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BACKGROUND: Responder analyses of SINUS phase 3 study data have shown clinically meaningful improvements across multiple chronic rhinosinusitis with nasal polyps (CRSwNP) outcomes with dupilumab. OBJECTIVE: To gain a better understanding of dupilumab response dynamics over 52 weeks. METHODS: Post hoc analysis using data from the SINUS-52 (NCT02898454) intention-to-treat population, of patients with severe CRSwNP who received dupilumab 300 mg once every 2 weeks (q2w) or placebo. Response, defined as an improvement from baseline of ≥ 1 point for Nasal Polyp Score (NPS), nasal congestion (NC), and loss of smell (LoS), and ≥ 8.9 points for 22-item Sino-Nasal Outcome Test (SNOT-22), was assessed for rapidity, maintenance, and durability. RESULTS: 303 patients (dupilumab, n = 150; placebo, n = 153) were included. For each outcome measure, a greater proportion of patients achieved first response by Week 16 (rapidity) with dupilumab vs placebo: NPS, 75.3% vs 39.2%; NC, 60.0% vs 24.2%; LoS, 60.7% vs 15.7%; and SNOT-22, 83.3% vs 66.0%. Among dupilumab patients with a response by Week 16, more than 80% maintained response at Week 52 (maintenance). Over 52 weeks, greater proportions of dupilumab patients were responders at ≥ 80% of time points: NPS, 46.7% vs 2.6%; NC, 46.7% vs 9.2%; LoS, 47.3% vs 3.9%; and SNOT-22, 62.0% vs 21.6% (durability). CONCLUSION: Most CRSwNP patients achieve clinically meaningful responses to dupilumab by Week 16, and most of these patients had maintenance and durability of response with continued treatment over time.
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AIMS: Benralizumab, a humanized, afucosylated monoclonal antibody against the interleukin 5 receptor, α subunit, causes rapid depletion of eosinophils by antibody-dependent cellular cytotoxicity. We investigated the pharmacokinetic and pharmacodynamic effects of benralizumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) from the phase III OSTRO trial. METHODS: Patients received a placebo or 30 mg of benralizumab by subcutaneous injection every 8 weeks (first three doses every 4 weeks) to week 48; a subset of patients continued in an extended follow-up period to assess treatment durability to week 80. Serum benralizumab concentrations and blood eosinophil and basophil counts were assessed to week 80. Biomarker assessments were performed on nasal polyp tissue biopsies at week 56 and nasal lining fluid at weeks 24 and 56 to examine changes in immune cells and inflammatory mediators. RESULTS: Among 185 patients in this analysis, 93 received benralizumab. Serum benralizumab concentrations reached a steady state by week 24 (median concentration 385.52 ng mL-1); blood eosinophils were almost fully depleted and blood basophils were reduced between weeks 16 and 56. Nasal polyp tissue eosinophils decreased with benralizumab from 57.6 cells mm-2 at baseline to 0 cells mm-2 at week 56 (P < .001 vs placebo), and tissue mast cells were numerically reduced. In nasal lining fluid, eosinophil-derived neurotoxin was significantly reduced at weeks 24 and 56 (P < .001) and interleukin-17 at week 56 (P < .05) with benralizumab. CONCLUSION: Benralizumab treatment led to rapid, sustained, nearly complete depletion of eosinophils from blood and nasal polyp tissue in patients with CRSwNP.
