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Lee JY, Kim DH, Kim SW, Im YH, Park CS, Kim DH, Alkhars Z, Kim SW. Diagnostic criteria for eosinophilic chronic rhinosinusitis: Comparative analysis and novel scoring system. Int Forum Allergy Rhinol 2024; 14:1746-1756. [PMID: 39039646 DOI: 10.1002/alr.23416] [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: 01/10/2024] [Revised: 06/25/2024] [Accepted: 07/05/2024] [Indexed: 07/24/2024]
Abstract
BACKGROUND Accurate identification of eosinophilic chronic rhinosinusitis is essentialg because its treatment and prognosis substantially differ from other subtypes. METHODS This retrospective observational study included 640 patients who underwent endoscopic sinus surgery for chronic rhinosinusitis in a single tertiary center from January 2021 to December 2022. Receiver operating characteristic curves were generated to compare accuracy, sensitivity, specificity of the novel scoring system, and previous diagnostic criteria (Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis, European Forum for Research and Education in Allergy and Airway Diseases, European Position Paper on Rhinosinusitis and Nasal Polyps, and Sakuma et al.) for predicting eosinophilic chronic rhinosinusitis (ECRS) by tissue eosinophil count ≥70 per high power field. RESULTS Patients were randomly divided into estimation (n = 430) and validation (n = 210) groups. The area under the receiver operating characteristic curve for the novel score was 0.753 (95% confidence interval [CI], 0.670-0.835) in the estimation group, 0.729 (0.629-0.830) in the validation group, and 0.661 (0.584-0.738) in the 20-fold cross-validation with the entire dataset. CONCLUSIONS We propose a novel scoring system that incorporates three key parameters: "novel score = blood eosinophil (%) + total Lund-Mackay score of anterior ethmoid sinuses + 2 if nasal polyp present" greater than 7 can be reliably used for diagnosing ECRS. This system can facilitate decision-making processes regarding the administration of oral steroids and biologics targeting type 2 inflammation prior to surgical intervention.
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Affiliation(s)
- Jae Yoon Lee
- Department of Otolaryngology-Head and Neck Surgery, Seoul Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Do Hyun Kim
- Department of Otolaryngology-Head and Neck Surgery, Seoul Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Sung Won Kim
- Department of Otolaryngology-Head and Neck Surgery, Seoul Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Yeon Hee Im
- Department of Otolaryngology-Head and Neck Surgery, Uijeongbu Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, South Korea
| | - Chan Soon Park
- Department of Otolaryngology-Head and Neck Surgery, Saint Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea
| | - Dong Hyun Kim
- Department of Otolaryngology-Head and Neck Surgery, Incheon Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea
| | - Zainab Alkhars
- Department of Otolaryngology-Head and Neck Surgery, Al Jabr Hospital, Ministry of Health, Al Ahsa, Saudi Arabia
| | - Soo Whan Kim
- Department of Otolaryngology-Head and Neck Surgery, Seoul Saint Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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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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Zou J, Lyu Y, Lin Y, Chen Y, Lai S, Wang S, Zhang X, Zhang X, Wu R, Kang W. A multi-view fusion lightweight network for CRSwNPs prediction on CT images. BMC Med Imaging 2024; 24:112. [PMID: 38755567 PMCID: PMC11100041 DOI: 10.1186/s12880-024-01296-3] [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: 01/03/2024] [Accepted: 05/08/2024] [Indexed: 05/18/2024] Open
Abstract
Accurate preoperative differentiation of the chronic rhinosinusitis (CRS) endotype between eosinophilic CRS (eCRS) and non-eosinophilic CRS (non-eCRS) is an important topic in predicting postoperative outcomes and administering personalized treatment. To this end, we have constructed a sinus CT dataset, which comprises CT scan data and pathological biopsy results from 192 patients of chronic rhinosinusitis with nasal polyps (CRSwNP), treated at the Second Affiliated Hospital of Shantou University Medical College between 2020 and 2022. To differentiate CRSwNP endotype on preoperative CT and improve efficiency at the same time, we developed a multi-view fusion model that contains a mini-architecture with each network of 10 layers by modifying the deep residual neural network. The proposed model is trained on a training set and evaluated on a test set. The multi-view deep learning fusion model achieved the area under the receiver-operating characteristics curve (AUC) of 0.991, accuracy of 0.965 and F1-Score of 0.970 in test set. We compared the performance of the mini-architecture with other lightweight networks on the same Sinus CT dataset. The experimental results demonstrate that the developed ResMini architecture contribute to competitive CRSwNP endotype identification modeling in terms of accuracy and parameter number.
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Affiliation(s)
- Jisheng Zou
- College of Engineering, Shantou University, Shantou, 515063, China
| | - Yi Lyu
- Department of Otolaryngology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
| | - Yu Lin
- Department of Otolaryngology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
| | - Yaowen Chen
- College of Engineering, Shantou University, Shantou, 515063, China
| | - Shixin Lai
- College of Engineering, Shantou University, Shantou, 515063, China
| | - Siqi Wang
- College of Engineering, Shantou University, Shantou, 515063, China
| | - Xuan Zhang
- College of Engineering, Shantou University, Shantou, 515063, China
| | - Xiaolei Zhang
- Department of Radiology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China.
| | - Renhua Wu
- Department of Radiology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China.
| | - Weipiao Kang
- Department of Otolaryngology, the Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, 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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Xiong P, Chen J, Zhang Y, Shu L, Shen Y, Gu Y, Liu Y, Guan D, Zheng B, Yang Y. Predictive modeling for eosinophilic chronic rhinosinusitis: Nomogram and four machine learning approaches. iScience 2024; 27:108928. [PMID: 38333706 PMCID: PMC10850747 DOI: 10.1016/j.isci.2024.108928] [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: 10/04/2023] [Revised: 12/04/2023] [Accepted: 01/12/2024] [Indexed: 02/10/2024] Open
Abstract
Eosinophilic chronic rhinosinusitis (ECRS) is a distinct subset of chronic rhinosinusitis characterized by heightened eosinophilic infiltration and increased symptom severity, often resisting standard treatments. Traditional diagnosis requires invasive histological evaluation. This study aims to develop predictive models for ECRS based on patient clinical parameters, eliminating the need for invasive biopsy. Utilizing logistic regression with lasso regularization, random forest (RF), gradient-boosted decision tree (GBDT), and deep neural network (DNN), we trained models on common clinical data. The predictive performance was evaluated using metrics such as area under the curve (AUC) for receiver operator characteristics, decision curves, and feature ranking analysis. In a cohort of 437 eligible patients, the models identified peripheral blood eosinophil ratio, absolute peripheral blood eosinophil, and the ethmoidal/maxillary sinus density ratio (E/M) on computed tomography as crucial predictors for ECRS. This predictive model offers a valuable tool for identifying ECRS without resorting to histological biopsy, enhancing clinical decision-making.
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Affiliation(s)
- Panhui Xiong
- Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Junliang Chen
- Department of Otorhinolaryngology, Xishui People’s Hospital, Xishui County, Zunyi, Guizhou Province 564600, China
| | - Yue Zhang
- Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Longlan Shu
- Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yang Shen
- Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yue Gu
- Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yijun Liu
- Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Dayu Guan
- Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Bowen Zheng
- Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yucheng Yang
- Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
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Kim J, Kwak S, Lee J, Park IH, Lee SH, Shin JM, Kim TH. Eosinophilic Chronic Rhinosinusitis and Pathogenic Role of Protease. Int J Mol Sci 2023; 24:17372. [PMID: 38139201 PMCID: PMC10744023 DOI: 10.3390/ijms242417372] [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: 10/21/2023] [Revised: 12/01/2023] [Accepted: 12/10/2023] [Indexed: 12/24/2023] Open
Abstract
Chronic rhinosinusitis (CRS) is an inflammation of the nasal and paranasal sinus mucosa, and eosinophilic CRS (eCRS) is a subtype characterized by significant eosinophil infiltration and immune response by T-helper-2 cells. The pathogenesis of eCRS is heterogeneous and involves various environmental and host factors. Proteases from external sources, such as mites, fungi, and bacteria, have been implicated in inducing type 2 inflammatory reactions. The balance between these proteases and endogenous protease inhibitors (EPIs) is considered important, and their imbalance can potentially lead to type 2 inflammatory reactions, such as eCRS. In this review, we discuss various mechanisms by which exogenous proteases influence eCRS and highlight the emerging role of endogenous protease inhibitors in eCRS pathogenesis.
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Affiliation(s)
- Jaehyeong Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Republic of Korea; (J.K.); (S.K.); (J.L.); (I.-H.P.); (S.H.L.); (J.M.S.)
- Mucosal Immunology Institute, College of Medicine, Korea University, Seoul 02841, Republic of Korea
| | - Sooun Kwak
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Republic of Korea; (J.K.); (S.K.); (J.L.); (I.-H.P.); (S.H.L.); (J.M.S.)
| | - Juhyun Lee
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Republic of Korea; (J.K.); (S.K.); (J.L.); (I.-H.P.); (S.H.L.); (J.M.S.)
| | - Il-Ho Park
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Republic of Korea; (J.K.); (S.K.); (J.L.); (I.-H.P.); (S.H.L.); (J.M.S.)
| | - Seung Hoon Lee
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Republic of Korea; (J.K.); (S.K.); (J.L.); (I.-H.P.); (S.H.L.); (J.M.S.)
| | - Jae Min Shin
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Republic of Korea; (J.K.); (S.K.); (J.L.); (I.-H.P.); (S.H.L.); (J.M.S.)
- Mucosal Immunology Institute, College of Medicine, Korea University, Seoul 02841, Republic of Korea
| | - Tae Hoon Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul 02841, Republic of Korea; (J.K.); (S.K.); (J.L.); (I.-H.P.); (S.H.L.); (J.M.S.)
- Mucosal Immunology Institute, College of Medicine, Korea University, Seoul 02841, Republic of Korea
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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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Gao Y, Wang X, Gao L, Li X, Bai W. Body mass index affects the association between plasma lipids and peripheral eosinophils in a general chinese population: a cross-sectional survey. Lipids Health Dis 2023; 22:146. [PMID: 37679775 PMCID: PMC10483721 DOI: 10.1186/s12944-023-01909-w] [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: 06/04/2023] [Accepted: 08/23/2023] [Indexed: 09/09/2023] Open
Abstract
BACKGROUND Lipid metabolism affects type 2 immunity; however, the association between plasma lipids and eosinophilic inflammation in humans is uncertain. This study analysed the relationship between plasma lipids and peripheral eosinophils and whether patterns differ with different body mass indexes (BMI). METHODS A cross-sectional survey including 62,441 healthy participants recruited from a regular health screening programme was conducted. Participants were divided into normal weight, overweight and obese subgroups according to BMI. RESULTS Multiple linear regression analysis revealed that elevated logarithmic-transformed eosinophil counts (log(EOS)) significantly correlated with high total cholesterol(TC), triglyceride(TG), low-density lipoprotein-cholesterol (LDL-C), and low high-density lipoprotein-cholesterol (HDL-C)levels in the overall population, as well as in men and women, while certain associations between peripheral blood eosinophil percentage and serum lipids varied by gender. These correlations existed across almost all BMI subgroups, and standardised β values decreased sequentially with increasing BMI. HDL-C had the most significant effect on eosinophils in obese women. Two-factor analysis of variance showed log(EOS) increased with higher BMI and hyperlipidemia whether in male or female and a synergistic effect exists of lipid levels (TG and LDL-C) and BMI in men. CONCLUSIONS Blood eosinophil counts were correlated with blood lipid levels and modified by body mass index status. The effects of lipid levels and body mass index on blood eosinophil counts were synergistic. Therefore, lipid metabolism may be involved in systemic eosinophil inflammation.
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Affiliation(s)
- Yu Gao
- Department of Otorhinolaryngology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical University, No. 29 of Twin Towers Temple Street, Taiyuan, Shanxi 030012 China
| | - Xiaocheng Wang
- Department of Statistics, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical University, No. 29 of Twin Towers Temple Street, Taiyuan, Shanxi 030012 China
| | - Lan Gao
- College of Basic Medicine, Shanxi University of Chinese Medicine, Jinzhong, Shanxi 030619 China
| | - Xin Li
- Department of Otorhinolaryngology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical University, No. 29 of Twin Towers Temple Street, Taiyuan, Shanxi 030012 China
| | - Weihong Bai
- Department of Otorhinolaryngology, Shanxi Provincial People’s Hospital Affiliated to Shanxi Medical University, No. 29 of Twin Towers Temple Street, Taiyuan, Shanxi 030012 China
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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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10
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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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11
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Che Mat CMH, Md Shukri N, Mohamad S, Tuan Sharif SE, Ramli R, Jais MH, Mat Jaeb MZ, Yaacob NM, Yusoff MY, Husna SMN, Abdullah B. Diagnostic value of serum and tissue eosinophil in diagnosis of asthma among patients with chronic rhinosinusitis. Eur Arch Otorhinolaryngol 2023; 280:2283-2291. [PMID: 36401099 DOI: 10.1007/s00405-022-07746-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 11/07/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Chronic rhinosinusitis (CRS) is one of the most common chronic inflammatory diseases of sinonasal mucosa. Asthma among CRS patients is often underdiagnosed which makes the management of CRS more challenging. Therefore, using serum and tissue eosinophil as an indicator and predictor of asthma in CRS patients is vital for further preventing recurrent and increasing the effectiveness of treatment for CRS. OBJECTIVE To determine the association and diagnostic ability of serum and tissue eosinophils in the diagnosis of asthma among CRS patients. METHODS A cross-sectional study was conducted involving 24 CRS patients with asthma and without asthma, respectively, from the Otorhinolaryngology clinic of two tertiary hospitals located on the East Coast of Peninsular Malaysia. Serum and tissue eosinophils (obtained from nasal polyp) levels between both groups were compared. Association between serum and tissue eosinophils with asthma was evaluated using logistic regression analysis, adjusting for important sociodemographic characteristics. The diagnostic ability of serum and tissue eosinophil was then evaluated by assessing the receiver operating characteristic curve. RESULTS A total of 48 CRS patients with a mean [SD] age of 47.50 [14.99] years were included. Patients with asthma had significantly higher serum [0.48 vs 0.35 × 109/L] and tissue eosinophil [100 vs 8.5 per HPF] levels. Tissue eosinophils were found to be an independent predictor of asthma with adjusted OR 1.05, p < 0.001, after adjusting for age and serum eosinophils. The area under the receiver operating characteristic curve for serum eosinophil was 69.0%. At optimal cut-off value (0.375 × 109/L), the sensitivity and specificity for serum eosinophil was 75.0% and 70.8%. The area under the receiver operating characteristic curve for tissue eosinophil was 93.4%. At the optimal cut-off value (58.0 per HPF), the sensitivity and specificity for tissue eosinophils were 79.2% and 91.7%, respectively. CONCLUSION This study indicates a significantly higher level of serum and tissue eosinophils in CRS with asthma. However, there was no correlation between serum and tissue eosinophils in both group. Based on this study, the CRS patient needs to be screened for asthma if the level of serum eosinophil is > 0.375 × 109/L and tissue eosinophil > 58 per HPF.
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Affiliation(s)
- Che Mohd Hilmi Che Mat
- Department of Otorhinolaryngology-Head and Neck Surgery, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
- Department of Otorhinolaryngology-Head and Neck Surgery, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, Malaysia
| | - Norasnieda Md Shukri
- Department of Otorhinolaryngology-Head and Neck Surgery, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.
| | - Sakinah Mohamad
- Department of Otorhinolaryngology-Head and Neck Surgery, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Sharifah Emilia Tuan Sharif
- Department of Pathology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Rosdi Ramli
- Department of Otorhinolaryngology-Head and Neck Surgery, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, Malaysia
| | - Murni Hartini Jais
- Department of Pathology, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, Malaysia
| | - Mat Zuki Mat Jaeb
- Department of Respiratory, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, Malaysia
| | - Najib Majdi Yaacob
- Department of Biostatistics and Research Methodology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Mohd Yusran Yusoff
- Department of Clinical Research Centre, Hospital Raja Perempuan Zainab II, Kota Bharu, Kelantan, Malaysia
| | - Siti Muhamad Nur Husna
- Department of Immunology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
| | - Baharudin Abdullah
- Department of Otorhinolaryngology-Head and Neck Surgery, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
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12
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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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13
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Chee J, Pang KW, Low T, Wang DY, Subramaniam S. Epidemiology and aetiology of chronic rhinosinusitis in Asia-A narrative review. Clin Otolaryngol 2023; 48:305-312. [PMID: 35997660 DOI: 10.1111/coa.13971] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 07/13/2022] [Accepted: 07/29/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Despite having a similar prevalence to Western populations, literature on chronic rhinosinusitis (CRS) in the Asian population is sparse. There is limited data on the epidemiology and aetiology of CRS in Asia. OBJECTIVES To review the current literature on the epidemiology and aetiology of CRS in Asia. METHODS This is a narrative review of published data on the epidemiology and aetiology of CRS. Studies on CRS in Asian countries, published in English and indexed on PubMed or Google Scholar were reviewed. Where available, data extracted included epidemiology, endotype and cytokine profiles and genetic profiles. RESULTS AND CONCLUSION The prevalence of CRS in Asia ranges widely from 2.1% to 28.4%. Type 2 inflammation has been reported in 5%-55% of Asian patients, with lower levels of Type 2 cytokines reported in head to head comparisons of Western versus Asian patients. Notably, there exists marked heterogeneity in criterion of the tissue eosinophilic infiltration for diagnosis of type 2 CRS. Our review suggests that differences in prevalence of CRS and proportion of eosinophilic CRS between Asia and Europe and the Americas requires further study. Large-scale Asian studies utilising standardised definitions are needed to bridge this gap. Head to head genetic and microbiomal analysis may also be useful in understanding differences in CRS between the Asian and Western populations.
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Affiliation(s)
- Jeremy Chee
- Department of Otolaryngology-Head & Neck Surgery, National University Health System, Singapore, Singapore
| | - Khang Wen Pang
- Department of Otolaryngology-Head & Neck Surgery, National University Health System, Singapore, Singapore
| | - Terese Low
- Department of Otolaryngology-Head & Neck Surgery, National University Health System, Singapore, Singapore
| | - De Yun Wang
- Department of Otolaryngology, Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Somasundaram Subramaniam
- Department of Otolaryngology-Head & Neck Surgery, National University Health System, Singapore, Singapore
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14
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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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15
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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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16
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Xu S, Vallei M, Hwang Siok Gek J, Tze Choong C, Wei Yang Teo N. Endotyping of nasal polyps in a multiracial Asian population. RHINOLOGY ONLINE 2022. [DOI: 10.4193/rhinol/22.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Background: Chronic rhinosinusitis is a heterogenous disease with variation in the endotypes of nasal polyps, with type 2 inflammation being more prevalent in Caucasian populations whereas Chinese populations are more heterogenous. We aim to describe the variation in endotypes for patients with chronic rhinosinusitis with nasal polyposis in our unique multiracial population. Methodology: Demographic, clinical and structured histopathological data of 66 patients who underwent sinus surgery for nasal polyposis were evaluated retrospectively. Results: 54.6% had eosinophilic disease, and 45.4% had non-eosinophilic disease with no significant demographic differences between the 2 populations. There were significantly higher peripheral eosinophil levels in patients with eosinophil-predominant inflammation on tissue histology (mean absolute eosinophil count 0.59 ± 0.18 x 109) compared with non-eosinophilic disease (mean absolute eosinophil count 0.24 ± 0.11 x 109). Structured histopathological reporting revealed that patients with eosinophilic disease had higher degree of inflammation and eosinophil aggregates. Conclusions: Our population is shown to have a slight preponderance toward eosinophilic disease, however the Chinese majority tended to have non-eosinophilic disease. Serum eosinophilia and the presence of asthma seems to correlate well with tissue eosinophilia, which can potentially be utilised as markers of type 2 inflammatory disease.
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17
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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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Tan H, Tong X, Gao Z, Xu Y, Tan L, Zhang W, Xiang R, Xu Y. The hMeDIP-Seq identified INPP4A as a novel biomarker for eosinophilic chronic rhinosinusitis with nasal polyps. Epigenomics 2022; 14:757-775. [PMID: 35765979 DOI: 10.2217/epi-2022-0053] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Background: Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is an endotype of chronic rhinosinusitis with nasal polyps characterized by more severe symptoms, a stronger association with asthma and a greater recurrence risk. It is unknown whether DNA hydroxymethylation could influence ECRSwNP. Methods: Hydroxymethylated DNA immunoprecipitation sequencing was carried out in three distinct groups (control, ECRSwNP and NECRSwNP). Additional qRT-PCR, immunohistochemistry and analysis of the receiver operating characteristic curve were performed. Results: Between ECRSwNP and NECRSwNP, 26 genes exhibited differential DNA hydroxymethylation. Consistent with their hydroxymethylation level, GNAL, INPP4A and IRF4 expression levels were significantly different between ECRSwNP and the other two groups. The receiver operating characteristic curve revealed that INPP4A mRNA has a high predictive accuracy for ECRSwNP. Conclusion: DNA hydroxymethylation regulates the expression of multiple genes in ECRSwNP. INPP4A mRNA was markedly decreased in ECRSwNP polyps and can predict ECRSwNP.
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Affiliation(s)
- Hanyu Tan
- Department of Otolaryngology - Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Xiaoting Tong
- Department of Otolaryngology - Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Ziang Gao
- Department of Otolaryngology - Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Yingying Xu
- Department of Otolaryngology - Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Lu Tan
- Department of Otolaryngology - Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Wei Zhang
- Department of Otolaryngology - Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Rong Xiang
- Department of Otolaryngology - Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Yu Xu
- Department of Otolaryngology - Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China
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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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Lin YT, Yeh TH. Studies on Clinical Features, Mechanisms, and Management of Olfactory Dysfunction Secondary to Chronic Rhinosinusitis. FRONTIERS IN ALLERGY 2022; 3:835151. [PMID: 35386650 PMCID: PMC8974686 DOI: 10.3389/falgy.2022.835151] [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: 12/14/2021] [Accepted: 02/01/2022] [Indexed: 12/14/2022] Open
Abstract
Chronic rhinosinusitis (CRS) is one of the most common causes of inflammation of the olfactory system, warranting investigation of the link between chronic inflammation and the loss of olfactory function. Type 2 inflammation is closely related to the clinical features and disease mechanisms of olfactory dysfunction secondary to CRS. Patients with eosinophilic CRS, aspirin-exacerbated respiratory disease, and central compartment atopic disease report increased olfactory dysfunction. Increased levels of interleukin-(IL-)2, IL-5, IL-6, IL-10, and IL-13 in the mucus from the olfactory slit have been reported to be associated with reduced olfactory test scores. The influence of several cytokines and signaling transduction pathways, including tumor necrosis factor-α, nuclear factor-κB, and c-Jun N-terminal kinases, on olfactory signal processing and neurogenesis has been demonstrated. Corticosteroids are the mainstay treatment for olfactory dysfunction secondary to CRS. Successful olfaction recovery was recently demonstrated in clinical trials of biotherapeutics, including omalizumab and dupilumab, although the treatment effect may diminish gradually after stopping the use of the medications. Future studies are required to relate the complex mechanisms underlying chronic inflammation in CRS to dysfunction of the olfactory system.
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Affiliation(s)
- Yi-Tsen Lin
- Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan
| | - Te-Huei Yeh
- Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan
- College of Medicine, National Taiwan University, Taipei, Taiwan
- *Correspondence: Te-Huei Yeh
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Suzuki S, Kudo N, Matsushita D, Hara R, Miura T, Matsubara A. Major basic protein deposited at intra mucosal epithelium with probable eosinophilic chronic rhinosinusitis. Asia Pac Allergy 2022; 12:e28. [PMID: 35966158 PMCID: PMC9353210 DOI: 10.5415/apallergy.2022.12.e28] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 07/02/2022] [Indexed: 01/21/2023] Open
Abstract
Background Eosinophilic chronic rhinosinusitis (ECRS) is diagnosed by Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scoring system and histopathological eosinophil counts of dissected nasal polyps. Patients with low JESREC score and small number of tissue eosinophils are diagnosed with non-ECRS (NECRS). Due to the 2 parameters of this diagnostic system, chronic rhinosinusitis is to be divided to 4 groups and some patients fall into the 2 groups other than ECRS and NECRS: probable ECRS (pECRS) and probable non-ECRS (pNECRS). We attempted to clarify clinical and histopathological similarities and differences, especially concerning major basic protein (MBP), among those groups. Methods One hundred twenty-eight patients treated by endoscopic sinus surgery was included. Clinical characteristics were compared among each group, and immunohistological analysis for MBP was performed to 35 randomly selected patients. MBP deposition at intra mucosal epithelium was evaluated by semiquantificational approach. Results ECRS patients showed significantly higher comorbidity rate with allergic rhinitis (36 patients, 78.3%), asthma (36 patients, 78.3%) compared with other groups. Also, percentage of the patients complaining olfactory dysfunction (42 patients, 91.3%) was significantly higher (p < 0.001). Lund-Mackay score (mean, 14.5; 6–24) and recurrence rate (27 patients, 61.4%) was the highest in ECRS patients. Regarding pECRS, the number of patients with olfactory dysfunction (5 patients, 55.6%) was higher than pNECRS and NECRS groups. Also, comorbidity of asthma and percentage of blood eosinophils tended to be higher than those 2 groups. MBP score of pECRS group was significantly higher than NECRS (p < 0.05), despite of smaller tissue eosinophil counts. Conclusion pECRS might share some characteristics with ECRS although tissue eosinophil count was significantly smaller compared with ECRS. The results of this study have shown that MBP score in pECRS nasal polyps was significantly higher than NECRS patients and close to ECRS. That might suggest that eosinophils have existed in the nasal polyps of pPECRS patients at some point before surgery.
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Affiliation(s)
- Satoshi Suzuki
- Department of Otorhinolaryngology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Naomi Kudo
- Department of Otorhinolaryngology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Daisuke Matsushita
- Department of Otorhinolaryngology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Ryutaro Hara
- Department of Otorhinolaryngology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Tomoya Miura
- Department of Otorhinolaryngology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Atsushi Matsubara
- Department of Otorhinolaryngology, Hirosaki University Graduate School of Medicine, Hirosaki, 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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Brown HJ, Tajudeen BA, Kuhar HN, Gattuso P, Batra PS, Mahdavinia M. Defining the Allergic Endotype of Chronic Rhinosinusitis by Structured Histopathology and Clinical Variables. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2021; 9:3797-3804. [PMID: 34174492 PMCID: PMC8511331 DOI: 10.1016/j.jaip.2021.06.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 05/20/2021] [Accepted: 06/03/2021] [Indexed: 11/25/2022]
Abstract
BACKGROUND Atopy has a strong association with chronic rhinosinusitis (CRS). OBJECTIVE To understand whether patients with atopy and CRS can be defined by markers of tissue histopathology, systemic biomarkers, and clinical factors, which may guide their response to new pharmacologic agents. METHODS In a retrospective cohort of CRS patients who underwent functional endoscopic sinus surgery, a structured histopathology report consisting of 12 variables, comorbid conditions, preoperative total serum IgE levels, and preoperative modified Lund-Kennedy endoscopic and sinonasal outcome test (SNOT-22) scores were compared between atopic CRS (aCRS) and non-aCRS control patients in a multivariable model. RESULTS A total of 380 CRS patients were enrolled, 286 of whom had comorbid atopy (aCRS). Compared with non-aCRS, aCRS patients had significantly higher preoperative total SNOT-22 scores (40.45 ± 22.68 vs 29.70 ± 20.68, P = .015) and symptom-specific SNOT-22 scores in all domains except psychological dysfunction. Relative to non-aCRS, aCRS patients had increased tissue eosinophilia (P < .0001), eosinophil aggregates (P < .0001), Charcot-Leyden crystals (P < .04), fibrosis (P < .02), total serum IgE levels (P < .04), polyploid disease (P < .001), and a prevalence of comorbid asthma (P < .0001) and aspirin exacerbated respiratory disease (AERD) (P < .003). Patients with aCRS demonstrated increased tissue eosinophilia compared with non-aCRS patients even after controlling for polypoid disease, asthma, and AERD. CONCLUSION In the context of CRS, atopy appears to be a specific predictor of CRS severity linked to specific histopathologic variables, including enhanced eosinophilic aggregates. Moving forward, allergic status may be a useful way to identify an atopic endotype of CRS patients. Furthermore, after surgery, patients are often maintained on intranasal corticosteroids. In patients whose disease is unresponsive to steroids, we may look to atopic status to identify another management therapy. Atopic CRS patients, irrespective of polyp and asthmatic status, could be optimal candidates for biologic agents such as T-helper cell, eosinophil, and/or IgE-targeted therapies.
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Affiliation(s)
- Hannah J Brown
- Rush Medical College, Rush University Medical Center, Chicago, Ill
| | - Bobby A Tajudeen
- Rush Sinus Program, Department of Otorhinolaryngology - Head and Neck Surgery, Rush University Medical Center, Chicago, Ill
| | - Hannah N Kuhar
- Department of Otolaryngology - Head and Neck Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Paolo Gattuso
- Department of Pathology, Rush University Medical Center, Chicago, Ill
| | - Pete S Batra
- Rush Sinus Program, Department of Otorhinolaryngology - Head and Neck Surgery, Rush University Medical Center, Chicago, Ill
| | - Mahboobeh Mahdavinia
- Section of Allergy/Immunology, Department of Internal Medicine, Rush University Medical Center, Chicago, Ill.
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Therapeutic indications for sinonasal topical steroid treatment and its effects on eosinophilic chronic rhinosinusitis after endoscopic sinus surgery. The Journal of Laryngology & Otology 2021; 135:858-863. [PMID: 34423758 DOI: 10.1017/s0022215121001985] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVE This study evaluated the post-operative indications for sinonasal topical steroid treatment using a corticosteroid (steroid)-eluting, sinus-bioabsorbable device and its effects in patients with eosinophilic chronic rhinosinusitis. METHOD Post-operative courses were investigated in two groups: group A with patients who underwent sinonasal topical steroid treatment, and group B with control patients who did not. RESULTS Group A was significantly younger than group B (p < 0.01), and the pre-operative computed tomography score was significantly higher in group A than in group B (p < 0.05). In the post-operative stage, the nasal symptoms questionnaire component of olfactory loss and the post-operative endoscopic appearance score were significantly worse in group A than in group B (p < 0.01). CONCLUSION These data suggest that younger age, more severe rhinosinusitis and post-operative olfactory loss led to the need for sinonasal topical steroid treatment to prevent relapsing inflammation after functional endoscopic sinus surgery in patients with eosinophilic chronic rhinosinusitis.
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Sousa JC, Etchbehere RM, Alves EAR, Stark LM, Murta EFC, Michelin MA. Interferon-α action in cytokine profile in eosinophilic nasal polyp cultures. Braz J Otorhinolaryngol 2021; 87:260-268. [PMID: 31870738 PMCID: PMC9422409 DOI: 10.1016/j.bjorl.2019.08.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 03/01/2019] [Accepted: 08/28/2019] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION Chronic rhinosinusitis is currently classified into two types: chronic rhinosinusitis without nasal polyps and chronic rhinosinusitis with nasal polyps. In the West, approximately 80% of chronic rhinosinusitis with nasal polyps cases are characterized by a predominantly eosinophilic cell infiltrate and a Th2 cytokine pattern. OBJECTIVE To evaluate the effect of Interferon-α on cytokine levels of the eosinophilic nasal polyp cell culture supernatant. METHODS Cell cultures were performed based on nasal polypoid tissue samples collected from 13 patients with eosinophilic chronic rhinosinusitis with nasal polyps. Polyps were considered eosinophilic according to the histopathological examination. Cell cultures were stimulated with 3000 IU of interferon-α. Before and after the stimulus, concentrations of Interferon-γ, tumor necrosis factor αand IL 2, 4, 6 and 10, using cytometric bead array, were assessed. RESULTS Cell samples from eosinophilic nasal polyps from 13 patients were included in the study. Twenty-four hours after interferon-α stimulation, eosinophilic nasal polyp culture supernatants showed significantly decreased IL-4 concentrations and increase in interferon-γ, IL-10 and IL-6 concentrations compared to controls. There were no significant differences in tumor necrosis factor -α and IL-2 concentrations. CONCLUSION We demonstrated that interferon-α in vitro alters the pattern of cytokines in cell cultures of eosinophilic nasal polyps. Analysis of these alterations suggests that interferon-α promotes a rebalancing of inflammatory profiles in cell cultures, favoring the expression of Th1 and regulatory cytokines over Th2 cytokines.
