Severe Chronic Rhinosinusitis With Nasal Polyps Research Articles

Dupilumab has an additional benefit in treatment of chronic rhinosinusitis with nasal polyps

HintergrundFür Patienten mit schwerer chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP), die durch eine Dauertherapie mit intranasalen Kortikosteroiden (INCS) und Gabe von systemischen Kortikosteroiden und/oder eine chirurgische Behandlung nicht ausreichend kontrolliert werden konnten, gab es für lange Zeit keine zugelassenen kurativen Therapieoptionen. Bei der CRSwNP ist eine Behandlung mit T2-adressierenden Biologika möglich. Am 24.10.2019 hat die Europäische Kommission für Dupilumab als erstes Biologikum eine Zulassungserweiterung zur Therapie von unzureichend kontrollierter, schwerer CRSwNP ausgesprochen. Der Gemeinsame Bundesausschuss (G‑BA) bewertet den Nutzen von erstattungsfähigen Arzneimitteln mit neuen Wirkstoffen. Hierzu gehört insbesondere die Bewertung des Zusatznutzens und seiner therapeutischen Bedeutung.MethodenAuf der Grundlage zweier Phase-III-Studien wurde eine Metaanalyse anhand von individuellen Patientendaten durchgeführt. In beiden Studien wurde die Wirksamkeit und Sicherheit von Dupilumab als Add-on-Therapie zu INCS zur Behandlung von Erwachsenen mit schwerer CRSwNP, die mit systemischen Kortikosteroiden und/oder chirurgischem Eingriff nicht ausreichend kontrolliert werden kann, im Vergleich zu INCS untersucht.ErgebnisseBasierend auf den Studiendaten hat der G‑BA entschieden, dass für Dupilumab als Add-On zu INCS ein Hinweis auf einen beträchtlichen Zusatznutzen gegenüber Mometasonfuroat vorliegt.SchlussfolgerungFür Patienten mit schwerer CRSwNP, die durch eine Erhaltungstherapie mit INCS und Gabe von systemischen Kortikosteroiden und/oder eine chirurgische Behandlung nicht ausreichend kontrolliert werden, besteht für die Gabe von Dupilumab als Add-On zu INCS ein Hinweis auf einen beträchtlichen Zusatznutzen gegenüber Mometasonfuroat allein.

Dupilumab: new opportunities for the treatment of asthma and chronic rhinosinusitis with nasal polyps

Airway inflammation plays a crucial role in the development of asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The severity of inflammation influences the clinical picture of the disease and, most importantly, the effectiveness of therapy. To date, the growth in the incidence rate of asthma and CRSwNP is still high and the effectiveness of existing therapy for severe asthma, especially associated with CRSwNP, is unsatisfactory. Therefore, the aim is to investigate novel diagnostic tools and therapies. The emergence of biologics that target specific inflammatory pathways is a promising step forward to achieve control of severe uncontrolled asthma and recurrent CRSwNP. Dupilumab is one of recently introduced monoclonal antibodies, which has shown significant advances in the treatment of asthma and CRSwNP. Dupilumab is a fully human monoclonal antibody targeted to interleukin-4 receptor alpha subunit (IL-4R) that is a receptor for both IL-4 and IL-13. Thus, it helps to inhibit cytokine T2-signaling (IL-4 and IL-13), since the IL-4/IL-13/STAT6 signaling pathway plays a crucial role in T2-inflammation. In Russia, dupilumab is currently approved as a treatment for atopic dermatitis (in children over 6 years of age), asthma (in children over 12 years of age) and severe CRSwNP in adults. This article summarizes the main data on dupilumab and its efficacy in patients with asthma and CRSwNP and presents a relevant case report.

Health-Related Quality of Life Impairment Among Patients With Severe Chronic Rhinosinusitis With Nasal Polyps in the SINUS-24 Trial

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease of the nasal cavity and paranasal sinuses, with a high symptom burden and significant impact on health-related quality of life (HRQoL). This analysis compared baseline generic physical and mental HRQoL, and overall health status, of patients with severe CRSwNP on background mometasone furoate from the SINUS-24 (NCT02912468) study, with general population norms.

A Responder Analysis To Demonstrate Dupilumab Treatment Effect Across Objective and Patient-Reported Subjective Endpoints For Patients with Severe Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)

Dupilumab has demonstrated reduction in nasal polyp score (NPS) and individual symptom scores in patients with severe CRSwNP; however, combined responder analyses using these endpoints have not been conducted. This post hoc analysis explored the overall effect of dupilumab across both objective and patient-reported subjective endpoints.

