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CD8(+) T cells implicated in the pathogenesis of allergic fungal rhinosinusitis. - Allergy & rhinology (Providence, R.I.)
Fungi in paranasal sinuses are characteristic and considered a major pathogenic factor in a subset of chronic rhinosinusitis (CRS) patients, known as allergic fungal rhinosinusitis (AFRS). CD8(+) T cells are enriched in AFRS sinuses but their role in fungal-specific responses is unknown. Alternaria alternata- and Aspergillus fumigatus-specific T lymphocyte responses were investigated in 6 AFRS patients, 10 eosinophilic mucus CRS (EMCRS) patients, 10 CRS with nasal polyps (CRSwNPs) patients, 6 allergic rhinitis with fungal allergy (ARFA) patients, and five controls. Fungal-specific proliferation of human peripheral blood mononuclear cells (PBMCs) was studied prospectively. Proliferating cells were examined for CD3, CD4, CD8, and CD25 expression. Relevant clinical characteristics, fungal allergy, detection of fungi in sinuses, and CD4(+) and CD8(+) composition of sinus T cells were also examined. CD4(+) T-cell division to fungi occurred in all samples, regardless of fungal allergy or CRS. Fungal-specific CD8(+) T-cell division occurred in all ARFA and control samples and the majority of CRSwNP patients; however, CD8(+) T cells failed to proliferate in AFRS and EMCRS patients. The CD8(+) T cells from AFRS patients also did not up-regulate the activation marker, CD25, with fungal antigen exposure. Presence of A. alternata- and A. fumigatus-specific CD4(+) and CD8(+) T-cell proliferation in healthy individuals, ARFA, and CRSwNP patients suggests that both T-cell subsets may be important in immune responses to these fungi. In AFRS and EMCRS patients, only fungal-specific CD4(+) T-cell proliferation occurred; hence, a lack of CD8(+) T-cell proliferation and activation in the presence of sinus eosinophilic mucus in these patients, regardless of fungal allergy, is a novel finding. This raises the question whether a dysfunctional CD8(+) T-cell response predisposes to ineffective clearance and accumulation of fungi in the sinuses of susceptible patients.
CD4(+) and CD8(+) regulatory T cells in chronic rhinosinusitis mucosa. - American journal of rhinology & allergy
Chronic rhinosinusitis (CRS) mucosal inflammation is characterized by an accumulation of effector-memory T cells, but their immune regulatory potential has not been adequately examined. Coexpression of transcription factor, forkhead box P3 (Foxp3), and interleukin-2 receptor, CD25, in CD4(+) and CD8(+) T cells is linked with regulatory function in humans. The aim of this study was to investigate the regulatory T cell (Treg) phenotype of CD4(+) (CD4Treg) and CD8(+) (CD8Treg) T cells in peripheral blood (PB) and sinus mucosa of CRS patients.Prospective study was performed involving 32 CRS with nasal polyp (CRSwNP), 14 CRS without nasal polyp (CRSsNP), and 8 control patients. Sinus and PB T lymphocytes were stained with CD3, CD4, CD8, CD25, and Foxp3 and analyzed using flow cytometry. Relevant clinical characteristics, sinus bacterial culture results, and eosinophilic mucus were examined.Sinus mucosa had a higher percentage of CD4Treg (CD3(+)CD4(+)CD25(+)Foxp3(+)) population compared with PB in all patients. The percentage of PB CD4Treg and CD8Treg (CD3(+)CD8(+)CD25(+)Foxp3(+)) was not significantly different between the study groups. CRS mucosal tissue had a higher percentage of CD4Treg and activated T-helper cells than controls. There was no significant difference in PB and mucosal CD4Treg populations in CRS patients based on the presence of allergy, sinus culture results, or eosinophilic mucus. In controls, increased mucosal CD4Treg correlated with coexisting allergy. Although overall CD4Treg numbers were higher, the regulatory potential of activated CD4(+) T cells (CD4Treg/activated T-helper cell ratio) was significantly lower in CRS mucosa compared with controls. The CD8Treg subset was also significantly reduced in CRSwNP mucosa compared with controls.A higher percentage of CD4Treg and activated T-helper cells in CRS mucosa suggests increased inflammation in CRS, independent of the presence of allergy, microbial culture results, or eosinophilic mucus. However, the decreased ratio of CD4Treg versus activated T-helper cells in CRS and reduced CD8Treg population in CRSwNPs indicates an inflammatory bias and the inability to control mucosal disease.
