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Yuan H, Yang Y, Zhang B, Li A, Su J, Ding X, Yan H, Zhang H. Construction and Analysis of Risk Prediction Model of Eosinophilic Chronic Rhinosinusitis With Nasal Polyps: A Cross-Sectional Study in Northwest China. Clin Otolaryngol 2025; 50:39-45. [PMID: 39275967 DOI: 10.1111/coa.14225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 08/17/2024] [Accepted: 09/01/2024] [Indexed: 09/16/2024]
Abstract
OBJECTIVE To provide guidance for clinical endotypes by constructing a risk-predictive model of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). DESIGN A cross-sectional study. SETTING Single-centre trial at tertiary medical institutions. PARTICIPANTS A cross-sectional study included 343 CRSwNP patients divided into ECRSwNP (n = 237) and non-ECRSwNP (n = 106) groups using surgical pathology. MAIN OUTCOME MEASURES Single-factor and multivariate analysis were used to identify statistically significant variables for constructing a nomogram, including the history of AR, hyposmia score, ethmoid sinus score, BEP and BEC. The model's performance was evaluated based on the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA). RESULTS Allergic rhinitis, hyposmia score, ethmoid sinus score, peripheral blood eosinophil percentage (BEP) and eosinophil count (BEC) were retained for the construction nomogram of ECRSwNP. The nomogram exhibited a certain accuracy, with an AUC of 0.897 (95% CI: 0.864-0.930), good agreement in the calibration curve and a 0.891 C-index of internal validation. Moreover, the DCA with a threshold probability between 0.0167 and 1.00 indicated a higher net benefit and greater clinical utility. CONCLUSION The construction of a predictive risk model of ECRSwNP based on easily accessible factors could assist clinicians in more conveniently defining endotypes to make optimal diagnoses and treatment choices.
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Affiliation(s)
- Huajie Yuan
- Department of Otolaryngology, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China
| | - Yuping Yang
- Department of Otolaryngology, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China
| | - Bo Zhang
- Department of Otolaryngology, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China
| | - Ang Li
- Department of Otolaryngology, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China
| | - Jiang Su
- Department of Otolaryngology, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China
| | - Xiaoyan Ding
- Department of Otolaryngology, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China
| | - Haisu Yan
- Department of Otolaryngology, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China
| | - Hua Zhang
- Department of Otolaryngology, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China
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Alsaleh S, Kamal N, Hopkins C, Al Rand H, Marglani OA, Alterki A, Abu Suliman O, Alandejani T, Kamel R, Al Abri R, Alotaibi NH, Al Amadi A, Bahakim A, Han JK, Javer A, Sedaghat AR, Gevaert P. Assessment of chronic rhinosinusitis with nasal polyps: Development of the Nasal Polyp Patient Assessment Scoring Sheet tool. Laryngoscope Investig Otolaryngol 2024; 9:e1277. [PMID: 38803462 PMCID: PMC11129554 DOI: 10.1002/lio2.1277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 04/08/2024] [Accepted: 05/10/2024] [Indexed: 05/29/2024] Open
Abstract
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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Affiliation(s)
- Saad Alsaleh
- Department of Otolaryngology—Head and Neck Surgery, College of MedicineKing Saud UniversityRiyadhSaudi Arabia
| | - Nehal Kamal
- Global Medical Immunology – Specialty CareSanofiUnited Arab Emirates
| | | | - Hussain Al Rand
- Health Centers and Clinics and Public HealthMinistry of HealthAbu DhabiUnited Arab Emirates
| | - Osama A. Marglani
- The Department of Ophthalmology and Otolaryngology, College of MedicineUmm Al‐Qura UniversityMakkahSaudi Arabia
- Department of OtolaryngologyKing Faisal Specialist Hospital & Research CenterJeddahSaudi Arabia
| | - Abdulmohsen Alterki
- Department of Otolaryngology, Head and Neck SurgeryZain and Al Sabah HospitalsKuwait CityKuwait
- Medical DepartmentDasman Diabetes InstituteKuwait CityKuwait
| | - Omar Abu Suliman
- Department of Rhinology, Sinus, and Skull Base SurgeryKing Abdullah Medical CityMakkahSaudi Arabia
| | - Talal Alandejani
- Department of Surgery, Faculty of MedicineKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
| | - Reda Kamel
- ENT Department, Kasr Al‐Ainy Faculty of MedicineCairo UniversityCairoEgypt
| | - Rashid Al Abri
- ENT Division, Department of Surgery, College of Medicine & Health SciencesSultan Qaboos UniversityMuscatSultanate of Oman
| | - Naif H. Alotaibi
- Otolaryngology, Head & Neck Surgery Department, King Faisal Specialist Hospital and Research CenterAlfaisal UniversityRiyadhSaudi Arabia
| | - Ahmad Al Amadi
- ENT DepartmentAl Kuwait Hospital, Ministry of HealthDubaiUnited Arab Emirates
| | - Abdullah Bahakim
- Department of Otolaryngology, Head, and Neck SurgeryKing Abdulaziz UniversityJeddahSaudi Arabia
| | - Joseph K. Han
- Department of Otolaryngology ‐ Head and Neck SurgeryEastern Virginia Medical SchoolNorfolkVirginiaUSA
| | - Amin Javer
- Rhinology and Skull Base Surgery, St. Paul's Sinus Center, Division of OtolaryngologyUniversity of British ColumbiaVancouverBritish ColumbiaCanada
| | - Ahmad R. Sedaghat
- Department of Otolaryngology – Head and Neck SurgeryUniversity of Cincinnati College of MedicineCincinnatiOhioUSA
| | - Philippe Gevaert
- Upper Airways Research Laboratory, Department of OtorhinolaryngologyGhent UniversityGhentBelgium
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AlBloushi S, Al-Ahmad M. Exploring the immunopathology of type 2 inflammatory airway diseases. Front Immunol 2024; 15:1285598. [PMID: 38680486 PMCID: PMC11045947 DOI: 10.3389/fimmu.2024.1285598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 03/22/2024] [Indexed: 05/01/2024] Open
Abstract
Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease's pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders.
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Affiliation(s)
| | - Mona Al-Ahmad
- Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait
- Microbiology Department, College of Medicine, Kuwait University, Kuwait City, Kuwait
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Khanzadeh S, Ghaedi A, Meidani FZ, Rahmati R, Bazrgar A, Lucke-Wold B, Khanzadeh M. Meta-analysis of the Relationship Between Neutrophil to Lymphocyte Ratio and Nasal Polyps. Indian J Otolaryngol Head Neck Surg 2024; 76:2191-2204. [PMID: 38566738 PMCID: PMC10982268 DOI: 10.1007/s12070-023-04306-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 10/19/2023] [Indexed: 04/04/2024] Open
Abstract
Our study aimed to enhance understanding of nasal polyp pathophysiology by reviewing the data for variations of NLR values between patients with nasal polyp and healthy controls. We searched Web of Science, PubMed, ProQuest, and Scopus up to 2 April 2023. The search strategy was not limited to any specific language. Twelve studies were included in our study. Of them, ten studies, involving 898 nasal polyp patients and 590 control patients, were included in the meta-analysis. The NLR levels in nasal polyp patients were statistically greater than in the control group (SMD = 0.56; 95%CI 0.04-1.08, P = 0.036). Subgroup analysis based on study design yielded that patients with nasal polyp exhibited significantly higher NLR levels than healthy controls in retrospective studies (SMD = 0.83; 95%CI 0.30-1.35, P = 0.002) but not in prospective studies (SMD = 0.10; 95%CI = -1.03 to 1.23, P = 0.85). Also, we found that the NLR levels in nasal polyp patients were significantly higher than healthy controls in high-quality studies (SMD = 1.00; 95%CI 0.38-1.62, P = 0.002) but not in low-quality studies (SMD = 0.11; 95%CI = -0.69 to 0.91, P = 0.79). A total of 312 patients with recurrence and 550 patients without recurrence were included in the study. The combined results revealed that NLR levels in nasal polyp recurrence patients were significantly higher than those of the nasal polyp without recurrence group (SMD = 0.06, 95% CI 0.39-0.81, P = 0.000). These results showed the relationship between the NLR in nasal polyps and can help medical doctors to predict the recurrence of the disease in such patients.
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Affiliation(s)
| | - Arshin Ghaedi
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Trauma Research Center, Shahid Rajaee (Emtiaz) Trauma Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fatemeh Zari Meidani
- Students Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Rahem Rahmati
- Students Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Aida Bazrgar
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Monireh Khanzadeh
- Geriatric and Gerontology Department, Medical School, Tehran University of Medical and Health Sciences, Tehran, Iran
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Li S, Zhang Z, Wang L, Yan X, Jiang Y, Yu L. Diagnostic significance of peripheral blood indices for eosinophilic chronic rhinosinusitis in Chinese adults. Eur Arch Otorhinolaryngol 2024; 281:1337-1345. [PMID: 37938374 DOI: 10.1007/s00405-023-08324-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 10/27/2023] [Indexed: 11/09/2023]
Abstract
OBJECTIVE Eosinophilic chronic rhinosinusitis (eCRS) is a refractory subtype of CRS. This study aimed to compare the differences in clinical features and peripheral blood indices between eCRS and non-eCRS Chinese patients and identify the predictive factors for eCRS. METHODS In this study, a total of 1352 patients with CRS were enrolled and divided into eCRS and non-eCRS groups based on the degree of eosinophilic infiltration in histopathology, and their demographic and clinical characteristics, as well as peripheral blood indices, were compared. Logistic regression analysis was used to identify the factors associated with eCRS, and the optimal cut-off values of predictors were determined using subject working curves. RESULTS As compared to those in the non-eCRS group patients, the proportion of males, age, proportion of smokers, peripheral blood eosinophil count, and erythrocyte count were significantly higher, while the peripheral blood neutrophil count, platelet count, neutrophil/lymphocyte count ratio (NLR), platelet/lymphocyte count ratio (PLR), and neutrophil × platelet/lymphocyte count ratio (SII index) were significantly lower in the eCRS group patients. Logistic regression analysis showed that age, peripheral blood neutrophil count, eosinophil count, and platelet count were independent predictors of eCRS, and eosinophil count > 2.05 × 108/L could be used as a diagnostic marker for eCRS with a sensitivity and specificity of 87.1% and 78.3%, respectively. CONCLUSIONS There were significant differences in the clinical features of eCRS and non-eCRS patients. Peripheral blood eosinophil count could early and more accurately predict eCRS.
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Affiliation(s)
- Shunke Li
- Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Laoshan District, Qingdao, 266003, China
| | - Zengxiao Zhang
- Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Laoshan District, Qingdao, 266003, China
| | - Lin Wang
- Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Laoshan District, Qingdao, 266003, China
| | - Xudong Yan
- Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Laoshan District, Qingdao, 266003, China
| | - Yan Jiang
- Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Laoshan District, Qingdao, 266003, China.
| | - Longgang Yu
- Department of Otorhinolaryngology Head and Neck Surgery, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Laoshan District, Qingdao, 266003, China.
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Wu S, Lao J, Jian F. Analysis of the Construction of a Predictive Model for Eosinophilic Chronic Rhinosinusitis. J Asthma Allergy 2024; 17:133-141. [PMID: 38434218 PMCID: PMC10909328 DOI: 10.2147/jaa.s450514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Accepted: 02/20/2024] [Indexed: 03/05/2024] Open
Abstract
Purpose This study aimed to determine indices to diagnose and predict eosinophilic chronic rhinosinusitis (ECRS) during the initial clinic visit. Patients and Methods We retrospectively analyzed 116 patients with chronic rhinosinusitis who underwent endoscopic sinus surgery and were classified according to the postoperative pathological diagnosis. General data and various clinical indicators were analyzed, and indicators with statistically significant differences between groups were further incorporated into a multivariate logistic regression to establish a comprehensive prediction model. The receiver operating characteristic (ROC) curve was used to compare the two significant valuable single factors from previous studies, the difference in CT scores between the ethmoid sinus and the sum difference of the maxillary sinus (EM difference) and the absolute value of peripheral blood eosinophil (bEOS), with a comprehensive prediction model. Results There were significant differences in history of allergic asthma (p < 0.001), visual analog scale (VAS) score (p=0.005), sino-nasal outcome test-22(SNOT-22) scale score (p=0.004), Lund-Mackay scale score (p=0.017), EM difference (p=0.002), percentage of bEOS (%)(p=0.001), and absolute value of bEOS (×109/L) (p=0.000) between the two groups (p< 0.05). The history of allergic disease, VAS and bEOS were screened out and included in the comprehensive prediction model. The area under the curve (AUC) of the comprehensive prediction model (0.804)> the AUC of the absolute value of the bEOS (0.764)>the AUC of the EM difference (0.655). The AUC of the EM difference and the comprehensive prediction model were statistically different (P=0.025). There was no statistical difference between the absolute value of bEOS and the AUC of the comprehensive prediction model. Conclusion The comprehensive prediction model covering the three aspects of allergic asthma history, VAS score, and bEOS count had the highest AUC compared to the other predictors and had good predictive power for the diagnosis of ECRS.
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Affiliation(s)
- Shuo Wu
- E.N.T. Department, the 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
- School of Biomedical Engineering, Sun Yat-Sen University, Shenzhen, People’s Republic of China
| | - Jiahong Lao
- E.N.T. Department, the 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Feitong Jian
- E.N.T. Department, the 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China
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Zhang L, Li H, Wang T, Wang Z, Wu Y, Guo S, Li W, Zhou Y, Xue H, You J. Association between peripheral eosinophilia, JESREC score, and olfactory dysfunction in patients with chronic rhinosinusitis. Front Immunol 2024; 15:1334656. [PMID: 38327522 PMCID: PMC10847329 DOI: 10.3389/fimmu.2024.1334656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 01/04/2024] [Indexed: 02/09/2024] Open
Abstract
Objective The purpose was to evaluate the relationship between peripheral eosinophilia, Japan Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score, and olfactory dysfunction in chronic rhinosinusitis (CRS) patients and to explore the accuracy and specific cut points of the JESREC score in predicting olfactory dysfunction. Methods In this cross-sectional, retrospective study, olfactory function was assessed by the Sniffin' Sticks 12-item test and multivariate logistic regression analyses were carried out. Receiver operating characteristic curves were plotted to derive accuracy and cutoff values for the JESREC scores of the olfactory dysfunction criterion. Results A total of 354 patients [mean (SD) age, 50.0 (14.9) years; 41.8% women] were included in the final analysis. The prevalence of olfactory dysfunction was 46.3%. Individuals who had olfactory dysfunction were more likely to be male (64.6% vs. 52.6%), have eosinophilic chronic rhinosinusitis (ECRS) (39.0% vs. 7.9%), have a longer course of CRS (2.3 years vs. 1.5 years), have higher JESREC scores (8.5 vs. 4.5), and have higher proportions of nasal polyps (78.7% vs. 18.9%) and peripheral eosinophilia (3.3% vs. 1.4%). In logistic analysis, the percentage of eosinophils (1.25, 1.13-1.37), JESREC score (1.31, 1.22-1.40), bilateral lesion (2.06, 1.25-3.41), nasal polyps (15.83, 9.23-27.16), CT shadow (2.73, 1.69-4.43), and ECRS (6.86, 3.68-12.80) were associated with olfactory dysfunction in CRS patients after controlling for covariates, while peripheral neutrophils were not significant. In addition, the area under the curve was 0.778 and the cutoff value for JESREC score for olfactory dysfunction was defined as 5.5. Conclusions Peripheral eosinophilia and high JESREC scores were significantly associated with the risk of olfactory dysfunction in CRS patients, and special attention should be paid to patients with a JESREC score ≥6.
