Sinonasal complications of severe acute respiratory syndrome coronavirus-2: A single center case series

Background: The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in an unprecedented global pandemic. Most infected patients are either asymptomatic or have mild upper respiratory infection symptoms. However, life-threatening sequelae have been observed. In this report, we reviewed nine cases of patients with severe complications from sinonasal disease in the setting of acute SARS-CoV-2 infection. Methods: IRB approval was obtained prior to study initiation. A retrospective chart review was performed of patients admitted to a tertiary hospital with complex sinonasal symptoms that required otolaryngologic evaluation and management in the setting of concomitant SARS-CoV-2 infection. Results: Nine patients, ranging from ages 3 to 71 years, with sinonasal disease and simultaneous SARS-CoV-2 infection were identified. Initial presentations ranged from asymptomatic infection to mild/moderate disease (nasal obstruction, cough) or more severe sequelae including epistaxis, proptosis, or neurologic changes. SARS-CoV-2 tests were positive from one to 12 days after symptom onset, with three patients receiving SARS-CoV-2-directed treatment. Complex disease presentations included bilateral orbital abscesses, suppurative intracranial infection, cavernous sinus thrombosis with epidural abscess, systemic hematogenous spread with abscess development in four distinct anatomic locations, and hemorrhagic benign adenoidal tissue. Eight of nine patients (88.8%) required operative intervention. Patients with abscesses also required prolonged, culture-directed antibiotic courses. Conclusion: Though most SARS-CoV-2 infections are asymptomatic and/or self-limited, there is significant morbidity and mortality in patients with severe disease sequela as outlined in our reported cases. This suggests early identification and treatment of sinonasal disease in this patient population is critical to minimizing poor outcomes. Further research on the pathophysiology of these atypical presentations is needed. Level of Evidence: 4 (Case Series)

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Review for the Otolaryngologist

Background: Cystic fibrosis (CF) is a genetic disease that may result in multiple systemic disorders and potentially fatal severe respiratory compromise. However, the advent of CF transmembrane conductance regulator (CFTR) modulators has changed the management of CF for patients with select mutations. Although clinical trials have highlighted increased pulmonary function and decreased exacerbations as a result of these novel therapies, their effect on the sinuses has not been well-described. Objective: Our objective is to review the CFTR modulators to provide otolaryngologists, physicians who frequently care for patients with CF, a basic understanding of these drugs and their effects on chronic rhinosinusitis (CRS) in patients with CF. Methods: The clinically approved and available CFTR modulators and specific indications for their use are reviewed. Additionally, a systematic review of these therapies and effects on CRS in CF was performed. Results: Four Food and Drug Administration approved CFTR modulators are available for patients with CF. Current drugs are approved for gating, residual function, or F508del mutations. Multiple reports describe CFTR modulators’ increase in transepithelial ion transport in nasal epithelial cultures; however, clinical studies regarding effects of these modulators on sinonasal health are limited to 5 studies that present new data of the effects of CFTR modulators in CRS. Conclusions: CFTR modulators have changed management of CF. Initial studies of these medications demonstrate promising results in CF; however, there is a paucity of literature describing the effect of CFTR modulators on CF-associated CRS, although initial results are encouraging

Comparative study of simulated nebulized and spray particle deposition in chronic rhinosinusitis patients

Background: Topical intranasal drugs are widely prescribed for chronic rhinosinusitis (CRS), although delivery can vary with device type and droplet size. The study objective was to compare nebulized and sprayed droplet deposition in the paranasal sinuses and ostiomeatal complex (OMC) across multiple droplet sizes in CRS patients using computational fluid dynamics (CFD). Methods: Three-dimensional models of sinonasal cavities were constructed from computed tomography (CT) scans of 3 subjects with CRS refractory to medical therapy using imaging software. Assuming steady-state inspiratory airflow at resting rate, CFD was used to simulate 1-µm to 120-µm sprayed droplet deposition in the left and right sinuses and OMC with spray nozzle positioning as in current nasal spray use instructions. Zero-velocity nebulization simulations were performed for 1-µm to 30-µm droplet sizes, maximal sinus and OMC deposition fractions (MSDF) were obtained, and sizes that achieved at least 50% of MSDF were identified. Nebulized MSDF was compared to sprayed droplet deposition. We also validated CFD framework through in vitro experiments. Results: Among nebulized droplet sizes, 11-µm to 14-µm droplets achieved at least 50% of MSDF in all 6 sinonasal cavities. Four of 6 sinonasal cavities had greater sinus and OMC deposition with nebulized droplets than with sprayed droplets at optimal sizes. Conclusion: Nebulized droplets may target the sinuses and OMC more effectively than sprayed particles at sizes achieving best deposition. Further studies are needed to confirm our preliminary findings. Several commercial nasal nebulizers have average particle sizes outside the optimal nebulized droplet size range found here, suggesting potential for product enhancement

