FIGURE 6 - uploaded by Joey Siu
Content may be subject to copyright.
Participant 6. MRI images following nasal spray. (A) T1-weighted MRI as seen in coronal section in a participant with history of previous bilateral sinus surgery (participant 6). Signal enhancement seen in white following administration of GBCA via nasal spray, present on right anterior septum in proximity to the internal nasal valve. (B). Signal enhancement color-labeled by region; yellow = posterior nasal cavity. (C) T1-weighted MRI as seen in sagittal section in participant 4. Signal enhancement seen in white following administration of GBCA via nasal spray, present on right anterior septum, inferior surface of right inferior turbinate, and posterior choana. (D) Signal enhancement color-labeled by region; yellow = posterior nasal cavity. GBCA = gadolinium-based contrast agent; MRI = magnetic resonance imaging.
Source publication
Background:
Optimizing intranasal distribution and retention of nasal sprays is essential in the management of patients with chronic rhinosinusitis (CRS), including those that have had functional endoscopic sinus surgery (FESS). Despite multiple existing distribution studies, there remains a need for a technique that allows regionalization of part...
Context in source publication
Citations
... The postoperative sinonasal cavity models were reconstructed for CFD modeling from either CT scans or MRI scans which were obtained retrospectively. MRI images were acquired according to a high-resolution imaging protocol [27]. Patients (1) F(t) = 478.57t ...
Purpose
Nasal saline irrigation is highly recommended in patients following functional endoscopic sinus surgery (FESS) to aid the postoperative recovery. Post-FESS patients have significantly altered anatomy leading to markedly different flow dynamics from those found in pre-op or non-diseased airways, resulting in unknown flow dynamics.
Methods
This work investigated how the liquid stream disperses through altered nasal cavities following surgery using Computational Fluid Dynamics (CFD). A realistic squeeze profile was determined from physical experiments with a 27-year-old male using a squeeze bottle with load sensors. The administration technique involved a head tilt of 45-degrees forward to represent a head position over a sink. After the irrigation event that lasted 4.5 s, the simulation continued for an additional 1.5 s, with the head orientation returning to an upright position.
Results
The results demonstrated that a large maxillary sinus ostium on the right side allows saline penetration into this sinus. The increased volume of saline entering the maxillary sinus limits the saline volume available to the rest of the sinonasal cavity and reduces the surface coverage of the other paranasal sinuses. The average wall shear stress was higher on the right side than on the other side for two patients. The results also revealed that head position alters the sinuses’ saline residual, especially the frontal sinuses.
Conclusion
While greater access to sinuses is achieved through FESS surgery, patients without a nasal septum limits posterior sinus penetration due to the liquid crossing over to the contralateral cavity and exiting the nasal cavity early.
... The distribution of fluids within the sinonasal cavity after the irrigation has been evaluated in nasal cast models, healthy participants, and cadaveric dissections using dyed or fluorescein-labeled irrigant, computational fluid dynamics, or imaging methods [16][17][18][19][20][21]. This evidence helps to understand the effect of sinus irrigation better. ...
Background Although different methods of nasal irrigation have been utilized, irrigation efficiency in nasal cavities has not been well assessed. The objective of this study was to develop an apparatus and procedure for evaluating the irrigation efficiency and to explore the optimal head position during irrigation.
Methods Casts of the left sinonasal cavity from a healthy volunteer were made from high-resolution computed tomography data using 3D printing with composite materials. An adjustable apparatus that allowed cast fixation at the different head positions was built. The yogurt was used to simulate mucus. The cast with 5ml yogurt filled around the superior, middle, and inferior turbinate was fixed in six head positions including head tilt 10, 45, and 60 degrees forward with or without leaning 30 degrees to the right. The cast was irrigated with 120ml, 175ml, and 240ml dyed water and was video recorded. The irrigation efficiency was calculated based on the weight difference of the cast before and after the irrigation.
Results Most residual yogurt was located around the superior meatus after the irrigation under different volumes and head positions. The irrigation efficiency of the rinse bottle or the pulsatile device was volume-dependent, with the highest irrigation efficiency under 240ml water. When the left sinonasal cavity was irrigated, the head position of tilt 45 degrees forward with leaning 30 degrees to the right was the optimal head position for these two devices when compared to other positions. The pulsatile device with 240ml water performed better than the rinse bottle with 240ml water regarding the irrigation efficiency under the optimal head position (0.87000.0138 vs 0.75360.0099, p=0.003).