Biologics: A New Option in Treatment of Severe Chronic Rhinosinusits with Nasal Polyps

Chronic rhinosinusitis (CRS) is defined as an inflammation of the nose and paranasal sinuses with prevalence of 10.9 % and by the presents of 2 or more symptoms, which last more than 12 weeks. The symptoms are nasal obstruction, nasal discharge (anterior/post nasal drip), facial pain or pressure and/or olfactory disorder. CRS has a high negative impact on an individual's quality of life. The pathogenesis is multifactorial and complex. CRS has been subclassified into 2 groups: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Regarding further knowledge of the inflammatory pathway the primary CRS is considered by endotype dominance, either type 2 or non-type 2. 80 % of the CRSwNP reveals a type 2 inflammation. The proteins, interleukin (IL)-4, IL-5, IL-13, and IgE were previously identified as key mediators in nasal polyp tissues pattern. CRSwNP is often refractory to medical and surgical management, especially in patients with asthma and aspirin intolerance. In most cases the control of the disease is a challenge. Patients with asthma but especially with Samter's triad are significantly more likely to have a recurrence of nasal polyps and undergo a second surgery following recurrence. In patients with severe CRSwNP, in whom the current standard of care including topical and oral corticosteroids, antibiotics and surgical procedures fail to control the disease, biologics can open new perspectives in treatment. They allow avoiding the possible adverse events resulting from repeated use of systemic corticosteroids and surgery. These biologics have a high impact on type 2 immune reaction and lead to a reduction of IgE as well as of local mucosal eosinophil migration and activation, resulting in a significant effect on nasal polyps, smell, quality of life and asthma comorbidity.

State-of-the-art overview on biological treatment for CRSwNP.

The majority of patients with uncontrolled severe CRSwNP, asthma and atopic dermatitis share a similar T helper 2 type inflammation linked to their underlying phenotype. This discovery has triggered new research around treatments targeting specific cytokines driving inflammation in CRSwNP like IL-4, IL-13, IL-5 and IgE. Biologicals are increasingly tested as additional tre- atment for patients suffering from severe chronic rhinosinusitis with nasal polyps (CRSwNP). Their efficacy has been demonstrated in multiple studies. All studies differ in terms of baseline characteristics of included patients and outcome parameters analysed. A comparative analysis of the efficacy of reported biologicals for CRSwNP based on the published data for phase 2 and 3 studies. The aim was to provide a comprehensive overview across the different biologicals and outcome parameters. In a first step we critically selected out of all available phase 2 and 3 clinical trials the ones containing the most rigorous and compatible study designs. Meaning studies that comply with a need for a clear definition of CRSwNP, at least two administra- tion doses, comparable timeframes and the same outcome parameters studied. This assessment was performed using a PRISMA search. We retained 7 studies with significant data for dupilumab, mepolizumab and omalizumab. In a second step the effect-sizes of treatment with those biologicals were compared for the most important outcome parameters both patient relevant (nasal con- gestion, smell loss and SNOT-22 scores) and patient irrelevant (CT scan Lund-Mackay, smell test and nasal polyp scores). Therapy duration of 16 to 25 weeks was chosen for evaluation of efficacy. A direct comparison of efficacy between dupilumab, mepolizumab and omalizumab is challenging given differences in inclusion criteria, outcome parameters and time-points of analyses. We have been able to conclude that effect sizes of dupilumab, mepolizumab and omalizumab seem large enough to reflect a major reduction in symptom burden as experienced by patients suffering from refractory CRSwNP. The effect size of dupilumab on both patient relevant and patient irrelevant parameters of smell loss are clearly significant and reflect the clinical experience of major reduction of smell impairment in treated patients. Despite the heterogeneity of protocols, dosages and time-points of analyses of biological trials in CRSwNP, this over- view highlights outcomes of biological treatment in CRSwNP in a comprehensive way. Real-life registries, comparative trials and/ or endotype-driven treatment plans are needed to provide the answers to the multiple questions that are still open today.

