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Objectives: To investigate whether hormone replacement therapy (HRT) impacts health care resource utilization in the management of chronic rhinosinusitis (CRS) in older women., Methods: Using the TriNetX US health record database, women 55 years or older with a diagnosis of CRS were included and followed for 3 years. The cohort was stratified into two groups: women who received HRT at the beginning of the study were compared to women who did not receive HRT. The groups were matched by age, race, ethnicity, history of asthma, and history of nasal polyps. Outcomes included whether the patient underwent endoscopic sinus surgery (ESS) and frequency of antibiotic use. Measures of association, Kaplan-Meier analysis, and cohort descriptive statistics were calculated., Results: Of the 65,400 women included, the mean age was 66.9 years. 27.0% and 3.6% of patients had a history of asthma or nasal polyps, respectively. Overall, 2.0% of CRS patients underwent ESS, with the HRT group less likely to undergo ESS [OR: 0.28; 95% CI: (0.25-0.32)] compared to patients who did not receive HRT. When stratified by polyp status, HRT patients with nasal polyps had a greater decrease in ESS rates compared to control than HRT patients without nasal polyps. The HRT group had a higher mean number of antibiotic prescriptions compared to the non-HRT group., Conclusion: HRT is associated with decreased utilization of ESS to treat CRS, with a greater effect size for ESS among CRSwNP patients. However, HRT was associated with higher antibiotic utilization., Level of Evidence: 3 Laryngoscope, 134:3921-3926, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective(s): Biologics for chronic rhinosinusitis with nasal polyposis (CRSwNP) are an evolving therapeutic option, but there are limited data on physician experiences in prescribing them. The goal of this study was to gain a better understanding of these experiences including prescribing practices, patient factors which guide prescriber decision, and physician and patient-reported issues which might limit cost-effectiveness of these therapies., Methods: A survey was distributed to attending otolaryngologists using the Canadian Society of Otolaryngology (CSOHNS) email distribution and eSurvey program. Responses were tabulated for the entire cohort and compared between rhinologists and non-rhinologists where appropriate. Frequencies and proportions were expressed as a percentage of total respondents. Fisher's exact test was used for statistical analysis between groups., Results: Seventy-nine total survey responses were recorded representing a response rate of 43%. Significantly more rhinologists reported prescribing biologic medications on their own (100% vs. 50%; p < 0.001) and a higher proportion (1 to 10% vs. <1%) of their patients were on biologics compared with non-rhinologists (p = 0.023). Rhinologists were more likely to consider poor response to medical therapies, need for rescue steroids, and comorbid type 2 conditions in their decision to pursue biologics than non-rhinologists, but they also experienced poorer assistance from patient support programs and less availability to medications., Conclusion: Rhinologists are more comfortable with prescribing and managing biologics for CRSwNP compared with non-rhinologist colleagues. Clinicians prescribing biologic medications for CRSwNP should be familiar with guidelines, indications, and potential adverse events., Level of Evidence: N/A Laryngoscope, 134:3493-3498, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To investigate the frequency and nature of adverse events related to type 2 biologic use in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), including dupilumab and mepolizumab., Methods: This is a single-institution retrospective study of real-world patient data. Patients were included if they have a diagnosis of CRSwNP, have undergone at least one endoscopic sinus surgery, and have taken at least two doses of dupilumab or mepolizumab between January 1, 2016, and July 1, 2023. Data collected include clinicodemographic information and past medical/surgical history. The primary outcomes are the incidence and types of adverse events. Adjusted odds ratio was calculated to compare the biologics using logistic regression. Risk factors for developing adverse events were investigated., Results: Eighty-seven patients on dupilumab and 51 patients on mepolizumab were included. Thirty-nine (45%) and 10 (20%) patients respectively encountered adverse events, which differed from phase 3 trial data. The adjusted odds ratio for adverse event rates between these two treatment groups was 3.8 (95% CI, 1.5-10.5). The most common adverse events for dupilumab were arthralgia (16%), rash (14%), and conjunctivitis or xerophthalmia (10%). The main adverse events for mepolizumab were headache (6%) and fatigue (6%). Seven dupilumab and three mepolizumab patients discontinued therapy due to adverse events. The average duration of treatment was 22.5 (range: 1-77) months for mepolizumab and 15.9 (range: 1-35) months for dupilumab., Conclusion: Dupilumab and mepolizumab have distinct adverse event profiles. This study contributes to informing clinicians' decisions regarding the use of type 2 biologics in CRSwNP patients., Level of Evidence: 3 Laryngoscope, 134:3054-3059, 2024., (© 2024 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To provide real-life evidence on long-term radiological changes in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) treated with dupilumab, and to assess possible differences between radiological and clinical results in terms of endoscopic findings and Patient-Reported-Outcomes (PROs)., Methods: Consecutive patients treated with dupilumab for recalcitrant CRSwNP were required to undergo CT scan at baseline (T0) and after 12 (T1) since first administration. A group of patients also performed CT scan at 52 weeks (T2) to assess long-term outcomes. At each timepoint, patients underwent nasal endoscopy, assessment of Nasal-Polyp-Score (NPS), Lund-Kennedy-Score (LKS), and had to fill in the 22-item Sinonasal-Outcome-Test (SNOT-22) and Visual-Analogue-Scales (VAS) for sinonasal symptoms., Results: In fifty-three included patients, from T0 to T1 we detected a significant reduction in mean Lund-Mackay score (LM), PROs (SNOT-22, VAS) and endoscopic (NPS, LKS) scores (p < 0.05). In the subset of patients that reached T2 (n = 30), compared to T1, we observed a further significant decrease in mean LM, SNOT-22, VAS, and NPS scores, but not in LKS (p = 0.420). At T1, the highest improvement was observed in PROs (SNOT-22: 56.26%), and polyp size (NPS: 49.83%). Conversely, between T1 and T2, sinus opacification was shown to be the most improved outcome (LM: 36.86%)., Conclusions: Our experience showed that poorly controlled CRSwNP patients treated with dupilumab experienced significant improvement in radiologic, endoscopic and clinical disease severity. While in the initial 3 months, PROs garnered attention for showing earlier effectiveness, radiological outcomes revealed sustained and gradual efficacy in a longer term., Level of Evidence: Level 4. According to the