OBJECTIVE:To evaluate whether treatment responses to the exhalation delivery system with fluticasone (EDS-FLU; XHANCE®) differ between patients with CRS with nasal polyps (CRSwNP) and patients without nasal polyps (CRSsNP). STUDY DESIGN:Post hoc analysis of the ReOpen clinical trials conducted between November 2018 and November 2021 for a 24-week duration. SETTING:Multinational, multicenter, randomized, EDS-placebo-controlled studies. METHODS:Data were pooled from the randomized trials in which patients with CRSwNP (n = 206) or CRSsNP (n = 341) were randomly assigned (1:1:1) to EDS-FLU 186 μg, 372 μg, or EDS-placebo, 1 or 2 sprays twice daily per nostril for 24 weeks. Endpoints included composite symptom score, Smell Identification Test (SIT), sinus opacification on computed tomography (CT) scan, frequency of acute exacerbations of CRS, 22-Item Sino-Nasal Outcome Test (SNOT-22), and Patient Global Impression of Change (PGIC). RESULTS:Patients with CRSwNP and CRSsNP reported substantially greater benefits with EDS-FLU versus EDS-placebo on symptoms, SIT, sinus opacification on CT scan, incidence of acute exacerbations of CRS, and quality-of-life outcomes (SNOT-22 and PGIC). Composite symptom score and SNOT-22 improvements were consistent in the subgroup of patients entering the trial reporting symptoms despite recent standard-delivery nasal steroid spray use. Treatment-by-subgroup interaction effects indicated similar magnitude EDS-FLU treatment effect for patients with CRSwNP and patients with CRSsNP. CONCLUSION:EDS-FLU improved subjective and objective measures of CRS irrespective of nasal polyp status. TRIAL REGISTRATION:Title: Study Evaluating the Efficacy and Safety of Intranasal Administration of OPN-375 in Subjects With Chronic Rhinosinusitis With or Without the Presence of Nasal Polyps; ID: NCT03781804 and NCT03960580, Clinicaltrials.gov.

BACKGROUND:The inability of topical medications to reach sinus cavities is a potential reason for lack of efficacy in chronic rhinosinusitis (CRS). One purpose of endoscopic sinus surgery (ESS) is to enable delivery of medications into the sinus cavities. The exhalation delivery system with fluticasone (EDS-FLU; XHANCE) creates unique biomechanics that enable deposition of intranasal corticosteroid into sinuses and sinus drainage pathways but may have differing efficacy in operated versus unoperated sinuses. Two 24-week randomized trials (ReOpen1/2) evaluated EDS-FLU versus EDS-placebo in patients with CRS, stratified by surgical status. METHODS:Surgery-naive (n = 332) and prior-surgery (n = 215) patient groups were analyzed as pooled data from ReOpen1/2. Outcome measures (least-squares mean change from baseline) included combined symptom score (CSS) and congestion score at weeks 4, 8, and 12 and average of percentages of opacified volume (APOV) of ethmoid/maxillary sinuses on CT and Sinonasal Outcome Test 22 (SNOT-22) total score at week 24. RESULTS:Baseline scores suggested moderate-severe disease: mean CSS = 5.8; APOV = 67.2%. EDS-FLU produced significant improvement versus placebo (p < 0.05): CSS (surgery-naive, -0.68 vs. -1.42; prior ESS, -0.70 vs. -1.87); congestion (surgery-naive, -0.24 vs. -0.59; prior ESS, -0.24 vs. -0.69); and SNOT-22 (surgery-naive, -7.56 vs. -18.30; prior ESS, -10.72 vs. -18.74). Similar results were observed for APOV (p < 0.05). No statistically significant difference was observed between surgery subgroups with either EDS-FLU dose. CONCLUSION:EDS-FLU improved symptoms, sinus opacification, and quality of life in patients with CRS with or without prior ESS, suggesting a role for EDS-FLU in both populations.

