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1
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Kryukov AI, Chernykh NM, Nosulya EV, Kunelskaya NL, Kim IA, Karnoukhova OG. [Control of hormonal rhinitis symptoms in patients with hypothyrosis: pathogenetic and clinical aspects]. Vestn Otorinolaringol 2023; 88:54-60. [PMID: 37767591 DOI: 10.17116/otorino20228804154] [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] [Indexed: 09/29/2023]
Abstract
BACKGROUND One of the poorly studied sections of the pathology of ENT organs is chronic rhinitis in patients with hypothyroidism, the pathogenesis of which has not been fully understood, the diagnosis causes significant difficulties, and there are no recommendations for treatment. Despite receiving replacement therapy with levothyroxine, the symptoms of rhinitis persist. OBJECTIVE To study the effectiveness of the use of intranasal glucocorticosteroids in patients with chronic rhinitis and hypothyroidism. MATERIAL AND METHODS Patients with chronic rhinitis and hypothyroidism used mometasone nasal spray 100 mcg 1 time per day for a course of treatment of 2 months (n=60). To assess the symptoms of rhinitis, a visual analog scale (0-10 points), endoscopic examination of ENT organs, anterior active rhinomanometry were used. Evaluation of mucociliary transport was used a saccharin test. The concentration of transforming growth factor (TGF-β1) in nasal secretion and blood serum was studied by ELISA (Enzyme-Linked Immunosorbent Assay), the number of metabolites of NO - nitrites+nitrates (NOx) was recorded by colorimetric method. RESULTS The use of mometasone nasal spray in patients with hypothyroidism helped to reduce complaints on a visual-analog scale (difficulty in nasal breathing, rhinorrhea) and improve nasal breathing according to anterior active rhinomanometry. The concentrations of TGF-β1 and NOx in nasal secretions before mometasone treatment were higher than after treatment, which probably indicates the contribution of these substances to the formation of edematous hypertrophic changes from the nose in patients with hypothyroidism.
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Affiliation(s)
- A I Kryukov
- L.A. Sverzhevsky Scientific Research Clinical Institute of Otorhinolaryngology, Moscow, Russia
- Pirogov Russian National Research Medical University of the Ministry of Health of Russia, Moscow, Russia
| | - N M Chernykh
- Irkutsk State Medical University of the Ministry of Health of the Russian Federation, Irkutsk, Russia
| | - E V Nosulya
- L.A. Sverzhevsky Scientific Research Clinical Institute of Otorhinolaryngology, Moscow, Russia
| | - N L Kunelskaya
- L.A. Sverzhevsky Scientific Research Clinical Institute of Otorhinolaryngology, Moscow, Russia
- Pirogov Russian National Research Medical University of the Ministry of Health of Russia, Moscow, Russia
| | - I A Kim
- Pirogov Russian National Research Medical University of the Ministry of Health of Russia, Moscow, Russia
- Research and Clinical Center of Otorhinolaryngology of FMBA of Russia, Moscow, Russia
| | - O G Karnoukhova
- Irkutsk State Medical University of the Ministry of Health of the Russian Federation, Irkutsk, Russia
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2
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Win H, Gowin K. Treatment of scleromyxedema with lenalidomide, bortezomib and dexamethasone: A case report and review of the literature. Clin Case Rep 2020; 8:3043-3049. [PMID: 33363876 PMCID: PMC7752349 DOI: 10.1002/ccr3.3302] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 07/28/2020] [Accepted: 08/12/2020] [Indexed: 11/16/2022] Open
Abstract
Scleromyxedema is a rare and progressive disease that currently has no standard treatment. Triplet therapy with lenalidomide, bortezomib, and dexamethasone can be an effective therapy for scleromyxedema, especially in patients with refractory or relapsed disease.
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Affiliation(s)
- Hninyee Win
- Department of MedicineUniversity of ArizonaTucsonArizona
| | - Krisstina Gowin
- Department of Hematology and OncologyUniversity of ArizonaTucsonArizona
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3
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Kim JS, Choi H, Oh JM, Kim YH, Kim SW, Kim SW, Kim BG, Cho JH, Lee J, Lee DC. Effect of fluticasone propionate on human nasal fibroblasts exposed to urban particulate matter. Auris Nasus Larynx 2020; 47:415-424. [PMID: 31822346 DOI: 10.1016/j.anl.2019.11.002] [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: 07/24/2019] [Revised: 11/08/2019] [Accepted: 11/15/2019] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Particulate matter (PM), which contains organic compounds and toxic metals, is the major cause of air pollution. PM enters the body, causing various health problems. Although the effects of PM on the lower respiratory tract have been extensively investigated, the effects on the upper respiratory tract (including the nasal cavity) require further evaluation. To investigate the effect of fluticasone propionate (FP) on nasal fibroblasts exposed to UPM. METHODS Samples of inferior turbinate tissue were obtained from six patients. The fibroblasts isolated from these samples were exposed to UPM and/or FP. The expression of interleukin (IL)-6, CXC chemokine ligand (CXCL) 1, IL-1β, and tumour necrosis factor-alpha (TNF-α) in nasal fibroblasts was analysed using real-time PCR and enzyme-linked immunosorbent assays. The protein levels of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) were analysed by western blotting. RESULTS FP reversed the UPM-induced reduction in cell viability. The mRNA and protein levels of IL-6, CXCL1, IL-1β, and TNF-α were significantly increased by UPM. FP reversed the UPM-induced increases in the protein levels of NF-κB and phosphorylated-STAT3 in a dose-dependent manner. In addition, TNF-α, an inducer of NF-κB, reversed the FP-induced reduction in the levels of signalling molecules. CONCLUSION UPM induces the expression of IL-6, CXCL1, IL-1β, and TNF-α in nasal fibroblasts and this effect is reversed by FP via the STAT3 and NF-κB signalling pathways. These results suggest that FP has therapeutic potential for nasal diseases related to UPM, such as allergic and chronic rhinitis.
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Affiliation(s)
- Ji-Sun Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hyunsu Choi
- Clinical Research Institute, Daejeon St. Mary's Hospital, Daejeon, Republic of Korea
| | - Jeong-Min Oh
- Clinical Research Institute, Daejeon St. Mary's Hospital, Daejeon, Republic of Korea
| | - Yoon-Ho Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung Won Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Soo Whan Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Byung Guk Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Hee Cho
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Joohyung Lee
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dong Chang Lee
- Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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4
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Bjermer L, Westman M, Holmström M, Wickman MC. The complex pathophysiology of allergic rhinitis: scientific rationale for the development of an alternative treatment option. Allergy Asthma Clin Immunol 2019; 15:24. [PMID: 31015846 PMCID: PMC6469109 DOI: 10.1186/s13223-018-0314-1] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 12/20/2018] [Indexed: 01/27/2023] Open
Abstract
Allergic rhinitis (AR) poses a global health problem and can be challenging to treat. Many of the current symptomatic treatments for AR have been available for decades, yet there has been little improvement in patient quality of life or symptom burden over the years. In this review, we ask why this might be and explore the pathophysiological gaps that exist within the various AR treatment classes. We focus on the benefits and drawbacks of different treatment options and delivery routes for AR treatments and consider how, given what is known about AR pathophysiology and symptomatology, patients may be offered more effective treatment options for rapid, effective, and sustained AR control. In particular, we consider how a new AR preparation, MP-AzeFlu (Dymista®, Meda, Sweden), comprising a formulation of an intranasal antihistamine (azelastine hydrochloride), an intranasal corticosteroid (fluticasone propionate), and excipients delivered in a single spray, may offer benefits over and above single and multiple AR therapy options. We review the evidence in support of this treatment across the spectrum of AR disease. The concept of AR control is also reviewed within the context of new European Union and Contre les Maladies Chroniques pour un VIeillissement Actif-Allergic Rhinitis and its Impact on Asthma initiatives.