Oxford Center for Evidence-Based Medicine 2011 level of evidence guidelines, this non-randomized retrospective cohort study is classified as level 4 evidence Laryngoscope, 134:2626-2633, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Ocular surface reactions (OSR) have been associated with dupilumab for atopic dermatitis (AD) treatment. However, the association of dupilumab-associated OSR (DA-OSR) for nasal polyps (CRSwNP) treatment has not been studied. We evaluated DA-OSR for CRSwNP treatment using the FDA Adverse Event Reporting System (FAERS)., Methods: FAERS was queried for any general ocular reactions (DA-GOR) from 2019Q1 to 2022Q4. DA-OSR were subcategorized from DA-GOR and compared between treatment groups (CRSwNP, asthma, AD). Logistic regression was used to predict DA-OSR. Disproportionality analysis (DPA) of DA-OSR was performed using OpenVigil., Results: There were 60,198 total observations, of which 5344 were treated for CRSwNP. The prevalence of DA-GOR and DA-OSR was greatest for AD (15.3%, 7.8%), followed by CRSwNP (12.2%, 6.7%) and asthma (9.2%, 3.5%). The most commonly reported OSRs were dry eyes (35.9%), conjunctivitis (15.7%), and increased lacrimation (11.0%). The reported odds ratio (ROR) of CRSwNP-treated DA-OSR was 0.84 (0.73-0.97; p = 0.015), compared to 1.29 (1.20-1.40; p < 0.001) for AD and 0.66 (0.59-0.73; p < 0.001) for asthma. For CRSwNP treatment, the DA-OSR ROR was 0.97 (0.90-1.03; p = 0.3) for men and 0.78 (0.73-0.83, p < 0.001) for older adults (age > 50). ROR in the DPA for DA-OSR was 12.5 (12.2-12.8; p < 0.001) for any indication and 0.58 (0.53-0.64; p < 0.001) for CRSwNP treatment only., Conclusions: While there are limitations to FAERS, this study confirms the association between dupilumab and OSR for AD treatment, and does not support an association between dupilumab and OSR for CRSwNP treatment. Younger adults experience more DA-OSR in CRSwNP treatment without a specific predilection for sex., Level of Evidence: IV Laryngoscope, 134:2602-2608, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To assess the efficacy and safety of budesonide as an intrapolyp injection in chronic rhinosinusitis with nasal polyps (CRSwNP) in comparison to control and systemic steroids., Method: In a prospective double-blinded controlled randomized clinical trial, 150 patients with CRSwNP were divided into 3 groups in a ratio 1:1:1 where group (A) was given oral prednisolone 1 mg/kg tapered daily for 2 weeks, group (B) was given budesonide intrapolyp injection weekly for 5 consecutive weeks, and group (C) was given intrapolyp injection with saline as the control group. Patients were assessed upon Sinonasal Outcome Test (SNOT-22) score, Total Nasal Polyp score (TNPS), Serum IgE, absolute eosinophilic count, and morning cortisol level before treatment, 1 week and 6 months after completing their treatment protocol., Results: SNOT 22 score improved significantly in all groups compared to those at baseline. Reduction in the oral and injection groups was much greater than the control group (P 2  < 0.001), (P 3  < 0.001), and the same trend concerning TNPS score (P 2  < 0.001), (P 3  < 0.001) but with no significant change in the control group., Conclusion: Intrapolyp steroid injection is considered a safe and effective method in nasal polyposis with limited side effects in comparison to systemic steroids. Using Budesonide as an agent for intrapolyp injection appears to be promising. It's advisable in patients with multiple relapses or high-risk patients to avoid repeated courses of oral steroids., Level of Evidence: 2 Laryngoscope, 134:2085-2092, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Guidelines recommend that the vast majority of patients with severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) should have at least one endoscopic sinus surgery (ESS) prior to starting biologics. Because ESS can be performed with a variable extension, the aim of this study would be to evaluate the association between surgical extensiveness, as measured by ACCESS score, and outcomes collected in patients treated with Dupilumab., Materials and Methods: This is a multicentric retrospective study; patients affected by CRSwNP who were subjected to Dupilumab therapy and who underwent at least one ESS prior to Dupilumab initiation were included. ACCESS score was assigned to each patient's pre-Dupilumab CT scan. Subjective and objective parameters (SNOT-22, NPS, VAS scores, Sniffin' Sticks) were collected before and during the administration of therapy. Statistical correlations between ACCESS scores and clinical outcomes were investigated., Results: A total of 145 patients were included; mean time from last previous ESS was 68.6 months, and on average, patients were subjected to 2.2 surgeries. Many correlations with ACCESS scores were demonstrated: better NPS at all timepoints and subjective scores (30-days SNOT-22, VAS nasal obstruction, and rhinorrhea) were achieved in patients with low ACCESS score (more extensive ESS). On the other hand, significantly worse VAS loss of smell values were demonstrated in patients with lower ACCESS scores., Conclusion: Dupilumab patients subjected to a prior extensive ESS may have reduced size of polyps and improved subjective indicators, together with a decreased chance to recover smell, when compared with patients who underwent a minimal excision., Level of Evidence: 3 Laryngoscope, 134:1556-1563, 2024., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Dupilumab was the first biologic approved to treat chronic rhinosinusitis with nasal polyps (CRSwNP). While the risk of adverse events in phase-III clinical trials was low, dupilumab-associated adverse reactions (DAR) with real-world use is unknown and potentially under-reported. We aimed to evaluate DAR for CRSwNP treatment (CRSwNP-tx) using the FDA Adverse Event Reporting System (FAERS)., Study Design: Retrospective database study., Methods: FAERS was queried for DAR from 2019Q1 to 2021Q2. Individual DAR (iDAR) were categorized and quantitatively compared between treatment groups (CRSwNP, asthma, atopic dermatitis). Zero-truncated Poisson regression was modeled to predict the number of iDAR, and logistic regression was modeled to predict serious DARs., Results: There were 15,411 DAR observations; 911 for CRSwNP-tx, of which 121 (13.3%) had serious reactions and 3 died. Common CRSwNP-tx iDAR were dermatologic (13.9%), generalized (13.3%), and injection-site (10.8%) symptoms. The number of CRSwNP-tx iDAR was 2.99 [2.81, 3.17], compared to 3.44 [3.32, 3.56] for asthma and 3.18 [3.13, 3.24] for atopic dermatitis (Kruskal-Wallis test, P < .001). For CRSwNP-tx, iDAR reported-risk-ratio was 0.84 [0.77, 0.92] among men and 1.12 [1.04, 1.22] among older adults (>50). Serious DAR reported-odds-ratio was 1.37 [0.91, 2.04] among men and 1.39 [0.93, 2.08] among older adults., Conclusions: While there are limitations with FAERS, this analysis suggests CRSwNP-tx is associated with fewer iDAR compared with other treatment indications. More iDAR are experienced among women and older adults, but men tend to have more serious DAR., Level of Evidence: 3 Laryngoscope, 132:2307-2313, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: The 22-item Sinonasal Outcome Test (SNOT-22) is a validated chronic rhinosinusitis health-related quality-of-life outcome (HRQoL) measure; however, SNOT-22 domains have not been validated specifically for chronic rhinosinusitis with nasal polyps (CRSwNP)., Study Design: Validation of SNOT-22 domain structure, using data from 3 randomized, placebo-controlled, double-blinded, multicenter clinical trials of dupilumab in adults with moderate-to-severe CRSwNP., Methods: Preliminary dimensional structure was derived by exploratory factor analyses of SNOT-22 data from a phase 2 trial (NCT01920893) of dupilumab for the treatment of CRSwNP. Data from 2 phase 3 clinical trials (NCT02912468 and NCT02898454) were then used for confirmatory factor analysis, and evaluated for reliability, construct validity, and responsiveness. In all three trials, the SNOT-22 was administered electronically on a tablet and trial participants were required to answer all items., Results: Factor analysis supported five domains: Nasal, Ear/Facial, Sleep, Function, and Emotion. Correlations between domains were moderate to high, ranging from 0.53 (Nasal-Emotion) to 0.88 (Function-Sleep). Construct validity was mostly supported; relationships with other measures were almost always in the intended direction and magnitude. Internal consistency reliability also confirmed questionnaire structure with strong Cronbach's alpha values (all >0.80). Moderate-to-high correlations were observed between change in SNOT-22 domain scores and other study patient-reported outcome measures, along with large effect-size estimates (≥0.7), demonstrating responsiveness of the Nasal, Sleep, and Function domains. Emotion and Ear/Facial domains had small-to-moderate effect sizes., Conclusions: Psychometric analyses support the validity, reliability, and responsiveness of five domains of SNOT-22 (Nasal, Ear/Facial, Sleep, Function, and Emotion) for assessing symptoms and impact on HRQoL in patients with CRSwNP. Laryngoscope, 132:933-941, 2022., (© 2021 RTI Health Solutions, Sanofi and Regeneron Pharmaceuticals, Inc. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Dupilumab, a fully human monoclonal antibody that blocks the shared interleukin (IL)-4/IL-13 receptor component, significantly improved outcomes for patients with chronic rhinosinusitis with nasal polyps (CRSwNP) in the SINUS-24 and SINUS-52 studies. This post hoc analysis evaluated dupilumab's effect on patient-reported symptoms and objective outcome measures using thresholds of clinically meaningful within-patient change from baseline., Methods: Patients with CRSwNP receiving subcutaneous dupilumab or placebo every 2 weeks in SINUS-24/SINUS-52 were analyzed. Patients recorded severity of nasal congestion (NC), loss of smell (LoS), and anterior/posterior rhinorrhea (each within range 0-3) daily. Total Symptom Score (TSS) was calculated as a composite severity score (0-9) for these symptoms. Objective measures included University of Pennsylvania Smell Identification Test (UPSIT; 0-40), nasal polyps score (NPS; 0-8), and Lund-Mackay computed tomography score (LMK-CT; 0-24). Thresholds of within-patient change in scores from baseline at weeks 24 and 52 considered clinically meaningful were ≥1.0 (NC, LoS), ≥3.0 (TSS), ≥8.0 (UPSIT), ≥1.0 (NPS), and ≥5.0 (LMK-CT)., Results: A total of 724 and 303 patients were included in the week 24 and 52 analyses, respectively. Responder rates were significantly higher with dupilumab versus placebo at week 24 for NC (64% vs. 24%), LoS (63% vs. 14%), TSS (62% vs. 15%), UPSIT (54% vs. 6%), NPS (63% vs. 14%), and LMK-CT (59% vs. 3%); all P < .0001. Results were consistent at week 52., Conclusion: Significantly greater proportions of dupilumab-treated patients with CRSwNP compared with placebo demonstrated clinically meaningful improvements in patient-reported sinonasal symptoms and objective outcomes., Level of Evidence: 2 Laryngoscope, 132:259-264, 2022., (© 2021 Sanofi Genzyme. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Clinical trials of biologics to treat chronic rhinosinusitis with nasal polyposis (CRSwNP) have evaluated objective outcomes (e.g., University of Pennsylvania Smell Identification Test [UPSIT], nasal polyps score [NPS], and computed tomography Lund-Mackay score [CT-LMK]) and patient-reported symptoms (e.g., nasal congestion/obstruction [NC], loss of smell [LoS], and total symptom score [TSS]). We estimated anchor-based thresholds for clinically meaningful change in objective and patient-reported outcomes in patients with CRSwNP using data from LIBERTY NP SINUS-24 and SINUS-52 trials (NCT02912468; NCT02898454)., Methods: Target patient-reported outcomes were NC, LoS, and TSS; target objective outcomes were UPSIT, NPS, and CT-LMK. Anchor measures were the 22-item sinonasal outcome test (SNOT-22) rhinologic symptoms domain and total score and rhinosinusitis visual analog scale (VAS). The appropriateness of each anchor measure was evaluated by reviewing correlations between change in anchor measures and target outcomes and descriptive scores on target outcomes by levels of change in the anchor measure. Established thresholds for anchor measures (3.8 points for SNOT-22 rhinologic symptoms, 8.9 points for SNOT-22 total, 1-category improvement for rhinosinusitis VAS) were used to estimate clinically meaningful score changes for each target outcome., Results: Based on correlations between change in anchor measures and target outcomes, SNOT-22 rhinologic symptoms domain was deemed the most appropriate anchor measure. Using this anchor measure, thresholds for clinically meaningful within-patient change were NC: 1 point; LoS: 1 point; TSS: 3 points; UPSIT: 8 points; NPS: 1 point; and CT-LMK: 5 points., Conclusion: These thresholds support interpretation of efficacy results for target outcomes in CRSwNP trials., Level of Evidence: 2 Laryngoscope, 132:265-271, 2022., (© 2021 Sanofi Genzyme and RTI Health Solutions. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Dupilumab, which blocks the shared receptor component for interleukin-4 and interleukin-13, reduced polyp size, sinus opacification, and symptom severity, and was well tolerated in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) in the SINUS-52 study (NCT02898454). We assessed dupilumab in patients enrolled at Japanese centers., Methods: Patients on a background of mometasone furoate nasal spray, received dupilumab 300 mg every 2 weeks (q2w) for 52 weeks (Arm A); dupilumab 300 mg q2w for 24 weeks, followed by every 4 weeks (q4w) for 28 weeks (Arm B); or placebo (Arm C). Co-primary endpoints were week 24 nasal polyp score (NPS), nasal congestion (NC) score, and sinus Lund-Mackay CT (LMK-CT) scores. Symptoms, sense of smell, health-related quality of life, and safety were assessed during the 52-week treatment period., Results: Of 49 patients enrolled in Japan, 45 completed the study. Week 24 least squares (LS) mean improvement versus placebo were as follows: NPS (Arm A: -3.1, P < .0001; Arm B: -2.1, P = .0011); NC score (Arm A: -1.2, P < .0001; Arm B: -0.9, P < .0001); and LMK-CT (Arm A: -5.1, P = .0005; Arm B: -2.8, P = .0425). The most common treatment-emergent adverse event in dupilumab and placebo-treated patients was nasopharyngitis., Conclusion: Dupilumab provided rapid, significant, and clinically meaningful improvements for patients with CRSwNP in Japan. Dupilumab was well tolerated, and safety and efficacy were consistent with the overall study population., Level of Evidence: 2 Laryngoscope, 131:E1770-E1777, 2021., (© 2020 Sanofi. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: The Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway play a key role in immune modulation, especially in the polarization of T helper cells. JAK inhibitors reduce inflammation by inhibiting the phosphorylation of STAT. We investigated whether a JAK inhibitor, tofacitinib, can reduce inflammation in a mouse model of chronic rhinosinusitis with nasal polyps (CRSwNP)., Methods: An eosinophilic CRSwNP model was induced using 4-week-old BALB/c mice. The therapeutic effects of topical tofacitinib were compared with the effects of triamcinolone acetonide (TAC). Polyp formation and eosinophilic infiltration were assessed by histology. Levels of phosphorylated STAT (pSTAT), eosinophil cationic protein, and eotaxin were measured by immunohistochemistry. Gene expression levels of GATA-3 was measured using quantitative PCR. The production of cytokines in sinonasal tissues, including interleukin IL-4, IL-5, IL-12, and interferon-γ, were measured using enzyme-linked immunosorbent assays (ELISA)., Results: Topical tofacitinib administration significantly reduced the number of polyp-like lesions and the degree of eosinophilic infiltration, with an efficacy comparable with that of systemic TAC administration. Similarly, the levels of pSTAT6, eosinophil cationic protein, and eotaxin decreased with tofacitinib treatment. Tofacitinib decreased the gene expression level of GATA-3. Lastly, tofacitinib significantly decreased IL-4 and IL-5 production to a similar extent as that by systemic or topical TAC administration. Tofacitinib, but not TAC, significantly increased the production of interferon-γ., Conclusion: Topical tofacitinib administration may be an effective treatment for eosinophilic CRSwNP by inhibiting phosphorylation of STATs., Level of Evidence: N/A. Laryngoscope, 131:E1400-E1407, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Objective: Both endoscopic sinus surgery (ESS) and biologic therapies have shown effectiveness for medically-refractory chronic rhinosinusitis with nasal polyps (CRSwNP) without severe asthma. The objective was to evaluate cost-effectiveness of dupilumab versus ESS for patients with CRSwNP., Study Design: Cohort-style Markov decision-tree economic model with a 36-year time horizon., Methods: A cohort of 197 CRSwNP patients who underwent ESS were compared with a matched cohort of 293 CRSwNP patients from the SINUS-24 and SINUS-52 Phase 3 studies who underwent treatment with dupilumab 300 mg every 2 weeks. Utility scores were calculated from the SNOT-22 instrument in both cohorts. Decision-tree analysis and a 10-state Markov model utilized published event probabilities and primary data to calculate long-term costs and utility. The primary outcome measure was incremental cost per quality-adjusted life year (QALY), which is expressed as an Incremental Cost Effectiveness Ratio. One-way and probabilistic sensitivity analyses were performed., Results: The ESS strategy cost $50,436.99 and produced 9.80 QALYs. The dupilumab treatment strategy cost $536,420.22 and produced 8.95 QALYs. Because dupilumab treatment was more costly and less effective than the ESS strategy, it is dominated by ESS in the base case. One-way sensitivity analyses showed ESS to be cost-effective versus dupilumab regardless of the frequency of revision surgery and at any yearly cost of dupilumab above $855., Conclusions: The ESS treatment strategy is more cost effective than dupilumab for upfront treatment of CRSwNP. More studies are needed to isolate potential phenotypes or endotypes that will benefit most from dupilumab in a cost-effective manner., Level of Evidence: 2C Laryngoscope, 131:E26-E33, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilia is a disease of the upper respiratory tract for which few therapies are available. Because the oral investigational drug dexpramipexole serendipitously decreased blood eosinophils in amyotrophic lateral sclerosis studies, we assessed its safety, eosinophil-lowering activity, and preliminary clinical efficacy in patients with CRSwNP and eosinophilia., Methods: Sixteen subjects with CRSwNP, absolute eosinophil count (AEC) ≥ 0.300 × 10 9 /L, and polyp tissue eosinophils were evaluable for efficacy in a 6-month open-label, multi-center study of dexpramipexole 150 mg twice daily. The coprimary endpoints were change in AEC and change in total polyp score (TPS) from baseline to month 6, with additional clinical and histologic endpoints assessed., Results: Thirteen of 16 subjects completed 6 months of dexpramipexole treatment. Geometric mean baseline AEC was 0.525 ± 0.465 eosinophils × 10 9 /L and decreased to 0.031 ± 0.019 after 6 months of dexpramipexole treatment, a 94% reduction (P < 0.001). Ten of 16 subjects had eosinophil counts reduced to ≤ 0.020 × 10 9 /L at month 6. In 12 subjects with nasal polyp biopsies at baseline and month 6, tissue eosinophils were reduced from a mean of 168 ± 134 to 5 ± 2 per high-power field (HPF) (P = 0.001), a 97% reduction from baseline. There was no significant reduction in TPS or improvement in other clinical endpoints. Dexpramipexole was well tolerated, with no drug-related serious adverse events., Conclusion: Dexpramipexole treatment produced profound eosinophil-lowering in peripheral blood and nasal polyp tissue. Despite the near-elimination of polyp eosinophils, decreased TPS and nasal symptom improvement were not observed., Level of Evidence: 2 Laryngoscope, 129:E61-E66, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Eosinophils and mast cells are among the key cells in inflammatory diseases like chronic rhinosinusitis (CRS) and asthma. Leukotriene antagonists have proven to be effective in the treatment of asthma, but data about their efficacy in CRS are scarce, whereas data on montelukast as an add-on treatment to intranasal corticosteroids (INCS) in a postoperative setting are completely lacking., Study Design: Prospective, randomized, open-label trial., Methods: In this trial with long-term follow-up, we evaluated the efficacy of montelukast as an add-on treatment to INCS in postoperative CRS with nasal polyp (CRSwNP) patients. CRSwNP patients (N = 72) undergoing endoscopic sinus surgery were randomized in two arms for the postoperative treatment. One group (N = 36) received INCS in monotherapy, whereas the other group (N = 36) received INCS in association with montelukast for 1 year. The efficacy of montelukast with INCS was evaluated by assessing both subjective (total five-symptom score [T5SS]) and objective (nasal polyp score [NPS], Lund-Mackay [LMK] score, and subjective olfactometry [Barcelona Smell Test 24]) outcome parameters and compared with the gold standard of INCS in monotherapy., Results: After 1 year of surgery, T5SS, NPS, and LMK score were significantly reduced in patients treated with