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Affiliation(s)
- Ling Zhang
- Department of Otorhinolaryngology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Soochow University, Changzhou, China
| | - Haifeng Li
- Department of Otorhinolaryngology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Soochow University, Changzhou, China
| | - Tao Wang
- Department of Otorhinolaryngology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Soochow University, Changzhou, China
| | - Zhu Wang
- Department of Otorhinolaryngology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Soochow University, Changzhou, China
| | - Yang Wu
- Department of Otorhinolaryngology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Soochow University, Changzhou, China
| | - Siquan Guo
- Department of Otorhinolaryngology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Soochow University, Changzhou, China
| | - Wenjing Li
- Department of Otorhinolaryngology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Soochow University, Changzhou, China
| | - Yeru Zhou
- Department of Otorhinolaryngology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Soochow University, Changzhou, China
| | - Haixiang Xue
- Department of Otorhinolaryngology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Soochow University, Changzhou, China
| | - Jianqiang You
- Department of Otorhinolaryngology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Soochow University, Changzhou, China
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Li F, Wang S, Cha X, Li T, Xie Y, Wang W, Ren W, Liao J, Liu H. Blood Eosinophil Percentage and Improved Sinus CT Score as Diagnostic Tools for ECRS. OTO Open 2024; 8:e106. [PMID: 38223492 PMCID: PMC10784852 DOI: 10.1002/oto2.106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 10/27/2023] [Accepted: 11/14/2023] [Indexed: 01/16/2024] Open
Abstract
Objective Differentiating 2 types of chronic rhinosinusitis with nasal polyps (CRSwNP) is important for the treatment. The current diagnostic methods using single indicators, including peripheral blood eosinophils and traditional sinus computed tomography (CT) scores, are not accurate. In this study, we aimed to investigate the diagnostic value of combining peripheral blood eosinophils and improved sinus CT scores for eosinophic chronic rhinosinusitis (ECRS). Study Design Retrospective cohort. Setting Tertiary medical center. Methods We conducted a study involving 81 patients with CRSwNP. Peripheral blood samples were collected from the non-ECRS and ECRS groups. Improved three-dimensional volume image analysis and Lund-Mackay scoring system were performed to quantify the thickening of sinus mucosa. Multivariate binary logistic regression analysis was carried out to detect the predictive value of the scoring indicators. For significant indexes, receiver operating characteristic (ROC) curve analysis was applied. Results The ECRS group had higher levels of blood eosinophil percentage and count, ethmoid sinus score, total sinus score, the ratio of ethmoid sinus score and maxillary sinus score, and the difference between ethmoid and maxillary score, compared to the non-ECRS group (P < 0.05). Binary logistic regression analysis demonstrated that both blood eosinophil percentage and the improved E - M score (subtraction of ethmoid and maxillary sinus scores) were significant predictors of ECRS diagnosis (P < .01). ROC curve analysis indicated that the combination of improved E - M score and blood eosinophil percentage had a higher diagnostic value compared to either factor alone (area under the curve = 0.874). Conclusion Our study suggested the combination of improved total ethmoid sinus-maxillary score and blood eosinophil percentage is more accurate in predicting the diagnosis of ECRS.
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Affiliation(s)
- Fengzhen Li
- Department of Otolaryngology–Head and Neck Surgery, Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Shenglei Wang
- Department of Otolaryngology–Head and Neck Surgery, Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Xudong Cha
- Department of Otolaryngology–Head and Neck Surgery, Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Tengfei Li
- Department of Otolaryngology–Head and Neck Surgery, Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Yingqi Xie
- Department of Otolaryngology–Head and Neck Surgery, Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Wenwen Wang
- Department of Neurology, Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Wenwen Ren
- Department of Otolaryngology–Head and Neck Surgery, Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Jianchun Liao
- Department of Otolaryngology–Head and Neck Surgery, Changzheng HospitalNaval Medical UniversityShanghaiChina
| | - Huanhai Liu
- Department of Otolaryngology–Head and Neck Surgery, Changzheng HospitalNaval Medical UniversityShanghaiChina
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Hatsukawa H, Ishikawa M. Clinical Utility of Machine Learning Methods Using Regression Models for Diagnosing Eosinophilic Chronic Rhinosinusitis. OTO Open 2024; 8:e122. [PMID: 38464815 PMCID: PMC10924764 DOI: 10.1002/oto2.122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 02/21/2024] [Indexed: 03/12/2024] Open
Abstract
Objective Machine learning methods using regression models can predict actual values of histological eosinophil count from blood eosinophil levels. Therefore, these methods might be useful for diagnosing eosinophilic chronic rhinosinusitis, but their utility still remains unclear. We compared 2 statistical approaches, and investigated the utility of machine learning methods for diagnosing eosinophilic chronic rhinosinusitis. Study Design Retrospective study. Setting Medical center. Methods Data, including eosinophilic levels, obtained from blood and sinonasal samples of 264 patients with chronic rhinosinusitis (257 with and 57 without nasal polyps) were analyzed. We determined factors affecting histopathological eosinophil count in regression models. We also investigated optimal cutoff values for blood eosinophil percentages/absolute eosinophil counts (AECs) through receiver operating characteristic curves and machine-learning methods based on regression models. A histopathological eosinophil count ≥10/high-power field was defined as eosinophilic chronic rhinosinusitis. Results Blood eosinophil levels, nasal polyp presence, and comorbid asthma were factors affecting histopathological eosinophil count. Cutoffs between the 2 statistical approaches differed in the group with nasal polyps, but not in one without nasal polyps. Machine-learning methods identified blood eosinophil percentages ≥1% or AEC ≥100/μL as cut-offs for eosinophilic chronic rhinosinusitis with nasal polyps, while ≥6% or ≥400/μL for one without nasal polyps. Conclusion Cut-offs of blood eosinophil levels obtained by machine-learning methods might be useful when suspecting eosinophilic chronic rhinosinusitis prior to biopsy because of their ability to adjust covariates, dealing with overfitting, and predicting actual values of histological eosinophil count.
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Affiliation(s)
- Hiroatsu Hatsukawa
- Department of Otolaryngology, Head and Neck SurgeryHyogo Prefectural Amagasaki General Medical CenterAmgasakiJapan
| | - Masaaki Ishikawa
- Department of Otolaryngology, Head and Neck SurgeryHyogo Prefectural Amagasaki General Medical CenterAmgasakiJapan
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Ma J, Hsieh B, Huang S, Li Y, Tsou Y, Lin C, Tai C, Shih L. Clinical feature-based diagnosis criteria of eosinophil and non-eosinophil chronic rhinosinusitis in Taiwan. Laryngoscope Investig Otolaryngol 2023; 8:1459-1467. [PMID: 38130259 PMCID: PMC10731519 DOI: 10.1002/lio2.1165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/29/2023] [Accepted: 09/23/2023] [Indexed: 12/23/2023] Open
Abstract
Background The prevalence of eosinophilic chronic rhinosinusitis (ECRS) has increased in Taiwan with a higher recurrence rate of nasal polyps after surgery. Therefore, we aimed to formulate the pre-operative diagnostic criteria for patients with ECRS in Taiwan. Methods This case-control study included patients diagnosed with CRS with nasal polyps (CRSwNP) who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. The patients were classified into ECRS and non-eosinophilic CRS (NECRS) groups based on their histopathology. Demographic data, symptom severity scores, and computed tomography findings of the two groups were analyzed. We utilized receiver operating characteristic curve (ROC) analysis to evaluate parameters that could predict the diagnosis of ECRS. Results Total 408 CRSwNP patients were enrolled (ECRS group: 163; NECRS group: 245). ECRS group was strongly associated with asthma (6.1% vs. 2.0%, p = .03), higher blood eosinophil counts (4.3% vs. 2.7%, p < .01), higher serum IgE (285.3 vs. 50.2 IU/mL, p = .02), and higher 22-item Sino-Nasal Outcome Test (SNOT-22) score (40.5 vs. 36.7, p = .03). The ECRS criteria based on ROC curve included the SNOT-22 (>45, 2 points), serum eosinophil count percentage (>4%, 4 points), asthma (4 points), total serum IgE (>140 IU/mL, 4 points), Lund-Mackay score (>9.5, 4 points), and ethmoid-to-maxillary opacification ratio on CT (>1.5, 5 points). The cutoff score was 14 points (sensitivity, 70.2%; specificity, 93.3%). Conclusions Clinical-feature-based criteria may predict the diagnosis of ECRS before FESS in Taiwan. Level of Evidence Level 3.
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Affiliation(s)
- Jia‐Hung Ma
- Department of Otorhinolaryngology‐Head and Neck SurgeryChina Medical University HospitalTaichungTaiwan
| | - Bing‐Han Hsieh
- Department of Otorhinolaryngology‐Head and Neck SurgeryChina Medical University HospitalTaichungTaiwan
| | - Shuang‐Shuang Huang
- Department of Otorhinolaryngology‐Head and Neck SurgeryChina Medical University HospitalTaichungTaiwan
| | - Yu‐Ting Li
- Department of Otorhinolaryngology‐Head and Neck SurgeryChina Medical University HospitalTaichungTaiwan
| | - Yung‐An Tsou
- Department of Otorhinolaryngology‐Head and Neck SurgeryChina Medical University HospitalTaichungTaiwan
- Department of Otorhinolaryngology‐Head and Neck SurgeryAsia University HospitalTaichungTaiwan
- School of MedicineChina Medical UniversityTaichungTaiwan
| | - Chia‐Der Lin
- Department of Otorhinolaryngology‐Head and Neck SurgeryChina Medical University HospitalTaichungTaiwan
- School of MedicineChina Medical UniversityTaichungTaiwan
| | - Chih‐Jaan Tai
- Department of Otorhinolaryngology‐Head and Neck SurgeryChina Medical University HospitalTaichungTaiwan
- School of MedicineChina Medical UniversityTaichungTaiwan
| | - Liang‐Chun Shih
- Department of Otorhinolaryngology‐Head and Neck SurgeryChina Medical University HospitalTaichungTaiwan
- Department of Otorhinolaryngology‐Head and Neck SurgeryAsia University HospitalTaichungTaiwan
- School of MedicineChina Medical UniversityTaichungTaiwan
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Huang A, Li T, Li MS, Huang ZX, Wang DH, Cheng L, Zhou B, Wang H, Liu Z. Association of Comorbid Asthma and the Efficacy of Bioabsorbable Steroid-eluting Sinus Stents Implanted After Endoscopic Sinus Surgery in Patients with Chronic Rhinosinusitis with Nasal Polyps. Curr Med Sci 2023; 43:1005-1012. [PMID: 37828371 DOI: 10.1007/s11596-023-2786-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 08/03/2023] [Indexed: 10/14/2023]
Abstract
OBJECTIVE To identify factors affecting the efficacy of steroid-eluting sinus stents implanted after endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS We performed a post-hoc analysis of a randomized self-controlled clinical trial on post-operative implantation of bioabsorbable steroid-eluting stents in patients with CRSwNP. Univariate logistic regression analysis was conducted to identify which of the following factors affect the response to post-operative stent implantation: sex, serum eosinophil levels, history of prior surgery, endoscopic scores, and comorbid conditions (asthma and allergic rhinitis). The primary outcome was the rate of post-operative intervention on day 30, and the secondary outcome was the rate of polypoid tissue formation (grades 2-3) on days 14, 30, and 90. RESULTS A total of 151 patients with CRSwNP were included in the post-hoc analysis. Asthma was identified as the only risk factor for a poor response to steroid-eluting sinus stents on post-operative day 30, with an odds ratio of 23.71 (95% CI, 2.81, 200.16; P=0.004) for the need for post-operative intervention and 19 (95% CI, 2.20, 164.16; P=0.003) for moderate-to-severe polypoid tissue formation. In addition, the asthmatic group showed higher rates of post-operative intervention and polypoid tissue formation than the non-asthmatic group on post-operative day 30. Blood eosinophil levels were not identified as a risk factor for poor outcomes after stent implantation. CONCLUSION Comorbid asthma, but not blood eosinophil level, impairs the efficacy of steroid-eluting sinus stents in the short term after ESS in patients with CRSwNP.
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Affiliation(s)
- Ao Huang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, 430030, China
| | - Tao Li
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, 430030, China
| | - Min-Shan Li
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, 430030, China
| | - Zhen-Xiao Huang
- Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100000, China
| | - De-Hui Wang
- Department of Otolaryngology-Head and Neck Surgery, Eye, Ear, Nose and Throat Hospital, Fudan University, Shanghai, 200000, China
| | - Lei Cheng
- Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, 210029, China
| | - Bing Zhou
- Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100000, China.
| | - Heng Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, 430030, China.
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, 430030, China.
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Yoo SH, Kim YA, Mo JH. Can EPOS2020 criteria of type 2 inflammation be applied to Asian patients with chronic rhinosinusitis? Acta Otolaryngol 2023; 143:789-795. [PMID: 37837274 DOI: 10.1080/00016489.2023.2264898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 09/20/2023] [Indexed: 10/15/2023]
Abstract
BACKGROUND There is a large diversity of mucosal immunologic chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes across Western and Asian patient populations. OBJECTIVES The objective of the study was whether the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 criteria for type 2 inflammation are appropriate for biological use in CRSwNP patients. METHODS A total of 207 participants are enrolled for the study. Retrospective evaluations of the tissues taken during surgery and the patients' clinical features were performed. We investigated whether the criteria described in the EPOS2020 guideline were appropriate based on the criteria for type 2 inflammation identified based on prior studies using receiver-operating characteristic (ROC) analyses. RESULTS The EPOS 2020 criteria are also shown to be an insufficient evaluation approach with low specificity (area under curve [AUC] = 0.645, specificity 8.4%). The authors created a novel scoring method using the total serum IgE level, blood eosinophil percentage, and tissue eosinophil percentage. This novel scoring system (AUC = 0.862, p < .001) fared better in ROC analyses than the EPOS 2020 criteria (AUC = 0.645) and Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis scoring system (AUC = 0.647). CONCLUSIONS AND SIGNIFICANCE A novel standard for type 2 inflammation in Asian CRSwNP patients must be established, as the EPOS 2020 criteria do not appear to be sufficient.
