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Baseline mucus cytokines predict 22-item Sino-Nasal Outcome Test results after endoscopic sinus surgery.
Chowdhury NI, Li P, Chandra RK, Turner JH
(2020) Int Forum Allergy Rhinol 10: 15-22
MeSH Terms: Adult, Aged, Biomarkers, Chronic Disease, Cytokines, Endoscopy, Female, Humans, Linear Models, Longitudinal Studies, Male, Middle Aged, Nasal Mucosa, Paranasal Sinuses, Prognosis, Prospective Studies, Rhinitis, Sino-Nasal Outcome Test, Sinusitis, Young Adult
Show Abstract · Added July 23, 2020
BACKGROUND - Mucus cytokines have been linked to baseline metrics of quality of life and olfactory function in patients with chronic rhinosinusitis (CRS). However, their potential utility in predicting postoperative outcomes has not been assessed. Therefore, in this study we evaluated the role of mucus cytokines in predicting 22-item Sino-Nasal Outcomes Test (SNOT-22) scores after endoscopic sinus surgery (ESS) in a prospective cohort of CRS patients.
METHODS - One hundred forty-seven patients with CRS electing surgical therapy were enrolled in a longitudinal cohort study. Mucus was collected intraoperatively from the middle meatus and tested for interleukin (IL)-1β, IL-2, -4, -5, -6, -7,- 8, -9, -10, -12, -13, -17A, and -21; tumor necrosis factor (TNF)-α; interferon-γ; eotaxin; and RANTES (regulated-on-activation, normal T-cell expressed and secreted) expression using a multiplex flow-cytometric bead assay. Sixty-two patients were followed postoperatively (average, 10.2 months) with baseline and follow-up SNOT-22 surveys. Stepwise multivariate linear regression was used to model relationships between baseline cytokines, phenotype, and average postoperative SNOT-22 total and domain scores. A machine learning approach using a random forest algorithm was also used to investigate potential nonlinear relationships.
RESULTS - IL-5 was an independent predictor of postoperative total SNOT-22 improvement (β = -8.8, p < 0.0001), whereas IL-2 levels predicted postoperative worsening (β = 6.97, p = 0.0015). Similar relationships were also seen for postoperative SNOT-22 domain scores. The overall model was also noted to be significant fit for the data (adjusted R = 0.398, p < 0.0001). The random forest model similarly identified IL-5, TNF-α, IL-13, and IL-2 as major predictors of postoperative SNOT-22 scores.
CONCLUSION - Mucus cytokine profiles may help identify CRS patients who are likely to obtain postoperative improvement after ESS.
© 2019 ARS-AAOA, LLC.
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20 MeSH Terms
Longitudinal stability of chronic rhinosinusitis endotypes.
Yancey KL, Li P, Huang LC, Sheng Q, Chandra RK, Chowdhury NI, Turner JH
(2019) Clin Exp Allergy 49: 1637-1640
MeSH Terms: Adult, Chronic Disease, Cytokines, Female, Humans, Male, Rhinitis, Sinusitis
Added July 23, 2020
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8 MeSH Terms
Advanced age adversely affects chronic rhinosinusitis surgical outcomes.
Yancey KL, Lowery AS, Chandra RK, Chowdhury NI, Turner JH
(2019) Int Forum Allergy Rhinol 9: 1125-1134
MeSH Terms: Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Chronic Disease, Endoscopy, Female, Humans, Male, Middle Aged, Nasal Surgical Procedures, Paranasal Sinuses, Prognosis, Quality of Life, Rhinitis, Sinusitis, Treatment Outcome, United States, Young Adult
Show Abstract · Added July 23, 2020
BACKGROUND - Patient-specific and disease-specific factors shape the course of chronic rhinosinusitis (CRS) and its response to treatment, with optimal management involving interventions tailored to these factors. Recent evidence suggests CRS inflammatory signatures depend on age. The objective of this study was to determine whether age also influences quality-of-life (QOL) and postoperative outcomes.