either INCS or INCS plus montelukast, without significant differences between the two treatment arms. Improvement of smell loss by olfactometry was also observed with no differences between arms. Similar findings were observed at 3 and 6 months., Conclusions: These results suggest that the addition of montelukast to INCS should not be recommended in the treatment of postoperative CRSwNP patients., Level of Evidence: 1b Laryngoscope, 1743-1751, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To evaluate the potential efficacy of steroid-soaked, absorbable calcium alginate nasal packing following endoscopic sinus surgery., Study Design: Prospective, randomized, single-blinded, placebo-controlled trial., Methods: Twenty-two patients (44 nostrils) who had chronic rhinosinusitis with polyps underwent bilateral endoscopic sinus surgery. Only those with an intersinus difference in Lund-Mackay severity score of 1 or less were included. In each patient, one randomly selected nostril was packed with calcium alginate soaked with 2 mL of triamcinolone (40 mg/mL) (triamcinolone group), whereas the contralateral nostril received an identical packing soaked in 2 mL of normal saline (saline group). Two independent investigators blinded to the packing allocation scored the surgical field using the validated Perioperative Sinus Endoscopy (POSE) scores 1, 4, and 8 weeks after surgery., Results: All 44 nostrils were analyzed; the Lund-Mackay scores did not differ significantly between the groups before surgery. Eight weeks after surgery, the total POSE scores were significantly lower in the triamcinolone group (P = .014). The POSE scoring parameters were then compared between groups, and the following variables were significantly different: middle turbinate synechiae with the lateral wall (P = .037), polypoid degeneration of the ethmoid cavity (P = .006), and sphenoid sinus severity (P = .036)., Conclusions: This study demonstrated that steroid-soaked, absorbable nasal packing can be used to enhance wound healing after endoscopic sinus surgery and to prevent polypoid changes in the nasal mucosa., Level of Evidence: 1b. Laryngoscope, 128:311-316, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Local and systemic steroid treatment is the mainstay of therapy for nasal polyposis. This study aims to evaluate the safety and effectiveness of intrapolyp steroid injection on nasal polyposis and to compare the outcomes with short-term oral steroid treatment., Study Design: Prospective, randomized, controlled endoscopic clinical trial., Methods: Ninety patients with nasal polyps were randomly assigned in a 1:1 ratio to receive oral prednisolone 1 mg/kg/day, tapering by 5 mg/day, for 2 weeks, or to receive intrapolyp steroid injection (40 mg/mL triamcinolone, 1 mL) for up to five times with intervals of 1 week. Both groups received fluticasone propionate nasal drops twice daily for 12 weeks after initial treatment. Total nasal symptoms scores and total nasal polyp scores of both groups were evaluated before and 3 and 6 months after treatment, whereas computed tomography (CT) scores were evaluated before and 6 months after treatment. Also, plasma cortisol and adrenocorticotropic hormone (ACTH) levels of the patients in the intrapolyp steroid injection group were evaluated before, during, and after treatment., Results: A total of 211 injections were given to 45 patients, and no serious complications were observed. Both groups showed significant decrease in symptom score, polyp score, and CT score (P > 0.001), with no significant difference between groups (P > 0.05). Plasma cortisol and ACTH levels of the injected patients were in normal limits before treatment, 1 week after the first injection, and 1 week after the last injection., Conclusion: Intrapolyp steroid injection appears to be an effective and safe method for treatment of nasal polyps, with comparable results to oral short-term steroid treatment., Level of Evidence: 1b. Laryngoscope, 126:1730-1735, 2016., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To investigate the effect of oral plus intranasal corticosteroid (CS) treatment on nasal polyp (NP) mucosa remodeling from patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP)., Study Design: Case series, retrospective study., Methods: Patients (n = 18) with severe CRSwNP were treated with oral prednisone for 2 weeks and intranasal budesonide for 12 weeks. NP biopsies were obtained from patients biopsies before (w0) and after 2 weeks (w2) and 12 weeks (w12) of CS treatment. Matrix metalloprotease 1 (MMP-1), MMP-2, MMP-7, MMP-9, and tissue inhibitor of metalloprotease type 1 (TIMP-1) expression was evaluated by immunohistochemistry in cell and tissue structures. Epithelial damage, eosinophil infiltration, and collagen content were also examined in NP tissues before and after CS treatment., Results: Compared to w0: 1) oral plus intranasal CS significantly (P < .01) increased presence of submucosal glands at w2, decreased epithelial cell hyperplasia at w12, and decreased tissue eosinophilia at w2 and w12; 2) CS treatment significantly (P < .05) increased immunoreactivity for MMP-1 and MMP-2 in the epithelium at w2, but decreased immunoreactivity for MMP-9 in the epithelium at w2 and w12; 3) at w12, CS significantly (P < .05) reduced MMP-9 immunoreactive positivity and intensity in the extracellular matrix, while increasing total collagen amount in the extracellular matrix; and 4) CS treatment significantly (P < .01) reduced the number of eosinophils and their MMP and TIMP-1 immunoreactive expression., Conclusions: CS treatment modulates NP mucosa remodeling, particularly by promoting epithelial repair, regulating tissue remodeling markers, increasing total collagen content, and reducing tissue eosinophil infiltration., Level of Evidence: 4, (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To assess the effect of oral plus intranasal corticosteroids on subjective outcomes (smell and nasal congestion) and objective outcomes (tissue eosinophilia and nitric oxide) in severe nasal polyposis (NP)., Study Design: After a 4-week steroid washout period (w0), severe NP were randomized into a treatment group (n = 67) that receive oral prednisone for 2 weeks (w2) plus intranasal budesonide for 12 weeks (w12), and a control group (n = 22) that received no steroid treatment., Methods: Barcelona Smell Test 24 (BAST-24), nasal congestion, tissue eosinophilia, and nasal nitric oxide (nNO) were assessed., Results: Before treatment, patients showed a significant impairment of smell detection (30.7 ± 39.5%), identification (7.1 ± 16.1%), and forced choice (13.8 ± 23.3%) in BAST-24 compared to healthy population. At w2, the treatment group showed a significant improvement in detection, identification, and forced choice. Positive effect was also seen after 12 weeks of intranasal corticosteroids. A significant reduction of nasal congestion (1.17 ± 1.0 vs. 2.73 ± 0.5) and polyp tissue eosinophilia (10.9 ± 4.2 vs. 41.2 ± 12.2) with an increase of nNO (650 ± 317 vs. 420 ± 221 ppb) were observed at w2 compared to w0 and to the control group. These effects were also seen at w12., Conclusions: Combined oral and intranasal corticosteroids