A Comparison of Sphenoid Sinus Osteoneogenesis in Aspirin-Exacerbated Respiratory Disease

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by excessive leukotriene production, diffuse polyp burden and osteitic bone changes. These bony changes have not been previously characterized. Objective: The aim of this radiographic study is to characterize the bony changes noted on computed tomography (CT) scans of the sphenoid sinus in patients with AERD compared to other diseased sinonasal inflammatory states and non-diseased controls. Methods: A retrospective review of 43 patients with clinically confirmed AERD were included and compared to 22 non-diseased, 9 allergic fungal sinusitis, and 43 chronic rhinosinusitis controls (23 without polyps and 18 with polyps). Comparative measurements were performed using fine-cut CT scans. Sites of comparison were the intersinus septum, the left and right lateral sphenoid wall, the roof, and left and right floor of the sphenoid sinus. Standardized measurements were averaged by two separate rhinologists. Results: Patients with AERD had an average statistically significant increase in bone thickness compared to healthy and diseased controls in nearly every site with the most pronounced changes in the intersinus septum (p < 0.05). Conclusion: Patients with AERD have significantly increased thickness of the sphenoid bone compared to control groups with the most pronounced difference in the intersinus septum. These findings may help clinicians increase suspicion for a diagnosis of AERD who clinically have diffuse nasal polyposis

Sinus Development and Pneumatization in a Primary Ciliary Dyskinesia Cohort

Background: Primary ciliary dyskinesia (PCD) is a genetically diverse disease which causes impaired mucociliary clearance, and results in pulmonary, otologic, and rhinologic disease in affected patients. Genetic mutations in multiple genes impair the ability of patients to clear mucous from the lungs, middle ear, and sinonasal cavity and lead to chronic pulmonary and sinonasal symptoms. Methods: We identified 17 PCD patients who had available CT scans. Volumes for bilateral maxillary, sphenoid, and frontal sinuses were calculated. A control population of patients who had preoperative CT scans for endoscopic endonasal resection of skull base pathology without sinonasal cavity involvement was also identified. Results: The mean age of PCD was 33 and ranged from 13 to 54 years. Patients were age- and gender-matched to a control group that underwent resection of anterior skull-base tumors and had a mean age of 35 that ranged between 17–53 years old. The volumes for all thee sinus cavities were significantly smaller (p < 0.007) compared to the control population. The average Lund-Mackay score was 10.6 in the PCD cohort (range 6–16) in comparison to an average of 0.7 in the control cohort (range 0–2). Conclusions: Overall sinus volumes were smaller in patients with PCD compared to our control population. Future studies will be aimed at understanding defects in sinus development as a function of specific genetic mutations in PCD patients. Ultimately, a better understanding of the underlying pathophysiology of PCD will allow us to identify the optimal treatment practices for this unique patient group

Mometasone absorption in cultured airway epithelium

Background: Topical mometasone is frequently used as an intranasal spray, on drug-eluting stents, and compounded by specialty pharmacies as a sinus rinse. A typical sinus rinse contains 1.2 mg of mometasone dissolved in 240 mL of buffered saline and is flushed through the sinonasal cavity. The mometasone irrigation rapidly flows to the contralateral sinonasal cavity or the nasopharynx with a contact time on the order of 5 to 10 seconds. However, no information is available on the absorption rate of topical mometasone on the sinonasal surface. Methods: To determine the absorption characteristics of mometasone, we harvested nasal epithelium from 2 healthy donors and differentiated them into a mature ciliated epithelium on Millicell membranes. We applied mometasone to the apical surface for various time intervals and then rinsed off non-absorbed mometasone with phosphate-buffered saline. Millicell membranes with the adherent epithelial cells were then harvested and stored in guanidine hydrochloride for quantification using high-performance liquid chromatography–mass spectrometry. Results: Fifty percent of the maximal absorption occurred after an average of 38 minutes after application, and maximal absorption occurred after an average of 114 minutes. Conclusion: Our data provide an estimate for rates of absorption of mometasone applied to the sinonasal cavity and suggest that the absorption rates poorly match contact time during saline lavage

Numerical evaluation of spray position for improved nasal drug delivery

Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic