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  1. Hamizan AW, Rimmer J, Alvarado R, Sewell WA, Tatersall J, Barham HP, et al.
    Am J Rhinol Allergy, 2019 Mar;33(2):178-183.
    PMID: 30656948 DOI: 10.1177/1945892418825224
    BACKGROUND: Specific immunoglobulin E (sIgE) within the nasal airway is likely to be the most ideal marker of allergic status, but little is known of the normative values in asymptomatic patients and those with rhinitis.

    OBJECTIVE: The aim of this study was to assess the diagnostic characteristics of inferior turbinate tissue biopsy sIgE in asymptomatic and rhinitic patients.

    METHODS: A diagnostic cross-sectional study was undertaken, involving patients who underwent inferior turbinate surgery with or without other surgical interventions. Inferior turbinate tissue biopsy was performed during surgery and was assessed for allergen sIgE (dust mite, grass [temperate or subtropical], and animal epithelium) using an automated immunoassay. Tissue sIgE was assessed among asymptomatic patients and those with nasal symptoms. Data were presented as median (interquartile range). A receiver operating curve was used to predict the diagnostic utility of turbinate tissue sIgE in determining allergic rhinitis.

    RESULTS: A total of 160 patients (41.89 ± 14.65 years, 36.9% females) were included. The median tissue sIgE concentration among the asymptomatic nonatopic group of patients was 0.09 (0.08-0.10) kUA/L and tissue sIgE > 0.10 kUA/L was determined as a positive threshold. Inferior turbinate tissue sIgE was shown to be a predictive test for allergic rhinitis (area under curve: 0.87, 95% confidence interval: 0.84-0.90) with 90% sensitivity and 89% negative predictive value.

    CONCLUSION: Inferior turbinate tissue biopsy sIgE is a sensitive tool to predict allergic rhinitis. The threshold value of 0.1 kUA/L corresponded well with the asymptomatic nonatopic group of patients. This method detects sIgE in the nasal mucosa and may be a useful test for allergic rhinitis in future research.

  2. Hamizan AW, Christensen JM, Ebenzer J, Oakley G, Tattersall J, Sacks R, et al.
    Int Forum Allergy Rhinol, 2017 01;7(1):37-42.
    PMID: 27530103 DOI: 10.1002/alr.21835
    BACKGROUND: Middle turbinate edema could be a characteristic feature of aeroallergen sensitization. In this study we sought to determine the diagnostic characteristics of middle turbinate edema as a marker of inhalant allergy.

    METHODS: A cross-sectional diagnostic study was performed on patients who had undergone nasal endoscopy and allergy testing. Allergy status was determined by positive serology or epicutaneous testing. Endoscopy was reviewed by blinded assessors for middle turbinate head edema. Appearance was graded as either normal, focal, multifocal, diffuse, or polypoid edema. Receiver-operator (ROC) analysis, likelihood ratio (LR), sensitivity, specificity, and positive predictive value (PPV) were determined.

    RESULTS: One hundred eighty-seven patients representing 304 nasal cavities were assessed (42% female, age 39.74 ± 14.7 years, 57% allergic). Diffuse edema (PPV 91.7%/LR = 8) and polypoid edema (PPV 88.9%/LR = 6.2) demonstrated the strongest association with inhalant allergy. Multifocal edema was used as a cut-off to represent inhalant allergy from ROC analysis, which demonstrated 94.7% specificity and 23.4% sensitivity. The PPV for multifocal was 85.1% and LR = 4.4.

    CONCLUSION: Middle turbinate edema is a useful nasal endoscopic feature to predict presence of inhalant allergy and, although not sensitive, has excellent PPV.