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Anticorpos Monoclonais Humanizados , Eosinófilos , Pólipos Nasais , Rinite , Sinusite , Humanos , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/complicações , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Sinusite/tratamento farmacológico , Sinusite/complicações , Masculino , Doença Crônica , Feminino , Rinite/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Eosinófilos/efeitos dos fármacos , Método Duplo-Cego , Basófilos/efeitos dos fármacos , Idoso , Contagem de Leucócitos , Injeções Subcutâneas , Resultado do Tratamento , RinossinusiteRESUMO
Background: Chronic rhinosinusitis (CRS) is a heterogeneous disorder with a wide range of validated subjective and objective assessment tools to assess disease severity. However, a comprehensive and easy-to-use tool that integrates these measures for determining disease severity and response to treatment is still obscure. The objective of this study was to develop a standardized assessment tool that facilitates diagnosis, uniform patient monitoring, and comparison of treatment outcomes between different centers both in routine clinical practice and in research. Methods: To develop this tool, published literature on assessment tools was searched on various databases. A panel of 12 steering committee members conducted an advisory board meeting to review the findings. Specific outcome measures to be included in a comprehensive assessment tool and follow-up sheet were then collated following consensus approval from the panel. The tool was further validated for content and revised with expert recommendations to arrive at the finalized Nasal Polyp Patient Assessment Scoring Sheet (N-PASS) tool. Results: The N-PASS tool was developed by integrating the subjective and objective measures for CRS assessment. Based on expert opinions, N-PASS was revised to be used as an easy-to-use guidance tool that captures patient-reported and physician-assessed components for comprehensively assessing disease status and response to treatment. Conclusion: The N-PASS tool can be used to aid in the diagnosis and management of CRS cases with nasal polyps. The tool would also aid in improved monitoring of patients and pave the way for an international disease registry. Level of evidence: Oxford Level 3.
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BACKGROUND: Inhalant allergens provide a source of environmental factors that contribute to the development of clinical symptoms in patients with atopic dermatitis (AD). OBJECTIVE: To review the relationship between inhalant allergens and AD. METHODS: A literature review was conducted using three databases: PubMed/MEDLINE, ClinicalKey, and Web of Science. Search terms, including "atopic dermatitis," "atopic eczema," and "eczema," were used in combination with "inhalant allergen," "inhaled allergen," and "aeroallergen" to identify relevant published manuscripts that highlight the relationship between AD and exposures to inhalant allergens. RESULTS: Fifteen articles were suitable for review. The studies included in the review investigated the effect of inhalant allergens on the clinical manifestations of AD through bronchial provocation, direct skin contact, and allergen sensitization. CONCLUSION: There is a significant relationship between exposures to inhalant allergens and AD. Inhalant allergens may aggravate AD symptoms by either bronchial provocation or direct skin contact. Sensitization of inhalant allergens, mainly house dust mites, follows a specific age-related pattern.
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Alérgenos , Dermatite Atópica , Humanos , Dermatite Atópica/imunologia , Dermatite Atópica/etiologia , Alérgenos/imunologia , Animais , Pyroglyphidae/imunologia , Testes de Provocação Brônquica , Exposição por Inalação/efeitos adversosRESUMO
BACKGROUND: In the 52-week Phase III SYNAPSE study, mepolizumab given every 4 weeks (100 mg subcutaneously) reduced nasal polyp (NP) size, improved symptoms and quality of life (QoL), and reduced corticosteroid use and number of sinus surgeries in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP), versus placebo. Because the durability of mepolizumab's efficacy after discontinuation is poorly understood in CRSwNP, the efficacy of mepolizumab after discontinuation was analyzed in severe CRSwNP, over a 24-week follow-up. METHODS: Changes from SYNAPSE baseline to end of treatment (week 52) and end of follow-up (week 76) were assessed for total endoscopic NP score, nasal obstruction and overall symptoms visual analog scale scores, and 22-item Sino-Nasal Outcome Test score. Time to first sinus surgery, time to first corticosteroid use, and geometric mean blood eosinophil counts (BECs) were also assessed. RESULTS: Among 134 follow-up patients, clinical improvements observed with mepolizumab versus placebo were partially evident 24 weeks after discontinuation despite BEC returning to baseline. The mean (95% confidence interval [CI]) change from baseline in NP score (week 52: -1.3 [1.8 to -0.9] vs. -0.3 [-0.6 to 0.1]; week 76: -1.2 [-1.6 to -0.7] vs. -0.1 [-0.5 to 0.3]) and the proportion of patients having sinus surgery (week 52: 4% vs. 25%; week 76: 9% vs. 31%) remained substantially improved with mepolizumab versus placebo. Mepolizumab-associated improvements in overall symptoms, quality of life, and corticosteroid use versus placebo were partially sustained at week 76. CONCLUSION: Fifty-two weeks of mepolizumab treatment is associated with sustained clinical benefits up to 24 weeks after discontinuation in patients with severe CRSwNP, which should be considered by physicians when making treatment decisions.