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Affiliation(s)
- Leif Bjermer
- 1Department of Respiratory Medicine & Allergology, Skane University Hospital, 22185, Lund, Sweden
| | - Marit Westman
- 2Dept. of ENT-diseases, Karolinska University Hospital, 171 76 Stockholm, Sweden.,3Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institutet, 171 77 Stockholm, Sweden
| | - Mats Holmström
- 4Dept. of Clinical Science, Intervention and Technology, Division of Ear, Nose and Throat Diseases, Karolinska Institutet, 171 77 Stockholm, Sweden
| | - Magnus C Wickman
- 5Department of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.,Sach's Children's Hospital, 118 83 Stockholm, Sweden
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5
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Jung HJ, Zhang YL, Kim DK, Rhee CS, Kim DY. The Role of NF-κB in Chronic Rhinosinusitis With Nasal Polyps. ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2019; 11:806-817. [PMID: 31552716 PMCID: PMC6761067 DOI: 10.4168/aair.2019.11.6.806] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 03/23/2019] [Accepted: 04/09/2019] [Indexed: 12/15/2022]
Abstract
PURPOSE Whereas the majority of nasal polyps observed in Western populations are eosinophilic, non-eosinophilic nasal polyps are significantly more frequent in Asian countries. Given the importance of nuclear factor-kappa B (NF-κB) in inflammation, this study focused on the role of NF-κB in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNPs) in Asian patients. METHODS A total of 46 patients were enrolled in this study (22 diagnosed with CRSwNPs, 10 with chronic rhinosinusitis without nasal polyps [CRSsNP], and 14 control subjects). Nasal polyps and uncinate tissues (UTs) were collected and the tissues prepared for hematoxylin-eosin staining and immunohistochemistric (IHC) analysis. Total RNA was isolated for real-time polymerase chain reaction for p65, interleukin (IL)-6, IL-8, intracellular adhesion molecule (ICAM)-1, IL-1β, tumor necrosis factor (TNF)-α, and eotaxin. RESULTS In the CRSwNPs group, 50% of nasal polyps were non-eosinophilic. IHC revealed a significantly higher fraction of NF-κB p65-positive cells in nasal polyps of the CRSwNPs group than in the UTs of control and CRSsNP groups. No difference in NF-κB p65-positive cell fraction was observed between eosinophilic and non-eosinophilic nasal polyps. The mRNA expression of p65, IL-6, IL-8, and eotaxin was significantly higher in nasal polyps of the CRSwNPs than in the UTs of control and CRSsNP group. However, no difference in expression was observed between eosinophilic and non-eosinophilic nasal polyps, with the exception of IL-1β expression. CONCLUSIONS Elevated expression of NF-κB- and NF-κB-associated inflammatory cytokines suggests NF-κB as the key factor for CRSwNPs pathogenesis in Asian patients. Understanding NF-κB-associated mechanisms will provide a deeper insight into CRSwNPs pathogenesis and ultimately improve therapeutic strategies for CRSwNPs.
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Affiliation(s)
- Hahn Jin Jung
- Department of Otorhinolaryngology-Head and Neck Surgery, Chungbuk National University College of Medicine, Chungbuk National University Hospital, Cheongju, Korea
| | - Yu Lian Zhang
- Center of Morphological Experiment, Medical College of Yanbian University, Yanji, China
| | - Dong Kyu Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital and Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, Korea
| | - Chae Seo Rhee
- Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Young Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
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Manji J, Thamboo A, Sunkaraneni V, Singh A, Tebbutt S, Garnis C, Javer A. The association of Leptospermum honey with cytokine expression in the sinonasal epithelium of chronic rhinosinusitis patients. World J Otorhinolaryngol Head Neck Surg 2018; 5:19-25. [PMID: 30775697 PMCID: PMC6364513 DOI: 10.1016/j.wjorl.2018.07.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 07/06/2018] [Accepted: 07/18/2018] [Indexed: 01/09/2023] Open
Abstract
Objective To identify the differences in cytokine expression between sinonasal tissue from patients treated with Leptospermum (Manuka) honey (LH) irrigation versus normal saline irrigation twice-daily for twelve weeks following sinus surgery (FESS). Methods Forty-six CRS patients were recruited. Sinus tissue biopsies were collected during FESS and then at 5 and 12 weeks postoperatively during the course of treatment. A multi-plex cytokine assay quantified the abundance of 17 cytokines in biopsied tissue. Cytokine expression fold-change was analyzed between each time point using a robust linear regression model and compared between the two treatment groups. Results Compared to the saline irrigation group, five cytokines were differently expressed (CI = 95%) in sinonasal tissue obtained from subjects in the LH irrigation group during the 12-week treatment period. Cytokines IL-6 (P = 0.0400), IL-8 (P = 0.0398), MCP-1 (P = 0.0284), and MIP-1β (P = 0.016) were significantly increased in the LH irrigation group compared to the saline irrigation group. IL-13 was significantly increased in the saline irrigation group compared to the LH group (P = 0.0086). Conclusion LH may potentially act to modulate the expression of IL-6, IL-8, IL-13, MCP-1 and MIP-1β in sinonasal tissue.
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Affiliation(s)
- Jamil Manji
- St. Paul's Sinus Centre, Division of Otolaryngology, Department of Surgery, St. Paul's Sinus Centre, Vancouver, BC, Canada.,BC Cancer Research Centre, Division of Otolaryngology, Department of Surgery, Vancouver, BC, Canada
| | - Andrew Thamboo
- St. Paul's Sinus Centre, Division of Otolaryngology, Department of Surgery, St. Paul's Sinus Centre, Vancouver, BC, Canada
| | - Vishnu Sunkaraneni
- St. Paul's Sinus Centre, Division of Otolaryngology, Department of Surgery, St. Paul's Sinus Centre, Vancouver, BC, Canada.,Royal Surrey County Hospital, Egerton Road, Guildford, UK
| | - Amrit Singh
- PROOF Centre of Excellence, St. Paul's Hospital, Vancouver, BC, Canada.,James Hogg Research Centre, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Scott Tebbutt
- PROOF Centre of Excellence, St. Paul's Hospital, Vancouver, BC, Canada.,James Hogg Research Centre, St. Paul's Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Cathie Garnis
- BC Cancer Research Centre, Division of Otolaryngology, Department of Surgery, Vancouver, BC, Canada
| | - Amin Javer
- St. Paul's Sinus Centre, Division of Otolaryngology, Department of Surgery, St. Paul's Sinus Centre, Vancouver, BC, Canada
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7
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Affiliation(s)
- Laura Atzori
- Dermatology Clinic, Department Medical Science and Public Health, University of Cagliari, Cagliari, Italy
| | - Caterina Ferreli
- Dermatology Clinic, Department Medical Science and Public Health, University of Cagliari, Cagliari, Italy
| | - Franco Rongioletti
- Dermatology Clinic, Department Medical Science and Public Health, University of Cagliari, Cagliari, Italy
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8
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Yariktas M, Doner F, Sutcu R, Demirci M, Dogru H, Yasan H. The Effect of Topical Corticosteroid on Basic Fibroblast Growth Factor in Nasal Polyp Tissue. ACTA ACUST UNITED AC 2018. [DOI: 10.1177/194589240501900306] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background The etiology of nasal polyposis and pathophysiological mechanisms of polyp formation is still poorly understood. Experimental models have suggested that nasal polyp growth requires extracellular matrix formation and is associated with fibroblast proliferation. Intranasal corticosteroids appear to be useful in reducing nasal polypoid lesions and the likelihood of polyp recurrence after surgery. Basic fibroblast growth factor (bFGF) is a potent angiogenesis factor and is mitogenic for a wide range of cell types. We investigated the alteration of bFGF levels in nasal polyp tissue after administration of topical corticosteroid. Methods Nasal polyp tissues were obtained from 36 patients with diffuse nasal polyposis before and after topical nasal steroid treatment. As a topical nasal steroid mometasone furoate was given for 4 weeks in a dosage of 200 μg/day. The bFGF levels were measured by competitive enzyme immunoassay method. Results The mean levels of tissue bFGF, before and after topical nasal steroid treatment, were 1485 ± 826 ng/mg protein (range, 416–3434 ng/mg) and 1340 ± 749 ng/mg protein (range, 330–3288 ng/mg), respectively. The levels of bFGF in nasal polyps were significantly lower than those before treatment after administration of topical nasal steroid (p = 0.011). Conclusion Administration of topical nasal steroid decreases bFGF levels of nasal polyp. It may be suggested that one of the effects in diminishing the size of nasal polyps is by decreasing the bFGF.
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Affiliation(s)
- Murat Yariktas
- Departments of Otorhinolaryngology, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | - Fehmi Doner
- Departments of Otorhinolaryngology, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | - Recep Sutcu
- Departments of Clinical Biochemistry, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | - Mustafa Demirci
- Departments of Clinical Microbiology, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | - Harun Dogru
- Departments of Otorhinolaryngology, Suleyman Demirel University School of Medicine, Isparta, Turkey
| | - Hasan Yasan
- Departments of Otorhinolaryngology, Suleyman Demirel University School of Medicine, Isparta, Turkey
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9
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Pavón-Romero GF, Reséndiz-Hernández JM, Ramírez-Jiménez F, Pérez-Rubio G, Camarena Á, Terán LM, Falfán-Valencia R. Single nucleotide polymorphisms in TNF are associated with susceptibility to aspirin-exacerbated respiratory disease but not to cytokine levels: a study in Mexican mestizo population. Biomark Med 2017; 11:1047-1055. [PMID: 29172674 DOI: 10.2217/bmm-2017-0164] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
AIM To evaluate the association of three single nucleotide polymorphisms in TNF and one in LTA in Mexican patients with aspirin-exacerbated respiratory disease (AERD) and the correlation of those single nucleotide polymorphisms with serum levels of TNF-α. PATIENTS & METHODS Case-control study including 133 patients with AERD, 135 patients with asthma (aspirin-tolerant asthmatics) and 182 healthy subjects. RESULTS GA genotype of rs1800629 in TNF was found to be associated with the risk of developing AERD (p < 0.05; odds ratio = 2.36) and by dominant model (p < 0.05; odds ratio = 2.51). Furthermore, there was a difference in the serum levels between the aspirin-tolerant asthmatics group and the other groups (p < 0.001). CONCLUSION The GA genotype of rs1800629 is associated with genetic susceptibility to AERD, but it does not correlate to protein serum levels.
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Affiliation(s)
- Gandhi F Pavón-Romero
- Department of Allergy & Clinical Immunology, Instituto Nacional Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico.,HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico.,Biomedicine In the Post-Genomic Era, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico
| | - Juan M Reséndiz-Hernández
- Department of Allergy & Clinical Immunology, Instituto Nacional Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico.,HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico.,Biomedicine In the Post-Genomic Era, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico
| | - Fernando Ramírez-Jiménez
- Department of Allergy & Clinical Immunology, Instituto Nacional Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico.,HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico.,Biomedicine In the Post-Genomic Era, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico
| | - Gloria Pérez-Rubio
- Department of Allergy & Clinical Immunology, Instituto Nacional Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico.,HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico.,Biomedicine In the Post-Genomic Era, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico
| | - Ángel Camarena
- Department of Allergy & Clinical Immunology, Instituto Nacional Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico.,HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico.,Biomedicine In the Post-Genomic Era, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico
| | - Luis M Terán
- Department of Allergy & Clinical Immunology, Instituto Nacional Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico
| | - Ramcés Falfán-Valencia
- HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Tlalpan 4502, Sección XVI, Tlalpan, 14080, Mexico City, Mexico
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10
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Niu YZ, Gong GQ, Chen S, Chen JJ, Kong WJ, Wang YJ. Effects of IL-17 on expression of GRO-α and IL-8 in fibroblasts from nasal polyps. ACTA ACUST UNITED AC 2014; 34:591-595. [PMID: 25135733 DOI: 10.1007/s11596-014-1321-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Revised: 07/04/2014] [Indexed: 12/17/2022]
Abstract
Recent studies indicated that interleukin (IL)-17, growth-related oncogene (GRO)-α and IL-8 play an important role in the pathogenesis of nasal polyps. However, the effects of the increased amount of IL-17 and the production of GRO-α and IL-8 in human nasal polyp fibroblasts are not completely understood. This study aimed to determine the effects of the increased IL-17 on the changes of GRO-α and IL-8 expression in human nasal polyp fibroblasts and further investigate the mechanism of neutrophil infiltration in nasal polyps. Nasal polyp fibroblasts were isolated from six cases of human nasal polyps, and the cells were stimulated with five different concentrations of IL-17. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GRO-α and IL-8. The mRNA of GRO-α and IL-8 was expressed in unstimulated controls and remarkably increased by stimulation with IL-17. Moreover, the levels of GRO-α and IL-8 produced by fibroblasts were increased gradually with the increases in IL-17 concentrations. The present study showed that nasal fibroblasts can produce GRO-α and IL-8, and their production is remarkably enhanced by IL-17 stimulation, thereby clarifying the mechanism of the IL-17 mediated neutrophil infiltration in nasal polyps. These findings might provide a rationale for using IL-17 inhibitors as a treatment for nasal inflammatory diseases such as nasal polyps.
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Affiliation(s)
- Yong-Zhi Niu
- Institute of Otorhinolaryngology, Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Guo-Qing Gong
- Institute of Otorhinolaryngology, Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Shan Chen
- Institute of Otorhinolaryngology, Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jian-Jun Chen
- Institute of Otorhinolaryngology, Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Wei-Jia Kong
- Institute of Otorhinolaryngology, Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
| | - Yan-Jun Wang
- Institute of Otorhinolaryngology, Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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11
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Van Crombruggen K, Jacob F, Zhang N, Bachert C. Damage-associated molecular patterns and their receptors in upper airway pathologies. Cell Mol Life Sci 2013; 70:4307-21. [PMID: 23673984 PMCID: PMC11113492 DOI: 10.1007/s00018-013-1356-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Revised: 04/23/2013] [Accepted: 04/29/2013] [Indexed: 12/17/2022]
Abstract
Inflammation of the nasal (rhinitis) and sinus mucosa (sinusitis) are prevalent medical conditions of the upper airways that are concurrent in many patients; hence the terminology "rhinosinusitis". The disease status is further defined to be "chronic" in case symptoms persist for more than 12 weeks without resolution. A diverse spectrum of external factors including viral and bacterial insults together with epithelial barrier malfunctions could be implicated in the chronicity of the inflammatory responses in chronic rhinosinusitis (CRS). However, despite massive research efforts in an attempt to unveil the pathophysiology, the exact reason for a lack of resolution still remains poorly understood. A novel set of molecules that could be implicated in sustaining the inflammatory reaction may be found within the host itself. Indeed, besides mediators of inflammation originating from outside, some endogenous intracellular and/or extracellular matrix (ECM) components from the host can be released into the extracellular space upon damage induced during the initial inflammatory reaction where they gain functions distinct from those during normal physiology. These "host-self" molecules are known to modulate inflammatory responses under pathological conditions, potentially preventing resolution and contributing to the development of chronic inflammation. These molecules are collectively classified as damage-associated molecular patterns (DAMPs). This review summarizes the current knowledge regarding DAMPs in upper airway pathologies, also covering those that were previously investigated for their intracellular and/or ECM functions often acting as an antimicrobial agent or implicated in tissue/cell homeostasis, and for which their function as a danger signaling molecule was not assessed. It is, however, of importance to assess these molecules again from a point of view as a DAMP in order to further unravel the pathogenesis of CRS.
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Affiliation(s)
- Koen Van Crombruggen
- Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium,
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Combination therapy with relaxin and methylprednisolone augments the effects of either treatment alone in inhibiting subepithelial fibrosis in an experimental model of allergic airways disease. Clin Sci (Lond) 2012; 124:41-51. [PMID: 22817662 DOI: 10.1042/cs20120024] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Although CSs (corticosteroids) demonstrate potent effects in the control of airway inflammation in asthma, many patients continue to experience symptoms and AHR (airway hyper-responsiveness) despite optimal treatment with these agents, probably due to progressive airway remodelling. Identifying novel therapies that can target airway remodelling and/or airway reactivity may improve symptom control in these patients. We have demonstrated previously that the anti-fibrotic hormone RLN (relaxin) can reverse airway remodelling (epithelial thickening and subepithelial fibrosis) and AHR in a murine model of AAD (allergic airways disease). In the present study, we compared the effects of RLN with a CS (methylprednisolone) on airway remodelling and AHR when administered independently or in combination in the mouse AAD model. Female mice at 6-8 weeks of age were sensitized and challenged to OVA (ovalbumin) over a 9-week period and treated with methylprednisolone, RLN, a combination of both treatments or vehicle controls. Methylprednisolone was administered intraperitoneally on the same day as nebulization for 6 weeks, whereas recombinant human RLN-2 was administered via subcutaneously implanted osmotic mini-pumps from weeks 9-11. RLN or methylprednisolone alone were both able to significantly decrease subepithelial thickness and total lung collagen deposition; whereas RLN but not methylprednisolone significantly decreased epithelial thickness and AHR. Additionally, combination therapy with CS and RLN more effectively reduced subepithelial collagen thickness than either therapy alone. These findings demonstrate that RLN can modulate a broader range of airway remodelling changes and AHR than methylprednisolone and the combination of both treatments offers enhanced control of subepithelial fibrosis.
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15
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Bassiouni A, Naidoo Y, Wormald PJ. Does mucosal remodeling in chronic rhinosinusitis result in irreversible mucosal disease? Laryngoscope 2012; 122:225-9. [PMID: 22183638 DOI: 10.1002/lary.22374] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Mucosal remodeling in the sinuses is a recently described phenomenon in which the mucosa undergoes potentially irreversible changes as a result of ongoing underlying inflammatory processes. Research into remodeling that occurs in the bronchial airways in asthmatic patients has led to modification of asthma treatment guidelines. However, remodeling in the sinuses has still not led to changes in current medical or surgical management of chronic rhinosinusitis. Upper airway remodeling constitutes a new area of research that poses many unanswered clinical questions and may potentially alter the management of patients with severe chronic rhinosinusitis.
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Affiliation(s)
- Ahmed Bassiouni
- Department of Surgery, Otorhinolaryngology-Head and Neck Surgery, University of Adelaide, Adelaide, Australia
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16
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Lower sensitivity of nasal polyp fibroblasts to glucocorticoid anti-proliferative effects. Respir Med 2010; 105:218-25. [PMID: 20829014 DOI: 10.1016/j.rmed.2010.08.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2010] [Revised: 07/09/2010] [Accepted: 08/03/2010] [Indexed: 12/31/2022]
Abstract
BACKGROUND Treatment with glucocorticoids (GCs) is the cornerstone of nasal polyp (NP) therapy, but some patients respond poorly to them. Fibroblasts are involved in both inflammation and remodelling of NP. We aimed to evaluate whether NP fibroblasts are less sensitive to GCs' anti-proliferative and anti-inflammatory effects, compared to nasal mucosa (NM) fibroblasts. METHODS Fibroblasts were obtained from NP (n = 8) from asthmatic patients undergoing endoscopic surgery and NM (n = 8) from patients undergoing nasal corrective surgery. Fibroblasts were stimulated with DMEM at 0.5% or 5% FBS, or TGF-β (5 ng/ml), with or without dexamethasone (10(-11) to 10(-5)M) for different times. Cell proliferation, collagen mRNA expression and IL-6 and IL-8 release were measured. RESULTS After 3-days, dexamethasone dose-dependently inhibited proliferation of NM (p < 0.001) but not that of NP fibroblasts. Dexamethasone (10(-6)M) reduced by 25% the proliferation of NM fibroblasts. Dexamethasone also inhibited proliferation of NM (p < 0.01) but not that of NP fibroblasts at 5-days. TGF-β induced collagen-1α1, -1α2, and -3α1 mRNA levels in both NM and NP fibroblasts (p < 0.05), and dexamethasone did not alter TGF-β-induced collagen mRNA levels in either fibroblast type at 24 h. Dexamethasone dose-dependently decreased (p < 0.05) FBS-induced IL-6 and IL-8 release in both NM and NP fibroblasts at 4 h, although at 10(-8)M, dexamethasone inhibited cytokine production in NM (p < 0.05) but not in NP fibroblasts. CONCLUSIONS This impaired sensitivity of nasal polyp fibroblasts to in vitro glucocorticoid effects concurs in part with the poor clinical response that these nasal polyp patients show to glucocorticoid treatment.
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Okano M. Mechanisms and clinical implications of glucocorticosteroids in the treatment of allergic rhinitis. Clin Exp Immunol 2009; 158:164-73. [PMID: 19737138 DOI: 10.1111/j.1365-2249.2009.04010.x] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Allergic rhinitis is a common airway disease characterized by hypersensitivity, exudation, hypersecretion, inflammatory cell infiltration and remodelling. Intranasal glucocorticosteroids are the most effective drugs for controlling the inflammation caused by allergic rhinitis. Glucocorticosteroids exert anti-inflammatory effects through at least two pathways: the transactivation pathway and the transrepression pathway. Glucocorticosteroids also exert regulatory functions by inducing regulatory cytokines and forkhead box P3 (FoxP3(+)) regulatory T cells. Evidence suggests that intranasal glucocorticosteroids control not only nasal symptoms but also ocular symptoms. In contrast to sedating H1 receptor antagonists, intranasal glucocorticosteroids can improve impaired performance symptoms, such as daytime sleepiness, associated with allergic rhinitis. Recent studies suggest that intranasal glucocorticosteroids might also be useful for the prophylactic treatment of pollinosis; this possibility is supported by the molecular mechanism of the anti-inflammatory action of glucocorticosteroids. These findings suggest that intranasal glucocorticosteroids might be positioned as first-line drugs for the treatment of both perennial and seasonal allergic rhinitis.
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Affiliation(s)
- M Okano
- Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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Valera FCP, Queiroz R, Scrideli C, Tone LG, Anselmo-Lima WT. Expression of transcription factors NF-kappaB and AP-1 in nasal polyposis. Clin Exp Allergy 2008; 38:579-85. [PMID: 18352974 DOI: 10.1111/j.1365-2222.2007.02929.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND The treatment and prognosis of nasal polyposis (NP) may be influenced by transcription factors, but their expression is poorly understood. OBJECTIVE To determine the expression of transcription factors [(nuclear factor-kappaB) NF-kappaB and (activator protein) AP-1], cytokines [IL-1beta, TNF-alpha and (granulocytes and macrophage colony-stimulating factor) GM-CSF], growth factor (b-FGF), chemokine (eotaxin-2) and adhesion molecule (ICAM-1) in NP in comparison with nasal mucosa controls. Methods Cross-sectional study. Twenty biopsies of nasal polyps were compared with eight middle turbinate biopsies. p65, c-Fos, IL-1beta, TNF-alpha, ICAM-1, b-FGF, eotaxin-2 and GM-CSF were analysed through RQ-PCR, and p65 and c-Fos were also analysed through Western blotting. RESULTS NF-kappaB expression was increased in patients with NP when compared with control mucosa (P<0.05), whereas AP-1 expression did not differ significantly between groups. Expressions of IL-1beta, eotaxin-2 and b-FGF were also increased in patients with NP compared with controls (P<0.05). CONCLUSIONS The transcription factor NF-kappaB is more expressed in NP than in control mucosa. This is important in NP because NF-kappaB can induce the transcription of cytokines, chemokines and adhesion molecules, which play an important role in the inflammatory process. Moreover, transcription factors influence the response to corticosteroids, which are the basis of NP treatment. Transcription factor AP-1 does not seem to have a significant role in the pathological process.
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Affiliation(s)
- F C P Valera
- Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
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Pietruszewska W, Olejniczak I, Durko T, Młynarski W. [Role of IFN-gamma and TNF-alpha in etiology of nasal polyps--initial studies]. Otolaryngol Pol 2008; 62:54-8. [PMID: 18637422 DOI: 10.1016/s0030-6657(08)70209-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
OBJECTIVE Nasal polyposis is a chronic inflammatory disease of the nasal mucosa. The pathogenesis of nasal polyps is still not entirely known and has been debated for many years. The aim of the present study was to evaluate the expression of interferon gamma and TNF-alpha secreted by Th1 lymphocytes and to analyze their role in the etiology of nasal polyps. METHODS 12 patients with nasal polyposis were selected - 6 of them allergic and 6 non-allergic. Patients with allergy were distinguished from those without allergy on the basis of positive allergy skin tests to dust and serum levels of IgE. Blood sample was obtained from patients and examined for the expression of IFN-gamma and TNF-alpha by intracellular staining procedure after stimulation with PMA/ionomycin and allergen. RESULTS Negative correlation was found between expression of IFN-gamma and TNF-alpha after PMA/ionomycin stimulation and allergen stimulation (p > 0,05). Statistical analysis of two groups of patients demonstrated that no significant differences in the cytokine expression in allergic versus non-allergic patients were observed although mean value of IFN-gamma and TNF-alpha were lower in allergic patients in comparison to non-allergic (p > 0,05). We didn't observed any correlation between expression of INF-gamma and TNF-alpha and: coexistence of bronchial asthma, allergy to aspirin and local corticosteroid treatment. In patients with recurrent polyposis the expression of INF-gamma was significantly lower (p = 0,05). CONCLUSION This research suggests that IFN-gamma and TNF-alpha play a role in the pathogenesis of nasal polyps but the allergic mechanism may not play a fundamental role in this process. It needs further investigations.
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Fernandes AM, Valera FCP, Anselmo-Lima WT. Mechanism of action of glucocorticoids in nasal polyposis. Braz J Otorhinolaryngol 2008; 74:279-83. [PMID: 18568209 PMCID: PMC9442608 DOI: 10.1016/s1808-8694(15)31101-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2006] [Accepted: 03/24/2007] [Indexed: 11/26/2022] Open
Abstract
UNLABELLED Glucocorticoids (GC) are the drugs of choice for the clinical treatment of nasal polyposis, according to the medical literature. Its mechanism of action in the regression of clinical symptoms and polyps, however, is not fully understood. The topical and/or systemic use of glucocorticoids lead to variable expression of cytokines, chemokines and lymphokines, as well as changes in cells. It is known that GC suppresses the expression of pro-inflammatory cytokines, chemokines and adhesion molecules such as ICAM-1 and E-selectin; GC also stimulate the transcription of anti-inflammatory cytokines such as TGF-b. GC suppress pro-fibrotic cytokines related to polyp growth, such as IL-11, the basic fibroblast growth factor (b-FGF), and the vascular endotelial growth factor (VEGF). The action of GC depends fundamentally on their interaction with receptors (GR); certain subjects have a degree of resistance to its effect, which appears to be related with the presence of a b isoform of GR. GC also act variably on the genes involved in immunoglobulin production, presentation, and antigen processing. AIM We present a review of the literature on the mechanisms of GC action in nasal polyosis. CONCLUSION Understanding the mechanism of action of GC in nasal polyposis will aid in the development of new, more efficient, drugs.