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Affiliation(s)
- Shin Hyuk Yoo
- Department of Otorhinolaryngology, Dankook University College of Medicine, Cheonan, Korea
| | - Yoon-Ah Kim
- Department of Otorhinolaryngology, Dankook University College of Medicine, Cheonan, Korea
| | - Ji-Hun Mo
- Department of Otorhinolaryngology, Dankook University College of Medicine, Cheonan, Korea
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Liu Y, Xing Z, Geng C, Liu Y, Cao J, Yang Y, Pan T, Yu L. Use of peripheral blood eosinophils to guide post-operative glucocorticoid therapy in patients with chronic rhinosinusitis with nasal polyps: a randomised, controlled trial. J Laryngol Otol 2023; 137:890-901. [PMID: 36444128 DOI: 10.1017/s0022215122002481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
OBJECTIVE This study aimed to explore the utility of the eosinophil percentage in peripheral blood for guiding post-operative glucocorticoid therapy in patients with chronic rhinosinusitis with nasal polyps. METHODS Forty-four patients with chronic rhinosinusitis with nasal polyps underwent functional endoscopic sinus surgery and were randomly divided into two groups. Patients in the standard treatment group used oral and nasal spray glucocorticoids. In the biomarker treatment group, patients with peripheral blood eosinophil percentage values less than 3.05 per cent did not receive glucocorticoid treatment, whereas patients with values 3.05 per cent or above were part of the standard treatment group. Visual Analogue Scale, Sino-Nasal Outcome Test-22 scores, endoscopic Lund-Kennedy scores, eosinophils, interleukin-5 and eosinophil cationic protein in peripheral blood, and nasal secretions were measured. RESULTS After functional endoscopic sinus surgery, the Visual Analogue Scale, Sino-Nasal Outcome Test-22 and Lund-Kennedy scores were significantly reduced in both groups; there were no significant differences in those indicators between the groups during the three follow-up visits. CONCLUSION Peripheral blood eosinophil percentage offers a potential biomarker to guide post-operative glucocorticoid therapy in patients with chronic rhinosinusitis with nasal polyps.
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Affiliation(s)
- Y Liu
- Department of Otorhinolaryngology, Head and Neck Surgery, Peking University People's Hospital, Peking University, Beijing, China
| | - Z Xing
- Department of Otorhinolaryngology, Head and Neck Surgery, Peking University People's Hospital, Peking University, Beijing, China
| | - C Geng
- Department of Otorhinolaryngology, Head and Neck Surgery, Peking University People's Hospital, Peking University, Beijing, China
| | - Y Liu
- Department of Otorhinolaryngology, Head and Neck Surgery, Peking University People's Hospital, Peking University, Beijing, China
| | - J Cao
- Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Y Yang
- Department of Otorhinolaryngology, Head and Neck Surgery, Peking University People's Hospital, Peking University, Beijing, China
| | - T Pan
- Department of Otorhinolaryngology, Head and Neck Surgery, Peking University People's Hospital, Peking University, Beijing, China
| | - L Yu
- Department of Otorhinolaryngology, Head and Neck Surgery, Peking University People's Hospital, Peking University, Beijing, China
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Nakayama T, Haruna SI. A review of current biomarkers in chronic rhinosinusitis with or without nasal polyps. Expert Rev Clin Immunol 2023; 19:883-892. [PMID: 37017326 DOI: 10.1080/1744666x.2023.2200164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 04/04/2023] [Indexed: 04/06/2023]
Abstract
INTRODUCTION Chronic rhinosinusitis (CRS) is a heterogeneous disease with a variety of cellular and molecular pathophysiologic mechanisms. Biomarkers have been explored in CRS using various phenotypes, such as polyp recurrence after surgery. Recently, the presence of regiotype in CRS with nasal polyps (CRSwNP) and the introduction of biologics for the treatment of CRSwNP has indicated the importance of endotypes, and there is a need to elucidate endotype-based biomarkers. AREAS COVERED Biomarkers for eosinophilic CRS, nasal polyps, disease severity, and polyp recurrence have been identified. Additionally, endotypes are being identified for CRSwNP and CRS without nasal polyps using cluster analysis, an unsupervised learning technique. EXPERT OPINION Endotypes in CRS have still being established, and biomarkers capable of identifying endotypes of CRS are not yet clear. When identifying endotype-based biomarkers, it is necessary to first identify endotypes clarified by cluster analysis for outcomes. With the application of machine learning, the idea of predicting outcomes using a combination of multiple integrated biomarkers, rather than a single biomarker, will become mainstream.
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Affiliation(s)
- Tsuguhisa Nakayama
- Department of Otorhinolaryngology and Head & Neck Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Shin-Ichi Haruna
- Department of Otorhinolaryngology and Head & Neck Surgery, Dokkyo Medical University, Tochigi, Japan
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Zhou A, Shi C, Fan Y, Zheng Y, Wang J, Liu Z, Xie H, Liu J, Jiao Q. Involvement of CD40-CD40L and ICOS-ICOSL in the development of chronic rhinosinusitis by targeting eosinophils. Front Immunol 2023; 14:1171308. [PMID: 37325657 PMCID: PMC10267736 DOI: 10.3389/fimmu.2023.1171308] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 03/20/2023] [Indexed: 06/17/2023] Open
Abstract
Background Chronic rhinosinusitis (CRS), whose prevalence and pathogenesis are age-related, is characterized by nasal tissue eosinophil infiltration. CD40-CD40 ligand (CD40L) pathway involves in the eosinophil-mediated inflammation, and inducible co-stimulator (ICOS)-ICOS ligand (ICOSL) signal can strengthen CD40-CD40L interaction. Whether CD40-CD40L and ICOS-ICOSL have a role in the development of CRS remains unknown. Objectives The aim of this study is to investigate the association of CD40-CD40L and ICOS-ICOSL expression with CRS and underlying mechanisms. Methods Immunohistology detected the expression of CD40, CD40L, ICOS, and ICOSL. Immunofluorescence was performed to evaluate the co-localizations of CD40 or ICOSL with eosinophils. Correlations between CD40-CD40L and ICOS-ICOSL as well as clinical parameters were analyzed. Flow cytometry was used to explore the activation of eosinophils by CD69 expression and the CD40 and ICOSL expression on eosinophils. Results Compared with the non-eCRS subset, ECRS (eosinophilic CRS) subset showed significantly increased CD40, ICOS, and ICOSL expression. The CD40, CD40L, ICOS, and ICOSL expressions were all positively correlated with eosinophil infiltration in nasal tissues. CD40 and ICOSL were mainly expressed on eosinophils. ICOS expression was significantly correlated with the expression of CD40-CD40L, whereas ICOSL expression was correlated with CD40 expression. ICOS-ICOSL expression positively correlated with blood eosinophils count and disease severity. rhCD40L and rhICOS significantly enhanced the activation of eosinophils from patients with ECRS. Tumor necrosis factor-α (TNF-α) and interleukin-5 (IL-5) obviously upregulated CD40 expression on eosinophils, which was significantly inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor. Conclusions Increased CD40-CD40L and ICOS-ICOSL expressions in nasal tissues are linked to eosinophils infiltration and disease severity of CRS. CD40-CD40L and ICOS-ICOSL signals enhance eosinophils activation of ECRS. TNF-α and IL-5 regulate eosinophils function by increasing CD40 expression partly via p38 MAPK activation in patients with CRS.
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Affiliation(s)
- Aina Zhou
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chenxi Shi
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuhui Fan
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yushuang Zheng
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jue Wang
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhichen Liu
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Huanxia Xie
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jisheng Liu
- Department of Ear, Nose, and Throat, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Qingqing Jiao
- Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Guo CL, Lu RY, Wang CS, Zhao JF, Pan L, Liu HC, Liao B, Liu Z. Identification of Inflammatory Endotypes by Clinical Characteristics and Nasal Secretion Biomarkers in Chronic Rhinosinusitis with Nasal Polyps. Int Arch Allergy Immunol 2023; 184:955-965. [PMID: 37253337 PMCID: PMC10614570 DOI: 10.1159/000530193] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 01/03/2023] [Indexed: 06/01/2023] Open
Abstract
INTRODUCTION The emergency of biologics and surgical techniques targeting the specific inflammatory endotype in chronic rhinosinusitis with nasal polyps (CRSwNP) asks for efficient identification of patients with different endotypes. Although mucosal IL-4, IL-5, IL-13, and IgE have been used to define type 2 (T2) inflammation, the optimal one remains unclear. In this study, we aimed to determine the optimal anchor for T2 inflammation and identify clinical characteristics and nasal secretion biomarkers predicting different endotypes in CRSwNP. METHODS Six mediators in sinonasal tissue and 36 mediators in nasal secretion samples were detected by the Bio-Plex suspension array system. Mucosal IFN-γ and IL-17A levels were used to define the T1 and T3 endotype, respectively. The efficacy of mucosal IL-4, IL-5, IL-13, and IgE to define the T2 endotype was compared. The power of clinical characteristics and nasal secretion biomarkers to predict the T1, T2, and T3 endotype was analyzed. RESULTS Among mucosal IL-4, IL-5, IL-13, and IgE, IL-13 was the best one to coincide with the expression of other T2 biomarkers. A combination of atopy, facial pain symptom score, ethmoid/maxillary computed tomography score ratio, and blood eosinophil percentage had a moderate predictive performance for T2 endotype (area under the receiver operating curve [AUC] = 0.815), comparable to that of nasal secretion IL-5 (AUC = 0.819). For the T3 endotype, nasal secretion IL-1Rα identified it with an AUC value of 0.756. No efficient marker for the T1 endotype was found. CONCLUSION IL-13 is a primary anchor for the T2 endotype in CRSwNP. Clinical characteristics and nasal secretion biomarkers are helpful for identifying the T2 and T3 endotype of CRSwNP.
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Affiliation(s)
- Cui-Lian Guo
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Insititue of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, PR China
| | - Ruo-Yu Lu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Insititue of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, PR China
| | - Chong-Shu Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Insititue of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, PR China
| | - Jie-Fang Zhao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Insititue of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, PR China
| | - Li Pan
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Insititue of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, PR China
| | - Hui-Cheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Insititue of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, PR China
| | - Bo Liao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Insititue of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, PR China
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Insititue of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
- Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, PR China
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Tang B, Tu J, Zhang M, Zhang Z, Yu J, Shen L, Luo Q, Ye J. Diagnostic value and underlying mechanism of nasal nitric oxide in eosinophilic chronic rhinosinusitis with nasal polyps. Mol Immunol 2023; 159:1-14. [PMID: 37224640 DOI: 10.1016/j.molimm.2023.05.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 05/09/2023] [Accepted: 05/09/2023] [Indexed: 05/26/2023]
Abstract
PURPOSE Nitric oxide (NO) is an important messenger molecule widely present in the human body. However, the role of nasal NO (nNO) in eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) remain unclear. This study aimed to investigate the diagnostic value and underlying mechanism of nNO in Eos CRSwNP. METHODS The medical records of 84 non-Eos CRSwNP patients, 55 Eos CRSwNP patients, and 37 control subjects were retrospectively reviewed. The diagnostic value of nNO for Eos CRSwNP was assessed. The expression of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and tight junctions (TJs) components claudin-1, occludin, and ZO-1 was detected in the nasal polyps. Primary human nasal epithelial cells (HNECs) were co-treated with eNOS inhibitor (L-NAME) or Akt inhibitor (MK-2206), interleukin (IL)-13, and dexamethasone (Dex). The level of NO and the expression of TJs and Akt/eNOS pathways were examined. RESULTS The nNO levels of the CRSwNP group were significantly lower than those of the control group. Compared with the non-Eos CRSwNP group, the Eos CRSwNP group showed higher nNO level. The combination of nNO level, eosinophilic percentage, and posterior ethmoid score had a better predictive value for Eos CRSwNP (AUC = 0.855). The expression of iNOS, eNOS, and p-eNOS was higher in the CRSwNP groups than in the control group, and p-eNOS expression was higher in the Eos CRSwNP group than in the non-Eos CRSwNP group. The expression of TJs was lower in the Eos CRSwNP group than in the non-Eos CRSwNP and control group. IL-13 decreased TJ expression in HNECs, while Dex promoted Akt and eNOS phosphorylation, NO production and TJ expression. Furthermore, these effects of Dex were inhibited by L-NAME and MK-2206 in HNECs. CONCLUSION nNO may have a high diagnostic value in Eos CRSwNP, and Akt/eNOS pathway may promote the generation of NO to protect TJs. NO may have a potentially important role in the diagnosis and treatment of Eos CRSwNP.
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Affiliation(s)
- Binxiang Tang
- Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Junhao Tu
- Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore
| | - Meiping Zhang
- Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Zhiqiang Zhang
- Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Jieqing Yu
- Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; Institute of Jiangxi Otorhinolaryngology Head & Neck Suegery, Nanchang, Jiangxi Province, China
| | - Li Shen
- Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Qing Luo
- Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China
| | - Jing Ye
- Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; Institute of Jiangxi Otorhinolaryngology Head & Neck Suegery, Nanchang, Jiangxi Province, China.
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Subjective symptoms as predictors for eosinophilic chronic rhinosinusitis with nasal polyps in the Chinese population. Eur Arch Otorhinolaryngol 2023:10.1007/s00405-023-07905-1. [PMID: 36917251 DOI: 10.1007/s00405-023-07905-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 02/27/2023] [Indexed: 03/16/2023]
Abstract
PURPOSE To evaluate the putative association between subjective symptoms and eosinophilic inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS A total of 102 patients with CRSwNP who underwent endoscopic sinus surgery were prospectively enrolled. The Sinonasal Outcomes Test-22 scores (SNOT-22), EuroQol 5-dimensional Questionnaire scores (ED-5D), and Lund-Mackay scores by computed tomography (CT) were obtained. Patients were grouped as eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP). ECRSwNP was defined if tissue eosinophils of nasal polyps were greater than or equal to 8/HPF according to positive major basic protein (MBP) staining, and neCRSwNP otherwise. RESULTS Thirty neCRSwNP and 72 eCRSwNP patients were included. ECRSwNP patients had higher incidences of asthma (p = 0.001), allergic rhinitis (p = 0.001), and ethmoid-to-maxillary opacification ratio on CT scans (p < 0.001), whereas the proportion of purulent discharge (p < 0.001) and maxillary sinus score (p = 0.002) was higher in the neCRSwNP patients. There were no significant differences between patients on the mains of the EQ-5D health utility values and total SNOT-22 score. However, eCRSwNP patients had higher SNOT-22 scores of sneezing (p = 0.006), runny nose (p < 0.001), and ear/facial domain (p = 0.012), and lower scores of thick nasal discharge (p = 0.015) and blockage (p = 0.042). Sneezing, thick nasal discharge, and blockage/congestion of nose were recognized as independent factors of CRSwNP. CONCLUSION Sneezing was an independent predictor of eCRSwNP, and thick nasal discharge and blockage/congestion of nose were independent predictors of neCRSwNP.
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MicroRNAs: Potential Biomarkers of Disease Severity in Chronic Rhinosinusitis with Nasal Polyps. Medicina (B Aires) 2023; 59:medicina59030550. [PMID: 36984551 PMCID: PMC10051206 DOI: 10.3390/medicina59030550] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/03/2023] [Accepted: 03/09/2023] [Indexed: 03/14/2023] Open
Abstract
Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRwNP) has multiple clinical presentations, and predictors of successful treatment are correlated to different parameters. Differentially expressed microRNAs in nasal polyps emerge as possible facilitators of precise endotyping in this disease. We aimed to evaluate the correlation between the clinical parameters of CRSwNP and two different microRNAs. Materials and Methods: The expression of miR-125b and miR-203a-3p in nasal polyps (n = 86) and normal nasal mucosa (n = 20) was determined through microarray analysis. Preoperative workup included CT scan, nasal endoscopy, blood tests, symptoms and depression questionnaires. Results: MiR-125b showed significant overexpression in NP compared to the normal nasal mucosa. miR-125b expression levels were positively and significantly correlated with blood eosinophilia (p = 0.018) and nasal endoscopy score (p = 0.021). Although high CT scores were related to miR-125b overexpression, the correlation did not reach statistical significance. miR-203a-3p was underexpressed in nasal polyps and was significantly underexpressed in CRSwNP patients with environmental allergies. Conclusions: Both miR-125b and miR-203a-3p are potential biomarkers in CRSwNP. miR-125b also correlates with the clinical picture, while miR-203a-3p could help identify an associated allergy.
