50 results on '"Adappa, Nithin D"'
Search Results
2. Predictive factors for decreased baseline quality of life in patients with sinonasal malignancies.
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Fleseriu CM, Beswick DM, Maoz SL, Hwang PH, Choby G, Kuan EC, Chan EP, Adappa ND, Geltzeiler M, Getz AE, Humphries IM, Le CH, Abuzeid WM, Chang EH, Jafari A, Kingdom TT, Kohanski MA, Lee JK, Nabavizadeh SA, Nayak JV, Palmer JN, Patel ZM, Pinheiro-Neto CD, Resnick AC, Smith TL, Snyderman CH, St John MA, Storm J, Suh JD, Wang MB, and Wang EW
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- Male, Humans, Female, Treatment Outcome, Quality of Life, Endoscopy, Skull Base, Chronic Disease, Skull Base Neoplasms, Rhinitis
- Abstract
Background: The impact of sinonasal malignancies (SNMs) on quality of life (QOL) at presentation is poorly understood. The Sinonasal Outcome Test (SNOT-22) and University of Washington Quality of Life (UWQOL) are validated QOL instruments with distinctive subdomains. This study aims to identify factors impacting pretreatment QOL in SNM patients to personalize multidisciplinary management and counseling., Methods: Patients with previously untreated SNMs were prospectively enrolled (2015-2022) in a multicenter observational study. Baseline pretreatment QOL instruments (SNOT-22, UWQOL) were obtained along with demographics, comorbidities, histopathology/staging, tumor involvement, and symptoms. Multivariable regression models identified factors associated with reduced baseline QOL., Results: Among 204 patients, presenting baseline QOL was significantly reduced. Multivariable regression showed worse total SNOT-22 QOL in patients with skull base erosion (p = 0.02). SNOT-rhinologic QOL was worse in women (p = 0.009), patients with epistaxis (p = 0.036), and industrial exposure (p = 0.005). SNOT extranasal QOL was worse in patients with industrial exposure (p = 0.016); worse SNOT ear/facial QOL if perineural invasion (PNI) (p = 0.027). Squamous cell carcinoma pathology (p = 0.037), palate involvement (p = 0.012), and pain (p = 0.017) were associated with worse SNOT sleep QOL scores. SNOT psychological subdomain scores were significantly worse in patients with palate lesions (p = 0.022), skull base erosion (p = 0.025), and T1 staging (p = 0.023). Low QOL was more likely in the presence of PNI on UW health (p = 0.019) and orbital erosion on UW overall (p = 0.03). UW social QOL was worse if palatal involvement (p = 0.023) or PNI (p = 0.005)., Conclusions: Our findings demonstrate a negative impact on baseline QOL in patients with SNMs and suggest sex-specific and symptom-related lower QOL scores, with minimal histopathology association. Anatomical tumor involvement may be more reflective of QOL than T-staging, as orbital and skull base erosion, PNI, and palate lesions are significantly associated with reduced baseline QOL., (© 2023 ARS‐AAOA, LLC.)
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- 2024
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3. Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2).
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Palmer JN, Adappa ND, Chandra RK, Davis GE, Mahdavinia M, Messina J, Ow RA, Patel ZM, Peters AT, Sacks H, Schlosser RJ, Sindwani R, Soler ZM, White AA, Wise SK, and Mahmoud RA
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- Adult, Humans, Chronic Disease, Fluticasone therapeutic use, Randomized Controlled Trials as Topic, Steroids therapeutic use, Nasal Polyps drug therapy, Nasal Polyps chemically induced, Rhinitis drug therapy, Rhinitis chemically induced, Rhinosinusitis, Sinusitis drug therapy, Sinusitis chemically induced
- Abstract
Background: Chronic rhinosinusitis (CRS) is a prevalent inflammatory disease. No medications are Food and Drug Administration-approved for the most common form, CRS without nasal polyps (also called "chronic sinusitis"). Novel biomechanics of the exhalation delivery system deliver fluticasone (EDS-FLU; XHANCE) to sinonasal areas above the inferior turbinate, especially sinus drainage pathways not reached by standard-delivery nasal sprays., Objective: Assess EDS-FLU efficacy for CRS (irrespective of nasal polyps)., Methods: Two randomized, EDS-placebo-controlled trials in adults with CRS irrespective of polyps (ReOpen1) or exclusively without polyps (ReOpen2) were conducted at 120 sites in 13 countries. Patients received EDS-FLU 1 or 2 sprays/nostril, or EDS-placebo, twice daily for 24 weeks. Coprimary measures were composite symptom score through week 4 and ethmoid/maxillary sinus percent opacification by computed tomography at week 24., Results: ReOpen1 (N = 332) composite symptom score least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -1.58 and -1.60 versus -0.62 (P < .001, P < .001); ReOpen2 (N = 223), -1.54 and -1.74 versus -0.81 (P = .011, P = .001). In ReOpen1, sinus opacification least-squares mean change for EDS-FLU 1 or 2 sprays/nostril versus EDS-placebo was -5.58 and -6.20 versus -1.60 (P = .045, P = .018), and in ReOpen2, -7.00 and -5.14 versus +1.19 (P < .001, P = .009). Acute disease exacerbations were reduced by 56% to 66% with EDS-FLU versus EDS-placebo (P = .001). There were significant, and similar magnitude, symptom reductions in patients using standard-delivery nasal steroid products just before entering the study (P < .001). Adverse events were similar to standard-delivery intranasal steroids., Conclusions: EDS-FLU is the first nonsurgical treatment demonstrated to reduce symptoms, intrasinus opacification, and exacerbations in replicate randomized clinical trials in CRS, regardless of polyp status., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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4. Utilizing Histopathology to Predict Success with Macrolide Therapy in CRS Patients.
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Workman AD, Chang J, Lerner DK, Wilensky J, Montone KT, Bosso JV, Palmer JN, Adappa ND, and Kohanski MA
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- Humans, Macrolides therapeutic use, Chronic Disease, Anti-Bacterial Agents therapeutic use, Sinusitis surgery, Rhinitis surgery, Eosinophilia complications, Nasal Polyps complications
- Abstract
There is currently interest regarding CRSsNP patients with refractory symptomatology following functional endoscopic sinus surgery, and which of these patients can derive benefit from low-dose macrolide therapy. In the present study, we analyze a cohort of over fifty CRSsNP patients on macrolide therapy; structured histopathological findings at the time of surgery were analyzed against the success of macrolide treatment. Independently, fibrosis, absence of squamous metaplasia, absence of eosinophilia, presence of neutrophilic infiltrate, and lymphoplasmocytic predominance were all associated with objective success of macrolide treatment; these findings may allow clinicians to more appropriately select patients for this therapy., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)
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- 2024
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5. Dupilumab-related adverse events among patients with chronic rhinosinusitis with nasal polyposis.
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Lee DJ, Cramer HB, Kshirsagar RS, Douglas JE, Kohanski MA, Palmer JN, Adappa ND, and Bosso JV
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- Humans, Antibodies, Monoclonal, Humanized adverse effects, Chronic Disease, Sinusitis drug therapy, Sinusitis epidemiology, Nasal Polyps drug therapy, Rhinitis drug therapy
- Published
- 2023
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6. Microbial metabolite succinate activates solitary chemosensory cells in the human sinonasal epithelium.
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Sell EA, Tan LH, Lin C, Bosso JV, Palmer JN, Adappa ND, Lee RJ, Kohanski MA, Reed DR, and Cohen NA
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- Humans, Succinic Acid metabolism, Calcium metabolism, Epithelium metabolism, Chronic Disease, Inflammation, Antimicrobial Peptides, Epithelial Cells metabolism, Rhinitis, Sinusitis
- Abstract
Background: Succinate, although most famous for its role in the Krebs cycle, can be released extracellularly as a signal of cellular distress, particularly in situations of metabolic stress and inflammation. Solitary chemosensory cells (SCCs) express SUCNR1, the succinate receptor, and modulate type 2 inflammatory responses in helminth and protozoal infections in the small intestine. SCCs are the dominant epithelial source of interleukin-25, as well as an important source of cysteinyl leukotrienes in the airway, and have been implicated as upstream agents in type 2 inflammation in chronic rhinosinusitis (CRS) and asthma., Methods: In this study, we used scRNAseq analysis, live cell imaging of intracellular calcium from primary sinonasal air-liquid interface (ALI) cultures from 1 donor, and measure antimicrobial peptide release from 5 donors to demonstrate preliminary evidence suggesting that succinate can act as a stimulant of SCCs in the human sinonasal epithelium., Results: Results from scRNAseq analysis show that approximately 10% of the SCC/ionocyte cluster of cells expressed SUCNR1 as well as a small population of immune cells. Using live cell imaging of intracellular calcium, we also demonstrate that clusters of cells on primary sinonasal ALI cultures initiated calcium-mediated signaling in response to succinate stimulation. Furthermore, we present evidence that primary sinonasal ALI cultures treated with succinate had increased levels of apical beta-defensin 2, an antimicrobial peptide, compared to treatment with a control solution., Conclusion: Overall, these findings demonstrate the need for further investigation into the activation of the sinonasal epithelium by succinate in the pathogenesis of CRS., (© 2022 ARS-AAOA, LLC.)
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- 2023
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7. Image guided dilation of sinus ostium in revision sinus surgery.
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Han JK, Palmer JN, Adappa ND, Nachlas NE, Chandra RK, Jacobs JB, Manes RP, and McKenzie K
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- Adult, Humans, Dilatation, Prospective Studies, Maxillary Sinus surgery, Catheterization, Endoscopy, Chronic Disease, Treatment Outcome, Rhinitis surgery
- Abstract
Purpose: Assess if a rigid, image-guided balloon could be used effectively and safely in revision sinus surgery., Materials and Methods: A prospective, non-randomized, single-arm, multicenter study to assess the safety and device performance of the NuVent™ EM Balloon Sinus Dilation System. Adults with CRS in need of revision sinus surgery were enrolled for balloon sinus dilation of a frontal, sphenoid, or maxillary sinus. The primary device performance endpoint was the ability of the device to (1) navigate to; and (2) dilate tissue in subjects with scarred, granulated, or previously surgically-altered tissue (revision). Safety outcomes included the assessment of any operative adverse events (AEs) directly attributable to the device or for which direct cause could not be determined. A follow-up endoscopy was conducted at 14 days post-treatment for assessment of any AEs. Performance outcomes included the surgeon's ability to reach the target sinus (es) and dilate the ostia. Endoscopic photos were captured for each treated sinus pre- and post-dilation., Results: At 6 US clinical sites, 51 subjects were enrolled; 1 subject withdrew before treatment due to a cardiac complication from anesthesia. 121 sinuses were treated in 50 subjects. The device performed as expected in 100 % of the 121 treated sinuses, with investigators able to navigate to the treatment area and dilate the sinus ostium without difficulty. Ten AEs were seen in 9 subjects, with 0 related to the device., Conclusion: The targeted frontal, maxillary or sphenoid sinus ostium were safely dilated in every revision subject treated, with no AEs directly attributed to the device., Competing Interests: Declaration of competing interest Author disclosures/conflicts of interest are: 1) Joseph K. Han works as a consultant for Medtronic Xomed, Inc.; 2) James Nathan Palmer is a consultant for OptiNose, Acclarent, and Medtronic Xomed, Inc.; 3) Nithin Adappa is a consultant for Acclarent and on the Clinical Trial Steering Committee for OptiNose; 4) Rakesh K. Chandra is a consultant for Regeneron, Astra Zeneca and GSK, and on the Clinical Trial Steering Committee for OptiNose; 5) Joseph B. Jacobs has no disclosures to report; 6) Peter Manes received Research and Grant Support from OptiNose; and 7) Karen McKenzie is an employee of Medtronic Xomed, Inc., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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8. SNOT-22 scores after 6 months of aspirin therapy are predictive of long-term quality of life in AERD.
