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Objective: To investigate the effects of obesity on superfertility.Design: Retrospective observational study.Setting: A tertiary referral implantation clinic.Population: Four hundred and fourteen women attending a tertiary implantation clinic with a history of recurrent miscarriage (RMC), over a 4-year period.Methods: Pattern of pregnancy loss and time to pregnancy intervals for each pregnancy were collected by medical staff from women with RMC. The women were categorised into normal, overweight and obese according to their body mass index (BMI). Kaplan-Meier curves were constructed estimating the cumulative probability of a spontaneous pregnancy over time. The pregnancy loss patterns were correlated with BMI and data were compared between the categories using the Kruskal-Wallis test.Main Outcome Measures: Pregnancy loss pattern and time to pregnancy intervals.Results: Overall, 23.2, 51.4 and 64.2% of women conceived within first 1, 3 and 6 months, respectively. Obese women had cumulative pregnancy rates of 65.2 and 80% by three and 6 months, respectively, which was more than the cumulative pregnancy rates for women with normal BMI (49.2 and 65.8%). Comparison of survival curves indicated a significant difference in time to conceive for obese when compared with normal and overweight women (*P = 0.01), suggesting a higher prevalence of superfertility in obese women with RMC.Conclusions: Our findings suggest that obese women may have a greater efficacy to achieve pregnancy, but with an increased risk of miscarriage, which may suggest the possible metabolic effects of obesity on endometrium. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) and asthma commonly co-occur. No studies have leveraged large samples needed to formally address whether preexisting CRS is associated with new onset asthma over time., Methods: We evaluated whether prevalent CRS [identified in two ways: validated text algorithm applied to sinus computerized tomography (CT) scan or two diagnoses] was associated with new onset adult asthma in the following year. We used electronic health record data from Geisinger from 2008 to 2019. For each year we removed persons with any evidence of asthma through the end of the year, then identified those with new diagnosis of asthma in the following year. Complementary log-log regression was used to adjust for confounding variables (e.g., sociodemographic, contact with the health system, comorbidities), and hazard ratios (HRs) and 95% confidence intervals (CI) were calculated., Results: A total of 35,441 persons were diagnosed with new onset asthma and were compared to 890,956 persons who did not develop asthma. Persons with new onset asthma tended to be female (69.6%) and younger (mean [SD] age 45.9 [17.0] years). Both CRS definitions were associated (HR, 95% CI) with new onset asthma, with 2.21 (1.93, 2.54) and 1.48 (1.38, 1.59) for CRS based on sinus CT scan and two diagnoses, respectively. New onset asthma was uncommonly observed in persons with a history of sinus surgery., Conclusion: Prevalent CRS identified with two complementary approaches was associated with a diagnosis of new onset asthma in the following year. The findings may have clinical implications for the prevention of asthma., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Viruses may drive immune mechanisms responsible for chronic rhinosinusitis with nasal polyposis (CRSwNP), but little is known about the underlying molecular mechanisms., Objectives: To identify epigenetic and transcriptional responses to a common upper respiratory pathogen, rhinovirus (RV), that are specific to patients with CRSwNP using a primary sinonasal epithelial cell culture model., Methods: Airway epithelial cells were collected at surgery from patients with CRSwNP (cases) and from controls without sinus disease, cultured, and then exposed to RV or vehicle for 48 h. Differential gene expression and DNA methylation (DNAm) between cases and controls in response to RV were determined using linear mixed models. Weighted gene co-expression analysis (WGCNA) was used to identify (a) co-regulated gene expression and DNAm signatures, and (b) genes, pathways, and regulatory mechanisms specific to CRSwNP., Results: We identified 5585 differential transcriptional and 261 DNAm responses (FDR <0.10) to RV between CRSwNP cases and controls. These differential responses formed three co-expression/co-methylation modules that were related to CRSwNP and three that were related to RV (Bonferroni corrected p < .01). Most (95%) of the differentially methylated CpGs (DMCs) were in modules related to CRSwNP, whereas the differentially expressed genes (DEGs) were more equally distributed between the CRSwNP- and RV-related modules. Genes in the CRSwNP-related modules were enriched in known CRS and/or viral response immune pathways., Conclusion: RV activates specific epigenetic programs and correlated transcriptional networks in the sinonasal epithelium of individuals with CRSwNP. These novel observations suggest epigenetic signatures specific to patients with CRSwNP modulate response to viral pathogens at the mucosal environmental interface. Determining how viral response pathways are involved in epithelial inflammation in CRSwNP could lead to therapeutic targets for this burdensome airway disorder., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Chronic rhinosinusitis (CRS) is a common clinical syndrome that produces significant morbidity and costs to our health system. The study of CRS has progressed from an era focused on phenotype to include endotype-based information. Phenotypic classification has identified clinical heterogeneity in CRS based on endoscopically observed features such as presence of nasal polyps, presence of comorbid or systemic diseases, and timing of disease onset. More recently, laboratory-based findings have established CRS endotype based upon specific mechanisms or molecular biomarkers. Understanding the basis of widespread heterogeneity in the manifestations of CRS is advanced by findings that the three main endotypes, Type 1, 2, and 3, orchestrate the expression of three distinct large sets of genes. The development and use of improved methods of endotyping disease in the clinic are ushering in an expansion of the use of biological therapies targeting Type 2 inflammation now and perhaps other inflammatory endotypes in the near future. The purpose of this review is to discuss the phenotypic and endotypic heterogeneity of CRS from the perspective of advancing the understanding of the pathogenesis and improvement of treatment approaches and outcomes., (© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objectives/hypothesis: Otolaryngologic symptoms of obstructive sleep apnea (OSA) and their diagnostic utility are not well studied. We aimed to elucidate the prevalence of otolaryngologic symptoms among patients being evaluated for OSA. Given findings that the Reflux Symptom Index (RSI) was strongly associated with OSA status, we evaluated the diagnostic utility of the RSI for predicting OSA status., Study Design: Cross-sectional., Methods: We recruited 101 adults presenting for ambulatory polysomnograms to the Northwestern Sleep Disorders Center from July 2017 to July 2018. The Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Leicester Cough Questionnaire (LCQ), RSI, Gastroesophageal Reflux Disease Questionnaire, Sino-Nasal Outcome Test-22, Nasal Obstruction Symptom Evaluation, Eustachian Tube Dysfunction Questionnaire 7, and Headache Impact Test were administered. Polysomnogram results were subsequently obtained. Patients with OSA (apnea-hypopnea index ≥ 5) and without OSA were compared., Results: Of the 101 participants, 98 had valid sleep study results. Of those, 72 were diagnosed with OSA and 26 were not. The two groups differed significantly in age and body mass index (BMI). Of the questionnaires, only the RSI and LCQ means differed significantly, with worse symptoms in the OSA group (P = .003 and .014, respectively). Upon univariate regression, age, BMI, and RSI were associated with OSA status. Using regression coefficients, a clinical score of 2 (RSI) + 1.5 (BMI) + age yielded a diagnostic model (C-statistic = 0.807, P < .001). A threshold score of 104.21 was 76.4% sensitive and 73.1% specific., Conclusions: Patients with OSA have worse symptoms of laryngopharyngeal reflux as measured by the RSI. The addition of the RSI to the recognized factors of age and BMI improves diagnostic utility for OSA., Level of Evidence: 2 Laryngoscope, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Chronic rhinosinusitis (CRS) epidemiology has been largely studied using symptom-based case definitions, without assessment of objective sinus findings., Objective: To describe radiologic sinus opacification and the prevalence of CRS, defined by the co-occurrence of symptoms and sinus opacification, in a general population-based sample., Methods: We collected questionnaires and sinus CT scans from 646 participants selected from a source population of 200 769 primary care patients. Symptom status (CRS S ) was based on guideline criteria, and objective radiologic inflammation (CRS O ) was based on the Lund-Mackay (L-M) score using multiple L-M thresholds for positivity. Participants with symptoms and radiologic inflammation were classified as CRS S+O . We performed negative binomial regression to assess factors associated with L-M score and logistic regression to evaluate factors associated with CRS S+O . Using weighted analysis, we calculated estimates for the source population., Results: The proportion of women with L-M scores ≥ 3, 4, or 6 (CRS O ) was 11.1%, 9.9%, and 5.7%, respectively, and 16.1%, 14.6%, and 8.7% among men. The respective proportion with CRS S+O was 1.7%, 1.6%, and 0.45% among women and 8.8%, 7.5%, and 3.6% among men. Men had higher odds of CRS S+O compared to women. A greater proportion of men (vs women) had any opacification in the frontal, anterior ethmoid, and sphenoid sinuses., Conclusion: In a general population-based sample in Pennsylvania, sinus opacification was more common among men than in women and opacification occurred in different locations by sex. Male sex, migraine headache, and prior sinus surgery were associated with higher odds of CRS S+O ., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objective: To assess the health utility of chronic Eustachian tube dysfunction (ETD)., Methods: This is a prospective study of 53 patients with chronic ETD recruited from a tertiary clinic from April 2017 to July 2018. The 7-Item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) was administered, and health utility was evaluated using the EuroQol-5 Dimensions-3 Level Instrument (EQ-5D-3L), the visual analogue scale (VAS), time tradeoff (TTO), and standard gamble (SG). Participants were grouped into medical or procedural management groups. One-week follow-up included repeated health utility measures and ETDQ-7., Results: Fifty-three patients were included in the final analysis. Of those, 34 were managed medically, and 19 received myringotomies ± PE tubes. The mean baseline ETDQ-7 was 4.26 ± 1.31; whereas health utility measures were different depending on the method utilized: EQ-5D-3L 0.90 ± 0.11; VAS 0.76 ± 0.21; TTO 0.85 ± 0.23; and SG 0.94 ± 0.11 (P < .001). There was a significant change in ETDQ-7 (P = .001) and TTO (P = .011) scores posttreatment. On the ETDQ-7, question 2 (pain in the ears) was significantly associated with VAS (P = .032), and question 4 (ear symptoms during a cold or sinusitis) was significantly associated with TTO (P = .006)., Conclusion: Chronic ETD has a significant burden on quality of life, with a health utility similar to gastroesophageal reflux disease and moderate asthma. Although treatment-related changes are measurable using disease-specific quality-of-life measures, only TTO was significantly changed after treatment. Health utility seemed to depend on the method of measurement but provided a benchmark for evaluating cost-effectiveness of innovations to manage ETD., Level of Evidence: 2 Laryngoscope, 130:E39-E44, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To assess if there is a significant difference in the prevalence and severity of chronic cough symptoms in obstructive sleep apnea (OSA) patients versus non-OSA patients and examine this relationship in regard to laryngopharyngeal reflux (LPR) symptoms., Study Design: Prospective cohort study., Methods: Patients referred to Northwestern Medicine Sleep Lab for home sleep testing were enrolled. Patients filled out the Leicester Cough Questionnaire (LCQ) and Reflux Symptom Index (RSI) before completing sleep testing. Home sleep testing results were reviewed, and patients were separated into non-OSA and OSA groups by standard Apnea-Hypopnea Index (AHI) criteria. Demographic characteristics and questionnaire scores of the two groups were compared. The relationship between OSA severity, as determined by AHI, and LCQ and RSI scores was assessed., Results: Of the 52 patients enrolled, 33 patients met criteria for OSA and 19 patients did not. Comparing patients without OSA versus those with OSA, there was a significant difference in mean LCQ score (129.9 vs. 120.0, respectively; P = .02), implying worse cough symptoms among OSA patients, and mean RSI score (3.2 vs. 11.2, respectively; P = .0013), implying worse upper-airway reflux symptoms among OSA patients. There was a significant correlation between LCQ score and AHI (r = -0.39, P = .0061) and between RSI score and AHI (r = 0.37, P = .0078)., Conclusions: OSA patients demonstrate worse chronic cough and LPR-related quality of life versus non-OSA patients. Furthermore, the severity of these quality-of-life measures was correlated with the severity of the AHI. Chronic cough and particularly the pharyngeal LPR symptoms may be associated with the presence and severity of OSA., Level of Evidence: 2 . Laryngoscope, 129:1244-1249, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Sinonasal symptoms are common and can have several underlying causes. When symptoms occur in specified patterns lasting 3 months or more they meet criteria for chronic rhinosinusitis (CRS). Approaches to CRS symptom measurement do not specify how to measure symptoms and