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Anticorpos Monoclonais Humanizados , Pólipos Nasais , Rinite , Rinossinusite , Sinusite , Humanos , Corticosteroides/uso terapêutico , Doença Crônica , Seguimentos , Pólipos Nasais/cirurgia , Qualidade de Vida , Rinite/tratamento farmacológico , Rinite/cirurgia , Rinite/complicações , Sinusite/tratamento farmacológico , Sinusite/complicações , Método Duplo-CegoRESUMO
Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP.
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Pólipos Nasais , Rinossinusite , Humanos , Doença Crônica , Gerenciamento Clínico , Pólipos Nasais/terapia , Pólipos Nasais/diagnóstico , Rinossinusite/diagnóstico , Rinossinusite/terapiaRESUMO
Purpose: Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced annualized asthma exacerbation rates (AAERs) versus placebo, irrespective of baseline disease characteristics, and improved lung function and symptom control versus placebo in adults and adolescents with severe, uncontrolled asthma. We assessed the efficacy of tezepelumab in patients with severe asthma with or without nasal polyps (NPs) in the 2 years before randomization in NAVIGATOR. Methods: Patients with severe asthma (N=1059) were randomized (1:1) and received tezepelumab 210 mg or placebo every 4 weeks subcutaneously for 52 weeks. Prespecified exploratory analyses included: AAER over 52 weeks and changes from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 second, Sino-Nasal Outcome Test (SNOT)-22 scores, and asthma control and health-related quality life (HRQoL) outcomes in NP subgroups. Changes from baseline in fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total immunoglobulin E (IgE), eosinophil-derived neurotoxin (EDN), matrix metalloproteinase-10 (MMP-10), and serum interleukin (IL)-5, IL-6, IL-8 and IL-13 were assessed (post hoc). Results: Tezepelumab reduced the AAER over 52 weeks versus placebo by 85% (95% confidence interval [CI]: 72, 92; n=118) and 51% (95% CI: 40, 60; n=941) in patients with and without NPs, respectively. At week 52, tezepelumab improved lung function, asthma control and HRQoL versus placebo in patients with and without NPs. Tezepelumab reduced SNOT-22 total scores (least-squares mean difference versus placebo [95% CI]) in patients with NPs at 28 weeks (-12.57 points [-19.40, -5.73]) and 52 weeks (-10.58 points [-17.75, -3.41]). At week 52, tezepelumab reduced blood eosinophil counts and FeNO, IgE, IL-5, IL-13, EDN and MMP-10 levels versus placebo, irrespective of NP status. Conclusion: Tezepelumab resulted in clinically meaningful improvements in sino-nasal symptoms and asthma outcomes in patients with severe asthma with comorbid NPs.
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BACKGROUND: Remission, defined as absence of symptoms and objective markers of disease, is emerging as the penultimate goal in the management of several chronic diseases. The concept of remission, well-established in Rheumatology as well as Gastroenterology, is currently emerging in Respiratory Medicine for asthma. It is interesting to consider whether the disease remission concept might successfully be applied to Otolaryngology-Head and Neck Surgery in the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). OBJECTIVE: The purpose of this letter is to explore the evidence supporting the concept of remission under continued medical therapy in chronic rhinosinusitis with nasal polyposis. METHODS: The authors reviewed the literature and summarized studies in chronic rhinosinusitis with nasal polyposis evaluating for evidence of clinical, biochemical, and endoscopic remission. RESULTS: Findings of the studies revealed that endoscopic sinus surgery with continued medical therapy achieved remission in approximately 50% of all patients. CRSwNP patients after primary endoscopic sinus surgery were able to achieve remission in 72% of instances, however this drops to 42% for patients having revision sinus surgery. For CRSwNP patients with co-morbidities such as asthma and aspirin exacerbated respiratory disease, remission rate drops to 23% and 23.5%, respectively compared to non-asthmatic CRSwNP patients who present a remission rate under continued medical therapy of 60%. CONCLUSION: Remission of symptoms and evidence of disease under medical therapy is indeed a concept achievable in patients with CRSwNP, as demonstrated by studies in the literature. Various co-morbidities, notably asthma, apparently influence rate of remission. Better defining this outcome through consensus-based definitions will allow for the development of strategies in CRSwNP care that can help affected patients attain complete relief from clinical, biochemical, and endoscopic markers of CRS with judicious use of medication and surgery. Future efforts will attempt to improve on these outcomes by achieving symptomatic and endoscopic control of disease following cessation of therapy, potentially paving the way towards clinical remission or a 'cure' in CRS.