METHODS - Retrospective analysis of prospectively collected QOL data from 403 adults with medically refractory CRS who underwent functional endoscopic sinus surgery (FESS) at a tertiary care medical center between 2014 and 2018 was undertaken. Total and subdomain scores from the 22-item Sino-Nasal Outcome Test (SNOT-22) and the Short Form 8 Health Survey (SF-8) measure of general health completed at preoperative and postoperative visits were reviewed.
RESULTS - Patients were divided into young (18 to 39 years, n = 100), middle-aged (40 to 59 years, n = 172), and elderly (≥60 years, n = 131) groups. Baseline total SNOT-22 scores differed between groups (p = 0.01), with middle-aged patients having the highest symptom burden and elderly patients having the lowest. Similar patterns were observed for SNOT-22 subdomains. Elderly patients reported smaller improvements and were less likely to achieve a minimally important clinical difference. CRS patients had worse SF-8 scores compared to the general population, and elderly patients were the least likely to match population norms following surgery. Age was an independent predictor of QOL outcomes after FESS.
CONCLUSION - Age may play a significant role in CRS pathophysiology, symptom burden, and surgical outcomes. Elderly patients report smaller improvements in disease-specific and general health QOL after surgery. CRS management in the elderly population should incorporate age-dependent differences in symptom burden and expectations into treatment algorithms.
© 2019 ARS-AAOA, LLC.
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MeSH Terms
Neuropsychological functioning in early and chronic stages of schizophrenia and psychotic bipolar disorder.
Menkes MW, Armstrong K, Blackford JU, Heckers S, Woodward ND
(2019) Schizophr Res 206: 413-419
MeSH Terms: Adolescent, Adult, Bipolar Disorder, Chronic Disease, Cognition, Cognitive Dysfunction, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Psychiatric Status Rating Scales, Psychotic Disorders, Schizophrenia, Schizophrenic Psychology, Young Adult
Show Abstract · Added January 31, 2020
BACKGROUND - Neuropsychological impairment is common in schizophrenia and psychotic bipolar disorder. It has been hypothesized that the pathways leading to impairment differ between disorders. Cognitive impairment in schizophrenia is believed to result largely from atypical neurodevelopment, whereas bipolar disorder is increasingly conceptualized as a neuroprogressive disorder. The current investigation tested several key predictions of this hypothesis.
METHODS - Current neuropsychological functioning and estimated premorbid intellectual ability were assessed in healthy individuals (n = 260) and a large, cross-sectional sample of individuals in the early and chronic stages of psychosis (n = 410). We tested the following hypotheses: 1) cognitive impairment is more severe in schizophrenia in the early stage of psychosis; and 2) cognitive decline between early and chronic stages is relatively greater in psychotic bipolar disorder. Additionally, individuals with psychosis were classified as neuropsychologically normal, deteriorated, and compromised (i.e. below average intellectual functioning) to determine if the frequencies of neuropsychologically compromised and deteriorated patients were higher in schizophrenia and psychotic bipolar disorder, respectively.
RESULTS - Neuropsychological impairment in the early stage of psychosis was more severe in schizophrenia. Psychotic bipolar disorder was not associated with relatively greater cognitive decline between illness stages. The frequency of neuropsychologically compromised patients was higher in schizophrenia; however, substantial portions of both schizophrenia and psychotic bipolar disorder patients were classified as neuropsychologically compromised and deteriorated.
CONCLUSIONS - While schizophrenia is associated with relatively greater neurodevelopmental involvement, psychotic bipolar disorder and schizophrenia cannot be strictly dichotomized into purely neuroprogressive and neurodevelopmental illness trajectories; there is evidence of both processes in each disorder.
Copyright © 2018 Elsevier B.V. All rights reserved.
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17 MeSH Terms
Nasal saline irrigation: a clinical update.
Succar EF, Turner JH, Chandra RK
(2019) Int Forum Allergy Rhinol 9: S4-S8
MeSH Terms: Chronic Disease, Humans, Hygiene, Nasal Lavage, Practice Guidelines as Topic, Rhinitis, Saline Solution, Sinusitis, Sodium Chloride
Show Abstract · Added July 23, 2020
BACKGROUND - Nasal saline irrigation (NSI) plays an important role in the treatment of chronic rhinosinusitis (CRS). It is a beneficial low-risk treatment that serves an adjunctive function in the medical and surgical management of CRS. NSI is hypothesized to function by thinning mucous, improving mucociliary clearance, decreasing edema, and reducing antigen load in the nasal and sinus cavities. Although its use in CRS is nearly universal, significant variety exists with regard to delivery volume, delivery pressure, frequency of use, duration of use, composition, and hygiene recommendations. Evidence is limited regarding the most optimal methods of NSI delivery. In addition, use of NSI has recently come under increasing scrutiny due to potential associations with cases of primary amebic meningoencephalitis.
METHODS - In this review we provide a clinical update summarizing use of NSI for treatment of CRS, including current recommendations for use, and data regarding overall efficacy, available delivery devices, solution composition, and hygiene.
RESULTS - Current evidence and recommendations for nasal saline delivery methods, composition, and hygiene are presented.
CONCLUSION - The most recent consensus statements and Cochrane Review recommend the use of NSI for CRS based on a preponderance of lower level evidence. A conclusion regarding the optimal method of delivery and solution composition cannot be drawn based on the current literature.
© 2019 ARS-AAOA, LLC.
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MeSH Terms
Recent advances in understanding chronic rhinosinusitis endotypes.
Succar EF, Turner JH
(2018) F1000Res 7:
MeSH Terms: Allergy and Immunology, Biomarkers, Chronic Disease, Disease Management, Humans, Inflammation, Rhinitis, Sinusitis
Show Abstract · Added July 23, 2020
Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease with an as-yet-undefined etiology. The management of CRS has historically been phenotypically driven, and the presence or absence of nasal polyps has frequently guided diagnosis, prognosis, and treatment algorithms. Research over the last decade has begun to question the role of this distinction in disease management, and renewed attention has been placed on molecular and cellular endotyping and a more personalized approach to care. Current research exploring immunologic mechanisms, inflammatory endotypes, and molecular biomarkers has the potential to more effectively delineate distinct and clinically relevant subgroups of CRS. The focus of this review will be to discuss and summarize the endotypic characterization of CRS and the potential diagnostic and therapeutic implications of this approach to disease management.
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Investigating the correlation between mucus cytokine levels, inflammatory cell counts, and baseline quality-of-life measures in chronic rhinosinusitis.
Chowdhury NI, Chandra RK, Li P, Ely K, Turner JH
(2019) Int Forum Allergy Rhinol 9: 538-544
MeSH Terms: Adult, Aged, Chronic Disease, Cytokines, Endoscopy, Female, Humans, Leukocyte Count, Male, Middle Aged, Mucus, Nasal Mucosa, Nasal Polyps, Nasal Surgical Procedures, Quality of Life, Rhinitis, Sino-Nasal Outcome Test, Sinusitis, Young Adult
Show Abstract · Added July 23, 2020
BACKGROUND - It is hypothesized that uncontrolled inflammation is responsible for many of the manifestations and symptoms of chronic rhinosinusitis (CRS). Although earlier work has demonstrated an association between olfactory loss and mucus cytokines, the impact on other symptoms is unknown. In this study we investigated the relationship between cytokines, inflammatory cell counts, and patient-reported outcomes measures to better understand how the inflammatory microenvironment correlates with CRS symptomatology.
METHODS - The 22-item Sino-Nasal Outcome Test (SNOT-22) and 8-item Short Form Health Survey (SF-8) were administered to 76 patients undergoing endoscopic sinus surgery for CRS. Mucus was collected intraoperatively from the middle meatus and tested for 17 cytokines using a multiplex flow cytometric bead assay. Eosinophil/neutrophil counts were obtained from histopathologic slide review. Spearman correlations between cytokines, cell counts, and quality-of-life subdomain scores were assessed without multiple comparisons correction due to the small sample size.