  3. Hamizan AW, Christensen JM, Ebenezer J, Oakley G, Tattersall J, Sacks R, et al.
    Int Forum Allergy Rhinol, 2017 06;7(6):634-635.
    PMID: 28481026 DOI: 10.1002/alr.21938
  4. Hamizan AW, Loftus PA, Alvarado R, Ho J, Kalish L, Sacks R, et al.
    Laryngoscope, 2018 09;128(9):2015-2021.
    PMID: 29602169 DOI: 10.1002/lary.27180
    OBJECTIVES/HYPOTHESIS: Polypoid edema of the middle turbinate is a marker of inhalant allergy. Extensive edematous changes may result in limited central nasal and sinus disease, which has been called central compartment atopic disease (CCAD). Radiologically, this is seen as soft tissue thickening in the central portion of the sinonasal cavity with or without paranasal sinus involvement. When the sinuses are involved, the soft tissue thickening spares the sinus roof or lateral wall (centrally limited). This centrally limited radiological pattern was assessed among chronic rhinosinusitis (CRS) patients and compared to allergy status.

    STUDY DESIGN: Diagnostic cross-sectional study.

    METHODS: This study included consecutive CRS patients without prior sinus surgery. Computed tomography (CT) scans of the paranasal sinuses were blindly assessed and allergy status was confirmed by serum or skin testing. Individual sinus cavities were defined as either centrally limited or diffuse disease. The radiological pattern that may predict allergy was determined, and its diagnostic accuracy was calculated.

    RESULTS: One hundred twelve patients diagnosed to have CRS, representing 224 sides, were assessed (age 46.31 ± 13.57 years, 38.39% female, 41.07% asthma, Lund-Mackay CT score 15.88 ± 4.35, 56.25% atopic). The radiological pattern defined by centrally limited changes in all of the paranasal sinuses was associated with allergy status (73.53% vs. 53.16%, P = .03). This predicted atopy with 90.82% specificity, 73.53% positive predictive value, likelihood positive ratios of 2.16, and diagnostic odds ratio of 4.59.

    CONCLUSIONS: A central radiological pattern of mucosal disease is associated with inhalant allergen sensitization. This group may represent a CCAD subgroup of patients with mainly allergic etiology.

    LEVEL OF EVIDENCE: 3b Laryngoscope, 128:2015-2021, 2018.

  5. Ho J, Hamizan AW, Alvarado R, Rimmer J, Sewell WA, Harvey RJ
    Am J Rhinol Allergy, 2018 Jul;32(4):252-257.
    PMID: 29862828 DOI: 10.1177/1945892418779451
    Background Eosinophilic chronic rhinosinusitis (eCRS) is linked with skewed T-helper 2 or immunoglobulin E (IgE)-mediated allergic responses, with differing diagnosis, prognosis, and management to non-eCRS. Objective The association between biomarkers and eCRS was investigated to assess the predictors of eCRS. Methods A cross-sectional study of adult patients with chronic rhinosinusitis (CRS) undergoing endoscopic sinus surgery was conducted. eCRS was defined by histopathological assessment showing >10 eosinophils/high-power field on sinus mucosal biopsy. Blood tests were performed preoperatively and assessed for a full blood count including eosinophils and a white cell count (WCC) as well as biochemical markers of inflammation and atopy including Immunoglobulin E (IgE), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and ImmunoCAP testing for serum-specific IgE. Comparisons between eCRS and non-eCRS patients were performed. Results 345 patients (48.1% female, age 48.72 ± 15.06 years) were recruited, with 206 (59.7%) identified as eCRS, 41% with asthma and 47% CRS with nasal polyps. eCRS patients were more likely to have asthma ( P 0.24 × 109/L), eosinophil ratio (>4.27% of total WCC), and lower ESR when compared with non-eCRS.
  6. Hamizan AW, Rimmer J, Alvarado R, Sewell WA, Kalish L, Sacks R, et al.
    Int Forum Allergy Rhinol, 2017 09;7(9):868-877.
    PMID: 28727909 DOI: 10.1002/alr.21988
    BACKGROUND: The diagnosis of allergic rhinitis (AR) is based on cutaneous and serological assessment to determine immunoglobulin E (IgE)-mediated disease. However, discrepancies between these tests and nasal provocation exist. Patients diagnosed as non-allergic rhinitis (NAR) but with positive nasal allergen provocation test (NAPT) may represent a local allergic condition or entopy, still suitable to allergy interventions. The objective of this study was to determine the frequency of nasal reactivity toward allergens among AR and NAR patients, and to describe the diagnostic characteristics of NAPT methodologies.