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Tripathi SH, Corr A, Kumar A, Ungerer H, Salmon M, Adappa ND, and Bosso JV
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- Humans, Aspirin adverse effects, Sino-Nasal Outcome Test, Retrospective Studies, Quality of Life, Chronic Disease, Treatment Outcome, Asthma, Aspirin-Induced diagnosis, Asthma, Aspirin-Induced therapy, Sinusitis therapy, Nasal Polyps surgery, Rhinitis therapy
- Abstract
Background: Aspirin exacerbated respiratory disease (AERD) is an inflammatory condition that consists of eosinophilic asthma, chronic rhinosinusitis with nasal polyps, and respiratory reactions to cyclooxygenase-1 inhibitors. Aspirin therapy after aspirin desensitization (ATAD) is the most extensively studied treatment paradigm for AERD. Objective: The objective was to identify which time point of ATAD was most predictive of long-term outcomes as measured by the 22-item Sino-Nasal Outcome Test (SNOT-22). Methods: A retrospective chart review was conducted of patients at a single institution who underwent endoscopic sinus surgery, followed by ATAD, and had remained on ATAD for 2 consecutive years. SNOT-22 scores were recorded at predesensitization as well as at the 3-, 6-, 12-, and 24-month postdesensitization time points. The patients were separated into two cohorts at each of the data collection time points based on whether their SNOT-22 scores were < 20 (responders) or ≥ 20 (nonresponders). Responder status was compared between each time point and at 24-month postdesensitization. The odds ratios (OR) were then calculated between the two groups at each of the following time points: postsurgery/predesensitization, and 3-, 6-, and 12-month postdesensitization. Results: There were 70 patients who met the inclusion criteria of having 24-month postdesensitization SNOT-22 scores available. Responder status at 6 months after surgery had the most predictive OR 16.5 (95% confidence interval, 3.71-73.44) for long-term outcomes at 24 months. Conclusion: The SNOT-22 scores after 6 months of ATAD showed the greatest predictive value for long-term quality-of-life outcomes and, therefore, poor 6-month SNOT-22 scores could serve as a basis for consideration of alternative therapies.
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- 2023
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9. Similarities between allergen sensitivity patterns of central compartment atopic disease and allergic rhinitis.
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Tripathi SH, Ungerer HN, Rullan-Oliver B, Patel T, Sweis AM, Maina IW, Kohanski MA, Palmer JN, Adappa ND, and Bosso JV
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- Allergens, Humans, Skin Tests, Rhinitis, Rhinitis, Allergic, Rhinitis, Allergic, Seasonal
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- 2022
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10. The management of cystic fibrosis chronic rhinosinusitis: An evidenced-based review with recommendations.
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Spielman DB, Beswick DM, Kimple AJ, Senior BA, Aanaes K, Woodworth BA, Schlosser RJ, Lee S, Cho DY, Adappa ND, DiMango E, and Gudis DA
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- Anti-Bacterial Agents, Chronic Disease, Cystic Fibrosis Transmembrane Conductance Regulator, Humans, Quality of Life, Cystic Fibrosis, Rhinitis, Sinusitis
- Abstract
Background: Cystic fibrosis (CF) chronic rhinosinusitis (CRS) has emerged as a distinct diagnostic entity, unique from other endotypes of CRS in its presentation, pathophysiology, diagnosis, treatment, and outcomes. As the sinonasal health of this patient population may have broad effects on pulmonary health and quality of life, a comprehensive understanding of the diagnostic and therapeutic approach to CF CRS is essential. In recognizing recent scientific advances and unique treatment modalities specific to this challenging patient population, in this review we systematically evaluate the scientific literature and provide an evidenced-based review with recommendations (EBRR) for fundamental management principles of CF CRS., Methods: A systematic review of the literature was performed. Studies evaluating interventions for the management of CF CRS were included. An iterative review process was implemented in accordance with EBRR guidelines. A treatment recommendation was generated based on an assessment of the benefits, harms, and the overall grade of evidence., Results: We evaluated the published literature on 5 unique topics. Each of the following therapeutic categories was investigated explicitly for treatment outcomes in patients with CF CRS: (1) nasal saline; (2) intranasal corticosteroids (INCS); (3) topical antibiotics; (4) cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy; and (5) endoscopic sinus surgery (ESS)., Conclusion: Based on the currently available evidence, nasal saline, ESS, and CFTR modulators are recommended in the management of CF CRS when appropriate. INCS and topical antibiotics are options. Clinical judgment and experience are essential in caring for patients with this uniquely challenging disorder., (© 2021 ARS-AAOA, LLC.)
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- 2022
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11. Comparison of aspirin desensitization outcomes between men and women with AERD.
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Tripathi SH, Kumar A, Kohanski MA, Kennedy DW, Palmer JN, Adappa ND, and Bosso JV
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- Aspirin adverse effects, Chronic Disease, Desensitization, Immunologic, Female, Humans, Male, Asthma, Aspirin-Induced therapy, Nasal Polyps, Rhinitis
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- 2022
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12. Pre-intervention SNOT-22 scores predict outcomes in aspirin exacerbated respiratory disease.
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Kuan EC, Kennedy WP, Patel NN, Goshtasbi K, Kohanski MA, Tong CCL, Papagiannopoulos P, Kennedy DW, Palmer JN, Adappa ND, and Bosso JV
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- Adult, Chronic Disease, Endoscopy, Female, Humans, Longitudinal Studies, Male, Middle Aged, Otorhinolaryngologic Surgical Procedures, Retrospective Studies, Rhinitis surgery, Severity of Illness Index, Sinusitis surgery, Treatment Outcome, Aspirin adverse effects, Research Design, Rhinitis chemically induced, Rhinitis diagnosis, Sino-Nasal Outcome Test, Sinusitis chemically induced, Sinusitis diagnosis
- Abstract
Purpose: This study evaluated whether stratified preoperative, pre- aspirin desensitization (AD) sinonasal symptom scores predict postoperative, post-AD outcomes in Aspirin exacerbated respiratory disease (AERD)., Materials and Methods: Retrospective chart review of patients with aspirin challenge-proven AERD who underwent endoscopic sinus surgery followed by AD was performed. Preoperative, postoperative/pre-AD, and postoperative/post-AD sinonasal symptom scores were collected (22-item Sino-Nasal Outcomes Test, SNOT-22). A longitudinal linear mixed-effects model was used for data analysis., Results: Forty-seven patients (59.6% female) aged 48.0 ± 13.2 were included. Average time from surgery to AD was 70.0 ± 52.8 days. Preoperative SNOT-22 scores (n = 47) were divided into tertiles (cutoffs of 36 and 54 indicating mild [22.5 ± 13.7], moderate [44.3 ± 12.2], and severe [72.9 ± 19.7] disease). This corresponded to 12 (25.5%), 18 (38.3%), and 17 (36.2%) subjects being categorized into mild, moderate, and severe tertiles, respectively. Postoperative, pre-AD SNOT-22 in all disease groups decreased and were not significantly different (12.3 ± 13.7, 11.1 ± 12.2, 22.7 ± 19.7; p = 0.074). At short-term post-AD, only the severe group worsened (35.0 ± 20.3, p < 0.001), whereas other groups demonstrated negligible change (9.3 ± 14.3 and 14.4 ± 12.2). At long-term post-AD, all groups redemonstrated convergence in symptom scores (23.7 ± 20.9, 19.4 ± 15.4, and 31.0 ± 27.6, p = 0.304)., Conclusion: Preoperative SNOT-22 scores may be used as a predictor of postoperative, post-AD patient-reported outcomes in AERD. Patients with mild and moderate disease may derive benefit from surgery and AD alone, while those with severe disease may require additional interventions (e.g., biologics)., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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13. Denatonium benzoate bitter taste perception in chronic rhinosinusitis subgroups.
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Civantos AM, Maina IW, Arnold M, Lin C, Stevens EM, Tan LH, Gleeson PK, Colquitt LR, Cowart BJ, Bosso JV, Palmer JN, Adappa ND, Kohanski MA, Reed DR, and Cohen NA
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- Chronic Disease, Humans, Quaternary Ammonium Compounds, Taste Perception, Nasal Polyps, Rhinitis, Sinusitis
- Abstract
Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP), and aspirin-exacerbated respiratory disease (AERD) have varying levels of inflammation and disease severity. Solitary chemosensory cells (SCCs) are enriched in nasal polyps, are the primary source of interleukin 25 (IL-25) in upper airways, leading to type 2 inflammation, and are activated by bitter-tasting denatonium benzoate (DB). Thus, we sought to evaluate DB taste perception at a range of concentrations in order to identify 1 that most differentiates CRS subgroups from controls., Methods: CRSsNP (n = 25), CRSwNP (n = 26), and AERD (n = 27) patients as well as controls (n = 25) tasted 6 DB concentrations in a fixed, random order, rating on a category scale of 0 (no intensity) to 12 (extremely intense). Sinonasal epithelial cultures were treated with and without denatonium and analyzed for IL-25 via flow cytometry., Results: CRSsNP patients rated DB as significantly less intense than did controls at all concentrations: 5.62 × 10
-9 M, 1.00 × 10-8 M, 1.78 × 10-8 M, 3.16 × 10-8 M, 5.62 × 10-8 M, and 1.00 × 10-7 M (all p < 0.0083). CRSwNP patients did not show significant differences from controls. AERD patients rated DB as significantly more intense than did controls at concentrations of 1.00 × 10-8 M and 3.16 × 10-8 M (p < 0.0083). In vitro data demonstrated significant increase in IL-25-positive cells after denatonium stimulation (n = 5), compared to control (n = 5) (p = 0.012)., Conclusion: Our findings link in vitro DB stimulation of sinonasal tissue with increased IL-25 and show differential DB taste perception in CRS subgroups relative to the control group, with CRSsNP being hyposensitive and AERD being hypersensitive. We propose a concentration of 3.16 × 10-8 M for future study of clinical utility., (© 2020 ARS-AAOA, LLC.)- Published
- 2021
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14. Exhalation Delivery Systems for Application of Intranasal Corticosteroids.
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Kovacs AJ, Adappa ND, and Kuan EC
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- Chronic Disease, Exhalation, Humans, Nasal Cavity, Paranasal Sinuses, Randomized Controlled Trials as Topic, Treatment Outcome, Administration, Intranasal methods, Adrenal Cortex Hormones administration & dosage, Drug Delivery Systems, Fluticasone administration & dosage, Rhinitis drug therapy, Sinusitis drug therapy
- Abstract
Background: Chronic rhinosinusitis (CRS) is a common sinonasal disorder which results in significant inflammation in the nasal cavity and paranasal sinuses. Topical nasal steroids play an important role in the treatment of CRS. Exhalation delivery system with fluticasone (EDS-FLU) utilizes a patient's forced exhalation to power the delivery of topical steroids to deeper areas of the nasal cavity and paranasal sinuses most affected by CRS. This review focuses on evidence surrounding the safety and efficacy of the EDS-FLU system., Methods: Literature search was conducted of articles investigating the safety and efficacy of EDS-FLU. Relevant efficacy and safety data were examined and summarized from the studies., Results: The efficacy and safety of EDS-FLU in CRS, both with and without polyps, has been established in open-label and placebo-controlled phase 3 trials. There was significant improvement in the cardinal symptoms of CRS and subjective patient-reported outcomes scores. Additionally, there was objective improvement in sinonasal inflammation as measured by polyp grade. Recent studies have also established significant improvement in health status and general quality of life following treatment using EDS-FLU. Emerging data have also examined patients who have previously had endoscopic sinus surgery and on appropriate medical therapy and noted improvement in polyp burden and overall Lund-Kennedy scores after using EDS-FLU., Conclusion: Exhalation delivery system with fluticasone demonstrates significant results in both patient-oriented outcomes and objective measures of sinonasal inflammation in patients with CRS with and without polyps. Further research is needed to investigate the long-term outcomes of EDS-FLU and to compare the effects of EDS-FLU with ESS. Exhalation delivery system with fluticasone provides an additional effective treatment modality for patients suffering from CRS.
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- 2021
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15. Incidence, risk factors, and outcomes of endoscopic sinus surgery after endoscopic skull-base surgery.
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Shah RR, Maina IW, Patel NN, Triantafillou V, Workman AD, Kuan EC, Tong CCL, Kohanski MA, O'Malley BW Jr, Adappa ND, and Palmer JN
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- Chronic Disease, Endoscopy, Humans, Incidence, Retrospective Studies, Risk Factors, Skull Base diagnostic imaging, Skull Base surgery, Treatment Outcome, Paranasal Sinuses diagnostic imaging, Paranasal Sinuses surgery, Rhinitis epidemiology, Rhinitis surgery
- Abstract
Background: Patients undergoing endoscopic resection of neoplasms with both sinonasal and skull base involvement can develop chronic rhinosinusitis (CRS) after treatment and may occasionally benefit from additional endoscopic sinus surgery (ESS). We investigate risk factors and outcomes associated with revision ESS (rESS) after endoscopic skull-base surgery (SBS) for neoplasms with combined sinonasal and skull base involvement., Methods: A retrospective review of patients with neoplasms with both sinonasal and skull base involvement who underwent endoscopic resection at a single tertiary care academic institution from 2004 through 2017 was performed. Eighty-three patients were included. Main outcome measures included incidence and timing of revision surgery, Lund-Mackay (LM) scores, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores., Results: rESS was performed in 21 (25%) cases, 15 (18%) of which were due to CRS. Time between initial resection and rESS was an average of 42 months (range, 6 to 142 months). Pre-SBS and post-SBS LM scores were not significantly different (5.0 vs 4.7, p = 0.640), although pre-SBS and post-SBS SNOT-22 scores showed significant improvement (32.6 vs 24.5, p = 0.030). Malignant pathology correlated with need for rESS (odds ratio [OR] 5.07, p = 0.04), as well as treatment including chemotherapy (OR 5.10, p = 0.003) and radiation (OR 4.15, p = 0.013)., Conclusion: A significant proportion of patients develop clinically significant sinusitis after endoscopic SBS for neoplasms with combined sinonasal and skull base involvement and may benefit from rESS. Intervention occurred, on average, 3.5 years after initial tumor resection. Malignant pathology, radiation therapy, and chemotherapy correlate with need for rESS., (© 2020 ARS-AAOA, LLC.)