Conclusions The developed apparatus provided a potential method for evaluating the irrigation efficiency. The head position of tilt 45 degrees forward with leaning 30 degrees was suitable for patients to perform the nasal irrigation.
... 2 Multiple deposition studies have shown that drugs administered by standard nasal spray devices rarely reach the level of the sinus outflow tracts through the middle meatus and primarily deposit medication at "the nasal valve, anterior septum, inferior surface of the inferior turbinate, nasal floor, and nasopharynx." [4][5][6][7][8] Guidelines recommend the use of nasally delivered corticosteroids to control ongoing inflammation following endoscopic sinus surgery (ESS), noting, for example, that ESS is "primarily aimed at creating better conditions for local treatment" and that "after surgery, continuous appropriate medical treatment is mandatory." 1,2 Evidence suggests that postsurgical CRS outcomes, including reduction of nasal polyp (NP) recurrence, improve when patients receive nasally delivered corticosteroids immediately after ESS (after healing occurs). ...
Background:
Sinus surgery removes inflamed tissue, restores airflow, and improves delivery of medication into surgically opened spaces. The exhalation delivery system with fluticasone (EDS-FLU; XHANCE®) uses a novel delivery system to create closed-palate, positive-pressure, bi-directional mechanics that significantly alter the deposition of the topically-acting anti-inflammatory medication. We ask if EDS-FLU efficacy differs for patients with recurrent symptoms after sinus surgery versus unoperated patients.
Objective:
Compare EDS-FLU treatment responses in patients with recurrent symptoms after endoscopic sinus surgery (ESS) and patients who have never had sinus surgery.
Methods:
Data were pooled from two large, controlled trials (NAVIGATE I and II) for exploratory analyses. CRS symptoms, polyp grade, and quality-of-life measures were compared between patients who had previous ESS and those without prior ESS.
Results:
Patients with prior ESS (EDS-placebo [n = 53], EDS-FLU 186μg [n = 52], and EDS-FLU 372μg [n = 49]) and unoperated patients (EDS-placebo [n = 108], EDS-FLU 186μg [n = 108], and EDS-FLU 372μg [n = 111]) treated with EDS-FLU reported similar and substantial benefits as measured by multiple symptom and quality-of-life/functioning outcomes (congestion score, Sinonasal Outcomes Test [SNOT-22], Rhinosinusitis Disability Index [RSDI], Patient Global Impression of Change) and by nasal polyp grade. In previously operated patients, unlike surgery-naive patients, multiple outcomes (SNOT-22, RSDI, polyp grade) consistently show numerically but not statistically greater responses to the higher dose.
Conclusions:
Patients with recurrent symptoms after sinus surgery who were treated with EDS-FLU demonstrated significant symptom and quality of life improvement. Unlike unoperated patients, patients with prior ESS had a numerically but not statistically greater response to the higher dose of EDS-FLU (2 sprays per nostril BID). This article is protected by copyright. All rights reserved.
... Furthermore, many factors, including the head position, delivery volume, and the degree of surgery, have been identified which significantly influenced the irrigation efficacy [9][10][11][12]. Moreover, the efficacy based on the degree of the staining, calculation of the stained area, percentage of the fill of the sinus, and retained amount of irrigants has been evaluated in nasal cast models, healthy participants, and cadaveric dissections using dyed or fluorescein-labeled irrigants, computational fluid dynamics (CFD) simulation, or imaging methods [6,[13][14][15][16][17]. These studies mainly focused on the effect of different irrigation techniques on the size and area of the fluid coverage and retained amount of fluid within the sinonasal cavity. ...
... Achieving increased liquid surface coverage and high irrigation penetration within the sinonasal cavity has been the primary goal of nasal irrigation devices. Previous studies have emphasized the importance of fluid coverage and the deposition of irrigants within the sinonasal cavity, and quantifiable metrics about these two aspects have been developed [6,[13][14][15][16][17]. It has been observed that large-volume irrigation (> 100 ml) with proper head position would cover all zones of the postoperative sinonasal cavity and promote drug delivery [6,10,19,27]. ...