EUFOREA expert board meeting on uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) and biologics: Definitions and management

Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is the most bothersome phenotype of chronic rhinosinusitis; it is typically characterized by a type 2 inflammatory reaction and by comorbidities, including asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, and allergies. Here, the European Forum for Research and Education in Allergy and Airway Diseases proposes structured definitions to enable communication between clinicians and provides a practical algorithm to define type 2 inflammation in CRSwNP in daily clinical practice. Arational approach for the treatment of uncontrolled severe CRSwNP is discussed; it consists of evaluating the perspective and risks of surgery and efficacy and adverse events of biologics on the basis of currently available data. Further, possible combinations of surgery and biologics are discussed, and a rationale is provided. Here, it is of importance to adequately counsel the patient about both approaches to enable a decision-making process with an informed patient. Criteria for the selection of a biologic drug are provided, as several biologics for uncontrolled severe CRSwNP will be available in many countries within a short time. Further, suggestions for monitoring of the drug effects that support recognition of responders to the therapy and, subsequently, the decision regarding continuation or discontinuation of the biologic are proposed.

Adult chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) occurs in >10% of the adult population in Europe and the USA and can be differentiated into CRS without nasal polyps and CRS with nasal polyps (CRSwNP). Both phenotypes are characterized by a high disease burden and an overlapping spectrum of symptoms, with facial pain and loss of smell being the most differentiating. Great progress has been made in the understanding of CRS pathophysiology: from the epithelium and epithelial-mesenchymal transition to innate and adaptive immunity pathways and, finally, on the role of eosinophils and Staphylococcus aureus in the persistence of disease. Although clinical manifestations and diagnostic tools (including nasal endoscopy and imaging) have undergone major changes over the past few years, management (including pharmacotherapy, surgery and biologics) has experienced enormous progress based on the growing knowledge of key mediators in severe CRSwNP. The introduction of endotyping has led to a differentiation of 'tailored' surgical approaches, focusing on the mucosal concept in those with severe CRSwNP and on the identification of patients eligible for extended surgery and possibly biologics in the future.

Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by IgE hyperproduction and eosinophilic inflammation. The anti-IgE antibody, omalizumab, has demonstrated efficacy in patients with CRSwNP and comorbid asthma previously. Our aim was to determine omalizumab safety and efficacy in CRSwNP in phase 3 trials (POLYP 1 and POLYP 2). Adults with CRSwNP with inadequate response to intranasal corticosteroids were randomized (1:1) to omalizumab or placebo and intranasal mometasone for 24 weeks. Coprimary end points included change from baseline to week 24 in Nasal Polyp Score (NPS) and Nasal Congestion Score. Secondary end points included change from baseline to week 24 in Sino-Nasal Outcome Test-22 (SNOT-22) score, University of Pennsylvania Smell Identification Test, sense of smell, postnasal drip, runny nose, and adverse events. Patients in POLYP 1 (n= 138) and POLYP 2 (n= 127) exhibited severe CRSwNP and substantial quality of life impairment evidenced by a mean NPS higher than 6 and SNOT-22 score of approximately 60. Both studies met both the coprimary end points. SNOT-22 score, University of Pennsylvania Smell Identification Test score, sense of smell, postnasal drip, and runny nose were also significantly improved for omalizumab versus placebo. In POLYP 1 and POLYP 2, the mean changes from baseline at week 24 for omalizumab versus placebo were as follows: NPS, -1.08 versus 0.06 (P< .0001) and -0.90 versus -0.31 (P= .0140); Nasal Congestion Score, -0.89 versus -0.35 (P= .0004) and -0.70 versus -0.20 (P= .0017); and SNOT-22 score, -24.7 versus -8.6 (P< .0001) and -21.6 versus -6.6 (P< .0001). Adverse events were similar between groups. Omalizumab significantly improved endoscopic, clinical, and patient-reported outcomes in severe CRSwNP with inadequate response to intranasal corticosteroids, and it was well tolerated.

Dupilumab: Clinical Efficacy of Blocking IL-4/IL-13 Signalling in Chronic Rhinosinusitis with Nasal Polyps.