- Published
- 2020
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16. Chronic rhinosinusitis precipitated by tumor necrosis factor alpha inhibitors is the phenotype of chronic rhinosinusitis without nasal polyps.
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Papagiannopoulos P, Devins K, Tong CCL, Yver C, Patel NN, Kuhar HN, Bosso JV, Kohanski MA, Tajudeen BA, Kuan EC, Batra PS, Cohen NA, Kennedy DW, Palmer JN, Montone K, and Adappa ND
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- Chronic Disease, Endoscopy, Female, Humans, Inflammation, Male, Middle Aged, Nasal Polyps pathology, Nasal Polyps surgery, Paranasal Sinuses pathology, Phenotype, Rhinitis pathology, Rhinitis surgery, Sinusitis pathology, Sinusitis surgery, Immunosuppressive Agents adverse effects, Rhinitis chemically induced, Sinusitis chemically induced, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Abstract
Background: Chronic rhinosinusitis (CRS) is a frequently observed condition in patients with immunodeficiency secondary to tumor necrosis factor alpha inhibitors (TNFαis). The histologic features of CRS caused by TNFαis have yet to be determined and may have important implications in understanding the pathophysiology of the disease process., Methods: A structured histopathology report was used to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). These structured histopathology variables were compared among patients with CRS on TNFαi (CRSαi), CRS without nasal polyps (CRSsNP) patients, and CRS with nasal polyps (CRSwNP) patients., Results: Eighteen CRSαi, 91 CRSwNP, and 113 CRSsNP patients undergoing FESS were analyzed. Compared to CRSsNP, CRSαi patients exhibited increased mucosal ulceration (16.7% vs 0.9%, p < 0.008), increased fibrosis (100% vs 34.5%, p < 0.001), and increased presence of Charcot-Leiden crystals (16.7% vs 0%, p < 0.002). Compared to CRSwNP, CRSαi patients demonstrated increased fibrosis (100% vs 54.9%, p < 0.001), decreased presence of subepithelial edema (44.4% vs 69.2% p < 0.043), decreased eosinophil aggregates (22.2% vs 47.3% p < 0.042), and fewer eosinophils per high-power field (44.4% vs 73.6%, p < 0.017)., Conclusion: CRSαi exhibits structured histopathology more similar to CRSsNP. In the appropriate clinical context, it may be reasonable that the medical regimen for these patients be focused on a more antineutrophilic, macrolide-based approach. This study provides insight into the inflammatory environment of patients with CRSαi and may have implications for disease management., (© 2019 ARS-AAOA, LLC.)
- Published
- 2020
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17. Impact of age on outcomes following endoscopic sinus surgery for chronic rhinosinusitis.
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Crosby DL, Jones J, Palmer JN, Cohen NA, Kohanski MA, and Adappa ND
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- Adult, Age Factors, Aged, Chronic Disease, Female, Humans, Male, Middle Aged, Paranasal Sinuses surgery, Sino-Nasal Outcome Test, Treatment Outcome, Endoscopy, Nasal Surgical Procedures, Rhinitis surgery, Sinusitis surgery
- Abstract
Background: Chronic rhinosinusitis (CRS) is a common condition that affects people of all ages and negatively impacts quality of life. The goal of this study was to identify differences in outcomes by age following endoscopic sinus surgery (ESS) for CRS utilizing 22-item Sino-Nasal Outcome Test (SNOT-22) scores., Methods: Data from 1252 adult CRS patients electing to undergo ESS (2007-2018) were collected retrospectively. The median age of 50 years was used to divide the data into 2 groups for comparison of the impact of age on SNOT-22 scores at 0, 3, and 6 months after surgery. Changes in SNOT-22 scores were analyzed using a mixed models analysis., Results: After adjusting for gender, race, polyp status, and number of prior ESSs, patients younger than 50 years had a higher mean pre-ESS SNOT-22 score (44.0) compared to those of at least 50 years of age (38.9). Among patients younger than 50 years, SNOT-22 scores declined by 20.7 points at 3 months post-ESS and 16.1 points at 6 months post-ESS. The rate of change between the dichotomized age groups was not significantly different at 3 and 6 months post-ESS (p = 0.7952 and p = 0.1057, respectively)., Conclusion: Both age groups showed significant and durable improvement in SNOT-22 scores after ESS. Patients younger than 50 years of age have higher pre-ESS SNOT-22 scores, but converge to the same SNOT-22 scores by 3 months post-ESS. The rate of change of SNOT-22 scores is not different between those younger than 50 years and those of at least 50 years., (© 2019 ARS-AAOA, LLC.)
- Published
- 2019
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18. Fungal extracts stimulate solitary chemosensory cell expansion in noninvasive fungal rhinosinusitis.
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Patel NN, Triantafillou V, Maina IW, Workman AD, Tong CCL, Kuan EC, Papagiannopoulos P, Bosso JV, Adappa ND, Palmer JN, Kohanski MA, Herbert DR, and Cohen NA
- Subjects
- Alternaria immunology, Aspergillus fumigatus immunology, Fungi immunology, Humans, Interleukin-17 immunology, Nasal Mucosa immunology, Allergens immunology, Antigens, Fungal immunology, Chemoreceptor Cells immunology, Mycetoma immunology, Nasal Mucosa cytology, Rhinitis immunology, Sinusitis immunology
- Abstract
Background: Solitary chemosensory cells (SCCs) are rare epithelial cells enriched in nasal polyps and are the primary source of interleukin-25 (IL-25), an innate cytokine eliciting T-helper 2 (Th2) immune response. Although it is proposed that SCCs are stimulated by antigens released by upper airway pathogens, the exogenous triggers of human SCCs remain elusive. We studied patients with noninvasive fungal rhinosinusitis to determine whether extracts of Aspergillus fumigatus and Alternaria alternata stimulate SCC proliferation as an early event in type 2 inflammation., Methods: Multicolor flow cytometry, immunofluorescence, and enzyme-linked immunoassay were used to interrogate mucosa from patients with mycetomas and allergic fungal rhinosinusitis (AFRS) for SCCs and IL-25. Primary sinonasal epithelial cells from AFRS patients and noninflamed inferior turbinates were stimulated with fungal extracts for 72 hours, and SCC population frequency as well as mitotic activity were quantified using flow cytometry., Results: SCCs producing IL-25 are enriched in inflamed mucosa compared with intrapatient noninflamed control tissue (38.6% vs 6.5%, p = 0.029). In cultured sinonasal epithelial cells from AFRS nasal polyps, Aspergillus fumigatus and Alternaria alternata stimulated higher SCC frequency compared with controls (27.4% vs 10.6%, p = 0.002; 18.1% vs 10.6%, p = 0.046), which led to increased IL-25 secretion in culture media (75.5 vs 3.3 pg/mL, p < 0.001; 32.3 vs 3.3 pg/mL, p = 0.007). Ki-67 expression was higher in SCCs grown in fungal stimulation conditions compared with controls., Conclusion: Although fungal antigens are known to potentiate immune response through innate cytokines, including IL-25, the early expansion of SCCs in the presence of fungus has not been described. This early event in the pathogenesis of noninvasive fungal rhinosinusitis may represent a target for intervention., (© 2019 ARS-AAOA, LLC.)
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- 2019
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19. Asymptomatic radiographic sinonasal inflammation does not affect pituitary surgery outcomes.
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Kuan EC, Rereddy SK, Patel NN, Maina IW, Triantafillou V, Kohanski MA, Tong CCL, Nabavizadeh SA, Lee JYK, Grady MS, O'Malley BW Jr, Palmer JN, and Adappa ND
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- Adult, Aged, Asymptomatic Diseases, Chronic Disease, Endoscopy methods, Female, Humans, Inflammation, Logistic Models, Male, Middle Aged, Multivariate Analysis, Nose, Paranasal Sinuses diagnostic imaging, Paranasal Sinuses pathology, Pituitary Diseases complications, Pituitary Diseases pathology, Pituitary Gland surgery, Postoperative Complications epidemiology, Preoperative Period, Retrospective Studies, Rhinitis diagnostic imaging, Rhinitis pathology, Sinusitis diagnostic imaging, Sinusitis pathology, Tomography, X-Ray Computed, Treatment Outcome, Endoscopy adverse effects, Pituitary Diseases surgery, Postoperative Complications etiology, Rhinitis complications, Sinusitis complications
- Abstract
Objective: Chronic rhinosinusitis (CRS) is a proposed risk factor for meningitis and other intracranial complications following the endoscopic endonasal transsphenoidal approach (TSA). Some have recommended staging TSA following surgery for CRS; however, delaying TSA has important ramifications. The objective of this study is to determine whether asymptomatic sinonasal inflammation (RSNI) on preoperative computed tomography scans, without clinical CRS, is associated with postoperative complications following TSA., Methods: All consecutive TSA cases performed at a single tertiary care institution from January 1, 2009, to December 31, 2017, were reviewed for patient demographics, prior surgery, presence of RSNI on preoperative computed tomography scan based on Lund-Mackay (LM) score, intraoperative cerebrospinal fluid (CSF) leak, and postoperative complications (postoperative CSF leak, bleeding, infection). The association between preoperative RSNI and postoperative complications was analyzed via multivariate logistic regression., Results: One hundred seventy-one cases of TSA were included with mean patient age of 52.6 years, 42.7% males, 18.1% revision cases, and mean LM score of 1.9 ± 2.7. Complications were identified in 9.9% of patients at the following rates: 5.3% postoperative CSF leak, 2.9% bleeding, and 1.8% infection (all sinusitis, no episodes of meningitis). Neither total LM score nor LM score > 5 (representative of clinically significant radiographic CRS) were predictors of any postoperative complication (both P > 0.05). Age, sex, revision status, intraoperative CSF leak, and total LM score were not independent predictors of any postoperative complication on multivariate analysis (all P > 0.05)., Conclusion: In asymptomatic patients, radiographic evidence of sinonasal inflammation is not associated with increased risk of complications following TSA., Level of Evidence: 4 Laryngoscope, 129:1545-1548, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)
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- 2019
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20. Efficacy of fluticasone exhalation delivery system in the management of chronic rhinosinusitis: what is the evidence?
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Kuan EC, Kovacs AJ, Workman AD, Bosso JV, and Adappa ND
- Subjects
- Administration, Intranasal adverse effects, Chronic Disease, Exhalation, Humans, Nasal Polyps drug therapy, Nasal Polyps pathology, Rhinitis pathology, Sinusitis pathology, Treatment Outcome, Drug Delivery Systems adverse effects, Fluticasone administration & dosage, Rhinitis drug therapy, Sinusitis drug therapy
- Abstract
Background: Intranasal steroids have become part of the mainstay in the long-term management of chronic rhinosinusitis. A long-standing problem remains in efficient and easy-to-use delivery of topical corticosteroids to the nasal mucosa. Currently available means of intranasal steroid delivery include sprays, which are generally limited to treating the anterior nasal cavity, and rinses, which are not FDA-approved for this indication. The exhalation delivery system is a novel method of delivering fluticasone to the deeper areas within the nasal cavities, including the posterior nasal cavity and middle and superior meatuses., Methods: Comprehensive literature review., Results: Recent large scale studies have suggested its efficacy and safety in the use of patients with both chronic sinusitis with polyposis and without polyps. Specifically, studies have demonstrated decreased Sinonasal Outcome Test scores of 20 points following treatment, as well as improvement of polyp grade by 1 or more point in more than 60% of patients. Furthermore, among patients with nasal polyps, there was approximately 60-70% decreased indication for surgery following EDS-FLU use., Conclusion: EDS-FLU is an important adjunct therapy for sinonasal inflammatory disease., (© 2019 ARS-AAOA, LLC.)
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- 2019
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21. Accuracy of Self-reported Diagnosis of Chronic Rhinosinusitis.