improve smell and nasal congestion and decrease nasal inflammation, as measured by reduced tissue eosinophilia and increased detection of nNO. Severity of smell loss correlates with degree of nasal congestion but not with inflammation, as measured by tissue eosinophilia or nasally exhaled nNO. Our findings suggest that improvement in smell may be related to improved conduction of odorants to the olfactory neuroepithelium., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Topical steroid therapy is an important strategy in the management of chronic rhinosinusitis (CRS) with nasal polyposis. The objective of this study was to determine the impact of topical steroid therapy on nasal symptoms in patients with nasal polyposis., Study Design: Systematic review with meta-analysis using standardized methodology., Methods: Study inclusion criteria included: randomized, placebo controlled trials, nasal polyposis, and topical steroid therapy. Exclusion criteria included: failure to report at least one symptom-based outcome measure, concurrent use of systemic steroids, or mixed CRS cohorts (polyp and nonpolyp patients). Quantitative analysis was performed using a random effect model. The PRISMA guidelines for meta-analysis reporting were followed., Results: A total of 19 studies fulfilled eligibility. Seven studies were excluded from the meta-analysis due to significant heterogeneity in outcome reporting. A total of 12 studies were combined for quantitative analysis and demonstrated a pooled risk ratio of 1.72 (95% confidence interval, 1.41-2.09), indicating a significant improvement in nasal symptoms. All three topical steroid preparations (fluticasone, mometasone, and budesonide) resulted in symptom improvement. All seven studies excluded from the meta-analysis qualitatively confirmed the overall findings., Conclusions: Topical nasal steroid therapy improves nasal symptoms in CRS patients with nasal polyposis. Future studies will need to evaluate the impact on quality of life, preferably using validated disease-specific instruments., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Objectives/hypothesis: Disease recurrence and adverse wound healing in the form of inflammation, polyposis, adhesions, and middle turbinate lateralization may induce suboptimal outcomes following sinus surgery. The study objective was to assess the safety and effectiveness of a bioabsorbable, steroid-eluting implant used following functional endoscopic sinus surgery in patients with chronic rhinosinusitis (CRS)., Study Design: Prospective, multicenter, single-cohort trial enrolling 50 patients., Methods: The study allowed bilateral or unilateral steroid-eluting implant placement. Oral and topical steroids were withheld for 60 days postoperatively. Endoscopic follow-up was performed to 60 days. Patient-reported outcomes (Sino-Nasal Outcome Test-22 Questionnaire, Rhinosinusitis Disability Index) were collected to 6 months. Efficacy was assessed by grading inflammation, polyp formation, adhesions, and middle turbinate position. Safety assessment included ocular exams at baseline and 30 days., Results: Implants were successfully placed in all 90 sinuses. Mean inflammation scores were minimal at all time points. At 1 month, the prevalence of polypoid edema was 10.0%, significant adhesions 1.1%, and middle turbinate lateralization 4.4%. Changes from baseline in patient-reported outcomes were statistically significant (P < .0001). No clinically significant changes from baseline in intraocular pressure occurred., Conclusions: This consecutive case series provides clinical evidence of the safety, effectiveness, and clinical utility of a bioabsorbable steroid-eluting implant for use in CRS patients. The implant was associated with favorable rates of sinus patency. At 1 month, minimal degrees of inflammation and adhesions were observed, suggesting a positive clinical impact of local steroid delivery without evidence of ocular risk., (Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.)

Background: It has been suggested that an exaggerated immune response to fungi is crucial in the pathogenesis of chronic rhinosinusitis (CRS). Based on this rationale, the use of topical antifungals (amphotericin B) has been advocated. Studies on its clinical effectiveness are, however, contradictory., Objectives: To examine the effect of nasal antifungal treatment on secreted mediators in samples of nasal lavage fluid from patients with CRS with or without nasal polyps (NP)., Methods: Part two of a prospective double-blind, placebo-controlled multicenter clinical trial investigating the effect of 13 weeks of treatment with amphotericin B or placebo on the levels of pro-inflammatory cytokines, chemokines and growth factors (i.e., IL-1beta, IL-1RA, IL-2, IL-2R, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p40/p70 subunits), IL-13, IL-15, IL-17, TNF-alpha, IFN-alpha, IFN-gamma, G-CSF, GM-CSF, MIP-1alpha, MIP-1beta, IP-10, MIG, eotaxin, RANTES, MCP-1, MCP-2, MCP-3, VEGF, EGF, FGF-basic, HGF, Gro-alpha) and albumin via a fluorescent enzyme immunoassay in nasal lavage specimens of CRS patients with or without NP., Results: Topical amphotericin B had no significant effect on the level of any of the tested pro-inflammatory cytokines, chemokines, and growth factors in CRS nasal lavage samples. Treatment with placebo, however, increased the level of MIP-1alpha and MIP-1beta, which are mediators involved in wound healing., Conclusions: Topical amphotericin B has no significant effect on activation markers of nasal inflammatory cells in chronic rhinosinusitis with or without nasal polyps.

Objectives/hypothesis: To determine the roles of vascular endothelial growth factor (VEGF), Angiopoietin (Ang)-1, and Ang-2 in nasal polyps (NPs) by assaying expression patterns and evaluating the effects of dexamethasone (DEX) on these factors in organ cultured NPs., Study Design: Prospective., Methods: Expression patterns of VEGF, Ang-1, and Ang-2 in NPs were compared with those in inferior turbinate mucosa samples. Tissue samples were analyzed using the enzyme-linked immunosorbent assay (ELISA) and immunofluorescent staining methods. To determine the effects of DEX, NP tissues were cultured using an air-liquid interface method. Cultures were maintained in the absence or presence of DEX (10 microM or 100 microM) for 24 hours, and tissue samples analyzed with ELISA., Results: VEGF and Ang-1 levels were significantly higher, whereas the Ang-2 level was significantly lower in NPs, compared to inferior turbinate mucosa (P < .05). In NPs, VEGF and Ang-1 were detected in glandular epithelial, vascular endothelial, as well as stromal inflammatory cells, whereas Ang-2 was detected only in stromal inflammatory cells. VEGF and Ang-1 levels were significantly lower, while Ang-2 levels were significantly higher in 100 microM DEX-treated group than nontreated group (P < .01)., Conclusions: Imbalance among VEGF, Ang 1, and Ang 2 may be important in the angiogenesis of NPs. Moreover, DEX can control the expression of these factors in NPs. We suggest that VEGF and Ang-1 act as positive regulatory factors, and Ang-2 functions as a negative regulatory factor of angiogenesis in NPs.