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Luo Q, Zhou S, Yuan B, Feng Z, Tan G, Liu H. Blood eosinophil count in the diagnosis of allergic-like rhinitis with chronic rhinosinusitis. Clin Otolaryngol 2023; 48:339-346. [PMID: 36222453 DOI: 10.1111/coa.13990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 09/12/2022] [Accepted: 09/25/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Allergic rhinitis (AR) and nonallergic rhinitis (NAR) often are comorbid with chronic rhinosinusitis (CRS). Finding a convenient test that distinguishes these complex conditions is helpful for effective treatment. We aimed to analyse blood parameter differences between AR and NAR patients with/without CRS. METHODS Eight hundred thirteen patients, including AR and NAR with different conditions [CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP)] were analysed in this retrospective study. Patients with a nasal deviation alone were included as healthy controls (HC). Receiver operating characteristic analysis was used to assess the value of blood parameters for diagnosing AR or NAR with/without CRS. RESULTS Compared to nonallergic-like rhinitis (HC, CRSwNP and CRSsNP), the blood eosinophil count was significantly increased in the allergic-like rhinitis groups, except for NAR-CRSsNP (AR, AR-CRSwNP, AR-CRSsNP, NAR and NAR-CRSwNP). The NAR-CRSsNP group had a higher level of eosinophils than the HC and CRSsNP groups. Among allergic-like rhinitis patients, eosinophils were higher in allergic-like rhinitis patients with CRSwNP (AR-CRSwNP and NAR-CRSwNP) than in allergic-like rhinitis patients without CRSwNP (AR, AR-CRSsNP, NAR and NAR-CRSsNP). However, no difference in blood eosinophils was observed between AR and NAR. There was also no difference among nonallergic-like rhinitis patients. Similar findings were found for the blood eosinophil proportion. Furthermore, the blood eosinophil count was a good predictor of allergic-like rhinitis, especially allergic-like rhinitis with CRSwNP. CONCLUSION The blood eosinophil count and proportion may be good diagnostic predictors of allergic-like rhinitis but cannot differentiate between AR and NAR. This indicator may be much better in predicting allergic-like rhinitis with CRSwNP.
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Affiliation(s)
- Qiqi Luo
- Department of Otorhinolaryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, China
| | - Siyi Zhou
- Department of Otorhinolaryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, China
| | - Bo Yuan
- Department of Otorhinolaryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, China
| | - Zeli Feng
- School of Medicine, Hunan Normal University, Changsha, China
| | - Guolin Tan
- Department of Otorhinolaryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, China
| | - Honghui Liu
- Department of Otorhinolaryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, China
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21
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Yao Y, Zhu HY, Zeng M, Liu Z. Immunological mechanisms and treatable traits of chronic rhinosinusitis in Asia: A narrative review. Clin Otolaryngol 2023; 48:363-370. [PMID: 36317525 DOI: 10.1111/coa.14001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/23/2022] [Accepted: 10/16/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES To review the current literature on immunological mechanisms and treatable traits of chronic rhinosinusitis (CRS) in Asia. DESIGN This is a narrative review of published data on the immunological mechanisms and treatable traits of CRS in Asia. Published English literature on CRS in Asian and Western countries was reviewed. Where available, the data extracted included epidemiology, immunology, bacterium, phenotype, endotype and treatment. RESULTS AND CONCLUSION CRS is a heterogeneous disease characterised by persistent locoregional mucosal inflammation of the paranasal sinuses. The inflammatory signatures of CRS vary across patients with distinct racial and ethnic backgrounds and geographic areas. Compared to CRS patients in Western countries, Asian CRS patients display less eosinophilic and Type 2 inflammation, which is associated with lower asthma and allergic rhinitis comorbidities. In contrast, Asian patients with CRS have more prominent non-eosinophilic inflammation than those in Western countries. In addition, Asian CRS patients may have different bacterial colonisation than patients in Western countries. Our review suggests that the distinct immunological mechanisms between Asian and Western CRS patients may influence the clinical phenotype, responses to treatment and outcomes. The treatable trait is a new strategy and therapeutic target identified by phenotype or endotype and has been proposed as a new paradigm for the management of diseases. Improved understanding of CRS phenotypic and endotypic heterogeneity and incorporation of treatable traits into clinical care pathways may facilitate more effective selections of therapeutic interventions, including surgery and biologics.
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Affiliation(s)
- Yin Yao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.,Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, Hubei, People's Republic of China
| | - Hong-Yu Zhu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Ming Zeng
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.,Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, Hubei, People's Republic of China
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.,Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, Hubei, People's Republic of China
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22
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Hua HL, Li S, Xu Y, Chen SM, Kong YG, Yang R, Deng YQ, Tao ZZ. Differentiation of eosinophilic and non-eosinophilic chronic rhinosinusitis on preoperative computed tomography using deep learning. Clin Otolaryngol 2023; 48:330-338. [PMID: 36200353 DOI: 10.1111/coa.13988] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 08/12/2022] [Accepted: 09/11/2022] [Indexed: 11/26/2022]
Abstract
OBJECTIVES This study aimed to develop deep learning (DL) models for differentiating between eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS (NECRS) on preoperative CT. DESIGN Axial spiral CT images were pre-processed and used to build the dataset. Two semantic segmentation models based on U-net and Deeplabv3 were trained to segment the sinus area on CT images. All patient images were segmented using the better-performing segmentation model and used for training and testing of the transferred efficientnet_b0, resnet50, inception_resnet_v2, and Xception neural networks. Additionally, we evaluated the performances of the models trained using each image and each patient as a unit. PARTICIPANTS A total of 878 chronic rhinosinusitis (CRS) patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University (Hubei, China) between October 2016 to June 2021 were included. MAIN OUTCOME MEASURES The precision of each model was assessed based on the receiver operating characteristic curve. Further, we analyzed the confusion matrix and accuracy of each model. RESULTS The Dice coefficients of U-net and Deeplabv3 were 0.953 and 0.961, respectively. The average area under the curve and mean accuracy values of the four networks were 0.848 and 0.762 for models trained using a single image as a unit, while the corresponding values for models trained using each patient as a unit were 0.893 and 0.853, respectively. CONCLUSIONS Combining semantic segmentation with classification networks could effectively distinguish between patients with ECRS and those with NECRS based on preoperative sinus CT images. Furthermore, labeling each patient to build a dataset for classification may be more reliable than labeling each medical image.
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Affiliation(s)
- Hong-Li Hua
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Song Li
- Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China
| | - Yu Xu
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Shi-Ming Chen
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Yong-Gang Kong
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Rui Yang
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Yu-Qin Deng
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
| | - Ze-Zhang Tao
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.,Department of Otolaryngology-Head and Neck Surgery, Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
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23
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Wang Y, Lou H, Xian M, Cui J, Piao Y, Wang C, Zhang L, Xian J. Investigation of the Value of T 2 Mapping in the Prediction of Eosinophilic Chronic Rhinosinusitis With Nasal Polyps. J Comput Assist Tomogr 2023; 47:329-336. [PMID: 36723408 PMCID: PMC10045955 DOI: 10.1097/rct.0000000000001411] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVES Patients with eosinophilic chronic rhinosinusitis with nasal polyps (eosCRSwNP) usually have more extensive sinus disease, severe symptoms, and poorer disease control compared with patients with non-eosCRSwNP. Separating these entities will be crucial for patient management. The purpose of this study is to investigate T 1, T 2 , and apparent diffusion coefficient (ADC) values of the nasal polyps in patients with CRSwNP and evaluate the usefulness of these parameters for differentiating these diseases. METHODS Sinonasal magnetic resonance imaging was performed in 36 patients with eosCRSwNP and 20 patients with non-eosCRSwNP (including T 1 mapping, T 2 mapping, and diffusion-weighted imaging) before surgery. The T 1 , T 2 , and ADC values were calculated and correlated with pathologically assessed inflammatory cells of nasal polyps. RESULTS Significant higher T 2 value, higher eosinophil count, and lower lymphocyte count of the nasal polyps were observed in eosCRSwNP than those in non-eosCRSwNP. There was no significant difference in T 1 or ADC values between the 2 groups. T 2 value was correlated with eosinophil count and lymphocyte count in CRSwNP. The area under the curve of T 2 value for predicting eosCRSwNP was 0.78 with 89.9% sensitivity and 60.0% specificity. CONCLUSION T 2 value is a promising imaging biomarker for predicting eosCRSwNP. It can help to distinguish eosCRSwNP from non-eosCRSwNP.
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Affiliation(s)
| | | | | | - Jing Cui
- From the Departments of Radiology
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24
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Seah JJ, Thong M, Wang DY. The Diagnostic and Prognostic Role of Biomarkers in Chronic Rhinosinusitis. Diagnostics (Basel) 2023; 13:diagnostics13040715. [PMID: 36832203 PMCID: PMC9955000 DOI: 10.3390/diagnostics13040715] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 02/07/2023] [Accepted: 02/09/2023] [Indexed: 02/16/2023] Open
Abstract
Chronic rhinosinusitis (CRS) refers to an inflammatory disease of the sinonasal mucosa, with a significant economic burden and impact on quality of life. The diagnosis of CRS is conventionally made on careful history and physical examination, including nasoendoscopic assessment which requires technical expertise. There has been increasing interest in using biomarkers in the non-invasive diagnosis and prognostication of CRS, tailored to the disease inflammatory endotype. Potential biomarkers currently being studied can be isolated from peripheral blood, exhaled nasal gases or nasal secretions, as well as sinonasal tissue. In particular, various biomarkers have revolutionized the way in which CRS is managed, revealing new inflammatory pathways where novel therapeutic drugs are employed to curb the inflammatory process, which may be different from one patient to the next. Biomarkers that have been extensively studied in CRS, such as eosinophil count, IgE, and IL-5, have been associated with a TH2 inflammatory endotype which correlates with an eosinophilic CRSwNP phenotype that predicts a poorer prognosis, tends to recur after conventional surgical treatment, but responds to glucocorticoid treatment. Newer biomarkers that demonstrate potential, such as nasal nitric oxide, can support a diagnosis of CRS with or without nasal polyps, especially when invasive tests such as nasoendoscopy are unavailable. Other biomarkers such as periostin can be used to monitor disease course after treatment of CRS. With a personalized treatment plan, the management of CRS can be individualized, optimizing treatment efficiency and reducing adverse outcomes. As such, this review aims to compile and summarize the existing literature regarding the utility of biomarkers in CRS in terms of diagnosis and prognostication, and also makes recommendations for further studies to fill current knowledge gaps.
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Affiliation(s)
- Jun Jie Seah
- Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
| | - Mark Thong
- Department of Otolaryngology-Head and Neck Surgery, National University Hospital, National University Health System, Singapore 119228, Singapore
| | - De Yun Wang
- Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
- Correspondence:
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25
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Dodi G, Di Filippo P, Ciarelli F, Porreca A, Cazzato F, Matonti L, Di Pillo S, Neri G, Chiarelli F, Attanasi M. The Role of Nasal Cytology and Serum Atopic Biomarkers in Paediatric Rhinitis. Diagnostics (Basel) 2023; 13:diagnostics13030555. [PMID: 36766659 PMCID: PMC9914856 DOI: 10.3390/diagnostics13030555] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/22/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
A Nasal Provocation Test allows the differentiation of allergic and non-allergic rhinitis, but it is difficult and expensive. Therefore, nasal cytology is taking hold as an alternative. We carried out a cross-sectional study, including 29 patients with persistent rhinitis according to ARIA definition and negative skin prick tests. Nasal symptoms were scored from 0 to 5 using a visual analogue scale, and patients underwent blood tests to investigate blood cell count (particularly eosinophilia and basophilia), to analyze serum total and specific IgE and eosinophil cationic protein (ECP), and to perform nasal cytology. We performed a univariate logistical analysis to evaluate the association between total serum IgE, serum eosinophilia, basophils, and ECP and the presence of eosinophils in the nasal mucosa, and a multivariate logistic model in order to weight the single variable on the presence of eosinophils to level of the nasal mucosa. A statistically significant association between serum total IgE levels and the severity of nasal eosinophilic inflammation was found (confidence interval C.I. 1.08-4.65, odds ratio OR 2.24, p value 0.03). For this reason, we imagine a therapeutic trial with nasal steroids and oral antihistamines in patients with suspected LAR and increased total IgE levels, reserving nasal cytology and NPT to non-responders to the first-line therapy.
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Affiliation(s)
- Giulia Dodi
- Pediatric Allergy and Pulmonology Unit, Department of Pediatrics, University of Chieti-Pescara, 66100 Chieti, Italy
- Correspondence:
| | - Paola Di Filippo
- Pediatric Allergy and Pulmonology Unit, Department of Pediatrics, University of Chieti-Pescara, 66100 Chieti, Italy
| | - Francesca Ciarelli
- Pediatric Allergy and Pulmonology Unit, Department of Pediatrics, University of Chieti-Pescara, 66100 Chieti, Italy
| | - Annamaria Porreca
- Department of Economic Studies, University of Chieti-Pescara, 66100 Chieti, Italy
| | - Fiorella Cazzato
- Department of Otolaryngology, University of Chieti-Pescara, 66100 Chieti, Italy
| | - Lorena Matonti
- Pediatric Allergy and Pulmonology Unit, Department of Pediatrics, University of Chieti-Pescara, 66100 Chieti, Italy
| | - Sabrina Di Pillo
- Pediatric Allergy and Pulmonology Unit, Department of Pediatrics, University of Chieti-Pescara, 66100 Chieti, Italy
| | - Giampiero Neri
- Department of Otolaryngology, University of Chieti-Pescara, 66100 Chieti, Italy
| | - Francesco Chiarelli
- Pediatric Allergy and Pulmonology Unit, Department of Pediatrics, University of Chieti-Pescara, 66100 Chieti, Italy
| | - Marina Attanasi
- Pediatric Allergy and Pulmonology Unit, Department of Pediatrics, University of Chieti-Pescara, 66100 Chieti, Italy
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Zhou H, Fan W, Qin D, Liu P, Gao Z, Lv H, Zhang W, Xiang R, Xu Y. Development, Validation and Comparison of Artificial Neural Network and Logistic Regression Models Predicting Eosinophilic Chronic Rhinosinusitis With Nasal Polyps. ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2022; 15:67-82. [PMID: 36693359 PMCID: PMC9880304 DOI: 10.4168/aair.2023.15.1.67] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 08/18/2022] [Accepted: 09/02/2022] [Indexed: 01/19/2023]
Abstract
PURPOSE Chronic rhinosinusitis with nasal polyps (CRSwNP) can be classified into eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (non-eCRSwNP) by tissue biopsy, which is difficult to perform preoperatively. Clinical biomarkers have predictive value for the classification of CRSwNP. We aimed to evaluate the application of artificial neural network (ANN) modeling in distinguishing different endotypes of CRSwNP based on clinical biomarkers. METHODS Clinical parameters were collected from 109 CRSwNP patients, and their predictive ability was analyzed. ANN and logistic regression (LR) models were developed in the training group (72 patients) and further tested in the test group (37 patients). The output variable was the diagnosis of eCRSwNP, defined as tissue eosinophil count > 10 per high-power field. The receiver operating characteristics curve was used to assess model performance. RESULTS A total of 15 clinical features from 60 healthy controls, 60 eCRSwNP and 49 non-eCRSwNP were selected as candidate predictors. Nasal nitric oxide levels, peripheral eosinophil absolute count, total immunoglobulin E, and ratio of bilateral computed tomography scores for the ethmoid sinus and maxillary sinus were identified as important features for modeling. Two ANN models based on 4 and 15 clinical features were developed to predict eCRSwNP, which showed better performance, with the area under the receiver operator characteristics significantly higher than those from the respective LR models (0.976 vs. 0.902, P = 0.048; 0.970 vs. 0.845, P = 0.011). All ANN models had better fits than single variable prediction models (all P < 0.05), and ANN model 1 had the best predictive performance among all models. CONCLUSIONS Machine learning models assist clinicians in predicting endotypes of nasal polyps before invasive detection. The ANN model has the potential to predict eCRSwNP with high sensitivity and specificity, and is superior to the LR model. ANNs are valuable for optimizing personalized patient management.
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Affiliation(s)
- Huiqin Zhou
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.,Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Wenjun Fan
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.,Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Danxue Qin
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.,Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Peiqiang Liu
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.,Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ziang Gao
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.,Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Hao Lv
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.,Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Wei Zhang
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.,Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Rong Xiang
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.,Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yu Xu
- Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.,Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China
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27
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Guthikonda MR, Gude A, Nutakki A. Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis with Nasal Polyps and Their Clinical Comparison in Indian Population. Indian J Otolaryngol Head Neck Surg 2022; 74:994-1000. [PMID: 36452721 PMCID: PMC9701980 DOI: 10.1007/s12070-020-02062-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 08/12/2020] [Indexed: 11/29/2022] Open
Abstract
Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) and non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP) are two distinct endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of the study was to find the prevalence of eCRSwNP and neCRSwNP, their clinical comparison and to establish predictive values for clinical and diagnostic factors to differentiate between eCRSwNP and neCRSwNP in Indian population with CRSwNP. This study was a prospective cohort, multi- institutional study. A total of 162 patients who were diagnosed with nasal polyps at different military hospitals in India during the period from 2011 to 2020 were selected for study. They were diagnosed in accordance with EPOS guidelines. They were randomly divided into two groups as eCRSwNP and neCRSwNP based on the response to oral corticosteroids for 2 weeks duration and the prevalence of eCRSwNP was established. Blood samples were collected and endoscopic sinus surgery was performed in all patients after atleast 2 months of last steroid dose. Preop CT scan scores, preop nasal endoscopy scores, preop blood eosinophil counts, preop tissue eosinophil counts were compared between the groups. Postop followup was done at 6 months by comparing CT scan scores and nasal endoscopy scores. Predictive values for clinical and diagnostic factors were established to diagnose eCRSwNP in Indian population. Out of a total 162 patients, 121 (74.6%) patients were classified into eCRSwNP and 41 (23.6%) into neCRSwNP out of a total of 162 patients with CRSwNP. CRSwNP was seen in the 4th decade. eCRSwNP was seen in the later part and neCRSwNP was seen in the early part. eCRSwNP was more common in males and neCRSwNP was more common in females. Smoking, asthma and aspirin intolerance were more commonly seen in eCRSwNP than neCRSwNP, p < 0.001, p = 0.020 respectively. Preop total CT scan score, preop bood absolute eosinophil count,preop blood eosinophil percentage, tissue eosinophil percentage, postop nasal endoscopy score, postop CT scan score were stastically significant in eCRSwNP, p < 0.001 except preop total nasal endoscopic score. Tissue absolute eosinophil count had best predictive accuracy plotted with receiver operating characteristic (ROC) curve analysis, area under curve (AUC) 0.923(95% CI, 0.876-0.970). The cutoff points determined to diagnose eCRSwNP were ≥ 15 for preop total CT scan score, ≥ 378 × 106/L for preop absolute blood eosinophil count, ≥ 6.5% for preop blood eosinophil percentage, ≥ 14% for tissue eosinophil percentage, ≥ 16 for absolute tissue eosinophil count, ≥ 1 for 6 months postop total nasal endoscopy score, ≥ 2 for 6 months postop total CT scan score. eCRSwNP and neCRSwNP are two distinct endotypes of nasal polyps present in Indian population with CRSwNP. Two thirds of the patients with nasal polyps were eCRSwNP and the prevalence in Indian population is more than the East Asian population but less than the Western population. There is a high chance of recurrence and treatment failures for eCRSwNP than neCRSwNP. The cutoff points for various non invasive diagnostic predictors are useful to diagnose the patients with eCRSwNP during the outpatient visits and hence plan for better treatment strategies.
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Affiliation(s)
- Mohan Raghav Guthikonda
- Present Address: 166 Military Hospital, Satwari Cantonment, Jammu, Jammu and Kashmir 180003 India
| | - Aswini Gude
- Department of Pathology, Gayatri Institute of Health Care and Medical Technology, GVP Medical College, Maridi Valley, Marikavalasa, Visakhapatnam, Andhra Pradesh 530048 India
| | - Aditya Nutakki
- Department of Radiology, Gayatri Institute of Health Care and Medical Technology, GVP Medical College, Maridi Valley, Marikavalasa, Visakhapatnam, Andhra Pradesh 530048 India
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De Corso E, Baroni S, Settimi S, Onori ME, Mastrapasqua RF, Troiani E, Moretti G, Lucchetti D, Corbò M, Montuori C, Cantiani A, Porru DP, Lo Verde S, Di Bella GA, Caruso C, Galli J. Sinonasal Biomarkers Defining Type 2-High and Type 2-Low Inflammation in Chronic Rhinosinusitis with Nasal Polyps. J Pers Med 2022; 12:jpm12081251. [PMID: 36013200 PMCID: PMC9410079 DOI: 10.3390/jpm12081251] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/24/2022] [Accepted: 07/25/2022] [Indexed: 11/16/2022] Open
Abstract
The complex pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP) generates a spectrum of phenotypes with a wide variety of inflammatory states. We enrolled 44 very-likely-to-be type 2 CRSwNP patients in order to evaluate the load of inflammation and to analyze human interleukins in nasal secretion. Clinical data were collected to evaluate the severity of the disease. High levels of IL-5, IL-4, IL-6, and IL-33 were detected in all type 2 CRSwNP patients. By analyzing type 2 cytokine profiles and local eosinophil count, we identified two coherent clusters: the first was characterized by high levels of IL-4, IL-5, IL-6, and a high-grade eosinophil count (type 2-high); the second had lower levels of cytokines and poor or absent eosinophilic inflammation (type-2 low). IL-5 levels were significantly higher within the type 2 cytokine and it was the most reliable biomarker for differentiating the two clusters. In type 2-high inflammatory profile clinical scores, the mean number of previous surgeries and need for systemic corticosteroids were significantly higher compared to type 2-low. Our research demonstrated the potential role of type 2 biomarkers, and in particular, of IL-5 in identifying patients with a more severe phenotype based on a high inflammatory load.
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Affiliation(s)
- Eugenio De Corso
- Unit of Otorhinolaryngology and Head-Neck Surgery, Fondazione Policlinico A. Gemelli IRCCS, 00168 Rome, Italy; (E.D.C.); (J.G.)
| | - Silvia Baroni
- Unit of Chemistry, Biochemistry and Molecular Biology, Fondazione Policlinico A. Gemelli IRCCS, 00168 Rome, Italy;
- Department of Basic Biotechnological Sciences, Intensive Care and Perioperative Clinics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.E.O.); (E.T.); (G.M.)
| | - Stefano Settimi
- Unit of Otorhinolaryngology and Head-Neck Surgery, Fondazione Policlinico A. Gemelli IRCCS, 00168 Rome, Italy; (E.D.C.); (J.G.)
- Department of Head-Neck and Sensory Organs, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (R.F.M.); (M.C.); (C.M.); (A.C.); (D.P.P.); (S.L.V.); (G.A.D.B.)
- Correspondence: ; Tel.: +39-0630154439
| | - Maria Elisabetta Onori
- Department of Basic Biotechnological Sciences, Intensive Care and Perioperative Clinics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.E.O.); (E.T.); (G.M.)
| | - Rodolfo Francesco Mastrapasqua
- Department of Head-Neck and Sensory Organs, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (R.F.M.); (M.C.); (C.M.); (A.C.); (D.P.P.); (S.L.V.); (G.A.D.B.)
| | - Eliana Troiani
- Department of Basic Biotechnological Sciences, Intensive Care and Perioperative Clinics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.E.O.); (E.T.); (G.M.)
| | - Giacomo Moretti
- Department of Basic Biotechnological Sciences, Intensive Care and Perioperative Clinics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (M.E.O.); (E.T.); (G.M.)
| | - Donatella Lucchetti
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy;
| | - Marco Corbò
- Department of Head-Neck and Sensory Organs, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (R.F.M.); (M.C.); (C.M.); (A.C.); (D.P.P.); (S.L.V.); (G.A.D.B.)
| | - Claudio Montuori
- Department of Head-Neck and Sensory Organs, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (R.F.M.); (M.C.); (C.M.); (A.C.); (D.P.P.); (S.L.V.); (G.A.D.B.)
| | - Alessandro Cantiani
- Department of Head-Neck and Sensory Organs, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (R.F.M.); (M.C.); (C.M.); (A.C.); (D.P.P.); (S.L.V.); (G.A.D.B.)
| | - Davide Paolo Porru
- Department of Head-Neck and Sensory Organs, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (R.F.M.); (M.C.); (C.M.); (A.C.); (D.P.P.); (S.L.V.); (G.A.D.B.)
| | - Simone Lo Verde
- Department of Head-Neck and Sensory Organs, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (R.F.M.); (M.C.); (C.M.); (A.C.); (D.P.P.); (S.L.V.); (G.A.D.B.)
| | - Giuseppe Alberto Di Bella
- Department of Head-Neck and Sensory Organs, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (R.F.M.); (M.C.); (C.M.); (A.C.); (D.P.P.); (S.L.V.); (G.A.D.B.)
| | - Cristiano Caruso
- Department of Medical and Surgical Sciences, Digestive Disease Center, Fondazione Policlinico A. Gemelli IRCCS, 00168 Rome, Italy;
| | - Jacopo Galli
- Unit of Otorhinolaryngology and Head-Neck Surgery, Fondazione Policlinico A. Gemelli IRCCS, 00168 Rome, Italy; (E.D.C.); (J.G.)
- Department of Head-Neck and Sensory Organs, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (R.F.M.); (M.C.); (C.M.); (A.C.); (D.P.P.); (S.L.V.); (G.A.D.B.)
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Predictive Values of Serum IL-33 and sST2 in Endotypes and Postoperative Recurrence of Chronic Rhinosinusitis with Nasal Polyps. Mediators Inflamm 2022; 2022:9155080. [PMID: 35633657 PMCID: PMC9135518 DOI: 10.1155/2022/9155080] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/26/2022] [Accepted: 04/29/2022] [Indexed: 11/18/2022] Open
Abstract
Background. Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disease with high heterogeneity and postoperative recidivation. The IL-33/ST2 axis is known to be involved in Th2 immune responses. This study is aimed at exploring levels of serum IL-33 and soluble ST2 (sST2) in CRSwNP patients and their potential for predicting CRSwNP endotypes and postoperative recurrence. Methods. The present study recruited 149 CRSwNP patients, 80 of whom were noneosinophilic (neCRSwNP) and 69 eosinophilic (eCRSwNP), as well as 60 healthy controls (HCs). Serum samples were collected from all participants, and sST2 and IL-33 concentrations were measured using ELISA. Multivariate analysis, receiver operating characteristic (ROC) curves, and Kaplan-Meier curves were used to evaluate the value of serum sST2 and IL-33 levels in distinguishing CRSwNP endotypes and predicting postoperative recurrence. Results. The levels of serum sST2 and IL-33 in CRSwNP patients were significantly higher than those in HCs, especially in the eCRSwNP group. Increased sST2 and IL-33 levels were associated with eosinophil counts and percentages in both tissue and blood. Multivariate regression and ROC curve analysis showed that serum sST2 and IL-33 exhibited potential for distinguishing CRSwNP endotypes, and the combination of serum IL-33 and sST2 showed even more predictive power. Finally, 124 CRSwNP patients completed the entire 3-year follow-up. Multivariate analysis and Kaplan-Meier curves showed that serum sST2 and IL-33 levels were associated with recurrence; serum sST2 and IL-33 each exhibited potential for predicting postoperative recurrence, and combining serum sST2 and IL-33 exhibited better accuracy and practicability. Conclusion. Our results suggested that serum sST2 and IL-33 levels were upregulated in CRSwNP patients and related to the degree of mucosal eosinophil infiltration and postoperative recurrence. Serum sST2 and IL-33 might serve as objective biomarkers for distinguishing phenotypes and predicting recurrence in CRSwNP, and their combined use outperformed either marker alone.
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Merrill T, Kanaan A. Managing Chronic Rhinosinusitis with Nasal Polyps in the Elderly: Challenges and Solutions. Clin Interv Aging 2022; 17:685-698. [PMID: 35535364 PMCID: PMC9077011 DOI: 10.2147/cia.s279765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 04/20/2022] [Indexed: 11/23/2022] Open
Abstract
The proportion of the population over 65 years old continues to grow. Chronic rhinosinusitis is common in this population and causes a reduction in quality of life and an increase in health care utilization. Diagnosis of chronic rhinosinusitis with nasal polyps follows the same principles for elderly patients as in the general population, but the elderly population presents some diagnostic challenges worth considering. Presbynasalis, the anatomic and functional changes of the nose and paranasal sinuses associated with aging must be accounted for when caring for these patients. In addition, polypharmacy and other medical issues that can cause similar symptoms must be considered. Medical therapy is generally similar to the general population but with additional concerns given the propensity for geriatric patients to be on multiple medications and to suffer from multiple medical issues. Sinus surgery should be considered following the same indications as in the general population. While some authors have found higher complication rates in endoscopic sinus surgery, others have found higher rates of success. As always, the risks of surgery must be considered with the possible benefits on a patient-to-patient basis.
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Affiliation(s)
- Tyler Merrill
- University of Arkansas for Medical Sciences, Department of Otolaryngology – Head and Neck Surgery, Little Rock, AR, USA
- Correspondence: Tyler Merrill, University of Arkansas for Medical Sciences, Department of Otolaryngology – Head and Neck Surgery, 4301 W. Markham Street, #543, Little Rock, AR, 72205, USA, Tel +1 (501) 686 5140; +1 (330) 285 1750, Fax +1 (501) 686 8029, Email
| | - Alissa Kanaan
- University of Arkansas for Medical Sciences, Department of Otolaryngology – Head and Neck Surgery, Little Rock, AR, USA
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Kim DH, Kim SW, Basurrah MA, Hwang SH. Clinical and laboratory features for various criteria of eosinophilic chronic rhinosinusitis: a systematic review and meta-analysis. Clin Exp Otorhinolaryngol 2022; 15:230-246. [PMID: 35413170 PMCID: PMC9441508 DOI: 10.21053/ceo.2022.00052] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 02/11/2022] [Indexed: 11/22/2022] Open
Abstract
Objectives: To evaluate the differences in clinical and laboratory features between eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS and to compare the diagnostic criteria for ECRS.Methods: We compared clinical features and/or laboratory findings classified as ECRS and non-ECRS according to various diagnostic criteria (histological and clinical criteria). In addition, we analyzed studies to compare endoscopic findings, symptom scores, laboratory findings, and computed tomography (CT) findings between ECRS and non-ECRS. Results: Our search included 55 studies with 6,143 patients. As a result of comparing clinical features and/or laboratory criteria with histological criteria, there were no significant differences regarding nasal symptom scores and CT scores according to criteria. Serum eosinophil levels showed differences according to criteria, however, ECRS were higher serum eosinophil levels than non-ECRS in all criteria. In the case of olfactory dysfunction, JESREC and tissue eosinophilia (
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Li K, Liu F. Analysis of competing endogenous RNA (ceRNA) crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol 2022; 12:1468-1479. [PMID: 35385217 PMCID: PMC10084371 DOI: 10.1002/alr.23008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/11/2022] [Accepted: 04/01/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the most common chronic inflammatory diseases, and has various phenotypes. Although its pathophysiology remains obscure, evidence has shown that dysregulation of noncoding RNAs (ncRNAs) is associated with CRSwNP. ncRNAs in the cytoplasm can act as competing endogenous RNAs (ceRNAs), which are involved in many inflammatory processes. However, the ceRNA crosstalk in CRSwNP is still unclear METHODS: We investigated expression profiles of messenger RNA (mRNA), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) in eosinophilic CRSwNP and constructed a global triple ceRNA network. RESULTS As a result, 964 differentially expressed mRNAs (DEmRs), 207 differentially expressed miRNAs (DEmiRs), and 15 differentially expressed lncRNAs (DElncRs) were identified, and a ceRNA network containing 598 miRNA-mRNA pairs and 70 lncRNA-miRNA pairs was finally constructed. Gene set enrichment analysis (GSEA) results indicated these DEmRs were mainly enriched in "cytokine-cytokine receptor interaction," "salivary secretion," "hematopoietic cell lineage," and "chemokine signaling pathway." Moreover, we also predicted the subcellular localization of the DElncRs identified in the network via bioinformatics approaches CONCLUSION: In summary, the present study provided the first comprehensive assessment of the ceRNA crosstalk in eosinophilic CRSwNP. These findings will be of interest to the understanding of the potential pathophysiology of this disease.
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Affiliation(s)
- Ke Li
- Department of Blood TransfusionTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Fang‐Fang Liu
- Department of PathologyThe Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
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Pavord ID, Bel EH, Bourdin A, Chan R, Han JK, Keene ON, Liu MC, Martin N, Papi A, Roufosse F, Steinfeld J, Wechsler ME, Yancey SW. From DREAM to REALITI-A and beyond: Mepolizumab for the treatment of eosinophil-driven diseases. Allergy 2022; 77:778-797. [PMID: 34402066 PMCID: PMC9293125 DOI: 10.1111/all.15056] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 08/13/2021] [Indexed: 12/11/2022]
Abstract
Effective treatment of inflammatory diseases is often challenging owing to their heterogeneous pathophysiology. Understanding of the underlying disease mechanisms is improving and it is now clear that eosinophils play a complex pathophysiological role in a broad range of type 2 inflammatory diseases. Standard of care for these conditions often still includes oral corticosteroids (OCS) and/or cytotoxic immune therapies, which are associated with debilitating side effects. Selective, biological eosinophil‐reducing agents provide treatment options that improve clinical symptoms associated with eosinophilic inflammation and reduce OCS use. Mepolizumab is a humanized monoclonal antibody that binds to and neutralizes interleukin‐5, the major cytokine involved in eosinophil proliferation, activation, and survival. Mepolizumab is approved for the treatment of severe eosinophilic asthma, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Additionally, the efficacy of add‐on mepolizumab has been observed in patients with severe chronic rhinosinusitis with nasal polyposis and chronic obstructive pulmonary disease with an eosinophilic phenotype. Here, we review the development, approval, and real‐world effectiveness of mepolizumab for the treatment of patients with severe eosinophilic asthma, from the DREAM to REALITI‐A studies, and describe how knowledge from this journey extended to the use of mepolizumab and other biologics across a broad spectrum of eosinophilic diseases.
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Affiliation(s)
- Ian D. Pavord
- Nuffield Department of Medicine and Oxford Respiratory NIHR BRC University of Oxford Oxford UK
| | - Elisabeth H. Bel
- Department of Respiratory Medicine Amsterdam UMC University of Amsterdam Amsterdam The Netherlands
| | - Arnaud Bourdin
- INSERM 12 F‐CRIN Clinical Research Initiative In Severe Asthma: a Lever for Innovation & Science (CRISALIS) France
- Service de Pneumologie and INSERM CNRS CHU Montpellier Université de Montpellier Montpellier France
| | | | - Joseph K. Han
- Department of Otolaryngology, Head & Neck Surgery Eastern Virginia Medical School Norfolk Virginia USA
| | | | - Mark C. Liu
- Divisions of Allergy and Clinical Immunology, Pulmonary and Critical Care Medicine Johns Hopkins Asthma and Allergy Center Baltimore MD USA
| | - Neil Martin
- Global Medical Affairs GSK Brentford UK
- Institute for Lung Health University of Leicester Leicester UK
| | - Alberto Papi
- Research Center on Asthma and COPD University of Ferrara Ferrara Italy
| | - Florence Roufosse
- Department of Internal Medicine Hôpital Erasme Université Libre de Bruxelles Brussels Belgium
| | | | - Michael E. Wechsler
- Department of Medicine National Jewish Health Cohen Family Asthma Institute Denver CO USA
| | - Steven W. Yancey
- Respiratory Therapeutic Area Unit GSK Research Triangle Park NC USA
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Ma L, Shi J, Wang K, Sun Y, Xu R. Clinical characteristics of patients with CRSwNP with intensely high eosinophil level. Laryngoscope Investig Otolaryngol 2022; 7:316-324. [PMID: 35434319 PMCID: PMC9008161 DOI: 10.1002/lio2.758] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 01/02/2022] [Accepted: 01/17/2022] [Indexed: 11/18/2022] Open
Abstract
Background High tissue and blood eosinophils are linked to poor treatment outcome in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, the difference between the patients with different level of blood or tissue eosinophilia in relation to disease control is still lacking. Objectives This study aimed to characterize patients with CRSwNP with intensely high eosinophil level. Methods A retrospective study of CRSwNP patients underwent endoscopic sinus surgery was conducted. The patients were subdivided with various cut‐off values of blood and tissue eosinophils. Tissue eosinophils of ≥50% and 10%–20% were defined as intensely high tissue eosinophils (IH‐tissue‐eos) and high tissue eosinophils (H‐tissue‐eos), respectively. Blood eosinophils of ≥0.6 × 109/L and 0.2 × 109/L–0.3 × 109/L were defined as intensely high blood eosinophils (IH‐blood‐eos) and high blood eosinophils (H‐blood‐eos). Clinical characteristics, Lund‐Mackay score (LMS), and disease control status were compared between subgroups. Results A total of 302 patients were enrolled. There was a trend toward a higher rate of uncontrolled disease when the patients subdivided by blood eosinophil cut‐off values ranged from 0.1 × 109/L to 0.6 × 109/L. The controlled patients accounted for 27%, 36%, 22%, and 31%, and the uncontrolled patients 46%, 32%, 52%, and 31% of patients in IH‐tissue‐eos, H‐tissue‐eos, IH‐blood‐eos, and H‐blood‐eos subgroup, respectively. The percentages of patients in the three categories of control were not significantly different between IH‐tissue‐eos and H‐tissue‐eos subgroups. By contrast, the IH‐blood‐eos subgroup had higher percentages of current smoker and asthma, preoperative LMS and tissue eosinophil percentage, and showed a trend toward a higher rate of uncontrolled subjects compare with the H‐blood‐eos subgroup. Conclusion CRSwNP patients with IH‐blood‐eos (≥0.6 × 109/L) may be possibly associated with a poorer disease control than those with levels near the threshold of blood eosinophilia (0.2 × 109/L–0.3 × 109/L). Further larger, preferably prospective studies are needed to confirm this relationship. Level of Evidence: 4.
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Affiliation(s)
- Ling Ma
- Jinan University Guangzhou China
- Department of Otorhinolaryngology The University of Hong Kong‐Shenzhen Hospital Shenzhen China
| | - Jianbo Shi
- Department of Otolaryngology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou China
| | - Kanghua Wang
- Department of Otolaryngology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou China
| | - Yueqi Sun
- Department of Otolaryngology The Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen China
| | - Rui Xu
- Department of Otolaryngology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou China
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Guo CL, Wang CS, Liu Z. Clinical and biological markers in disease and biologics to treat chronic rhinosinusitis. Curr Opin Allergy Clin Immunol 2022; 22:16-23. [PMID: 34789677 DOI: 10.1097/aci.0000000000000799] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Chronic rhinosinusitis (CRS) is a heterogeneous disorder with diverse responses to conventional anti-inflammatory medical and surgical treatments. Even for the newly developed mAbs targeting type 2 (T2) reaction, a considerable number of patients with CRS with nasal polyps (CRSwNP) exhibited unsatisfying response. Identifying patients with a tendency to poor prognosis is critical for selecting targeted therapies to improve the treatment outcome. This review focuses on clinical and biological markers associated with prognosis of CRS patients under conventional medical and surgical treatments and provides an update summary of potential markers for T2 biologics. RECENT FINDINGS Allergic rhinitis, asthma, prior sinus surgery, nasal polyps, tissue eosinophilia and neutrophilia, blood eosinophilia and high levels of Charcot-Leyden crystal, cystatin SN, chemokine (C-C motif) ligand 17, macrophage inflammatory protein-1β and interleukin (IL)-5 in nasal secretions have been associated with poor prognosis in CRS patients under conventional medical and surgical treatments. Blood eosinophil level might be a biomarker for anti-IL-5 (mepolizumab) and anti-IL-5R (benralizumab) biologic in patients with refractory CRSwNP. SUMMARY Several clinical and biological markers have been associated with poor response to conventional treatments in CRS patients; however, majority of them should be verified by large-scale multicentre studies. More efforts are needed to identify biomarkers for biologics.
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Affiliation(s)
- Cui-Lian Guo
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
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Imoto Y, Ueki S, Kato Y, Yoshida K, Morikawa T, Kimura Y, Kidoguchi M, Tsutsumiuchi T, Koyama K, Adachi N, Ito Y, Ogi K, Sakashita M, Yamada T, Schleimer RP, Takabayashi T, Fujieda S. Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis. Front Pharmacol 2022; 12:793607. [PMID: 35046816 PMCID: PMC8762296 DOI: 10.3389/fphar.2021.793607] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 11/26/2021] [Indexed: 12/02/2022] Open
Abstract
Background: Eosinophilic chronic sinusitis (ECRS) is a subtype of CRS with nasal polyps (CRSwNP) that is frequently comorbid with asthma. Notably, ECRS patients often show a high recurrence of NPs after surgical resection. Leptin is a hormone produced by adipocytes that has been implicated in airway inflammatory diseases. However, to date, the role of leptin in ECRS has not been investigated. Objective: To determine whether the serum levels of leptin are altered in patients with ECRS. Methods: In total, 40 patients with ECRS, 15 patients with non-eosinophilic CRS (non-ECRS), and 12 individuals without CRS (control) were included in this study. Patient's serum leptin levels were assessed, and the number of eosinophils in their NPs were measured through a histological evaluation of the three densest areas with cellular infiltrate beneath the epithelial surface. Finally, nasal fibroblast cultures established from NPs were stimulated with varying concentrations of recombinant leptin in vitro to determine whether leptin affects eotaxin-3 (Chemokine (C-C motif) ligand 26 :26: CCL26) expression. Results: The serum leptin levels in both the ECRS and non-ECRS groups were significantly higher than those in the control subjects (p < 0.0001 vs. ECRS; p < 0.05 vs. non-ECRS). Furthermore, ECRS patients displayed significantly elevated serum leptin levels compared to non-ECRS patients (p < 0.001), although there was no difference in body mass index between the groups. Notably, serum leptin levels were correlated with the proportion of eosinophils in peripheral blood (r = 0.3575, p < 0.01) and the number of eosinophils in NPs (r = 0.5109, p < 0.0001). Serum leptin levels were also correlated with eotaxin-3 mRNA expression in NPs (r = 0.5374, p < 0.01). Finally, leptin significantly augmented eotaxin-3 expression in nasal fibroblasts established in vitro from NPs in a leptin receptor-dependent manner (p < 0.05). Conclusion: Leptin levels are elevated in ECRS patients and may both promote and indicate the severity of ECRS as well as systemic type 2-biased inflammatory responses. Combined, these data indicate that circulating leptin may play a significant role in the development of eosinophilic inflammation in NPs.
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Affiliation(s)
- Yoshimasa Imoto
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Shigeharu Ueki
- Department of General Internal Medicine and Clinical Laboratory Medicine, Akita University Graduate School of Medicine, Akita, Japan
| | - Yukinori Kato
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Kanako Yoshida
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Taiyo Morikawa
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yukihiro Kimura
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Masanori Kidoguchi
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Toshiki Tsutsumiuchi
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Keisuke Koyama
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Naoto Adachi
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yumi Ito
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Kazuhiro Ogi
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Masafumi Sakashita
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Takechiyo Yamada
- Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Akita University, Akita, Japan
| | - Robert P. Schleimer
- Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
| | - Tetsuji Takabayashi
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Shigeharu Fujieda
- Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
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Fujieda S, Matsune S, Takeno S, Ohta N, Asako M, Bachert C, Inoue T, Takahashi Y, Fujita H, Deniz Y, Rowe P, Ortiz B, Li Y, Mannent LP. Dupilumab efficacy in chronic rhinosinusitis with nasal polyps from SINUS-52 is unaffected by eosinophilic status. Allergy 2022; 77:186-196. [PMID: 33993501 PMCID: PMC9290136 DOI: 10.1111/all.14906] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 04/16/2021] [Accepted: 05/05/2021] [Indexed: 12/18/2022]
Abstract
Background The human monoclonal antibody dupilumab blocks interleukin (IL)‐4 andIL‐13, key and central drivers of type 2 inflammation. Dupilumab, on background mometasone furoate nasal spray (MFNS), improved outcomes in the phase III SINUS‐52 study (NCT02898454) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). This posthoc analysis of SINUS‐52 examined whether eosinophilic status of CRSwNP was a predictor of dupilumab efficacy. Methods Patients were randomized 1:1:1 to dupilumab 300 mg every 2 weeks (q2w) until week 52; dupilumab 300 mg q2w until Week 24, then 300 mg every 4 weeks until week 52; or placebo (MFNS) until week 52. Coprimary endpoints were change from baseline in nasal polyps score (NPS), nasal congestion (NC), and Lund‐Mackay score assessed by CT (LMK‐CT) at week 24. Patients (n = 438) were stratified by eosinophilic chronic rhinosinusitis (ECRS) status according to the Japanese Epidemiological Survey of Refractory Eosinophilic Rhinosinusitis algorithm. Results Dupilumab significantly improved NPS, NC, and LMK‐CT scores versus placebo at week 24 in all ECRS subgroups (p < 0.001), with improvements maintained or increased at week 52 (p < 0.001). There was no significant interaction between ECRS subgroup (non‐/mild or moderate/severe) and dupilumab treatment effect for all endpoints at weeks 24 and 52 (p > 0.05), except LMK‐CT at week 24 (p = 0.0275). Similar results were seen for the secondary endpoints. Dupilumab was well tolerated across all ECRS subgroups. Conclusion Dupilumab produced consistent improvement in symptoms of severe CRSwNP irrespective of ECRS status. Therefore, blood eosinophil level may not be a suitable biomarker for dupilumab efficacy in CRSwNP.
