Local eosinophils are associated with increased IgA subclass levels in the sinonasal mucosa of chronic rhinosinusitis with polyp patients

Background Currently, no consensus exists on the appropriate control specimen site to utilize in studies evaluating for biomarkers in chronic rhinosinusitis (CRS). Studies thus far have utilized tissue from various anatomic sites despite regional heterogeneity. Objective We set out to quantify the differences in biomarker levels present in inferior turbinate versus sphenoid sinus mucosa in paired healthy control patients. We hypothesize that statistically significant differences in cytokine/chemokine expression exist between these two distinct sites. Methods A 38-plex commercially available cytokine/chemokine Luminex Assay was performed on 54 specimens encompassing paired inferior turbinate and sphenoid sinus mucosa samples from 27 patients undergoing endoscopic anterior skull base surgery. Patients with a history of CRS were excluded. Paired sample t-tests and Fisher’s exact tests were performed. Results Twenty-seven patients were included in the study, including 10 male and 17 female patients with an average age of 48 years. The following 8 biomarkers had statistically significant concentration differences between inferior turbinate mucosa and sphenoid mucosa sites: Flt-3L, Fractalkine, IL-12p40, IL-1Ra, IP-10, MCP-1, MIP-1β, and VEGF, with all P-values <0.01. Conclusion No consensus exists regarding the optimal choice of control specimen for CRS research. We present statistically significant quantitative differences in biomarker levels between paired inferior turbinate and sphenoid mucosa samples. This confirms the presence of heterogeneity between different subsites of sinonasal mucosa and highlights the need for standardization in future CRS research.

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Mucus composition abnormalities in sinonasal mucosa of chronic rhinosinusitis with and without nasal polyps

Inflammation ◽

10.1007/s10753-021-01471-6 ◽

2021 ◽

Author(s):

Yanyi Tu ◽

Jing Liu ◽

Tao Li ◽

Xiangmin Zhou ◽

Kai Sen Tan ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Sinonasal Mucosa

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Raman Spectroscopy for Inverted Papilloma: A Proof-of-Concept Study

Otolaryngology ◽

10.1177/0194599818776640 ◽

2018 ◽

Vol 159 (3) ◽

pp. 587-589 ◽

Cited By ~ 1

Author(s):

Marco A. Mascarella ◽

Abdulaziz Alrasheed ◽

Naif Fnais ◽

Ophelie Gourgas ◽

Ghulam Jalani ◽

...

Keyword(s):

Principal Component Analysis ◽

Raman Spectroscopy ◽

Chronic Rhinosinusitis ◽

Principal Component ◽

Inverted Papilloma ◽

Proof Of Concept ◽

Linear Discriminant ◽

Acceptable Accuracy ◽

Sinonasal Mucosa ◽

Inverted Papillomas

Inverted papillomas are tumors of the sinonasal tract with a propensity to recur. Raman spectroscopy can potentially identify inverted papillomas from other tissue based on biochemical signatures. A pilot study comparing Raman spectroscopy to histopathology for 3 types of sinonasal tissue was performed. Spectral data of biopsies from patients with normal sinonasal mucosa, chronic rhinosinusitis, and inverted papillomas are compared to histopathology using principal component analysis and linear discriminant analysis after data preprocessing. A total of 18 normal, 15 chronic rhinosinusitis, and 18 inverted papilloma specimens were evaluated. The model distinguished normal sinonasal mucosa, chronic rhinosinusitis, and inverted papilloma tissue with an overall accuracy of 90.2% (95% confidence interval, 0.86-0.94). In conclusion, Raman spectroscopy can distinguish inverted papilloma, normal sinonasal mucosa, and chronically rhinosinusitis tissue with acceptable accuracy.