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Affiliation(s)
- Júlio Cláudio Sousa
- Universidade Federal do Triângulo Mineiro (UFTM), Faculdade de Medicina, Disciplina de Otorrinolaringologia, Uberaba, MG, Brazil.
| | - Renata Margarida Etchbehere
- Universidade Federal do Triângulo Mineiro (UFTM), Faculdade de Medicina, Disciplina de Patologia Especial, Uberaba, MG, Brazil
| | - Eduardo Arthur Rodovalho Alves
- Universidade Federal do Triângulo Mineiro (UFTM), Faculdade de Medicina, Instituto de Pesquisa em Oncologia (IPON), Uberaba, MG, Brazil
| | - Letícia Montes Stark
- Universidade Federal do Triângulo Mineiro (UFTM), Faculdade de Medicina, Instituto de Pesquisa em Oncologia (IPON), Uberaba, MG, Brazil
| | - Eddie Fernando Cândido Murta
- Universidade Federal do Triângulo Mineiro (UFTM), Faculdade de Medicina, Instituto de Pesquisa em Oncologia (IPON), Uberaba, MG, Brazil
| | - Márcia Antoniazi Michelin
- Universidade Federal do Triângulo Mineiro (UFTM), Faculdade de Medicina, Instituto de Pesquisa em Oncologia (IPON), Uberaba, MG, Brazil
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Li W, Ho J, Grayson JW, Alvarado R, Rimmer J, Sewell WA, Campbell R, Kalish L, Sacks R, Harvey RJ. Evaluation of Diffuse Type 2 Dominant or Eosinophilic Chronic Rhinosinusitis With Corticosteroid Irrigation After Surgical Neosinus Cavity Formation. JAMA Otolaryngol Head Neck Surg 2021; 147:360-367. [PMID: 33538760 DOI: 10.1001/jamaoto.2020.5286] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Importance Eosinophilic chronic rhinosinusitis (eCRS), contemporarily classified as diffuse type 2 dominant chronic rhinosinusitis (CRS), is characterized by eosinophil-dominant mucosal inflammation. Contemporary management of eCRS as an inflammatory airway condition is multimodal with corticosteroid irrigations after the surgical creation of a neosinus cavity. Objectives To assess long-term treatment outcomes in patients with primary diffuse type 2 CRS or eCRS receiving multimodal treatment. Design, Setting, and Participants A prospective cohort study of patients seen in a tertiary rhinology practice recruited from May 2010 to November 2018 was conducted. Follow-up duration was 12 months or more following endoscopic sinus surgery (ESS) with a neosinus cavity formed. Data analysis was performed from August to November 2020. Consecutive adult (≥18 years) patients diagnosed with primary diffuse type 2 dominant CRS or eCRS based on the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 criteria were included. Type 2 inflammation was defined as more than 10 eosinophils per high-power field obtained from sinus mucosal biopsy and managed with neosinus cavity ESS and ongoing corticosteroid irrigations. Exclusion criteria were less than 12 months of follow-up and secondary CRS. Interventions Endoscopic sinus surgery with complete removal of intersinus bony partitions to create a neosinus cavity. Nasal irrigation (240 mL) with betamethasone, 1 mg, or budesonide, 1 mg, daily for 3 to 6 months after ESS and tapered to an as-needed basis (minimum, 2-3 per week). Main Outcomes and Measures Poor control was defined as polyp recurrence (polyp growth in >1 sinus area on a single side), use of long-term systemic therapy (biologic therapy or ≥3 consecutive months of oral corticosteroids), and revision surgery involving polypectomy. The disease in patients with no poor control criteria was defined as well controlled, and the disease in those with 1 or more criteria was considered poorly controlled. Maintenance medical therapy use and patient-reported outcomes based on the 22-item Sinonasal Outcomes Test for preoperative and last follow-up were collected. Results Of the 222 participants recruited with primary diffuse type 2 dominant CRS or eCRS and minimum of year of follow-up, 126 were men (56.8%). Mean (SD) age was 54.8 (13.6) years, and median (SD) follow-up was 2.2 (2.2) years. Of the 222 patients, 195 (87.8%) had well-controlled disease, 16 (7.2%) had polyp recurrence, 7 (3.2%) continued to receive long-term oral corticosteroid therapy, 5 (2.3%) received biologic therapy, and 8 (3.6%) underwent a revision polypectomy. Clinically meaningful change on the 22-item Sinonasal Outcomes Test and the nasal subdomain score was maintained at the last follow-up in 134 patients (67.0%). Poor disease control was not associated with poor adherence to irrigation use. Conclusions and Relevance The findings of this cohort study suggest that long-term disease control and reduction in symptom burden in patients with primary diffuse type 2 CRS or eCRS might be achieved when managed as an inflammatory disorder. Maintenance corticosteroid irrigations in the population examined appeared to be successfully self-tapered to disease activity.
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Affiliation(s)
- William Li
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
| | - Jacqueline Ho
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia
| | - Jessica W Grayson
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,Department of Otolaryngology Head and Neck Surgery, University of Alabama Birmingham
| | - Raquel Alvarado
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
| | - Janet Rimmer
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,Woolcock Institute, University of Sydney, Sydney, Australia.,Faculty of Medicine, Notre Dame University, Sydney, Australia
| | - William A Sewell
- St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia.,Immunology Division, Garvan Institute of Medical Research, Sydney, Australia
| | - Raewyn Campbell
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,Department of Otolaryngology Head and Neck Surgery, Royal Prince Alfred Hospital, Sydney, Australia.,Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia
| | - Larry Kalish
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,Department of Otolaryngology, Head and Neck Surgery, Concord General Hospital, University of Sydney, Sydney, Australia
| | - Raymond Sacks
- Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia.,Department of Otolaryngology, Head and Neck Surgery, Concord General Hospital, University of Sydney, Sydney, Australia
| | - Richard J Harvey
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia
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Lin YT, Lin CF, Liao CK, Chiang BL, Yeh TH. Clinical characteristics and cytokine profiles of central-compartment-type chronic rhinosinusitis. Int Forum Allergy Rhinol 2021; 11:1064-1073. [PMID: 33529479 DOI: 10.1002/alr.22759] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 11/25/2020] [Accepted: 12/06/2020] [Indexed: 02/03/2023]
Abstract
BACKGROUND The clinical characteristics of central-compartment-type chronic rhinosinusitis (CRS) in East Asian individuals are not clear. We sought to investigate the clinical features and the cytokine profiles of central-compartment-type CRS in our patient group. METHODS Adult patients diagnosed with bilateral CRS were recruited, and patients who had previously undergone sinus surgery and pansinusitis (Lund-Mackay scores >23) were excluded. Central-compartment-type CRS was defined by both endoscopic and radiological features. The symptoms, inhalant allergen sensitization status, endoscopic findings, and radiological assessments were recorded and compared between patients with central-compartment-type CRS and other types of CRS. We also examined the extent of tissue eosinophilia and specific cytokine protein levels (eosinophil cationic protein [ECP], myeloperoxidase [MPO], immunoglobulin E [IgE], interleukin [IL]-4, IL-5, and IL-13) in the sinonasal tissues. RESULTS Central-compartment-type CRS was found in 16 (23.9%) patients, and non-central-compartment-type CRS was found in 51 (76.1%) patients. Hyposmia or anosmia as the major symptom was more common in the central-compartment-type CRS group. The numbers of eosinophils in tissue and serum were significantly higher in the central-compartment-type CRS patients. The presence of allergen sensitization was not significantly different between groups. The levels of IL-5 and IL-13 were increased in middle turbinate tissues of patients with central-compartment-type CRS. CONCLUSION Central-compartment-type CRS was associated with hyposmia or anosmia, eosinophilic subtypes, and elevated levels of IL-5 and IL-13 in middle turbinate tissues but not necessarily correlated with allergic disease in our patients.
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Affiliation(s)
- Yi-Tsen Lin
- Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chih-Feng Lin
- Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Kang Liao
- Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan
| | - Bor-Luen Chiang
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Te-Huei Yeh
- Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.,College of Medicine, National Taiwan University, Taipei, Taiwan
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Beswick DM, Smith TL, Mace JC, Alt JA, Farrell NF, Ramakrishnan VR, Schlosser RJ, Soler ZM. Ethmoid-to-maxillary opacification ratio: a predictor of postoperative olfaction and outcomes in nasal polyposis? Int Forum Allergy Rhinol 2021; 11:48-57. [PMID: 32558260 PMCID: PMC7746627 DOI: 10.1002/alr.22625] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 04/21/2020] [Accepted: 05/13/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Inflammatory profiles for patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) vary between North American and Asian populations. An elevated ethmoid-to-maxillary (E/M) opacification ratio on preoperative imaging is associated with certain postoperative outcomes in Asian populations and populations that are non-type 2 dominant. In this study we explore this factor in North American/type 2-based populations. METHODS Adult patients (n = 165) from a North American population with CRSwNP who underwent endoscopic sinus surgery (ESS) were prospectively enrolled into an observational, multi-institutional study. The 22-item Sino-Nasal Outcome Test (SNOT-22), Brief Smell Identification Test (BSIT), and Lund-Kennedy (LK) endoscopic scores were obtained pre- and postoperatively. Patients were stratified according to increasing E/M ratios based on Lund-Mackay (LM) scores. RESULTS On average, significant within-subject postoperative improvement was found in all patients for SNOT-22 total and domain scores, and also BSIT results (p ≤ 0.019). Preoperatively, elevated E/M ratio correlated with worse BSIT scores (r = -0.343, p < 0.001). Postoperatively, elevated E/M ratio correlated with BSIT improvement (r = 0.284, p = 0.002), but did not correlate with SNOT-22 improvement or polyp recurrence. An elevated E/M ratio was associated with greater likelihood of reporting a minimal clinically important difference in BSIT scores (χ2 = 9.96, p = 0.041). CONCLUSION Elevated E/M ratios were found to associated with worse baseline olfaction and an increased likelihood of achieving a clinically meaningful postoperative improvement in olfaction in this North American population with CRSwNP. Elevated E/M ratios did not predict postoperative changes in SNOT-22 measures or polyp recurrence. This suggests that prognostic factors may vary according to geography and generalized inflammatory profiles (type 2 vs non-type 2) in patients with CRS.
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Affiliation(s)
- Daniel M. Beswick
- Department of Otolaryngology, University of Colorado, Aurora, CO, USA
| | - Timothy L. Smith
- Division of Rhinology and Sinus/Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University; Portland, OR, USA
| | - Jess C. Mace
- Division of Rhinology and Sinus/Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University; Portland, OR, USA
| | - Jeremiah A. Alt
- Sinus and Skull Base Surgery Program, Division of Otolaryngology - Head and Neck Surgery, Department of Surgery; University of Utah, Salt Lake City, UT, USA
| | - Nyssa F. Farrell
- Division of Rhinology and Sinus/Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University; Portland, OR, USA
| | | | - Rodney J. Schlosser
- Department of Otolaryngology-Head & Neck Surgery, Medical University of South Carolina, Charleston, SC., USA
| | - Zachary M. Soler
- Department of Otolaryngology-Head & Neck Surgery, Medical University of South Carolina, Charleston, SC., USA
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Xiong G, Xie X, Wang Q, Zhang Y, Ge Y, Lin W, Li M. Immune cell infiltration and related core genes expression characteristics in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps. Exp Ther Med 2020; 20:180. [PMID: 33101470 PMCID: PMC7579783 DOI: 10.3892/etm.2020.9310] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 09/04/2020] [Indexed: 12/31/2022] Open
Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) refers to chronic inflammation of the sinonasal mucosa. It can either be eosinophilic (ECRSwNP) or non-eosinophilic (non-ECRSwNP). However, immune cell infiltration in the microenvironment and pathogenesis of ECRSwNP and non-ECRSwNP are still unclear. The aim of the present study was to assess the immune cell infiltration and molecular mechanisms of ECRSwNP and non-ECRSwNP. In the present study, 22 immune cell types in ECRSwNP and non-ECRSwNP were investigated by CIBERSORT based on transcriptome data. The core gene related pathophysiology of CRSwNP was analyzed using Weighted Gene Correlation Network Analysis according to the phenotype of the infiltrated eosinophils and nasal polyps (NP). A total of four types of immune cells (mast cells, activated dendritic cells, M2 macrophages and activated natural killer cells) were demonstrated to have a direct and indirect correlation with eosinophilic infiltration in ECRSwNP. M1 macrophages and activated CD4+ memory T cells were correlated with major immune cell types in non-ECRSwNP. NP could affect the expression of ‘olfactory receptor activity’ and ‘channel activity’ genes to impair the olfactory signaling pathway and neuroactive ligand receptor pathway. ‘Cell adhesion molecule binding’, ‘cytokine receptor binding’ and ‘glucocorticoid receptor binding’ were significantly enriched in ECRSwNP, whereas epithelial cell injury, autophagy and the mTOR pathway (hsa04140 and hsa04150) may serve an important role in the pathogenesis of non-ECRSwNP. There were significantly different immune cell infiltration and related core genes expression characteristics between ECRSwNP and non-ECRSwNP. The results of the present study provide an improved basis for elucidation of the mechanism and treatment of CRSwNP.