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Asma , Pólipos Nasais , Seios Paranasais , Rinite , Sinusite , Humanos , Rinite/complicações , Rinite/terapia , Rinite/diagnóstico , Sinusite/complicações , Sinusite/terapia , Sinusite/diagnóstico , Seios Paranasais/cirurgia , Pólipos Nasais/complicações , Pólipos Nasais/cirurgia , Doença CrônicaRESUMO
PURPOSE: Assess if a rigid, image-guided balloon could be used effectively and safely in revision sinus surgery. MATERIALS AND METHODS: A prospective, non-randomized, single-arm, multicenter study to assess the safety and device performance of the NuVent™ EM Balloon Sinus Dilation System. Adults with CRS in need of revision sinus surgery were enrolled for balloon sinus dilation of a frontal, sphenoid, or maxillary sinus. The primary device performance endpoint was the ability of the device to (1) navigate to; and (2) dilate tissue in subjects with scarred, granulated, or previously surgically-altered tissue (revision). Safety outcomes included the assessment of any operative adverse events (AEs) directly attributable to the device or for which direct cause could not be determined. A follow-up endoscopy was conducted at 14 days post-treatment for assessment of any AEs. Performance outcomes included the surgeon's ability to reach the target sinus (es) and dilate the ostia. Endoscopic photos were captured for each treated sinus pre- and post-dilation. RESULTS: At 6 US clinical sites, 51 subjects were enrolled; 1 subject withdrew before treatment due to a cardiac complication from anesthesia. 121 sinuses were treated in 50 subjects. The device performed as expected in 100 % of the 121 treated sinuses, with investigators able to navigate to the treatment area and dilate the sinus ostium without difficulty. Ten AEs were seen in 9 subjects, with 0 related to the device. CONCLUSION: The targeted frontal, maxillary or sphenoid sinus ostium were safely dilated in every revision subject treated, with no AEs directly attributed to the device.
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Rinite , Adulto , Humanos , Dilatação , Estudos Prospectivos , Rinite/cirurgia , Seio Maxilar/cirurgia , Cateterismo , Endoscopia , Doença Crônica , Resultado do TratamentoRESUMO
INTRODUCTION: Topical corticosteroid therapies are the most popular prescribed medications for patients with chronic rhinosinusitis (CRS). While topical corticosteroids effectively reduce the inflammatory burden associated with CRS, their distribution inside the nasal cavity is limited and primarily dependent on their delivery device. Corticosteroid-eluting implants serve as relatively novel technology, allowing targeted, sustained release of a high concentration of corticosteroids directly onto the sinus mucosa. Three types of corticosteroid-eluting implants can be characterized: 1. intraoperatively inserted corticosteroid-eluting sinus implants, 2. postoperatively inserted, office-based corticosteroid-eluting sinus implants, and 3. office-based corticosteroid-eluting implants for naïve paranasal sinuses. AREAS COVERED: The review summarizes the different steroid-eluting sinus implants, their indications for use in CRS patients, and the existing evidence regarding their clinical efficacy. We also highlight potential areas for improvement and development. EXPERT OPINION: Corticosteroid-eluting sinus implants highlight an evolving field that is constantly investigating and adding new treatment options to the market. Presently, corticosteroid-eluting implants for CRS are most commonly applied intraoperatively and postoperatively with endoscopic sinus surgery, providing significant improvements in mucosal healing and reducing the amount of surgical failures. Future development around corticosteroid-eluting implants should focus on strategies to reduce the amount of crusting around the implants.