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Workman AD, Parasher AK, Blasetti MT, Palmer JN, Adappa ND, and Glicksman JT
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- Adult, Aged, Chronic Disease, Female, Humans, Logistic Models, Male, Middle Aged, Prospective Studies, Sensitivity and Specificity, Rhinitis diagnosis, Self Report, Sinusitis diagnosis
- Abstract
Large cohort studies of chronic rhinosinusitis (CRS) prevalence often include patients who have been inappropriately diagnosed with the disease. In this investigation, new patients presenting to a tertiary rhinology practice completed a screening questionnaire that included questions about self-reported CRS status, demographic information, and symptomatology. Treating rhinologists evaluated patients according to clinical practice guideline criteria for CRS; 91 patients were ultimately diagnosed with CRS. The sensitivity of self-report for CRS was 84%; the specificity was 82%; and the estimated negative predictive value ranged from 97% to 99%. Prior sinus surgery or oral steroid use correlated with CRS self-report, and a concurrent self-report of nasal polyps or nasal steroid use improved the positive predictive value of CRS self-report. Self-report of CRS status may represent an effective and relatively inexpensive screening mechanism for CRS in large cohort studies, particularly when combined with other associated diagnostic features that improve performance parameters of self-report.
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- 2019
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22. Dexpramipexole depletes blood and tissue eosinophils in nasal polyps with no change in polyp size.
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Laidlaw TM, Prussin C, Panettieri RA, Lee S, Ferguson BJ, Adappa ND, Lane AP, Palumbo ML, Sullivan M, Archibald D, Dworetzky SI, Hebrank GT, and Bozik ME
- Subjects
- Adult, Chronic Disease, Female, Humans, Male, Prospective Studies, Treatment Outcome, Antioxidants therapeutic use, Eosinophilia drug therapy, Eosinophils drug effects, Nasal Polyps drug therapy, Pramipexole therapeutic use, Rhinitis drug therapy, Sinusitis drug therapy
- Abstract
Objective: Chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilia is a disease of the upper respiratory tract for which few therapies are available. Because the oral investigational drug dexpramipexole serendipitously decreased blood eosinophils in amyotrophic lateral sclerosis studies, we assessed its safety, eosinophil-lowering activity, and preliminary clinical efficacy in patients with CRSwNP and eosinophilia., Methods: Sixteen subjects with CRSwNP, absolute eosinophil count (AEC) ≥ 0.300 × 10
9 /L, and polyp tissue eosinophils were evaluable for efficacy in a 6-month open-label, multi-center study of dexpramipexole 150 mg twice daily. The coprimary endpoints were change in AEC and change in total polyp score (TPS) from baseline to month 6, with additional clinical and histologic endpoints assessed., Results: Thirteen of 16 subjects completed 6 months of dexpramipexole treatment. Geometric mean baseline AEC was 0.525 ± 0.465 eosinophils × 109 /L and decreased to 0.031 ± 0.019 after 6 months of dexpramipexole treatment, a 94% reduction (P < 0.001). Ten of 16 subjects had eosinophil counts reduced to ≤ 0.020 × 109 /L at month 6. In 12 subjects with nasal polyp biopsies at baseline and month 6, tissue eosinophils were reduced from a mean of 168 ± 134 to 5 ± 2 per high-power field (HPF) (P = 0.001), a 97% reduction from baseline. There was no significant reduction in TPS or improvement in other clinical endpoints. Dexpramipexole was well tolerated, with no drug-related serious adverse events., Conclusion: Dexpramipexole treatment produced profound eosinophil-lowering in peripheral blood and nasal polyp tissue. Despite the near-elimination of polyp eosinophils, decreased TPS and nasal symptom improvement were not observed., Level of Evidence: 2 Laryngoscope, 129:E61-E66, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)- Published
- 2019
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23. Solitary chemosensory cells are a primary epithelial source of IL-25 in patients with chronic rhinosinusitis with nasal polyps.
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Kohanski MA, Workman AD, Patel NN, Hung LY, Shtraks JP, Chen B, Blasetti M, Doghramji L, Kennedy DW, Adappa ND, Palmer JN, Herbert DR, and Cohen NA
- Subjects
- Animals, Cells, Cultured, Chronic Disease, Doublecortin-Like Kinases, Flow Cytometry, Humans, Interleukin-13 metabolism, Intracellular Signaling Peptides and Proteins metabolism, Mice, Protein Serine-Threonine Kinases metabolism, Taste physiology, Transducin metabolism, Chemoreceptor Cells physiology, Interleukin-17 metabolism, Nasal Polyps immunology, Paranasal Sinuses pathology, Respiratory Mucosa physiology, Rhinitis immunology, Sinusitis immunology
- Abstract
Background: IL-25 can function as an early signal for the respiratory type 2 response characteristic of allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In the mouse gut, tuft cells are the epithelial source of IL-25. However, the source of human airway epithelial IL-25 has remained elusive., Objective: In this study we sought to determine whether the solitary chemosensory cell (SCC) is the predominant source of IL-25 in the sinonasal epithelium., Method: Flow cytometry and immunofluorescence for SCCs and IL-25 were used to interrogate polyp and turbinate tissue from patients with CRSwNP. Mucus was collected during acute inflammatory exacerbations from patients with CRSwNP or chronic rhinosinusitis without nasal polyps and IL-25 levels determined by using ELISA. Lastly, sinonasal epithelial cultures derived from polyp and turbinate tissue were stimulated with IL-13 and analyzed for SCC proliferation and IL-25 production., Results: This study demonstrates that a discrete cell type, likely an SCC, characterized by expression of the taste-associated G protein gustducin and the intestinal tuft cell marker doublecortin-like kinase 1, is the predominant source of IL-25 in the human upper airway. Additionally, we show that patients with CRSwNP have increased numbers of SCCs in nasal polyp tissue and that in vitro IL-13 exposure both increased proliferation and induced apical secretion of IL-25 into the mucosal layer., Conclusions: Inflammatory sinus polyps but not adjacent turbinate tissue show expansion of the SCC population, which is the source of epithelial IL-25., (Published by Elsevier Inc.)
- Published
- 2018
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24. Preoperative Lund-Mackay computed tomography score is associated with preoperative symptom severity and predicts quality-of-life outcome trajectories after sinus surgery.
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Brooks SG, Trope M, Blasetti M, Doghramji L, Parasher A, Glicksman JT, Kennedy DW, Thaler ER, Cohen NA, Palmer JN, and Adappa ND
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- Chronic Disease, Female, Humans, Male, Middle Aged, Preoperative Care methods, Prospective Studies, Quality of Life, Rhinitis diagnostic imaging, Severity of Illness Index, Sinusitis diagnostic imaging, Tomography, X-Ray Computed methods, Treatment Outcome, Rhinitis surgery, Sinusitis surgery
- Abstract
Background: Disagreement exists about the relationship between Lund-Mackay CT scores (LMCTS) and quality-of-life outcome (QoL) measures. We investigated whether preoperative LMCTS are associated with preoperative QoL, and whether LMCTS is predictive of postoperative QoL outcomes in chronic rhinosinusitis (CRS) patients., Methods: Adult patients with medically recalcitrant CRS (n = 665) were enrolled in a prospective, observational cohort study. Preoperative LMCTS and pre- and postoperative self-reported QoL outcomes (22-item Sino-Nasal Outcomes Test [SNOT-22]) were collected and evaluated over 12 months. Five hundred sixty-eight patients met the inclusion criteria. Longitudinal linear mixed-effects modeling was used to investigate the effect of LMCTS on QoL after functional endoscopic sinus surgery (FESS)., Results: Preoperative LMCTS were significantly associated with preoperative SNOT-22 scores (p < 0.01) and postoperative SNOT-22 scores (p < 0.001), driven by Extranasal and Rhinologic subdomains of the QoL questionaire. Patients in the lowest preoperative LMCTS quartile had the lowest mean change in SNOT-22 scores at 12 months (16.8 points; 95% confidence interval [CI], 12.2-21.3). Patients in the second and third lowest preoperative LMCTS quartiles had mean changes at 12 months of 21.1 points (95% CI, 16.7-25.4) and 23.1 points (95% CI, 18.3-27.9). Patients in the highest preoperative LMCTS quartile had the greatest improvement in SNOT-22 scores after FESS (29.9 points; 95% CI, 24.9-34.8). The difference in QoL change at 12 months between the highest and lowest preoperative LMCTS quartiles was 13.1 points (95% CI, 6.0-20.2; p < 0.001)., Conclusion: Our study demonstrates that preoperative LMCTS correlate with preoperative extranasal and rhinologic symptom severity and that the LMCTS is an indicator of postsurgical QoL outcomes for medically recalcitrant chronic rhinosinusitis patients in a large tertiary otolaryngology setting., (© 2018 ARS-AAOA, LLC.)
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- 2018
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25. Bitter and sweet taste tests are reflective of disease status in chronic rhinosinusitis.
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Workman AD, Brooks SG, Kohanski MA, Blasetti MT, Cowart BJ, Mansfield C, Kennedy DW, Palmer JN, Adappa ND, Reed DR, and Cohen NA
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- Adult, Chronic Disease, Cohort Studies, Disease Progression, Female, Humans, Male, Middle Aged, Nasal Polyps complications, Phenotype, Quaternary Ammonium Compounds administration & dosage, Rhinitis complications, Sinusitis complications, Sucrose administration & dosage, Nasal Polyps diagnosis, Respiratory Mucosa metabolism, Rhinitis diagnosis, Sinusitis diagnosis, Taste immunology
- Published
- 2018
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26. The Role of Quinine-Responsive Taste Receptor Family 2 in Airway Immune Defense and Chronic Rhinosinusitis.
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Workman AD, Maina IW, Brooks SG, Kohanski MA, Cowart BJ, Mansfield C, Kennedy DW, Palmer JN, Adappa ND, Reed DR, Lee RJ, and Cohen NA
- Subjects
- Biomarkers, Chronic Disease, Cilia metabolism, Humans, Immunity, Innate, Immunomodulation, Nitric Oxide metabolism, Prospective Studies, Receptors, G-Protein-Coupled metabolism, Taste, Cilia drug effects, Paranasal Sinuses metabolism, Quinine immunology, Receptors, G-Protein-Coupled agonists, Respiratory System immunology, Rhinitis immunology, Sinusitis immunology
- Abstract
Background: Bitter (T2R) and sweet (T1R) taste receptors in the airway are important in innate immune defense, and variations in taste receptor functionality in one T2R (T2R38) correlate with disease status and disease severity in chronic rhinosinusitis (CRS). Quinine is a bitter compound that is an agonist for several T2Rs also expressed on sinonasal cells, but not for T2R38. Because of this property, quinine may stimulate innate immune defense mechanisms in the airway, and functional differences in quinine perception may be reflective of disease status in CRS., Methods: Demographic and taste intensity data were collected prospectively from CRS patients and non-CRS control subjects. Sinonasal tissue from patients undergoing rhinologic surgery was also collected and grown at an air-liquid interface (ALI). Nitric oxide (NO) production and dynamic regulation of ciliary beat frequency in response to quinine stimulation were assessed in vitro ., Results: Quinine reliably increased ciliary beat frequency and NO production in ALI cultures in a manner consistent with T2R activation ( p < 0.01). Quinine taste intensity rating was performed in 328 CRS patients and 287 control subjects demonstrating that CRS with nasal polyps (CRSwNP) patients rated quinine as significantly less intense than did control subjects., Conclusion: Quinine stimulates airway innate immune defenses by increasing ciliary beat frequency and stimulating NO production in a manner fitting with T2R activation. Patient variability in quinine sensitivity is observed in taste intensity ratings, and gustatory quinine "insensitivity" is associated with CRSwNP status. Thus, taste tests for quinine may be a biomarker for CRSwNP, and topical quinine has therapeutic potential as a stimulant of innate defenses.
- Published
- 2018
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27. Sinonasal T2R-mediated nitric oxide production in response to Bacillus cereus .