Computational fluid dynamics (CFD) has been used to investigate the intranasal deposition of corticosteroid sprays. CFD Lagrangian tracking models terminate particle motion once particles come into contact with a surface ("trap" boundary condition) and disregard the liquid film buildup on the mucosal surfaces of the sinonasal cavity walls. However, the interaction between spray droplets and the mucosal surface is critical for corticosteroid delivery using the exhalation delivery system (EDS) nasal spray device. Droplets coalesce on sinonasal walls, forming a thin "wall-film" on which droplets spread along the surface, splash, and/or break into secondary particles, depending on impact energy. To advance nasal drug delivery modeling, three CFD models of fluticasone propionate deposition using the EDS device in a Draf III post-surgical ge-ometry were developed: (1) using traditional "trap" boundary conditions; (2) using "wall-film" boundary conditions and one-way coupling; and (3) using "wall-film" boundary conditions with two-way coupling (to account for the high-mass loading in the near-nozzle spray field). Contour plots and data sets for each CFD model were qualitatively compared with physical models in the same geometry (visualized in a 3D-printed sinonasal cast). The CFD simulations showed that EDS delivers fluticasone to all sinonasal regions, including areas superiorly and posteriorly in the sinonasal cavity. In addition, deposition improved and more closely correlated with physical experiments as the CFD model complexity evolved. "Wall-film" modeling of EDS delivery demonstrated increased surface coverage compared to the "trap" model. The "wall-film/two-way coupling" model demonstrated substantially higher deposition in the remote frontal and maxil-lary sinuses, agreeing with physical cast experiments. In conclusion, CFD simulation of EDS de-livery using the "wall-film" boundary/two-way coupling model appears to most accurately represent observations from physical model experiments in the same geometry.

interests from OptiNose US, Inc; leadership or fiduciary role in other board, society, committee or advocacy group, from Delegate, CO mem-ber.

Patients with CRSwNP frequently suffer from poor quality of sleep, significantly lower quality-of-life scores, and chronic depression. EDS-FLU has been shown to significantly improve symptoms of CRSwNP. This post-hoc analysis reports the effects on sleep from EDS-FLU pivotal trials. NAVIGATE I/II were similarly designed, prospective, randomized, 24-week [16 double-blind (DB) + 8 open-label (OL)], placebo-controlled studies. Patients (N=482) with moderate-severe CRSwNP received EDS-FLU 186μg (n=160), EDS-FLU 372μg (n=161), or EDS-placebo (n=161) twice-daily. Data were pooled for this post-hoc analysis. Outcomes were assessed with the MOS Sleep-R Problems Index, Sinonasal Outcome Test (SNOT-22) sleep function subscale, and Patient Global Impression of Change (PGIC). Baseline demographics were similar across treatments. By week-16, greater improvements in the MOS Sleep-R Problems Index were observed with EDS-FLU 186ug and 372ug compared with EDS-placebo [least squares (LS) mean change: −14.90 and −12.4 vs −9.1; P<.001 and P<.05, respectively]. EDS-FLU also improved MOS-Sleep-R subscales. Patients receiving EDS-FLU showed improvements in the SNOT-22 Sleep Function subscale that were consistent with the MOS-Sleep Problems Index. At week-16, LS mean changes from baseline were −3.86 and −4.13 with EDS-FLU 186ug and 372ug, respectively, vs −2.23 with EDS-placebo (P<.001, both comparisons). At week-24 (OL: all patients received EDS-FLU 372ug), patients reported continued improvement (−4.05, −4.29, −3.66, respectively). At week-16, ≈66% receiving EDS-FLU reported being "much/very much" improved as assessed by PGIC versus 33% with EDS-placebo. At 24-weeks, 72% to 81% reported "much/very much" improvement. In patients with moderate-severe CRSwNP, EDS-FLU treatment is associated with improved sleep scores and satisfaction

Nasal nitric oxide (nNO) is produced within the sinuses and has anti-inflammatory activity. In patients with chronic rhinosinusitis (CRS), nNO is depressed, likely because inflammation restricts nNO release from the sinuses. The positive pressure produced by the Exhalation Delivery System (EDS) in the nasal cavity has the potential to open up the sinus ostia, allowing release of nNO. Increasing nNO may improve patient symptoms. A single-center, randomized, 3-way crossover, pilot study measuring nNO levels in patients with CRS without nasal polyps (CRSsNP) and healthy participants for up to 60 minutes after use of empty EDS, EDS-placebo (saline), or forceful nasal exhalation (without EDS device). 12 patients with CRSsNP (7 females, mean age 39, BMI 25 kg/m2, mean SNOT-22 score 49,) and 6 healthy participants (5 females, mean age 37, BMI 23 kg/m2, mean SNOT-22 score 3) were enrolled. The mean percent change from baseline to 30 minutes in nNO levels was greater in patients with CRSsNP (EDS-empty [+26.2%], EDS-placebo [+25.9%], and forceful nasal exhalation [+44.9%]) compared with healthy participants (−3.1%, −9.5%, and +12.9%, respectively). These results show a trend suggesting that the EDS potentiates the release of nNO in patients with CRSsNP compared with healthy individuals.