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Pólipos Nasais , Seios Paranasais , Rinite , Sinusite , Humanos , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/cirurgia , Rinite/cirurgia , Rinite/tratamento farmacológico , Sinusite/cirurgia , Sinusite/tratamento farmacológico , Seios Paranasais/cirurgia , Seios Paranasais/patologia , Glucocorticoides/uso terapêutico , Resultado do Tratamento , Endoscopia , Doença CrônicaRESUMO
Nasal allergen challenge (NAC) is applied in a variety of settings (research centers, specialty clinics, and hospitals) as a useful diagnostic and research tool. NAC is indicated for diagnosis of seasonal and perennial allergic rhinitis, local allergic rhinitis, and occupational rhinitis; to design the composition of allergen immunotherapy in patients who are polysensitized; and to investigate the physio-pathological mechanisms of nasal diseases. NAC is currently a safe and reproducible technique, although it is time- and resource-consuming. NAC can be performed by a variety of methods, but the lack of a uniform technique for performing and recording the outcomes represents a challenge for those considering NAC as a clinical tool in the office. The availability of standardized allergens for NAC is also different in each country. The objective of this workgroup report is to review the current information about NAC, focusing on the practical aspects and application for diagnosis of difficult rhinitis phenotypes (eg, local allergic rhinitis, occupational rhinitis), taking into account the particular context of practice in the United States and the European Union.
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Rinite Alérgica Perene , Rinite Alérgica , Rinite , Sinusite , Humanos , Alérgenos/uso terapêutico , Rinite/diagnóstico , Rinite/terapia , Rinite Alérgica/terapia , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica Perene/diagnóstico , Dessensibilização Imunológica , Testes de Provocação Nasal/métodosRESUMO
OBJECTIVE: To critically review the literature on nasal nitric oxide (nNO) and its current clinical and research applicability in the diagnosis and treatment of different sinonasal inflammatory diseases, including acute bacterial rhinosinusitis (ABRS), allergic rhinitis (AR), and chronic rhinosinusitis (CRS). METHODS: A search of the PubMed database was conducted to include articles on nNO and sinonasal diseases from January 2003 to January 2020. All article titles and abstracts were reviewed to assess their relevance to nNO and ABRS, AR, or CRS. After selection of the manuscripts, full-text reviews were performed to synthesize current understandings of nNO and its applications to the various sinonasal inflammatory diseases. RESULTS: A total of 79 relevant studies from an initial 559 articles were identified using our focused search and review criteria. nNO has been consistently shown to be decreased in ABRS and CRS, especially in cases with nasal polyps. While AR is associated with elevations in nNO, nNO levels have also been found to be lower in AR cases with higher symptom severity. The obstruction of the paranasal sinuses is speculated to be an important variable in the relationship between nNO and the sinonasal diseases. Treatment of these diseases appears to affect nNO through the reduction of inflammatory disease burden and also mitigation of sinus obstruction. CONCLUSION: nNO has been of increasing interest to researchers and clinicians over the last decade. The most compelling data for nNO as a clinical tool involve CRS. nNO can be used as a marker of ostiomeatal complex patency. Variations in measurement techniques and technology continue to impede standardized interpretation and implementation of nNO as a biomarker for sinonasal inflammatory diseases.