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Carey RM, Workman AD, Yan CH, Chen B, Adappa ND, Palmer JN, Kennedy DW, Lee RJ, and Cohen NA
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- Bodily Secretions, Cells, Cultured, Chronic Disease, Cilia physiology, Humans, Immunity, Innate, Mucociliary Clearance, Nasal Mucosa microbiology, Phospholipase C beta metabolism, Signal Transduction, TRPM Cation Channels metabolism, Taste, Bacillus cereus immunology, Gram-Positive Bacterial Infections immunology, Nasal Mucosa physiology, Nitric Oxide metabolism, Receptors, G-Protein-Coupled metabolism, Rhinitis immunology, Sinusitis immunology
- Abstract
Background: Upper airway epithelial cells produce bactericidal nitric oxide (NO) in response to both gram-positive and gram-negative bacteria. Our previous work demonstrated that T2R38, a bitter taste receptor (T2R) expressed in airway epithelium, produces NO in response to quorum-sensing molecules secreted by Pseudomonas aeruginosa. We also demonstrated that Staphylococci products elicit an NO response when using a T2R-independent pathway. When screening additional human pathogens for epithelial T2R activation, we found that the gram-positive aerobe Bacillus cereus secretes a T2R agonist that yields NO production., Objective: The objective of this study was to characterize the activating B. cereus product(s) and to describe the epithelial cell signaling pathway involved., Methods: Sinonasal air-liquid interface cultures were treated with B. cereus conditioned medium (CM), and NO production was measured by using 4-amino-5-methylamino-2',7'-difluorofluorescein fluorescence imaging. Ciliary beat frequency (CBF) was assessed in response to B. cereus CM. Pharmacologic studies that use inhibitors of the T2R-signaling pathway were used to determine if the production of NO was mediated by a T2R. Purification studies were performed to analyze the physical properties of the activating product(s) contained in the CM., Results: A product(s) secreted by B. cereus induced NO production and increased CBF. The response varied markedly between individual patients and involved two important components of bitter taste signaling, phospholipase C isoform β-2 and the transient receptor potential melastatin isoform 5 ion channel., Conclusions: This study demonstrated that a B. cereus product(s) elicited an NO-mediated innate defense response in upper airway epithelium that seemed to be partially mediated by a T2R signaling pathway. The active product that elicited the NO response was likely a small nonpeptide compound, but further purification is required for identification. Patient variation in the NO response to B. cereus products could potentially be due to genetic differences in T2Rs.
- Published
- 2017
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28. Denatonium-induced sinonasal bacterial killing may play a role in chronic rhinosinusitis outcomes.
- Author
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Carey RM, Workman AD, Hatten KM, Siebert AP, Brooks SG, Chen B, Adappa ND, Palmer JN, Kennedy DW, Lee RJ, and Cohen NA
- Subjects
- Antimicrobial Cationic Peptides metabolism, Bacteriolysis, Calcium Signaling, Cell Growth Processes, Cells, Cultured, Chronic Disease, Cilia pathology, Disease Progression, Endoscopy, Female, Humans, Immunity, Innate, Male, Nasal Polyps microbiology, Rhinitis microbiology, Sinusitis microbiology, Treatment Outcome, Cilia metabolism, Nasal Polyps immunology, Pseudomonas Infections immunology, Pseudomonas aeruginosa physiology, Quaternary Ammonium Compounds metabolism, Rhinitis immunology, Sinusitis immunology
- Abstract
Background: Sinonasal bitter taste receptors (T2Rs) contribute to upper airway innate immunity and correlate with chronic rhinosinusitis (CRS) clinical outcomes. A subset of T2Rs expressed on sinonasal solitary chemosensory cells (SCCs) are activated by denatonium, resulting in a calcium-mediated secretion of bactericidal antimicrobial peptides (AMPs) in neighboring ciliated epithelial cells. We hypothesized that there is patient variability in the amount of bacterial killing induced by different concentrations of denatonium and that the differences correlate with CRS clinical outcomes., Methods: Bacterial growth inhibition was quantified after mixing bacteria with airway surface liquid (ASL) collected from denatonium-stimulated sinonasal air-liquid interface (ALI) cultures. Patient ASL bacterial killing at 0.1 mM denatonium and baseline characteristics and sinus surgery outcomes were compared between these populations., Results: There is variability in the degree of denatonium-induced bacterial killing between patients. In CRS with nasal polyps (CRSwNP), patients with increased bacterial killing after stimulation with low levels of denatonium undergo significantly more functional endoscopic sinus surgeries (FESSs) (p = 0.037) and have worse 6-month post-FESS 22-item Sino-Nasal Outcome Test (SNOT-22) scores (p = 0.012)., Conclusion: Bacterial killing after stimulation with low levels of denatonium correlates with number of prior FESS and postoperative SNOT-22 scores in CRSwNP. Some symptoms of CRS in patients with hyperresponsiveness to low levels of denatonium may be due to increased airway immune activity or inherent disease severity., (© 2017 ARS-AAOA, LLC.)
- Published
- 2017
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29. Association between the CDHR3 rs6967330 risk allele and chronic rhinosinusitis.
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Chang EH, Willis AL, McCrary HC, Noutsios GT, Le CH, Chiu AG, Mansfield CJ, Reed DR, Brooks SG, Adappa ND, Palmer JN, Cohen NG, Stern DA, Guerra S, and Martinez FD
- Subjects
- Age Factors, Cadherin Related Proteins, Chronic Disease, Female, Genetic Association Studies, Humans, Male, Multicenter Studies as Topic, Odds Ratio, Polymorphism, Single Nucleotide, Retrospective Studies, Sex Factors, Alleles, Cadherins genetics, Genetic Predisposition to Disease, Membrane Proteins genetics, Rhinitis genetics, Sinusitis genetics
- Published
- 2017
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30. Nitric oxide production is stimulated by bitter taste receptors ubiquitously expressed in the sinonasal cavity.
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Yan CH, Hahn S, McMahon D, Bonislawski D, Kennedy DW, Adappa ND, Palmer JN, Jiang P, Lee RJ, and Cohen NA
- Subjects
- Bacteriolysis, Cells, Cultured, Chronic Disease, Humans, Immunity, Innate, Mucociliary Clearance, Nasal Mucosa microbiology, Nitric Oxide metabolism, Primary Cell Culture, Bacterial Infections immunology, Nasal Mucosa immunology, Paranasal Sinuses metabolism, Receptors, G-Protein-Coupled metabolism, Rhinitis immunology, Sinusitis immunology, Taste
- Abstract
Background: Bitter taste receptors (T2R) have recently been demonstrated to contribute to sinonasal innate immunity. One T2R, T2R38, regulates mucosal defense against gram-negative organisms through nitric oxide (NO) production, which enhances mucociliary clearance and directly kills bacteria. To determine whether additional T2Rs contribute to this innate defense, we evaluated two other sinonasal T2Rs (T2R4 and T2R16) for regulation of NO production and expression within the human sinonasal cavity., Methods: Primary human sinonasal cultures were stimulated with ligands specific to T2R4 and T2R16, colchicine and D-salicin, respectively. Cellular NO production was measured by intracellular 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate fluorescence. For T2R expression mapping, sinonasal tissue was obtained from patients who underwent sinus surgery of the middle turbinate, maxillary sinus, ethmoid sinus, or sphenoid sinus. The expression of T2R4, T2R16, and T2R38 was evaluated by using immunofluorescence with validated antibodies., Results: Similar to T2R38, T2R4 and T2R16 trigger NO production in a dose-dependent manner by using the canonical taste signaling pathway in response to stimulation with their respective ligands. All three receptors were expressed in the cilia of human epithelial cells of all regions in the sinonasal cavity., Conclusion: These three T2Rs signaled through the same NO-mediated antimicrobial pathway and were ubiquitously expressed in the sinonasal epithelium. Additional T2Rs besides T2R38 may play a role in sinonasal immune defense. Mapping of T2R expression demonstrated the potential widespread role of T2Rs in sinonasal defense, whereas the genetics of these T2Rs may contribute to our understanding of specific endotypes of chronic rhinosinusitis and develop into novel therapeutic targets.
- Published
- 2017
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31. Correlation of T2R38 taste phenotype and in vitro biofilm formation from nonpolypoid chronic rhinosinusitis patients.
- Author
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Adappa ND, Truesdale CM, Workman AD, Doghramji L, Mansfield C, Kennedy DW, Palmer JN, Cowart BJ, and Cohen NA
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Chronic Disease, Female, Genotype, Humans, Male, Middle Aged, Phenylthiourea, Receptors, G-Protein-Coupled genetics, Young Adult, Biofilms, Pseudomonas physiology, Receptors, G-Protein-Coupled physiology, Rhinitis physiopathology, Sinusitis physiopathology, Taste
- Abstract
Background: Sinonasal biofilms have been demonstrated in specimens collected from chronic rhinosinusitis (CRS) patients. Mounting evidence suggests that biofilms contribute to therapeutically recalcitrant CRS. Recently, the bitter taste receptor T2R38 has been implicated in the regulation of the sinonasal mucosal innate immune response. TAS2R38 gene polymorphisms affect receptor functionality and contribute to variations seen in sinonasal innate defense as well as taste perception reflected in gustatory sensitivity to the bitter compound phenylthiocarbamide (PTC). In a population of CRS patients with active infection or inflammation, we sought to determine if a correlation between T2R38 phenotype and in vitro biofilm formation existed., Methods: Endoscopically guided sinonasal swabs were obtained prospectively from CRS (±polyp) patients with evidence of persistent inflammation or mucopurulence. In vitro biofilm formation was assessed with a modified Calgary Biofilm Detection Assay. Patients' phenotypic (functional) expression of the bitter taste receptor T2R38 was evaluated with a taste test including the compound PTC. Linear regression was used to determine the level of significance between mean in vitro biofilm formation levels and mean PTC taste test intensity ratings across CRS patients., Results: Sinonasal swabs were obtained from 59 patients, with 42 of the 59 samples demonstrating in vitro biofilm formation. Analysis revealed an inverse linear association between in vitro biofilm formation and PTC taste intensity ratings (p = 0.019) for all patients. This association was exclusively driven by nonpolypoid CRS patients (p = 0.0026)., Conclusion: In vitro biofilm formation from sinonasal clinical isolates is inversely correlated with PTC taste sensitivity in nonpolypoid CRS patients., (© 2016 ARS-AAOA, LLC.)
- Published
- 2016
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32. T2R38 genotype is correlated with sinonasal quality of life in homozygous ΔF508 cystic fibrosis patients.
- Author
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Adappa ND, Workman AD, Hadjiliadis D, Dorgan DJ, Frame D, Brooks S, Doghramji L, Palmer JN, Mansfield C, Reed DR, and Cohen NA
- Subjects
- Adolescent, Adult, Chronic Disease, Female, Genotype, Humans, Male, Quality of Life, Severity of Illness Index, Young Adult, Cystic Fibrosis genetics, Receptors, G-Protein-Coupled genetics, Rhinitis genetics, Sinusitis genetics
- Abstract
Background: Chronic rhinosinusitis (CRS) is very prevalent in the cystic fibrosis (CF) patient population, and leads to high morbidity and markedly decreased quality of life (QOL). Identification of genetic markers that contribute to CRS symptoms in these patients can allow for risk stratification and tailoring of medical and surgical treatments. T2R38 is a bitter taste receptor expressed in the sinonasal tract, and nonfunctional alleles of this receptor have been implicated in treatment-refractory CRS in non-CF patients. The purpose of this study is to investigate the significance of T2R38 genotype in the variability of sinonasal QOL and CRS disease severity in a sample of CF patients., Methods: ΔF508 homozygous CF patients were recruited from the University of Pennsylvania Cystic Fibrosis Center and were genotyped for the TAS2R38 locus. To assess sinonasal symptom severity, a 22-item Sino-Nasal Outcome Test (SNOT-22) was collected from each patient. Additional demographic and medical history data was obtained at the time of patient enrollment., Results: A total of 49 ΔF508 homozygous CF patients aged 18 to 32 years were included in the final SNOT-22 score analysis. Individuals with 2 functional T2R38 alleles (PAV/PAV) had significantly lower SNOT-22 scores (n = 49, p < 0.05). On further breakdown of SNOT-22 subcategories, rhinologic symptoms specifically were less severe in PAV/PAV patients than patients with other genotypes (n = 47, p < 0.05)., Conclusion: Our investigation indicates that T2R38 genotype correlates both with SNOT-22 scores and rhinologic-specific QOL in ΔF508 homozygous CF patients., (© 2015 ARS-AAOA, LLC.)
- Published
- 2016
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33. TAS2R38 genotype predicts surgical outcome in nonpolypoid chronic rhinosinusitis.
- Author
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Adappa ND, Farquhar D, Palmer JN, Kennedy DW, Doghramji L, Morris SA, Owens D, Mansfield C, Lysenko A, Lee RJ, Cowart BJ, Reed DR, and Cohen NA
- Subjects
- Adult, Aged, Female, Follow-Up Studies, Genetic Markers, Genotype, Humans, Male, Middle Aged, Phenotype, Prospective Studies, Quality of Life, Rhinitis genetics, Sinusitis genetics, Treatment Outcome, Polymorphism, Genetic, Receptors, G-Protein-Coupled genetics, Rhinitis surgery, Sinusitis surgery
- Abstract
Background: Over 550,000 sinus surgeries are performed annually in the United States on patients with chronic rhinosinusitis (CRS). Although the results of sinus surgery vary widely, no known genetic factor has been identified to predict surgical outcomes. The bitter taste receptor T2R38 has recently been demonstrated to regulate upper airway innate defense and may affect patient responses to therapy. Our goal was to determine whether TAS2R38 genetics predicts outcomes in CRS patients following sinus surgery., Methods: A prospective study of patients undergoing sinus surgery evaluating postoperative outcomes through the 22-item Sino-Nasal Outcome Test (SNOT-22). Patients were genotyped for TAS2R38., Results: A total of 123 patients with CRS were initially analyzed; 82 patients showed nasal polyps (CRSwNP) and 41 patients were without nasal polyps (CRSsNP). Six months after surgery, the overall SNOT-22 improvement was 25 ± 23 points. The TAS2R38 genotype was found to significantly correlate with surgical outcomes in patients without polyps; homozygotes for the functional receptor had a mean improvement of 38 ± 21, whereas heterozygotes or homozygotes for the nonfunctional receptor had a mean improvement of 12 ± 22 (p = 0.006). This result was confirmed with a multivariate regression that incorporated further patients with 1-month and 3-month scores (n = 207)., Conclusion: In patients undergoing sinus surgery for CRS, we have identified a genetic polymorphism that predicts variability in quality of life improvement following surgery at 6 months in nonpolypoid CRS. This is the first genetic polymorphism identified that has demonstrated to predict surgical outcome for a select group of CRS patients., (© 2015 ARS-AAOA, LLC.)