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Olejniczak I, Kobos J, Gryczyński M, Durko M, Pietruszewska W. [Expression of adhesion molecule ICAM-1 in patients with nasal polyps]. Otolaryngol Pol 2008; 61:607-11. [PMID: 18260262 DOI: 10.1016/s0030-6657(07)70495-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
INTRODUCTION Nasal polyposis is a chronic inflammatory disease of the nasal mucosa. The prevalence of nasal polyps seems to vary between 1 and 4% of the population. The pathogenesis of nasal polyps is still not entirely known and has been debated for many years. The aim of the present study was to evaluate the expression of adhesion molecule ICAM-1 in patients with nasal polyps. MATERIALS AND METHODS 53 patients with nasal polyposis were selected and divided into two groups--allergic and non-allergic. Patients with allergy were distinguished from those without allergy on the basis of positive allergy skin tests to dust and serum levels of IgE. Immunohistochemical studies with monoclonal antibody against ICAM-1 antigen (NCL-CD54, Novocastra) using immunoperoxidase method were performed to evaluate expression of ICAM-1. RESULTS Immunoexpression of ICAM-1 was present on some epithelial cells and on fibroblast, inflammatory cells and endothelium in the submucosa. The mean +/-SD values of the immunoexpression of ICAM-1 were significantly increased in dust-sensitive patients compared with dust-tolerant patients (1.93 +/- 0.83 vs 0.83 +/- 0.73 (p < 0.001). CONCLUSIONS This research suggests that ICAM-1 plays an important role in the pathogenesis of nasal polyps and the allergic mechanism may play a fundamental role in this process. However, further examinations to confirm this need to be undertaken.
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Petecchia L, Serpero L, Silvestri M, Sabatini F, Scarso L, Rossi GA. The histamine-induced enhanced expression of vascular cell adhesion molecule-1 by nasal polyp-derived fibroblasts is inhibited by levocetirizine. ACTA ACUST UNITED AC 2007; 20:445-9. [PMID: 17063735 DOI: 10.2500/ajr.2006.20.0796] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Histamine, a key chemical mediator in allergic reaction, exhibits an array of pro-inflammatory effects that include the activation of fibroblasts. The aim of this study was to evaluate whether histamine could stimulate nasal polyp-derived fibroblasts to express vascular cell adhesion molecule (VCAM)-1, a surface molecule involved in structural-inflammatory cell interaction and whether levocetirizine could inhibit this induction. METHODS Primary nasal polyp tissue-derived fibroblasts were stimulated with histamine (10-1000 microM) or interleukin (IL)-4 plus tumor necrosis factor (TNF)-alpha (0.5-5 ng/mL) and VCAM-1 expression was evaluated by flow cytometry analysis. The inhibitory effect of the selective H1-antagonist levocetirizine (0.01-10.0 microM) on VCAM-1 expression was also tested. RESULTS Compared with unstimulated cultures, histamine or IL-4 + TNF-alpha, at the highest concentrations tested, significantly increase VCAM-1 expression (p < 0.05). To evaluate the ability of levocetirizine to downregulate VCAM-1 expression, fibroblasts were stimulated with histamine (1000 microM) or IL-4 + TNF-alpha (5 ng/mL), in the presence of the drug (0.01-10.0 microM). The histamine-induced VCAM-1 expression was effectively inhibited by levocetirizine (0.1-10.0 microM) (p < 0.05). No effect of the drug on IL-4 + TNF-alpha-induced VCAM-1 expression was observed. CONCLUSIONS Histamine upregulates VCAM-1 expression on nasal polyp-derived fibroblasts and this phenomenon, relevant to allergic late-phase inflammation, is effectively inhibited by levocetirizine.
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Taha Y, Raab Y, Carlson M, Larsson A, Lördal M, Lööf L, Thörn M. Steroids reduce local inflammatory mediator secretion and mucosal permeability in collagenous colitis patients. World J Gastroenterol 2006; 12:7012-8. [PMID: 17109497 PMCID: PMC4087346 DOI: 10.3748/wjg.v12.i43.7012] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the effect of oral steroids upon clinical response and rectal mucosa secretion of eosinophil cationic protein (ECP), myeloperoxidase (MPO), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and albumin in patients with collagenous colitis (CC).
METHODS: A segmental perfusion technique was used to collect perfusates from rectum of CC patients once before and twice (one and four weeks) after the start of steroid treatment. Clinical data was monitored and ECP, MPO, bFGF, VEGF and albumin concentrations were analyzed by immunochemical methods in perfusates and in serum.
RESULTS: Steroids reduced the number of bowel movements by more than five times within one week and all patients reported improved subjective well-being at wk 1 and 4. At the same time, the median concentrations of ECP, bFGF, VEGF and albumin in rectal perfusates decreased significantly. MPO values were above the detection limit in only 3 patients before treatment and in none during treatment. VEGF, bFGF, ECP and albumin concentrations correlated with each other with the exception of ECP and albumin. A decrease of serum ECP and VEGF concentrations was also seen even if the overtime reduction was not significant.
CONCLUSION: Oral steroid treatment in CC patients induced a simultaneous reduction of bowel movements and rectal release of ECP, bFGF, VEGF and albumin, suggesting that these polypeptides and increased mucosal permeability are important components of the pathophysiology in collagenous colitis.
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Affiliation(s)
- Yesuf Taha
- Departments of Medical Sciences, University Hospital, Uppsala, Sweden.
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Ohori J, Ushikai M, Sun D, Nishimoto K, Sagara Y, Fukuiwa T, Matsune S, Kurono Y. TNF-alpha upregulates VCAM-1 and NF-kappaB in fibroblasts from nasal polyps. Auris Nasus Larynx 2006; 34:177-83. [PMID: 16934424 DOI: 10.1016/j.anl.2006.05.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2006] [Revised: 04/25/2006] [Accepted: 05/26/2006] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Lung and synovial fibroblasts produce VCAM-1 in response to TNF-alpha. However, the massive infiltration of eosinophils, the effects of the increased amount of TNF-alpha and the production of VCAM-1 in human nasal polyp fibroblasts are not yet fully understood. The present study examines the role of VCAM-1 and the molecular mechanism of its expression in nasal fibroblasts. METHODS Nasal fibroblasts were isolated from human nasal polyps and after four passages, the cells were stimulated with TNF-alpha and VCAM-1 expression was examined by ELISA, flow cytometry, and RT-PCR. The activation of NF-kappaB induced by TNF-alpha was determined by electrophoretic mobility shift assays and the influence on the expression of VCAM-1 was investigated. RESULTS VCAM-1 protein and mRNA were expressed in unstimulated controls and remarkably increased by TNF-alpha stimulation. NF-kappaB activity was enhanced by TNF-alpha stimulation and remarkably suppressed by NF-kappaB proteasome inhibitor. CONCLUSIONS The present study discovered that nasal fibroblasts produce VCAM-1 protein and mRNA and that production is increased by TNF-alpha stimulation. Furthermore, VCAM-1 expression in nasal fibroblasts is induced through an NF-kappaB-dependent pathway. These findings might provide a rationale for using NF-kappaB inhibitors as a treatment for nasal inflammatory diseases such as polyps.