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Affiliation(s)
| | - Shoji Matsune
- Nippon Medical School Musashi Kosugi Hospital Kanagawa Japan
| | - Sachio Takeno
- Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan
| | - Nobuo Ohta
- Department of Otolaryngology Tohoku Medical and Pharmaceutical University Sendai Japan
| | - Mikiya Asako
- Department of Otolaryngology Kansai Medical University Osaka Japan
| | - Claus Bachert
- Department of Ear, Nose, and Throat Science Ghent University Ghent Belgium
- Department of Clinical Science, Intervention and Technology Karolinska Institutet Stockholm Sweden
| | | | | | | | - Yamo Deniz
- Regeneron Pharmaceuticals, Inc. Tarrytown NY USA
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Yao Y, Zeng M, Liu Z. Revisiting Asian chronic rhinosinusitis in the era of type 2 biologics. Clin Exp Allergy 2021; 52:231-243. [PMID: 34854144 DOI: 10.1111/cea.14065] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 11/25/2021] [Accepted: 11/27/2021] [Indexed: 01/08/2023]
Abstract
Chronic rhinosinusitis (CRS) is a highly heterogeneous disorder exhibiting considerable epidemiological, clinical and immunopathological variations across patients with distinct ethnic backgrounds and in different geographic locations. Asian CRS patients present less eosinophilic and type 2 (T2) inflammation, but more prominent neutrophilic inflammation compared with patients in Western countries. Although several biologics targeting important elements of T2 inflammation, such as IL-4, IL-5, IL-13 and IgE, demonstrate promising benefit for Caucasian patients with recurrent nasal polyps, their efficacy in Asian patients remains poorly defined. The distinct endotypes in Asian patients warrant the identification and selection of patients who would benefit from T2 biologics in Asian countries. Additionally, developing novel treatments targeting neutrophilic, type 1, and type 3 inflammation may benefit approximately 50% of Asian CRS patients with non-T2 inflammation. In this review, we summarized and discussed recent progress in the study of Asian CRS endotypes in comparison with those in patients in Western countries, and the methods of identifying Asian patients with eosinophilic or T2 inflammation. T2 biologic treatment of Asian CRS patients, potential therapeutic candidates targeting non-T2 inflammation in Asian CRS patients and the progress on developing other T2 biologics were discussed.
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Affiliation(s)
- Yin Yao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ming Zeng
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Wen S, Cheng S, Xie S, Zhang H, Xie Z, Jiang W. Serum YKL-40 Levels Predict Endotypes and Associate with Postoperative Recurrence in Patients with Chronic Rhinosinusitis with Nasal Polyps. J Asthma Allergy 2021; 14:1295-1306. [PMID: 34744439 PMCID: PMC8565991 DOI: 10.2147/jaa.s335964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 10/08/2021] [Indexed: 12/02/2022] Open
Abstract
Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a global health concern with high heterogeneity and rate of postoperative recidivation. YKL-40 is a pivotal pro-inflammatory mediator to promote Th2 immune response which is involved in many inflammatory diseases. This study aimed to investigate the predictive value of serum YKL-40 in CRSwNP endotypes and postoperative recurrence. Methods We recruited 80 primary CRSwNP, 40 recurrent CRSwNP patients and 40 healthy controls (HCs) in this study, and the serum and tissue specimens were collected. The middle turbinate mucosa tissue collected from patients undergoing septoplasty was used as control. Serum YKL-40 concentrations were detected by enzyme-linked immunosorbent assay (ELISA), and tissue YKL-40 mRNA and protein levels were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The difference of YKL-40 expression was compared among different group. Multivariate analysis and receiver operating characteristic (ROC) curve were performed to evaluate the value of serum YKL-40 in discriminating eosinophilic CRSwNP (eCRSwNP) and predicting postoperative recurrence. Results The serum YKL-40 levels in CRSwNP patients were higher than HCs, especially in eCRSwNP patients (p < 0.05). The elevated YKL-40 levels positively correlated with blood eosinophil percentage, tissue eosinophil counts and percentages (p < 0.05). The serum YKL-40 levels in recurrent CRSwNP patients were markedly enhanced than primary CRSwNP patients (p < 0.05). The YKL-40 mRNA and protein levels were significantly elevated in CRSwNP patients compared to HCs, especially in eCRSwNP and recurrent CRSwNP group. Multivariate analysis and ROC curve exhibited that serum YKL-40 might be a promising indicator in distinguishing CRSwNP endotypes and predicting postoperative recurrence. Conclusion Our data suggested that YKL-40 might be unregulated in CRSwNP and associated with mucosal eosinophilia and recurrence. Serum YKL-40 appeared to a novel biomarker for predicting CRSwNP endotypes and postoperative recurrence of CRSwNP.
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Affiliation(s)
- Sihui Wen
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University & Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, 410008, People's Republic of China
| | - Shenghao Cheng
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University & Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, 410008, People's Republic of China
| | - Shaobing Xie
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University & Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, 410008, People's Republic of China
| | - Hua Zhang
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University & Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, 410008, People's Republic of China
| | - Zhihai Xie
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University & Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, 410008, People's Republic of China
| | - Weihong Jiang
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University & Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, 410008, People's Republic of China
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Yu L, Jiang Y, Yan B, Fang G, Wang C, Zhang L. Predictive value of clinical characteristics in eosinophilic chronic rhinosinusitis with nasal polyps: A cross-sectional study in the Chinese population. Int Forum Allergy Rhinol 2021; 12:726-734. [PMID: 34569170 DOI: 10.1002/alr.22901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 08/16/2021] [Accepted: 08/23/2021] [Indexed: 11/08/2022]
Abstract
BACKGROUND Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a refractory subtype of chronic rhinosinusitis with nasal polyps (CRSwNP), with clinical characteristics differing from those of non-ECRSwNP. We aimed to explore the predictive value of clinical characteristics, including medical history, symptoms, and signs, prior to ECRSwNP diagnosis, and to develop a nomogram for use in clinical practice. METHODS A total of 502 patients with CRSwNP were enrolled. Based on the degree of eosinophilic infiltration in nasal polyps (NPs), patients were classified as ECRSwNP or non-ECRSwNP group. Participants' demographic characteristics, asthma history, severity of nasal symptoms (nasal obstruction, rhinorrhea, hyposmia, and facial pain/headache) according to the visual analog scale, and nasal polyp scores based on polyp scoring system were recorded. Logistic regression analysis was performed to screen for independent risk factors, and a model nomogram was constructed. RESULTS The percentage of asthmatic patients and the hyposmia, rhinorrhea, and total nasal symptom scores were significantly higher in ECRSwNP patients than that in non-ECRSwNP patients. The nasal polyp score was lower in the eosinophilic group than that in the non-eosinophilic group. Logistic regression analysis revealed that asthma history and hyposmia, rhinorrhea and nasal polyp scores were independent predictors of ECRSwNP. A nomogram consisting of these four independent risk factors was constructed, and its C-index was 0.808 (95% CI, 0.771 to 0.846). CONCLUSIONS The nomogram based on asthma history and olfactory, rhinorrhea, and nasal polyp scores could help predict ECRSwNP, providing a simple, fast, and practical way to distinguish ECRSwNP from non-ECRSwNP cases in clinical practice.
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Affiliation(s)
- Longgang Yu
- Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.,Department of Otolaryngology, Head and Neck Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yan Jiang
- Department of Otolaryngology, Head and Neck Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China
| | - Bing Yan
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Gaoli Fang
- Department of Otolaryngology, Head and Neck Surgery, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Chengshuo Wang
- Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Luo Zhang
- Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China.,Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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Efficacy of triamcinolone acetonide-impregnated Gelfoam nasal pack in management of chronic sinusitis with nasal polyps following endoscopic sinus surgery: a perfectly matched, placebo-controlled trial study. Eur Arch Otorhinolaryngol 2021; 279:2915-2924. [PMID: 34559269 DOI: 10.1007/s00405-021-07071-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 09/05/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE This perfectly matched, double-blinded, placebo-controlled trial study was performed to investigate the efficacy of triamcinolone acetonide (TAA)-impregnated Gelfoam nasal pack in management of different endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) following endoscopic sinus surgery (ESS). METHODS One hundred and four patients with bilateral CRSwNP undergoing ESS were selected and randomized to receive TAA-soaked nasal packing in one nostril and saline-impregnated dressing contra-laterally. Validated Perioperative Sinus Endoscopy (POSE) scoring system was used to assess the participants' condition at postoperative months 1, 3, 6, 12, and 18. RESULTS The treatment side of eosinophilic CRSwNP (EosCRSwNP) group had significantly better endoscopic scores than the contralateral control side in all follow-up visits (P < 0.05 for all comparisons) except for the first postoperative month. No significant difference was detected between the TAA- and saline-treated nostrils in the non-eosinophilic CRSwNP (nonEosCRSwNP) subgroup during the follow-up period. Intergroup comparisons revealed a borderline better POSE score for the treatment side of the EosCRSwNP group compared with the treatment nostril of the nonEosCRSwNP group at months 12 (P = 0.041) and 18 (P = 0.044). At the end of the study period, the treatment side of the EosCRSwNP group demonstrated better clinical response than the saline-treated side in terms of the total POSE scores (P = 0.019), middle turbinate synechia (P = 0.008), middle meatal narrowing (P = 0.010), ethmoid polypoid changes (P = 0.039), ethmoid polyposis (P = 0.027), ethmoid cavity secretions (P = 0.042), and sphenoid severity (P = 0.018). CONCLUSION TAA-soaked Gelfoam dressing following bilateral ESS was found to be an effective method for treating CRSwNP particularly for the eosinophilic endotype of the disease.
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Damask C, Chen M, Holweg CTJ, Yoo B, Millette LA, Franzese C. Defining the Efficacy of Omalizumab in Nasal Polyposis: A POLYP 1 and POLYP 2 Subgroup Analysis. Am J Rhinol Allergy 2021; 36:135-141. [PMID: 34382434 DOI: 10.1177/19458924211030486] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with variable underlying pathophysiologies. Numerous patient factors have been linked to differences in disease severity, control, and response to treatment, including asthma status, aspirin sensitivity, previous sinonasal surgery, and blood eosinophil levels. OBJECTIVE The present study examines the efficacy of the anti-immunoglobulin E therapy, omalizumab, versus placebo in patients with CRSwNP from the replicate POLYP 1 (NCT03280550) and POLYP 2 (NCT03280537) trials, grouped by inherent patient characteristics to determine the response to therapy. METHODS Patients in prespecified subgroups from POLYP 1 and POLYP 2 (studies pooled for analysis) were examined. Subgroups included blood eosinophil count at baseline (>300 or ≤300 cells/μL), previous sinonasal surgery (yes or no), asthma status (yes or no), and aspirin sensitivity status (yes or no). Subgroups were examined for subgroup-specific adjusted mean difference (95% confidence interval [CI]) (omalizumab-placebo) in change from baseline at week 24 in Nasal Congestion Score (NCS), Nasal Polyp Score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22), Total Nasal Symptom Score (TNSS), and University of Pennsylvania Smell Identification Test (UPSIT). RESULTS Adjusted mean difference (95% CI) (omalizumab-placebo) in NCS, NPS, SNOT-22, TNSS, and UPSIT change from baseline at week 24 consistently favored omalizumab treatment over placebo in patients with blood eosinophil count >300 and ≤300 cells/μL, with or without previous sinonasal surgery, asthma, and aspirin sensitivity. CONCLUSION Together, these data suggest broad efficacy of omalizumab across clinical and patient-reported outcomes in patients with CRSwNP, independent of the underlying patient factors examined, including those with high eosinophil levels and those who have undergone previous surgery, which are associated with high recurrence. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov identifiers: POLYP 1: ClinicalTrials.gov identifier NCT03280550 (https://clinicaltrials.gov/ct2/show/NCT03280550); POLYP 2: ClinicalTrials.gov identifier NCT03280537 (https://clinicaltrials.gov/ct2/show/NCT03280537).
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Affiliation(s)
| | - Meng Chen
- 7412Genentech, Inc., South San Francisco, California.,8785University of California, San Francisco, California
| | | | - Bongin Yoo
- 7412Genentech, Inc., South San Francisco, California
| | | | - Christine Franzese
- Department of Otolaryngology, 14716University of Missouri, MU Health Care, Columbia, Missouri
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Abstract
Periostin, an extracelluar matrix protein belonging to the fasciclin family, has been reported to play a key role in the process of Th2-inflammation disease. As eoshinophilic chronic rhinosinusitis has a higher incident rate, studies show that periostin has participated in the process of inflammation and remodeling. This review mainly to summarize researches of periostin in ECRS and to investigate the clinical significance and expression of periostin.
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Affiliation(s)
- Lei Yu
- Weihai Municipal Hospital, Weihai, China
| | | | - Kai Liu
- Weihai Municipal Hospital, Weihai, China
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Feng T, Miao P, Liu B, Liu Y, Bao X, Xu J, Ren N, Li Y, Shi J, Cao W, Fang J, Li M, Liu Q, Li J. Sinus Microbiota in Patients With Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis With Nasal Polyps. Front Cell Infect Microbiol 2021; 11:672355. [PMID: 34368010 PMCID: PMC8346020 DOI: 10.3389/fcimb.2021.672355] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 06/04/2021] [Indexed: 12/15/2022] Open
Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by Th2-skewed inflammation and increased colonization by Staphylococcus aureus. CRSwNP can be distinguished as eosinophilic (ECRSwNP) and non-eosinophilic (NECRSwNP) by the infiltration of eosinophils. The local microbiota plays an important role in the persistent inflammation of CRSwNP. To evaluate the bacterial community composition on the distinct types of CRSwNP patients, we collected nasal swabs from 16 ECRSwNP patients, 18 NECRSwNP patients, and 39 healthy control subjects. The microbiome structure for all the samples were analyzed by high-throughput 16S rRNA gene sequencing. Concentration of S. aureus was determined using TaqMan quantitative polymerase chain reaction (qPCR) targeting the nuclease (nuc) gene. The result showed significant differences in the sinus microbiome among healthy control subjects and CRSwNP patients. Microbiota community diversity was significantly lower in NECRSwNP samples compared to that of healthy control subjects. Interestingly, the abundance of several pathogenic bacteria was diverse between ECRSwNP and NECRSwNP patients. Although Staphylococcus prevailed in all groups, the abundance of Staphylococcus was significantly higher in the healthy control group than the ECRSwNP group. More importantly, the abundance of S. aureus was much higher in NECRSwNP patients. This study highlights that microbiota composition may contribute to the different clinical types of CRSwNP, inspiring new therapeutic strategies to resolve this chronic inflammation process.