- Published
- 2016
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34. Different clinical factors associated with Staphylococcus aureus and Pseudomonas aeruginosa in chronic rhinosinusitis.
- Author
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Zhang Z, Adappa ND, Doghramji LJ, Chiu AG, Cohen NA, and Palmer JN
- Subjects
- Chronic Disease, Endoscopy methods, Female, Humans, Male, Middle Aged, Nasal Polyps microbiology, Prospective Studies, Pseudomonas Infections, Pseudomonas aeruginosa isolation & purification, Rhinitis microbiology, Sinusitis microbiology, Staphylococcal Infections, Staphylococcus aureus isolation & purification
- Abstract
Background: Staphylococcus aureus and Pseudomonas aeruginosa are common culture isolates in chronic rhinosinusitis (CRS). We aimed to determine whether they were associated with different clinical factors of CRS., Methods: Adult CRS patients who underwent functional endoscopic sinus surgery (FESS) between October 1, 2007 and December 31, 2011 were recruited. Patient demographics, Lund-Mackay computed tomography (CT) scores, 22-item Sino-Nasal Outcome Test (SNOT-22) scores, disease characteristics, and medication use were collected prior to FESS. Intraoperative culture was obtained in a standard manner. We compared patients with isolates of S. aureus or P. aeruginosa to patients with other culture results and no bacterial growth, respectively. Multivariate logistic regression was performed., Results: A total of 376 patients met criteria; 104 patients (28%) had S. aureus, 32 (9%) had P. aeruginosa, and 10 patients (3%) had no bacterial growth. After adjusting for all clinical factors, compared to patients with positive culture other than S. aureus, patients with S. aureus had 1.9 times increased odds of having nasal polyps (odds ratio [OR] = 1.9; 95% confidence interval [CI], 1.0 to 3.3; p = 0.036); when compared to patients with positive culture other than P. aeruginosa, patients with P. aeruginosa had 7.8 times increased odds of having prior FESS (OR = 7.8; 95% CI, 2.1 to 28.9; p = 0.002) (91% vs 58%; p < 0.001) and 3.6 times increased odds of having diabetes with marginal significance (OR = 3.6; 95% CI, 1.0 to 13.2; p = 0.053). The sample size in the no bacterial growth group was too small to draw firm conclusions., Conclusion: S. aureus was more common in CRS patients with nasal polyps, whereas P. aeruginosa was more common in CRS patients with prior FESS history and possibly diabetes., (© 2015 ARS-AAOA, LLC.)
- Published
- 2015
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35. Biofilm-forming bacteria and quality of life improvement after sinus surgery.
- Author
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Zhang Z, Adappa ND, Chiu AG, Doghramji LJ, Cohen NA, and Palmer JN
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Postoperative Period, Pseudomonas aeruginosa isolation & purification, Pseudomonas aeruginosa physiology, Retrospective Studies, Rhinitis psychology, Rhinitis surgery, Sinusitis psychology, Sinusitis surgery, Staphylococcus aureus isolation & purification, Staphylococcus aureus physiology, Streptococcus pneumoniae isolation & purification, Streptococcus pneumoniae physiology, Bacterial Physiological Phenomena, Biofilms, Nasal Surgical Procedures, Paranasal Sinuses surgery, Quality of Life psychology, Rhinitis microbiology, Sinusitis microbiology
- Abstract
Background: It remains unclear how much chronic rhinosinusitis (CRS) patients with bacterial biofilms can benefit from functional endoscopic sinus surgery (FESS). We aimed to evaluate whether biofilm-forming bacteria was associated with quality of life (QOL) improvement after FESS., Methods: This retrospective cohort study included adult CRS patients who underwent FESS from 2008 to 2011. Sinus samples were taken to evaluate for biofilm-formation in vitro using a modified Calgary Biofilm Detection Assay. QOL was measured before FESS, and 1-month, 3-month, and 6-month after FESS using 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Patients' characteristics and medications were collected. Clinical significant QOL change was defined as a difference of at least 0.5 standard deviation (SD) of baseline SNOT-22 score in the reference group., Results: A total of 156 patients had complete data, and 15% had biofilm-forming bacteria (n = 24). Patients with biofilm-forming bacteria had significantly worse preoperative SNOT-22 scores compared to patients without biofilm-forming bacteria (48 ± 20 vs 38 ± 23, p = 0.048). Both groups had clinically significant QOL improvement after FESS, and the differences in their 1-month (23 ± 19 vs 17 ± 20) and 3-month (27 ± 18 vs 18 ± 19) post-FESS SNOT-22 scores were not significant. However, patients with biofilm-forming bacteria demonstrated significantly less QOL improvement than patients without biofilm-forming bacteria from pre-FESS to 6-month post-FESS visits after adjusting for clinical factors (35 ± 25 vs 14 ± 15; β-coefficient = 0.71; 95% confidence interval [CI], 0.13 to 1.28; p = 0.016)., Conclusion: CRS patients with biofilm-forming bacteria demonstrated clinically significant QOL improvement following FESS, but the degree of improvement was decreased overtime and became significantly worse than patients without biofilm-forming bacteria by 6-month follow-up. This QOL worsening was independent of other risk factors for CRS., (© 2015 ARS-AAOA, LLC.)
- Published
- 2015
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36. Corticosteroid use does not alter nasal mucus glucose in chronic rhinosinusitis.
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Hatten KM, Palmer JN, Lee RJ, Adappa ND, Kennedy DW, and Cohen NA
- Subjects
- Administration, Intranasal, Administration, Oral, Adult, Case-Control Studies, Chronic Disease, Female, Follow-Up Studies, Humans, Male, Middle Aged, Nasal Mucosa metabolism, Prospective Studies, Reference Values, Rhinitis diagnosis, Risk Assessment, Sinusitis diagnosis, Treatment Outcome, Adrenal Cortex Hormones therapeutic use, Glucose metabolism, Nasal Mucosa drug effects, Rhinitis drug therapy, Sinusitis drug therapy
- Abstract
Objectives: To evaluate nasal mucus glucose concentrations in patients with and without chronic rhinosinusitis and determine if corticosteroid therapy alters mucus glucose., Study Design: Prospective observational study., Setting: Single tertiary care center., Subjects: Ninety-five patients presenting to an otolaryngology clinic., Methods: Participants completed questionnaires that included a history of medical and surgical therapies as well as sinusitis-specific quality-of-life measurements. Nasal mucus was collected in an outpatient clinic using an open cell foam technique. The nasal mucus glucose concentrations of patients with and without chronic rhinosinusitis were compared to the use of systemic and topical glucocorticoid treatment., Results: A statistically significant difference was measured between mean nasal glucose secretions of control patients, 10.2 mg/dL, compared with patients diagnosed with chronic rhinosinusitis, 18.4 mg/dL (P < .0001). Use of corticosteroids, both topical and systemic, did not correlate with nasal glucose concentrations., Conclusion: Patients diagnosed with chronic rhinosinusitis have elevated nasal glucose concentrations compared with control patients, and this elevated nasal glucose level was independent of corticosteroid use. Nasal glucose may independently contribute to the pathophysiology of chronic rhinosinusitis., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)
- Published
- 2015
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37. Coagulase-negative Staphylococcus culture in chronic rhinosinusitis.
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Zhang Z, Adappa ND, Lautenbach E, Chiu AG, Doghramji LJ, Cohen NA, and Palmer JN
- Subjects
- Adult, Chronic Disease, Endoscopy methods, Female, Humans, Male, Middle Aged, Regression Analysis, Retrospective Studies, Rhinitis surgery, Sinusitis surgery, Rhinitis microbiology, Sinusitis microbiology, Staphylococcal Infections, Staphylococcus isolation & purification
- Abstract
Background: Coagulase-negative Staphylococcus (CoNS) is commonly isolated from patients with chronic rhinosinusitis (CRS). However, the role of CoNS in CRS remains controversial. We aimed to determine the association between positive CoNS culture at functional endoscopic sinus surgery (FESS) and CRS severity., Methods: Adult CRS patients who underwent FESS between October 1, 2007 to December 31, 2011 were recruited. Patient demographics, disease characteristics, medication use, Lund-Mackay computed tomography (CT) scores, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were collected at baseline before FESS. Intraoperative cultures were obtained in a standard manner. Patients were placed into 2 groups based on culture findings: patients with CoNS as the sole positive culture result and patients with all other positive culture results, including CoNS, as part of a polymicrobial culture., Results: A total of 376 CRS patients met the criteria; 106 patients (28%) had CoNS as their only isolate, 260 (69%) had other positive cultures, and 10 (3%) had no bacterial growth. Compared to patients with other positive cultures, patients with the sole result of CoNS were significantly less likely to have a history of FESS (52% vs 65%, p = 0.019), nasal polyps (50% vs 65%, p = 0.006), and had a better Lund-Mackay CT score (11.95 vs 14.18, p = 0.020). After adjusting for all factors in the multiple logistic regression model, CoNS as the sole positive culture result was independently associated with having no history of FESS (odds ratio [OR] = 0.45; 95% confidence interval [CI], 0.22 to 0.94; p = 0.034)., Conclusion: Positive intraoperative CoNS cultures alone do not result in increased CRS disease burden by objective or subjective measures as compared to patients with other bacterial or polymicrobial culture isolates., (© 2014 ARS-AAOA, LLC.)
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- 2015
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38. Phenylthiocarbamide taste sensitivity is associated with sinonasal symptoms in healthy adults.
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Farquhar DR, Kovatch KJ, Palmer JN, Shofer FS, Adappa ND, and Cohen NA
- Subjects
- Adolescent, Adult, Aged, Female, Healthy Volunteers, Humans, Male, Middle Aged, Quality of Life, Receptors, G-Protein-Coupled metabolism, Respiratory Tract Infections diagnosis, Young Adult, Phenylthiourea, Rhinitis diagnosis, Sinusitis diagnosis, Taste physiology
- Abstract
Background: The bitter taste receptor T2R38, expressed in the tongue and nasal epithelium, has been shown to trigger sinonasal innate immunity contributing to the prevention of gram-negative upper airway bacterial infections. Common polymorphisms of the T2R38 gene, correlating with bitter taste sensitivity to phenylthiocarbamide (PTC), have been linked to differences in sinonasal innate immune response, with specific genotypes significantly more common in medically recalcitrant chronic rhinosinusitis patients. The purpose of this study was to examine this association between T2R38 function and sinonasal infection or symptoms in a healthy population., Methods: A survey of the frequency of sinus infections, as well as other nasal symptoms such as colds, allergies, and overall nasal quality of life (nQOL), was administered to healthy adult participants. nQOL was measured using a 0 to 3 scale of worsening symptoms. A PTC compound taste strip was administered with T2R38 taste sensitivity classified as extremely, somewhat, or not sensitive., Results: Among 217 participants (55% female, 70% Caucasian, 42% age 21 to 25 years), 30% did not detect bitterness (nontasters), 34% were moderate tasters, and 36% were "supertasters," experiencing a strong, unpalatable bitterness. Supertasters were associated with less frequent sinus infections (p = 0.04), and PTC sensitivity was predictive of nasal symptoms: Supertasters had the best nQOL scores, followed by moderate tasters and nontasters (means: 0.65, 0.81, 1.00, respectively; p = 0.014 for trend). There were no significant associations with other variables., Conclusion: This study provides evidence that T2R38 functionality in the tongue correlates with nasal symptoms in healthy individuals., (© 2014 ARS-AAOA, LLC.)
- Published
- 2015
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39. Quality of life improvement from sinus surgery in chronic rhinosinusitis patients with asthma and nasal polyps.