RESULTS - Interleukin-4 (IL-4) correlated significantly with the Rhinologic domain (R = 0.25, p = 0.03), whereas eosinophil and neutrophil counts were inversely correlated with the Extranasal Rhinologic domain (R = -0.32, p = 0.01; and R = -0.27, p = 0.03). Subgroup analysis for nasal polyposis (CRSwNP) showed significant correlations between IL-6 and Total SF-8 (R = 0.35, p = 0.02), General Health (R = 0.34, p = 0.03), and Emotional (R = 0.47, p = 0.002) scores. In patients without polyps (CRSsNP), IL-21 correlated positively with Extranasal Rhinologic Symptoms domain (R = 0.41, p = 0.01).
CONCLUSION - This pilot study identifies possible pairwise correlations between mucus cytokine levels and baseline quality-of-life measures that need confirmation in larger, targeted studies. Due to the exploratory methodology, positive results may be spurious and should only be used as a starting point for future confirmatory work.
© 2019 ARS-AAOA, LLC.
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Preoperative quality-of-life measures predict acute postoperative pain in endoscopic sinus surgery.
Chowdhury NI, Turner JH, Dorminy C, Wu J, Chandra RK
(2019) Laryngoscope 129: 1274-1279
MeSH Terms: Adolescent, Adult, Aged, Chronic Disease, Endoscopy, Female, Humans, Male, Middle Aged, Otorhinolaryngologic Surgical Procedures, Pain, Postoperative, Paranasal Sinuses, Preoperative Period, Prognosis, Quality of Life, Rhinitis, Severity of Illness Index, Sinusitis, Young Adult
Show Abstract · Added July 23, 2020
OBJECTIVES - Recent increases in opioid-related mortality have prompted a critical evaluation of postoperative pain management across all specialties. However, successfully limiting narcotic overprescription requires perioperative identification of patients who are at risk for high postoperative pain. Unfortunately, quality data to guide practice patterns are lacking. We therefore prospectively investigated several possible predictive factors of postoperative pain after endoscopic sinus surgery (ESS).
METHODS - Sixty-four consecutive patients undergoing ESS were enrolled. Baseline 22-item SinoNasal Outcomes Test (SNOT-22) and Short-Form 8 (SF-8) scores were obtained. Pain scores were collected postoperatively using a numeric rating scale. Spearman correlations and univariate linear regression models were used to investigate relationships between postoperative pain, patient factors, and SNOT-22/SF-8 domain scores. Multivariate linear regression was then performed to control for potential confounding variables.
RESULTS - Day-of-surgery pain scores were significantly correlated with the SF-8 role-physical domain (Rs = 0.32, P = 0.04). Whereas SF-8 pain scores were initially nonsignificant, at postoperative day 3 (POD3) the preoperative SF-8 pain score became correlated with self-reported pain (Rs = 0.39, P = 0.02). SNOT-22 total and subdomain scores were not associated with pain scores at any time point. Multivariate linear regression modelling identified baseline SF-8 role-physical and pain scores, smoking status, and undergoing a modified Lothrop procedure as significant independent predictors of POD3 pain (adjusted R = 0.359, P < 0.0001).
CONCLUSION - Baseline patient-reported global quality-of-life measures are associated with postoperative pain after ESS. Large multicenter studies are necessary to validate these findings and investigate additional factors associated with postoperative pain following ESS.
LEVEL OF EVIDENCE - 2c Laryngoscope, 129:1274-1279, 2019.
© 2019 The American Laryngological, Rhinological and Otological Society, Inc.
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Patterns of olfactory dysfunction in chronic rhinosinusitis identified by hierarchical cluster analysis and machine learning algorithms.