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Seios Paranasais , Rinite Alérgica , Rinite , Sinusite , Humanos , Rinite/diagnóstico , Óxido Nítrico , Sinusite/diagnóstico , Biomarcadores , Doença CrônicaRESUMO
BACKGROUND: Sinus surgery removes inflamed tissue, restores airflow, and improves delivery of medication into surgically opened spaces. The exhalation delivery system with fluticasone (EDS-FLU; XHANCE® ) uses a novel delivery system to create closed-palate, positive-pressure, bidirectional mechanics that significantly alter the deposition of the topically acting anti-inflammatory medication. We ask whether EDS-FLU efficacy differs for patients with recurrent symptoms after sinus surgery versus patients without surgery. OBJECTIVE: We aimed to compare EDS-FLU treatment responses in patients with recurrent symptoms after endoscopic sinus surgery (ESS) and patients who have never had sinus surgery. METHODS: Data were pooled from two large, controlled trials (NAVIGATE I and II) for exploratory analyses. Chronic rhinosinusitis symptoms, polyp grade, and quality-of-life measures were compared between patients with prior ESS and those without prior ESS. RESULTS: Patients with prior ESS (exhalation delivery system-placebo [n = 53], EDS-FLU 186 µg [n = 52], and EDS-FLU 372 µg [n = 49]) and unoperated patients (exhalation delivery system-placebo [n = 108], EDS-FLU 186 µg [n = 108], and EDS-FLU 372 µg [n = 111]) treated with EDS-FLU reported similar and substantial benefits as measured by multiple symptom and quality-of-life/functioning outcomes (congestion score, 22-Item Sinonasal Outcomes Test [SNOT-22], Rhinosinusitis Disability Index [RSDI], Patient Global Impression of Change) and by nasal polyp grade. In previously operated patients, unlike surgery-naive patients, multiple outcomes (SNOT-22, RSDI, polyp grade) consistently showed numerically but not statistically greater responses to the higher dose. CONCLUSIONS: Patients with recurrent symptoms after sinus surgery who were treated with EDS-FLU demonstrated significant symptom and quality-of-life improvement. Unlike unoperated patients, patients with prior ESS had a numerically but not statistically greater response to the higher dose of EDS-FLU (two sprays per nostril twice a day).
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Pólipos Nasais , Rinite , Sinusite , Humanos , Doença Crônica , Endoscopia , Expiração , Fluticasona/uso terapêutico , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/cirurgia , Rinite/tratamento farmacológico , Rinite/cirurgia , Sinusite/tratamento farmacológico , Sinusite/cirurgia , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To analyze published reports on the efficacy and safety of CSI in CRS and evaluate the clinical implications of current gaps in evidence. Corticosteroid irrigation (CSI) is commonly used for management of chronic rhinosinusitis (CRS) with nasal polyps; however, such use is not approved by the US Food and Drug Administration (FDA). DATA SOURCES: Publications were obtained through PubMed searches through January 2022. STUDY SELECTION: Searches were conducted using 2 terms: "chronic rhinosinusitis" or "nasal polyps" as the first term and "corticosteroid irrigation," "steroid nasal lavage," or "sinus rinse" as the second term. We reviewed relevant, peer-reviewed literature (19 original research [9 controlled, 10 uncontrolled trials], 7 reviews, and 1 meta-analysis) reporting safety and efficacy of CSI in patients with CRS. RESULTS: Studies were difficult to compare because they used a variety of solution volumes (60 mL to 125 mL per nostril), corticosteroid agents (budesonide, betamethasone, mometasone, or fluticasone), corticosteroid doses, preparation protocols (by compounding pharmacy or by patient), and administration (frequency, time of day, body positioning). It is difficult to determine which parameters might substantially influence clinical effects because studies were generally small, showed marginal benefits, and rarely assessed safety. To date, no studies evaluating CSI have shown statistically significant differences in a type-I error-controlled primary end point over any comparator, possibly owing to small sample sizes. CONCLUSION: Designing more robust clinical trials may help determine whether CSI is a valid treatment option. Until more evidence supporting CSI use exists, health care professionals should strongly consider choosing FDA-approved therapies for the treatment of CRS.