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Affiliation(s)
- Gaoyun Xiong
- Department of Otolaryngology, Head and Neck Surgery, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China
| | - Xiaoxing Xie
- Department of Otolaryngology, Head and Neck Surgery, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China
| | - Qingliang Wang
- Department of Otolaryngology, Head and Neck Surgery, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China
| | - Yanyan Zhang
- Department of Otolaryngology, Head and Neck Surgery, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China
| | - Yanping Ge
- Department of Otolaryngology, Head and Neck Surgery, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China
| | - Wei Lin
- Department of Otolaryngology, Head and Neck Surgery, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China
| | - Mingqian Li
- Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China
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Fadda GL, Galizia A, Galizia G, Castelnuovo P, Bignami M, Cavallo G. Multiparametric Analysis of Factors Associated With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps. EAR, NOSE & THROAT JOURNAL 2020; 101:NP256-NP262. [PMID: 33023335 DOI: 10.1177/0145561320960357] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Previous studies have reported a diverse range of threshold values for blood eosinophilia. In addition, a single predictive biomarker for eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (ECRSwNP) has not yet been identified. OBJECTIVES The aim of this study is to compare the clinical characteristics of ECRSwNP and non-ECRSwNP to evaluate the preoperative risk of tissue eosinophilia of chronic rhinosinusitis with nasal polyps (CRSwNP) through a multiparametric statistical analysis. METHODS One hundred ten patients with evidence of chronic polypoid rhinosinusitis were included in this study and clinical records were retrospectively reviewed. Eosinophilic CRSwNP was diagnosed based on the presence of at least 10 eosinophils per high-power field. The demographic and clinical features of ECRSwNP and non-ECRSwNP are described. The values of blood eosinophilia as predictors of tissue eosinophilia have been identified using receiver operating characteristic curves. As the predictive value of the identified cutoff through regression analysis was low, we evaluated whether other risk factors could be statistically associated with ECRSwNP, and from this, a new predictive model was proposed for the identification of eosinophilic nasal polyps before surgery. RESULTS We found that the best method for predicting ECRSwNP is based on a model having asthma, blood eosinophil percentage, posterior ethmoid value in Lund-Mackay score, and modified Lund-Kennedy score as explanatory variables. CONCLUSIONS This study provides new data for a better understanding of the polypoid CRS endotypes, and the proposed model allows the endotype to be identified preoperatively.
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Affiliation(s)
- Gian Luca Fadda
- Department of Otorhinolaryngology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy
| | - Andrea Galizia
- Department of Otorhinolaryngology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy
| | - Giuseppe Galizia
- Department of Otorhinolaryngology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy
| | - Paolo Castelnuovo
- Department of Otorhinolaryngology, University of Insubria, Varese, Italy
| | - Maurizio Bignami
- Department of Otorhinolaryngology, University of Insubria, Varese, Italy
| | - Giovanni Cavallo
- Department of Otorhinolaryngology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy
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Predictive significance of arachidonate 15-lipoxygenase for eosinophilic chronic rhinosinusitis with nasal polyps. Allergy Asthma Clin Immunol 2020; 16:82. [PMID: 32973910 PMCID: PMC7493848 DOI: 10.1186/s13223-020-00480-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 09/04/2020] [Indexed: 12/20/2022] Open
Abstract
Background Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) exhibits a poorer outcome compared with non-eosinophilic chronic rhinosinusitis with nasal polyps (nonECRSwNP), so it is significant to identify effective markers to differentiate ECRSwNP in guiding the treatment strategies of these patients. Although arachidonate 15-lipoxygenase (ALOX15) is positioned as a marker of eosinophilic inflammation, its study in differentiating ECRSwNP has not been reported. The aim of this study is to assess the potential of ALOX15 in distinguishing and predicting ECRSwNP. Methods Forty-eight patients with chronic rhinosinusitis with nasal polyps (CRSwNP), including 30 ECRSwNP and 18 nonECRSwNP patients, were enrolled. ALOX15 mRNA level was determined in polyps by real-time polymerase chain reaction (RT-PCR). The patients’ baseline characteristics were evaluated and analyzed for correlations with ALOX15. Receiver operating characteristic (ROC) curve was used to assess the predictive significance of the potential predictors for ECRSwNP. Results ALOX15 mRNA level was significantly higher in ECRSwNP patients than in nonECRSwNP patients (P < 0.001). ALOX15 mRNA was significantly correlated with tissue and blood eosinophil percentages (r = 0.565, P < 0.001 and r = 0.395, P = 0.006), olfaction scores (r = 0.400, P = 0.005), total visual analogue scale (VAS) symptom scores (r = 0.383, P = 0.007), ethmoid/maxillary sinus (E/M) ratio (r = 0.463, P = 0.001), and endoscopy scores (r = 0.409, P = 0.004). Logistic regression analysis showed ALOX15 mRNA level and percentage of blood eosinophils to be predictive factors for ECRSwNP (P = 0.004 and P = 0.036, respectively). ROC curve indicated ALOX15 to have high predictive accuracy for ECRSwNP (area under the curve (AUC) = 0.909), which was further improved by combination of ALOX15 with percentage of blood eosinophils (AUC = 0.933). Conclusions The relative ALOX15 mRNA level alone or in combination with blood eosinophils might be a reliable biomarker for predicting a diagnosis of ECRSwNP.
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Lv H, Liu PQ, Xiang R, Zhang W, Chen SM, Kong YG, Xu Y. Predictive and Diagnostic Value of Nasal Nitric Oxide in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps. Int Arch Allergy Immunol 2020; 181:853-861. [PMID: 32690852 DOI: 10.1159/000509211] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 06/06/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND A hallmark of eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is mucosal eosinophil-predominant inflammation. Nasal nitric oxide (nNO) is a known biomarker of eosinophilic inflammation in the upper airway. However, the utility of nNO measurement in the upper airway remains controversial. The present study aimed to compare the use of other clinical parameters with nNO to prediagnose patients with eCRSwNP from Central China. METHODS From June 2019 to December 2019, 70 patients with CRSwNP undergoing endoscopic sinus surgery and 30 healthy subjects were enrolled. nNO measurements were performed in all of these subjects. Computed tomography scans, full blood count with differential analysis, and determination of total immunoglobulin E (total IgE) and plasma cytokines were performed before surgery. Receiver operating characteristic curves and logistic regression analysis were used to assess the predictive potential of the clinical parameters. RESULTS We recruited 24 patients with eCRSwNP and 46 with noneosinophilic CRSwNP (non-eCRSwNP). In patients with eCRSwNP, nNO levels were significantly higher than those in patients with non-eCRSwNP (p < 0.0001). Blood eosinophil percentages and counts, total IgE, and CT-derived ethmoid sinus and maxillary sinus ratio (E/M ratio) were all significantly higher compared with those in patients with non-eCRSwNP (p < 0.05). To diagnose eCRSwNP, the highest area under the curve (0.803) was determined for nNO. At a cutoff of >329 parts per billion (ppb), the sensitivity was 83.30% and the specificity was 71.70%. However, the levels of plasma cytokines Th1/Th2 were not significantly different between the histological types of CRSwNP (p > 0.05). CONCLUSION Measurement of nNO is useful for the early diagnosis of eCRSwNP.
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Affiliation(s)
- 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
| | - Pei-Qiang 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
| | - 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
| | - 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
| | - Shi-Ming Chen
- 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
| | - Yong-Gang Kong
- 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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Differentiation Between Eosinophilic Otitis Media and Otitis Media Associated With Eosinophilic Granulomatosis With Polyangiitis. Otol Neurotol 2020; 40:e796-e802. [PMID: 31290803 DOI: 10.1097/mao.0000000000002295] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To perform comparisons and clarify differences in clinical manifestations between eosinophilic otitis media (EOM) and otitis media associated with eosinophilic granulomatosis with polyangiitis (EGPA). STUDY DESIGN Retrospective case review. SETTING Tertiary referral center. PATIENTS Twenty-two ears of 11 patients exhibiting EOM (EOM group) and 20 ears of 12 patients exhibiting otitis media associated with EGPA (EGPA group). MAIN OUTCOME MEASURES Otological manifestations, nasal and paranasal manifestations, incidence of asthma, positivity for serum antineutrophil cytoplasmic antibodies (ANCA), total serum immunoglobulin (Ig) E level, peripheral blood eosinophil fraction, and hearing outcomes. RESULTS The incidence and age of onset of asthma and chronic rhinosinusitis were comparable between the EOM and EGPA groups. Moreover, otological findings and hearing outcomes at the initial visit were similar in both groups. Computed tomography images of the paranasal sinus showed predominant opacification of the ethmoid sinus in both groups. Although the total serum IgE level was not significantly different, the peripheral blood eosinophil fraction was significantly larger in the EGPA group than in the EOM group (p = 0.0035). Furthermore, the rate of myeloperoxidase-antineutrophil cytoplasmic antibodies (ANCA) positivity was significantly higher in the EGPA group than in the EOM group (p = 0.019). CONCLUSIONS The findings of the present study suggest that the phenotypic characteristics of EOM closely resemble those of otitis media associated with EGPA in early stages before the appearance of vasculitis. Therefore, it is challenging to differentiate the two conditions purely on the basis of otorhinological examinations.