Background The ability of saline irrigation to detach the mucous and the flow-limiting effect of the nasal valve has not been well explored. The objective of this study was to compare the removal efficiency of a novel irrigation device with an extended nozzle versus a classic rinse bottle.
Methods Transparent casts of the unoperated sinonasal cavity were made by 3D printing. Yogurt was used to simulate mucous. The cast filled with 5ml yogurt was fixed in six head positions and irrigated with 120ml, 175ml, and 240ml dyed water through the novel device and the rinse bottle. The irrigation efficiency was the ratio of the weight of yogurt washed away divided by the total weight of yogurt.
Results The irrigation stream of a long nozzle with a side opening was different from the irrigation stream of the outlet within the nasal vestibule. The novel devices presented with continuous water stream directly upwards to the anterior part of the olfactory cleft. Depending on different head positions, it was easy for the novel devices to achieve an irrigation efficiency of 100% when the cast was irrigated with 120ml or 175ml water. There was still a tiny amount of yogurt left in the olfactory cleft when the cast was irrigated with 240ml water under each head position for the rinse bottle. The irrigation efficiency was volume-dependent, and the average irrigation efficiency of the rinse bottle at 240 ml only reached 69.1%.
Conclusions. The novel irrigation device presented with superior nasal irrigation efficiency to the classic rinse bottle. A continuous water stream directly upwards to the anterior part of the olfactory cleft combined with an extended nozzle overcoming the flow-limiting effect of the nasal valve promotes nasal irrigation efficiency.
... Optimisation of spray parameters is made difficult by the inability to accurately quantify drug deposition, as the nasal cavity is not easily accessed for drug deposition sampling. In vivo studies show a high level of impaction by nasal sprays in the vestibule anterior to the nasal cavity (13)(14)(15)(16)(17)(18)(19)(20)(21). Deposition is further restricted by the nasal valve, an elliptical constriction just behind the vestibule, resulting in most particles > 10 µm being trapped anteriorly (22). ...
Background
Optimising intranasal distribution and retention of topical therapy is essential for effectively managing patients with chronic rhinosinusitis, including those that have had functional endoscopic sinus surgery (FESS). This study presents a new technique for quantifying in vitro experiments of fluticasone propionate deposition within the sinuses of a 3D-printed model from a post-FESS patient.
Methods
Circular filter papers were placed on the sinus surfaces of the model. Deposition of fluticasone on the filter paper was quantified using high-performance liquid chromatography (HPLC) assay-based techniques. The deposition patterns of two nasal drug delivery devices, an aqueous nasal spray (Flixonase) and metered dose inhaler (Flixotide), were compared. The effects of airflow (0 L/min vs. 12 L/min) and administration angle (30° vs. and 45°) were evaluated.
Results
Inhaled airflow made little difference to sinus deposition for either device. A 45° administration angle improved frontal sinus deposition with the nasal spray and both ethmoidal and sphenoidal deposition with the inhaler. The inhaler provided significantly better deposition within the ethmoid sinuses (8.5x) and within the maxillary sinuses (3.9x) compared with the nasal spray under the same conditions.
Conclusion
In the post-FESS model analysed, the inhaler produced better sinus deposition overall compared with the nasal spray. The techniques described can be used and adapted for in vitro performance testing of different drug formulations and intranasal devices under different experimental conditions. They can also help validate computational fluid dynamics modelling and in vivo studies.
... However, the ideal delivery vehicle and method has not been established. The current literature examining the efficacy of nasal sprays of corticosteroids have yielded inconsistent results, largely due to the variability in the ability of sprays to reach the affected mucosa (Saijo et al., 2004;Kimbell et al., 2007;Snidvongs et al., 2013;Djupesland et al., 2019;Siu et al., 2019). ...
... According to the results of the CFD modelling, not only do some particles deposit (form the droplets) around the ostium edge, but many particles are also delivered into the MS, which will eventually deposit on its wall. According to Fig. 14, the reason for the absence of particles in the anterior and posterior regions of the NC, which is in contrast with Siu et al. (2019), is that the particles were initially released in the middle part of the NC with zero velocity to reduce the computational cost. The focus of CFD modelling in this study was to visualise the effect of the acoustic wave on particle movements in the NC-MS combination as well as to investigate the particle deposition in the ostium and MS; hence the mean flow rate was ignored (zero inlet airflow velocity was assumed) and particles were distributed in the NC with zero velocity and then the effect of the acoustic wave on them was investigated. ...
