.01) and 1 month (p = 0.04), mean GAD-7 at 1 month (p = 0.02) and 3 months (p = 0.02), and mean PHQ-9 at 1 week (p = 0.01) and 1 month (p = 0.004) postinjection.Transient, focal airway bulking via submucosal filler injection at sites of inferior turbinate tissue loss markedly benefits ENS patients, suggesting that aberrant nasal aerodynamics from inferior turbinate tissue loss contributes to (potentially reversible) ENS symptoms.

OBJECTIVES/HYPOTHESIS We sought to report the long-term, symptom-focused, prospective outcomes in empty nose syndrome (ENS) patients after undergoing inferior meatus augmentation procedure (IMAP) through use of four validated questionnaires: Empty Nose Syndrome 6-Item Questionnaire (ENS6Q), 22-item Sino-Nasal Outcome Test (SNOT-22), Generalized Anxiety Disorder 7-Item Scale (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). STUDY DESIGN Prospective case series. METHODS A single-center prospective case series was performed for patients diagnosed with ENS who underwent IMAP between July 2017 and February 2020. Diagnosis of ENS was based on the following criteria: 1) reported discomfort with nasal breathing and/or paradoxical nasal obstruction after inferior turbinate reduction, 2) a positive ENS6Q score of at least 11, and 3) a positive cotton test. Questionnaire responses were recorded prior to surgery as well as 1, 3, 6, and 12 months postoperatively. RESULTS Seventeen eligible patients were included. Mean ENS6Q scores were significantly reduced at all postoperative time points (p

Importance Although oral corticosteroids are commonly prescribed following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) without nasal polyposis, there are little data to suggest that this is a beneficial practice. Objective To assess the efficacy of oral corticosteroids following ESS in CRS without polyps. Design, Setting, and Participants This prospective double-blinded, placebo-controlled, randomized noninferiority clinical trial conducted in a single academic tertiary rhinology practice included adults with CRS without polyps undergoing ESS. Of 81 patients recruited, 72 completed the study. Interventions Patients were randomized into 2 treatment groups: a 12-day postoperative taper of oral prednisone vs matched placebo tablets. All study patients also received a uniform 2-week postoperative regimen of oral antibiotics, fluticasone nasal spray, and saline rinses. Main Outcomes and Measures The primary outcome measures were Sinonasal Outcome Test-22 (SNOT-22) scores and Lund-Kennedy endoscopy scores, collected preoperatively and postoperatively at 1 week, 1 month, 3 months, and 6 months. Scores were compared between treatment groups at each time point using longitudinal difference between treatment groups and analyzed using 2-way, repeated measures analysis of variance. Secondary outcome measures included treatment-related adverse effects. Results Overall, 72 patients (mean [SD] age, 49.4 [14.9] years; 36 men, 36 women) completed the study, with 33 in the prednisone arm and 39 in the placebo arm. When comparing longitudinal differences between treatment groups, there was no clinically meaningful difference observed in SNOT-22 total (F[4254] = 1.71, η2 = 0.01 [95% CI, 0.00-0.05]) or Lund-Kennedy scores (F[4247] = 1.23, η2 = 0.02 [95% CI, 0.00-0.50]). In SNOT-22 subdomain analyses, there was no clinically meaningful difference between treatment groups for rhinologic, extranasal rhinologic, ear/facial, or sleep subdomains. However, the prednisone group had worse longitudinal scores for psychological dysfunction compared with the placebo group (F[4254] = 3.18, η2 = 0.05 [95% CI, 0.02-0.09]). Reported adverse effects were similar between the 2 treatment groups. Conclusions and Relevance In this randomized clinical trial of patients with CRS without polyps, oral prednisone following ESS conferred no additional benefit over placebo in terms of SNOT-22 total scores, SNOT-22 rhinologic subscores, or Lund-Kennedy endoscopy scores up to 6 months after surgery. Patients receiving prednisone, however, did demonstrate worse SNOT-22 psychologic subdomain scores. These results suggest that the risks of oral corticosteroids may outweigh the benefits; thus use of oral corticosteroids after ESS for CRS without polyps should be carefully considered. Trial Registration ClinicalTrials.gov Identifier:NCT02748070

The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen., Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile cilia of the human nasal and respiratory tract and is not affected by the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.