    METHODS: EMBASE (1947-) and Medline (1946-) were searched until December 8, 2015. A search strategy was used to identify studies on AR or NAR patients subjected to diagnostic local nasal provocation. All studies providing original NAPT data among the AR or NAR population were included. Meta-analysis of proportion data was presented as a weighted probability % (95% confidence interval [CI]).

    RESULTS: The search yielded 4504 studies and 46 were included. The probability of nasal allergen reactivity for the AR population was 86.3% (95% CI, 84.4 to 88.1) and in NAR was 24.7% (95% CI, 22.3 to 27.2). Reactivity was high with pollen for both AR 97.1% (95% CI, 94.2 to 99.2) and NAR 47.5% (95% CI, 34.8 to 60.4), and lowest with dust for both AR 79.1% (95% CI, 76.4 to 81.6) and NAR 12.2% (95% CI, 9.9 to 14.7). NAPT yielded high positivity when defined by subjective end-points: AR 91.0% (95% CI, 86.6 to 94.8) and NAR 30.2% (95% CI, 22.9 to 37.9); and lower with objective end-points: AR 80.8% (95% CI, 76.8 to 84.5) and NAR 14.1% (95% CI, 11.2 to 17.2).

    CONCLUSION: Local allergen reactivity is demonstrated in 26.5% of patients previously considered non-allergic. Similarly, AR, when defined by skin-prick test (SPT) or serum specific IgE (sIgE), may lead to 13.7% of patients with inaccurate allergen sensitization or non-allergic etiologies.

  7. Wong E, Hamizan AW, Alvarado R, Orgain CA, Kalish L, Sacks R, et al.
    Am J Otolaryngol, 2018 06 22;39(5):570-574.
    PMID: 29961655 DOI: 10.1016/j.amjoto.2018.06.019
    PURPOSE: Middle turbinate head edema has recently been found to have high specificity for diagnosis of inhalant allergy. However, subtle mucosal edema can be difficult to appreciate under white light endoscopy. Narrow band imaging (NBI) has the potential to demonstrate edema by identifying reduced mucosal vascularity and improve sensitivity for the detection of mucosal edema. Narrow band imaging was assessed to determine its utility in objectifying mucosal edema.

    MEATERIALS AND METHODS: A cross-sectional diagnostic study was performed on patients with edematous mucosa of the middle turbinate head. Under traditional white light endoscopy, areas of edematous mucosa were identified. Using NBI, these areas were compared to areas of normal mucosa on the middle turbinate head. NBI images of these same areas were then converted to grey scale and a vascularity index was created by pixel analysis and brightness in Fiji Image J software (Wisconsin, US).

    RESULTS: Thirty-three middle turbinates were assessed (age 42.4 ± 12.5, 42.4% female). NBI discriminated between areas identified under white light endoscopy as edematous and normal (158.2 ± 48.4 v 96.9 ± 32.7 p 

  8. Hamizan AW, Rimmer J, Husain S, Alvarado R, Tatersall J, Sewell W, et al.
    Rhinology, 2019 Feb 01;57(1):10-20.
    PMID: 30219822 DOI: 10.4193/Rhin18.074
    BACKGROUND: Allergen specific immunoglobulin can be present in the nasal mucosa of patients with non-allergic rhinitis (NAR). This condition is defined as local allergic rhinitis. However, the reported presence of nasal specific immunoglobulin E (nspIgE) among NAR is variable. The aim of this review was to summarize the studies which reported the presence of nspIgE among patients diagnosed as NAR.

    METHODS: Embase (1947- ) and Medline (1946-) were searched until 6th June 2017. A search strategy was utilized to identify studies on nspIgE among patients with NAR. The target population was patients with symptoms of rhinitis, but negative systemic allergen sensitization. Studies with original data on detectable nspIgE among the NAR population were included. Meta-analysis of single proportions as a weighted probability %(95%CI) was performed. Heterogeneity was explored amongst studies.