Morse JC, Shilts MH, Ely KA, Li P, Sheng Q, Huang LC, Wannemuehler TJ, Chowdhury NI, Chandra RK, Das SR, Turner JH
(2019) Int Forum Allergy Rhinol 9: 255-264
MeSH Terms: Adult, Algorithms, Chronic Disease, Cluster Analysis, Cytokines, Eosinophils, Female, Humans, Inflammation Mediators, Machine Learning, Male, Middle Aged, Nasal Polyps, Olfaction Disorders, Rhinitis, Sinusitis, Smell
Show Abstract · Added July 23, 2020
BACKGROUND - Olfactory dysfunction is a common symptom of chronic rhinosinusitis (CRS). We previously identified several cytokines potentially linked to smell loss, potentially supporting an inflammatory etiology for CRS-associated olfactory dysfunction. In the current study we sought to validate patterns of olfactory dysfunction in CRS using hierarchical cluster analysis, machine learning algorithms, and multivariate regression.
METHODS - CRS patients undergoing functional endoscopic sinus surgery were administered the Smell Identification Test (SIT) preoperatively. Mucus was collected from the middle meatus using an absorbent polyurethane sponge and 17 inflammatory mediators were assessed using a multiplexed flow-cytometric bead assay. Hierarchical cluster analysis was performed to characterize inflammatory patterns and their association with SIT scores. The random forest approach was used to identify cytokines predictive of olfactory function.
RESULTS - One hundred ten patients were enrolled in the study. Hierarchical cluster analysis identified 5 distinct CRS clusters with statistically significant differences in SIT scores observed between individual clusters (p < 0.001). A majority of anosmic patients were found in a single cluster, which was additionally characterized by nasal polyposis (100%) and a high incidence of allergic fungal rhinosinusitis (50%) and aspirin-exacerbated respiratory disease (AERD) (33%). A random forest approach identified a strong association between olfaction and the cytokines interleukin (IL)-5 and IL-13. Multivariate modeling identified AERD, computed tomography (CT) score, and IL-2 as the variables most predictive of olfactory function.
CONCLUSION - Olfactory dysfunction is associated with specific CRS endotypes characterized by severe nasal polyposis, tissue eosinophilia, and AERD. Mucus IL-2 levels, CT score, and AERD were independently associated with smell loss.
© 2018 ARS-AAOA, LLC.
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Chronic rhinosinusitis in elderly patients is associated with an exaggerated neutrophilic proinflammatory response to pathogenic bacteria.
Morse JC, Li P, Ely KA, Shilts MH, Wannemuehler TJ, Huang LC, Sheng Q, Chowdhury NI, Chandra RK, Das SR, Turner JH
(2019) J Allergy Clin Immunol 143: 990-1002.e6
MeSH Terms: Adult, Aged, Bacteria, Bacterial Infections, Chronic Disease, Cluster Analysis, Cytokines, Female, Humans, Male, Middle Aged, Mucus, Nasal Polyps, Neutrophils, Paranasal Sinuses, Rhinitis, Sinusitis
Show Abstract · Added July 23, 2020
BACKGROUND - Potential effects of aging on chronic rhinosinusitis (CRS) pathophysiology have not been well defined but might have important ramifications given a rapidly aging US and world population.
OBJECTIVE - The goal of the current study was to determine whether advanced age is associated with specific inflammatory CRS endotypes or immune signatures.
METHODS - Levels of 17 mucus cytokines and inflammatory mediators were measured in 147 patients with CRS. Hierarchical cluster analysis was used to identify and characterize inflammatory CRS endotypes, as well as to determine whether age was associated with specific immune signatures.
RESULTS - A CRS endotype with a proinflammatory neutrophilic immune signature was enriched in older patients. In the overall cohort patients 60 years and older had increased mucus levels of IL-1β, IL-6, IL-8, and TNF-α when compared with their younger counterparts. Increases in levels of proinflammatory cytokines were associated with both tissue neutrophilia and symptomatic bacterial infection/colonization in aged patients.
CONCLUSIONS - Aged patients with CRS have a unique inflammatory signature that corresponds to a neutrophilic proinflammatory response. Neutrophil-driven inflammation in aged patients with CRS might be less likely to respond to corticosteroids and might be closely linked to chronic microbial infection or colonization.
Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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