Background: inhaled nasal corticosteroid sprays (INS) are often inadequate to treat chronic rhinosinusitis (CRS). The exhalation delivery system with fluticasone (EDS-FLU; XHANCE1 may improve outcomes in CRS by increasing medication delivery to target superior/posterior anatomic sites. This study assessed safety and efficacy of EDS-FLU in a large population with moderate-tosevere CRS with or without nasal polyps (CRSwNP, CRSsNP). Methods: Prospective, multicenter, 12-week, single-arm study of EDS-FLU 372 mu g twice daily (BID) at 38 U.S. sites. Safety was assessed by adverse-event evaluations, nasal endoscopy, and ocular examinations. Efficacy was serially assessed by outcomes including nasal endoscopy (Lund-Kennedy Score, polyp grade), patient- and physician-reported outcomes (22-item Sinonasal Outcome Test [SNOT-22]), study-defined surgical indicator assessment, and Patient Global Impression of Change (PGIC). Results: 705 comparatively refractory subjects were enrolled, 603 CRSsNP and 102 CRSwNP [moderate-to-severely symptomatic; baseline SNOT-22 similar to 43, high rates of prior INS use (92.3%) and/or prior surgery (27.5%)]. More than 90% reported improvement on treatment by PGIC. SNOT-22 scores improved substantially and similarly in patients with NP (-23.7) and without NP (-24.4). Among patients with baseline Lund-Kennedy edema scores >0, 33.3% (CRSwNP) and 54.8% (CRSsNP) had complete resolution of edema. In CRSwNP patients, 48% had polyp elimination in >= 1 nostril, 63% had >= 1-point improvement in polyp grade, mean bilateral polyp grade decreased from 2.9 to 1.6, and study-defined surgical eligibility decreased. EDS-FLU was generally well tolerated, with a safety profile similar to conventional INS sprays when used to treat CRS. Conclusion: EDS-FLU 372 mu g BID in the treatment of CRS with or without polyps was safe, well-tolerated, and produced substantial improvement across a broad range of both objective and subjective measures.

Background:Nasal casts may characterize intranasal drug deposition.Methodology:The Koken cast, described as 'anatomically correct', and the Optinose cast, derived from MRI of a healthy male during velum closure, were dimensionally compared and assessed for deposition assessment suitability.Results:Smallest vertical cross-sectional areas (valve region) for Koken and Optinose right/left: 2.55/2.75 and 1.18/1.18 cm(2), respectively, versus a 'normative' mean (range) of 0.85 cm(2)(0.2-1.6 cm(2)). Intranasal volumes differed (computed tomography/water fill): Koken, 35.8/38.6 cm(3)and Optinose, 24.1/25.0 cm(3), versus a 'normative' mean (range) of 26.4 cm(3)(20.9-31.1 cm(3)).Conclusion:Koken cast dimensions are larger than the normal range and the Optinose cast. The validity of casts for regulatory drug deposition studies is suspect.