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Affiliation(s)
- Junichiro Ohori
- Department of Otolaryngology, Field of Sensory Organology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890-8520, Japan.
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Bergeron C, Boulet LP. Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation. Chest 2006; 129:1068-87. [PMID: 16608960 DOI: 10.1378/chest.129.4.1068] [Citation(s) in RCA: 145] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
In airway diseases such as asthma and COPD, specific structural changes may be observed, very likely secondary to an underlying inflammatory process. Although it is still controversial, airway remodeling may contribute to the development of these diseases and to their clinical expression and outcome. Airway remodeling has been described in asthma in various degrees of severity, and correlations have been found between such features as increase in subepithelial collagen or proteoglycan deposits and airway responsiveness. Although the clinical significance of airway remodeling remains a matter of debate, it has been suggested as a potential target for treatments aimed at reducing asthma severity, improving its control, and possibly preventing its development. To date, drugs used to treat airway diseases have a little influence on airway structural changes. More research should be done to identify key changes, valuable treatments, and proper interventional timing to counteract these changes. The potential of novel therapeutic agents to reverse or prevent airway remodeling is an exciting avenue and warrants further evaluation.
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Bellodi S, Tosca MA, Pulvirenti G, Petecchia L, Serpero L, Silvestri M, Sabatini F, Battistini E, Rossi GA. Activity of budesonide on nasal neutrophilic inflammation and obstruction in children with recurrent upper airway infections. A preliminary investigation. Int J Pediatr Otorhinolaryngol 2006; 70:445-52. [PMID: 16140398 DOI: 10.1016/j.ijporl.2005.07.015] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2005] [Accepted: 07/24/2005] [Indexed: 11/28/2022]
Abstract
OBJECTIVE While it is widely accepted that inhaled glucocorticosteroids represent an effective treatment for allergic rhinitis, little is known on the specific effects of this therapeutic approach in other upper airway disorders of childhood. The aim of the study was to evaluate the improvement of clinical symptoms and changes in local cellular inflammatory reaction induced by budesonide inhalation suspension in children with recurrent nasal infections using budesonide inhalation suspension delivered by Rinowash, a nebulizer designed to treat upper airway structures. METHODS In a randomized, controlled-open study, 14 children (5.88+/-0.56 years of age) with recurrent upper airway infections and chronic nasal obstruction were enrolled and randomly treated for 7-10 days either with budesonide inhalation suspension (250 microg/bidie) (nine patients) or with saline solution (five patients). Before and after treatment, inflammatory cells in nasal brushing and nasal symptom score were evaluated. RESULTS Out of the nine patients treated with budesonide, two were excluded from the analysis because of acute respiratory infections requiring systemic antibiotic treatment. A significant decrease in nasal brushing neutrophil percentage was observed after treatment with budesonide (P=0.016) but not after saline solution treatment (P=1.00). No significant changes in nasal brushing mononuclear cell or eosinophil proportions were observed after treatment with budesonide inhalation suspension or saline solution (P=NS, each comparison). Treatment with budesonide, but not with saline solution, was associated with a significant reduction in nasal obstruction (P=0.016). CONCLUSIONS These preliminary data indicate that short-term treatment with budesonide inhalation suspension, used for an indication out of label, may significantly reduce local neutrophilic inflammation and nasal obstruction in children with recurrent upper airway infections.
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Affiliation(s)
- Simona Bellodi
- U.O.C. di Pneumologia, I.R.C.C.S. G. Gaslini, Istituto G. Gaslini, Largo G. Gaslini, 5, 16147 Genoa, Italy
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Sabatini F, Petecchia L, Tavian M, Jodon de Villeroché V, Rossi GA, Brouty-Boyé D. Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. J Transl Med 2005; 85:962-71. [PMID: 15924148 DOI: 10.1038/labinvest.3700300] [Citation(s) in RCA: 190] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate along different pathways including chondrogenic, osteogenic and adipogenic lineages. MSCs with a fibroblast-like morphology have been identified in human fetal lung. However, their frequency and characterization in human adult lung have not been yet evaluated. Therefore, we analyzed the mesenchymal phenotype and differentiation ability of cultured human adult bronchial fibroblast-like cells (Br) in comparison with those of mesenchymal cell progenitors isolated from fetal lung (ICIG7) and adult bone marrow (BM212) tissues. Surface immunophenotyping by flow cytometry revealed a similar expression pattern of antigens characteristic of marrow-derived MSCs, including CD34 (-), CD45 (-), CD90/Thy-1 (+), CD73/SH3, SH4 (+), CD105/SH2 (+) and CD166/ALCAM (+) in Br, ICIG7 and BM212 cells. There was one exception, STRO-1 antigen, which was only weakly expressed in Br cells. Analysis of cytoskeleton and matrix composition by immunostaining showed that lung and marrow-derived cells homogeneously expressed vimentin and nestin proteins in intermediate filaments while they were all devoid of epithelial cytokeratins. Additionally, alpha-smooth muscle actin was also present in microfilaments of a low number of cells. All cell types predominantly produced collagen and fibronectin extracellular matrix as evidenced by staining with the monoclonal antibodies to collagen prolyl 4-hydroxylase and fibronectin isoforms containing the extradomain (ED)-A together with ED-B in ICIG7 cells. Br cells similarly to fetal lung and marrow fibroblasts were able to differentiate along the three adipogenic, osteogenic and chondrogenic mesenchymal pathways when cultured under appropriate inducible conditions. Altogether, these data indicate that MSCs are present in human adult lung. They may be actively involved in lung tissue repair under physiological and pathological circumstances.
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Ishikawa T, Okamoto Y, Masuyama K. Nasal Immunologic Reactivity, Rhinitis, and Polyps. Mucosal Immunol 2005. [DOI: 10.1016/b978-012491543-5/50091-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Horn KB, Horn MA, Swan J, Singhal S, Guitart J. A complete and durable clinical response to high-dose dexamethasone in a patient with scleromyxedema. J Am Acad Dermatol 2004; 51:S120-3. [PMID: 15280830 DOI: 10.1016/j.jaad.2004.03.023] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
We report a case of a patient with scleromyxedema limited to the skin with an associated IgG lambda monoclonal protein treated successfully with high-dose dexamethasone. We encourage the continued investigation of this complex relationship between the clinical presentation of scleromyxedema and its frequently associated paraproteinemia.