treat specified sinonasal symptoms as generally interchangeable, suggesting that such symptoms should cluster on 1 or 2 latent factors., Methods: We used questionnaire responses to 37 questions on the presence, severity, bother, and frequency of cardinal sinonasal and related symptoms lasting 3 months, from 3535 subjects at 3 time points over 16 months. We completed 5 exploratory factor analyses (EFA) to identify symptom clustering, 1 for each time point and 2 for the differences between adjacent questionnaires. The baseline EFA was used to provide factor scores that were described longitudinally and examined by CRS status., Results: Five EFAs identified the same 5 factors (blockage and discharge, pain and pressure, asthma and cold/flu symptoms, smell loss, and ear and eye [mainly allergy] symptoms), with clustering determined by symptom frequency, severity, and degree of bother. Responses to individual questions showed changes over time but when combined into factor scores showed less longitudinal change. All symptom factor scores were progressively higher from never to past to current CRS status., Conclusions: Although the current approaches to symptom characterization in CRS imply a single underlying latent construct, our results suggest that there are at least 3 latent constructs relevant to CRS. Further studies are needed to evaluate whether these clusters have identifiable underlying pathobiologies., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Nasal and sinus symptoms (NSS) are common to many health conditions, including chronic rhinosinusitis (CRS). Few studies have investigated the occurrence and severity of, and risk factors for, acute exacerbations of NSS (AENSS) by CRS status (current, past, or never met European Position Paper on Rhinosinusitis [EPOS] criteria for CRS)., Methods: Four seasonal questionnaires were mailed to a stratified random sample of Geisinger primary care patients. Logistic regression was used to identify individual characteristics associated with AENSS occurrence and severity by CRS status (current long-term, current recent, past, never) using EPOS subjective symptoms-only (EPOS S ) CRS criteria. We operationalized 3 AENSS definitions based on prescribed antibiotics or oral corticosteroids, symptoms, and symptoms with purulence., Results: Baseline and at least 1 follow-up questionnaires were available from 4736 subjects. Self-reported NSS severity with exacerbation was worst in the current long-term CRS group. AENSS was common in all subgroups examined and generally more common among those with current EPOS S CRS. Seasonal prevalence of AENSS differed by AENSS definition and CRS status. Associations of risk factors with AENSS differed by definition, but CRS status, body mass index, asthma, hay fever, sinus surgery history, and winter season consistently predicted AENSS., Conclusions: In this first longitudinal, population-based study of 3 AENSS definitions, NSS and AENSS were both common, sometimes severe, and differed by EPOS S CRS status. Contrasting associations of risk factors for AENSS by the different definitions suggest a need for a standardized approach to definition of AENSS., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objective: To evaluate if molecular markers of eosinophilia in olfactory-enriched mucosa are associated with olfactory dysfunction., Study Design: Cross-sectional study of tissue biopsies from 99 patients, and an additional 30 patients who underwent prospective olfactory testing prior to sinonasal procedures., Methods: Tissue biopsies were processed for analysis of inflammatory markers using quantitative real time polymerase chain reaction (qRT-PCR). Ipsilateral olfactory performance was assessed using the Sniffin' Sticks (Burghart, Wedel, Germany) threshold component and the University of Pennsylvania Smell Identification Test (Sensonics, Haddon Heights, NJ). Age-adjusted data was correlated with inflammatory marker expression and clinical measures of obstruction from computed tomography and endoscopy., Results: Gene expression of the eosinophil marker CLC (Charcot Leyden crystal protein) was elevated in superior turbinate (ST) tissue in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) compared to ST and inferior turbinate tissue in CRS without nasal polyps (CRSsNP) and control patients (all P < 0.001, respectively). CLC in ST tissue was correlated with IL-5 and eotaxin-1 expression (all P < 0.001; P = 0.65, and 0.49, respectively). CLC expression was strongly correlated with eosinophilic cationic protein levels (P < 0.001; r = -0.76), and ST CLC expression was inversely related to olfactory threshold (P = 0.002, r = -0.57) and discrimination scores (P = 0.05, r = -0.42). In multiple linear regression of CLC gene expression, polyp status, and radiographic and endoscopic findings with olfactory threshold, CLC was the only significantly correlated variable (P < 0.05)., Conclusion: Markers of eosinophils are elevated in the ST of patients with CRSwNP and correlate with olfactory loss. These findings support the hypothesis that olfactory dysfunction in CRS correlates local eosinophil influx into the olfactory cleft., Level of Evidence: NA. Laryngoscope, 127:2210-2218, 2017., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The objective of this study was to describe the first US-based study to use the European Position Paper on Rhinosinusitis (EPOS) criteria to study the prevalence of chronic rhinosinusitis (CRS) in a general-population sample., Methods: A CRS symptom questionnaire was mailed to 23 700 primary care patients from Geisinger Clinic, a health system serving 45 counties in Pennsylvania. CRS cases were categorized into four unique subgroups based on EPOS symptoms: obstruction and discharge with no smell loss or pain/pressure; smell loss without pain/pressure; facial pain and/or pressure without smell loss; and both smell loss and pain/pressure. All cases were required to have nasal obstruction or discharge. Logistic regression was used to evaluate potential factors associated with CRS subgroups., Results: We found that 11.9% of patients met criteria for CRS. Prevalence peaked at 15.9% between ages 50 and 59 years and then dropped to 6.8% after age 69. The odds of CRS was higher among patients who were white, younger, smokers, had a history of Medical Assistance, and had other diseases. When CRS subgroups were modeled separately, these associations were no longer significant for some CRS subgroups. Comorbid diseases were most strongly associated with CRS cases who reported smell loss and facial pain and/or pressure and had the weakest associations with CRS cases who did not report these symptoms., Conclusions: CRS is a highly prevalent and heterogeneous condition. Differences in risk factors and health outcomes across symptom subgroups may be indicative of differences in etiology that have implications for disease management., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chronic rhinosinusitis (CRS) has a broad range of comorbidities. Due to a lack of longitudinal studies, it is not known whether these comorbidities cause CRS, are promoted by CRS, or share a systemic