Purpose: The exhalation delivery system with fluticasone propionate (Xhance (R)) has been shown to deliver drug substantially more broadly in the nasal cavity (particularly into superior/posterior regions), with less off-target loss of drug to drip-out and swallowing, than conventional nasal sprays. This open-label study evaluated the systemic bioavailability of Xhance (R) by comparing the pharmacokinetic (PK) properties of a single dose of fluticasone from 3 products administering the drug using 3 different devices: Xhance (R), Flonase (R) (fluticasone propionate inhalational nasal spray), and Flovent (R) HFA (fluticasone propionate inhalational aerosol). Methods: This open-label study was conducted in 2 parts. Study part 1 compared systemic exposure with a single dose of Xhance (R) 186 or 372 mu g versus Flonase (R) 400 mu g (3-way, 3-treatment, 3-sequence, randomized crossover in healthy subjects; n = 90). A separate study, part 2, under the same umbrella protocol, compared systemic exposure with Xhance (R) 372 mu g versus Flovent (R) HFA 440 mu g (2-way, 2-treatment, 2-sequence, randomized crossover in patients with mild to moderate asthma; n = 30). Findings: With Xhance (R) 186 jig, the geometric least squares mean (LSM) C-max was higher than with Flonase (R) 400 mu g (16.02 vs 11.66 pg/mL, respectively; geometric mean ratio [GMR], 137.42%) and the geometric LSM AUC(0-infinity), values were similar (97.30 vs 99.61 pg . h/mL; GMR, 97.78%). With Xhance (R) 372 mu g, the geometric LSM C-max and AUC(0-infinity) were higher than with Flonase (R) 400 mu g (C-max, 23.50 vs 11.66 pg/mL [GMR, 201.53%]; AUC(0-infinity), 146.61 vs 99.61 pg . h/mL [GMR, 147.19%]). In part 2, the geometric LSM C-max and AUC(0-infinity) values were lower with Xhance (R) 372 jag than with Flovent (R) HFA 440 mu g (C-max, 25.28 vs 40.02 pg/mL [GMR, 63.18%]; AUC(0-infinity), 205.78 vs 415.16 pg . h/mL [GMR, 49.57%]). (C) 2019 The Authors. Published by Elsevier Inc.

Chronic rhinosinusitis with/without nasal polyps (CRSwNP/CRSsNP) is a debilitating inflammatory disorder commonly diagnosed in working age adults, and is characterized by significant morbidity and poor outcomes with standard medical therapy. CRS affects approximately 15% of adults, generating ∼$60B in lost productivity annually. In two randomized controlled trials in CRSwNP (NAVIGATE I/II), treatment with the exhalation delivery system with fluticasone (EDS-FLU; XHANCE®), was associated with a 52.7% improvement in self-reported work productivity. We model the long-term impact of EDS-FLU treatment on work productivity in specialist-treated CRSwNP patients from a societal perspective. Using the human capital approach, a 30-year Markov model was developed comparing EDS-FLU vs. standard medical therapy. Mean cohort age was 40 years. Health state transition probabilities and lost productivity associated with health state and sinonasal surgery were obtained from NAVIGATE I/II and published literature. Costs were discounted to 2018 dollars. A probabilistic sensitivity analysis was conducted. Over 30 years, standard medical therapy was associated with 2.9 years with $134,823 in productivity losses per specialist-treated patient, while treatment with EDS-FLU was associated with productivity losses of 1.6 years, worth $74,978. If EDS-FLU replaced current medical therapy, the societal savings would be $19.5B. The model was most sensitive to health state transition probabilities, and the proportion of patients with severe disease at baseline. In this model, EDS-FLU treatment was associated with 1.3 productive years gained per patient over 30 years vs. standard medical treatment, with estimated societal savings of nearly $20B.

Background: Chronic rhinosinusitis is common and sometimes complicated by nasal polyps (NPs). Corticosteroid nasal sprays are often unsatisfactory because they are ineffective at delivering medication to high/deep sites of inflammation. Objective: We sought to assess whether an exhalation delivery system with fluticasone (EDS-FLU) capable of high/deep drug deposition improves outcomes. Methods: Patients (n = 323) 18 years and older with moderate-to-severe congestion and NPs were randomized to twice-daily EDS-FLU (93, 186, or 372 mg) or exhalation delivery system (EDS)-placebo for 24 weeks (16 double-blind plus 8 open-label when all received 372 mg). Coprimary end points were change in nasal congestion/obstruction at 4 weeks and summed bilateral polyp grade at 16 weeks. Secondary end points included symptoms, polyp elimination, and functioning. Results: EDS-FLU was superior on both coprimary end points (P <.001 vs EDS-placebo, all doses). Mean polyp grade improved continuously through week 24 (P <.009, all comparisons), with polyps eliminated on at least 1 side in approximately 25% of patients at week 24 versus 8.7% with EDS-placebo (P <.014, all comparisons). Sino-Nasal Outcomes Test scores also improved significantly versus those in patients receiving EDS-placebo (221.1 to 221.4 vs 211.7 at week 16, P <. 05 all doses). At the end of the double-blind period, EDS-FLU (all doses) significantly improved all 4 defining disease symptoms. In most patients (68%), those receiving EDS-FLU reported "much" or "very much" improvement. The number of patients eligible for surgery decreased by 62%-67%. The safety profile was similar to that reported in prior trials evaluating conventional corticosteroid nasal sprays in comparable populations. Conclusion: EDS-FLU produces clinically and statistically significant improvement in all 4 diagnostically defining disease symptoms, polyp grade, and quality of life in patients with chronic rhinosinusitis with NPs.