    RESULTS: A search strategy returned 2286 studies and 21 were included. These studies involved 648 participants with NAR. NspIgE was detected using either; 1. nasal secretions, 2. epithelial mucosa sampling, 3. tissue biopsies or 4. In-situ tests. Metaanalysis was performed on studies with nasal secretions. The weighted proportion of detectable nspIgE in nasal secretions within patients with NAR was 10.2 (7.4-13.4) %. Population definitions partly explained variability. Detection of nspIgE was lower in patients without a history suggestive of allergy compared to those with a positive allergic history (0 (0-3.1) % v 19.8 (14.5-25.6) %, p<0.01).

    CONCLUSION: NAR with positive allergy history suggests presence of nspIgE. These patients warrant further allergology evaluation to confirm localized nasal allergy, as they benefit from allergy therapy such as immunotherapy.

  9. Mo S, Gupta SS, Stroud A, Strazdins E, Hamizan AW, Rimmer J, et al.
    Laryngoscope, 2021 02;131(2):260-267.
    PMID: 32386248 DOI: 10.1002/lary.28682
    OBJECTIVES: Nasal peak inspiratory flow (NPIF) is a practical and affordable tool that measures maximum inspiratory flow rate through both nostrils. Although NPIF values for healthy controls and patients appear to differ considerably, a generally expected value for populations with and without nasal obstruction has yet to be established. The aim of this systematic review and meta-analysis was to determine the mean NPIF value in populations with and without nasal obstruction.

    METHODS: Medline (1946-) and Embase (1947-) were searched until July 1, 2017. A search strategy was used to identify studies that reported NPIF values for defined healthy or disease states. All studies providing original data were included. The study population was defined as having either normal nasal breathing or nasal obstruction. A meta-analysis of the mean data was presented in forest plots, and data were presented as mean (95% confidence interval [CI]).

    RESULTS: The search yielded 1,526 studies, of which 29 were included. The included studies involved 1,634 subjects with normal nasal breathing and 817 subjects with nasal obstruction. The mean NPIF value for populations with normal nasal breathing was 138.4 (95% CI: 127.9-148.8) L/min. The mean value for populations with nasal obstruction was 97.5 (95% CI: 86.1-108.8) L/min.

    CONCLUSIONS: Current evidence confirms a difference between mean NPIF values of populations with and without nasal obstruction. The mean value of subjects with no nasal obstruction is 138.4 L/min, and the mean value of nasally obstructed populations is 97.5 L/min. Prospective studies adopting a standardized procedure are required to further assess normative NPIF values. Laryngoscope, 131:260-267, 2021.

  10. Stroud A, Dhaliwal P, Alvarado R, Winder MJ, Jonker BP, Grayson JW, et al.
    Pituitary, 2020 Oct;23(5):595-609.
    PMID: 32691356 DOI: 10.1007/s11102-020-01066-8
    PURPOSE: Transsphenoidal surgery (TSS) is the first-line treatment for Cushing's disease (CD). This review aimed to synthesize the remission and recurrence rates following TSS for CD and identify predictors of these outcomes.

    METHODS: Medline (1946-) and Embase (1947-) were searched until 23rd January 2019 for original studies. A meta-analysis was performed of remission and recurrence rates. Studies were excluded if patients had prior radiosurgery/radiotherapy, mixed pathologies or interventions without separated data, follow-up not reported or population size 