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Affiliation(s)
- Keren B Horn
- Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
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Steinke JW, Crouse CD, Bradley D, Hise K, Lynch K, Kountakis SE, Borish L. Characterization of interleukin-4-stimulated nasal polyp fibroblasts. Am J Respir Cell Mol Biol 2004; 30:212-9. [PMID: 12920052 DOI: 10.1165/rcmb.2003-0071oc] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Chronic hyperplastic eosinophilic sinusitis is an inflammatory disease that results in the accumulation of eosinophils, fibroblasts, mast cells, and goblet cells at the site of injury. A common feature of this disease is the presence of nasal polyposis (NP). The current studies were designed to assess the contribution of interleukin (IL)-4 to fibroblast-mediated inflammation in chronic hyperplastic eosinophilic sinusitis/NP. In addition, we hypothesized that cysteinyl leukotrienes (CysLT) may directly influence fibroblast-mediated fibrotic and remodeling pathways in this disorder. Fibroblasts were isolated from NP tissue. All fibroblast lines expressed the IL-4 receptor. IL-4 induced changes in mRNA and protein expression of fibrotic (transforming growth factor-beta1 and -beta2) and inflammatory cytokines and chemokines (IL-6 and CCL11) by fibroblasts as measured by semiquantitative and quantitative polymerase chain reaction, RNase protection assay, and enzyme-linked immunosorbent assay. The expression of CysLT and other proinflammatory lipid receptors on fibroblasts was evaluated. CysLT1 and CysLT2 receptors were not expressed on fibroblasts; however, LPA(1) receptor was constitutively expressed and LPA(2) receptor expression was upregulated by IL-4. The metabolic cascade involved in CysLT synthesis was not expressed in fibroblasts and could not be induced by IL-4 treatment.
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Affiliation(s)
- John W Steinke
- Department of Medicine, , University of Virginia Health System, Charlottesville, VA 22908, USA.
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31
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Sabatini F, Silvestri M, Sale R, Serpero L, Giuliani M, Scarso L, Favini P, Rossi GA. Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling. Pulm Pharmacol Ther 2003; 16:287-97. [PMID: 12877820 DOI: 10.1016/s1094-5539(03)00068-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Lung fibroblasts play a key role in the pathogenesis of airway inflammation and remodeling through the release of mediators and the expression of surface molecules connected with cell-cell and cell-extracellular matrix interaction. The aim of the study was to evaluate the inhibitory effect of two corticosteroids, mometasone furoate (MOM) and dexamethasone (DEX), respectively, on a variety of fibroblast functions: DNA synthesis and proliferation, expression of adhesion molecules [intercellular adhesion molecule-1 (ICAM-1, CD54) and hyaluronic cellular adhesion molecule (HCAM, CD44)] and release of chemokines/cytokines [monocyte chemoattractant protein (MCP)-1, eotaxin, interleukin (IL)-6 and transforming growth factor (TGF)-beta]. Cells from a human foetal lung fibroblast cell line (GM 06114) were stimulated with basic fibroblast growth factor (bFGF) or tumour necrosis factor (TNF)-alpha in the presence of different concentrations (0.01-100.0nM) of MOM or DEX. A significant increase in fibroblast DNA synthesis and proliferation was observed when the cells were stimulated with bFGF (p<0.05), whereas TNF-alpha induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release (p<0.05, each comparison). No changes in HCAM expression and in TGF-beta release were observed (p>0.05, each comparison). The addition of MOM or DEX at the beginning of the cell cultures induced a significant downregulation in fibroblast DNA synthesis and proliferation, ICAM-1 and HCAM expression and chemokine/cytokine release (p<0.05, each comparison). At all the concentrations tested, MOM was more effective than DEX in inhibiting ICAM-1 expression and MCP-1 release (p<0.05, each comparison), whereas no potency advantage for MOM was detected in DNA synthesis, cell proliferation, HCAM expression and in eotaxin, IL-6 and TGF-beta release (p>0.05, each comparisons). These results extend the profile of the anti-inflammatory activity of mometasone furoate to lung fibroblast functions involved in airway inflammation and remodeling.
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Affiliation(s)
- F Sabatini
- Pulmonary Division, G. Gaslini Institute, Largo G. Gaslini 5, 16147, Genoa, Italy
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Abstract
Even since the late 19th century, a relationship has been suspected between upper airway disease and the subsequent development or aggravation of asthma symptoms. To date, it has been generally accepted that pathologic conditions of the upper airways, e.g. allergic rhinitis, chronic sinusitis and nasal polyposis, may influence the lower airways. However, the mechanisms underlying this relationship were, for a long time, poorly understood. Recently, evidence has been accumulating which indicates a systemic connection as one of the responsible mechanisms in nasobronchial crosstalk. In this review, the pathophysiologic and immunologic aspects of the interaction between upper and lower airways will be discussed.
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Affiliation(s)
- G-J Braunstahl
- Department of Pulmonary Medicine, Erasmus Medical Center Rotterdam, The Netherlands
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Cayé-Thomasen P, Larsen K, Tingsgaard P, Tos M. Basic fibroblast growth factor expression in recurrent versus non-recurrent nasal polyposis. Eur Arch Otorhinolaryngol 2003; 261:321-5. [PMID: 14551786 DOI: 10.1007/s00405-003-0673-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2003] [Accepted: 07/30/2003] [Indexed: 11/24/2022]
Abstract
Various growth factors are expressed in nasal polyps, and some of these have been suggested to play a role in polyp formation. A potential relation between growth factor expression and polyp recurrence, however, is undetermined. Basic fibroblast growth factor (bFGF) is expressed in mononuclear cells, as well as in endothelial and epithelial surface and gland cells of nasal polyps. To determine whether bFGF may play a role in the recurrence of nasal polyps, the present study aimed at a comparison of bFGF expression in recurrent versus non-recurrent polyps. Further, the expression in polyps from asthmatic patients was compared with that from non-asthmatics. Thirty patients with newly diagnosed nasal polyposis were included. Polypectomy was performed at entry to the long-term follow-up study. Fifteen patients only had one polypectomy (no recurrence group, with a median observation time of 81 months). Fifteen patients had a median of 6.4 polypectomies (multiple recurrence group, with a median observation time of 108 months). Five of nine patients with asthma belonged to the non-recurrence group and four to the recurrence group. The polyp from the entrance polypectomy was examined for expression of bFGF by immunohistochemistry, using a polyclonal antibody. A masked semi-quantification of staining intensity was performed in recurrent versus non-recurrent polyps, as well as in asthmatics versus non-asthmatics. bFGF expression was seen as varying staining of the polyp surface and gland epithelium, as well as of some mononuclear cells and some fibroblast-like cell profiles in the polyp stroma. Vascular endothelium was labeled occasionally. Semi-quantification of the staining intensity showed no significant differences between recurrent and non-recurrent polyps, or between asthmatics and non-asthmatics. We conclude that the level of immunohistochemical expression of bFGF in recurrent and non-recurrent nasal polyposis is equivalent. Thus, the level of bFGF expression in the primary polyp can not predict a subsequent recurrence. The expression of bFGF is not up-regulated in patients with asthma. Further studies are needed to determine a potential role of bFGF in nasal polyposis, with special reference to different stages of polyp formation and growth.
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Affiliation(s)
- Per Cayé-Thomasen
- Department of Otorhinolaryngology and Head and Neck Surgery, Gentofte University Hospital of Copenhagen, Copenhagen, Denmark
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