Project description:ObjectiveChronic rhinosinusitis with nasal polyps (CRSwNP) is a common and heterogeneous inflammatory condition, for which the drivers of the underlying inflammation are not yet fully understood. The use of biologic therapies to target specifically relevant effector cells or cytokines in CRSwNP is a growing field of interest. The objectives of this review are to provide an update on the existing studies of biologics in CRSwNP and to identify potential future areas for further research.Data sourcesAn initial literature review of biologic therapies in CRS was performed through publications gathered from a PubMed search for title/abstract containing "biologic" and "chronic rhinosinusitis." Further manuscripts describing scientific premise for each biologic were then reviewed.Study selectionsA detailed review of all studies describing biologic therapies targeting inflammation in CRSwNP was performed.ResultsBiologic therapies targeting interleukin (IL)-4Rα, IL-5, IL-5Rα, IL-33, immunoglobulin (Ig)E, and thymic stromal lymphopoietin (TSLP) have all been developed and have been investigated for treatment in CRSwNP, or current research suggests that they may have utility in this area. Only dupilumab, which inhibits IL-4Rα, has gained Food and Drug Administration approval for the treatment of adults with inadequately controlled CRSwNP.ConclusionRecent advances in our understanding of the fundamental drivers of the chronic respiratory inflammation in CRSwNP has led to the identification of several potential therapeutic targets for this disease. Future clinical success will rely on the availability of biomarker-based endotyping and responder analyses so that clinicians can precisely match each patient to the appropriate biologic, thereby optimizing the proper treatment strategy.
Project description:Background Potential biologic therapies for chronic rhinosinusitis (CRS) is a growing field of interest and research. Biologics target specific immune cells or inflammatory pathways within a disease process, increasing drug efficacy while reducing complications. The success of biologics in other inflammatory conditions such as asthma and atopic dermatitis has spurred much of the corresponding research in CRS. A rapid expansion in the volume of research concerning biologic therapies with potential crossover to treating CRS has made it difficult to stay current. Furthermore, much of the literature has been focused on allergy, asthma, and immunology subspecialties. As the role for biologic therapies in CRS continues to expand, it is increasingly important for otolaryngologists to remain up to date on their progression. Objective The objectives of this review are to provide an update on the growing field of biologics for otolaryngologists who treat CRS and discuss potential future areas of research. Methods A literature review of biologic therapies studied in CRS was performed. In addition, a detailed review of all biologic therapies targeting inflammatory markers involved in Th1-, Th2-, and Th17-mediated inflammation was performed to identify potential areas for future research. The role for biologic therapies in CRS, endotypes of CRS, current biologic therapies studies in CRS, and future areas for research were reviewed. Results Sixty-nine unique biologic therapies have been developed for Th1-, Th2-, and Th17-mediated inflammation. Five biologics are currently being investigated for use in patients with CRS with nasal polyposis. Conclusions As the field of biologics continues to expand, remaining up to date on the current literature may help clinicians identify patients who may benefit from biologic therapies. In addition, ongoing research in other inflammatory disorders with shared pathophysiology to CRS may reveal other potential therapies for CRS that have not previously been investigated.
Project description:Purpose of reviewChronic rhinosinusitis with nasal polyposis (CRSwNP) is a phenotypic designation of the broader condition of chronic rhinosinusitis. The advent of targeted biologics has shown promise in targeting different aspects of the inflammatory pathway, yet there remains a lack of consensus on the correct timing and use of these medications. This review seeks to provide a concise update of the available literature on the pathophysiology of CRSwNP, the evolution and cost utility of biologics as it pertains to management of patients with CRSwNP, and evidence for each available biologic and its use in CRSwNP.Recent findingsThere are two biologics with FDA approval for use in CRSwNP: dupilumab and omalizumab. Recent clinical trials of other biologic therapies targeting type 2 inflammatory pathways have also demonstrated efficacy both in symptom scores and nasal polyp reduction. However, studies have questioned the cost utility of these medications compared to other interventions. Furthermore, timing of use with respect to other interventions including surgery remains challenging.