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Pólipos Nasais , Rinite , Sinusite , Humanos , Rinite/tratamento farmacológico , Corticosteroides/uso terapêutico , Pólipos Nasais/tratamento farmacológico , Esteroides/uso terapêutico , Lavagem Nasal , Sinusite/tratamento farmacológico , Doença CrônicaRESUMO
Purpose: Endoscopic transsphenoidal surgery (ETSS) is an increasingly utilized approach for resection of pituitary tumors. Prior studies have evaluated preoperative tumor size, location, and extent as prognostic factors for surgical resection. There is little data on the relationship between preoperative pituitary tumor radiographic morphology and surgical outcomes. Study Design: Retrospective longitudinal study. Setting: Single tertiary care institution. Subjects and Methods: Preoperative magnetic resonance imaging and computed tomography scans from patients undergoing ETSS for pituitary tumor resections from 2007 to 2017 were retrospectively evaluated. A neuroradiologist classified these pituitary tumors into six morphologic groups, each defined by volume, dimensions, extension, and shape. Surgical difficulty, rates of incomplete resection, and postoperative complications were then stratified in relation to the morphologic groups. Results: Pituitary tumors from 131 patients were classified from preoperative imaging into six characteristic morphologies: (1) microtumor, (2) round, (3) transverse oblong, (4) superior-inferior oblong, (5) bilobed, and (6) large lobulated. Tumors that were characterized with the large lobulated, bilobed, and transverse oblong morphologies correlated with higher rates of postoperative evidence of residual tumor (70%, 36%, and 47%, respectively, all P < 0.002). Likewise, large lobulated, bilobed, and transverse oblong morphologies were also associated with intraoperative cerebrospinal fluid leaks (70%, 31%, and 35%, respectively, all P < 0.05). Conclusions: We describe a novel descriptive system for the morphology of pituitary tumors that can be determined from preoperative imaging. Different tumor morphologic groups are associated with varying degrees of gross tumor resection, complications, and surgical difficulty. Utilizing pituitary tumor morphology may aid surgeons in planning the extent of resection, need for complex closure, and patient counseling.
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Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease of the nasal and paranasal sinuses. Dupilumab is a monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, which are key and central drivers of type 2 inflammation. In clinical trials, dupilumab significantly improved objective and patient-reported measures of CRSwNP versus placebo and was well tolerated. Dupilumab is approved in the European Union, USA and Japan as add-on maintenance treatment for adults with inadequately controlled CRSwNP. There exists an important evidence gap between efficacy and effectiveness data for dupilumab in severe CRSwNP. In order to bridge this gap, the AROMA prospective global registry (ClinicalTrials.gov: NCT04959448) was established. AROMA will collect long-term data on the utilisation, effectiveness and safety of dupilumab for CRSwNP treatment in real-world clinical practice. AROMA will enrol approximately 1000 adults starting dupilumab for severe CRSwNP across 120 global sites. Baseline data will include patient demographics, medical/surgical history and presence of type 2 comorbidities. Effectiveness outcome assessments will include objective measures of CRSwNP assessed as part of routine clinical care and various patient-reported questionnaires. Treatment patterns, concomitant medications and long-term safety will also be recorded. Results from AROMA, the first prospective, real-world, global registry to characterise patients with severe CRSwNP starting dupilumab, will provide evidence on the real impact of dupilumab in patients with CRSwNP and complement the data from randomised clinical trials. The registry will also provide evidence on disease progression in patients with CRSwNP, including those with coexisting diseases.
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Objective: To characterize healthcare burden, treatment patterns, and clinical characteristics associated with chronic rhinosinusitis with nasal polyps (CRSwNP). Study Design: Retrospective cohort. Setting: Real-world study using US health insurance claims database. Methods: Adults with ≥1 CRSwNP diagnosis (index date: first claim for nasal polyps [NPs] between January 1, 2008, and March 31, 2019) and continuous health insurance coverage for ≥180 days preindex (baseline) and postindex were included. Follow-up spanned from index to the earliest of disenrollment, death, or data end. Assessments included patient demographics, comorbidities, and blood eosinophil count at baseline, healthcare resource utilization (HCRU), and costs during follow-up in the overall population and stratified by number of surgeries. Results: Of the 119,357 patients who met the inclusion criteria, 33,748 (28%) had ≥1 surgery during follow-up, among whom 3262 (9.7%) had ≥2 surgeries. At baseline, patients with ≥1 vs no NP surgeries had a greater comorbidity burden; a higher proportion of patients had comorbid asthma (37.8% vs 21.8%) and blood eosinophil count ≥300 cells/µL (42.6% vs 38.1%). During follow-up, patients with NP surgeries had higher all-cause and CRSwNP-related HCRU and costs than patients without NP surgery. All-cause healthcare costs per person per year increased with the number of surgeries during follow-up (no surgery, $10,628; ≥1 surgery, $20,747; ≥2 surgeries, $26,969). Conclusion: Patients with CRSwNP and surgery had a greater disease burden than those without surgery, with higher HCRU and costs, and were more likely to have comorbid conditions (most commonly asthma) and elevated blood eosinophil count, indicating a subset of patients with recalcitrant CRSwNP.