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Lin L, Lan J, Dai F, Wei J, Chen Z, Sun G. Efficacy of Budesonide Nasal Spray on Neutrophilic Chronic Rhinosinusitis with Nasal Polyps: A Combined Clinical and Experimental Study. Int Arch Allergy Immunol 2020; 181:551-562. [PMID: 32369807 DOI: 10.1159/000507395] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 03/20/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Neutrophilic chronic rhinosinusitis with nasal polyps (CRSwNP) occur predominantly in Asian subjects. Appropriate treatments for this endotype have not been elucidated. This study aimed to evaluate the efficacy of budesonide nasal spray on neutrophilic CRSwNP. MATERIALS AND METHODS Fifteen neutrophilic CRSwNP patients were included, and then they received budesonide nasal spray treatment for 3 months. Biopsies of nasal polyps (NPs) were obtained from these subjects. Their clinical indexes were scored using Visual Analog Scale (VAS), Sino-Nasal Outcome Test (SNOT)-22, and Endoscopic Appearances (EAs). Histological analyses were used to assess numbers of neutrophils, goblet cells, and submucosal gland cells in NPs. Percentages of CD8+ T cells and CD4+CD25+Foxp3+ regulatory T cells (Tregs) were evaluated using flow cytometry. Mucin 5AC (MUC5AC), MUC5B, myeloperoxidase (MPO), interferon (IFN)-γ, and interleukin (IL)-1β and their mRNAs were also examined. After that, we cultured NP tissues in vitro and evaluated the abovementioned inflammatory parameters before and after the administration of budesonide. RESULTS Budesonide nasal spray did not improve clinical evaluations including VAS, SNOT-22, and EA scores. Numbers of neutrophils and goblet cells, the score of submucosal gland cells, percentages of CD8+ T cells and Tregs, MUC5AC, MUC5B, MPO, IFN-γ, and IL-1β and their mRNAs were not decreased in NPs after the budesonide treatment. Furthermore, the administration of budesonide into NP cultures also did not reduce their levels in comparison with those before the treatment. CONCLUSION These findings demonstrate that budesonide treatment may not alleviate the inflammatory condition in neutrophilic CRSwNP.
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Affiliation(s)
- Lin Lin
- Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, China,
| | - Jing Lan
- Department of Gynecology and Obstetrics, Huashan Hospital North of Fudan University, Shanghai, China
| | - Fei Dai
- Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, China
| | - Jinjin Wei
- Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, China
| | - Zheng Chen
- Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, China
| | - Guangbin Sun
- Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, China
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McHugh T, Levin M, Snidvongs K, Banglawala SM, Sommer DD. Comorbidities associated with eosinophilic chronic rhinosinusitis: A systematic review and meta-analysis. Clin Otolaryngol 2020; 45:574-583. [PMID: 32243094 DOI: 10.1111/coa.13536] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 03/09/2020] [Accepted: 03/22/2020] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Eosinophilic chronic rhinosinusitis (ECRS) is a histological subtype of CRS that is generally recognised as being more difficult to manage. Patients with ECRS tend to have greater disease severity and poorer treatment outcomes after sinus surgery when compared with non-ECRS patients. The histopathology and biomarker assessments of ECRS are often unavailable prior to surgery and may be impractical and costly to analyse. Thus, the primary objective of this study was to understand clinical comorbidities associated with ECRS. DESIGN/SETTING We searched three independent databases for articles that reported clinical CRS comorbidities associated with tissue eosinophilia. Data from studies with the same reported comorbidities were pooled, and a forest plot analysis was used to assess potential associations with four different conditions including allergic rhinitis, ASA sensitivity, asthma and atopy. The association between the phenotype of nasal polyps and ECRS was also quantified as a secondary objective. ECRS cut-off levels were as defined by papers included. MAIN OUTCOME/RESULTS Eighteen articles were identified. The presence of nasal polyps (the first numbers in brackets represent odds ratios) (5.85, 95% CI [3.61, 9.49], P < .00001), ASA sensitivity (5.63, 95% CI [3.43, 9.23], P < .00001), allergic rhinitis (1.84, 95% CI [1.27, 2.67], P = .001) and asthma (3.15, 95% CI [2.61, 3.82], P < .00001) were found to be significantly associated with tissue eosinophilia. Atopy, however, was not significantly associated with tissue eosinophilia (1.71, 95% CI [0.59, 4.95], P = .32). CONCLUSION Certain clinical disease characteristics such as ASA sensitivity, allergic rhinitis and asthma are more associated with CRS patients with eosinophilia when compared to those without eosinophilia. The phenotype of nasal polyps was also associated with ECRS. It is important for surgeons to recognise these comorbidities to ensure correct diagnoses, management and follow-up are implemented.
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Affiliation(s)
- Tobial McHugh
- Division of Otolaryngology, Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | - Marc Levin
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada
| | - Kornkiat Snidvongs
- Division of Otolaryngology, Head and Neck Surgery, Chulalongkorn University, Bangkok, Thailand
| | - Sarfaraz M Banglawala
- Division of Otolaryngology, Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
| | - Doron D Sommer
- Division of Otolaryngology, Head and Neck Surgery, Department of Surgery, McMaster University, Hamilton, ON, Canada
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Grayson JW, Li W, Ho J, Alvarado R, Rimmer J, Sewell WA, Harvey RJ. Topography of polyp recurrence in eosinophilic chronic rhinosinusitis. Int Forum Allergy Rhinol 2020; 10:604-609. [PMID: 32107886 DOI: 10.1002/alr.22529] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 11/22/2019] [Accepted: 01/03/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Eosinophilic chronic rhinosinusitis (eCRS) is an inflammatory endotype of CRS. Contemporary treatment includes creation of a "neo-sinus" cavity and postoperative corticosteroid irrigations. Not all patients gain control with local therapy. This study aims to determine, in patients with polyp recurrence, the most common sinuses involved. METHODS A prospective case-series was conducted on consecutive adult (≥18 years) post-FESS eCRS patients followed for a minimum of 12 months. All patients had a neo-sinus cavity created surgically and used corticosteroid irrigations daily for 3-6 months, then tapered to disease control. Sinus cavities were assessed by endoscopy on last follow-up. Polyp recurrence was defined as a score of 5 or 6 in the MLMES in ≥3 sinus cavities. Patient-reported outcomes based on SNOT22 and NSS, frequency of corticosteroid irrigations, and courses of systemic antibiotics and corticosteroid were collected. The pattern of sinus involvement was analyzed. RESULT A total of 342 sinus cavities were assessed (mean ± standard deviation, 54.9 ± 13.4 years, 43.2% female). Polyp recurrence occurred in 4.3% (6.4% of patients, n = 7 unilateral) of sinus cavities. Frontal and ethmoid sinus cavities were most affected in those with polyp recurrence, compared to the maxilla and sphenoid (100% vs 100% vs 53% vs 53%, p < 0.01). Although those patients with polyp recurrence utilized more systemic corticosteroids courses per year (0.4 ± 0.4 vs 0.1 ± 0.3, p < 0.01), the use of corticosteroid irrigations was similar (% >4/week; 66.7% vs 48.9%, p = 0.13). Prior surgery was more common in patients with polyp recurrence (86.7% vs 53.5%, p = 0.01). CONCLUSION The frontal and ethmoid sinuses were most affected in those patients with polyp recurrence. Whether the disease is more active in this location or topical therapy has limited access requires further evaluation.
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Affiliation(s)
- Jessica W Grayson
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
| | - William Li
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
| | - Jacqueline Ho
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia
| | - Raquel Alvarado
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia
| | - Janet Rimmer
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,Woolcock Institute, University of Sydney, Sydney, Australia.,Faculty of Medicine, Notre Dame University, Sydney, Australia
| | - William A Sewell
- St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia.,Immunology Division, Garvan Institute of Medical Research, Sydney, Australia
| | - Richard J Harvey
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.,Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia
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Xu Q, Du K, Zheng M, Duan S, Jia S, Chen H, Wang X, Zhang L. Application of Clinical Scores in the Differential Diagnosis of Chronic Rhinosinusitis With Nasal Polyps in a Chinese Population. Am J Rhinol Allergy 2020; 34:401-408. [PMID: 31992047 DOI: 10.1177/1945892420901996] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background Eosinophilic (Eos) and non-eosinophilic (non-Eos) chronic rhinosinusitis with nasal polyps (CRSwNP) react differently to clinical treatment, with eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) being more likely to recur after surgery. Objective To explore the clinical value of the visual analog scale (VAS), nasal endoscopy score (Lund–Kennedy, L–K), computed tomography (CT) score (Lund–Mackay scoring system, L–M), and blood Eos percentage in the differential diagnosis of Eos CRSwNP and non-Eos CRSwNP. Methods Ninety-nine patients with CRSwNP were enrolled in this study and assigned to 2 groups (Eos CRSwNP and non-Eos CRSwNP). The blood Eos percentage and VAS, L–K, and L–M scores in the 2 groups of patients were compared. A receiver operating characteristic (ROC) was used to assess the usefulness of VAS, L–K, and L–M scores for differentiating Eos CRSwNP and non-Eos CRSwNP. Results There were significantly differences between the Eos CRSwNP group and non-Eos CRSwNP group in the following scores: blood Eos percentage, mean VAS score, olfaction/VAS, general discomfort/L–K, edema score/L–K, olfactory cleft (OC) score via endoscopy, mean L–M score, anteriorethmoid sinus score, posterior ethmoid sinus score, sphenoid sinus score, frontal sinus score, and OC score via CT. An ROC analysis showed that blood Eos percentage had the highest area under the ROC curve (AUC) value (0.749); however, several other scores (olfaction score/VAS, edema score/L–K, and mean L–M score) also had high AUC values. The combination of olfaction score/VAS and blood Eos percentage had the highest clinical convenience score as well as high sensitivity and specificity. A combination of cutoff values for the 2 predictors (blood Eos percentage ≥3.85%, olfaction score/VAS score ≥3) showed a sensitivity of 75.5% and a specificity of 78.0%. Conclusion The olfaction score/VAS score and the blood Eos percentage can be combined to differentiate Eos CRSwNP from non-Eos CRSwNP in a Chinese population.
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Affiliation(s)
- Qingqing Xu
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Kun Du
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Ming Zheng
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Su Duan
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Shuangshuang Jia
- Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Hui Chen
- Department of Otolaryngology, Wang Jing Hospital of CACMS, Beijing, PR China
| | - Xiangdong Wang
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China
| | - Luo Zhang
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China
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Bauer AM, Turner JH. Personalized Medicine in Chronic Rhinosinusitis: Phenotypes, Endotypes, and Biomarkers. Immunol Allergy Clin North Am 2020; 40:281-293. [PMID: 32278451 DOI: 10.1016/j.iac.2019.12.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Chronic rhinosinusitis (CRS) is a heterogeneous disease process with a complex underlying cause. Improved understanding of CRS pathophysiology has facilitated new approaches to management of the patient with CRS that rely on targeting patient-specific characteristics and individual inflammatory pathways. A more personalized approach to care will ultimately incorporate a combination of phenotypic and endotypic classification systems to guide treatment. This review summarizes current evidence with respect to CRS phenotypes and endotypes, as well as the identification of potential biomarkers with potential to guide current and future treatment algorithms.
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Affiliation(s)
- Ashley M Bauer
- Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, 1215 21st Avenue South, Suite 7209, Nashville, TN 37232-8605, USA
| | - Justin H Turner
- Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, 1215 21st Avenue South, Suite 7209, Nashville, TN 37232-8605, USA.