Objectives: Churg-Strauss syndrome (CSS) is a systemic vasculitic disorder of unknown etiology that affects small-to-medium-size blood vessels. Patients affected by CSS frequently show ear, nose, and throat manifestations, which are often present at the time of disease onset. The purpose of this study was to determine the frequency of nasal polyposis in a series of 29 patients with CSS and to correlate the nasal findings to the total health situation of these patients., Study Design: Retrospective analysis., Setting: Department of Otolaryngology and Department of Clinical Medicine, Nephrology and Health Science, University of Parma., Methods: Twenty-nine patients with CSS were identified. Of the 29 patients, 17 (58.6%) had nasal polyposis and were enrolled in this study. The nasal polyps were graded according to the Lund and Mackay endoscopic and radiological classifications., Results: At diagnosis, endoscopic intranasal evaluation identified nasal polyposis of grade 3 in nine cases (52.9%), grade 2 in six cases (35.2%), and grade 1 in the remaining case (5.8%). After corticosteroid and immunosuppressive therapy, clinical remission was achieved in 14 patients (82.3%), whereas 3 patients experienced a relapse. Posttreatment endoscopic evaluation showed a permanent disappearance (grade 0) of nasal polyps in eight patients (47%). The other nine patients (52.92%) were found to have a small polyp situated in the middle meatus (grade 1)., Conclusions: Nasal polyposis in patients with CSS may represent the initial phase of the syndrome, though patients often have concurrent pulmonary disease. Corticosteroid therapy either alone or combined with immunosuppressive drugs usually yielded improvement or stabilization.

Objectives/hypothesis: Among the airway mucin genes, the MUC4 gene is an important gene in its response to inflammatory diseases of the upper airway. However, the expression and regulation of the MUC4 gene in the nasal polyps remains unclear., Study Design: The purpose of this study was to evaluate the expression of MUC4 mRNA and synthesis of mucin glycoprotein in the nasal polyps before and after treatment with a topical steroid in vivo and in vitro., Methods: Nasal polyps were obtained from 20 patients with chronic rhinosinusitis and were subsequently cultured. The level of MUC4 mRNA was measured by reverse-transcription polymerase chain reaction, and the amount of the MUC4 mucin glycoprotein was estimated by the enzyme-linked immunosorbent assay method., Results: The expression of MUC4 mRNA was found to be significantly higher in the nasal polyps than in the inferior turbinate (P < .05). The addition of interleukin (IL)-1 beta and lipopolysaccharide (LPS) increased the expression of MUC4 mRNA and mucin glycoprotein synthesis in cultured nasal polyp epithelial cells. Treatment with glucocorticoid inhibited the expression of MUC4 mRNA in the nasal polyps; it also inhibited the expression of IL-1 beta and LPS-induced MUC4 mRNA and mucin glycoprotein synthesis in cultured nasal polyp epithelial cells. The inhibitory effects of glucocorticoid were restored by treatment with a glucocorticoid receptor antagonist (RU-486)., Conclusions: These results suggest that the MUC4 gene is expressed in the nasal polyps and that glucocorticoid can control the expression of the MUC4 gene and mucin glycoprotein synthesis.

Objective: To determine clinical and comparative outcomes for endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) with polyposis., Methods: Two cohorts of adult patients with refractory CRS with and without nasal polyps were prospectively studied before and after ESS (minimum follow-up, 12 months) with the Rhinosinusitis Symptom Inventory (RSI). For the non-polyp and polyp cohorts, RSI symptom domains and medical resource utilization were compared in the preoperative and postoperative states. Corresponding effect sizes were computed and compared between cohorts to determine the effect of polyps on prognosis after ESS., Results: A total of 165 non-polyp and 86 polyp patients were enrolled. Polyps were more common in female patients (2:1, P = .025); age (mean, 42.9 years) and follow-up (18.5 months) were similar between groups. Lund scores were significantly higher for polyp patients (13.7, SD 4.8) vs. non-polyp patients (8.1, SD 5.3, P < .001). At baseline, polyp patients reported lower symptom scores for facial, oropharyngeal, and systemic RSI symptom domains (all P < .012); nasal and total symptom domains were similar between groups. Both non-polyp and polyp groups obtained significant symptomatic benefit from ESS with effect sizes for RSI symptom domain improvements ranging from 0.89 to 1.38 and 0.43 to 1.19, respectively (all P < .001). There were no significant differences between groups in symptomatic improvement, excepting oropharyngeal symptoms (better improvement in non-polyp group, P = .024). Non-polyp patients decreased medical resource consumption more significantly than did polyp patients., Conclusions: Both non-polyp and polyp patients derive similar clinically significant symptomatic improvement after ESS. These similarities suggest that polyp patients do not necessarily have a poorer symptomatic outcome after ESS.

Background: Nasal polyposis is an inflammatory disease of unknown etiology. This study aimed to evaluate the effect of a short course of oral prednisone followed by intranasal budesonide on nasal symptoms, polyp size, nasal flow, and computed tomography scan., Methods: Eighty-four patients with severe nasal polyps were included. After a steroid washout period, patients were randomized into two groups: group A (n = 63) received oral prednisone for 2 weeks and group B (n = 21) did not receive any steroid treatment. Patients from group A received intranasal budesonide for 12 weeks., Results: Atopy was positive in 36.8% of patients. Blood eosinophilia was higher in asthmatic (7.2 +/- 0.7%, P < .05) than in nonasthmatic (3.0 +/- 0.4%) patients. Asthmatic patients showed higher scores on nasal obstruction and loss of smell than nonasthmatics. Oral steroids caused a significant improvement in all nasal symptoms and improved polyp size (2.1 +/- 0.1, P < .05) and nasal flow (560 +/- 35 cm/s, P < .05) compared with nontreated patients (2.8 +/- 0.1 and 270 +/- 34 cm/s, respectively). Intranasal budesonide maintained the improvement on nasal symptoms, polyp size, and nasal flow. Steroid treatment reduced the computed tomography scan score (15.4 +/- 1, P < .05) compared with before treatment (18.2 +/- 0.8)., Conclusion: A short course of oral steroids improved all nasal symptoms, polyp size, and nasal flow, whereas intranasal steroid maintain this effect.

Objective: In order to study a new mechanism of efficacy of 14-membered ring macrolides in treating chronic rhinosinusitis, inhibitory effects of macrolides on vascular endothelial growth factor production were examined in vitro., Methods: Vascular endothelisal growth factor production in cultured fibloblasts from human nasal polyps obtained from surgery for chronic paranasal sinusitis stimulated by hypoxia or tumor necrosis factor-alpha was assessed under the administration of Clarithromycin or Roxisthromycin by enzyme linked immunosorbent assay and reverse transcriptase polymerase chain-reaction., Results: Dose-dependent inhibitory effects on vascular endothelisal growth factor production stimulated by hypoxia or tumor necrosis factor-alpha were noted in the groups treated with Clarithromycin and Roxisthromycin, including inhibition of vascular endothelisal growth factor mRNA levels., Conclusion: While, to date, several evidences have indicated that the mechanisms by which 14-membered ring macrolides reduce inflammation are not simply bactericidal, these results suggest another new mechanism of efficacy of macrolides in treating chronic rhinosinusitis.