Acoustic drug delivery (ADD) is an innovative method for drug delivery to the nose and paranasal sinuses and can be used to treat chronic rhinosinusitis (CRS). The underlying mechanism of ADD is based on the oscillatory exchange of air between the nasal cavity (NC) and the maxillary sinus (MS) through the ostium, which assists with the transfer of the drug particles from the NC to the sinuses. This study aims to examine the efficacy of ADD for drug delivery to the MS using an acoustic wave applied to nebulised aerosols entering the nostril. Here, the effect of acoustic frequency, amplitude, and nebulisation flowrate on the efficiency of ADD to the MS is investigated experimentally. A computational fluid dynamics model was also developed to understand the deposition and transport patterns of the aerosols. The results showed that superimposing an acoustic frequency of 328 Hz, which is the resonance frequency of the selected 3D printed model of the NC-MS combination, on the nebulised aerosols could improve the efficiency of the drug delivery to the MS by 75-fold compared with non-acoustic drug delivery case (p<0.0001). The experimental data also shows that an increase in the amplitude of excitation, increases the concentration of aerosol deposition in the MS significantly; however, it reaches to a plateau at a sound pressure level of 120 dB re 20 µPa.
... [23][24][25] This has been investigated and a simple explanation identified: standard nasal delivery does not get the topically-acting medication adequately and consistently to the anatomic regions that need to be targeted in CRS. [26][27][28][29][30] Conventional nasal sprays deliver <5% of metered drug into the middle meatus, the area of the nose critical for drainage of the maxillary, anterior ethmoid, and frontal sinuses. 31 In fact, multiple studies have shown that conventional nasal sprays deliver medication primarily to the anterior and inferior regions of the nasal cavity-specifically the internal nasal valve, anterior septum, inferior surface of the inferior turbinate, nasal floor, and nasopharynx-regardless of disease or prior surgery. ...
... 31 In fact, multiple studies have shown that conventional nasal sprays deliver medication primarily to the anterior and inferior regions of the nasal cavity-specifically the internal nasal valve, anterior septum, inferior surface of the inferior turbinate, nasal floor, and nasopharynx-regardless of disease or prior surgery. 30,31 The limited delivery of drug into the more superior/posterior regions of the nasal passages with conventional nasal sprays, especially the middle meatus and ostiomeatal complex where CRS inflammation produces symptoms, is a plausible explanation for the discrepancy in activity between systemic and topical glucocorticoid treatment of CRS. [32][33][34] Since 2018, a "nonstandard" nasal product using an exhalation delivery system (EDS) to deliver a secondgeneration topical glucocorticoid (fluticasone [FLU]) has become available in the United States (EDS-FLU; XHANCE®; OptiNose US, Yardley, PA). ...
Background:
Standard nasal steroid sprays are often first-line treatment for chronic rhinosinusitis (CRS), but many patients remain symptomatic despite their use. The exhalation delivery system with fluticasone (EDS-FLU) has been shown to be efficacious in mixed populations of symptomatic patients, but the question remains whether benefits would be similar in those already on traditional steroid sprays. The goal of this study was to compare EDS-FLU treatment outcomes in patients who have previously failed nasal steroids.
Methods:
Using pooled data from the NAVIGATE I and II trials, EDS-FLU efficacy was compared in the subgroup treated with a conventional nasal steroid at trial entry (mean duration, ≈3 years) to efficacy in the overall study population. Sensitivity analyses were performed for more restrictive definitions of the subgroup changing from prior standard nasal steroids.
Results:
Of 482 total subjects, 218 (45.2%) reported using standard nasal steroid sprays at entry (mean duration, 1051 days). Across multiple outcome measures, improvements for "switchers" receiving EDS-FLU (least squares mean change from baseline vs EDS plus placebo) were comparable with improvements in the overall population. For EDS-FLU 372 μg, comparable improvements were observed in congestion (-0.73 vs -0.62), rhinorrhea (-0.71 vs -0.57), facial pain/pressure (-0.48 vs -0.41), and sense of smell (-0.35 vs -0.30) at week 4 and 22-item Sino-Nasal Outcome Test (-21.01 vs -20.52), Patient Global Impression of Change, and other outcomes at week 16. Results for EDS-FLU 186 μg were similar.