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Affiliation(s)
- Tingting Feng
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ping Miao
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Bin Liu
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Yao Liu
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ximing Bao
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ji Xu
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Nana Ren
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ying Li
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Jiali Shi
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Wanxin Cao
- Department of Otorhinolaryngology, Peking University Third Hospital, Peking University, Beijing, China
| | - Jianchen Fang
- Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Min Li
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Qian Liu
- Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Jiping Li
- Department of Otorhinolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
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Pan X, Zhang Y, Wang C, Zhang L. Evaluation of nasal symptoms to distinguish eosinophilic from noneosinophilic nasal polyps based on peripheral blood. Allergy Asthma Proc 2021; 42:214-221. [PMID: 33980334 DOI: 10.2500/aap.2021.42.210004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Background: Patients with eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) have poorer outcomes after endoscopic sinus surgery and a higher recurrence rate. Objective: This study aimed to investigate the profile of clinical symptoms of eCRSwNP and the related risk factors. Methods: We prospectively enrolled 298 inpatients with CRSwNP from February 2019 to December 2019. The patients were divided into eCRSwNP and non-eCRSwNP groups based on the percentage of blood eosinophils; the cutoff value was set at 3.05%. Clinical data on questionnaires, visual analog scale (VAS) scores, and laboratory tests were collected. The differences in clinical symptoms, including nasal congestion, rhinorrhea, olfactory disorders, and head and/or facial pain, between the two groups were analyzed to identify the influential factors. Logistic analysis and receiver operating characteristic curves were used to determine the diagnostic benefit for the specific symptom in the patients in the eCRSwNP group. Results: Nasal congestion and olfactory disorders were significantly different between the eCRSwNP and non-eCRSwNP groups. The patients in the eCRSwNP group more frequently had concerns about olfactory disorders (p = 0.002), whereas patients in the non-eCRSwNP group mostly had nasal congestion (p = 0.001). The logistic analysis showed that the primary risk factors for olfactory disorders of eCRSwNP were disease duration (p = 0.014) and alcohol intake (p = 0.012). Olfactory disorders were not associated with the disease course of the eCRSwNP group but were correlated with the disease duration of non-eCRSwNP (p = 0.008). A VAS score for the olfactory disorders of >5.75 could be used to predict the diagnosis of eCRSwNP (area under the curve, 0.674 [95% confidence intervals, 0.559-0.689]; P < 0.001). Conclusion: Olfactory disorder might be the major nasal symptom that could be used to distinguish a peripheral eosinophilia-based definition of eCRSwNP and non-eCRSwNP. The disease duration was a limiting factor for using olfactory to distinguish two subgroups of nasal polyp. The investigation with regard to the accurate time boundary should be further addressed.
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Affiliation(s)
- Xiaodan Pan
- From the Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
| | - Yuan Zhang
- From the Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
| | - Chengshuo Wang
- From the Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
| | - Luo Zhang
- From the Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
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Kim S, Ward LA, Butaric LN, Maddux SD. Ancestry-based variation in maxillary sinus anatomy: Implications for health disparities in sinonasal disease. Anat Rec (Hoboken) 2021; 305:18-36. [PMID: 33890723 DOI: 10.1002/ar.24644] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 02/18/2021] [Accepted: 03/17/2021] [Indexed: 12/23/2022]
Abstract
Paranasal sinus drainage is mediated by mucociliary transport and gravity. However, human orthograde posture, along with the superior positioning of the maxillary sinus (MS) ostium, increases reliance on the mucociliary system. Previous research has thus suggested that differences in MS size and shape may impede mucociliary clearance, potentially contributing to disparities in sinusitis susceptibility. To further investigate this hypothesis, this study collected 29 three-dimensional (3D) coordinate landmarks and seven linear measurements of MS morphology from 167 computed tomography (CT) scans of crania of European, East Asian, or Equatorial African ancestry. MANOVA results reveal the Asian-derived individuals are characterized by both a significantly taller MS (F = 14.15, p < 0.0001) and a significantly greater distance from the MS floor to the ostium (F = 17.22, p < 0.0001) compared to those of European and African ancestry. A canonical variate (CV) analysis conducted on 3D landmark data provides corroborative results, distinguishing Asian-derived individuals predominantly on the basis of a relatively lower MS floor. As a greater distance between the MS floor and ostium may impede mucociliary clearance, our results suggest MS anatomy may be a more prominent factor in chronic sinusitis among individuals of Asian ancestry compared to those of European and African ancestries. This provides tentative evidence of an anatomical etiology for chronic sinusitis even in the absence of anatomical variants/abnormalities (e.g., nasal polyps, concha bullosa, Haller's cells, and Agger nasi cells). Further research into the relationship between MS anatomy and sinusitis, in addition to socioeconomic inequalities of healthcare, is warranted to continue evaluating possible contributions to health disparities.
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Affiliation(s)
- Suhhyun Kim
- Center for Anatomical Sciences, Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas, USA
| | - Lyndee A Ward
- Center for Anatomical Sciences, Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas, USA
| | - Lauren N Butaric
- Department of Anatomy, College of Osteopathic Medicine, Des Moines University, Des Moines, Iowa, USA
| | - Scott D Maddux
- Center for Anatomical Sciences, Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas, USA
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Wu Q, Chen J, Ren Y, Qiu H, Yuan L, Deng H, Zhang Y, Zheng R, Hong H, Sun Y, Wang X, Huang X, Shao C, Lin H, Han L, Yang Q. Artificial intelligence for cellular phenotyping diagnosis of nasal polyps by whole-slide imaging. EBioMedicine 2021; 66:103336. [PMID: 33857906 PMCID: PMC8050855 DOI: 10.1016/j.ebiom.2021.103336] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 03/12/2021] [Accepted: 03/24/2021] [Indexed: 11/11/2022] Open
Abstract
Background artificial intelligence (AI) for cellular phenotyping diagnosis of nasal polyps by whole-slide imaging (WSI) is lacking. We aim to establish an AI chronic rhinosinusitis evaluation platform 2.0 (AICEP 2.0) to obtain the proportion of inflammatory cells for cellular phenotyping diagnosis of nasal polyps and to explore the clinical significance of different phenotypes of nasal polyps on the WSI. Methods a total of 453 patients were enrolled in our study. For the development of AICEP 2.0, 179 patients (WSIs) were obtained from the Third Affiliated Hospital of Sun Yat-Sen University (3HSYSU) from January 2008 to December 2018. A total of 24,625 patches were automatically extracted from the regions of interest under a 400× HPF by Openslide and the number of inflammatory cells in these patches was counted by two pathologists. For the application of AICEP 2.0 in a prospective cohort, 158 patients aged 14–70 years old with chronic rhinosinusitis with nasal polyps (CRSwNP) who had undergone endoscopic sinus surgery at 3HSYSU from June 2020 to December 2020 were included for preoperative demographic characteristics. For the application of AICEP 2.0 in a retrospective cohort, 116 patients with CRSwNP who had undergone endoscopic sinus surgery from May 2016 to June 2017 were enrolled for the recurrence rate. The proportion of inflammatory cells of these patients on WSI was calculated by our AICEP 2.0. Findings for AICEP 2.0, the mean absolute errors of the ratios of eosinophils, lymphocytes, neutrophils, and plasma cells were 1.64%, 2.13%, 1.06%, and 1.22%, respectively. The four phenotypes of nasal polyps were significantly different in clinical characteristics (including asthma, itching, sneezing, total IgE, peripheral eosinophils%, tissue eosinophils%, tissue neutrophils%, tissue lymphocytes%, tissue plasma cells%, and recurrence rate; P <0.05), but there were no significant differences in age distribution, onset time, total VAS score, Lund-Kennedy score, or Lund-Mackay score. The percentage of peripheral eosinophils was positively correlated with the percentage of tissue eosinophils (r = 0.560, P <0.001) and negatively correlated with tissue lymphocytes% (r = -0.489, P <0.001), tissue neutrophils% (r = -0.225, P = 0.005), and tissue plasma cells% (r = -0.266, P = 0.001) in WSIs.
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Affiliation(s)
- Qingwu Wu
- Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China; Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Jianning Chen
- Department of Pathology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Yong Ren
- Artificial Intelligence Innovation Center, Research Institute of Tsinghua, Pearl River Delta, Guangzhou 510735, China; Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, China
| | - Huijun Qiu
- Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Lianxiong Yuan
- Department of Science and Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Huiyi Deng
- Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Yana Zhang
- Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Rui Zheng
- Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Haiyu Hong
- Department of Otolaryngology-Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519020, China
| | - Yueqi Sun
- Department of Otorhinolaryngology-Head and Neck Surgery, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, China
| | - Xinyue Wang
- Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Xuekun Huang
- Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Chunkui Shao
- Department of Pathology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
| | - Haotian Lin
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China
| | - Lanqing Han
- Artificial Intelligence Innovation Center, Research Institute of Tsinghua, Pearl River Delta, Guangzhou 510735, China.
| | - Qintai Yang
- Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China; Department of Allergy, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
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Wang M, Bu X, Fang G, Luan G, Huang Y, Akdis CA, Wang C, Zhang L. Distinct expression of SARS-CoV-2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps. Allergy 2021; 76:789-803. [PMID: 33210729 PMCID: PMC7753806 DOI: 10.1111/all.14665] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 11/02/2020] [Accepted: 11/15/2020] [Indexed: 01/08/2023]
Abstract
Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. However, the association between SARS‐CoV‐2 and nasal inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been investigated. We thus investigated the expression of SARS‐CoV‐2 entry factors in nasal tissues of CRSwNP patients, and their associations with inflammatory endotypes of CRSwNP. Methods The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated. Results ACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN‐γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. IFN‐γ up‐regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. Genes co‐expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected. Conclusion These findings indicate that ACE2 expression, regulated by IFN‐γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation.
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Affiliation(s)
- Ming Wang
- Department of Otolaryngology, Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China
- Beijing Key Laboratory of Nasal Diseases Beijing Institute of Otolaryngology Beijing China
| | - Xiangting Bu
- Department of Otolaryngology, Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China
- Beijing Key Laboratory of Nasal Diseases Beijing Institute of Otolaryngology Beijing China
| | - Gaoli Fang
- Department of Otolaryngology, Head and Neck Surgery Beijing Ditan Hospital Capital Medical University Beijing China
| | - Ge Luan
- Department of Otolaryngology, Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China
- Beijing Key Laboratory of Nasal Diseases Beijing Institute of Otolaryngology Beijing China
| | - Yanran Huang
- Department of Otolaryngology, Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China
- Beijing Key Laboratory of Nasal Diseases Beijing Institute of Otolaryngology Beijing China
| | - Cezmi A. Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
- Christine Kühne – Center for Research and Education (CK‐CARE) Davos Switzerland
| | - Chengshuo Wang
- Department of Otolaryngology, Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China
| | - Luo Zhang
- Department of Otolaryngology, Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China
- Beijing Key Laboratory of Nasal Diseases Beijing Institute of Otolaryngology Beijing China
- Department of Allergy Beijing TongRen Hospital Capital Medical University Beijing China
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Xie S, Zhang H, Liu Y, Gao K, Zhang J, Fan R, Xie S, Xie Z, Wang F, Jiang W. The Role of Serum Metabolomics in Distinguishing Chronic Rhinosinusitis With Nasal Polyp Phenotypes. Front Mol Biosci 2021; 7:593976. [PMID: 33511154 PMCID: PMC7835901 DOI: 10.3389/fmolb.2020.593976] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 12/03/2020] [Indexed: 01/17/2023] Open
Abstract
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease characterized by different clinical features and treatment responsiveness. This study aimed to compare the serum metabolomics profiles between eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP) and healthy controls (HC) and explore objective biomarkers for distinguishing eCRSwNP before surgery. Methods: Serum samples were collected from 33 neCRSwNP patients, 37 eCRSwNP patients, and 29 HC. Serum metabolomics profiles were investigated by ultra-high-performance liquid chromatography-mass spectrometry. Results: The analysis results revealed that neCRSwNP, eCRSwNP, and HC exhibited distinctive metabolite signatures. In addition, eCRSwNP could be distinguished from neCRSwNP referring to their serum metabolic profiles, and the top ten different metabolites were citrulline, choline, linoleic acid, adenosine, glycocholic acid, L-serine, triethanolamine, 4-guanidinobutyric acid, methylmalonic acid, and L-methionine, which were related to several most important pathways including arginine and proline metabolism; glycine, serine, and threonine metabolism; linoleic acid metabolism; and purine metabolism. Among these distinctive metabolites, citrulline, linoleic acid, adenosine, and 4-guanidinobutyric acid showed good predictabilities, and the serum levels of citrulline, linoleic acid, and adenosine were significantly correlated with tissue eosinophil (T-EOS) percentage and T-EOS count. Conclusion: eCRSwNP patients exhibited discriminative serum metabolic signatures in comparison with neCRSwNP patients and HC. These results suggested that metabolomics profiles contributed to understanding the pathophysiological mechanisms of CRSwNP and distinguishing its phenotypes.
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Affiliation(s)
- Shaobing Xie
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.,Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, China
| | - Hua Zhang
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.,Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, China
| | - Yongzhen Liu
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.,Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, China
| | - Kelei Gao
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.,Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, China
| | - Junyi Zhang
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.,Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, China
| | - Ruohao Fan
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.,Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, China
| | - Shumin Xie
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.,Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, China
| | - Zhihai Xie
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.,Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, China
| | - Fengjun Wang
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.,Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, China
| | - Weihong Jiang
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.,Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, China
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Zeng M, Wang H, Liao B, Wang H, Long XB, Ma J, Liu JX, Liu Z. Clinical and Biological Markers Predict the Efficacy of Glucocorticoid- and Macrolide-Based Postoperative Therapy in Patients With Chronic Rhinosinusitis. Am J Rhinol Allergy 2020; 35:596-606. [PMID: 33348995 DOI: 10.1177/1945892420982236] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Although subsequent anti-inflammatory treatments are indispensable for patients with chronic rhinosinusitis (CRS) undergoing sinus surgery, few studies have explored the factors influencing the efficacy of postoperative anti-inflammatory treatment. OBJECTIVE We aimed to develop prediction models for the response to glucocorticoid- and macrolide-based postoperative therapy in CRS patients. METHODS We performed a post-hoc analysis of our previous study comparing the efficacy of fluticasone propionate and clarithromycin in the postoperative treatment of CRS patients. Clinical characteristics and treatment outcome information were collected. In addition, diseased sinonasal mucosal tissues obtained during surgery were processed for Bio-Plex analysis of protein levels of 34 biomarkers. Classification trees were built to predict refractory CRS based on clinical characteristics and biological markers for patients treated with fluticasone propionate or clarithromycin. A random forest algorithm was used to confirm the discriminating factors that formed the classification trees. RESULTS One year after surgery, 22.7% of the patients (17/75) treated with fluticasone propionate, and 24.3% of those (18/74) treated with clarithromycin were diagnosed with refractory CRS. Nasal tissue IL-8 and IgG3 levels and headache VAS scores in the fluticasone propionate group, and nasal tissue IgG4 levels and overall burden of symptoms VAS scores in the clarithromycin group, were identified as discriminating factors forming the classification tree to predict refractory CRS. The overall predictive accuracy of the model was 89.3% and 87.8% for fluticasone propionate- and clarithromycin-based postsurgical treatment, respectively. CONCLUSIONS Classification trees built using clinical and biological parameters could be helpful in identifying patients with poor response to fluticasone propionate- and clarithromycin-based postoperative treatment.
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Affiliation(s)
- Ming Zeng
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Heng Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Bo Liao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Hai Wang
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Xiao-Bo Long
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Jin Ma
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Jin-Xin Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
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