Objectives/hypothesis: Intranasal lysine-aspirin has been used as a method of desensitization in patients with aspirin-sensitive nasal polyps to control their recurrence and prevent frequent surgical intervention. However, the studies are limited in number, and their design is open to criticisms. Thus, we conducted a controlled trial to study the clinical effectiveness of topical lysine-aspirin in patients with aspirin-sensitive nasal polyposis., Study Design: Prospective, randomized, double blind, placebo controlled, crossover trial., Methods: Aspirin-sensitive patients confirmed by intranasal challenge were enrolled and randomized to receive 16 mg of topical lysine-aspirin every 48 hours or placebo for 6 months before crossover. Polyp growth and nasal and chest symptoms were monitored using acoustic rhinometry, nasal inspiratory peak flow, peak expiratory flow rate, and a daily diary of symptom scores., Results: Twenty-two patients were enrolled. After withdrawals and drop outs, data were available on 11 patients for analysis. Multivariate analysis of measured parameters did not reveal a significant clinical benefit to patients receiving topical lysine-aspirin compared with placebo. Deterioration was similar while on lysine-aspirin or placebo., Conclusions: This is the first controlled clinical trial of topical desensitization in aspirin-sensitive nasal polyp patients. Despite the failure to demonstrate clinical benefit, tissue studies have shown a significant improvement at the microscopic level. Further work with larger numbers of patients along with conventional treatment may show a clinical improvement in these patients.

Objectives/hypothesis: Chronic hyperplastic sinusitis (CHS) with nasal polyps (NP) is characterized by extensive mucosal thickening, goblet cell hyperplasia, and subepithelial fibrosis. These features are described to be part of remodeling in the lower airways. The cytokines interleukin (IL)-11 and IL-17 are believed to play a role in lower airway remodeling, but there has been very little work so far examining these cytokines and their relationship to fibrosis in CHS/NP. The aims of this study were to examine the deposition of collagens types I, III, and V in CHS/NP, evaluate the relationship of collagen deposition to expression of IL-11 and IL-17, and to examine the effect of treatment with intranasal fluticasone on these features., Study Design: Sixteen subjects were included in this double-blind, placebo-controlled study. NP biopsies were obtained at the baseline and after 4 weeks of treatment with intranasal fluticasone propionate (FP, Flonase) or placebo. Normal control middle turbinate biopsies from eight nonallergic subjects without sinusitis were used as a control for cytokine and collagen expression., Methods: Tissues were assessed for deposition of collagen types I, III, and V using immunocytochemistry. The expression of the cytokines IL-11 and IL-17 was examined by immunostaining or in situ hybridization. The pre- to posttreatment results were analyzed using paired t test, and the magnitude of changes were estimated using one-way analysis of variance (ANOVA) statistical test followed by least significance difference post hoc comparisons of means., Results: Compared with normal control nasal turbinate tissues, collagen types I, III, and V were increased in all NP tissues, with a predominance of types III and V. Collagen deposition was most abundant in the submucosal connective tissue and in the basement membrane zone. FP treatment had no significant effect on deposition of any collagen type. Expression of IL-11 and IL-17 was also greatly increased in NP compared with control nasal turbinate tissues. IL-11 expression was observed in both inflammatory cells and the epithelium, whereas IL-17 expression was primarily associated with inflammatory cells. In the pretreatment NP, a correlation was found between the presence of IL-11 and collagen type I (r = 0.59, P =.02) and also between IL-17 and both CD4+ and CD8+ T lymphocytes (r = 0.52, P =.05; r = 0.60, P =.02, respectively). Treatment with FP significantly reduced IL-11 expression in subepithelial inflammatory cells and in the epithelial compartment. In contrast, although IL-17 expression was reduced by FP, this effect did not reach statistical significance., Conclusion: NP manifest an increased expression of collagen types III, V, and I and an increase in profibotic cytokines IL-11 and IL-17. A correlation exists between deposition of collagen type I and expression of IL-11, suggesting a possible role for IL-11 in NP remodeling. Collagen deposition was not reversed by FP treatment, whereas IL-11 expression was suppressed. These results are consistent with a partial insensitivity of NP to FP treatment but also suggest that longer-term treatment or perhaps earlier intervention with FP might reduce proinflammatory cytokine signals and ultimately have a beneficial effect in preventing airway remodeling in NP.

Objectives/hypothesis: The management of nasal polyposis is undoubtedly a controversial subject. The part played by surgery seems to be steadily growing, if the number of published reports dedicated to this approach is any yardstick. Although the medical treatment remains the undisputed therapeutic mainstay, trials dedicated to the long-term assessment of its overall efficacy are scarce., Study Design: Retrospective medical record review., Methods: The aim of the study is focused on the evaluation of a dual modality, topical and systemic, over a follow-up period of 3 years. In all, 100 patients were treated according to a standardized therapeutic protocol combining short-term oral administration of prednisolone and daily intranasal spray of beclomethasone., Results: Over the follow-up period of 3 years, this dual modality proved to be successful in 85% of the patients; only 15% had to undergo surgery after its failure. The average symptom reduction reached an improvement rate varying from 58% to 80%, according to the symptom type. The daily dosage of prednisolone and beclomethasone was progressively decreased while the gain in nasal comfort was being preserved., Conclusions: Management of nasal polyps should be primarily medical. Resorting to surgical procedures should not be envisaged before a trial is conducted of dual steroid therapy under a regimen of strict compliance to treatment.

Objective/hypothesis: Corticosteroids are an effective treatment for nasal polyposis. The exact mechanism of action is not certain. Recent research demonstrates that apoptosis (programmed cell death) in inflammatory cells is an important factor in the resolution of inflammation, and apoptosis is induced in eosinophils in cell culture with steroids. We hypothesized that inflammatory cell apoptosis is a key feature of regression of nasal polyps on exposure to steroids and examined this hypothesis in vivo and in vitro., Methods: A double-blind, placebo-controlled pilot study of fluticasone propionate aqueous nasal spray (FPANS) in nasal polyposis in humans in vivo was undertaken, and the effect of treatment on indices of cell death and proliferation measured. In addition, explants of nasal polyp tissue were maintained in vitro in short-term tissue culture with dexamethasone at increasing doses (0.1-50 micromol) over varying time intervals and then analyzed for similar indices of proliferation and cell death., Results: Apart from a marginal increase in apoptotic:mitotic ratio in epithelium, little difference between the effect of FPANS and placebo was demonstrated in vivo. However, in vitro, apoptotic index was significantly increased in the stromal layers in relation to time of incubation (P = .0169), and a significant dose-response relationship was demonstrated at 24 hours between stromal cell apoptosis and dexamethasone concentration (P = .001). Eosinophil apoptosis was confirmed by in situ end labeling and transmission electron microscopy. No steroid or time effect on epithelial cells was demonstrated in vitro., Conclusion: Corticosteroids induce apoptosis in inflammatory cells in human nasal polyps in vitro. This is not reflected by a similar response to FPANS at 14 days in vivo, but may still play a part in regression of polyps with other forms of administration or at other time points.