Harshita Pant

The microbiome of chronic rhinosinusitis: culture, molecular diagnostics and biofilm detection

BackgroundBacteria 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.MethodsSinonasal 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.ResultsMicrobes 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.ConclusionsThis 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.

Quality of life following endonasal skull base surgery.

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.

Carotid artery injury during endoscopic endonasal skull base surgery: incidence and outcomes.

BACKGROUND: Injury to the internal carotid artery (ICA) during endoscopic endonasal skull base surgery is a feared complication that is not well studied or reported. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. ABBREVIATIONS: EES, endoscopic nasal surgery ICA, internal carotid artery

Fungal-specific humoral response in eosinophilic mucus chronic rhinosinusitis.

Objectives/Hypothesis: An immunoglobulin (Ig)E‐mediated allergic pathogenesis is presumed in allergic fungal sinusitis (AFS), yet extensive polyps and eosinophilic mucus (EM) in the paranasal sinuses may also occur in the absence of allergy. Although a noninvasive fungal pathogenesis is presumed in all chronic rhinosinusitis with EM (EMCRS), fungal‐specific nonallergic immune responses have not been thoroughly investigated. We tested the hypothesis that there is a fungal‐specific humoral response in EMCRS and that it is not confined to IgE.

A new endoscopic staging system for angiofibromas.

OBJECTIVE To develop a new staging system for juvenile nasopharyngeal angiofibroma that reflects changes in surgical approaches (endonasal), route of intracranial extension, and the extent of vascular supply from the internal carotid artery. DESIGN Retrospective review of case series. SETTING Academic medical center. PATIENTS Patients undergoing endoscopic endonasal surgery for juvenile nasopharyngeal angiofibroma at the University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania, from 1998 through 2008. INTERVENTION Patients were staged according to current systems and compared with a new staging system that also incorporated the route of skull base extension and tumor vascularity. MAIN OUTCOME MEASURES Estimated blood loss, number of operations, and tumor recurrence. RESULTS Skull base erosion was observed in 74% of cases. Following embolization of external carotid artery tributaries, residual vascularity from the internal carotid artery was seen in 51% of patients. Residual vascularity, classified as UPMC stage IV and V, strongly correlated with blood loss, requirement for multiple procedures, and residual or recurrent tumor. CONCLUSIONS Tumor size and extent of sinus disease are less important in predicting complete tumor removal with endonasal surgical techniques. The UPMC staging system for juvenile nasopharyngeal angiofibroma accounts for 2 important prognostic factors, route of cranial base extension, and vascularity and is applicable to endoscopic or open approaches. Compared with other staging systems, the UPMC staging system provides a better prediction of immediate morbidity (including blood loss and need for multiple operations) and tumor recurrence.

Eosinophilic mucus chronic rhinosinusitis: Clinical subgroups or a homogeneous pathogenic entity?

Background: Eosinophilic mucus chronic rhinosinusitis (EMCRS) can be subclassified using the criteria of detection of fungi in eosinophilic mucus and systemic fungal allergy. Allergic fungal sinusitis (AFS), a subgroup of EMCRS characterized by the presence of fungal allergy, is proposed to be an immunoglobulin (Ig)E‐driven disease, distinct from other EMCRS subgroups. However, our recent studies cast doubt on the central pathogenic role of allergy in AFS. The purpose of this study was to examine the clinical features of EMCRS patients from the different subcategories to determine the relevance of this classification system.

When surgery, antibiotics, and steroids fail to resolve chronic rhinosinusitis.

This article examines the modalities in the treatment of chronic rhinosinusitis (CRS). A correct diagnosis is the first requirement in the successful management of CRS. CRS-directed therapy might fail if the actual cause of symptoms is nonsinogenic. Nasal endoscopy and sinus computed tomography are the primary modalities used in the diagnosis of sinusitis. Allergy and gastroesophageal reflux, may not directly cause sinusitis, but they frequently mimic the symptoms of sinusitis. Therapy can include avoidance of allergens and desensitization in the former and antireflux therapy in the latter. Underlying systemic causes of refractory sinusitis include immunodeficiency and systemic granulomatous and eosinophilic syndromes. Correct diagnosis is essential to directed therapy. Patients with aspirin exacerbated respiratory disease may benefit from aspirin desensitization. Optimization of mucociliary clearance can be augmented with nasal lavage and mucolytics. Additional nonsteroidal antiinflammatory modalities include use of the leukotriene modulators, montelukast and zileuton. Patients with elevated IgE may benefit from omalizumab (anti-IgE); however, cost constraints restrict use to those patients who have severe asthma. This article also includes management strategies beyond the usual antibiotics, steroids, and sinus surgery. Once immunodeficiency and confounding local mimics of sinusitis are addressed, additional interventions should be tried separately initially to assess the individual patients response to therapy.

The role of allergy in rhinosinusitis.

Purpose of reviewTo examine the current evidence for IgE and non-IgE-mediated hypersensitivity mechanisms in acute and chronic rhinosinusitis. Recent findingsEpidemiological studies show that classical IgE-mediated allergy is present in a proportion of acute rhinosinusitis patients. There is conflicting evidence whether the prevalence of IgE-mediated allergy is greater in chronic rhinosinusitis than in individuals without chronic rhinosinusitis. Despite presence of classical IgE-mediated allergy, based on elevated allergen-specific serum IgE levels and positive skin prick tests, currently there is no direct evidence for allergy as a major cause of sinonasal inflammation in chronic rhinosinusitis. There is increasing evidence that non-IgE-mediated fungal hypersensitivity and nonallergic IgE-associated inflammation may contribute to the pathogenesis in some forms of chronic rhinosinusitis, including allergic fungal sinusitis. Specific IgE to bacterial superantigens may also be elevated in nasal polyps and modulate eosinophilic inflammation. Recent insights into mucosal immune mechanisms yield intriguing prospects for the roles of mucosal IgE, mast cells and non-IgE-mediated hypersensitivity mechanisms that require further examination in rhinosinusitis. SummaryThere is a need for further immunological studies of the systemic and mucosal cellular and humoral mechanisms in well defined patient groups and controls to better understand the role of IgE and non-IgE-mediated hypersensitivity mechanisms and nonhypersensitivity functions of IgE in rhinosinusitis.

IgE-mediated fungal allergy in allergic fungal sinusitis

This review will address the current knowledge of the pathogenic mechanisms in allergic fungal sinusitis (AFS) and the basis for the current classification of a subgroup of chronic rhinosinusitis patients. Special attention is directed to the role of immunoglobulin E (IgE)‐mediated fungal allergy in the pathogenesis of AFS. Concepts relating to the mucosal inflammatory response are introduced, as a knowledge of the reactions of the sinus mucosal cells can lead to a better understanding of the mechanisms perpetuating and maintaining the chronic inflammation. Laryngoscope, 2009

CD4+ and CD8+ Regulatory T Cells in Chronic Rhinosinusitis Mucosa:

Background 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), an 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 ell (T phenotype of CD4+ (CD4Treg) and CD8+ (CD8Treg) T cells in peripheral blood (PB) and sinus mucosa of CRS patients. Methods 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. Results Sinus mucosa had a higher percentage of CD4Treg (CD3+CD4+CD25+Foxp3+) population compared with PB 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 creased 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. Conclusion 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. How, 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.BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION 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.