Nasal steroids are first-line treatment for chronic rhinosinusitis (CRS), with nasal polyps. Some physicians prescribe once-daily (QD) regimens and some twice-daily (BID). This literature review compares once- vs twice-daily dosing. We reviewed select reasonably sized randomized controlled trials (RCTs) testing the efficacy of QD or BID nasal steroids vs placebo in reducing polyp burden. Six RCTs exposing a total of 1,712 patients to conventional nasal steroid sprays or placebo were identified. In addition, two RCTs using a novel exhalation delivery system with fluticasone (EDS-FLU) were identified (N=643). In four RCTs (N=142, 310, 354, 748), mean total bilateral polyp grade (polyp grade) was significantly reduced with BID nasal steroid vs placebo. In contrast, three RCTs (N's=104, 142, 310) found that polyp grade improvement was not significantly better with QD nasal steroid compared to placebo. Only one large RCT (N=354) showed significant reduction in polyp grade with QD treatment, while one additional very small RCT (N=54) reported reduction in polyp volume with a nonstandard scale. Notably, efficacy with mometasone nasal spray using BID dosing was replicated in 2 independent registration studies, but not with QD dosing. Both RCTs with EDS-FLU (NAVIGATE I/II) studied BID showed significant symptom reduction of comparatively large magnitude and statistically significant polyp grade reduction vs placebo. Evidence suggests that twice-daily treatment with topical corticosteroid is likely to offer more reliable efficacy than once-daily treatment for patients with moderate-to-severe CRS with nasal polyps.

High-volume nasal irrigation has been shown to have benefits in CRS patients. Addition of high-dose corticosteroid to saline irrigations is increasingly common, though guidelines note inadequate evidence to confirm efficacy. We summarize existing evidence and usage trends. Reviewed literature on corticosteroid irrigation in CRS. Budesonide claims data [2007-2016; Covance Inc] were evaluated for patients with a CRS-related diagnosis. Seventeen efficacy (15 budesonide; 1 mometasone; 1 fluticasone) and/or safety studies (3 weeks-22 months) were identified. Most were uncontrolled (n=12) versus randomized (n=5); small and underpowered (≤10 subjects: n=3; 11-49: n=9; 50-100: n=4; ≥100: n=1) and conducted in CRS sub-populations (eg, post-sinus surgery: n=9). The 3 which were generalizable (ie, n≥50) and controlled, failed to show a statistically significant difference versus control (saline irrigation). One small study (n=35) demonstrated benefit on imaging but mixed results on symptoms. Evidence of, or a trend toward, HPA axis suppression was apparent in 2/6 studies. Annual claims data showed increasing use of Budesonide Respules® with increased costs (mean prescription number=6 among patients with ≥1 prescription; mean cost=$210/prescription). Adherence was reported to be adversely affected by third party coverage and irrigation solution preparation time, and 2.5% ± 1.6% of irrigation doses are retained in the nose. Evidence for efficacy of adding corticosteroid to nasal irrigations is low-quality, with reported possible benefits limited to a sub-population with previous surgery. Adequate, well-controlled studies are needed to address dosing issues, efficacy, safety, adherence, and patient selection in order to understand the role of adding corticosteroid to nasal irrigations in CRS.

Intranasal steroids, usually by inhalation (INS), are first-line therapy for chronic rhinosinusitis, but most patients are frustrated with treatment efficacy. We compare patient satisfaction and ease-of-use with INS vs an exhalation delivery system (EDS-FLU; XHANCE™), that can help achieve better superior/posterior drug deposition. Analysis of ease-of-use and comfort in two 24-week (16 double-blind+8 open-label; N=322/321) RCTs with EDS-FLU in patients with CRS with nasal polyps. Patients reported current (or most recent) prescription intranasal steroid at screening and compared to EDS-FLU at weeks 4, 16, and 24. Self-reported "real world" survey results from patients prescribed EDS-FLU outside clinical trials were also evaluated. In the RCTs, at screening, 77-84% and 71-74% of patients reported their current/most recent inhaled INS was easy-to-use and comfortable-to-use, respectively. At weeks 4, 16, and 24, 86-88%, 87-91%, and 90% reported EDS-FLU was easy-to-use and 80-85%, 82-88%, and 83-85%, reported it was comfortable to use, respectively. Compared to their current/most recent inhaled nasal steroid, at 4 weeks, EDS-FLU patients reported less loss of drug to drip down the back of the throat (61-67.0%) or out the front of the nose (55-64%). In a "real world" patient survey (N=2733), 89% of patients electing to complete the survey reported treatment satisfaction and 77% preferred EDS-FLU to prior inhaled steroids or steroid rinses. Large RCTs and a large survey of 'real-world' patients suggest that patients find EDS-FLU easy-to-use, comfortable, and associated with improved symptoms and high patient satisfaction.