Project description:BackgroundComparative effectiveness research between endoscopic sinus surgery (ESS) and biologic therapy for severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a nascent field as new therapeutic modalities become clinically available.MethodsA prospective, multicenter cohort of CRSwNP patients, undergoing ESS between 2011 and 2019, were compared to phase-3 biologic trial data. Patients undergoing ESS received baseline nasal endoscopy quantified via Lund-Kennedy (LK) grading. Patients meeting inclusion criteria, modified from Dupilumab-LIBERTY-NP-24&52, omalizumab-POLYP-1&2, and Mepolizumab-SYNAPSE clinical trials, were included in this study. Baseline characteristics and outcome measures were compared between these cohorts at 24 weeks and 52 weeks, when possible.ResultsA total of 111 CRSwNP patients met modified inclusion criteria. There were no statistically significant differences in baseline age, sex, asthma status, aspirin-exacerbated respiratory disease status, smell identification, LK-polyp score, and Lund-Mackay computed tomography (CT) scores between ESS and biologic groups. At 24 weeks, ESS demonstrated significantly greater improvements in 22-item Sino-Nasal Outcome Test (SNOT-22) compared to one (of two) dupilumab trials (p < 0.05) and both omalizumab trials (p < 0.001). ESS associated with significantly lower nasal polyp scores (NPS) compared to dupilumab (p < 0.001) and omalizumab (p < 0.001), despite comparable improvements in smell identification (p > 0.05). At 52 weeks, ESS resulted in statistically similar improvement in SNOT-22 scores compared to dupilumab (p = 0.21), but NPS remained significantly lower in the ESS group compared to dupilumab (p < 0.001) and mepolizumab (p < 0.001).ConclusionAt 24 weeks and 52 weeks, ESS offers comparable SNOT-22 improvements compared to dupilumab. ESS and dupilumab offer comparable improvement in smell identification at 24 weeks. Compared to omalizumab, ESS offers superior SNOT-22 improvements. ESS offers significantly greater reductions in polyp size compared to omalizumab, dupilumab, and mepolizumab therapies.
Project description:Increasing evidence suggests that CRS is a heterogeneous group of sinus disorders involving overlapping but distinct disease entities.The factors leading to different CRS phenotypes remain enigmatic. The role of miRNAs in the regulation of immunological and inflammatory processes is beginning to emerge.Thus, we examined microRNAs expression profiles in eosinophilic CRSwNP adn CRSsNP. Compared with controls, 31 differentially expressed miRNAs (30 downregulated and 1 upregulated miRNAs) in eosinophilic CRSwNP and 4 differentially expressed miRNAs (2 downregulated and 2 upregulated miRNAs) in CRSsNP were indentified. Real time RT-PCR was subsequently performed to verify the miRNA microarray result.
Project description:Chronic rhinosinusitis (CRS) is a public health problem that has a significant socio-economic impact. Moreover, the complexity of this disease due to its heterogeneous nature based on the underlying pathophysiology - leading to different disease variants - further complicates our understanding and directions for the most appropriate targeted treatment strategies. Several International/national guidelines/position papers and/or consensus documents are available that present the current knowledge and treatment strategies for CRS. Yet there are many challenges to the management of CRS especially in the case of the more severe and refractory forms of disease. Therefore, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), a collaboration between EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus (ICON) on Chronic Rhinosinusitis. The purpose of this ICON on CRS is to highlight the key common messages from the existing guidelines, the differences in recommendations as well as the gaps in our current knowledge of CRS, thus providing a concise reference. In this document we discuss the definition of the disease, its relevance, pharmacoeconomics, pathophysiology, phenotypes and endotypes, genetics and risk factors, natural history and co-morbidities as well as clinical manifestations and treatment options in both adults and children comprising pharmacotherapy, surgical interventions and more recent biological approaches. Finally, we have also highlighted the unmet needs that wait to be addressed through future research.
Project description:Increasing evidence suggests that CRS is a heterogeneous group of sinus disorders involving overlapping but distinct disease entities.The factors leading to different CRS phenotypes remain enigmatic. The role of miRNAs in the regulation of immunological and inflammatory processes is beginning to emerge.Thus, we examined microRNAs expression profiles in eosinophilic CRSwNP adn CRSsNP. Compared with controls, 31 differentially expressed miRNAs (30 downregulated and 1 upregulated miRNAs) in eosinophilic CRSwNP and 4 differentially expressed miRNAs (2 downregulated and 2 upregulated miRNAs) in CRSsNP were indentified. Real time RT-PCR was subsequently performed to verify the miRNA microarray result. Examination of miRNAs expression in eosinophilic CRSwNP and CRSsNP
Project description:Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways which persists for at least 12 weeks. CRS is one of the most common chronic diseases in adults in the United States, affecting over 30 million Americans. CRS is frequently divided into 2 types: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Histologic studies have demonstrated significant tissue eosinophilia in CRSwNP. T cells in the mucosa are elevated in both forms of CRS and are skewed towards Th2 cytokine expression in CRSwNP. However pathogenic role of CRS has not been fully explored. To screen for pathogenic factors in CRS, we performed a microarray study. We collected uncinate tissues (UT) from 6 subjects with CRSsNP, 6 subjects with CRSwNP and 6 control subjects and nasal polyp (NP) tissues from 6 subjects with CRSwNP and then evaluated gene expression profiles using Affymetrix Human Genome U133 plus 2.0 array.