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Sinonasal T-Cell Expression of Cytotoxic Mediators Granzyme B and Perforin is Reduced in Patients with Chronic Rhinosinusitis

American Journal of Rhinology and Allergy ◽

10.2500/ajra.2017.31.4474 ◽

2017 ◽

Vol 31 (6) ◽

pp. 352-356 ◽

Cited By ~ 1

Author(s):

Sarah E. Smith ◽

Rodney J. Schlosser ◽

James R. Yawn ◽

Jose L. Mattos ◽

Zachary M. Soler ◽

...

Keyword(s):

Flow Cytometry ◽

T Cells ◽

T Cell ◽

Nk Cells ◽

Chronic Rhinosinusitis ◽

Nasal Polyp ◽

Granzyme B ◽

Cytotoxic Cells ◽

Sinonasal Mucosa ◽

Perforin Expression

Background CD8+ T cells and natural killer (NK) cells are cytotoxic cells that use granzyme B (GrB) and perforin. Defective cytotoxic function is known to play a role in dysregulated immune response as seen in chronic sinusitis, also referred to as chronic rhinosinusitis (CRS). However, to our knowledge, in the United States, neither GrB or perforin expression has been reported in patients with CRS. Objective The aim of this study was to investigate sinonasal cytotoxic cells, their mediators, and cell-specific distribution of these mediators in patients with CRS with nasal polyp (CRSwNP) and in patients with CRS without nasal polyp (CRSsNP). Methods Blood and sinus tissue samples were taken from patients with CRSsNP (n = 8) and CRSwNP (n = 8) at the time of surgery. Control subjects (n = 8) underwent surgery for cerebrospinal fluid leak repair or to remove non-hormone-secreting pituitary tumors. The cells were analyzed via flow cytometry by using CD8 expression to identify cytotoxic T cells and CD56 expression to identify NK cells. Intracellular GrB and perforin expression were analyzed with flow cytometry. Results We observed no significant differences in plasma or peripheral blood immune cell numbers or specific levels of GrB or perforin among the groups. In the sinonasal mucosa of the patients with CRSsNP and the patients with CRSwNP, there was a significant decrease in GrB and perforin levels (p <0.05) despite similar or increased numbers of cytotoxic cells when compared with the controls. The overall decrease in GrB and perforin in the sinonasal mucosa of the patients with CRSsNP and the patients with CRSwNP was due to decreased T cell production. There was no difference in total NK cell count or expression of perforin or GrB among all the groups. Conclusion Total levels of sinonasal GrB and perforin were decreased in the sinonasal mucosa of both the patients with CRSwNP and the patients with CRSsNP compared with the controls, whereas sinonasal CD8+ T cells, (but not NK cells,), intracellular stores of GrB and perforin were reduced in the patients with CRSwNP compared with the controls.

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Aquaporin expression profiles in normal sinonasal mucosa and chronic rhinosinusitis

International Forum of Allergy & Rhinology ◽

10.1002/alr.21415 ◽

2014 ◽

Vol 4 (11) ◽

pp. 901-908 ◽

Cited By ~ 3

Author(s):

Claire Frauenfelder ◽

Charmaine Woods ◽

Damian Hussey ◽

Eng Ooi ◽

Sonja Klebe ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Expression Profiles ◽

Sinonasal Mucosa

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Biofilms in Chronic Rhinosinusitis: A Review

American Journal of Rhinology and Allergy ◽

10.2500/ajra.2009.23.3319 ◽

2009 ◽

Vol 23 (3) ◽

pp. 255-260 ◽

Cited By ~ 73

Author(s):

Michael Cohen ◽

Jennifer Kofonow ◽

Jayakar V. Nayak ◽

James N. Palmer ◽

Alexander G. Chiu ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Disease Process ◽