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Importance: Nasal valve collapse is a primary cause of nasal airway obstruction (NAO). Patients with NAO and nasal valve collapse experience a variety of symptoms that lower their quality of life, such as nasal congestion, headache, sleep disturbance, daytime sleepiness, and snoring. Objective: To determine if active treatment of the nasal valve with a temperature-controlled radiofrequency (TCRF) device, previously demonstrated superior to a sham procedure at 3 months, was safe and associated with sustained improvements in symptoms of NAO through 12 months. Design, Setting, and Participants: In a prospective, multicenter, single-blinded, randomized clinical trial, patients in 16 centers in the US with index procedures between August and December 2020 were assigned to TCRF device treatment of the nasal valve or a sham control procedure (no RF energy). Patients had a baseline Nasal Obstruction Symptom Evaluation (NOSE) Scale score of 55 or greater with nasal valve collapse as the primary or substantial contributor to NAO. After primary end point evaluation at 3 months, eligible patients in the sham control arm crossed over to active treatment. Data analysis was performed between April and May 2022. Interventions: Patients were treated bilaterally with the TCRF device at 4 or fewer nonoverlapping areas on the nasal mucosa at the junction of the upper and lower lateral cartilage on the lateral nasal wall. Main Outcomes and Measures: The primary end point measure was responder rate, defined as 20% or greater reduction in NOSE Scale score or 1 or greater reduction in NOSE Scale clinical severity category. Results: A total of 108 patients received active treatment (77 as index active treatment, 31 after crossover). The mean (SD) age of patients was 48.5 (12.3) years; 66 (61.1%) were women. The combined group of patients receiving active treatment had a mean baseline NOSE Scale score of 76.3 (95% CI, 73.6-79.1). At 12 months (n = 88), the responder rate was 89.8% (95% CI, 81.7%-94.5%). The NOSE Scale score improved from baseline (mean change, -44.9 [95% CI, -52.1 to -37.7]). No device/procedure-related serious adverse events were reported. Conclusions and Relevance: In this follow-up of a cohort from a randomized clinical trial, the minimally invasive TCRF device, previously demonstrated to be superior to a sham procedure, was safe and associated with improvement in symptoms of NAO through 12 months postprocedure. Trial Registration: ClinicalTrials.gov Identifier: NCT04549545.
Assuntos
Obstrução Nasal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obstrução Nasal/complicações , Obstrução Nasal/cirurgia , Estudos Prospectivos , Qualidade de Vida , Temperatura , Resultado do TratamentoRESUMO
Patient care in the allergy and respiratory fields is advancing rapidly, offering the possibility of the inclusion of a variety of digital tools that aim to improve outcomes of care. Impaired access to several health care facilities during the COVID-19 pandemic has considerably increased the appetite and need for the inclusion of e-health tools amongst end-users. Consequently, a multitude of different e-health tools have been launched worldwide with various registration and access options, and with a wide range of offered benefits. From the perspective of both patients and healthcare providers (HCPs), as well as from a legal and device-related perspective, several features are important for the acceptance, effectiveness,and long-term use of e-health tools. Patients and physicians have different needs and expectations of how digital tools might be of help in the care pathway. There is a need for standardization by defining quality assurance criteria. Therefore, the Upper Airway Diseases Committee of the World Allergy Organization (WAO) has taken the initiative to define and propose criteria for quality, appeal, and applicability of e-health tools in the allergy and respiratory care fields from a patient, clinician, and academic perspective with the ultimate aim to improve patient health and outcomes of care.