Accumulation of effector memory CD8+ T cells in nasal polyps. - American journal of rhinology & allergy
T lymphocytes are prevalent in sinus mucosa and are implicated in chronic rhinosinusitis (CRS) pathogenesis. However, the major T-cell subpopulations, helper (CD4+) and cytotoxic (CD8+), have not been adequately examined in CRS. This study was designed to characterize human sinus mucosa and peripheral blood (PB) CD4+ and CD8+ T cells and their level of differentiation in CRS with nasal polyps (NPs), CRS without NPs, and control patients.A prospective study was performed. Percentages of CD4+ and CD8+ T cells and their levels of differentiation were analyzed in sinus mucosa and PB by flow cytometry. Cell populations were defined as naive, central memory, effector memory, and effector T cells using cell surface markers CD45RA, CD62L, and CD27. The influence of coexisting allergy, sinus eosinophilic mucus (EM), and culture results were examined.In all patients, sinus mucosa had a lower percentage of CD4+ and a higher percentage of CD8+ T cells compared with PB. However, CRS with NPs (n = 86) had a significantly higher percentage of mucosal CD8+ T cells compared with CRS without NPs (n = 40) in control (n = 13) patients (p < 0.0001). Effector memory T cells were increased in sinuses compared with PB in all patients; however, the percentage of effector memory CD8+ T cells was greatest in CRS with NP mucosa (p = 0.002). Surprisingly coexisting allergy or culture results did not influence the mucosal T-cell phenotype. CRS with NP patients with sinus EM had a significantly higher percentage of mucosal CD8+ T cells.Sinus mucosa in CRS with NPs is characterized by a significant enrichment of CD8+ T cells and a relative deficiency of CD4+ T cells. The majority of NP CD8+ T cells had a terminally differentiated, mature, effector memory phenotype, which raises the question, whether these cells are pathogenic or appear as a consequence of inflammation, independent of the presence of allergy or positive microbial culture.
Carotid artery injury during endoscopic endonasal skull base surgery: incidence and outcomes. - Neurosurgery
Injury to the internal carotid artery (ICA) during endoscopic endonasal skull base surgery is a feared complication that is not well studied or reported.To evaluate the incidence, to identify potential risk factors, and to present management strategies and outcomes of ICA injury during endonasal skull base surgery at our institution.We performed a retrospective review of all endoscopic endonasal operations performed at our institution between 1998 and 2011 to examine potential factors predisposing to ICA injury. We also documented the perioperative management and outcomes after injury.There were 7 ICA injuries encountered in 2015 endonasal skull base surgeries, giving an incidence of 0.3%. Most injuries (5 of 7) involved the left ICA, and the most common diagnosis was chondroid neoplasm (chordoma, chondrosarcoma; 3 of 7 [2% of 142 cases]). Two injuries occurred during 660 pituitary adenoma resections (0.3%). The paraclival ICA segment was the most commonly injured site (5 of 7), and transclival and transpterygoid approaches had a higher incidence of injury, although neither factor reached statistical significance. Four of 7 injured ICAs were sacrificed either intraoperatively or postoperatively. No patient suffered a stroke or neurological deficit. There were no intraoperative mortalities; 1 patient died postoperatively of cardiac ischemia. One of the 3 preserved ICAs developed a pseudoaneurysm over a mean follow-up period of 5 months that was treated endovascularly.ICA injury during endonasal skull base surgery is an infrequent and manageable complication. Preservation of the vessel remains difficult. Chondroid tumors represent a higher risk and should be resected by surgical teams with significant experience.
The microbiome of chronic rhinosinusitis: culture, molecular diagnostics and biofilm detection. - BMC infectious diseases
Bacteria and fungi are believed to influence mucosal inflammation in chronic rhinosinusitis (CRS). However their presence and relationship to disease is debated. This study used multiple detection methods to compare microbial diversity and microbial abundance in healthy and diseased sinonasal mucosa. The utility of contemporary detection methods is also examined.Sinonasal mucosa was analyzed from 38 CRS and 6 controls. Bacterial and fungal analysis was performed using conventional culture, molecular diagnostics (polymerase chain reaction coupled with electrospray ionization time-of-flight mass spectrometry) and fluorescence in situ hybridization.Microbes were detected in all samples, including controls, and were often polymicrobial. 33 different bacterial species were detected in CRS, 5 in control patients, with frequent recovery of anaerobes. Staphylococcus aureus and Propionibacterium acnes were the most common organisms in CRS and controls, respectively. Using a model organism, FISH had a sensitivity of 78%, and a specificity of 93%. Many species were detected in both CRS and controls however, microbial abundance was associated with disease manifestation.This study highlights some cornerstones of microbial variations in healthy and diseased paranasal sinuses. Whilst the healthy sinus is clearly not sterile, it appears prevalence and abundance of organisms is critical in determining disease. Evidence from high-sensitivity techniques, limits the role of fungi in CRS to a small group of patients. Comparison with molecular analysis suggests that the detection threshold of FISH and culture is related to organism abundance and, furthermore, culture tends to select for rapidly growing organisms.
Confounding factors in rhinological research. - Current opinion in otolaryngology & head and neck surgery
Basic science studies directed at understanding the inflammatory mechanisms in chronic rhinosinusitis (CRS) are increasing, yet their relevance to the underlying disease process is often conflicting and confounded by the enrollment of a heterogeneous CRS population. This review is aimed at exploring the issues affecting the basic science mucosal studies of CRS patients, with special attention to the inclusion criteria for CRS and the control group, and the site from which the mucosal tissue sample is obtained.A common confounding factor is an inadequate documentation of selection criteria for patients, controls, and tissue sites examined. Inconsistent definitions for CRS and for maximum medical therapy, and a lack of histopathology confirmation of mucosal inflammation (eosinophilic or neutrophilic) can bias the disease population entering a given study. Further confounding factors include the influence of coexisting diseases, pollution and cigarette smoke, and a need for same-site tissue comparisons, meticulous selection of relevant controls, and consensus on 'nondiseased' mucosal inflammatory cell populations and microbiology.Documentation of well defined patient and control groups, standardized specimen collection methods, and detection assays are critical in minimizing the bias and conflicting findings among investigators. With standardized sampling of tissue sites and tight controls on subcategories of CRS patients enrolled, studies will more likely identify the findings that can increase our understanding of the disparate group of CRS patients and identify new therapeutic targets in the CRS subcategories.
Bacterial-induced epithelial damage promotes fungal biofilm formation in a sheep model of sinusitis. - International forum of allergy & rhinology
Fungal biofilms have been discovered in chronic rhinosinusitis (CRS) patients, but factors contributing to their establishment are obscure. A recent animal study showed bacterial co-inoculation was required. We examine the role of 4 bacterial species and a cilia toxin on fungal biofilm formation in a sheep sinusitis model. The importance of epithelial integrity on fungal biofilm formation is also examined.Forty-eight frontal sinuses were inoculated with Aspergillus fumigatus alone, with 1 of 4 bacteria, or a cilia toxin. Bacterial and fungal biofilm was determined using confocal scanning laser microscopy. Inflammation and cilia integrity were assessed using light microscopy and transmission electron microscopy, respectively.No fungal biofilm formed when inoculated alone. Florid fungal biofilm developed in more than 75% of sinuses associated with bacterial biofilm of all species, except Haemophilus influenzae, which failed to establish bacterial biofilm. Fungal biofilm also established in association with cilia toxin. Significant cilial damage was incited by all bacterial biofilms and cilia toxin, and was associated with fungal proliferation. Fungal biofilm formation did not significantly increase mucosal inflammation or epithelial damage over that caused by the bacteria or cilia toxin alone.Bacterial biofilms cause sinonasal mucosal inflammation and epithelial injury, which provides conditions appropriate for fungal biofilm proliferation. The role of cilia in sinonasal mucosal defense against fungal organisms has been demonstrated. Without such an insult, fungal biofilms fail to proliferate in occluded sinuses. Improving cilial recovery postoperatively and treating bacterial biofilms may be key factors in reducing recalcitrance in allergic fungal rhinosinusitis patients.Â© 2013 ARS-AAOA, LLC.
Chronic rhinosinusitis: observation or treatment. - Current opinion in allergy and clinical immunology
Several treatment options have been proposed for chronic rhinosinusitis (CRS). Our purpose is to present a protocol/tool to treat patient symptoms, which is initially independent of assessment for presence of CRS.This protocol is called the Rational Patient Experiment (RPE), and its concept is largely based on the fact that CRS is overrepresented in incidence based on surveys, because symptoms of CRS are nonspecific and overlap multiple other disorders. Patients whose symptoms persist, despite the RPE, require further objective assessment of CRS with endoscopy and computed tomography.This review outlines the RPE and the evidence base for observation versus treatment with saline washes, steroids, or antibiotics.
Rhinitis medicamentosa as a cause of increased intraoperative bleeding. - The Laryngoscope
Rhinitis medicamentosa occurs with repeated and prolonged use of topical decongestants. The resultant reduced ability to respond to decongestants mediated via enlarged capillary endothelial gaps can lead to profuse bleeding during turbinate surgery. We recommend that patients with rhinitis medicamentosa be weaned off topical decongestants prior to elective turbinate surgery to minimize this complication. The management of rhinitis medicamentosa and a case of intraoperative hemorrhage are presented.
Quality of life following endonasal skull base surgery. - Skull base : official journal of North American Skull Base Society ... [et al.]
The importance of quality of life (QOL) outcomes following treatments for head and neck tumors are now increasingly appreciated and measured to improve medical and surgical care for these patients. An understanding of the definitions in the setting of health care and the use of appropriate QOL instruments and measures are critical to obtain meaningful information that guides decision making in various aspects of patient health care. QOL outcomes following cranial base surgery is only recently being defined. In this article, we describe the current published data on QOL outcomes following cranial base surgery and provide preliminary prospective data on QOL outcomes and sinonasal morbidity in patients who underwent endonasal cranial base surgery for management of various skull base tumors at our institution. We used a disease-specific multidimensional instrument to measure QOL outcomes in these patients. Our results show that although sinonasal morbidity is increased, this is temporary, and the vast majority of patients have a very good QOL by 4 to 6 months after endonasal approach to the cranial base.
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