Conclusion:
EDS-FLU comparably improves symptoms, irrespective of whether patients are symptomatic while using conventional nasal steroids before treatment.
... Nasal cavity mucosal health was confirmed with endoscopy. Reconstruction of nasal models was performed from MRI images for healthy subject A and CT images for healthy subject B. The MRI scan was performed according to a high-resolution MRI protocol (15) . The combination of parameters was sufficient to distinguish the air and soft tissue interface for the segmentation of the sinuses and ostia. ...
Background:
The aim of this study was to investigate using computational fluid dynamics (CFD) the effects on nasal aerodynamics of two different techniques for reducing the inferior turbinate. This may assist in surgical planning to select the optimal procedure.
Methods:
Virtual surgery using two techniques of turbinate reduction was performed in eight nasal airway obstruction patients. Three bilateral nasal airway models for each patient were compared: 1) Pre-operative 2) Bilateral inferior turbinoplasty 3) Bilateral total inferior turbinate resection (ITR). Two representative healthy models were included. CFD modeling of airflow was performed under steady-state, laminar, inspiratory conditions.
Results:
Nasal airway resistance was slightly more reduced following ITR compared to turbinoplasty due to loss of the pressure gradient at the head of the IT. Turbinoplasty resulted in ventilation, pressure and wall shear stress profiles closer to those of healthy models. A more prominent jet-like course of the main flow stream was observed inferiorly in the ITR group.
Conclusions:
Nasal air conditioning was significantly altered following IT surgery. Overall differences between the groups were small and are unlikely to bear influence on nasal function in normal environments. Further studies using a larger number of patients and healthy subjects are required, attempting to establish a clinical correlation with long-term outcomes such as the perception of nasal patency, mucosal crusting and drying, and air conditioning in different environments. Since a large proportion of IT mucosa remains following turbinoplasty, future dependence on topical therapy should also be considered.
... Eight postoperative sinonasal cavity models were reconstructed for CFD modeling from either CT scans or MRI scans of these patients which were obtained retrospectively. MRI images were acquired according to a highresolution imaging protocol (12) . Patients underwent scans more than four months from their last surgery. ...
... Segmentation and the reconstruction of models suitable for airflow studies relies on accurate representation of bony cavities. The MR scanning protocol was able to image the entire sinonasal cavity with a high resolution (0.8mm isotropic) (12) . The combination of parameters was sufficient to distinguish the air and soft tissue interface for the segmentation of the sinuses and ostia. ...
Background:
Despite functional endoscopic sinus surgery (FESS) being the standard of care in medically recalcitrant chronic rhinosinusitis (CRS), its effect on sinus ventilation has not been fully characterized. Airflow simulations can help improve our understanding of how surgical strategies affect post-surgical sinus ventilation.
Methods:
Eight postoperative sinonasal cavity models were reconstructed from a wide spectrum of CRS patients who had undergone FESS. Computational fluid dynamics modeling of steady-state, laminar, inspiratory airflow was performed. Ventilation was quantified and observed for all the sinuses in each model.
Results:
Sinus aeration was enhanced following FESS, particularly in the maxillary and ethmoid sinuses. The degree of improvement was related to the extent of surgery performed. This finding was accentuated at a higher inhalational flow rate of 15L/min. The relationship between ostium size and corresponding sinus inflow was stronger for the maxillary and sphenoid sinuses. Maxillary inflow reached 50% in a mega-antrostomy patient, while negligible flow occurred in the frontal sinuses for except one whom had undergone a modified Lothrop procedure.
Conclusions:
This study has quantified sinus airflow in the largest set of post-FESS patients to date, to show that with increasing extensive surgery, the sinus and nasal cavity become more interconnected and functionally interdependent. Accordingly, sinus ventilation is improved. This may have important consequences for pre- and post-surgical assessment and planning, and on predicting how drug delivery treatments and devices can be designed to target the postoperative sinuses.