In September 2019, The Lancet published details of two large Phase III double-blind placebo-controlled studies (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52) confirming the clinical efficacy of the biologic dupilumab in simultaneously blocking both IL-4/IL-13 signalling in chronic rhinosinusitis with nasal polyps (CRSwNP). The studies demonstrated that dupilumab (Dupixent®, Sanofi and Regeneron) 300mg subcutaneously administered was clinically effective when added for patients with moderate to severe CRSwNP already maintained on the standard intranasal steroid mometasone furoate. Duration of treatment ranged from injections either 2 weekly for 24 weeks (SINUS-24) or every 2 weeks for 52 weeks or finally every 2 weeks for 24 weeks stepping down thereafter to every 4 weeks for a further 28 weeks (SINUS-52). Rapid improvements in all important parameters of disease burden were seen with such improvement maintained even where the frequency of injections was decreased. In patients with co-existent asthma, lung function and asthma control scores improved. This is consistent with the one airway hypothesis of shared T2 inflammatory programmes driving both disease syndromes. The studies formed the basis for FDA registration and clinical launch in the US, and EMA approval in Europe. Dupilumab presents a significant new treatment option in an area of urgent unmet therapeutic need in CRSwNP. Should dupilumab prove to be as effective in the real-life clinical environment as it has been in the studies, then a paradigm shift from sinonasal surgery to medical treatment of CRSwNP may need to occur in the ENT community. Questions in relation to best patient selection, combined upper and lower airway therapeutic pathways, long-term safety along with health economics and cost constraints ought now to be addressed.

P452 DUPILUMAB IMPROVES PATIENT-REPORTED OUTCOMES IN CHRONIC RHINOSINUSITIS WITH NASAL POLYPS AND COMORBID ASTHMA: SINUS-24/SINUS-52 TRIALS

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP), a type 2 inflammatory disease of the upper airways, frequently have comorbid asthma, which increases symptom burden and quality-of-life impairment. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4/interleukin-13, key drivers of type 2 inflammation. We report the effect of dupilumab on prespecified patient-reported outcomes (PROs) in patients with severe CRSwNP and comorbid asthma in the pooled population of the phase 3 trials SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454).

Analysis of the impact of bronchial asthma and hypersensitivity to aspirin on the clinical course of chronic sinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease with still not enough known pathogenesis despite the development of genetics, immunological and microbiological research. The number of patients with CRS has been constantly growing. The coexistence of CRS, bronchial asthma and aspirin intolerance (aspirin triad) is an adverse prognostic factor with higher risk of recurrences. The aim of study was to compare the severity of CRSwNP depending of coexistence of bronchial asthma and/or aspirin intolerance. The research was performed in the group of 204 patients operated 2009-2013 with 5 years follow-up. Higher nasal polyps growth in groups of patients with aspirin triad and CRSwNP and bronchial asthma in endoscopic examination (p=0,0005 and p=0,0030 respectively) and CT-scan according to Lund-Mackay point scale (p&lt;0,0001 and p=0,0009) was showed. Also, these patients presented increased severity of nasal symptoms before surgical treatment according to VAS scale (p=0,0126 for CRSwNP with bronchial asthma; p=0,0390 for aspirin triad). Similarly, 6 months after surgery the same groups of patients presented higher severity of the disease symptoms (p&lt;0,0001 for aspirin triad' patients; p=0,0174 for CRSwNP and bronchial asthma' patients) . Patients with aspirin triad had also statistically more surgeries in past (p=0,001), what proves that recurrences in this group are very likely to be observed in spite of the use of proper conservative treatment. No such differences have been shown in the group of patients with CRSwNP and isolated aspirin intolerance (without bronchial asthma). Allergy to inhaled allergens, hypersensitivity to aspirin are factors significantly worsening the course of CRSwNP. It would be advisable to consider, despite a lack of history of aspirin intolerance, a hypersensititvity to aspirin test in patients with particularly severe CRSwNP, especially those associated with bronchial asthma. It also seems reasonable to carry out such a test on every patient with newly diagnosed CRSwNP and bronchial asthma in order to be able to plan further treatment in this group of patients accordingly including biological treatment with antimonoclonal therapy against interleukin 4, 5 or13.

Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) generally have a high symptom burden and poor health-related quality of life, often requiring recurring systemic corticosteroid use and repeated sinus surgery. Dupilumab is a fully human monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation, and has been approved for use in atopic dermatitis and asthma. In these two studies, we aimed to assess efficacy and safety of dupilumab in patients with CRSwNP despite previous treatment with systemic corticosteroids, surgery, or both. LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52 were two multinational, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies assessing dupilumab added to standard of care in adults with severe CRSwNP. SINUS-24 was done in 67 centres in 13 countries, and SINUS-52 was done in 117 centres in 14 countries. Eligible patients were 18 years or older with bilateral CRSwNP and symptoms despite intranasal corticosteroid use, receiving systemic corticosteroids in the preceding 2 years, or having had sinonasal surgery. Patients in SINUS-24 were randomly assigned (1:1) to subcutaneous dupilumab 300 mg or placebo every 2 weeks for 24 weeks. Patients in SINUS-52 were randomly assigned (1:1:1) to dupilumab 300 mg every 2 weeks for 52 weeks, dupilumab every 2 weeks for 24 weeks and then every 4 weeks for the remaining 28 weeks, or placebo every 2 weeks for 52 weeks. All patients were randomly assigned centrally with a permuted block randomisation schedule. Randomisation was stratified by asthma or non-steroidal anti-inflammatory drug-exacerbated respiratory disease status at screening, previous surgery at screening, and country. Patients with or without comorbid asthma were included. Coprimary endpoints were changes from baseline to week 24 in nasal polyp score (NPS), nasal congestion or obstruction, and sinus Lund-Mackay CT scores (a coprimary endpoint in Japan), done in an intention-to-treat population. Safety was assessed in a pooled population of both dupilumab groups in SINUS-52 up to week 24 and the dupilumab group in SINUS-24 and the placebo groups in both studies until week 24. The trials are complete and registered at ClinicalTrials.gov, NCT02912468 and NCT02898454. Between Dec 5, 2016, and Aug 3, 2017, 276 patients were enrolled in SINUS-24, with 143 in the dupilumab group and 133 in the placebo group receiving at least one study drug dose. Between Nov 28, 2016, and Aug 28, 2017, 448 patients were enrolled in SINUS-52, with 150 receiving at least one dose of dupilumab every 2 weeks, 145 receiving at least one dose of dupilumab every 2 weeks for 24 weeks and every 4 weeks until week 52, and 153 receiving at least one dose of placebo. Dupilumab significantly improved the coprimary endpoints in both studies. At 24 weeks, least squares mean difference in NPS of dupilumab treatment versus placebo was -2·06 (95% CI -2·43 to -1·69; p<0·0001) in SINUS-24 and -1·80 (-2·10 to -1·51; p<0·0001) in SINUS-52; difference in nasal congestion or obstruction score was -0·89 (-1·07 to -0·71; p<0·0001) in SINUS-24 and -0·87 (-1·03 to -0·71; p<0·0001) in SINUS-52; and difference in Lund-Mackay CT scores was -7·44 (-8·35 to -6·53; p<0·0001) in SINUS-24 and -5·13 (-5·80 to -4·46; p<0·0001) in SINUS-52. The most common adverse events (nasopharyngitis, worsening of nasal polyps and asthma, headache, epistaxis, and injection-site erythema) were more frequent with placebo. In adult patients with severe CRSwNP, dupilumab reduced polyp size, sinus opacification, and severity of symptoms and was well tolerated. These results support the benefits of adding dupilumab to daily standard of care for patients with severe CRSwNP who otherwise have few therapeutic options. Sanofi and Regeneron Pharmaceuticals.

Efficacy and Safety of Dupilumab in Patients with Chronic Rhinosinusitis with Nasal Polyps: Results from the Randomized Phase 3 Sinus-24 Study

Dupilumab, a human IL-4R-α mAb inhibiting IL-4 and IL-13, key drivers of type 2-mediated inflammation, is approved for uncontrolled moderate-to-severe atopic dermatitis in adults and in the USA for patients aged ≥12 years with moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma. In a phase 2a study, dupilumab improved endoscopic, radiologic, clinical, and patient-reported outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. For the first time we report results from a phase 3 dupilumab study (SINUS-24; NCT02912468) in severe CRSwNP patients (with/without comorbid asthma) on daily intra-nasal mometasone furoate (MFNS). Adults with CRSwNP previously treated with systemic corticosteroids (SCS) and/or surgery (n = 276) were randomized 1:1 to subcutaneous dupilumab 300mg or placebo every 2 weeks for 24 weeks. Outcomes included change from baseline to Week 24 in nasal polyp score (NPS), patient-reported nasal congestion (NC), CT Lund-Mackay (LMK), UPSIT smell test, SNOT-22, FEV1, and ACQ-6 scores. Mean [SD] baseline values were comparable in dupilumab/placebo for NPS (5.64 [1.23] / 5.86 [1.31]), NC (2.26[0.57]/2.45[0.55]), LMK (18.55 [4.55] / 19.55 [4.26]), UPSIT (14.68 [8.66] / 14.44[8.31]), and SNOT-22 (48.00 [20.16] / 50.87[20.22]). Dupilumab significantly (P<0.0001) improved NPS (−2.06), NC (−0.89), LMK (−7.44), UPSIT (+10.56), and SNOT-22 (−21.12) from baseline to Week 24 (LS-mean differences vs placebo). Dupilumab treatment reduced SCS use/NP surgery (P<0.001), and in comorbid asthma patients (58.3%) improved lung function (FEV1; P<0.001) and asthma control (ACQ-6; P<0.0001). The most common adverse event occurring at higher frequency with dupilumab was epistaxis (7.7% vs 3.0% placebo). Add-on dupilumab to MFNS significantly improved endoscopic, radiologic, clinical, and patient-reported sino-nasal outcomes, and asthma outcome measures in severe CRSwNP patients, and was well-tolerated.