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Zhang Z, Adappa ND, Doghramji LJ, Chiu AG, Lautenbach E, Cohen NA, and Palmer JN
- Subjects
- Asthma psychology, Chronic Disease, Endoscopy methods, Female, Humans, Male, Middle Aged, Nasal Polyps psychology, Nasal Surgical Procedures methods, Retrospective Studies, Rhinitis complications, Rhinitis psychology, Severity of Illness Index, Sinusitis complications, Sinusitis psychology, Asthma complications, Nasal Polyps complications, Quality of Life, Rhinitis surgery, Sinusitis surgery
- Abstract
Background: It is unclear whether chronic rhinosinusitis (CRS) patients with both nasal polyps and asthma have different quality of life (QOL) improvement after functional endoscopic sinus surgery (FESS). We aimed to determine whether CRS patients with asthma and nasal polyps had a greater QOL improvement after FESS compared to patients without asthma or polyps., Methods: This retrospective analysis included adult CRS patients who underwent FESS between 2007 and 2011. QOL was measured using the 22-item Sino-Nasal Outcome Test (SNOT-22). Variables collected included baseline demographics, clinical factors, SNOT-22 scores before FESS, and 1 month, 3 months, and 6 months post-FESS. Groups tested were asthma alone, polyps alone, asthma and polyps, and no asthma or polyps. Linear mixed-effects regression model was performed to calculate β-coefficients, which represent the adjusted mean QOL differences., Results: Among the 376 patients included, 40.16% had both asthma and polyps (n = 151), 14.36% had asthma alone (n = 54), 19.45% had polyps alone (n = 75), and 25.53% had no asthma or polyps (n = 96). After adjusting for all factors, there were significantly more QOL improvements in patients with both asthma and nasal polyps from baseline to 1-month (β-coefficient = -10.05; 95% CI, -15.86 to -4.23; p = 0.001) and 3-month follow-up (β-coefficient = -8.27; 95% CI, -14.98 to -1.56; p = 0.016), and patients with asthma alone from baseline to 6-month follow-up (β-coefficient = -8.78; 95% CI, -17.45 to -0.11; p = 0.047), when compared to patients without asthma or nasal polyps., Conclusion: CRS patients with both asthma and nasal polyps or asthma alone experience a larger QOL benefit from FESS immediately after FESS compared to CRS patients without asthma or polyps., (© 2014 ARS-AAOA, LLC.)
- Published
- 2014
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40. Culture-inappropriate antibiotic therapy decreases quality of life improvement after sinus surgery.
- Author
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Zhang Z, Palmer JN, Morales KH, Howland TJ, Doghramji LJ, Adappa ND, Chiu AG, Cohen NA, and Lautenbach E
- Subjects
- Adult, Chronic Disease, Clindamycin administration & dosage, Clindamycin adverse effects, Cohort Studies, Drug Resistance, Bacterial, Female, Follow-Up Studies, Humans, Male, Middle Aged, Paranasal Sinuses surgery, Postoperative Period, Quality of Life, Retrospective Studies, Treatment Outcome, Trimethoprim, Sulfamethoxazole Drug Combination administration & dosage, Trimethoprim, Sulfamethoxazole Drug Combination adverse effects, Antibiotic Prophylaxis adverse effects, Endoscopy, Paranasal Sinuses drug effects, Rhinitis therapy, Sinusitis therapy
- Abstract
Background: Despite their widespread use, antibiotics have not been shown to improve chronic rhinosinusitis (CRS) outcomes. We aimed to determine whether culture-inappropriate postoperative antibiotic therapy was associated with less quality-of-life (QOL) improvement following functional endoscopic sinus surgery (FESS)., Methods: This retrospective cohort study recruited 376 adult CRS patients undergoing FESS between October 1, 2007 to December 31, 2011. Patient demographics, comorbidities and medications were collected at baseline. Trimethoprim-sulfamethoxazole and clindamycin were administered for 2 weeks postoperatively. The antibiotic appropriateness was determined based on bacterial resistance profile of organisms identified during intraoperative culture. The QOL outcome was defined as change of 22-item Sinonasal Outcome Test scores from preoperative visit to 1-month, 3-month, and 6-month post-FESS. Clinically significant difference was defined as at least 0.5 standard deviations (SD) of baseline QOL score in the reference group. Mixed-effects regression models were performed., Results: Seven percent of patients (n = 27) had culture-inappropriate antibiotic therapy, and additional 5% (n = 19) had culture-specific antibiotic adjustment. Compared to patients with culture-appropriate antibiotics, patients with culture-inappropriate antibiotics had significantly less improvement of QOL from baseline to postoperative 1-month and 3-month follow-up where the difference became clinically significant; patients with antibiotic adjustment had more QOL improvement from baseline to 1-month follow-up, but their QOL worsened at 3-month follow-up, and these changes were not clinically significant. However, all effects washed out at 6-month follow-up with no significant differences., Conclusion: Culture-inappropriate postoperative antibiotic therapy decreased short-term QOL improvement to a clinically meaningful level after FESS. Culture guided selection of antibiotics may improve short-term FESS outcome., (© 2014 ARS-AAOA, LLC.)
- Published
- 2014
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41. The effect of diabetes mellitus on chronic rhinosinusitis and sinus surgery outcome.
- Author
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Zhang Z, Adappa ND, Lautenbach E, Chiu AG, Doghramji L, Howland TJ, Cohen NA, and Palmer JN
- Subjects
- Adult, Chronic Disease, Cohort Studies, Diabetes Mellitus, Type 1 microbiology, Diabetes Mellitus, Type 1 surgery, Diabetes Mellitus, Type 2 microbiology, Diabetes Mellitus, Type 2 surgery, Endoscopy, Female, Gram-Negative Bacterial Infections microbiology, Gram-Negative Bacterial Infections surgery, Humans, Male, Middle Aged, Paranasal Sinuses microbiology, Paranasal Sinuses surgery, Pseudomonas aeruginosa isolation & purification, Quality of Life, Rhinitis microbiology, Rhinitis surgery, Sinusitis microbiology, Sinusitis surgery, Staphylococcus aureus isolation & purification, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 2 epidemiology, Gram-Negative Bacterial Infections epidemiology, Rhinitis epidemiology, Sinusitis epidemiology
- Abstract
Background: Patients with diabetes mellitus (DM) are known to be prone to infection. However, the association between diabetes and chronic rhinosinusitis (CRS) has not been well studied. We sought to determine the effects of DM on CRS culture results and quality of life (QOL) after functional endoscopic sinus surgery (FESS)., Methods: We conducted a retrospective cohort study. Adult CRS patients undergoing FESS were recruited from October 1, 2007 to December 31, 2011. Patient demographics, comorbidities, medication use, and Lund-Mackay CT scores were collected prior to FESS. Intraoperative culture was obtained. Preoperative and 1-month, 3-month, and 6-month postoperative QOL was measured by scores on the 22-item Sinonasal Outcome Test (SNOT-22). A mixed effects model was performed for analysis., Results: Among the 376 CRS patients included, 19 patients (5.05%) had DM. Compared to non-DM patients, DM patients were significantly more likely to have Pseudomonas aeruginosa (26.32% vs 7.56%; p = 0.004) and Gram-negative rods (26.32% vs 8.96%; p = 0.013), but there was no significant difference in the prevalence of Staphylococcus aureus; DM patients were also significantly more likely to have nasal polyps and gastroesophageal reflux disease. Additionally, DM patients had significantly less improvement of postoperative SNOT-22 scores from baseline to 6-month follow-up than non-DM patients (adjusted mean = 11.14, 95% CI (0.14, 22.15), p = 0.047) after adjusting for all the other risk factors for CRS., Conclusion: DM patients may be prone to Gram-negative bacterial sinus infections, and have significantly worse short-term postoperative QOL. Special postoperative care may need to be considered in CRS patients with DM., (© 2014 ARS-AAOA, LLC.)
- Published
- 2014
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42. What is the optimal management of chronic rhinosinusitis in cystic fibrosis?
- Author
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Crosby DL and Adappa ND
- Subjects
- Chronic Disease, Humans, Cystic Fibrosis complications, Rhinitis therapy, Sinusitis therapy
- Abstract
Purpose of Review: Over the past four decades, the average life expectancy for patients with cystic fibrosis (CF) has increased from 13 to 37 years of age. With increasing survival and improved pulmonary management, otolaryngologists are now seeing an increasing number of CF patients with chronic rhinosinusitis (CRS). Although CRS is a commonly treated disease process, there are a number of subtleties specific to CF. As the life expectancy of CF patients increases, quality of life issues gain importance. It is essential for otolaryngologists to understand the current therapeutic modalities to treat this challenging subset of CRS patients., Recent Findings: The sinonasal mucosa of CF patients has distinct differences including impaired mucociliary clearance and a predominantly neutrophilic polyp profile. Performing more aggressive surgical intervention, especially in the setting of revision cases may lead to improved outcomes. A recent study demonstrated that extensive sinus surgery with postoperative management can eradicate pathogenic bacteria from the sinuses of CF patients for up to 1 year., Summary: With increasing life expectancy in CF, patients will require long-term follow-up with an otolaryngologist. Understanding the intricacies of the presentation of this disease in patients with CF is important for optimizing management.
- Published
- 2014
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43. The bitter taste receptor T2R38 is an independent risk factor for chronic rhinosinusitis requiring sinus surgery.
- Author
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Adappa ND, Zhang Z, Palmer JN, Kennedy DW, Doghramji L, Lysenko A, Reed DR, Scott T, Zhao NW, Owens D, Lee RJ, and Cohen NA
- Subjects
- Case-Control Studies, Chronic Disease, Female, Humans, Male, Middle Aged, Polymorphism, Genetic, Prospective Studies, Rhinitis surgery, Risk Factors, Sinusitis surgery, Taste, White People genetics, Receptors, G-Protein-Coupled genetics, Rhinitis genetics, Sinusitis genetics
- Abstract
Background: The bitter taste receptor T2R38 was recently described to play a role in upper airway innate mucosal defense. When activated by bacterial quorum-sensing molecules, T2R38 stimulates the ciliated epithelial cells to produce nitric oxide (NO), resulting in bactericidal activity and an increase in mucociliary clearance (MCC). Polymorphisms within the T2R38 gene (TAS2R38) confer variability in activation of the receptor yielding dramatic differences in upper airway defensive responses (NO production and accelerated MCC) to microbial stimulation based on genotype. Our objective was to determine whether the nonprotective TAS2R38 polymorphisms, which render the receptor inactive, correlate with medically recalcitrant chronic rhinosinusitis (CRS) necessitating surgical intervention in the context of known risk factors, and thus identify whether the TAS2R38 genotype is an independent risk factor for patients undergoing functional endoscopic sinus surgery (FESS)., Methods: CRS patients undergoing primary FESS were prospectively genotyped for TAS2R38. Chi-square analysis was performed on the genotype distribution with respect to other risk factors, including allergies, asthma, nasal polyposis, aspirin sensitivity, diabetes, and smoking exposure., Results: Seventy primary FESS patients were genotyped demonstrating a statistically significant skewing from the expected distribution of the general population (p < 0.0383). CRS patients with a particular polymorphism seemed less likely to have allergies, asthma, nasal polyposis, aspirin sensitivity, and diabetes, but this did not demonstrate statistical significance., Conclusion: Our investigation suggests that TAS2R38 genotype is an independent risk factor for patients failing medical therapy, necessitating surgical intervention., (© 2013 ARS-AAOA, LLC.)
- Published
- 2014
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44. Use of topical nasal therapies in the management of chronic rhinosinusitis.
- Author
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Wei CC, Adappa ND, and Cohen NA
- Subjects
- Antifungal Agents administration & dosage, Budesonide administration & dosage, Chronic Disease, Humans, Glucocorticoids administration & dosage, Nasal Sprays, Rhinitis drug therapy, Sinusitis drug therapy
- Abstract
Objectives/hypothesis: To determine whether the use of topical nasal therapies with saline alone and in combination with antibiotics, antifungals, or corticosteroids is effective in the treatment of patients with chronic rhinosinusitis (CRS)., Data Sources: A systematic literature search was performed utilizing the MEDLINE database (1966 to May 2012), EMBASE database (1980 to May 2012), and the Cochrane Central Register of Controlled Trials., Review Methods: Electronic databases were searched by three otolaryngologists. Studies on five major categories of topical nasal therapies searched included saline (hypotonic, isotonic and hypertonic); topical antibiotics, topical steroids, and topical antifungals were obtained. Randomized controlled trials and meta-analyses of randomized controlled trials were included., Results: Sixteen randomized controlled trials were identified examining topical saline (hypertonic or isotonic) in CRS patients. Two randomized controlled trials were found studying the effect of topical antibiotics in patients with CRS. Four randomized controlled trials were identified studying topical antifungal treatment for CRS. Twenty-five randomized controlled trials were found studying topical steroids in CRS patients., Conclusion: A high aggregate quality of evidence supports the effectiveness of saline irrigations in treating CRS. There is insufficient evidence to support a clear benefit of topical antibiotics in patients with chronic rhinosinusitis. Topical antifungal therapies have not been shown to be significantly different in efficacy than saline controls on CRS outcomes. Topical steroids are beneficial in the treatment of CRS with nasal polyps, but have not been shown to be effective in CRS without nasal polyps., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)
- Published
- 2013
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45. Genetics of the taste receptor T2R38 correlates with chronic rhinosinusitis necessitating surgical intervention.