Therapeutic Interventions ◽

Bacterial Biofilms ◽

Planktonic Bacteria ◽

Acute Infections ◽

Abiotic Surfaces ◽

Live Bacteria ◽

Sinonasal Mucosa ◽

Substantial Effort

Background Bacterial biofilms consist of a complex, organized community of bacteria that anchor to both biotic and abiotic surfaces. They are composed of layers of embedded, live bacteria within extruded exopolymeric matrix. This configuration allows for evasion of host defenses and decreased susceptibility to antibiotic therapy while maintaining the ability to deliberately release planktonic bacteria, resulting in recurrent acute infections. Thus, bacterial biofilms were hypothesized to contribute to the progression and persistence of chronic rhinosinusitis. Methods This review summarizes several of the seminal papers supporting this hypothesis. Results Multiple reports using various imaging modalities have demonstrated the presence of biofilms in sinonasal mucosa of patients with chronic rhinosinusitis. More recently, several studies have correlated the presence of biofilms with poor clinical outcomes in the disease process. Early therapeutic interventions have generated mixed results. Conclusions Bacterial biofilms appear to contribute to the progression of chronic rhinosinusitis in a subset of patients, although substantial effort toward therapeutic intervention is still necessary.

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Long-term low-dose antibiotics in recalcitrant chronic rhinosinusitis: a retrospective analysis

Rhinology Journal ◽

10.4193/rhino11.123 ◽

2012 ◽

Vol 50 (1) ◽

pp. 45-55

Author(s):

W.J.M. Videler ◽

K. van Hee ◽

S.M. Reinartz ◽

C. Georgalas ◽

F.W. van der Meulen ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Outpatient Clinic ◽

Low Dose ◽

Group Discussion ◽

Sinus Surgery ◽

Dose Treatment ◽

Intranasal Corticosteroids ◽

Significant Difference ◽

Sinonasal Mucosa

Introduction: In recalcitrant Chronic RhinoSinusitis (CRS) treatment with intranasal corticosteroids, short-term antibiotics and even sinus surgery is frequently insufficient. Long-term low-dose administration of antibiotics has been suggested as a treatment option in these patients. We analysed the outpatient clinic population treated with different long-term low-dose antibiotics at the AMC Amsterdam. Patients and methods: Eligible patients, who were treated with trimethoprim-sulfamethoxazole or macrolides, were retrospectively identified from our outpatient clinic in 2009. The two main outcome measures were sinonasal complaints and nasal endoscopic findings. A 5-point grading scale was used to score the results compared with the pre-treatment situation. This was measured at several time-points during, and after the antibiotic course, and at the end of the follow-up term. Results: Seventy-six patients were included, 53 per cent had asthma and all of them had undergone sinus surgery. Seventy-eight per cent showed improvement of the symptoms, and 84 per cent demonstrated improvement of the sinonasal mucosa at the end of the course. No significant difference was found between the trimethoprim-sulfamethoxazole and macrolide group. Discussion: Long-term low-dose treatment with antibiotics seems to improve CRS symptoms and the appearance of the sinonasal mucosa on nasal endoscopy. However, at this stage, strong conclusions are immature because no placebo-group has been included. Despite increasing use of long-term low-dose treatment of recalcitrant CRS in referral centres, hard clinical evidence is lacking. More research is urgently required.

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The Expression of ephrinA1/ephA2 Receptor Increases in Chronic Rhinosinusitis and ephrinA1/ephA2 Signaling Affects Rhinovirus-Induced Innate Immunity in Human Sinonasal Epithelial Cells

Frontiers in Immunology ◽

10.3389/fimmu.2021.793517 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sang Hag Lee ◽

Sung Hoon Kang ◽

Mun Soo Han ◽

Ji Won Kwak ◽

Hyeon Geun Kim ◽

...