  11. Oakley GM, Ebenezer J, Hamizan A, Sacks PL, Rom D, Sacks R, et al.
    J Neurol Surg B Skull Base, 2018 Aug;79(4):361-366.
    PMID: 30009117 DOI: 10.1055/s-0037-1608650
    Introduction  Identifying the internal carotid artery (ICA) when managing petroclival and infratemporal fossa pathology is essential for the skull base surgeon. The vidian nerve and eustachian tube (ET) cartilage come together at the foramen lacerum, the vidian-eustachian junction (VEJ). The ICA position, relative to the VEJ is described. Methods  Endoscopic dissection of adult fresh-frozen cadaver ICAs and a case series of patients with petroclival pathology were performed. The relationship of the VEJ to the ICA horizontal segment, vertical segment, and second genu was assessed. The distance of the ICA second genu to VEJ was determined in coronal, axial, and sagittal planes. The length of the vidian nerve and ET was measured from the pterygopalatine fossa (PPF) and nasopharyngeal orifice to the VEJ. Results  In this study, 10 cadaver dissections (82.3 ± 6.7 years, 40% female) were performed. The horizontal petrous ICA was at or behind VEJ in 100%, above VEJ in 100%, and lateral to VEJ in 80%. The vertical paraclival segment was at or behind VEJ in 100%, above in 100%, and medial in 100%. The second genu was at or behind VEJ in 100% (3.3 ± 2.4 mm), at or above in 100% (2.5 ± 1.6 mm), and medial in 100% (3.4 ± 2.0 mm). The VEJ was successfully used to locate the ICA in nine consecutive patients (53.3 ± 13.6 years, 55.6% female) where pathology was also present. The VEJ was 15.0 ± 6.0 mm from the ET and 17.4 ± 4.1 mm from the PPF. Conclusion  The VEJ is an excellent landmark as it defines both superior and posterior limits when isolating the ICA in skull base surgery.
  12. Nyunt TPK, Abdullah B, Khaing MM, Seresirikachorn K, Shukri NM, Aeumjaturapat S, et al.
    Asian Pac J Allergy Immunol, 2023 Dec;41(4):347-352.
    PMID: 33274959 DOI: 10.12932/AP-310720-0934
    BACKGROUND: Patients with diabetes mellitus (DM) are susceptible to invasive fungal rhinosinusitis (IFRS). The mortality rate of IFRS varies greatly among the patients with DM.

    OBJECTIVE: To identify the prognostic factors for the overall survival of patients with DM and IFRS.

    METHODS: A retrospective study was conducted in four tertiary hospitals in Thailand, Malaysia and Myanmar. Patients diagnosed with IFRS and DM from 2008 to 2019 were identified. The outcome was the overall survival. Variables analyzed for risk factors were age, HbA1C level, ketoacidosis, white blood cell count, hyperglycemia, duration of DM, current use of diabetic medications, serum creatinine level, and the extensions of IFRS to the orbit, the cavernous sinus and intracranial cavity.

    RESULTS: Sixty-five diabetic patients with IFRS (age 57.9 ± 13.4 years, male 60%) were identified. The mortality rate was 21.5%. The extensions of IFRS to the cavernous sinus (hazard ratio 5.1, 95% CI [1.4-18.2], p = 0.01) and intracranial cavity (hazard ratio 3.4, 95% CI [1.1-11.3, p = 0.05) predicted mortality. Current use of diabetic medications decreased the mortality risk (hazard ratio 0.2, 95% CI [0.1-0.9], p = 0.03). The 6-month overall survival of the patients with and without the cavernous sinus extension were 51.4% and 83.6%, (p = 0.001), with and without intracranial extension 53.3% and 88.9%, (p = 0.001), and with and without current diabetic medications 82.3% and 57.5%, respectively (p = 0.045).

    CONCLUSIONS: The extensions of IFRS to the cavernous sinus and intracranial cavity increased the risk of death in patients with DM. Survival was primarily related to current use of diabetic medications.

  13. Jafari A, Adappa ND, Anagnos VJ, Campbell RG, Castelnuovo P, Chalian A, et al.
    Int Forum Allergy Rhinol, 2023 Oct;13(10):1852-1863.
    PMID: 36808854 DOI: 10.1002/alr.23141
    BACKGROUND: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs.

    METHODS: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class.

    RESULTS: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p 

  14. Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, et al.
    Rhinology, 2020 Feb 20;58(Suppl S29):1-464.
    PMID: 32077450 DOI: 10.4193/Rhin20.600
    The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.
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