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Brescia G, Franz L, Alessandrini L, Parrino D, Barion U, Marioni G. Prognostic role of blood eosinophil and basophil levels in allergic fungal rhinosinusitis (AFRS). Am J Otolaryngol 2020; 41:102301. [PMID: 31732306 DOI: 10.1016/j.amjoto.2019.102301] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 09/09/2019] [Indexed: 10/26/2022]
Abstract
PURPOSE Allergic fungal rhinosinusitis (AFRS) forms a subset of chronic rhinosinusitis with nasal polyps (CRSwNP) that is mainly characterized by eosinophilic nasal polyps, allergic mucin detected in the sinuses at surgery, and specific features on computerized tomography. Which biological markers predict disease recurrence in AFRS is still not clear, and the role of blood inflammatory cells in predicting recurrent polyps after surgery has yet to be investigated. The aim of this study was to newly investigate the prognostic role (in terms of recurrence rate) of preoperative blood eosinophil and basophil levels in AFRS. MATERIALS AND METHODS A consecutive series of 17 adult patients who underwent endoscopic sinus surgery for AFRS was retrospectively assessed. RESULTS Sinonasal polyps recurred in 7 of 17 patients. Considering the whole cohort, a significant positive correlation emerged between blood eosinophil and basophil counts, but not between blood and tissue eosinophil counts. Statistical analysis found significantly higher blood eosinophil and basophil levels in AFRS patients who relapsed than in those who did not. CONCLUSIONS Considering the current difficulty of identifying more effective, personalized approaches to postoperative disease management in AFRS, our preliminary data support the impression that blood eosinophil and basophil levels warrant testing in further prospective and larger (preferably multi-institutional) investigations as part of the preoperative work-up for patients with AFRS in order to administer dedicated postoperative medical treatments for patients at higher risk of relapse.
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Ganti A, Kuhar HN, Eggerstedt M, Mahdavinia M, Gattuso P, Batra PS, Tajudeen BA. The Association of Serum Eosinophilia with Structured Histopathology in Chronic Rhinosinusitis. Ann Otol Rhinol Laryngol 2019; 129:512-516. [DOI: 10.1177/0003489419898200] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Background: Prior studies have demonstrated associations between serum eosinophilia and chronic rhinosinusitis (CRS) pathogenesis. However, the association of serum eosinophilia with histopathology profiling in CRS has not been fully delineated and may help better characterize CRS disease burden prior to surgery. Methods: A structured histopathology report of 13 variables was utilized to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). Complete blood count (CBC) with differential was drawn within 4 weeks prior to FESS. Serum eosinophilia was defined as >6.0% (>0.60 th/μL). Histopathology variables were compared among patients. Results: A total of 177 CRS patients (37 with serum eosinophilia and 140 with normal serum eosinophilia) were analyzed. Compared to CRS patients with normal serum eosinophil counts, CRS patients with serum eosinophilia demonstrated increased polypoid disease (67.6% vs 35.0%, P < .001), eosinophil aggregates (45.9% vs 20.7%, P = .003), and eosinophils per high-power field (>5/HPF) (67.6% vs 40.7%, P = .003). Conclusion: CRS patients with serum eosinophilia demonstrated severe disease burden on histopathology with high levels of polypoid disease and tissue eosinophilia. However, a considerable number of patients without serum eosinophilia demonstrated eosinophilic disease on histopathology, indicating that preoperative serum eosinophilia alone could not be reliably used to predict eosinophilic CRS. Level of evidence: 4
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Affiliation(s)
- Ashwin Ganti
- Rush Medical College, Rush University, Chicago, IL, USA
| | | | - Michael Eggerstedt
- Department of Otorhinolaryngology—Head and Neck Surgery, Rush Sinus Program, Rush University Medical Center, Chicago, IL, USA
| | - Mahboobeh Mahdavinia
- Department of Internal Medicine, Division of Allergy/Immunology, Rush University Medical Center, Chicago, IL, USA
| | - Paolo Gattuso
- Department of Pathology, Rush University Medical Center, Chicago, IL, USA
| | - Pete S. Batra
- Department of Otorhinolaryngology—Head and Neck Surgery, Rush Sinus Program, Rush University Medical Center, Chicago, IL, USA
| | - Bobby A. Tajudeen
- Department of Otorhinolaryngology—Head and Neck Surgery, Rush Sinus Program, Rush University Medical Center, Chicago, IL, USA
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Rai G, Roy P, Gupta N, Sharma S, Dar SA, Ansari MA, Ramachandran VG, Das S. Computed Tomography Score an Excellent Marker: Differentiates Eosinophilic and Non-eosinophilic Variants of Chronic Rhinosinusitis with Nasal Polyp. Indian J Otolaryngol Head Neck Surg 2019; 71:1787-1792. [PMID: 31763246 PMCID: PMC6848347 DOI: 10.1007/s12070-017-1154-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Accepted: 07/17/2017] [Indexed: 11/24/2022] Open
Abstract
Eosinophilic and non-eosinophilic subtypes of chronic rhinosinusitis with nasal polyp (CRSwNP) have different clinical profile and management. Currently the 2 subtypes are differentiated based on tissue eosinophilic infiltration, which is identified after surgery by histopathological examination. Hence this study was conducted to compare utility of computed tomography (CT) scans, serum IgE levels, absolute eosinophil count (AEC) and Sino-nasal Outcome Test (SNOT)-20 score for discriminating the 2 subtypes. In this prospective study of 1 year duration, patients suspected of CRSwNP were recruited. Serum IgE levels and AEC estimation were performed by ELISA and standard numerical formula respectively, along with histopathological examination of nasal polyp biopsies. CT score and ratio of CT score for ethmoid sinus and maxillary sinus (E/M ratio) were calculated. Patients were asked to fill SNOT-20 questionnaire. Receiver-operating characteristic (ROC) curve analysis was performed. Out of 52 patients studied, 38 and 14 were no. of eosinophilic and non-eosinophilic CRSwNP cases respectively on the basis of histopathological examination. E/M ratio and overall CT score were found to be highly accurate with area under ROC curve of 0.990 and 0.964 respectively, while rest 3 parameters had low accuracy. Optimal cut-off of CT score and E/M ratio for eosinophilic CRSwNP were 6 and 2.065 respectively. This study demonstrated E/M ratio and total CT score as the most useful surrogate markers for preoperative differentiation of eosinophilic and non-eosinophilic CRSwNP, and hence can be used to predetermine postoperative management before surgery.
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Affiliation(s)
- Gargi Rai
- Department of Microbiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, 110095 India
| | - Priyamvada Roy
- Department of Microbiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, 110095 India
| | - Neelima Gupta
- Department of Otorhinolaryngology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, 110095 India
| | - Sonal Sharma
- Department of Pathology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, 110095 India
| | - Sajad Ahmed Dar
- Department of Microbiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, 110095 India
| | - Mohammad Ahmed Ansari
- Department of Microbiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, 110095 India
| | - V. G. Ramachandran
- Department of Microbiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, 110095 India
| | - Shukla Das
- Department of Microbiology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, 110095 India
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Matsumoto N, Shigekusa T, Matsuo A, Tsubouchi H, Yanagi S, Nakazato M. Allergic bronchopulmonary aspergillosis complicated by eosinophilic chronic rhinosinusitis successfully treated with mepolizumab. Respirol Case Rep 2019; 7:e00465. [PMID: 31346471 PMCID: PMC6635141 DOI: 10.1002/rcr2.465] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 05/16/2019] [Accepted: 06/13/2019] [Indexed: 12/22/2022] Open
Abstract
A 67-year-old woman was admitted to our hospital because of frequent asthma attacks and refractory chronic rhinosinusitis. She was diagnosed with allergic bronchopulmonary aspergillosis (ABPA) concomitant with eosinophilic chronic rhinosinusitis (ECRS) on the basis of peripheral blood eosinophilia, precipitating antibodies against Aspergillus fumigatus, elevated total serum IgE, pulmonary infiltration, central bronchiectasis, mucoid impaction, and bilateral rhinosinusitis with nasal polyps, which showed remarkable eosinophil accumulation histologically, especially in the ethmoid sinuses. Treatment with mepolizumab, 100 mg every 4 weeks, was initiated for both the ABPA and ECRS. Consistent with the decrease in the peripheral eosinophil count, the asthma and rhinosinusitis symptoms were drastically ameliorated. Not only her airway symptoms but also her exercise tolerance and pulmonary function test results remarkably improved. Mepolizumab therapy enhanced the quality of life for this patient with intractable ABPA and ECRS.
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Affiliation(s)
- Nobuhiro Matsumoto
- Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
| | - Takafumi Shigekusa
- Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
| | - Ayako Matsuo
- Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
| | - Hironobu Tsubouchi
- Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
| | - Shigehisa Yanagi
- Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
| | - Masamitsu Nakazato
- Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of MedicineUniversity of MiyazakiMiyazakiJapan
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do Amaral JB, Bloise AC, França CN, Perez-Novo C, Machado-Santelli GM, Alencar AM, Pezato R. Alterations in cellular force parameters and cell projections in Nasal polyps-derived fibroblasts. Auris Nasus Larynx 2019; 47:98-104. [PMID: 31272842 DOI: 10.1016/j.anl.2019.06.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 06/07/2019] [Accepted: 06/20/2019] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a disease that features a mechanical dysfunction involving chronic inflammation and altered tissue remodeling. In this study, we aim to evaluate the fibroblast morphology and its cellular traction force in primary fibroblasts cell cultures obtained from both healthy individuals (n=7) and patients with CRSwNP (n=8). METHODS Using a Traction-force Microscopy we analyzed parameters of Force/Tension in fibroblasts cultures in both experimental groups. RESULTS The analysis of the Projected Area of Cell revealed that fibroblasts derived from nasal mucosa of healthy individuals have an area on average 39.24% larger than the fibroblasts obtained from the nasal polyp tissue. We also observed that the parameters directly related to the force of the cell, Max Cumulative Force and Net Contractile Moment, presented a high Force/Tension per unit of area in the fibroblasts derived from the healthy nasal mucosa (on average 41% and 52.54% higher than the fibroblasts of the nasal polyp respectively). CONCLUSION Our results demonstrate a cellular mechanism that may be associated with the mechanical dysfunction found in the Nasal Polyp tissue. The weak traction force of nasal polyp-derived fibroblast may, in lower dimensions, impact on the remodeling of nasal mucosa in CRSwNP.