Keyword(s):

Immune Response ◽

Epithelial Cells ◽

Chronic Rhinosinusitis ◽

Cultured Cells ◽

Normal Mucosa ◽

Poly I:C ◽

Type I ◽

Antiviral Immune Response ◽

Immune Mediators ◽

Sinonasal Mucosa

EphA2 receptor and its ephrin ligands are involved in virus infection, epithelial permeability, and chemokine secretion. We hypothesized that ephrinA1/ephA2 signaling participates in rhinovirus (RV)-induced antiviral immune response in sinonasal mucosa of patients with chronic rhinosinusitis (CRS). Therefore, we investigated the expression of ephrinA1/ephA2 in normal and inflamed sinonasal mucosa and evaluated whether they regulate chemokine secretion and the production of antiviral immune mediators including interferons (IFNs) in RV-infected human primary sinonasal epithelial cells. For this purpose, the expression and distribution of ephrinA1/ephA2 in sinonasal mucosa were evaluated with RT-qPCR, immunofluorescence, and western blot. Their roles in chemokine secretion and the production of antiviral immune mediators such as type I and III IFNs, and interferon stimulated genes were evaluated by stimulating ephA2 with ephrinA1 and inactivating ephA2 with ephA2 siRNA or inhibitor in cells exposed to RV and poly(I:C). We found that ephrinA1/ephA2 were expressed in normal mucosa and their levels increased in inflamed sinonasal mucosa of CRS patients. RV infection or poly(I:C) treatment induced chemokine secretion which were attenuated by blocking the action of ephA2 with ephA2 siRNA or inhibitor. The production of antiviral immune mediators enhanced by rhinovirus or poly (I:C) is increased by blocking ephA2 compared with that of cells stimulated by either rhinovirus or poly(I:C) alone. In addition, blocking ephA2 attenuated RV replication in cultured cells. Taken together, these results describe a novel role of ephrinA1/ephA2 signaling in antiviral innate immune response in sinonasal epithelium, suggesting their participation in RV-induced development and exacerbations of CRS.

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Evaluation of Performance and Tolerability of Nebulized Hyaluronic Acid Nasal Hypertonic Solution in the Treatment of Chronic Rhinosinusitis

American Journal of Rhinology and Allergy ◽

10.1177/1945892420923927 ◽

2020 ◽

Vol 34 (6) ◽

pp. 725-733 ◽

Cited By ~ 1

Author(s):

Daniele Monzani ◽

Giulia Molinari ◽

Chiara Gherpelli ◽

Laura Michellini ◽

Matteo Alicandri-Ciufelli

Keyword(s):

Hyaluronic Acid ◽

Chronic Rhinosinusitis ◽

Signs And Symptoms ◽

Global Evaluation ◽

Hypertonic Solution ◽

Evaluation Instrument ◽

Evaluation Of Performance ◽

Before And After ◽

Safety Parameters ◽

Sinonasal Mucosa

Background Nasal solutions are part of the recommended therapy of chronic rhinosinusitis (CRS). Formulations containing hyaluronic acid (HA) may represent a promising topical treatment in CRS patients in light of the anti-inflammatory and protective effect of HA on the sinonasal mucosa. Objective Primary aim was to evaluate the performance of a new nebulized HA nasal hypertonic solution in the relief of symptoms of CRS. Secondarily, evaluation of symptoms improvement, endoscopic nasal findings, and safety profile were assessed. Methods A monocenter, single arm, not controlled, premarket clinical trial on a new nasal solution containing HA was performed. All the included patients had a history of previously diagnosed or recurrent CRS or they had received a clinical diagnosis of CRS defined, according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Each patient was evaluated on 3 visits. Endoscopic nasal examination and Nasal Obstruction Symptom Evaluation Instrument questionnaire filling were performed during each visit. Patients’ adherence to treatment and overall satisfaction, patients’ and investigator’s global evaluation of performance, and safety parameters were also assessed. Results Eighty patients were enrolled. The use of the investigated HA nasal solution revealed to be significantly effective in the relief of symptoms of CRS. According to daily patients’ diaries, several signs and symptoms significantly improved after therapy. The comparison between endoscopic assessments before and after treatment confirmed improvement of the condition in at least 75% of patients. Seventy-four percent of the patients were quite or very satisfied with the treatment and 80% reported an improvement. The investigator’s global assessment of performance was in agreement with this view, as more than 80% of the patients were considered clinically improved. Conclusions The use of the investigated new nebulized HA nasal hypertonic solution is an effective and safe the treatment of CRS.

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