disease process with CRS., Objective: The objective of this study was to determine the risk of incident disease within 5 years after a new diagnosis of CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP)., Methods: We conducted a case-control study nested within the longitudinal cohort of primary care patients in the Geisinger Clinic using electronic health record data. We evaluated incident disease over 5 years in newly diagnosed CRSwNP and CRSsNP cases compared to controls using multivariable Cox regression models., Results: CRSsNP (n = 3612) cases were at greater risk (HR, 95% confidence interval) than controls for incidence of: upper airway diseases, including adenotonsillitis (3.29, 2.41-4.50); lower aerodigestive tract diseases, including asthma (2.69, 2.14-3.38); epithelial conditions, including atopic dermatitis (2.75, 1.23-6.16); and hypertension (1.38, 1.19-1.61). CRSwNP (n = 241) cases were at greater risk for obesity than controls (1.74, 1.08-2.80), but CRSwNP was not associated with other diseases., Conclusion: The risk of other diseases associated with CRS adds to the burden of an already highly burdensome condition, and suggests either that CRS promotes onset of other diseases or is an indicator of systemic disease processes. Different patterns of association with diseases by CRS phenotype may be due to CRSwNP sample size limitations or reflect a different pattern of disease onset by phenotype. These findings have implications for screening guidelines and care of CRS patients., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives/hypothesis: The objective of this study was to report patients' knowledge and comfort level with computed tomography (CT) imaging for sinus disease and evaluate patient willingness to undergo empiric medical therapy (EMT) versus CT-directed therapy (CTDT)., Study Design: Prospective survey study., Methods: A 22-item survey was administered to patients with nasal/sinus symptoms in a tertiary care rhinology clinic. Questions elicited patient demographics, imaging history, and knowledge/comfort regarding imaging-related radiation exposure. Patients were presented with the theoretical choice of EMT versus CTDT, given the expected positive predictive value, in chronic rhinosinusitis (CRS) management., Results: Two hundred patients (52% female, age range 18-83 years) participated. Of these, 85% had symptoms for over 3 months. Only 91 patients (45.5%) were aware that CT imaging involved radiation exposure. Prior CT experience and past sinus surgery (P < .05), but not sex or education level, were associated with increased comfort with CT imaging. Most patients (78%) preferred CTDT over EMT. If a CT sinus was recommended, 77 patients (38.5%) had concerns, of which 26% identified radiation exposure as the leading concern. The majority (70%) were unsure about the relative radiation dose of a conventional CT., Conclusions: Patients with CRS symptoms prefer CTDT over EMT if a diagnosis cannot be established definitively using exam findings. Although most patients deferred to the physician regarding the decision to utilize CT imaging, there is low awareness of CT-related radiation exposure, and a significant minority of patients have radiation-related concerns with regard to medical imaging for nasal and sinus symptoms., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Nasal irrigations are commonly employed to promote nasal hygiene in the treatment of various sinonasal conditions. Few studies have evaluated how the ionic composition of irrigation solutions affects olfactory performance. The purpose of this study was to determine the dose responsiveness of human olfactory thresholds for each of the following ions: potassium, sodium, and calcium., Study Design: Prospective translational study., Methods: Irrigation solutions with variable potassium, sodium, and calcium were tested in 25 healthy human participants. Six potassium concentrations (range, 2-10 mM), six sodium concentrations (range, 73.7-113.7 mM), and three calcium concentrations (range, 0.44-0.64 mM) were used. Before and immediately following irrigations, olfactory thresholds were determined using the Sniffin' Sticks test. Differences in olfactory threshold scores before and after irrigations were compared to assess the effect of ionic composition on olfactory sensitivity., Results: Physiologic concentrations of potassium, sodium, and calcium at 5.7, 89.5, and 0.54 mM, respectively, did not significantly change olfactory thresholds. Variations in both potassium and sodium concentrations demonstrated statistically significant dose-dependent elevations in olfactory thresholds (P < .05). Only the calcium concentration that was lower than the physiologic level led to significant elevations in olfactory thresholds., Conclusions: Different potassium and sodium concentrations in irrigation solutions provide distinctive dose-dependent shifts in olfactory thresholds. Calcium concentrations also elevate olfactory thresholds, but calcium plays a less significant role than potassium and sodium in modulating olfactory thresholds. These results highlight the importance of the intranasal ionic microenvironment in olfactory physiology and suggest that optimal ionic concentrations in irrigation solutions exist to preserve olfactory function., Level of Evidence: NA., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To study the utilization of balloon catheter dilation (BCD) compared to traditional endoscopic sinus surgery (ESS) STUDY DESIGN: Cross-sectional analysis, Methods: Cases identified by Current Procedural Terminology codes as BCD (2,717) or traditional ESS (31,059) were extracted from the State Ambulatory Surgery Databases 2011 for California, Florida, Maryland, and New York. Patient demographics, surgical center and surgeon volume, mean charge, and operating room (OR) time were compared., Results: There were 33,776 patients who underwent sinus surgery in the included states in 2011. Of these, 4.6% of maxillary, 5.6% of sphenoid, and 13.9% of frontal procedures were performed using BCD. Adjusted analyses found increased use of BCD in patients with chronic diseases(P < .001). Patients who had limited sinus surgery were less likely to have BCD compared to patients who had all four sinuses instrumented (P < .001). Surgeons who performed a medium (odds ratio 1.38 [1.14-1.65]) or high (odds ratio 1.71 [1.42-2.07]) volume of ESSs were more likely to use BCD compared to those who performed a low volume (P < .001). However, among surgeons who utilized BCD, there was a minimal relationship between the percentage of surgeries performed with BCD and the surgeon's total number of cases (R(2) = 0.055). Compared to traditional ESS, the median charges for maxillary/ethmoid procedures (mini-ESS) involving BCD were approximately $4,500 (P < .001) and maxillary/ethmoid/sphenoid/frontal procedures (pan-ESS) were approximately $2,950 (P = .003) greater, whereas the median OR time involving BCD was 8 minutes less for mini-ESS procedures(P = .01) but not statistically different for pan-ESS procedures (P = .58)., Conclusions: In the study sample, balloon technology was used in 8.0% of ESS cases in 2011. Procedures using BCD were on average more expensive compared to traditional ESS procedures, with minimal decrease in OR time., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To systematically assess the prevalence of bacterial infection in adults with acute rhinosinusitis (ARS)., Methods: Electronic databases were systematically searched for relevant studies published up to June 2012., Results: Twenty-nine articles, evaluating a total of 9,595 patients with a clinical diagnosis of ARS, were included in the study. Of these, 14 (48%) studies required radiographic confirmation of sinusitis, one study (3%) required evidence of purulence, 10 studies (35%) required both for inclusion in the study population, and four studies (14%) required neither. The random effects model estimate of prevalence of bacterial growth on all cultures was 53.7% (CI 48.4%-59.0%), ranging from 52.5% (CI 46.7%-58.3%) in studies requiring radiographic confirmation of sinusitis to 61.1% (CI 54.0%-68.1%) in studies requiring neither radiographic evidence nor purulence on exam. Studies that obtained cultures from antral swab had a prevalence of bacterial growth of 61.0% (CI 54.7%-67.2%), whereas those utilizing endoscopic meatal sampling had a prevalence of 32.9% (CI 19.0%-46.8%)., Conclusions: Few studies evaluate the recovery of bacteria via culture in adults with a diagnosis of ABRS or ARS based on clinical criteria alone. With radiographic and/or endoscopic confirmation, antral puncture and endoscopically guided cultures produce positive bacterial cultures in approximately one-half of patients. Opportunities exist to improve diagnostic accuracy for bacterial infection in ARS., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: To diagnose chronic rhinosinusitis (CRS), current guidelines require either endoscopic or computed tomography (CT) findings of sinus disease. To a primary care physician, this means a referral to an otolaryngologist or obtaining a CT scan. Unfortunately, the sensitivity of endoscopy for detecting CRS is low, and examination by the Otolaryngologist may not yield a definitive diagnosis. This leaves CT scanning. However, this is contradicted by recommendations to limit CT scanning for only preoperative planning purposes due to cost concerns. This study aims to provide an evidence-based cost-efficient recommendation for primary care practice., Study Design: Health care economics-based decision analysis model., Methods: A cost-based decision analysis based on literature-reported probabilities and Medicare costs was constructed for two scenarios: 1) primary care physicians who are comfortable initiating first-line treatment for chronic rhinosinusitis, rhinitis, and atypical facial pain; and 2) primary care physicians who are less comfortable with medical management of these conditions., Results: Under both scenarios and the extremes of sensitivity analysis, upfront CT scanning provides cost-efficient diagnosis over presuming a diagnosis of chronic rhinosinusitis. Primary care physicians who attempt first-line treatment can expect $503 (range = $296-$761) saved per patient. Meanwhile, primary care physicians who prefer to refer may expect $326 (range = $299-$353) saved per patient., Conclusions: In all scenarios, confirming diagnosis with CT scanning prior to treatment or referral is more cost-efficient than presuming a diagnosis of CRS based on symptoms alone., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Sinonasal diseases are often treated with topical agents administered through various application techniques, but few prior studies have examined their distribution to the olfactory mucosa. The purpose of this study was to compare the distribution of nasal irrigations to sprays within the olfactory cleft., Study Design: Human cadaveric study., Methods: Eight cadaveric heads, providing a total of 15 nasal sides, underwent treatment with methylene blue solution. Application utilized a pressurized spray device followed by an irrigation squeeze bottle, both used according to manufacturer instructions. Videos and images from six standardized anatomical positions were recorded by rigid nasal endoscopy prior to and following each method of agent delivery. Using the acquired images, three reviewers blinded to the means of application scored the approximate surface area stained. An image-analysis program was additionally calibrated and used to measure pixel intensity in order to quantify surface delivery of methylene blue., Results: Based on both blinded reviewer ratings and image pixel intensity measurements, irrigations demonstrated a greater extent and intensity of staining than sprays within the sphenoethmoid recess, superior turbinate, and superior olfactory cleft (all P < 0.05). Sprays and irrigations, however, were comparable in the extent of staining at the nasal vestibule (P > 0.05), inferior turbinate (P = 0.04), and middle turbinate (P > 0.05)., Conclusions: Compared to sprays, irrigations provide a more effective method of delivering topical agents to the posterior and superior aspects of the nasal cavity. The thorough distribution of irrigations has important clinical implications for improving the delivery of therapeutic agents to the olfactory mucosa., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives/hypothesis: Chronic Rhinosinusitis (CRS) is accompanied by evidence of a vigorous adaptive immune response, and emerging studies demonstrate that some nasal polyps manifest a polyclonal autoantibody response. We previously found that antibodies against BP180, a component of the hemidesmosome complex and the dominant epitope in autoimmune bullous pemphigoid, were found at elevated levels in nasal polyp tissue. Given the critical role of hemidesmosomes in maintaining epithelial integrity, we sought to investigate the distribution of BP180 in nasal tissue and evaluate for evidence of systemic autoimmunity against this antigen in CRS., Study Design: Case-control experimental study., Methods: The expression and distribution of BP180 in cultured nasal epithelial cells and normal nasal tissue were confirmed using real-time polymerase chain reaction (PCR), Western immunoblotting, immunofluorescence and immunohistochemistry. Sera were collected from three groups: control, CRSsNP, and CRSwNP. A commercially available ELISA was utilized to compare anti-BP180 autoantibody levels in sera., Results: BP180 is expressed in nasal epithelium, but is not confined to the basement membrane as it is in human skin. In cultured nasal epithelial cells, confocal immunofluorescence showed a punctate distribution of BP180 along the basal surface, consistent with its distribution in epithelial keratinocytes. There are significantly higher levels of circulating nonpathologic anti-BP180 autoantibodies in CRS patients compared with normal controls (P <0.05)., Conclusions: BP180 is more widely expressed in nasal epithelium versus skin, although it appears to play a similar role in the formation of hemidesmosomes along the basement membrane. Further investigations are ongoing to characterize the pathogenicity of the anti-epithelial antibody response in CRS.

Background: Chronic rhinosinusitis (CRS) is a disease characterized by inflammation of the nasal mucosa and paranasal sinuses. This inflammation may result in part from decreased epithelial barrier and innate immune responses, leading to frequent bacterial and fungal colonization. The objectives of this study were to investigate the expression of innate immune proteins of the palate lung and nasal epithelium clone (PLUNC) family in patients with CRS., Methods: Nasal tissue samples were collected from control subjects and CRS patients with and without nasal polyps. Expression of the members of the PLUNC family was analyzed by real-time PCR. Expression of SPLUNC1 and LPLUNC2 proteins was analyzed by ELISA, immunoblot, and immunohistochemical analysis., Results: Levels of mRNA for most of the members of the PLUNC family were profoundly reduced in nasal polyps (NPs) compared to uncinate tissue from control subjects or patients with CRS. LPLUNC2 and SPLUNC1 proteins were decreased in NPs of patients with CRS compared to uncinate tissue from control subjects. Immunohistochemical data revealed that within submucosal glands of sinonasal tissues, SPLUNC1 and LPLUNC2 were differentially expressed, in serous and mucous cells, respectively. The decrease in the expression of these molecules is probably explained by a decrease in the number of glands in NPs as revealed by correlations with levels of the glandular marker lactoferrin., Conclusions: Decreased SPLUNC1 and LPLUNC2 in NPs reflect a profound decrease in the number of submucosal glands. Decreased glands may lead to a localized defect in the production and release of glandular innate defense molecules., (© 2012 John Wiley & Sons A/S.)

Background:   Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the upper airways and sinuses and is frequently divided into polypoid CRS (CRSwNP) and nonpolypoid CRS (CRSsNP). However, the mechanism of inflammation in CRS has still not been fully elucidated. The aim of the study was to investigate the role of interleukin-32 (IL-32), a recently discovered proinflammatory cytokine, in CRS., Methods:   We collected nasal epithelial cells and nasal tissue from patients with CRS and control subjects. We assayed mRNA for IL-32 by real-time PCR and measured IL-32 protein using ELISA, Western blot, and immunohistochemistry., Results:   The expression of mRNA for IL-32 was elevated in epithelial cells from uncinate tissue from patients with CRSsNP compared with patients with CRSwNP (P < 0.05), control subjects (P=0.06), and epithelial cells from nasal polyp (NP) tissue (P < 0.05). Production of IL-32 was induced by IFN-γ, TNF, and dsRNA in primary airway epithelial cells. In whole-tissue extracts, the expression of IL-32 protein was significantly elevated in patients with CRSwNP compared with patients with CRSsNP and control subjects. Immunohistochemistry data showed that IL-32 was detected in mucosal epithelial cells and inflammatory cells in the lamina propria. Levels of IL-32 were correlated with the levels of CD3 and macrophage mannose receptor in NP tissue. Immunofluorescence data showed IL-32 co-localization with CD3-positive T cells and CD68-positive macrophages in NPs., Conclusion:   Overproduction of IL-32 may be involved in the pathogenesis of CRS, although the role of IL-32 in the inflammation in CRSsNP and CRSwNP may be different., (© 2011 John Wiley & Sons A/S.)

Background: Hyperglycemia-induced superoxide production in the mitochondria is known to be the primary cause of diabetic micro- and macro-vascular complications and mitochondrial membranal damage. This study in streptozotocin-induced diabetic Wistar rats investigated the anti-hyperglycemic and mitochondrial membrane protection effects of baicalin, a flavonoid known for its radical scavenging activity., Methods: The following oral treatments were given to diabetic rats for 30 days: (1) metformin 500 mg/kg, (2) baicalin 120 mg/kg, and (3) metformin 500 mg/kg & baicalin 120 mg/kg, with vehicle-treated diabetic and non-diabetic groups serving as controls., Results: Transmission electron microscopy imaging of pancreatic beta-cells revealed loss of integrity of the inner membrane of the mitochondria in the diabetic rats, which was not observed in the baicalin-treated group. In addition, baicalin and the combined treatment of metformin and baicalin had significantly reduced (p < 0.05) the number of mitochondria with a damaged membrane compared to the diabetic control as well as the metformin-treated group in the hepatic tissues. Baicalin had also increased the plasma leptin content (p < 0.05) versus the diabetic control, which in turn had effected the total expression of hepatic mitochondria per cell indicating its effects in SIRT1 activity. The increase in mitochondrial number was further complemented with similar trends in the hepatic citrate synthase activity., Conclusions: Baicalin had reduced the hyperglycemia-induced mitochondrial membrane damage, as well as enhanced the effects of metformin, as was observed in the results from the metformin and baicalin treated groups., ((c) 2009 John Wiley & Sons, Ltd.)

Objective: To determine current practice in the management of recurrent in vitro fertilisation (IVF) treatment failure in licensed UK infertility centres., Design: National postal questionnaire study and literature review., Setting: University Hospital, Centre for Reproductive Medicine, Coventry, UK., Sample: Human Fertilisation and Embryology Authority licensed centres providing IVF/intracytoplasmic sperm injection (ICSI) in the UK (n = 79)., Methods: A survey was designed that sought to determine how recurrent treatment failure was defined and which, if any, investigations were initiated. Furthermore, we asked which therapeutic options were subsequently recommended., Main Outcome Measures: Definition of recurrent treatment failure. Investigations undertaken. Clinical or embryology changes recommended following recurrent treatment failure., Results: The response rate was 82%. The most common definition was three unsuccessful IVF cycles (range 2-6). Nineteen percent included frozen embryo replacements (FERs) in this figure. Anticardiolipin antibodies and lupus anticoagulant were the most frequent investigations suggested, followed by hysteroscopy and karyotype. A majority of centres would use a different treatment strategy in a subsequent cycle with blastocyst culture and assisted hatching being most popular., Conclusions: The results of this survey suggest that there is considerable variation in the approach to investigation and management of recurrent IVF treatment failure in the UK, although in some areas (e.g. the definition) there was broad concordance. Not all of these approaches are evidence based.

1. The present study found that, compared with mouse heart and liver, P388 ascitic tumour had significantly lower superoxide dismutase (SOD) activity and that compared with the mouse liver, the heart had significantly lower SOD and catalase activities, as well as a lower glutathione content. 2. At 7.5 mg/kg, doxorubicin (DOX), a superoxide radical inducer, induced significant lipid peroxidation only in the tumour, whereas 15.0 mg/kg DOX induced lipid peroxidation in both the tumour and heart, but not in the liver. 3. Overall, the results of the present study suggest that the differential anti-oxidant activities in P388 ascitic tumour, heart and liver in mice may explain their differential responses and, hence, susceptibility to DOX-induced lipid peroxidation.

1. Oxidative stress is believed to be a pathogenetic factor in the development of diabetic complications. In the present study, we investigated the ethanolic extract of the aerial parts of Andrographis paniculata for antihyperglycaemic and anti-oxidant effects in normal and streptozotocin-induced type I diabetic rats. 2. Normal and diabetic rats were randomly divided into groups and treated orally by gavage with vehicle (distilled water), metformin (500 mg/kg bodyweight) or the extract (400 mg/kg bodyweight), twice a day for 14 days. 3. At the end of the 14 day period, the extract, like metformin, significantly increased bodyweight (P < 0.01) and reduced fasting serum glucose in diabetic rats (P < 0.001) when compared with vehicle, but had no effect on bodyweight and serum glucose in normal rats. Levels of liver and kidney thiobarbituric acid-reactive substances (TBARS) were significantly increased (P < 0.0001, P < 0.01, respectively), while liver glutathione (GSH) concentrations were significantly decreased (P < 0.005) in vehicle-treated diabetic rats. Liver and kidney TBARS levels were significantly lower (P < 0.0001, P < 0.005, respectively), whereas liver GSH concentrations were significantly higher (P < 0.05) in extract- and metformin-treated diabetic rats compared with vehicle-treated diabetic rats. Andrographis paniculata significantly decreased kidney TBARS level (P < 0.005) in normal rats. Hepatic superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were significantly lower in vehicle-treated diabetic rats compared with vehicle-treated normal rats. The extract, as well as metformin, significantly increased the activity of SOD and CAT, but had no significant effect on GSH-Px activity in diabetic rats. The extract and metformin did not produce significant changes in the activity of these anti-oxidant enzymes in normal rats. 4. Our results show that oxidative stress is evident in streptozotocin-diabetic rats and indicate that the ethanolic extract of A. paniculata not only possesses an antihyperglycaemic property, but may also reduce oxidative stress in diabetic rats.

1. The pharmacological effects of 14-deoxyandrographolide on rat isolated thoracic aorta were examined. 2. 14-Deoxyandrographolide (2.5-120 mumol/L) inhibited contractions induced by phenylephrine (PE; 0.1 mumol/L) and high K+ (80 mmol/L) in a concentration-dependent manner in endothelium-intact aorta. The effect was attenuated in endothelium-denuded aorta without modifying the maximal response. Like verapamil, 14-deoxyandrographolide produced a much greater vasorelaxant effect in aorta precontracted by KCl than by PE. 14-Deoxyandrographolide (20-60 mumol/L) also inhibited responses of the rat aorta to PE. 3. In Ca(2+)-free medium (KCl 55 mmol/L), 14-deoxyandrographolide (20-80 mumol/L) antagonized Ca(2+)-induced vasocontraction in a concentration-dependent manner and transient contractions induced by both caffeine (10 mmol/L) and nor-adrenaline (1 mumol/L) were suppressed or almost abolished by 14-deoxyandrographolide. 4. The vasorelaxant effect of 14-deoxyandrographolide was partially antagonized by NG-nitro-L-arginine methyl ester (25 mumol/L), a specific and competitive nitric oxide synthase (NOS) inhibitor, and methylene blue (10 mumol/L), a soluble guanylate cyclase inhibitor, but was not affected by indomethacin (20 mumol/L), a cyclo-oxygenase inhibitor, or glibenclamide (10 mumol/L), an ATP-sensitive K(+)-channel blocker. 5. These results suggest that the vasorelaxant activity of 14-deoxyandrographolide may be mediated via the activation of NOS and guanylate cyclase, as well as the blockade of Ca2+ influx through both voltage- and receptor-operated Ca2+ channels.