Chronic rhinosinusitis with nasal polyps (CRSwNP), although commonly associated with Th2/eosinophilic inflammation, can also be characterized by Th1, Th3, or a combination. Corticosteroids inhibit multiple inflammatory pathways, eliciting broad immunosuppressive effects and well-characterized treatment responses. EDS-FLU improves outcomes in CRSwNP. This post-hoc analysis compared EDS-FLU response by baseline blood eosinophils to determine if there was a differential response to EDS-FLU among cohorts.

Background: Endoscopic sinus surgery is often performed to improve delivery of topical medication into sinus cavities.Intranasal steroids are guideline recommended in post-surgical patients, and experiments with cadavers suggest that surgery improves delivery of drug into sinuses.Exhalation delivery systems (EDS) use a new mechanism for intranasal delivery and have been shown to reach superior/posterior regions of the nasal cavity better than nasal sprays in unoperated patients.Methods: Silicone casts of the nasal cavity and sinuses from a patient after Draf II, and then Draf III, were made from high-resolution computed tomography (CT) data using 3D printing.Internal surfaces were coated with liquid-sensitive, color-changing gel.Color changes were evaluated following conventional nasal spray delivery (0.1 mL × 2) (Nasonex®), EDS delivery (0.1 mL × 2) (XHANCE™), and high-volume, low-flow (HVLF) delivery (≈80 mL) with head tilted either 45° or 90°.Results: Conventional nasal spray deposited liquid only in anterior nasal segments.EDS deposited liquid throughout the nasal cavity, in surgically opened ethmoid and maxillary spaces, at entrances of the frontal sinuses in Draf II geometry, and into frontal sinuses in Draf III.Tilted 45°, HVLF delivery enters the maxillary sinuses but not the frontal sinuses or the ethmoid region.At full 90° inclination, HVLF delivery reaches most of the frontal and maxillary sinuses but not the roof and posterior wall of the ethmoid region.Conclusions: HVLF and EDS produced a deep intranasal/intrasinal deposition in the silicone cast compared with conventional nasal spray delivery; both deposited liquid inside the surgically opened sinuses.HVLF offers the benefit of lavage, whereas EDS may be more efficient and convenient.

Background: Chronic rhinosinusitis (CRS) is believed to create a substantial population-level disease burden in the United States due to its high prevalence and significant disease morbidity, but many studies of CRS epidemiology are based on administrative or historical record sources rather than primary population sources. Objective: To characterize CRS symptoms, burden, and patient characteristics by using a primary U.S. population-based representative sample. Methods: A demographically and geographically representative sample of 10,336 U.S. adults recruited from a general panel of 4.3 million were obtained by using three-stage randomization. Data collected included a range of respondent-reported CRS symptoms, symptom impact and severity, symptom duration, and treatment. Results: Approximately 11.5% of the respondents (n = 1189) reported defining symptom and duration criteria for CRS. A previous diagnosis of nasal polyps was reported by ∼10% of this population. The remaining respondents reported severe (7.3%) or moderate (3.1%) symptom severity. The most frequently reported defining symptoms were nasal congestion and/or obstruction (94-97%) and drainage (89-92%). CRS participants reported a high average degree of symptom burden (e.g., on a 0-10 scale, 8.2 for CRS with nasal polyps, 8.4 for CRS without nasal polyps with severe symptoms, and 6.4 for CRS without nasal polyps with moderate symptoms). The participants with CRS reported high health-care use for CRS, adverse effects of CRS symptoms on multiple areas of daily life, and high dissatisfaction with currently available treatments. Conclusion: More than 10% of the general U.S. adult population have CRS symptoms. Most report severe symptoms, lack of satisfaction with current treatment options, and a substantial adverse impact on daily functioning.