- Author
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Adappa ND, Howland TJ, Palmer JN, Kennedy DW, Doghramji L, Lysenko A, Reed DR, Lee RJ, and Cohen NA
- Subjects
- Adult, Antigens, Bacterial immunology, Chronic Disease, Female, Genotype, Gram-Negative Bacterial Infections immunology, Humans, Immunity, Innate, Male, Middle Aged, Mucociliary Clearance, Nitric Oxide metabolism, Polymorphism, Genetic, Quorum Sensing, Receptors, G-Protein-Coupled genetics, Rhinitis immunology, Rhinitis surgery, Sinusitis immunology, Sinusitis surgery, Taste Perception, Gram-Negative Bacteria immunology, Nasal Mucosa immunology, Receptors, G-Protein-Coupled metabolism, Rhinitis genetics, Sinusitis genetics
- Abstract
Background: We recently demonstrated the bitter taste receptor T2R38 upregulates sinonasal mucosal innate defense in response to gram-negative quorum-sensing molecules through increased nitric oxide production and mucociliary clearance. T2R38 was initially identified in the quest to understand the variability in bitter taste perception to the compound phenylthiocarbamide (PTC) and demonstrated to have polymorphisms generating diplotypes dividing people into PTC supertasters, heterozygotes (with variable PTC detection), and nontasters. We have further demonstrated that sinonasal epithelial cultures derived from supertasters significantly increase innate defenses in response to gram-negative quorum-sensing molecules compared with sinonasal cultures derived from heterozygotes and nontaster individuals. Based on this data, we hypothesize that supertasters are less likely to require sinus surgery compared with heterozygous or nontasters and that supertasters have improved surgical outcomes., Methods: Banked sinonasal tissue samples from patients who had undergone primary functional endoscopic sinus surgery at the University of Pennsylvania or the Philadelphia Veterans Affairs Medical Center were genotyped for T2R38 and compared to the expected population distribution. Necessity for additional antibiotic therapy following the postoperative healing time frame was evaluated., Results: A total of 28 patients were included in the study. Only 1 supertaster was identified (expected 5.6, p < 0.043). Additionally, 14 heterozygous and 13 nontaster patients were identified., Conclusion: This pilot study investigating the genetics of the bitter taste receptor T2R38 in the context of primary sinonasal surgery demonstrates supertaster patients are less likely to need surgical intervention for chronic rhinosinusitis. Additional study is necessary to ascertain postsurgical outcomes., (© 2013 ARS-AAOA, LLC.)
- Published
- 2013
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46. T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection.
- Author
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Lee RJ, Xiong G, Kofonow JM, Chen B, Lysenko A, Jiang P, Abraham V, Doghramji L, Adappa ND, Palmer JN, Kennedy DW, Beauchamp GK, Doulias PT, Ischiropoulos H, Kreindler JL, Reed DR, and Cohen NA
- Subjects
- Cell Line, Female, Humans, Immunity, Innate genetics, Male, Quorum Sensing immunology, Genetic Predisposition to Disease, Nasal Mucosa immunology, Nasal Mucosa metabolism, Nasal Mucosa microbiology, Paranasal Sinuses immunology, Paranasal Sinuses metabolism, Paranasal Sinuses microbiology, Polymorphism, Genetic, Pseudomonas Infections genetics, Pseudomonas Infections immunology, Pseudomonas Infections metabolism, Pseudomonas aeruginosa immunology, Pseudomonas aeruginosa metabolism, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled immunology, Receptors, G-Protein-Coupled metabolism, Rhinitis genetics, Rhinitis immunology, Rhinitis metabolism, Rhinitis microbiology
- Abstract
Innate and adaptive defense mechanisms protect the respiratory system from attack by microbes. Here, we present evidence that the bitter taste receptor T2R38 regulates the mucosal innate defense of the human upper airway. Utilizing immunofluorescent and live cell imaging techniques in polarized primary human sinonasal cells, we demonstrate that T2R38 is expressed in human upper respiratory epithelium and is activated in response to acyl-homoserine lactone quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Receptor activation regulates calcium-dependent NO production, resulting in stimulation of mucociliary clearance and direct antibacterial effects. Moreover, common polymorphisms of the TAS2R38 gene were linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria. Lastly, TAS2R38 genotype correlated with human sinonasal gram-negative bacterial infection. These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation contributes to individual differences in susceptibility to respiratory infection.
- Published
- 2012
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47. Nasal irrigation with or without drugs: the evidence.
- Author
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Adappa ND, Wei CC, and Palmer JN
- Subjects
- Administration, Intranasal, Anti-Bacterial Agents administration & dosage, Antibodies, Monoclonal, Humanized administration & dosage, Biofilms drug effects, Chronic Disease, Humans, Interleukin-5 immunology, Mupirocin administration & dosage, Rhinitis microbiology, Sinusitis microbiology, Sodium Chloride, Staphylococcus aureus physiology, Nasal Lavage, Rhinitis therapy, Sinusitis therapy
- Abstract
Purpose of Review: To review the recent literature of nasal irrigations with or without drugs, including delivery systems, nasal saline, antibiotics, antifungals, steroids, surfactants, and interleukin (IL)-5 modulators, for the treatment of chronic rhinosinusitis (CRS)., Recent Findings: As antibiotic resistance increases in CRS, culture-directed, rather than empiric, topical antibiotics are increasingly critical in optimal treatment. Topical irrigation with mupirocin significantly reduces Staphylococcus aureus biofilm mass in vitro. Surfactants and humanized anti-IL-5 monoclonal antibody are novel therapies demonstrating promising results in CRS., Summary: Physiologic saline irrigation is beneficial in the treatment of symptoms of CRS. Low-level evidence supports the effectiveness of topical antibiotics in the treatment of CRS. The use of topical antifungals is not supported by the majority of studies. Intranasal steroids are beneficial in the treatment of CRS with nasal polyposis. There is insufficient evidence to demonstrate a clear overall benefit for topical steroids in CRS without nasal polyposis.
- Published
- 2012
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48. Management of refractory chronic rhinosinusitis in children.
- Author
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Adappa ND and Coticchia JM
- Subjects
- Adenoidectomy, Adolescent, Anti-Bacterial Agents administration & dosage, Child, Child, Preschool, Chronic Disease, Combined Modality Therapy, Female, Humans, Infant, Injections, Intravenous, Male, Rhinitis drug therapy, Rhinitis surgery, Sinusitis drug therapy, Sinusitis surgery, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Rhinitis therapy, Sinusitis therapy
- Abstract
Objective: Pediatric chronic rhinosinusitis (CRS) continues to be a difficult problem for the medical community. Traditionally, oral antibiotic therapy has been the cornerstone of treatment, but some patients, who are resistant to multiple trials of oral antibiotics, require alternative therapeutic modalities. One such option, the use of intravenous (IV) antibiotics, has shown a high success rate in a limited study. Our goal is to estimate the success of a therapy consisting of culture directed IV antibiotics, adenoidectomy, and sinus aspiration in ameliorating long-term (>12 months) clinical symptoms of CRS in pediatric patients who are resistant to oral antibiotic therapy., Methods: We conducted a retrospective review of the medical records of 22 patients who received treatment, focusing on patient age, initial CRS presenting symptoms, computed tomography scan finding, length, duration, and type of prior oral antibiotic treatment, length and type of IV antibiotic treatment, and long-term follow-up of clinical symptom resolution., Results: Initial clinical improvement after cessation of IV therapy was achieved in all 22 (100%) patients. Seventeen (77%) of the patients demonstrated long-term resolution of clinical symptoms of CRS. Excluding 4 immunocompromised patients, 16 of 18 (89%) of patients demonstrated long-term amelioration of CRS symptoms., Conclusions: The results suggest that IV antibiotics may prove beneficial for pediatric patients who demonstrate CRS not responsive to traditional oral therapy. Although other treatment options are currently available for this subpopulation of patients, this IV antibiotic therapy provides both a maximally effective outcome while using a relatively minimally invasive intervention.
- Published
- 2006
- Full Text
- View/download PDF
49. Culture-inappropriate antibiotic therapy decreases quality of life improvement after sinus surgery
- Author
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Zhang, Zi, Palmer, James N., Morales, Knashawn H., Howland, Timothy J., Doghramji, Laurel J., Adappa, Nithin D., Chiu, Alexander G., Cohen, Noam A., and Lautenbach, Ebbing
- Subjects
Adult ,Male ,Clindamycin ,Endoscopy ,Antibiotic Prophylaxis ,Middle Aged ,Article ,Cohort Studies ,Treatment Outcome ,Chronic Disease ,Drug Resistance, Bacterial ,Paranasal Sinuses ,Trimethoprim, Sulfamethoxazole Drug Combination ,Quality of Life ,Humans ,Female ,Postoperative Period ,Sinusitis ,Follow-Up Studies ,Retrospective Studies ,Rhinitis - Abstract
Despite their widespread use, antibiotics have not been shown to improve chronic rhinosinusitis (CRS) outcomes. We aimed to determine whether culture-inappropriate postoperative antibiotic therapy was associated with less quality-of-life (QOL) improvement following functional endoscopic sinus surgery (FESS).This retrospective cohort study recruited 376 adult CRS patients undergoing FESS between October 1, 2007 to December 31, 2011. Patient demographics, comorbidities and medications were collected at baseline. Trimethoprim-sulfamethoxazole and clindamycin were administered for 2 weeks postoperatively. The antibiotic appropriateness was determined based on bacterial resistance profile of organisms identified during intraoperative culture. The QOL outcome was defined as change of 22-item Sinonasal Outcome Test scores from preoperative visit to 1-month, 3-month, and 6-month post-FESS. Clinically significant difference was defined as at least 0.5 standard deviations (SD) of baseline QOL score in the reference group. Mixed-effects regression models were performed.Seven percent of patients (n = 27) had culture-inappropriate antibiotic therapy, and additional 5% (n = 19) had culture-specific antibiotic adjustment. Compared to patients with culture-appropriate antibiotics, patients with culture-inappropriate antibiotics had significantly less improvement of QOL from baseline to postoperative 1-month and 3-month follow-up where the difference became clinically significant; patients with antibiotic adjustment had more QOL improvement from baseline to 1-month follow-up, but their QOL worsened at 3-month follow-up, and these changes were not clinically significant. However, all effects washed out at 6-month follow-up with no significant differences.Culture-inappropriate postoperative antibiotic therapy decreased short-term QOL improvement to a clinically meaningful level after FESS. Culture guided selection of antibiotics may improve short-term FESS outcome.
- Published
- 2014
50. Concha Bullosa: A Shield against Allergens?
- Author
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Worrall, Douglas M., Campbell, Raewyn G., Palmer, James N., Kennedy, David W., and Adappa, Nithin D.
- Subjects
INFLAMMATION treatment ,ALLERGENS ,INTRANASAL medication ,SINUSITIS ,ENDOSCOPIC surgery ,MEDICAL radiography ,CHRONIC diseases ,COMPUTED tomography ,ENDOSCOPY ,LONGITUDINAL method ,RHINITIS ,SKIN tests ,TURBINATE bones ,RETROSPECTIVE studies ,DIAGNOSIS - Abstract
Purpose: Concha bullosa (CB) alters the intranasal anatomy and may influence the buffering of inhalant allergens and the inflammatory microenvironment central to chronic rhinosinusitis (CRS). By investigating the link between allergies and CB, we can examine this theoretical benefit, which has implications on the extent of resection in endoscopic sinus surgery.Methods: Forty-three adults treated between 2010 and March 2014 with chronic sinonasal symptoms were retrospectively analyzed by skin prick allergy testing, maxillofacial computed tomography scan, and Lund-Mackay score. x03C7;2 analysis and t tests were employed to determine statistical significance.Results: Subjects were divided into 30 positive cases and 13 pan-negative allergy controls. No difference in CB prevalence was observed between those with positive (70%) and those with negative (69.2%) allergy tests (p = 0.93). Furthermore, no association between CB and Lund-Mackay score was identified (p = 0.69). Overall, 83.3% of CB were located in the middle turbinate, 16.7% in the superior turbinate, and 20% occurred in the middle turbinate bilaterally.Conclusions: Although an enlarged, pneumatized turbinate could function as a physical barrier to inhalant allergens, documented allergies demonstrate no association with CB formation. Furthermore, this study finds no correlation between CB and radiographic evidence of CRS. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
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