1. The hypotensive activity of an aqueous extract of Andrographis paniculata was studied using chronic intraperitoneal (i.p.) infusions by osmotic pumps. The extract exhibited a dose-dependent hypotensive effect on the systolic blood pressure (SBP) of spontaneously hypertensive rats (SHR). 2. The optimum hypotensive dose determined was repeated in a study in SHR and their normotensive controls, Wistar-Kyoto (WKY) rats, to demonstrate its comparative effects on the SBP, plasma and lung angiotensin-converting enzyme (ACE) activities, as well as on lipid peroxidation in the kidneys, as measured by the thiobarbituric acid (TBA) assay. 3. The extract significantly lowered the SBP of both SHR and WKY rats. 4. Plasma, but not lung, ACE activity and kidney TBA level were significantly lower in extract-treated SHR when compared with vehicle-treated SHR controls. 5. Plasma and lung ACE activities as well as kidney TBA levels were not significantly different between extract- and vehicle-treated WKY rats. 6. This study indicates that the aqueous extract of A. paniculata lowers SBP in the SHR possibly by reducing circulating ACE in the plasma as well as by reducing free radical levels in the kidneys. The mechanism(s) of hypotensive action seems to be different in WKY rats.

1. Aqueous celery extract was administered intraperitoneally to genetically hypercholesterolaemic (RICO) and normocholesterolaemic (RAIF) rats via Alzet osmotic pumps over a 13 day period. 2. The serum cholesterol concentration of the celery extract-treated RICO rats was found to be significantly lower (P < 0.05) than the control rats. Aqueous celery extract was effective in preventing the rise of cholesterol level in the RICO rats. However, no such observation was seen in the RAIF rats. The serum triglyceride level was unchanged in both strains of rats. 3. When 3-n-butylphthalide (BuPh), a unique component in celery, was administered in the same manner to the RICO and RAIF rats, it did not produce significant changes in the serum and liver lipid profiles of these rats. The activities of hepatic 3-hydroxy-3-methylglutaryl CoA reductase in both strains of rats were also not significantly different from their respective controls. 4. Together with our recently reported thin-layer chromatography findings that BuPh was not detected in the aqueous celery extract, this study suggests that the effect of celery extract on serum cholesterol levels in the RICO rats could be attributed to chemical constituents other than BuPh.

1. The effects of a 13-day intraperitoneal (i.p.) infusion of bromocriptine, delivered by osmotic pump, on plasma and pituitary thyroid-stimulating hormone (TSH) levels were investigated in New Zealand genetically hypertensive (GH) rats and their normotensive (NT) controls. 2. In both the GH and NT rats, bromocriptine significantly reduced plasma TSH level but did not have any significant effect on pituitary TSH content. 3. No significant difference was found in the plasma TSH level and pituitary TSH content between the vehicle-treated GH and NT rats. 4. These results suggest that there are no differences between the GH and NT rats with regard to the activity of the central dopaminergic system influencing TSH release and also that TSH does not play a role in the hypertension of the GH rats.

1. We have previously reported on the effects of a 13-day intraperitoneal infusion of bromocriptine delivered by osmotic pump on blood pressure, plasma and pituitary PRL levels in genetically hypertensive (GH) rats and their normotensive (NT) controls. This paper reports further on that study in describing the changes in saline and water intakes in rats as a result of bromocriptine (BRC) treatment. 2. In the GH rats, bromocriptine did not have any significant effect on saline or water intake. 3. In the NT rats, bromocriptine significantly decreased saline intake and increased water intake. 4. The saline intake in the vehicle-treated GH rats was significantly lower than that in the vehicle-treated NT rats while the water intake was not significantly different. 5. These results indicate that differences exist between the GH and NT rats with regard to their saline and water intakes and their responses to chronic bromocriptine treatment. The changes in saline and water intakes in the GH rats seem to be different from those seen in the spontaneously hypertensive rat in another study.

1. The effects on blood pressure (BP) and plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine delivered by osmotic minipump were investigated in spontaneously hypertensive rats (SHR) and their normotensive controls, the Wistar-Kyoto rats (WKY). 2. In the SHR, a fall in BP which was steepest over the initial few days and sustained up to day 12 was observed in the bromocriptine-treated group compared with the lack of a change in BP observed in the vehicle-treated group. The plasma PRL level taken on day 13 was found to be significantly lower in the bromocriptine-treated group than in the vehicle-treated group. 3. In the WKY, bromocriptine had no significant effect on either BP or plasma PRL. 4. Pituitary PRL content was significantly lower in the SHR than in the WKY. The suppression by bromocriptine treatment was greater in the SHR than in the WKY. 5. These results provide further evidence for a central dopaminergic insufficiency in the SHR and raise the possibility that PRL may, either directly or indirectly by interacting with other factors in the SHR, influence BP.

1. The effects on blood pressure (BP), plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine (BRC) delivered by osmotic minipump were investigated in genetically hypertensive rats (GHR) and their normotensive (NT) controls. 2. In the GHR, the mean BP in the BRC-treated group over the 13 day period of study was significantly lower than in the vehicle-treated group. In the NT rats, the mean BP in the BRC-treated group over the 13 day period was also significantly lower than in the vehicle-treated group. 3. Mean plasma PRL concentration in the GHR and NT rats were comparable. In the GHR, the mean plasma PRL concentration taken on day 13 was significantly lower in the BRC-treated group than in the vehicle-treated group. In the NT rats, the mean plasma PRL concentration taken on day 13 in the BRC-treated group was, however, not significantly different from that in the vehicle-treated group. 4. The mean pituitary PRL content was not significantly different in the GH and NT rats. There was a greater suppression of pituitary PRL content in the BRC-treated GHR than in the BRC-treated NT rats compared with their respective vehicle-treated groups. 5. The results raise the possibility that PRL may have an indirect role in the pathogenesis of the hypertension of the GHR.