Omalizumab treats chronic rhinosinusitis with nasal polyps and asthma together-a real life study

Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma often coexist and thus treating both with one intervention is an attractive strategy. To prospectively evaluate whether treatment with the monoclonal antibody against IgE Omalizumab for severe allergic asthma also effectively treats co-existent CRSwNP. SNOT-22 and the ACQ-7 scores were recorded at 4 and 16 weeks of treatment in a cohort of patients with both CRSwNP and severe refractory allergic asthma treated with Omalizumab (n=13) according to UK guidelines for their severe asthma. SNOT-22 in a surgery only treated CRSwNP with asthma group (n=24) was compared. Rapid improvement was seen at 4 weeks and 16 weeks of treatment in both CRSwNP and asthma control. The improvement in CRSwNP with Omalizumab was similar to that seen in a group of patients who received upper airway surgery. Omalizumab treatment for severe allergic asthma also improves co-existent CRSwNP. Further clinical studies of current and emerging biological agents for severe asthma should include upper airway outcomes. These agents may be effective for severe CRSwNP and comparative studies with surgery are warranted.

Omalizumab treats chronic rhinosinusitis with nasal polyps and asthma together-a real life study.

Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma often coexist and thus treating both with one intervention is an attractive strategy. To prospectively evaluate whether treatment with the monoclonal antibody against IgE Omalizumab for severe allergic asthma also effectively treats co-existent CRSwNP. SNOT-22 and the ACQ-7 scores were recorded at 4 and 16 weeks of treatment in a cohort of patients with both CRSwNP and severe refractory allergic asthma treated with Omalizumab (n=13) according to UK guidelines for their severe asthma. SNOT-22 in a surgery only treated CRSwNP with asthma group (n=24) was compared. Rapid improvement was seen at 4 weeks and 16 weeks of treatment in both CRSwNP and asthma control. The improvement in CRSwNP with Omalizumab was similar to that seen in a group of patients who received upper airway surgery. Omalizumab treatment for severe allergic asthma also improves co-existent CRSwNP. Further clinical studies of current and emerging biological agents for severe asthma should include upper airway outcomes. These agents may be effective for severe CRSwNP and comparative studies with surgery are warranted.

Altered Quality of Life and Psychological Health (SCL-90-R) in Patients With Chronic Rhinosinusitis With Nasal Polyps.

To investigate the impact of olfactory dysfunction on quality of life (QOL) and psychological status in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). A retrospective observational study was conducted from January 2011 to May 2012 with 130 patients with septal deviation (SD) (n = 59) and CRSwNP (n = 71). All patients underwent computed tomography (CT), allergy tests, and sniffin' stick olfactory test. Anosmia was defined by Threshold-Discrimination-Identification (TDI) scores less than 16. QOL and psychological symptoms were assessed with the Sinonasal Outcome Test-20 (SNOT-20) and Symptom Checklist-90-Revised (SCL-90-R). Odor discrimination and identification scores were significantly lower in CRSwNP than in SD (P = .008 and P = .005, respectively). In CRSwNP, identification score decreased with higher CT score (r = -0.29, P = .014). CRSwNP with anosmia showed a decreased QOL (P = .044), and SNOT-20 negatively correlated with TDI in severe CRSwNP (CT score ≥15, r = -0.714, P = .001). Anosmia patients had higher anxiety and phobia scores of SCL-90-R in both SD and CRSwNP. However, depression score increased only in CRSwNP with anosmia (P = .025). Olfactory dysfunction may have significant effects on QOL and psychological health. CRSwNP with anosmia is a distinct phenotype having mixed type of olfactory loss that might have a detrimental effect on depression.

Corticosteroid treatment regulates mucosal remodeling in chronic rhinosinusitis with nasal polyps.

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). Case series, retrospective study. 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. 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. CS treatment modulates NP mucosa remodeling, particularly by promoting epithelial repair, regulating tissue remodeling markers, increasing total collagen content, and reducing tissue eosinophil infiltration. 4