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Affiliation(s)
- Jônatas Bussador do Amaral
- ENT Research Lab., Department of Otorhinolaryngology - Head and Neck Surgery, Federal University of Sao Paulo, Rua Coronel Lisboa, 958, Vila Clementino, São Paulo, SP, 04020-041, Brazil.
| | - Antonio Carlos Bloise
- Institute of Physics, University of Sao Paulo, Rua do Matão, Travessa R Número 187, Cidade Universitária, São Paulo, SP 05508-090, Brazil
| | - Carolina Nunes França
- Universidade Santo Amaro, Pós Graduação em Ciências da Saúde, Rua Enéas de Siqueira Neto, 340 Jardim das Imbuias, São Paulo, SP 04829-300, Brazil
| | - Claudina Perez-Novo
- Laboratory of Proteinchemistry, Proteomics and Epigenetic Signalling Department of Biomedical Sciences, Campus Drie Eiken, building T, first floor Universiteitsplein 1 2610 Wilrijk University of Antwerp, Belgium
| | - Gláucia Maria Machado-Santelli
- Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Avenida Prof Lineu Prestes, 1524, dade Universitária, Sao Paulo, SP 05508-900, Brazil
| | - Adriano Mesquita Alencar
- Institute of Physics, University of Sao Paulo, Rua do Matão, Travessa R Número 187, Cidade Universitária, São Paulo, SP 05508-090, Brazil
| | - Rogério Pezato
- ENT Research Lab., Department of Otorhinolaryngology - Head and Neck Surgery, Federal University of Sao Paulo, Rua Coronel Lisboa, 958, Vila Clementino, São Paulo, SP, 04020-041, Brazil
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Meng Y, Zhang L, Lou H, Wang C. Predictive value of computed tomography in the recurrence of chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol 2019; 9:1236-1243. [PMID: 31237991 DOI: 10.1002/alr.22355] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Revised: 03/26/2019] [Accepted: 04/28/2019] [Indexed: 01/07/2023]
Abstract
BACKGROUND Chronic rhinosinusitis with nasal polyps (CRSwNP) is a nasal disease with a high tendency for recurrence. The aim of this study was to compare the use of computed tomography (CT) scan with other clinical parameters in predicting the recurrence of CRSwNP. METHODS A total of 272 consecutive CRSwNP patients undergoing endoscopic functional sinus surgery were recruited. The demographic characteristics and clinical parameters, including CT scores, level of exhaled nitric oxide, and peripheral eosinophilia, were recorded. The degree of infiltration of inflammatory cells in the sinus mucosa was evaluated. RESULTS Two hundred thirty of the 272 patients completed the study (118 patients with recurrence and 112 patients with no recurrence). The average follow-up time was 24 months after the first surgery. The 2 groups were not significantly different with respect to age, gender distribution, comorbid allergy, exhaled oral fractional exhaled nitric oxide levels, nasal obstruction/runny nose/headache/facial pain scores, Lund-Mackay score, peripheral eosinophil percentage, and peripheral eosinophil absolute count. The onset of surgical history and asthma, visual analog scores of CRS, anosmia score, ratio of total ethmoid sinus scores for both sides and maxillary sinus score for both sides (E/M ratio), Lund-Kennedy score, tissue eosinophil percentage, and tissue eosinophil absolute count were significantly higher in the recurrence group. The E/M ratio showed high accuracy as a predictor for CRSwNP recurrence. The cut-off point of 2.55 for E/M ratio indicated the highest predictive value of CRSwNP recurrence. CONCLUSION The E/M ratio is a useful predictor for the recurrence of CRSwNP in the Chinese population.
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Affiliation(s)
- Yifan Meng
- 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
| | - Hongfei Lou
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
| | - Chengshuo Wang
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
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Predictors of disease progression after endoscopic sinus surgery in patients with chronic rhinosinusitis. The Journal of Laryngology & Otology 2019; 133:678-684. [PMID: 31218991 DOI: 10.1017/s0022215119001245] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVE This study aimed to determine the predictors of disease progression after functional endoscopic sinus surgery in patients with chronic rhinosinusitis. METHOD A total of 281 adult chronic rhinosinusitis patients who underwent primary bilateral functional endoscopic sinus surgery between 2007 and 2017 and had at least 12 months of follow-up endoscopic evaluation were examined. Patients were divided into eosinophilic (n = 205) and non-eosinophilic chronic rhinosinusitis groups (n = 76). In order to determine adverse factors, post-operative endoscopic appearance scores were analysed in relation to the pre- and intra-operative findings using multiple regression analyses. RESULTS The post-operative course of eosinophilic cases deteriorated over time, like the early period for non-eosinophilic cases. Frontal sinus polyps recurred early in eosinophilic chronic rhinosinusitis. Multivariate analyses indicated young adulthood, asthma, high computed tomography score and frontal sinus polyps as significant adverse predictors. CONCLUSION Early, appropriate estimation of sinonasal conditions appears to be crucial for successful surgical management of chronic rhinosinusitis.
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Mastalerz L, Tyrak KE, Ignacak M, Konduracka E, Mejza F, Ćmiel A, Buczek M, Kot A, Oleś K, Sanak M. Prostaglandin E 2 decrease in induced sputum of hypersensitive asthmatics during oral challenge with aspirin. Allergy 2019; 74:922-932. [PMID: 30446997 DOI: 10.1111/all.13671] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 11/01/2018] [Accepted: 11/05/2018] [Indexed: 01/03/2023]
Abstract
BACKGROUND A special regulatory role for prostaglandin E2 (PGE2 ) has been postulated in nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD). OBJECTIVE To investigate the effect of systemic aspirin (acetylsalicylic acid) administration on airway PGE2 biosynthesis in induced sputum supernatant (ISS) among subjects with NERD or aspirin-tolerant asthma with chronic rhinosinusitis with nasal polyposis (ATA-CRSwNP), as well as healthy controls (HC). METHODS Induced sputum (IS) was collected from patients with NERD (n = 26), ATA-CRSwNP (n = 17), and HC (n = 21) at baseline and after aspirin challenge. Sputum differential cell count and IS supernatant (ISS) levels of prostanoids, PGE2 , 8-iso-PGE2 , tetranor-PGE-M, 8-iso-PGF2 α, and leukotriene C4 , D4 , and E4 , were determined using mass spectrometry. Urinary excretion of LTE4 was measured by ELISA. RESULTS NERD subjects had elevated sputum eosinophilic count as compared to ATA-CRSwNP and HC (median NERD 9.1%, ATA-CRSwNP 2.1%, and HC 0.4%; P < 0.01). Baseline ISS levels of PGE2 were higher in asthmatics as compared to HC at baseline (NERD vs HC P = 0.04, ATA-CRSwNP vs HC P < 0.05). Post-challenge ISS levels of PGE2 compared to baseline significantly decreased in NERD and HC (P < 0.01 and P = 0.01), but not in ATA-CRSwNP. In NERD, a similar decrease in PGE2 as in HC resulted from 2.8 times lower dose of aspirin. CONCLUSION Aspirin-precipitated bronchoconstriction is associated with a decrease in airway PGE2 biosynthesis. These results support the mechanism of PGE2 biosynthesis inhibition as a trigger for bronchoconstriction in NERD.
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Affiliation(s)
- Lucyna Mastalerz
- Department of Internal Medicine Jagiellonian University School of Medicine Cracow Poland
| | - Katarzyna E. Tyrak
- Department of Internal Medicine Jagiellonian University School of Medicine Cracow Poland
| | - Maria Ignacak
- Department of Internal Medicine Jagiellonian University School of Medicine Cracow Poland
| | - Ewa Konduracka
- Coronary and Heart Failure Department Jagiellonian University School of Medicine John Paul II Hospital Cracow Poland
| | - Filip Mejza
- Department of Internal Medicine Jagiellonian University School of Medicine Cracow Poland
| | - Adam Ćmiel
- Department of Applied Mathematics AGH University of Science and Technology Cracow Poland
| | - Michał Buczek
- Department of Internal Medicine Jagiellonian University School of Medicine Cracow Poland
| | - Adrianna Kot
- Department of Internal Medicine Jagiellonian University School of Medicine Cracow Poland
| | - Krzysztof Oleś
- Department of Oncological and Reconstructive Surgery The Maria Sklodowska‐Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch Gliwice Poland
| | - Marek Sanak
- Department of Internal Medicine Jagiellonian University School of Medicine Cracow Poland
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Massoth L, Anderson C, McKinney KA. Asthma and Chronic Rhinosinusitis: Diagnosis and Medical Management. Med Sci (Basel) 2019; 7:E53. [PMID: 30934800 PMCID: PMC6524348 DOI: 10.3390/medsci7040053] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 03/21/2019] [Accepted: 03/22/2019] [Indexed: 12/17/2022] Open
Abstract
Asthma is a prevalent inflammatory condition of the lower airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchial hyperresponsiveness (BHR). Symptomatically, these patients may demonstrate wheezing, breathlessness, chest tightness, and coughing. This disease is a substantial burden to a growing population worldwide that currently exceeds 300 million individuals. This is a condition that is frequently encountered, but often overlooked in the field of otolaryngology. In asthma, comorbid conditions are routinely present and contribute to respiratory symptoms, decreased quality of life, and poorer asthma control. It is associated with otolaryngic diseases of the upper airways including allergic rhinitis (AR) and chronic rhinosinusitis (CRS). These conditions have been linked epidemiologically and pathophysiologically. Presently, they are considered in the context of the unified airway theory, which describes the upper and lower airways as a single functional unit. Thus, it is important for otolaryngologists to understand asthma and its complex relationships to comorbid diseases, in order to provide comprehensive care to these patients. In this article, we review key elements necessary for understanding the evaluation and management of asthma and its interrelatedness to CRS.
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Affiliation(s)
- Landon Massoth
- College of Medicine, University of Oklahoma, Oklahoma City, OK 73104, USA.
| | - Cody Anderson
- College of Medicine, University of Oklahoma, Oklahoma City, OK 73104, USA.
| | - Kibwei A McKinney
- College of Medicine, University of Oklahoma, Oklahoma City, OK 73104, USA.
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Kim MB, Lim GC, Park JA, Kim YS, Kim JH, Kang JW. Computed Tomography Findings in Patients with Samter's Triad: An Observational Study. Open Med (Wars) 2019; 14:241-246. [PMID: 30847401 PMCID: PMC6401393 DOI: 10.1515/med-2019-0018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Accepted: 01/14/2019] [Indexed: 11/17/2022] Open
Abstract
Samter’s Triad is a disorder characterized by chronic rhinosinusitis (CRS) with nasal polyps (NPs), asthma, and intolerance to cyclooxygenase-1 inhibitors. However, there have been no studies investigating the prediction of Samter’s Triad using imaging findings. Therefore, the authors aimed to investigate whether there is a difference in computed tomography (CT) findings between patients who have CRS with NPs and those with Samter’s Triad. Patients were classified into a CRS group and a Samter group. Opacification was measured using data from CT scans by scoring each sinus on a numerical rating scale ranging from 0 to 4. The opacification scores of the ethmoid and frontal sinuses were significantly higher in the Samter’s Triad group. Furthermore, Samter’s Triad was more common in patients who scored ≤ 2 for maxillary opacification (7/16) than in those who scored ≥3 (4/45, p=0.005). Patients with Samter’s Triad exhibited a tendency toward higher opacification scores for the ethmoid and frontal sinuses, with a relatively lower opacification score for the maxillary sinus. These findings could be helpful in distinguishing patients with Samter’s Triad from those who have CRS with NPs, and to plan treatment strategies without having to perform additional laboratory or radiological tests.
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Affiliation(s)
- Min Bum Kim
- Department of Otorhinolaryngology, Jeju National University School of Medicine, 102 Jejudaehakno, Jeju 63243, Jeju, South Korea
| | - Gil Chai Lim
- Department of Otorhinolaryngology, Jeju National University School of Medicine, 102 Jejudaehakno, Jeju 63243, Jeju, South Korea
| | - Jin A Park
- Department of Otorhinolaryngology, Jeju National University School of Medicine, 102 Jejudaehakno, Jeju 63243, Jeju, South Korea
| | - Yoo Suk Kim
- Department of Otorhinolaryngology, Jeju National University School of Medicine, 102 Jejudaehakno, Jeju 63243, Jeju, South Korea.,Department of Otolaryngology, Ajou University School of Medicine, Suwon, South Korea
| | - Jeong Hong Kim
- Department of Otorhinolaryngology, Jeju National University School of Medicine, 102 Jejudaehakno, Jeju 63243, Jeju, South Korea
| | - Ju Wan Kang
- Department of Otorhinolaryngology, Jeju National University School of Medicine, 102 Jejudaehakno, Jeju 63243, Jeju, South Korea
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