BACKGROUND Empty nose syndrome (ENS) is a controversial upper airway disorder most commonly associated with tissue loss from the inferior turbinates. The inferior meatus augmentation procedure (IMAP) has been shown to effectively reduce ENS symptoms in a durable manner, but the precise mechanisms that may govern this symptomatic improvement remain unknown. METHODS Five patients with ENS who underwent bilateral IMAP via submucosal costal cartilage implant were assessed. Pre-implant and 6 months post-implant computed tomography (CT) imaging for each ENS patient was analyzed in a blinded fashion using computational fluid dynamics (CFD) modeling to investigate intrapatient changes in airflow parameters. RESULTS Following surgery, ENS patients have significantly improved symptoms as indexed by Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) scoring (pre-implant: 14.00 ± 4.06 [mean ± standard deviation]; 95% confidence interval [CI], 10.44 to 17.56; post-implant: 4.8 ± 2.77; 95% CI, 2.37 to 7.23; Cohen's d = 2.64; p = 0.02). Using CFD, a significant shift in nasal airflow patterns was observed, where airflow deviates away from the middle meatus upon hitting the implant (pre-implant: 67.13% ± 11.14%; 95% CI, 60.22% to 74.04%; post-implant: 46.18% ± 12.81%; 95% CI, 38.23% to 54.12%; d = 1.74; p < 0.05) toward the inferior meatus (pre-implant: 30.55% ± 11.29%; 95% CI, 23.55% to 37.55%; post-implant: 42.59% ± 9.60%; 95% CI, 36.63 to 48.54%; d = 1.14; p < 0.05). No significant changes were found in nasal resistance (pre-implant: 0.102 ± 0.015; 95% CI, 0.092 to 0.112 Pa*s/mL; post-implant: 0.105 ± 0.041; 95% CI, 0.081 to 0.130 Pa*s/mL). In addition, the improvement of ENS6Q scoring significantly correlated with percent reduction in aberrant airflow through the middle meatus (R2 = 0.60, p = 0.04). CONCLUSION This study supports our prior working hypothesis that disordered vectors of nasal airflow congregate in the middle meatus contribute to ENS symptoms, not nasal resistance. Moreover, these data illuminate a paradoxical, but consistent, restoration of nasal airflow to the inferior meatus following the replacement of turbinate tissue volume in the inferior meatus via IMAP surgery, potentially due to the Coanda effect.

Background The objective of this study is to determine whether the infiltration of 1% lidocaine with 1:100,000 epinephrine in addition to topical application of 1:1000 epinephrine significantly improves surgical field grading scale score over topical 1:1000 epinephrine alone. Methods A prospective, double-blind, randomized, controlled study was performed of 40 patients undergoing bilateral endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). Patients were enrolled and randomly assigned to receive infiltration with 1% lidocaine with 1:100,000 epinephrine on 1 side of the nasal cavity vs plain saline on the other side in preparation for ESS. Both groups received topical application of 1:1000 epinephrine. Surgical videos were recorded and Wormald surgical field grading scale was assigned by 2 blinded reviewers. The number of extra 1:1000 epinephrine pledgets used during the surgery, estimated blood loss, and surgical duration were also recorded. Results There were no statistically significant differences in Wormald surgical field grading scale, number of extra pledgets used, or estimated blood loss between the nasal cavity side infiltrated with 1% lidocaine with 1:100,000 epinephrine in comparison to infiltration with saline. The side infiltrated with 1% lidocaine with 1:100,000 epinephrine had a reduced operative time compared to the side infiltrated with saline (p = 0.002). There were no differences in postoperative bleeding from questionnaire completed by patient at the first postoperative visit. Conclusion Addition of infiltration of 1% lidocaine with epinephrine 1:100,000 to topical application of epinephrine 1:1000 for preparation of ESS does not significantly improve surgical field of view compared to topical epinephrine alone.